Chapter S1. Continuous flow alcoholysis of furfuryl alcohol to alkyl levulinates using zeolites Chapter S2. Conversion of alkyl levulinates into γ-valerolactone in the presence of Ru/C in continuous flow Chapter S4. Insights into the microwave-assisted oxidation of hydroxymethyl furfural to added-value compounds over ruthenium based catalysts in batch and continuous flow reactors Chapter S5. One-pot FDCA diester synthesis from mucic acid and their solvent-free regioselective polytransesterification for production of glycerol-based furanic polyesters Achievements ........

ParisTech) for 2 years and a half, the PhD work was under the supervision of Prof.

Christophe Len.

First of all, I would like to thank the director of my thesis, Prof. Christophe Len for his scientific help, support and guidance during my PhD. Three and a half years before, Christophe gave me this opportunity of learning abroad. I enjoy my life in France, a developed, democratic state with beautiful environment. Most importantly, the study with Christophe is unforgettable; he is always a humorous, modest, kind-hearted, decent and reliable supervisor. I appreciate his trust for giving me the freedom to design my experiment. The opportunity of an oral presentation in an international conference (ISGC 2018 in La Rochelle, France), the first time attending the international meeting, was unforgettable experience for me.

I also want to thank China Scholarship Council (CSC) for the financial support during my PhD. Without it I can't finish my PhD studying. It's also a great honor to me.

Thank you so much my motherland. The 70th anniversary is a landmark in the history, as well as a new starting point of a journey towards a more promising future. I wish my motherland all the best in the year ahead. Thanks to Prof. Rafael Luque, leader of FMQ-383 NANOVAL group in Universidad de Cordoba (Spain) for giving me the opportunity to work in his group from 01/10/2017 to 30/12/2017. Even only three months, but it was a good chance to learn knowledge about catalyst characterization, flow chemistry and so on, it broadened my horizon. Most importantly, it's a good platform to communicate with a lot of brilliant researchers in the groups. Rafael is the person I'd want to be. Efficient, energized, confidence and knowledgeable.

I want to express my gratitude to the members of the jury that participate in my PhD defense. I would especially like to acknowledge the referees of my thesis, and besides, I would like thank Prof. Konstantinos from the department of chemistry, Aristotle University of Thessaloniki (Greece) for helping me to analyze the catalysts. I particularly thank Daily and Yantao for guiding me how to perform the experiments when I was confused, the time spending on my manuscript too. We are on good terms. We are great buddies. No needs more words.

I would like to thank my colleagues Frédéric, Sarra, Sophie, Audrey and Denis, they come from the group in Compiègne. Pepijn, Weiyi, Ana, Antonio, and all the colleagues from Rafael's group, 2017 Christmas holiday, the happy time in Cordoba. Comparison of catalytic activity in continuous flow alcoholysis of 0.2 M FA in MeOH (170 °C, 50 bar, 0.2 mL min -1 ), using 200 mg of (a) fresh H-ZSM-5-50.

Special thanks to

List of Tables

List of Figures

(b) spent H-ZSM-5-50 recovered after 800 °C for 9 h. (c) spent H-ZSM-5-50 recovered after 500 °C for 4 h. (a) 13 C-NMR spectrum of PEF in DMSO-d6; (b,d) 13 C-and 1 H-NMR spectra of PHPF in DMSO-d6 and (c) 13 C-NMR of PDGF measured in DMSO-d6.

General Introduction

Fossil fuels such as coal, oil, and natural gas provided more than three quarters of the world's energy. The consumption of fossil fuel resources has surged during the 20th century, partially because of the rise of automobile industry. Unfortunately, the growing demand for fossil fuel resources comes at a time of diminishing reserves of these nonrenewable resources, such that the worldwide reserves of oil are sufficient to supply energy and chemicals for only about another 40 years [1]. The strong fluctuations (variation, instability) of fossil fuel prices and the increase of greenhouse gas emissions [2] require the discovery of alternative and renewable resources to release the burden of fossil fuels and chemicals.

The renewable energy sources such as solar, wind, hydroelectric, biomass and geothermal power. The nuclear powered sources are fission and fusion. Among them, biomass provides a clean, renewable energy source that could dramatically improve our environment, economy and energy security. Production of energy from biomass also has the potential to generate lower greenhouse gas emissions when compared to the combustion of fossil fuels, because the CO2 released during energy conversion is consumed during subsequent biomass regrowth. Furthermore, it can reduce the amount of waste sent to landfills and decrease our reliance on fossil resources. Biomass energy also creates thousands of jobs and helps revitalize rural communities. The advantages above have made it the best candidate to replace fossil resources.

Biomass is a general term for material derived from growing plants: including wood and wood wastes, agricultural crops and their waste byproducts, municipal solid waste, animal wastes, waste from food processing and aquatic plants and algae. It has been used to meet a variety of energy needs, including generating electricity, heating homes, fueling vehicles and providing process heat for industrial facilities. The U.S.

Department of Energy in collaboration with the U.S. Department of Agriculture have indicated that there will be an increase in the commodities of bio-chemicals and biomaterials to 25% in 2030 [3].

Bioenergy conversion technologies are used to convert biomass into useful energy.

These technologies are mainly divided into two categories: thermochemical and biochemical conversion. In thermochemical conversion pathways, heat and chemical catalysts are used for the production of energy from biomass, while biochemical Heating method plays an important role in biomass valorization process.

Conventional thermal heating is known as a traditional heating system (with an external heat source such as an oil bath or heating mantle) where heat is transferred from the surface towards the center of the material by conduction, convection, and radiation.

This heating system is relatively slow and inefficient and depends on the thermal conductivity of the material and convection currents. Microwaves are generally defined as non-ionizing radiations, namely electromagnetic waves that are comprised of two perpendicular components (i.e., electric and magnetic fields) as shown in Fig. 0.2 [4]. Microwave heating is different with conventional heating since it can be transmitted, reflected or absorbed toward the reagent. The microwaves can penetrate materials and deposit energy, thus the heat can be produced throughout the volume of the materials rather than an external source (in core volumetric heating). The difference in mechanism for conventional and microwave heating systems was illustrated in Fig. 0.3, the center of the material is at a higher temperature than the surrounding material in microwave heating [5,6].

Thermochemical

Biochemical

Main conversion routs Products

According to the literature, there are three possible ways (combination of two or all three contributions) of chemical reaction enhancement using microwave irradiation technique [7], including (i) thermal effects (the influence of a high reaction temperature which can be rapidly attained when irradiating polar materials in a microwave field) [8], (ii) specific microwave effects (can be caused by the unique nature of the microwave irradiation heating mechanism in a microwave field and cannot be achieved by conventional heating) [9], and (iii) non-thermal effects (chemical transformation accelerations that cannot be defined in terms of thermal or specific microwave effects) [10]. GHz (corresponding to a 12.25 cm wavelength), and this same frequency has also been widely adopted by companies manufacturing scientific microwave apparatus for use in preparative chemistry, with only a few exceptions [11,12]. Microwave energy was originally applied for heating food. Until the mid-1980s, Gedye et al. first reported the use of microwave heating to accelerate chemical synthesis [13]. Since then, microwave technologies and equipment have been significantly developed, and the number of publications related to microwave-assisted organic synthesis increased dramatically (up to ≈ 5000). In 1998, Grant and Halstead [14] provided a thorough explanation of the underlying theory of the microwave dielectric heating. The microwave heating involves two main mechanisms: dipolar polarization and ionic conduction as sketched in Fig. 0.5 which adapted from Bilecka and Niederberger [15].

In case of dipolar polarization, to absorb microwaves irradiations, a substance structure must be partly negatively and partly positively charged. The dipolar polarization mechanism could be vividly exemplified when water is used. Under the microwave heating, water molecules try to orientate with the rapidly changing alternating electric field; thus heat is generated by the rotation, friction, and collision of molecules.

As for ionic migration, dissolved charged particles oscillate back and forth under microwave irradiation, and they also collide with neighboring molecules, thereby generating heat. As an example: if equal amounts of distilled water and tap water are heated by microwave irradiation, more rapid heating will occur for the tap water because of its ionic content in addition to the dipolar rotation of water molecules. Under microwave irradiation conditions, the ability of a specific substance to convert electromagnetic energy into heat is determined by the so-called loss tangent, tan δ. The high tan δ, the high microwaves absorbing ability a material has. The definition of the loss factor tan δ is: tan δ = ε''/ε. Where the dielectric constant (ε), describing the ability of molecules to be polarized by the electric field, and the dielectric loss (ε''), indicating the efficiency with which electromagnetic radiation is converted into heat. Commonly used organic solvents with high (tan δ > 0.5), medium (tan δ 0.1-0.5), and low microwave absorbing (tan δ < 0.1) are summarized in The first purpose built, mono-mode microwave reactor was introduced in the early 1990s by Prolabo, a French company. Today, the main manufacturers of small scale, performance. This instrument's high-end specifications enable the chemist to explore new areas and perform the latest of innovations in chemistry. A reliable and upgradeable platform that allows chemists to make great discoveries in less time. that is, solvents or reaction mixtures [16]. In addition, when moving to larger and larger batch reactors many of the genuine benefits of small scale microwave chemistry are in fact lost. In particular, the rapid heating and cooling profiles obtained on a small scale in high-power-density microwave reactors can often not be duplicated on a larger scale, leading to extended processing times.

As a consequence of these apparent limitations in scalability, recent efforts have focused on translating microwave batch reactions to a high temperature continuous flow format ("microwave to flow" paradigm). The main advantage of continuous flow processing is the ease with which reactions can be scaled (without the need for reoptimization) through the operation of multiple systems in parallel (numbering up, scaling out) or related strategies, thereby readily achieving production scale quantities [17].

In flow chemistry, a chemical reaction is run in a continuously flowing stream (Fig.

0.7).

It is a well-established technique for using at a large scale when manufacturing large quantities of a given material. Indeed, the short residence times associated with this type of reactors could avoid long contact between reactants and products and thus increase desired products selectivity. The typically short reaction times (in the order of a few minutes or even seconds) experienced in high-temperature microwave chemistry protocols form an ideal basis for continuous flow processing, in which short residence times within the flow device are essential to achieve efficient throughput. Most importantly perhaps, using standard micro or meso-fluidic reactor (Fig. 0.7 a and b) type flow instrumentation with coils, chips or capillary dimensions <1 mm, heat transfer to and from the reaction mixture is very fast owing to the high surface to volume ratio in these systems. This ensures very rapid heating and cooling rates and therefore eliminates the rationale to apply microwave heating, significantly simplifying the design and construction of flow reactors. The important characteristics in translating organic synthesis from microwave ü Flow processing also facilitates scaling up which is an important point taking into consideration that many of the biomass processes are still in the lab scale.

ü The utilization of flow processing technologies allows intensification of the chemical processes, thereby significantly contributing to simplify technologies.

ü Unlike batch processing, fixed-bed flow technologies do not require catalyst separation after reaction and regeneration, if required, is readily performed over the same catalytic bed.

ü Safety is increased, as flow operation allows continuous removal of gases, which may not interfere in the main catalytic process, however, gases build up in the reactor leading to increasing pressure and, potentially, new and uncontrolled processes in batch conditions.

ü Multi step reactions can be arranged in a continuous sequence. This can be especially beneficial if intermediate compounds are unstable, toxic, or sensitive to air, since they will exist only momentarily and in very small quantities.

Of course, the drawbacks of continuous flow should be recognized, for example:

l Dedicated equipment is needed for precise continuous dosing (e.g. pumps), connections, etc… l Start up and shut down procedures have to be established.

l Scale up of micro effects such as the high area to volume ratio is not possible and economy of scale may not apply. Typically, a scale up leads to a dedicated plant.

l Safety issues for the storage of reactive material still apply.

The majority of the commercially available laboratory scale high temperature and

Gamma-Valerolactone

Lignocellulose ethanol, acetic acid and sugar [18]. It could be found in many processed foods and beverages. The name of FF comes from the Latin word furfur, meaning bran, referring to its originally preparation from the co-heating of rice bran with dilute acid. FF is a colorless, transparent, oily liquid with a distinctive odor similar to benzaldehyde, but the color quickly changed when exposed to light and air, that's why commercial samples are often amber. FF is the most important derivative of the furanic compounds, and it has high reactive activity due to its special function groups: aldehyde group and a dienyl ether group. The fundamental information of FF was listed in Table 0.2 [19]. It can also be used to synthesize FF resin, furan resin, rubber vulcanization accelerator, rubber anti-aging agent and preservative. FF is mainly used in medicine, pesticides, veterinary drugs, food as well.

Another important building block is 5-hydroxymethylfurfural (HMF) (formula C6H6O3), is an organic compounds formed by the dehydration of certain sugars [20].

HMF is a white low-melting solid (although commercial samples are often yellow); which is highly soluble in both water and organic solvents. The molecule consists of a furan ring, containing both aldehyde and alcohol functional groups. The fundamental information of HMF was listed in Table 0.3 [21]. According to the Top Value Added of Energy, HMF is one of the top building block chemicals obtained from biomass [22]. The complex primary aromatic alcohol, an aldehyde, and a furan ring system can be transformed to 2,5-diformylfuran (DFF), 5hydroxymethylfuroic acid (HMFCA), 5-formyl-2-furancarboxylic acid (FFCA), or 2,5furandicarboxylic acid (FDCA) through oxidation reaction. FDCA is a monomer either to replace terephthalic acid in polyethylene terephthalate (PET) or to fabricate novel bioplastic materials, for example, polyethylene 2,5-furandicarboxylate (PEF) [23]. The annual market volume of FDCA is estimated at 200 kiloton in 2020 [24].

HMF hydrogenation can yield hydroxymethyl tetrahydrofurfural (HMTHF), 2,5dihydroxymethyl furan (DHMF), or 2,5-dihydroxymethyl tetrahydrofuran (DHMTHF).

The aldol condensation leads to the production of C7-C15 liquid alkanes, while rehydration gives levulinic and formic acid. It can also be used to synthesize a broad range of other value added compounds currently derived from petroleum [25].

Therefore, HMF has been called "a sleeping giant" [26], which means HMF with infinity prosperity. However, the fully utilization of HMF deserved more deep investigation to realize HMF industrialization. It has already been used in the production of resins [27], but it has much greater potential as an intermediate for other 2,5-disubstituted furan derivatives. Such derivatives can be subsequently used in the production of fine chemicals, pharmaceuticals, polymers (polyesters, polyamides, or polyurethanes), solvents, or liquid transportation fuels [28][29][30][31][32].

The production of HMF, from carbohydrates has been reviewed regularly [33]. The first one was published by Newth [34]. During the rest of the 20th century, a number of reviews appeared. Lewkowski's furan chemistry review, published in 2001, provides a comprehensive overview of the history of HMF synthesis and its fields of application [35]. In 2004, Moreau et al. updated this with a review on furan chemistry [36],

followed by updates in 2010 by Ton [37] and 2011 by Rosatella [38], Lima [39],

and Zakrzewska [40] reviewed the use of ionic liquids as green and benign solvents for selective sugar dehydration. A broader picture of biomass conversion into useful chemicals by Corma in 2007 [41] also included sugar dehydration and subsequent conversion of the furan products obtained in useful chemicals and polymers.

Therefore, the aim of this PhD work is to: 1) valorize FF and HMF into high valueadded products, such as furfural alcohol (FA), methyl levulinate (ML), gammavalerolactone (GVL), HMFCA and FDCA etc... Several key issues were identified in order to design processes greener than the current ones. Microwave irradiation has been chosen as the heating method to accelerate the reaction process in batch and continuous flow processes. Flow reactors, such as Pheonix, H-cube Pro as well as microwave continuous flow with micro-reactor, were also identified as interesting alternatives to improve the productivities of target compounds.

The first chapter (Chapter I) reports the conversion of FA to ML in continuous flow with efficient zeolite (HZSM-5-50) as catalyst.

The second chapter (Chapter II) reports our contribution on the conversion of ML to produce GVL using heterogeneous 5% Ru/C as catalyst in continuous flow using isopropanol as hydrogen donor.

The third chapter (Chapter III) reports HMF oxidation to HMFCA with silver oxide Ag2O as catalyst in both conventional heating and microwave heating method.

The forth chapter (Chapter IV) reports HMF oxidation to FDCA with 5% Ru/C in both microwave batch condition and microwave continuous flow condition.

The last chapter (Chapter V) mainly deals with the work we did starting for mucic acid) through dehydration to FDCA, and then use the under colbalt (II) acetate (Co(OAc)2 to synthesize FDCA based oligomers. Most importantly glycerol-FDCA oligomer has been synthesized and first reported.

In the last part, after the concluding remarks, the supporting information will be added.

Chapter 1. Alcoholysis of furfuryl alcohol to alkyl levulinates using zeolites in continuous flow

Abstract

The present work explores the catalytic activity of various zeolites for the production of methyl levulinates (ML) from hemicellulose derived furfuryl alcohol (FA)

and explores the performance of H-ZSM-5-50 zeolite in continuous flow alcoholysis.

ML yields up to 80 % were achieved at 170 °C (50 bar) using a high load (1.6 M FA) feed at 0.2 mL min -1 flow rate. Angelica lactones were produced in significant amounts as one of the side products, albeit in lower amounts in continuous flow mode. Catalyst deactivation occurred at high FA load through formation of pore blocking polyfurfuryl alcohols. The zeolites showed good re-usability after regeneration at 500 °C. The levulinates yields in ethanol and n-propanol were 20 % lower.

Introduction

Recent advances in the field of catalytic valorization of lignocellulose for the production of biofuels and chemicals aim to reach high yields of 5hydroxymethylfurfural (HMF) through isomerization and dehydration of glucose or oligomers, produced from cellulose hydrolysis [1,2]. Furfural (FF) can be produced from xylose, as the major hydrolysis product from hemicelluloses [3,4]. Levulinic acid (LA) is among the top target chemicals in lignocellulose biorefinery and it can be converted into various derivatives with several applications, particularly into alkyl levulinates (AL) as biofuel additive or precursor [5]. AL can be obtained via esterification of LA with various alcohols [6]. LA can be produced directly from various biomass sources in acidic aqueous media, but this process deals with the production of waste, a high cost for mineral acid recovery, humin formation and a rather difficult separation of the highly polar molecule LA [7,8]. Some promising results were obtained using ionic liquids and with the carbohydrate derived solvent γ-valerolactone (GVL), and by using solid acid catalysts, like demonstrated recently for H-ZSM-5 in aqueous THF [9]. Alcoholysis is a promising alternative to tackle these problems and opens ways for direct conversion of sugar monomers [10,11], like demonstrated very recently for ML starting from glucose using sulfated zirconia [12]. The alcoholysis processes can also be started from HMF (Scheme 1.1, pathway displayed in green), without the need for isolation of LA from aqueous product streams. Likewise, AL can also be produced via selective hydrogenation of FF to FA followed by conversion in various alcohols (ROH), as illustrated in Scheme 1.1 (pathway displayed in blue). This conversion allows to increase the overall yield of a levulinate production plant from lignocellulose by converting a minor co-product, FF or FA, into its main product. Various solid acid catalysts have been demonstrated to work pretty fine for the conversion of FA to AL, as recently reviewed for ethyl levulinate (EL) by Haider and co-workers [11]. The AL yield increases with higher reaction temperature, higher catalyst dosage, longer reaction time and lower FA load. Considerable time laps were observed between FA conversion and the formation of AL, as multiple reaction intermediates are formed in the alcoholysis [13]. A series of side products can be formed, originating from the reactants and intermediates. One particular side product is polyfurfuryl alcohol, which may cause pore blocking and occupation of the catalytic site. The formation of this oligomeric/polymeric side product can be suppressed by operating at moderate temperatures and reducing the reaction time. Most of the research studies on FA alcoholysis operated at temperatures between 110 and 140 °C [4,[14][15][16][17][18][20][21][22], with some exceptions at 80 °C [19]. Although strongly depending on the catalyst load and the alcohol chain length, most of the studies required at least 2 h to attain full conversion and typically 2-6 h to obtain high AL yields using 0.2-0.4 M feedstocks, with some exceptions in 60 min [18,21]. [22]. Sulfated zircona dioxide (Table 1.1, entry 2) and titanium dioxide are also catalyst candidates [14]. All the experiments reported in the literature on FA conversion to AL were performed in batch reactors. Haan and co-workers produced EL in semi-batch mode as a strategy to overcome polyfurfuryl alcohol side product formation, by feeding the FA slowly to the batch reactor [23]. To the best of our knowledge, only one recent study from 2017 reported the continuous flow alcoholysis of FA [24]. More research is required here, not only because of the already known advantages of continuous flow reactors such as better mass transfer, but also because it is likely that FA feedstocks will be produced by selective continuous flow hydrogenation of FF [25], because FF itself can also be produced in relatively high yields in continuous flow [26][27][28] and because it may lower the formation of polyfurfuryl alcohol side products and humin as well. The present study explores various zeolites for the conversion of FA to ML and studies the behavior in continuous flow using a catalytic bed packed with the best performing zeolite. The alcoholysis in ethanol and n-propanol was also demonstrated.

Experiment section

Catalyst synthesis and characterization

The commercial zeolite catalysts were calcined at 600 °C during 24 h prior to use in the catalytic experiments.

The Fe/H-ZSM-5-50 catalyst was prepared mechanochemically in dry conditions:

1.0 g H-ZSM-5-50 and 0.040 g FeCl2.4H2O (equivalent to 1.0 wt% Fe to reach a theoretical amount of 1.5 mol% Fe with respect to the FA load) were milled together in a planetary ball mill (Retsch 100) under optimized conditions (350 rpm, 10 min). The solids were recovered and heated under air atmosphere for 4 h at 400 °C.

The Cu/H-ZSM-5-50 catalyst was prepared similarly using 0.030 g CuCl2.2H2O.

Thermogravimetric (TGA) analysis was performed on a Perkin-Elmer thermal analyzer, by heating the sample up to 900 ºC at 10 ºC min -1 under dynamic air atmosphere (10 mL min -1 ). Powder X-ray diffraction patterns (XRD) were recorded on a Bruker D8advance X-ray diffractometer with Cu Kα radiation (0.154 nm) over the 2Ө range of 10-80 º.

Batch alcoholysis experiments

The experiments were carried out in a closed pressure-controlled vessel under continuous stirring, assisted by microwave irradiation using a CEM-DISCOVER model with PC control, using 50 mg catalyst in 3 mL of a 0.2 M FA solution in MeOH. When reaching the set temperature (150 °C, 14 bar) after 1-2 min, time was set to zero and the reactions proceeded for 5 min. After the reaction, the mixture was cooled to room temperature (3 min) and filtered on 0.22 µm syringe filters. The filtrate was used for GC-FID analysis. All results (conversion and yield) are expressed as molar percentages.

Continuous flow alcoholysis experiments

The experiments were carried out in a high-temperature high-pressure Phoenix Flow Reactor (ThalesNano TM , Hungary, see Note that zeolites may swell and that higher catalyst amounts, for this cartridge type, may lead to operational problems. The cartridge was tightened with appropriate membrane films and placed in the reactor module. The total flow through volume (including feed, reactor and product sections) was 14 mL. First, pure MeOH, EtOH or n-PrOH was pumped through the system and then the feed was changed to the FA feedstock. The flow was continued until the temperature (90-190 °C) and hydrodynamic pressurization (0-50 bar) of the reactor module were reached. Then, in function of the flow rate (0.2-0.5 mL min -1 ), the reaction proceeded during a certain time (12-30 min.) before collecting the first sample (sample at time = 0 min). Further samples were collected after regular time intervals. For recycle experiments, the catalysts were recovered by rinsing and washing with MeOH, centrifugation (4000 rpm, 10 min, 20 °C), drying at 100 °C and finally calcination at 500 or 800 °C, prior to reutilization in the next experiment.

Product analysis

The identification of the compounds was performed by comparison of the retention times with pure standards and by GC/MS analysis. The solvent delay time was 3.00 min. The retention times of 2-methoxy-2-methylfuran (MMF), furfuryl alcohol (FA), 5-methyl-2(3H)-furanone (α-angelica lactone, AAL), 5-methyl-2(5H)-furanone (βangelica lactone, BAL), methyl levulinate (ML) and n-decane were 9.2, 9.8, 10.0, 11.7, 13.7 and 15.6 min, respectively. The response factors (RF) of FA, ML and γvalerolactone (GVL) relative to a fixed concentration (5.0 mg mL -1 ) of n-decane as internal standard were experimentally determined at 0.619, 0.415 and 0.549, respectively. The linear regression coefficients of the calibrations were high in all cases (r 2 > 0.99). The RF for angelica-lactones were calculated according to the Effective Carbon Number (ECN) method [29], based on the RF and ECN factor of GVL (3.75) and the ECN factor of α/β-angelica lactone (3.65). The yield and conversion in batch and continuous flow were calculated according to eqs. ( 1) -( 4) whereas the selectivity) was determined using eq. ( 5):

!"#$% (%) = +,$ -./0123 +,$ 4563678 × 100 (<=>?ℎ) (1)
!"#$% (%) = AB -./0123 ACD EFF0 × 100 (A,G>"GH,HI J$,K)

(2)

A,GL#MI",G (%) = [+,$ 4563678 -+,$ E6578 ] +,$ E6578 × 100 (<=>?ℎ), (3)
A,GL#MI",G (%) = [ACD 4563678 -ACD E6578 ] ACD 4563678 × 100 (A,G>"GH,HI J$,K) (4)
R#$#?>"L">S (%) = +,$ -./0123 A,GL#MI",G × 100 (<=>?ℎ =G% ?,G>"GH,HI J$,K)

CFA and CP are the concentrations of FA and alcoholysis product (mol mL -1 ). The total volume in the system of the continuous flow experiments was assumed to remain constant during the experiments (no evaporation loss). All results (conversion and yield) are expressed as molar percentages. The metal-based weight hourly space velocity (WHSV) was calculated using eq. ( 6): Thus, the difference between the amounts of PY(total acidity) and DMPY (Bronsted acidity) adsorbed, should correspond to Lewis acidity in the materials.

TURV (W W XY ℎ XY ) = [C$,K M=># (Z[ Z"G XY ) × 0.06 × CD ?,G?#G>M=>",G (+) × 98.1 (W Z,$ XY ) ] A=>=$SI> Z=II (W) (6
The nitrogen adsorption-desorption isotherms at -196 °C of the zeolites were all type IV. The corresponding total specific surface areas (TSSA), average pore size (APS) and total pore volume (TPV) are shown in Table 1.2. The H-Y zeolites showed substantial higher TPV as compared with the H-ZSM zeolites. The proportions of pore volume attributed to meso/macropores were 63, 50, 49 and 57 % for H-ZSM-5-30, H-ZSM-5-50, H-Y-5.2 and H-Y-60, respectively. It's important to mention that H-ZSM-5-50 showed higher TSSA than H-ZSM-5-30 (400 vs 350), it indicated more total specific surface areas contributed to higher catalytic performance. What's more, the surface acidity was studied using pyridine and 2,6-dimethylpyridine as probe molecules for Brønsted + Lewis and Brønsted acid sites only, respectively (Table 1.

3). The values

obtained for H-Y-5.2 and H-Y-60 (72 and 70 % Brønsted acidity, respectively) agree fairly well with previously reported values (77 and 69 %). HY type zeolites showed more Brønsted sites than HZSM types zeolites, 70, 72% than 19, 20%. However, total acidity in HZSM zeolites showed more percentages than HY zeolites, which attributed to more Lewis acidity (192, 162 vs. 39 and 12). In the following optimization reaction, both surface area and acidic properties demonstrated synergetic effect, which attributed to catalytic performance. Whereas the blank experiment (no catalyst) resulted in 18 % conversion without any significant ML formation (< 0.5 %), all the zeolites gave conversions near 100 % with high ML yields after only 5 min microwave irradiation at 150 °C (Fig. 1.

1).

Whereas reaction intermediates such as 2-methoxy-2-methylfuran (MMF), 5,5-dimethoxy-2-pentanone and others were only present in small amounts (6-13 %) for H-ZSM-5 zeolites, higher amounts (57-64 %) remained with the H-Y zeolites. The exact structure of the other reaction intermediates remained not fully clear from the GC/MS analysis, but their mass spectra clearly indicated structures equal or similar to those reported in the literature [13][14][15]. Although previously reported as reaction intermediates [15], angelica lactones and particularly b-angelica lactone in the present study were produced as side products in significant amounts. Their yield (33-34 %) was especially high when using H-ZSM-5 zeolites as the catalyst. According to the H-ZSM-5 catalytic activity reported by Xin et al. [30] based on the mechanistic insights reported by Karwa et al. [31], this side product arises via dehydration of LA to 5-hydroxy-γvalerolactone, which reacts further to α-angelica lactone (AAL), which can further isomerize to β-angelica lactone (BAL). LA is no reaction intermediate, it is a side product resulting from the hydrolysis of levulinate or reaction intermediates within the acidic zeolite itself. Small amounts of water residues in the feed, adsorbed on the zeolite surface or formed as intermediate during the reaction itself can result in important changes in selectivity from levulinate to LA [13,21]. The main product, ML, was produced in yields between 54-60 and 30-37 % for H-ZSM-5 and H-Y zeolites, respectively. This substantial difference between both type of zeolites is mainly related to the lower acidity for H-Y as compared to H-ZSM-5

zeolites, as recently reported by Lima's research group [32]. Although H-ZSM-5-30 is slightly more acidic than H-ZSM-5-50, 6 % lower ML yield was observed with the former catalyst. Other characteristics such as specific surface area, pore volume and pore shape also may play a role. H-ZSM-5-50 exhibits higher total specific surface area than H-ZSM-5-30 (400 vs. 350 m 2 g -1 ) and offers higher external surface area (100 vs. 70 m 2 g -1 ), which may explain this difference in ML yield. Another important difference between both is that H-ZSM-5-30 is more disordered and contains pores in the 24-40 nm range whereas H-ZSM-5-50 contains more micropores in the 2-5 nm range. H-ZSM-5-50 is also more hydrophobic as it contains less Al and therefore it may adsorb less water or exhibit better levulinate desorption. Anyhow, the H-ZSM-5-50 zeolite was the most efficient catalyst for conversion into ML and this zeolite was used for further experiments. Taken the positive effects observed from copper chloride, iron chloride and iron oxide nanoparticles for the production of AL [18,21,22], H-ZSM-5-50 was modified by depositing CuCl2 and FeCl2 particles under mechanochemical conditions followed by a calcination at 400 °C. Slightly lower ML yields (58 %) were observed for Cu/HZSM and slightly higher for Fe/HZSM-5-50 (63 %). This difference was rather small and therefore commercial H-ZSM-5-50 as such was further used for the experiments in continuous flow mode. Continuous flow chemistry generally offers a better control and allows a higher flexibility in reaction conditions, which typically require optimization to improve the conversion and selectivity. First, the effect of the hydrodynamic pressure was studied during 2-3 h continuous flow alcoholysis using a 0.2 M FA feedstock in MeOH. The results (Fig. 1.2) show that ca. 12 % more ML was produced, 5% less AL and 8 % less reaction intermediates when the pressurization was set at 50 bar instead of 0 bar.

Effect of reaction pressure for the production of ML

Effect of FA concentration with flow rate for the production of ML

To further optimize the reaction, feedstocks with increasing loads of FA (0.1-1.6 M) were tested at different flow rates (0.2-0.5 mL min -1 ). The results show that conversions stayed close to 100 % at FA concentrations from 0.1 to 0.8 M whereas with 1.6 M feedstocks the conversion started to drop with higher flow rate (Fig.

1.3 a).
Surprisingly, at least at low flow rate (0.2 mL min -1 ), the yield to the target product ML increased when using higher FA loads (Fig. 1.3 b), in contrast with the findings in the literature. This effect tended to be less pronounced when moving to high flow rate (0.5 mL min -1 ). Increasing flow rates lead to slightly lower ML yields and higher BAL yields Based on the literature [30,31], the higher angelica lactones yield resulted from the hydrolysis of levulinate or reaction intermediates to levulinic acid, followed by dehydration to 5-hydroxy-γ-valerolactone. The reason why its yield increases with higher flow rate remains not fully clear, but it may be related to water residues present in the alcohol feedstocks. At high FA load (1.6 M), however, the yield of both products decreased drastically. Instead, the reaction intermediate MMF ( WHSV (g g -1 h -1 ) is the mass feed rate of FA (g h -1 ) divided by the amount of catalysts employed alcohol excess of 24 (MeOH-FA) [14].

Effect of reaction temperature for the production of ML

Finally, the effect of the reaction temperature was studied (Fig. 1.5) using a high load feed solution (1.6 M). The results show that temperature ca. 150 °C is required to fully convert the FA into ML (only small amount of reaction intermediates left). The yield of ML increased further at 170 °C, but significant amounts of polyfurfuryl alcohols started to form at this higher temperature. At 90 °C, the yield of β-angelica lactone (BAL) was low but then started to increase with increasing temperature, because the isomerization of α-angelica lactone (AAL) to BAL was favored at higher temperature, in agreement with the literature [30]. At temperatures ≥ 150 °C the BAL yields dropped again.

Effect of the alcohol chain length for the production of AL

Finally, the continuous flow alcoholysis using H-ZSM-5-50 was also tested in ethanol and n-propanol to study the effect of the alcohol chain length on the catalytic activity (Table 1.2). The alkyl levulinates yield dropped 19-20 %, while the angelica lactones yield remained the same in ethanol (21-23 %) while it dropped to 8 % in npropanol. In both experiments, more than 95 % of the angelica lactones consisted of BAL. Instead, some other weak signals appeared of unidentified peaks appeared in the chromatograms of the alcoholysis product in ethanol and n-propanol. The results of the present study show the high potential of H-ZSM-5 zeolites for the alcoholysis of furfuryl alcohol in methanol. FA feedstocks with high load (up to 1.6 M) were efficiently converted in continuous flow mode at 170 °C, but were susceptible to catalyst deactivation due to polyfurfuryl alcohol formation. To suppress the formation of this undesired side product, apart from using lower FA loads, lower temperatures should be employed, in compromise with the yield to MF. Further catalyst stability studies using 0.5-1.5 M feedstocks during prolonged times are required to establish the optimal FA load, flow rate and reaction temperature. Although the H-ZSM-5 zeolite showed good catalyst regeneration capacity by thermal treatment, further research is highly desired to adapt the zeolite synthesis procedure or to include post-synthesis methods to increase their activity, allowing to operate at temperatures lower than 170 °C. β-angelica lactone (BAL) was the only one major side product produced. BAL was used as a promising biofuel precursor via C-C coupling and subsequent hydrogenation [30]. Recently, angelica lactone isomers were reviewed as biomass platform chemicals and as high-value end-products in various food applications [33]. They are also naturally occurring compounds, particularly present in grapes, soybean, etc. Alcoholysis in higher alcohols would be preferred to enable an efficient separation of the lactones from the levulinates (ML and BAL have boiling points ca. 196 and 191 °C, respectively). In view of minimizing the lactone yield and maximizing the levulinate yield for large-scale biofuel applications, n-propanol would be more suitable as the results indicate higher selectivity to levulinate in n-propanol compared to methanol and ethanol. Further research on how to adapt the porosity and surface acidity landscape or on exploring other zeolite types is highly desired to develop more active and selective zeolites for alcoholysis in higher alcohols. Although Brønsted sites being the effective catalytic site [21], positive effects were demonstrated by introducing Brønsted sites in an integrated manner along with Lewis acid sites [34].

The results in the present study also suggest this, as the H-Y zeolites showed much poorer performance, despite having higher contents in Brønsted sites, but lower contents in Lewis acid sites [33].

Plausible mechanism

According to the literatures, multiple pathways have been proposed for the formation of ML from FA. In our case, we proposed a plausible mechanism concerning MMF as the key intermediate (Fig. 1.9) including some other key intermediates, which can be detected from GC-MS in our case, such as BAL, AAL and 5,5-dimethoxy-2pentanone (DMOP). This routes started from FA to form intermediate B under acidic catalytic condition and seems more reasonable as lower energy was needed for the formation of alkoxymethylfuran [36]

Conclusion

Two FAU zeolites and two MFI zeolites were tested for the catalytic alcoholysis of 0.2 M furfuryl alcohol in methanol, yielding methyl levulinate (ML), α-angelica lactone (AAL) as the side product from levulinic acid dehydration and β-angelica lactone (BAL) as the corresponding isomerization product, along with some reaction intermediates. H-ZSM-5-50 zeolite (SiO2/Al2O3 molar ratio 50) showed the best activity with 60 % ML and 33 % BAL yields after 5 min microwave irradiation at 150 °C. A modified zeolite catalyst (Fe/H-ZSM-5-50), resulted in higher ML yield

O OH O OH 2 O OMe H H 2 O MeOH H H-ZSM-5-50 CH 2 O MeOH FA O B O O O O BAL AAL MeOH hydrogen shift O O O DMOP MMF A C CH 2 O H 2 O O H 2 O H 2 O D -H O HO E F O HO H 3 CO G O O O ML O O OH H MeOH O O O P * electron shift
(63 %) and lower BAL yield (28 %) but the improved yields did not justify the impact of added iron. Using a catalytic bed packed with H-ZSM-5-50 catalyst in continuous flow, higher selectivity to ML and lower selectivity to angelica lactones was observed, at least for flow rates up to 0.4 mL min -1 . Interestingly, at 0.

Introduction

The development of efficient processes to convert biomass resource into liquid fuels and valuable chemicals is a key research area in the next few decades [1][2][3][4][5][6][7][8]. γ-Valerolactone (GVL) as one of the most appealing molecules from biomass resource shows a very promising versatile intermediate for production of fuel additives, a renewable solvent, food ingredient, liquid fuel, and ideal precursor for the production of more valuable chemicals [9,10] in a wide range of applications (e.g., cutting oils and brake fluids) [11]. Due to very high interest towards GVL, its efficient production is currently a topic of intensive research.

The production of GVL from biomass has received extensive research interests.

Starting from cellulose and hemicellulose [8], successive hydrolysis, dehydration/rehydration and then hydrogenation furnished GVL. The use of intermediates such as carbohydrate [12,13], 5-hydroxymethylfurfural (HMF) and furfuryl alcohol (FA) [14] was also developed efficiently for the production of GVL (Scheme 1). The hydrogenation of levulinic acid (LA) to GVL using heterogeneous and homogeneous catalysts in combination with molecular hydrogen has been studied extensively [15,16]. Unfortunately, the synthesis of LA in acidic aqueous media has got some drawbacks: production of a large amount of waste, a high cost for mineral acid recovery, humin formation and a rather difficult separation of the highly polar molecule LA [17,18]. Comparatively, the hydrogenation of alkyl levulinates (AL) to GVL is more attractive because AL was obtained in better yield with a more efficient separation process. Thus, it is meaningful to establish a new integrated route to produce GVL from hemicellulose via successive formation of xylose, furfural, FA and AL. Heterogeneous Zr-based catalysts, such as ZrO2 [26], hydrated zirconia (ZrO(OH)2•xH2O) [27] and Zr-beta [28] having amphoteric nature permitted to produce GVL with good result under high temperature (around 200 °C) .

Continuous flow chemistry as alternative technology offers significant processing advantages as has been discussed in general introduction part [29][30][31][32][33]. In the context to develop a new green process, few works on the production of GVL in continuous flow have been reported [19,30]. Starting from LA, the use of heterogeneous 5% Ru/C in the presence of sulfonated phosphine as ligand and hydrogen under 10 bar at 140 °C permitted the production of GVL in continuous flow with a high productivity (0.8 mol g -1 h -1 ) [19]. In parallel, our group described a high GVL productivity via CTH with Zrbased catalyst (0.0923 mol g -1 h -1 ) starting from methyl levulinate (ML) in the presence of functional metal organic framework at elevated temperature (240 o C) in continuous flow [30]. To date, an outstanding of the continuous flow catalytic transfer hydrogen process to produce GVL from AL is requested. In this context, the present work tested some commercial catalyst: 5%Ru/C, 5%Pd/C, 10%Pt/C and 5% Ru/Al2O3 for a continuous flow conversion of biosourced ML to GVL using CTH process.

Experiment section

Continuous flow experiments

The experiments were carried out in a high-temperature high-pressure H-Cube Identical procedure was done starting from ethyl levulinate (EL) and butyl levulinate (BL). The yield and conversion in continuous flow were calculated according to eqs. ( 1) -( 2):

Product analysis

(1)

!"#$% (%) = AB -./0123 A+[ EFF0 × 100 (A,G>"GH,HI J$,K) (2)
A,GL#MI",G (%) = [A+[ 4563678 -A+[ E6578 ] A+[ 4563678 × 100 (A,G>"GH,HI J$,K)
CML and CP are the concentrations of ML and product (mol mL -1 ). The total volume in the system of the continuous flow experiments was assumed to remain constant during the experiments (no evaporation loss). All results (conversion and yield) are expressed as molar percentages. The metal-based catalyst productivity (Z,$(`V[) W(Z#>=$) XY ℎ XY ) was calculated using eq. ( 3):

(3)

BM,%H?>"L">S (Z,$ W XY ℎ XY ) = [C$,K M=># (Z[ Z"G XY ) × 0.06 × +[ ?,G?#G>M=>",G (+) × ! "#%(`V[) ] A=>=$SI> Z#>=$ Z=II (W)

Results and discussion

Catalyst screening

Continuous flow chemistry generally offers a better control and allows a higher flexibility in reaction conditions, which typically require optimization to improve the conversion and selectivity. 2-PrOH has been reported as an active hydrogen donor, which could provide good conversion and product selectivity when compared with other primary alcohols such as methanol, ethanol, 1-propanol [45,46]. Thus, 2-PrOH was selected as hydrogen donor for CTH of ML under continuous flow conditions.

Starting from ML (0.2 M) in 2-PrOH at 130 °C, four commercial catalysts 5%Pd/C, 5%Ru/C, 5%Ru/Al2O3 and 10%Pt/C were tested for the hydrogenation and lactonization aiming to reach high GVL yields (Fig. 2.1). The blank experiment (activated carbon as catalyst) did not give any ML conversion whatever the residence time (0-120 min). However, when the tested noble metals were supported on activated carbon GVL was obtained in moderate to good yield. In our hands, the highest GVL yield (89%) was achieved in the presence of 5%Pd/C with 10% higher than that with 5% Ru/C. Nevertheless, 5% Ru/C was used for the next step of our optimization since this catalyst permitted to have the highest GVL productivity (0.2 mol g -1 h -1 ). This result was in accordance with that reported in the literature [47].

Effect of reaction temperature for the production of GVL

In a first step, the effect of reaction temperature was studied using ML (0.2 M) at 20 bar in a continuous flow system (0.4 mL min -1 ) (Fig. and unidentified side compounds with a full conversion. With the increase of reaction temperature from 100 °C to 150 °C, the GVL yield increase from 30% to 85% and productivity (Pr) from 0.084 to 0.254, respectively. It was obvious that the MHP yield decrease from 60% to 8% with the increase of temperature because the lactonization of MHP to GVL was favored at higher temperature [48]. Whatever the temperature used, the amount of side products was almost similar (3%). Among them, isopropyl 4hydroxypentanoate obtained by transesterification between ML and 2-PrOH was identified. Besides, the 5%Ru/C catalyst showed an excellent catalytic stability at the temperatures investigated. Due to the maximum temperature limitation of H-Cube ProTM Flow Reactor, higher reaction temperature than 150 ºC was not available.

Effect of reaction pressure for the production of GVL

The effect of hydrodynamic pressure (20, 40, 60 bar) at 150 °C was also investigated for 120 min, which corresponded to the processing capacity 58 mL (120 min × 0.4 mL min -1 + 10 mL) in continuous flow (Fig. 2.3). Whatever the pressure used, full conversion of ML was obtained. The yield of GVL was improved ca. 7% with the increase of reaction pressure from 20 bar to 40 bar and the yield of MHP decreased 5%.

Effect of flow rate for the production of GVL

The effect of flow rate (0.2, 0.4 and 0.8 mL min -1 ) on GVL and MHP yields at 150 °C and 40 bar in the presence of 5% Ru/C was studied and compared at different processing capacity (10 mL to 58 mL) (Fig. 2.4). Whatever the flow rate used, ML was

Effect of ML concentration for the production of GVL

With the perspectives to obtain a higher productivity and to have a solvent economy, variation of ML concentration was studied. In the present work, ML feeding rate was kept constant (0.16 mmol min -1 ) and ML concentration was increased while flow rate was decreased (Fig. 2.5). Although the ML feeding rate was constant the conversion of ML, yields of GVL and MHP were different between 0.2 mL min -1 and 0.4-0.8 mL min - 1 . With a low flow rate (0.2 mL min -1 ), the conversion of ML was lower than that obtained with a flow rate of 0.4-0.8 mL min -1 (90% vs 100%). Similar observations were observed with the GVL yields (80% vs. 87-90%) and the MHP yields (6% vs. 9%).

Whatever the flow rate, these experiments showed that the target GVL and the acyclic MHP were obtained as the main chemicals and as the minor chemicals, respectively.

The best results obtained using 0.8 mL min -1 and ML (0.2 M) can be explained by a short residence time and low concentration of starting material. The reactant adsorption on catalyst surface as well as the desorption of the target product were more efficient and favor high mass transfer rate. With ML concentration (0.2 M and 0.4 M), almost the same GVL productivity (ca. 0.55) because similar ML conversion and GVL yield was achieved. From the point of saving solvent, higher feedstock concentration could be a better choice. ML feeding rate was increased to 0.32 mmol min -1 (ML 0.4 M and flow rate 0.8 mL min -1 ). The conversion of ML (98%) and the yield of GVL (85%) with ca.11% MHP yield were obtained and the productivity (0.99 mol g -1 h -1 ) was remarkably superior to several systems in previous report ( 12 bar) permitted to have a better productivity (2.25 mol g -1 h -1 vs. 1.12 mol g -1 h -1 ) (Table 2.1, entries 3 and 4). Due to practical considerations, microwave-assisted hydrogenation of LA and AL was studied in batch reactor and not in continuous flow reactor. In this context, the use of 2-PrOH and LA as well as ML permitted to produce GVL with a good productivity (> 2 mol g -1 h -1 ) (Table 2.1, entries 5 and 6).

Unfortunately, when the alkyl chain was higher than one carbon atom the productivity decreased drastically (Table 2.1, entries 7 and 8). Starting from LA in the presence of 2-BuOH the microwave-assisted organic synthesis did not furnished GVL with good yield but the productivity was significant (1.92 mol g -1 h -1 ) (Table 2.1, entry 9). In accordance with literature, microwave-assisted reaction permitted to have a short reaction time (30 minutes). The main problem of this process was the formation of side compounds, which limit their further utilization. For continuous flow as alternative technology, the production of GVL was studied using hydrogenation and CTH processes. Whatever the pressure used, LA furnished GVL in good to excellent yields with a productivity lower than 0.9 mol g -1 h -1 (Table 2.1, entries 10-12). Starting from AL such as BL in the presence of primary alcohol (1-BuOH) as hydrogen donor, the productivity decreased ten times (0.085 mol g -1 h -1 vs. 0.832 mol g -1 h -1 ) (Table 2.1, entry 13). Our optimized process (ML (0.4 M), 5%Ru/C (330 mg), 2-PrOH, 150 °C, 40 bar, 0.8 mL min -1 ) furnished the target lactone in 83% yield with a productivity of 0.99 mol g -1 h -1 , which is the best reported in the literature for a continuous flow process.

Effect of the nature of the alkyl levulinate (AL) for the production of GVL

The nature of the alcohol was investigated (Table 2.2) under optimized conditions (ML (0.4 M), 5% Ru/C, 2-PrOH, 150 °C, 40 bar, 0.8 mL min -1 ). With the increase of carbon atoms (from C1 to C4) (Table 2.2, entries 1-3), the yield of GVL decreased from 85% to 31% while the intermediate AHP yield increased from 13% to 63%. As a consequence, the productivity decreased from 0.99 to 0.25 mol g -1 h -1 . In accordance with the literature, the subsequent reduction of the ketone to the corresponding alcohol and the lactonization were facilitated with an AL having a little molecular weight [48].

When the carboxylic acid LA was used as starting material, GVL was obtained in 59% with a low conversion (67%) but the productivity was similar to that starting from EL (ca. 0.5 mol g -1 h -1 ) (Table 2.2, entry 4).

Stability of the catalyst and recycling

Further catalyst stability experiments were performed using our optimized conditions. The conversion remained stable over 9 hours at least, the yields of GVL and MHP were ca.83% and 10 %, respectively (Fig. 2.6). In our lab-scale process, the stability of 5% Ru/C catalyst was good.

Conclusion

This works reports a new efficient process using commercial heterogeneous Optimum yields were obtained under microwave batch conditions, exhibiting quantitative HMF conversion with 97 % HMFCA yield in only 24 min reaction (30 W).

Continuous flow approach was also investigated using the optimum condition, displaying 36% HMF conversion and 33% HMFCA yield with no oxidizing agent.

Reusability studies revealed catalyst deactivation, most likely associated with the reduction of silver oxide to metallic silver and nanoparticles sintering after the catalytic reaction.

Introduction

5-Hydroxymethyfurfural (HMF), a renewable resource obtained from lignocellulosic biomass (LCB) derived molecules, including D-glucose or D-fructose, was considered as one of the most relevant bio-based chemicals [1,2]. Its high reactivity due to the presence of active groups such as primary hydroxyl and formyl makes HMF a promising candidate to be upgraded into a variety of useful intermediates [3,4]. HMF could be transformed into 2,5-bis (hydroxymethyl)furan (BHMF) and 2,5dimethylfuran (DMF) via selective hydrogenation. Comparably, the selective oxidation of HMF could furnish 2,5-diformethylfuran (DFF), 5-hydroxymethyl-2furancarboxylic acid (HMFCA), 5-formyl-2-furancarboxylic acid (FFCA) and 2,5furandicarboxylic acid (FDCA) (Scheme 3.1). A less known oxidative product, HMFCA, derived from the oxidation of the formyl group in HMF, is a highly relevant compound in the production of furanic polyesters, that can replace those obtained from fossil sources [5], as well as for the synthesis of an interleukin inhibitor [6]. In addition,

HMFCA was reported to have antitumoral activities [7].

However, the selective oxidation of HMF is generally challenging due to the relatively easy over-oxidation to FDCA. Two research groups reported the synthesis of HMFCA from HMF in good yields via the Cannizzaro reaction in basic conditions [8,9]. Nonetheless, the theoretical selectivity of the desired product was 50% because of the formation of an equal molar by-product (BHMF). Various noble metal catalysts were developed for HMFCA synthesis. Most noticeably, Zhang et al. reported that HMF could be selectively oxidized to HMFCA in toluene within 3 h using an immobilized molybdenum acetylacetonate complex, with a yield of ca. 87% [10].

Recently, Han and co-workers reported a selective and mild photocatalytic approach for the production of carboxyl compounds over Au/TiO2, where HMFCA was synthesized from HMF under UV and visible light in aqueous Na2CO3 solution (90-95% yields) [11]. The use of solvents including toluene, results into nonenvironmentally-friendly processes. Furthermore, the majority of noble metal catalysts such as Pt, Au, Pd, Ru, often result in low HMFCA selectivity for over oxidation to FDCA, hence giving poor product yields [12][13][14]. Therefore, it is highly important to find alternative routes employing environmentally sound and affordable metal catalyst with high HMFCA selectivity and greener reaction credentials.

Silver has attracted recent extensive attention in catalysis. Grunwaldt et al.

developed a new method to produce HMFCA from HMF using Ag/ZrO2 as catalyst. In their work, a high selectivity toward HMFCA (≥98%) could be achieved under optimized reaction conditions [15]. Ag nanoparticle catalysts usually exhibit sizedependent, surface and macroscopic quantum tunneling effects (plasmonic-related) in catalytic applications [16]. However, Ag NPs also possess some disadvantages due to their easy aggregation by Ostwald ripening, especially at high temperatures. A stabilizer or capping agent is usually needed to prevent such aggregation. Silver oxide (Ag2O) has also been employed as a mild oxidizing agent in organic chemistry, particularly for the efficient mild oxidation of aldehydes to carboxylic acids. Silver oxide may then be a potentially useful catalyst for the proposed HMF to HMFCA oxidation. Scheme 3.1. HMF and its value-added derivatives.

Hydrogen peroxide has been successfully employed in biomass conversion as oxidizing agent due to its affordable price and safe storage as oxidizing agent [17].

Several examples have been described in this regard including the production of gluconic acid from D-glucose [18], synthesis of succinic acid from levulinic acid [19] and oxidation of furfural into maleic or fumaric acid [20]. Nonetheless, the use of H2O2 also possesses some drawbacks related to its facile decomposition in the presence of base or metal catalysts, thus leading to uncontrolled selectivity [21]. Commercial H2O2 is thus presented in acid media in order to suppress its decomposition. Conversion of HMF to HMFCA requires an alkali environment to maintain fast reaction rates. Hence, finding the optimum catalytic system for general oxidation reactions with hydrogen peroxide, and specially oxidation of HMF is still a challenge for the scientific community.

Microwave technologies have been demonstrated to be an efficient tool to improve reaction yields and product selectivities [22][23][24][25][26][27]. Among the advantages of microwave heating, uniform temperatures, fast heating rates and easy reaction control can be highlighted [28,29]. A recent study recently compared the energy efficiency between conventional oil bath heating and microwave heating at laboratory scale. Such investigations concluded that energy savings of up to 85-fold could be achieved for some chemical reaction by using microwaves as energy input [29]. Due to the aforementioned advantages, microwave irradiation was employed for the development of the present work.

In addition, taking into account the advantages of flow chemistry (efficient energy utilization, easy scale-up and facile purification, among others), more efforts are required in this area since it could provide a more appealing route for the industrial production of HMFCA.

In this study, aqueous H2O2 was investigated as oxidizing agent for HMF to HMFCA using commercial Ag2O as catalyst. Microwave-assisted methodologies were studied and compared with conventional heating methods.

Experiment section

Materials, solvents and reagents

Water for HPLC, HMF (≥ 99.5%) and Ag2O were purchased from Acros Organic and further used without purification. Silver (II) oxide (AgO) was purchased from CHIMICA and further used without purification. Silver chloride (AgCl) was purchased from STREM CHEMICALS and further used without purification. HMFCA, FFCA, DFF, FDCA were all purchased from Sigma-ALDRICH. Other reagents such as sodium carbonate (Na2CO3) were purchased from Honeywell. Sodium bicarbonate (NaHCO3), sodium hydroxide (NaOH), were purchased from VWR CHEMICALS Hydrogen peroxide 30 wt% solution was purchased from CHEM-LAB.

Catalyst characterization

A post-characterization analysis was performed by X-ray Diffraction (XRD), Xray Photoelectronic Spectroscopy (XPS), Scanning Electronic Microscopy (SEM)mapping and Transmission Electronic Microscopy (TEM) measurements.

XRD analysis was performed in the Bruker D8 Advance Diffractometer with the LynxEye detector. The XRD patterns were recorded in a 2θ scan range from 10° to 70°.

Bruker Diffrac-plus Eva software, supported by Power Diffraction File database, was used for phase identification.

XPS experiments were accomplished in an ultrahigh vacuum multipurpose surface analysis instrument SpecsTM. The samples were evacuated overnight under vacuum (10 -6 Torr) and subsequently, measurements were performed at room temperature using a conventional X-ray source with a Phoibos 150-MCD energy detector. XPS spectra were analyzed employing the XPS CASA software.

In addition, SEM-EDX images were acquired in the JEOL-SEM JSM-7800 LV scanning microscope. To observe size and shape of the particles, Transmission electron microscopy (TEM) was performed on a JEOL 2010 operated at an acceleration voltage of 200 kV and with a FEI Tecnai G2 system, equipped with a CCD ("charge coupling device") camera. Samples were ground and then suspended in ethanol. One drop of this suspension was put on a holey-carbon coated copper grid of 300 mesh and left to air to dry.

Catalytic experiments

Conventional heating-assisted reaction was carried out at 90 ºC in an oil bath.

Typically, aqueous H2O2 (8.1 wt%) was added with a flow rate of 2 mL min -1 to a mixture of HMF (37.8 mg, 0. of HMF and FFCA, HMFCA, DFF and FDCA were experimentally determined at 1.39×10 -5 , 1.29×10 -5 , 2.19×10 -5 , 1.43×10 -5 and 1.87×10 -5 respectively. The linear regression coefficients of the calibrations were high in all cases (r 2 > 0.99).

The yield and conversion were calculated according to equations ( 1) and ( 2):

!"#$% (%) = +, -./0123
+456 7880 × 100

(1)

<=>?#@A"=> (%) = [+456 CDE3EFG H+456 7EDFG ] +456 CDE3EFG × 100 (2)
CHMF and CP are the concentrations of HMF and product (mg mL -1 ), respectively.

All results (conversion and yield) are expressed as molar percentages.

Results and discussion

Catalyst and base screening

The catalysts and bases played an important role in HMF oxidation. The effect of different silver compounds such as AgNO3, AgCl, Ag2O and AgO with Na2CO3 were examined (Table 3.1, entries 1-5). Different bases including NaOH, Na2CO3 and NaHCO3 were also examined (Table 3.1, entries 6-8). All reactions were performed with a continuous adding (0.2 mL min -1 flow rate) of 8.1 wt % H2O2 aqueous during 1 h.

By using different silver compounds as catalyst, only HMFCA was detected, with no presence of other products such as DFF, FFCA and FDCA (Table 3.1, entries 1-5).

Such results pointed out that Ag cannot further oxidize HMFCA into FFCA and FDCA as compared to other noble metals including Ru, Pd, Pt and Au [30]. The blank experiment, performed in absence of catalyst, permitted to obtain a HMF conversion of 92% but very low HMFCA selectivity (13%) (Table 3.1, entry 1). These findings indicate that HMF could not be converted to HMFCA without an efficient catalytic system. It is also worth to mention that, as reported in the literature, HMF is unstable in basic solution, since it undergoes polymerization to dark solid products (humins) [31], being the carbon balance ca. 20% in the absence of catalyst. Comparably, a 94%, 92%, 93% and 94% carbon balance was observed using different types of catalysts (Table 3.1, entries 2-5). Under the same Ag + amount (HMF/Ag + =1: 0.4) with different anion species compounds, the reaction gave rise to different HMFCA yields: AgNO3 vs.

AgCl vs. Ag2O, (74% vs. 58% vs. 80% respectively). The aforementioned three compounds also provided a similar high HMFCA selectivity (92% vs. 87% vs. 92% for AgNO3, AgCl and Ag2O, respectively). In order to compare the results with Ag 2+ species (entry 5), commercial AgO was also investigated under otherwise identical reaction conditions, resulting in a 71% HMF conversion, 65% HMFCA yield and 91%

HMFCA selectivity. Ag 2+ turned out to be comparably less active to Ag + in HMF oxidation. Considering the catalytic efficiency performance, Ag2O was chosen for subsequent optimization.

Quantitative HMF conversion at a moderate HMFCA selectivity (61%) could be reached using a strong base such as NaOH for HMF oxidation (Table 3.1, entry 6). In the absence of any alkali (Table 3.1, entry 9), the oxidation of HMF to HMFCA hardly happened, with only 12% HMF conversion (11% HMFCA yield, almost 92% HMFCA selectivity). These results suggested that sodium hydroxide could promote HMF conversion, concomitantly with large quantities of humins, thus decreasing HMFCA selectivity. Other bases were subsequently screened including Na2CO3 and NaHCO3.

As can be seen from Table 3.1, entries 7-8, NaHCO3, a weak base, lead to a low HMF conversion (28%) and HMFCA yield (25%) but a high HMFCA selectivity (89%) under identical conditions. These results clearly showed strong or too weak bases were unfavorable for HMFCA formation. Interestingly, the use of Na2CO3 could provide 87% HMF conversion and 80% HMFCA yield (92% HMFCA selectivity, Table 3.1, entry 7

vs. entries 6, 8). Therefore, Na2CO3 was chosen as the best candidate base for HMF oxidation to HMFCA.

Effect of base amount for the production of HMFCA

The effect of Na2CO3 eq. on HMF conversion and HMFCA yield were examined, the corresponding results were illustrated in Fig. 3.1. HMF conversion increased from 12% (0 eq. Na2CO3) to 100% (4 eq. Na2CO3), the yield of HMFCA also increased from 11% (0 eq. Na2CO3) to 98% (4 eq. Na2CO3). However, for 5 eq. Na2CO3, a lower catalyst performance (HMF conversion 100% with HMFCA yield 90%) could be due to its strong alkalinity causing slight HMF decomposition to humins in comparison to 4 eq. Na2CO3. Therefore, 4 eq. Na2CO3 was selected as the optimum amount, considering the balance between cost-efficiency and catalytic performance.

Effect of catalyst amount for the production of HMFCA

The influence of Ag2O catalyst amount was also investigated. As it can be seen in Fig. 3.2, 92% HMF conversion (12% HMFCA yield, 13% HMFCA selectivity) was only obtained in the absence of catalyst. Increasing the catalyst amount from 5 mg to 20 mg, the conversion of HMF increased from 82% to 100% as well the yield of HMFCA (78% to 98%), respectively. High HMFCA selectivity 95% could be achieved.

A further increase in the amount of catalyst (25 mg and over), did not seem to have any increase in HMF and HMFCA yields. Considering the balance between catalytic performance and cost-efficiency, 20 mg catalyst was selected as optimum catalytic

Effect of reaction temperature and reaction time for the production of HMFCA

The effect of the reaction temperature on HMF conversion and HMFCA selectivity was also studied employing the optimum Ag2O catalyst (20 mg) (Table 3.2). HMF conversion could reach ca. 55%, (52% HMFCA yield, 94% HMFCA selectivity) when the reaction was performed at 30 ºC. Further increasing the temperature from 30 ºC to 90 ºC, HMF conversion and HMFCA yield increased dramatically to a maximum of quantitative HMF conversion and 98 % HMFCA yield (Table 3.2, entries 1-3).

Importantly, no side products including DFF, FFCA and FDCA could be detected at higher temperatures (even up to 120 ºC), where conversion, yields and selectivities remained almost identical to those observed at 90 ºC. Remarkably, no significant humins formation could be observed even at high temperatures under the optimized reaction conditions using Ag2O. In order to obtain deeper insights into the catalyst oxidation of HMF to HMFCA at different temperatures, HMF conversion, HMFCA yield and selectivity were monitored as a function of the reaction time, as illustrated in Fig. 3.3. Different temperatures, namely 90 and 120 ºC were investigated, respectively. As showed in Fig.

3.3, HMF conversion and

Effect of aq. H2O2 amount for the production of HMFCA

The effects of the amount of aq. H2O2 in HMF oxidation were also studied, and the corresponding results were displayed in Fig. 3.4. In the absence of H2O2, 63% of HMF conversion could be achieved (60% of HMFCA yield), which suggested that the oxidative conditions were not enough for the efficient formation of HMFCA. In turn, by increasing the volume of aqueous H2O2 from 0 to 8.1 wt%, the yield of HMFCA and HMF conversion further continuous increased to quantitative HMF conversion and 98 % HMFCA yield. However, 8.1 wt% aqueous H2O2 afforded a higher HMFCA yield (98%) as compared to 10 wt% H2O2 aqueous (87%). Comparison of the latest results indicated that high H2O2 concentration could trigger the decomposition of HMF [32]. Therefore, the concentration of the oxidizing agent (H2O2) resulted to be a critical factor in the investigated system.

Effect of microwave and continuous flow for the production of HMFCA

The effect of different reaction processes, microwave heating method and continuous flow regime, were performed as reported in Table 3.3. Entries 1-4 were carried out under 90 ºC in oil bath condition, entries 5-8 were performed under microwave power (30 W) in batch with the same reaction condition. The temperature ranged from 87 to 92 ºC, the results showed, in different reaction time: 6 min, 12 min, 24 min and 60 min, that microwave heating method was more efficient than conventional heating method, under the same reaction condition (by comparing entries 1-4 with entries 5-8). Using microwave heating, 99 % of HMF conversion and HMFCA yield 97% could be achieved in 24 min, almost the same value obtained with conversional heating in 60 min (entry 4), confirming the improved the higher efficiency that can be afforded by microwave irradiation. 36% HMF conversion, 33% HMFCA yield and 91% HMFCA selectivity could be observed in the first sample (Table 3.3, entry 9). Unfortunately, 8% HMF conversion, 5% HMFCA yield and 62% selectivity were found in the second sample only after 30 min (Table 3.3, entry 10). Thereafter, the selectivity decreased from 62% to 40% in the following samples (Table 3.3, entry 11-12). The reason for the loss of catalyst activity was attributed to the absence of aq. H2O2 and further catalyst deactivation.

Stability of the catalyst and recycling

Recycling of the catalyst is an important step for the development of sustainable and economically feasible catalytic processes. Reusability experiments for Ag2O catalyst were subsequently carried out under optimum reaction conditions. In each successive cycle, the catalyst was filtered, rinsed with water three times, then acetone for three times and finally oven-dried at 60 o C. 100 mg fresh Ag2O was used in reaction.

After filtration washing with water and acetone, 80 mg spent Ag2O was recycled. 44 mg of spent catalyst were calcined in muffle furnace under 400 o C for 4 hours.

37 mg catalyst can be recycled. The observed weight lost (7 mg) was mainly attributed to the formation and adsorption of humins during the reaction, in addition to the oxygen released from Ag2O structure (Ag2O totally decomposed at temperatures above 300 ºC).

A 9 wt% of humins deposition on the spent catalyst surface was estimated from this analysis.

The recovered catalyst without calcination was directly used in another reaction run with fresh reagents. As shown in Fig. 3.5, quantitative HMF conversion and 98%

HMFCA yield was obtained using the fresh catalyst. Comparably, the first reuse could only achieve 85% HMF conversion and 80% HMFCA yield under conventional heating conditions. Further decreased could be found until the fifth time with 57% HMF conversion and 42% HMFCA yield. Further catalyst post-characterization was performed to better understand the observed catalyst deactivation.

Pristine and spent Ag2O were investigated to see the changes in pH values during the reaction process (Table 3.4). The starting basic solution displayed a pH around 10 in the presence of 4 eq. Na2CO3 at time 0. Negligible changes in pH values were observed when the reaction time is prolonged from 15 min to 60 min. A similar trend was also found for the spent Ag2O (Table 3.4, entry 2).

XRD analysis

XRD measurements of the fresh and spent materials, after batch and continuous flow reactions, were performed in order to analyze their arrangement and crystal structure (Fig. 220) and (311) planes of metallic silver [36]. Such results indicated that after the batch reaction, the material was completely reduced. In addition, continuous flow reaction just resulted in a partial reduction of silver oxide. For the latest sample, XRD pattern showed the same signals observed for the fresh Ag2O and, additionally, it also exhibited small contributions of metallic silver.

XPS analysis

In order to confirm the results obtained by XRD and to get more insights into the chemical composition of the fresh and spent samples, XPS analysis was performed (Fig.

3.7).

In the three cases, it was observed the presence of carbon, oxygen and silver. eV) bonds [37]. No significant differences were found in the carbon signal of the fresh and spent catalyst. However, it is worth to mention that after the batch reaction, C=O signal clearly increased, which could suggest the adsorption of organic entities in the catalytic material. Remarkably, O 1s XPS region of the spent catalyst, exhibited considerable changes in comparison with the fresh sample. As displayed in Fig. 3.7 B, E and H. For the fresh sample and the spent catalyst after the continuous flow reaction, deconvoluted O1s XPS region presented two contributions at ca. 529.4 eV and 530.9

eV, associated to Ag-O and O-O bonds, respectively [38]. In turn, after the batch reaction, O 1s region of the spent catalyst presented an unique signal at 531.1 eV. Such result suggest that after the reaction performed in the batch, silver oxide was reduced to metallic silver. These conclusions were also supported by the data of Ag 3d region.

While for the fresh material, Ag 3d5/2 peak was found at 367.8 eV, for the material analyzed after reaction, Ag 3d5/2 signal was located at 368.2 eV. If well is true that in the literature, certain ambiguity about Ag 3d region for Ag0 and AgI species, has been found due to the very similar peak position detected, the shift observed in the spent material suggest the formation of metallic silver [39][40][41][42], In addition, for the spent sample after the continuous flow reaction, Ag 3d5/2 peak could be deconvoluted in two contributions related to Ag 0 and Ag I species, with a minor contribution of Ag 0 .

Therefore, from the latest data, it could be inferred that Ag2O is partially reduced to metallic silver, being in good-accordance with XRD results.

SEM-mapping analysis

The morphology and chemical composition of the fresh and spent samples was investigated by SEM-mapping analysis. As shown in Fig. 3.8, the three materials exhibited the presence of silver, oxygen and carbon, homogeneously distributed. Silver was identified as the main component in the three samples. In particular, oxygen was detected with higher intensity in the fresh sample, in comparison with the spent catalysts, which could be related to the reduction of silver. As well, no significant variation of the carbon content was found in the samples. Nonetheless, it could be mentioned that for the spent catalyst, certain carbon agglomeration was observed, most likely associated to the adsorption of organic moieties.

TEM analysis

In order to get more insights into the morphology and size distributions of the materials, TEM images were recorded (Fig. 3.9). The three samples displayed a homogeneous distribution with the presence of quasi-spherical nanoparticles.

Interestingly, while the fresh catalyst presented a mean radius of 3.0 nm, the spent material exhibited an increased mean radius of 3.5 nm. Such result revealed that a nanoparticle sintering process is taking place during the catalytic reactions. Sintering due to a thermal treatment is one of the main reasons for catalyst deactivation. In this regard, it has been proposed two main mechanisms of sintering of nanoparticles, namely: particle migration and coalescence (PMC) and Ostwald ripening (OR), being the last one the dominant process [43]. It has been reported that such phenomena results into the loss of surface area and hence catalytic activity.

Plausible mechanism

A plausible reaction mechanism has been proposed in Fig. 3.10 involving Ag2O and aqueous H2O2. Silver (I) is reduced in the process while the carbonyl group is oxidized. The formed oxidized aldehyde (radical cation) was nucleophilically attacked by the hydroxide anion to form a tetrahedral intermediate, followed by the formation of a gem-diol intermediate via hydrogen shift. Hydrogen is finally subtracted from one of the hydroxyl groups under basic conditions, resulting in the formation of a carboxylic acid group and subsequently in the final formation of a carboxylate anion. The mechanism involved in the Ag + -mediated aldehyde oxidation was the same reported for Tollens' reagent in the silver mirror reaction.

The effect of aqueous H2O2 in the reaction arose significant interest. The use of silver nanoparticles (AgNPs) coupled with H2O2 in oxidations was reported by David et al [44]. AgNPs could react with H2O2 to form Ag + and superoxide anions (O2 •-) which subsequently interact with in-situ-formed AgNPs following an electron charging-discharging model mechanism. 2) and/or (ii) the oxygen-mediated oxidation of Ag 0 (eq 3).

Ag 0 + H2O2→ intermediate (1) intermediate + H2O2 →Ag + + O2 •-+ H2O (2)

Ag 0 +O2 →Ag + + O2 •-(3)
Ag 0 can be partially oxidized to Ag + with the presence of H2O2, releasing O2, which can further boost the conversion of HMF to HMFCA. Such ideas are in accordance with the obtained results, where in the absence of H2O2, only 60 % of HMFCA yield was found, while a 97 % of HMFCA yield can be achieved by adding aqueous H2O2. In any case, decomposition of aq. H2O2 under basic conditions and 'silver mirror' reaction pathway for Ag + reduction will predominantly be occurring.

The use of Ag2O as catalyst for oxidation reaction have been reported. For instance, furfural has been converted to furoic acid via aerobic oxidation employing 150 nmsized Ag2O/CuO (92%) or simply CuO (86.6%) [45]. Aromatic and aliphatic aldehydes were also converted to the corresponding acids in good yields using Ag2O under optimum conditions. Upon recycling, the gradually catalyst aged, originated for example leaching of Ag2O from CuO. In such case, the major reason for catalyst deactivation was the reduction of Cu 2+ to Cu 0 and Cu + , similar phenomenon was found in XRD for Ag2O.

Another work reported by Li et al [46]. was focused on silver (I)-catalyzed aerobic oxidation of aldehydes in water. Several examples of different aliphatic and aromatic aldehydes were investigated under 5 mol% Ag2O/IPr with 1 bar of O2 and 1 eq. NaOH, at 50 o C during 12 h. Results pointed to successful aerobic oxidations to the respective carboxylic acids. Such work demonstrated the usefulness of "silver mirror" reactions under O2 which led to good results at long reaction times.

Catalyst regeneration

Two important factors need to be considered for catalyst regeneration: (i) the organic matter adsorbed on the catalyst, so called humins (which also can be found in

Production purification

Recovery of HMFCA from the reaction media was achieved by liquid-liquid extraction with ethyl acetate, providing a facile separation technique for the recovery of pure HMFCA [47].

The product solution was adjusted to around PH=3 using 0.1 M HCl, and then the catalyst was removed through filtration. The obtained filtrate was dried in order to remove H2O, obtaining a solid composed of HMFCA and NaCl. The isolation of HMFCA from NaCl can be accomplished through anhydrous ethyl acetate extraction.

Isolated HMFCA yield resulted to be roughly 68 %.

Conclusion

HMF oxidation reaction to HMFCA was explored using several methodologies, including conventional heating and microwave assisted irradiation. Commercial Ag2O material proved to be an efficient catalyst for the production of HMFCA from HMF with H2O2 as oxidizing agent. Upon the optimization, 98% HMFCA yield were obtained in 60 min under 90 ºC in oil bath conditions in the presence of base and H2O2

aqueous. 97% HMFCA yield can be obtained in 24 min under microwave irradiation (30 W). Continuous flow methodology without oxidizing agent was also investigated, and it was found that 33% HMFCA yield were obtained. Possible causes of catalyst deactivation were deeply investigated by a post-characterization analysis, showing that the main reasons could be associated with the reduction of silver oxide to metallic silver and to the sintering of nanoparticles after the catalytic reactions. This contribution offers an extensive analysis of the reaction conditions on HMF oxidation, being HMFCA as one of the target compounds for the development of biomass-derived application in the future. The present study provided a promising pathway for HMFCA synthesis using a cheap, commercially available and environmentally benign catalyst. Noticeably, microwave continuous flow approach was also investigated using the optimum conditions, displaying fully HMF conversion with 38% FFCA and 47% FDCA yield. Reusability studies revealed the reason for catalyst deactivation, most likely associated with the deteriorated textural properties after MW batch and MW continuous flow. Ru leaching was found to be more serious under continuous flow process (8%) than in batch conditions (2%). The present study provided a promising pathway for FDCA synthesis using a cheap, commercially available and environmentally benign catalyst.

Introduction

5-Hydroxymethyfurfural (HMF), a renewable resource has been considered as one of the most valued-added chemicals. HMF can be further oxidized to 2,5diformethylfuran (DFF), 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), 5formyl-2-furancarboxylic acid (FFCA) and 2,5-furandicarboxylic acid (FDCA) (Scheme 4.1) [1]. The catalytic oxidation of HMF to FDCA has attracted great attention [2] since FDCA can be used as a substitute of terephthalic acid in the production of polyethylene terephthalate (PEF), which in turn was utilized in film and fiber production, packing materials and soft drink bottles [3]. Several industries have started to consider the use of bio-based chemicals to produce bioplastics [4]. Hence, FDCA was listed as one of the top-12 value added chemicals from LCB [5]. Heterogeneous catalytic process possesses inherent advantages as compared to homogenous catalysis, related to the easy separation and good recyclability of the catalyst. Various supported noble metals (Au, Ag, Pt, Ru and Pd) [6][7][8][9][10][11] have been employed as catalytic systems in the current FDCA research (Scheme 4.1). In comparison with non-noble metal heterogeneous catalysts, noble metal catalysts, which have been developed and successfully applied in HMF oxidation to FDCA, showed a good catalytic activity, recyclability and stability with higher yield [12]. Among the different noble metals that have been considered, Ru could give rise to the less expensive catalysts [13], displaying as well competitive catalytic efficiency. For instance, Vuyyuru et al. [14] reported quite limited FDCA yield (6.4%) with Ru/C as catalyst even at high oxygen pressure (10 bar) (Table 4.1 entry 1). Yi et al. [15] improved FDCA yield to 95% by increasing reaction temperature to 120 o C with CaCO3 as base, and strong alkali (such as NaOH) favors the degradation of HMF, leading to lower FDCA yields (Table 4.1 entry 2 to 4). This phenomenon indicated that weak bases are preferable to strong bases in terms of HMF stability. Noticeably, a heterogeneous base, namely hydrotalcite (HT), gave rise to a good FDCA yield of 90 % (Table 4.1 entry 5). The group also reported the oxidation of HMF to FDCA in a base free system over commercial Ru/C, achieving an 88% FDCA yield under 0.2 MPa of O2 pressure at 120 o C (Table 4.1 entry 7). However, a high Ru/HMF molar ratio (100) and long reaction time (10 h) were employed during this study. Chen et al. [16] have reported the HMF oxidation using aq. H2O2 in the presence of Ru-based catalyst under conventional heating condition, obtaining 91% yield after 6 h (Table 4.1 entry 8). Kerdi et al. [17] achieved 75 % of FDCA yield under 40 bar of air pressure and with a low catalyst loading (Ru/HMF molar ratio 0.01).Such studies have presented Ru as a good candidate for HMF oxidation. In order to enhance the selectivity of the reaction, eliminating the possible intermediates, a closed system has demonstrated to be auspicious since it allows to increase the solubility of gaseous oxygen. Hence, this reaction has been usually carried out under high pressure (> 0.3 MPa with O2 or > 1.0 MPa with air), high temperature (100-150 ºC) and long reaction times (4-24 h) to maximize the reaction conversion.

However, the employment of high-pressure conditions could cause risk of explosion, hindering industrial applications. In turn, the replacement of such conditions by using H2O2 has several advantages associated with its affordable price and safe storage and so on [18]. Particularly for biomass conversion, H2O2 has employed in this work as oxidizing agent. Due to the advantages of microwave irradiation has been introduced in Chapter 3, MW was employed for the development of the present work.

Up to now, most reported studies have been performed in batch conditions. To the best of our knowledge, only three recent study reported the production of FDCA from HMF under continuous flow regime. Michael et al. [19] reported HMF oxidation in continuous flow regime using basic, neutral and acidic feed solution. It was found that basic conditions favored HMF conversion and FDCA formation. In the aforementioned investigation, 9.65% Pt/C gave almost quantitative FDCA yield with complete HMF conversion in the presence of 2.4 wt% Na2CO3, while 5% Pt/ZrO2 furnished a high selectivity (up to 98%) for FDCA. Ali Hussain et al. [20] investigated the continuous flow oxidation of HMF in a tubular fixed bed reactor, achieving 60% FDCA and 38%

FFCA yield with 5% Pt/C at 100 C under 40 bar of O2 pressure. Recently, Francesca et al. [21] also reported a base free strategy, using resin-supported Pt as catalyst in home-made continuous flow equipment, under 7.7 bar of O2 pressure and 1.2 mL min - 1 of O2 flow rate in neat water. FDCA was continuously obtained in 99% yield (spacetime-yield (STY) 46 g L -1 h -1 ) at 120 o C. The catalyst also showed high stability (no obvious deactivation in 5 days). The positive performance of the Pt@Dowex-Na catalyst can be attributed to the appropriate combination of Pt loading, support swelling ability in water, bead size, and steric and electrostatic stabilization of the resinsupported metal nanoparticles [22,23]. All the research that have been performed so far on continuous flow suggests that such methodologies could be feasible for the industrial production of FDCA. Taking into account the advantages of flow chemistry (efficient energy utilization, easy scale-up and facile purification, among others), more efforts are required in this area since it could provide a more appealing route for the industrial production of FDCA in the presence of H2O2 as oxidizing agent.

In this study, aqueous H2O2 and air flow were investigated as oxidizing agents.

Moreover, microwave methodologies under both, batch and continuous flow regimens were studied. Three different pathways for HMF oxidation to FDCA with commercial 5% Ru/C have been designed and explored, namely using (i) H2O2 as oxidant agent at atmospheric pressure and under microwave heating in batch reactor; (ii) air flow at atmospheric pressure and under conventional heating in batch reactor and (iii) H2O2 as oxidant agent under microwave heating in continuous flow regime.

Experiment section 4.3.1. Materials, solvents and reagents

Water for HPLC, HMF (≥ 99.5%), ruthenium(III) chloride (99.9%), ziconium(IV) chloride (98%), nickel(II) chloride hexahydrate (97%), sodium borohydride (98+%)

were purchased from Acros Organic and further used without purification. Other reagent such as sodium carbonate (Na2CO3) was purchased from Honeywell. Sodium bicarbonate (NaHCO3), potassium carbonate (K2CO3), potassium hydroxide (KOH), potassium bicarbonate (KHCO3) and 230 mm disposable glass pasteur pipettes were purchased from VWR CHEMICALS. Hydrogen peroxide 30 wt % solution was purchased from CHEM-LAB. The commercial 5% Ru/C and 5% Ru/Al2O3 and magnesium chloride anhydrous (98%) were purchased from Sigma-Aldrich and further used without purification.

Catalyst synthesis and characterization

Three ruthenium catalysts, namely 5% Ru/Ni(OH)2, 5% Ru/Mg(OH)2, 5%

Ru/Zr(OH)2 were prepared by simple wet impregnation method using aqueous solution of RuCl3 on different support. Ni(OH)2, Mg(OH)2 and Zr(OH)2 supports were prepared by using NiCl2, MgCl2 and ZrCl4 in NaOH aqueous to get three solid metallic hydroxides. Samples were filtered and dried at 363 K for 12 h in oven to achieve Ni(OH)2, Mg(OH)2 and Zr(OH)2. Subsequently, 0.5 g of each hydroxide was respectively suspended in 50 mL of water. Then, 51 mg of RuCl3 were added to each solution, under stirring and an aqueous sodium borohydride solution (0.5 mol L -1 ) was dropwise into each mixture along 2 h. After filtration and washing with HPLC-water and acetone, the samples were dried at 363 K for 12 h in oven.

A post-characterization analysis was performed by XRD, N2 physisorption and ICP-OES measurements. Powder XRD experiments were conducted on a Shimadzu Xray 7000 diffractometer using a CuKα X-ray radiation operating at 45 kV and 100 mA; counts were accumulated in the range of 10-80 o 2θ every 0.02 o (2θ) with counting time 2 sec per step. Nitrogen adsorption/desorption experiments at -196 o C were performed for the determination of specific surface area (multi-point BET method), total pore volume (at P/Po = 0.99), mircopore area by t-plot analysis and pore size distribution (BJH method using adsorption data or DFT analysis) of the samples which were previously outgassed at 150 o C for 16 h under 5x10 -9 Torr vacuum, using an Automatic Volumetric Sorption Analyzer (Autosorb-1MP, Quantachrome). Before measuring final concentrations of Ru element on ICP-OES (Optima 7300, Perkin Elmer corporation, Massachusetts, USA), the filtrate solutions were acidified with 10 % HCI to make solution PH < 7. 10 mL 10% HCI and 1 mL filtrate solution samples were mixed for further measurements. 1000 ppm commercial Ru standard solution were diluted with 10 % HCI aq. to 50 ppm, 30 ppm, 15 ppm and 5 ppm for the calibration curve.

Catalytic experiments

Conventional heating-assisted reaction was carried out in an oil bath at 80 ºC using air flow as oxidant agent. Firstly, the reaction was carried out using HMF (37.8 mg, 0.3 mmol), Na2CO3 (31 mg, 0.3 mmol), 5% Ru/C (25 mg) and water (15 mL) in the presence of air flow (3 mL min -1 ). After 6 hours, solid NaOH (95.9 mg, 2.4 mmol) was added and the mixture was maintained at 80 °C in the presence of air flow (3 mL min - 1 ) during 16 hours to furnish the desired targed FDCA in 84% yield.

Microwave batch experiments were carried out in a MiniFlow 200SS with a transversal magnetic (TM) cavity for small batch operation with a Pyrex flask (see Fig.

S4.1).

Firstly, aqueous H2O2 (12.7 wt %) was added with a flow rate of 1 mL min -1 to a mixture of HMF (37.8 mg, 0.3 mmol), Na2CO3 (31 mg, 0.3 mmol), 5% Ru/C (25 mg) and water (5 mL) under microwave activation (8 W) for 5 minutes. Then, solid NaOH (95.9 mg, 2.4 mmol) was added to the mixture and aqueous H2O2 (12.7 wt %) was added with a flow rate of 0.2 mL min -1 . After microwave activation (8W) for 25 minutes, the desired targed FDCA was obtained in 88% yield.

Furthermore, microwave continuous flow experiments were carried out in a continuous flow-reactor under microwave heating (see Fig. S4.2), connected to two HPLC pumps. A mixture of HMF (0.06 M), Na2CO3 (0.06 M) in water and aqueous H2O2 (6.5 wt %) were flowed at a flow rate of 0.1 mL min -1 and 0.2 mL min -1 , respectively. The two solutions were mixed in a T-mixer and then flowed through a cartridge with 5% Ru/C (250 mg) at a flow rate of 0.3 mL min -1 under microwave activation (32 W) for 20 min.

Products analysis

All recovered samples were then analyzed by high-performance liquid chromatography (HPLC, Agilent Technologies 1260) equipped with Photodiode Array Detectors with C-18 column (Poroshell 120 EC-C18 4 μm 4.6×100 mm) with 1 mL min -1 acetonitrile-water mixture (1:9, v/v) as the mobile phase. Injection was 2 μL, with a column temperature of 30 ºC, mobile phase flow rate was 0.2 mL min -1 . The retention times for FDCA, FFCA, HMFCA, HMF and DFF were 3.2, 4.1, 4.9, 10.1, and 13.0 min, respectively. The wavelength of FDCA, FFCA, HMFCA, HMF and DFF were 263 nm, 293 nm, 249 nm, 284 nm and 284nm respectively. The response factors (RF) of HMF and FFCA, HMFCA, DFF and FDCA were experimentally determined at 1.39×10 -5 , 1.29×10 -5 , 2.19×10 -5 , 1.43×10 -5 and 1.87×10 -5 respectively. The linear regression coefficients of the calibrations were high in all cases (r 2 > 0.99).

The yield of FDCA, HMF conversion, the metal catalyst productivity (mmol (FDCA) g (metal) -1 h -1 ), weight hourly space velocity (WHSV) (g (HMF) g (catalyst) - 1 h -1 ) and space-time-yield (g (FDCA) L (reactor) -1 h -1 ) were calculated according to equations ( 1) and ( 5):

"#$%& (%) = ,-./01234
,567 8991 × 100

<=>?$@A#=> (%) = [,567 CDE4EFG H,567 8EDFG ] ,567 CDE4EFG × 100 (1)
J@=&KLM#?#MN (OO=%(PQ<R) S(O$MT%) HU ℎ HU ) =

[7WXY Z[\] ^_` _ab cd e ×f.fh ×567 iXbi]b\Z[\aXb (6) × 7j,k la]Wm × Ufff] ,[\[Wln\ _]\[W _[nn (o) (3)
pqrs (S(HMF) S(LTMT%NAM) HU ℎ HU ) =

[7WXY Z[\] ^_` _ab cd e ×f.fh ×567 iXbi]b\Z[\aXb (6) ×Uwh.U (o _XW cd ) ] ,[\[Wln\ _[nn (o) (4)
ry" (S(PQ<R)z(@$TLM=@) HU ℎ HU ) =

[P%={ @TM$ (Oz O#> HU ) × 0.06 × q}P L=>L$>M@TM#=> (}) × PQ<R N#$%& × 156.1 (S O=% HU )] $TLM=@ ?=%KO$ (z)

CHMF and CP are the concentrations of HMF and product (mg mL -1 ). The total volume in the system of the continuous flow experiments was assumed to remain constant during the experiments (no evaporation loss). All results (conversion and yield) are expressed as molar percentages. HMF oxidation has been deeply investigated by analyzing the effect of microwave activation, the continuous flow regime conditions as well as the influence of the catalytic system, the oxidant agent and the employed base. The outstanding features of microwave technologies have attracted the attention of the scientific community for their implementation in biomass valorization processes. Microwave-assisted heating, which generally offers lower reaction times and higher yields, will be compared with conventional heating in oil bath. Microwave assisted reaction will be performed under both batch reactor and continuous flow regime for comparison as well.

Results and discussion

As one of the most crucial factors, the selection of the best catalytic system was firstly carried out in batch process. Ruthenium was chosen as noble metal due to its competitive price, as previously mentioned. Then the analysis of different supports including commercial carbon (5% Ru/C) and alumina (5% Ru/Al2O3), and three synthesized metal hydroxides, namely zirconium (5% Ru/Zr(OH)4), magnesium (5% Ru/Mg(OH)2) and nickel (5% Ru/Ni(OH)2) hydroxides were studied. The five materials were tested in the batch microwave-assisted oxidation of HMF. Firstly, MW power 30 W 2 min to reach aqueous temperature 80 o C, then 6.5 wt % H2O2 solution dropwise into the flask with a flow rate of 1 mL min -1 under MW 8 W to maintain 80 o C for 10 min. HMF converted and the formation of different intermediates including DFF, HMFCA, FFCA and FDCA for each catalytic system in particular was studied (Fig.

4.1).

All the catalysts were found to be active in the oxidation reaction, being the catalytic performance greatly influenced by the type of support. In our hands, 5% Ru/C catalytic material displayed the best results, 100% HMF conversion and 83% FFCA yield, in comparison with 5% Ru/Ni(OH)2, 5% Ru/Zr(OH)4, 5% Ru/Mg(OH)2 and 5% Ru/Al2O3. Moreover, for 5% Ru/C catalyst, 2% FDCA yield was also found. In a twostep process, ruthenium nanoparticles can firstly catalyze the oxidation of HMF to DFF and then further conversion to FFCA. No HMFCA was found for most of the Ru-based catalyst. Only by using 5% Ru/Ni(OH)2, formation of HMFCA was detected in a very low yield. In the presence of Na2CO3 as base and H2O2 as oxidant agent the kinetic suggested that the primary hydroxyl group of HMF was readily oxidized to the corresponding aldehyde and then one of the two formyl groups was converted to carboxylic acid group furnishing FFCA (Scheme 4.2). Particularly, 5% Ru/Al2O3 and 5% Zr(OH)4 materials gave rise to 45% and 55% of HMF conversion, with 25% and 30% FFCA yield, respectively. Both materials achieved less than 10% of DFF yield.

Yury et al. [24] synthesized a series of Ru-based catalyst with different supports such as aluminum, zirconium, and magnesium, the results showed ZrO2 and Al2O3 supports induced the formation of formic acid, and led to the formation of solid humins, suggesting that such supports were not suitable to afford a high selectivity to HMF oxidized products. Moreover, 5% Ru/Ni(OH)2 and 5% Ru/Mg(OH)2 exhibited low HMF conversion (21% and 32%) and FFCA yield ( less than 10 and 20% respectively), which could be most likely associated to the basic nature of Ni(OH)2 and Mg(OH)2. In 1990, Grabowski and co-worker [25] reported on the selective electrochemical oxidation of HMF to FDCA in NaOH (1.0 M) using a Ni(OH)2 electrode. However, the yield was only 71%. The comparatively low yield despite high selectivity can be explained by the decomposition of HMF in alkaline solutions and the basic property of Ni(OH)2 electrode . In our case, it could be suggested that the supports, which possess both acidic and basic sites favor the HMF conversion and FFCA formation. Besides, the morphology, surface area, porous diameter, as well as ruthenium particle size, etc. also played a vital role in the catalytic performance.

As mentioned above, it is tough to have a parallel comparison between different supports. Since 5% Ru/C afforded the best catalytic performance with good FFCA selectivity and thus it was employed for the subsequent experiments. Blank experiments were also accomplished in absence of oxidant agent and catalyst, respectively (Table 4.1, entries 1 and 2). Such measurements showed that in absence of oxidant agent (H2O2), the conversion of HMF was only 15%. Additionally, it was confirmed that the presence of an effective catalyst was a crucial factor for the progress of the reaction, as inferred from experiments in absence of 5% Ru/C, giving rise to a negligible HMF conversion. Oxidation of aldehyde group in HMF could be favored by the presence of a base through the nucleophilic attack of OH-groups, achieving high FFCA yields even at atmospheric pressure and in short reaction times.

Variation of the nature and the amount of the homogeneous bases was examined (Table 4.1, entries 3-14). It was observed that a strong basic environment, provided for instance by using NaOH or KOH, could trigger the decomposition of HMF (Table 4.1, entries 8 and 14). Although HMF conversion achieved 100%, just traces of FDCA were detected, FFCA yield was around 61-62%, with a low carbon balance (66-69%). The yields were calculated from liquid chromatography analysis with a calibration curve.

a The reactions were performed under stirring at room temperature. b H2O2 was added into the reactor once time. Reaction conditions: HMF (37.8 mg, 0.3 mmol), base (0.5-2 eq.), catalysts (0-50 mg) in water (5 mL), 2 min under MW (30 W) and then addition of aqueous H2O2 (0-10.7 wt%) with a flow rate of 1 mL min -1 or 2 mL min - 1 during 10 min or 5 min under MW (8 W).

In turn, the use of weak bases such as NaHCO3, Na2CO3, KHCO3 and K2CO3 could notably increase the carbon balance and FFCA selectivity. In this regard, it was found that after 10 min of reaction, NaHCO3 (Table 4 This result was superior in comparison with the one obtained with other weak bases at the same reaction time (Table 4.1, entries 3, 9 and 11). Therefore, for the next steps, Na2CO3 and 5 min of reaction time were chosen as the optimum conditions.

Effect of base amount for the first step production of FFCA

The influence of the base amount (Na2CO3) in this reaction system was also studied (Table 4.1, entries 5, 15 and 16). In this regard, the use of 0.5 eq. Na2CO3 resulted in a 21% DFF yield and 53% of FFCA indicating that the basic environment was not strong enough for HMF oxidation, since DFF was formed. Further increment of base amount (2 eq. Na2CO3) provoked that the reaction move forward, thus resulting in higher FFCA yield (73%). Nonetheless, no FDCA formation was observed by increasing the base amount.

Effect of oxidizing agent for the first step production of FFCA

Effect of H2O2 concentration on the progress of the studied reaction was also investigated. By modifying H2O2 concentration to 3.6 wt % (Table 4.1, entry 17), 98%

of HMF conversion was achieved with 16% of DFF yield, which suggested that the oxidative conditions were not strong enough for the selective formation of FFCA. In turn, by increasing the concentration of H2O2 to 10 wt % (Table 4.1, entry 18), the HMF conversion values raised 100%, and the yield of FFCA greatly increased to 73%.

Comparison of the latest results with the reaction performed using 6.5 wt % of H2O2, affording 83% FFCA yield, indicated that high H2O2 concentration could trigger the decomposition of HMF. Therefore, the concentration of the oxidant agent (H2O2) resulted to be a critical factor in the investigated system.

Gaseous air (Table 4.1, entry 21) bubbled into the solution could also be used as oxidant agent. In this regard, the reaction gave rise to 4% DFF yield, 3% FFCA with only 15% HMF conversion, suggesting that under the investigated conditions and for the employed catalytic system, a stronger oxidant was required. The reaction was performed by adding, at once, H2O2 (6.5 wt %) into the system, instead of pumping it dropwisely (Table 4.1, entry 23). It was observed the formation of bubbles in the solution, indicating that H2O2 was decomposed to oxygen and water quickly. In addition, conversion of HMF was only 40% with 13% FFCA yield. This result showed that a continuous and controlled addition of H2O2 was crucial to complete the conversion of HMF into the desired products. In order to reach higher FDCA yields, the progress of the reaction time was monitored from 5 to 60 min, and several samples were collected along the reaction progress (see Fig. 4.2). After 10 min, the yield of FFCA reached the maximum value (83-85%), with the consequent decrease of DFF yield. Longer reaction times (until 60 min) resulted in the decrease of FFCA yield to 63% and the increment of FDCA yield to 25%. The enhancement of the chemical oxidation of HMF to FDCA requires harsh reaction condition (long reaction time, temperature, high pressure and additives) [6].

Based on the reaction results, FFCA could be synthesized quickly from HMF, while the From the above results, it can be concluded that the optimum reaction conditions are: Na2CO3 (1eq.), 6.5 wt % H2O2 solution, dropwisely added into the system and 25 mg of 5% Ru/C catalyst. In addition, the optimum reaction time could be settled as 5 min for the first oxidative step, from HMF to FFCA, while, so far, for the further oxidation and consequently FDCA formation, the best results were obtained after 60 min. Nonetheless, the still low FDCA yield (25%) obtained for this reaction, could suggest that Na2CO3 was not strong enough for the transformation of FFCA to FDCA, even after adding additional Na2CO3 (1 eq.) (Fig. 4.3, entry 1). In this regard, it has been reported that the use of strong bases would facilitate the production of FDCA, with the drawback that at the same time HMF could be easily decomposed to other side products [16]. In order to deeply investigate the effect of a strong base on the further oxidation of FFCA to FDCA, NaOH was added in a second oxidation step (see Fig. NaOH amounts (2 eq. and 4 eq.) were added into the reaction during 50 min (Fig.

4.3, first two lines)

. Consequently, the increase of the base amount resulted in higher FDCA yields, rising from 38% to 88%. Such data clearly indicated that higher amount of a strong base could promote the conversion of FFCA to FDCA. Further experiments were performed during 35 min using 4 and 6 eq. NaOH, giving rise from 63% to 86% FDCA yield (Fig. 4.3, third and fourth lines). Further decrease of the reaction time to 25 min, using 6 and 8 eq. of NaOH, resulted in 70% (Fig. 4.3, fifth line) and 88 % (sixth line) of FDCA yield, respectively. These results improved with the adding of NaOH, more OH -ion will speed up the process of nucleophilic attack, further decrease the

Air flow under conventional heating for the production of FDCA

So far, hydrogen peroxide has been used as oxidant agent for the development of the present work. Previous works reported HMF oxidation process under oxygen or air pressure in special reactors like autoclaves [6]. In turn, HMF oxidation reaction under ambient atmosphere with air has not been reported yet. In comparison with H2O2, air flow is a cheaper and greener oxidant agent. Based on the optimum conditions described above for the microwave-assisted reaction, the process was conducted in conventional heating using 3 mL min -1 air flow, employing the same reaction temperature, substrate molar ratio and catalyst loading (see Fig. 4.4). The reaction was monitored from 10 min to 21 h. In particular, from 10 min to 6 h, the conversion of HMF increased from 20% to 100%, while FFCA yield raised to 80% with the consequent decreased of DFF from 15% to 0. Moreover, from 6 h to 21 h, FFCA yield decreased from 80% to 60%, and FDCA yield increased from 10% to 30%. The observed trend, using both H2O2 or air flow as oxidant agents, indicated that Na2CO3 was not strong enough for the production of FDCA even with 21 h of reaction. To increase the reaction efficiency, 8 eq. of NaOH were added after 6 h of reaction (see Fig. 4.5). Yield of FDCA can achieved 31% after only 2 h (Fig. 4.5, entry 1). Such results greatly improved the catalytic performance observed when no NaOH was added, even after 21 h of reaction. The data also confirmed that a strong base can promote the reaction even using air as oxidant agent. Subsequently, by prolonging the reaction time from 2 h to 20 h, the yield of FDCA increased from 31% to 84% (Fig.

MW continuous flow for the production of FDCA

The use of microwave continuous flow methodologies, as an efficient way for the continuous production of target compounds, was also investigated in the oxidation of HMF. Under the optimum conditions, obtained from the studies in microwave batch, 0.3 mmol HMF with 0.3 mmol Na2CO3 and 6.5 % wt H2O2 solution were employed.

The two different solutions were pumped through the catalyst with 0.1 mL min -1 and 0.2 mL min -1 flow rate under microwave irradiation. Using a microwave power of 8 W (Temperature was lower than 70 o C), the residence time (the amount of time that the substrate spends inside the reactor, depending on the solution flow) [26]. was less than 50 min (Table 4.3, entries 1-4), HMF was fully converted and it was obtained a FFCA and FDCA yield of 86% and 7%, (FDCA productivity 6.0 mmol g (metal) -1 h -1 ), respectively. Remarkably, yield of FFCA was slightly higher than by using microwave batch conditions, which offered 83% FFCA and 2% FDCA yield in 5 min. After increasing the power to 16 W (Temperature around 83 o C), FFCA yield decreased from 86% to 57%, and in turn, FDCA yield raised from 7% to 30% (Table 4.3, entry 5-8).

Further increasing trend was found when the power was settled as 32 W, (Temperature around 95 o C), The higher microwave power led to a higher reaction temperature.

Consequently, the yield of FDCA increased to 47%, with a higher productivity of 40.6 mmol (FDCA) g (metal) -1 h -1 , and the STY of FDCA was 39.5 g (FDCA) L -1 h -1 . Using 32 W of microwave-power, FDCA yield decreased from 47% to 42%, which was in accordance with the productivity decrease from 40.6 mmol (FDCA) g (metal) -1 h -1 to 36.2 mmol (FDCA) g (metal) -1 h -1 in 30 min, probably suggesting the deactivation of the catalyst. Slight activity decrease could also be observed from the lower STY value, even under 8 W and 16 W conditions. WHSV was 0.54 g (HMF) g (catalyst) -1 h -1 . It is worth to note that a good mass balance was achieved in the present study and no additional products to FFCA and FDCA were detected by HPLC, in microwave continuous flow regime. The yields were calculated from liquid chromatography analysis with a calibration curve.

Reaction conditions: A mixture of HMF (0.06 M), Na2CO3 (0.06 M) in water and aqueous H2O2 (6.5 wt %) were flowed at a flow rate of 0.1 mL min -1 and 0.2 mL min - 1 , respectively. The two solutions were mixed in a T-mixer and then flowed through a cartridge with 5% Ru/C (250 mg) at a flow rate of 0.3 mL min -1 under microwave activation (8-32 W) for 20-50 min. WHSV: 0.54 g (HMF) g (catalyst) -1 h-1. Residence time: < 6.6 min. The yields were calculated from liquid chromatography analysis with a calibration curve.

Stability of the catalyst and recycling

Reaction conditions: Entries 1 and 2, HMF (37.8 mg, 0.3 mmol), Na2CO3 (31 mg, 0.3 mmol), catalysts (25 mg) in water (5 mL), 2 min under MW (30 W) and then addition of aqueous H2O2 (6.5

wt %) with a flow rate of 2 mL min -1 during 5 min under MW (8 W). Entries 3 and 4, Catalysts (250 mg). 0.1 mL min -1 flow rate of a mixture of HMF (7.56 mg/mL, 0.06 mmol/mL) and Na2CO3 (6.2 mg mL -1 , 0.06 mmol mL -1 ). 0.2 mL min -1 flow rate of aqueous H2O2 (6.5 wt %) in 20 min under MW 32 W.

Recycling of the catalyst is an important step for the development of sustainable and economically feasible catalytic processes. Therefore, reusability experiments for 5%

Ru/C catalyst were also carried out under microwave irradiation for 5 min (Table 4.4, entry 2). The fresh catalyst exhibited 100% HMF conversion and 83% FFCA yield. In turn, reusability analysis showed serious catalyst deactivation after the first use under microwave-batch conditions, only achieving 62% HMF conversion and 35% FFCA yield. In addition, after continuous flow microwave-assisted reaction, catalyst deactivation phenomenon was also observed the resulting in 3% FDCA yield (Table 4.4, entry 4). In order to understand the deactivation of the catalyst, a postcharacterization analysis was performed for both spent catalysts, after batch and continuous flow reactions. Samples were titrated in order to estimate acid and basic groups, following a protocol reported in the literature [27]. It was observed a clear decrease of acid and basic groups in both reused materials, in comparison with fresh catalyst, acid groups decreasing from 1.1675 to 1.0095 and 1.0527 mmol g -1 , for batch and continuous flow used materials, respectively. The same was observed for basic groups from 0.6464 to 0.3975 mmol g -1 , in both cases. The decrease of both acid, and particularly basic groups followed a trend, which could be correlated with HMF conversion decreasing and FFCA yield behavior, most likely associated with the important role of basic group in HMF oxidation reaction [28]. 4.5). Noticeable differences were clearly observed for the reused catalysts, especially after the batch reaction. The fresh 5% Ru/C (Table 4.5, entry 1) showed a microporous structure with high contribution of meso/macroporosity. About 55 % of its total surface area and 22 % of its total pore volume is attributed to micropores, the rest being mainly due to meso/macropores and external surface area. After the microwave batch reaction, the micropore surface area drastically decreased a 99%, while the meso/macro-pore and external surface area decreased a 42%. These changes in the porosity of the catalyst after the microwave-batch reaction, could be most likely attributed to occlusion phenomena on the porous of the material. It was observed, after the first catalysts use, that HMF was partially decomposed (17% HMF lost) with the possible formation of humins, which could be covering the surface of the catalyst, causing the blocking of the pores and specially of the micropores. On the other hand, continuous flow catalytic tests also induced a less pronounced negative effect, leading to a 30% lower surface area, in comparison with the fresh 5%Ru/C. This surface area reduction is mainly related to the decrease of micropore area, since no considerable changes of meso/macropores and external surface area were observed. Accordingly, only the micropore volume was reduced a 30% (see Table 4.5).

N2 adsorption analysis

analyzed by ICP-OES in Table 4.6. Entry 1 showed that no Ru leaching was found by water washing, hence suggesting that the catalyst is stable in water. However, 2 % of Ru leaching was found after HMF and Na2CO3 were added into the system (Table 4.6, entry 2). Based on the analysis of ICP-OES, higher amount of Ru leaching was observed in continuous flow (8%), in comparison to batch conditions (2%) (Table 4.6, entry 3). We believe that the longer performing time (>50 min) in continuous flow (vs.

5 min in batch) could cause Ru leaching, being considered as the main reason for the catalyst deactivation under continuous flow regime. The stabilization of the catalytic performance under the continuous flow could be complex involving certain accumulation of carbon entities (humins) on the surface of the catalyst, leaching processes as well as stabilization of hydrodynamic conditions.

Conclusion

In summary, liquid-phase oxidation of HMF in both batch and continuous flow using commercially available Ru/C under microwave irradiations was reported. High yield of FFCA (83%) and FDCA (88%) were efficiently achieved by adjusting the type and amount of base, as well as the reaction time. Interestingly, comparable FDCA yield (84%) was produced with air as oxidizing agent in 22 h. Moreover, microwave continuous flow experiments were also performed, and 47% of FDCA with 38% of FFCA was obtained under optimized conditions. However, the catalyst showed a poor stability under both batch and continuous flow regimes. Catalyst post-characterization revealed that the disruption of microporous structure and Ru leaching were the main causes for catalyst deactivation. This contribution offers an extensive analysis of HMF oxidation in different reaction regimes under microwave irradiation.

Introduction

2,5-Furandicarboxylic acid (FDCA) is recognized as one of the twelve buildingblock chemicals by the US Department of Energy. This aromatic compound is easily synthesized through the dehydration of fructose to 5-hydroxymethylfurfural (HMF) under acidic conditions and then peroxidation using various oxidants in one-pot onestep and one-pot two-step reactions (Scheme 5.1) [1][2][3][4]. The direct conversion of HMF to FDCA is technically feasible, but faces problems of cost, stability and availability.

Catalytic oxidation of HMF to FDCA using homogeneous catalysis was reported but these processes were less attractive as compared with heterogeneous catalysis due to the separation and recycling problems [5][6][7]. Modern heterogeneous catalysts such as nanosized bimetallic catalysts could also become a good alternative for the FDCA production [5,[8][9][10]. Using homogeneous catalyst or heterogeneous catalyst the main limitation of the process remains the cost of HMF itself. In fact, this furanic intermediate is industrially produced in moderate yields by the dehydration of hexoses (fructose and glucose) isolated as sub-units from the depolymerization of polysaccharides such as cellulose or starch [11,12]. Nowadays, it appears important to find more efficient pathway to access FDCA analogs. One of the most promising routes should be the dehydration of mucic acid in the presence of strong mineral acid (H2SO4, H3PO4, HBr) [13] or para-toluenesulfonic acid (PTSA) [14]. Mucic acid offers the advantage of having two carboxylic acid groups. FDCA is often employed as one of the components for the preparation of linear or branched polyesters showing relevant thermal and mechanical properties [15]. FDCA polyesters express good biocompatibility with the human body. These polymers are expected to be useful in a near future in the field of commodity thermoplastic engineering polymers like the well-exploited polyethylene terephthalate (PET). More exactly, FDCA is used to replace the p-terephthalic acid (PTA), which is overall an oxidation product of p-xylene, an aromatic compound issued from refined oil. Besides, PET is mainly composed of two Y-X-Y type monomers: PTA and ethylene glycol (EG).

In case of EG, this diol is now a biobased building block generated by the biochemical transformation of D-xylose. The polymerization of FDCA or its counterparts with EG is already set up in industry for producing polyethylene-2,5-furan dicarboxylate (PEF)

for commercial applications such as beverage bottles. From a physicochemical point of view PEF is a polyester of higher glass transition and structurally less linear than PET due to the angle of 129° formed between the two consecutive ester function hold by the melting polycondensation of FDCA mixed with a diol [16], to access to these polymers the furanic diacid need to be activated leading to the formation of its corresponding furan-2,5-dicarboxylic acid dichloride (FDCC) [17,18], but the process requires hazardous chlorination reagents such as phosphorous pentachloride or thionyl chloride.

Once the diacyl chloride derivative is formed, it could react with various diols or diamines to form their respective polyesters and polyamides, but the main problem of FDCC accessibility is caused by the low solubility of FDCA in the common organic solvents. In comparison, the diesters of FDCA are easier to handle and far more soluble and could react with various diols in presence of catalysts such as tetraalkyl titanates [19][20][21], tin (II) 2-ethylhexanoate [22,23], antimony trioxide (III) [24][25][26][27][28][29][30] but always active at temperatures superior to 200 °C. A recent paper reported the use of 1,8diazabicyclo [5.4.0] undec-7-ene (DBU) as an organocatalyst to perform the polytransesterification of FDCA dimethyl ester (DMFDC) in the presence of EG [31].

Another strategy to synthesize PEF involves the polymerization of a prepolymer named bis(hydroxyethyl)-2,5-furandicarboxylate (BHEFDC) [32]. This material is obtained by reaction of DMFDC immersed in a large excess of EG and heated at temperatures between 160 and 220 °C. The following polymerization must be carried out under reduced pressure to remove the released EG by-product. This kind of procedure is generally a source of possible degradation of the product and an energy consuming process. Generally, the solid polymers are obtained as dark brown solids only soluble in halogenated solvents such as trifluoacetic acid (TFA) or tetrachloroethane.

The first objective of this present work was to define greener reaction conditions to rapidly produce FDCA diethyl ester from mucic acid in ethanol, its transformation via metal-catalyzed transesterification into prepolymer counterparts using three really different polyols (EG, glycerol and α,α-diglycerol). Each prepolymer was allowed to react with one equivalent of the FDCA diester in the presence of cobalt (II) acetate to generate at a moderate temperature the target linear polymers. All compounds and materials reported in this present paper were studied by NMR and FT-IR spectroscopies.

The polymeric materials were characterized by XRD, TGA and DSC analysis and the morphology of the solid were observed by FE-SEM. Other reagents such as p-toluenesulfonic acid monohydrate (PTSA•H2O; 98%), furan-2,5-dicarboxylic acid (98%) and glycerol (reagent plus > 99% GC) were obtained from Alfa Aesar and Sigma Aldrich. All chemicals were used as received without further purification.

Experiment section

Detecting instruments

Microwave apparatus (Monowave 300, Anton Parar at 600 rpm for the desired time.

The reaction vessel was purged three times with nitrogen. The temperature in the reaction vessel was monitored by means of an IR sensor and the vial was pressurized in regard to the normal vapor pressure of the mixture at defined reaction temperature.

Nuclear magnetic resonance ( A suspension of mucic acid (210.0 mg, 1.0 mmol) in the presence of methanesulfonic acid (MSA) (192.0 mg, 2.0 mmol) was stirred at 160 °C for 30 min using an oil bath until the reaction mixture turned brown. Then, after cooling the mixture to 70 °C, dry ethanol (5 mL) was added and the mixture was heated progressively from 70 to 90 °C for additional 8 h. The reaction mixture was allowed to return to the room temperature, poured in water and extracted with ethyl acetate. The organic layer was separated, washed with aqueous NaHCO3 saturated solution. The organic liquid was isolated, dried on MgSO4 and evaporated in vacuum to afford a brown solid which was purified on silica gel column chromatography using a mixture of EtOAc-cyclohexane (1:1) as eluent to afford the target DEFDC as a white crystal (m = 61.5 mg; yield = 29% for two steps); Mp = 86 °C;

Results and Discussion

In order to produce the furanic polyesters, a simple synthetic route was set up starting from mucic acid (Scheme 5.2). The main challenge remains the choice of mucic acid as the exclusive starting material for the production of furanic polyesters. In order to achieve the polymerizations, this method required the preparation of prepolymers through solvent-free transesterifications between the produced diethyl furan-2,5dicarboxylate (DEFDC) and a chosen polyol in the presence of a transition metal diacetate.

Scheme 5.2. Entire synthetic routes to linear furanic polyesters from mucic acid.

Effect of catalyst variety and catalyst amount for the production of FDCA

For the purpose of carbon economy, the transformation of mucic acid into diethyl ester DEFDC was carried out in the presence of PTSA (4 eq. ) as acid catalyst in ethanol at 160 °C for 1 h. However, despite our efforts using a one-pot two-step procedure (formation of FDCA and then formation of the diester), only traces of the target diester DEFDC was obtained due to the low formation of FDCA. In this context, the decision of modifying our process was taken to optimize the FDCA production. Once produced in neat conditions by mixing mucic acid and acid catalyst, ethanol was added to the crude mixture containing the crude FDCA leading to the formation of the target compound (Scheme 5.1). Variations of the nature and loading of the acid catalyst was investigated. Mucic acid (1 mmol) and catalyst (from 1 eq. to 5 eq.) at 160 °C for 60 min. Under our conditions, the target FDCA was obtained in 32% yield. Variations of the catalyst loading showed that a maximal yield of FDCA (41%) was obtained in the presence of two eq. of PTSA (Table 5.1, entry 2). The use

FDCA

of more catalyst did not permit us to increase the productivity. The performance of MSA showed similar FDCA yield trend when compare with PTSA. The maximum yield of FDCA was also found in 2 eq. MSA with 39 % (Table 5.1, entry 7). Interestingly, CSA was not efficient for producing FDCA, despite its low pKa value of 1.2. In contrast with the results claimed by Taguchi et al. [33], our method did not afford the dialkyl 2,3-furandicarboxylate by-product. The effect of two catalysts (PTSA and MSA) on the dehydration of mucic acid (1 mmol) was studied at different temperatures (140-170 °C) for 60 min keeping the same amount of catalyst (2 eq. ) in a solvent-free reaction under conventional heating (Table 5.2). At temperatures above 160 °C, the FDCA yield decreased (28% vs. 41%), probably due to some degradation and for temperatures below 160 °C, the production of FDCA was only 12% at 140 °C (Table 5.2, entries 1 to 3). The same catalytic performance was found with MSA, with the increasing of temperature from 140 °C to 170 °C, the yield of FDCA decreased from 15 % to 25 %. The maximum yield of FDCA was 39% in 160 °C. The effect of two catalysts (PTSA and MSA) on the dehydration of mucic acid (1 mmol) was studied at different reaction time (5-120 min) under 160 °C keeping the same amount of catalyst (2 eq. ) in a solvent-free reaction under conventional heating (Table 5.3). Similar reaction profiles were obtained for PTSA and MSA as acid catalyst (2 eq ) at 160 °C. MSA showed more efficiency in 30 min when compared with PTSA in the same condition (39% vs. 30 % FDCA yield). Thus, MSA was chosen for the next step optimization.

Effect of reaction temperature for the production of FDCA

Effect of reaction time for the production of FDCA

Optimization of DEFDC

Using the optimized conditions for the synthesis of FDCA (Table 5.3, entry 8), the second stage of the process was realized by adding dry ethanol (5 mL) to the crude material. Varying the reaction time (4-16 h) at 70 °C and 90 °C the maximal yield of DEFDC was obtained at 90 °C for 8 h (Table 5.4, entry 5). The DEFDC yield was calculated from liquid chromatography analysis with a calibration curve.

Optimization of BHEFDC

After isolated and purified the diethyl ester DEFDC, the synthesis of three types of prepolymers such as BHEFDC, bis(2,3-dihydropropyl)-2,5-furandicarboxylate (BDHPFDC) and diglycerol analogue have been investigated. For BHEFDC, a study was realized under conventional heating. When heated at 150 °C for two hours DEFDC conversion was limited to 71% and the yield of BHEFDC never exceeded 60%.

Keeping this temperature unchanged, by solely increasing the reaction time, a real enhancement of the BHEFDC yield has never been recorded. On the other hand, when the reaction was carried out at 170 and 190 °C, respectively, the DEFDC conversion went up progressively by extending both reaction time and temperature. Under the optimized conditions, at 190 °C, the almost complete conversion of DEFDC (95%) needs two hours to yield the prepolymer target in 67% yield. The effect of microwave irradiation on the above reaction was also investigated. After a short survey, batch microwave radiation gave similar results (68% yield) with conventional heating for 2 h but at a lower temperature (150 °C vs. 190 °C) (Scheme 5.3).

Optimization of BDHPFDC

With a similar pKa for the two primary hydroxyl groups and the secondary group, the reactivity of glycerol did not permit regioselectivity without a sequence of protection/deprotection steps or a functionalization of the secondary hydroxyl group.

Usually, there are only a few methods to direct the regioselective monoacylation of glycerol on the primary hydroxyl group. Recently, Slavko et al. developed a new catalyst-controlled polycondensation of glycerol using diacyl chlorides of terephtalic acids or adipic acids [34]. Herein, the authors employed an additional diarylboronic acid catalyst to form preferentially glycerol-derived linear polyester. Besides, it is well known that enzymatic controlled polymerization of glycerol is more or less able to generate linear and branched polyesters [35][36][37]. In order to produce the corresponding the tetrahydroxylated prepolymer BDHPFDC, our preceding procedure was applied at 160 °C for 13 h. Similarly, the batch microwave radiation permitted us to reduce the reaction time (2 h vs. 13 h) and the temperature (150 °C vs. 160 °C) with the synthesis of BDHPFDC in 80% yield (Scheme 5.4). It was notable that an unexpected efficient regioselective monoacylation of glycerol on its primary hydroxyl group was observed permitting the formation of linear polymer. To clearly determine the regioselectivity of our trans-esterification, 2D-NMR experiments were employed to estimate the selectivity of the reaction between the primary hydroxyl group and the secondary Applying the process to diglycerol as polyol was not successful and it was impossible for us to isolate the desired diol derivatives whatever the temperatures used (160 and 180 °C).

Optimization of PEF

Currently, our strategy involved to mix DEFDC (1 eq.) with BHEFDC (1 eq.),

BDHPFDC (1 eq.) and diglycerol (1 eq.), separately in the presence of catalytic amount of Co(Ac)2 in solvent free conditions at 160 °C for 3 h. In several cases, dark brown Starting from DEFDC and BHEFDC, the target polymer PEF was obtained (Scheme 5.5). The 1 H-NMR spectrum of PEF corroborated the result reported in the literature [21,26] and showed in different samples studied at successive residence time the progressive disappearance of signal of methyl group at 1.36 ppm which is representative of the DEFDC ester moieties (Fig. S5.2). The small peak located at 3.34 ppm was attributed to the primary alcohol of BHEFDC. The 13 C-NMR spectrum of PEF was identical with that published [21,26] (Fig. 5.1a). Apparently, one of the major defaults of this synthetic method is the absence of control regarding chain termination with an apparent suppression of the ethyl ester functions.

Optimization of PHPF

Starting from DEFDC and BDHPFDC, the target polymer PHPF having a glycerol moiety was obtained (Scheme 5.6. The principal risk of this reaction was the possibility of forming branched polyesters due to the presence of two secondary hydroxyl groups on the glycerol-based prepolymer. However, compared to an already described nonlinear polymer [28], our result is coherent with a linear structure. The signal of the primary alcohol of the prepolymer does not remained observable on the 1 H-NMR spectrum of the sample. Moreover, the 1 H-NMRs of the glycerol-based copolymer clearly showed bands between 3.17 and 3.38 ppm that match the -CH-of the secondary hydroxyl group of glycerol (Fig. 5.1d). Another broad signal was also observable from 4.01 and 4.33 ppm that corresponds to the methylene groups of the polyol included in the polyester chains. The 13 C-NMR spectrum of PHPF was also more simplified compared to its branched counterparts [28] showing only five peaks: 48.5, 65.9, 119.

Optimization of PDGF

Starting from DEFDC and diglycerol, a more usual poly transesterification was carried out under conventional heating at 160 °C for 3 h. Compared to the 13 C-NMR spectrum of PHPF, the number of peaks was higher considering those initially expected, evidence of possible branching of the polymer chains (Fig.

FT-IR analysis

In order to complete the spectrochemical analysis, FT-IR spectra of the three polymers PEF, PHPF and PDGF provided us important information about our materials (Fig. S5.5). Thus, all characteristic vibration bands of PEF were detected in the spectrum and reported as follows: 2881 (λ CH2), 1717 (C=0), 1582 (λ C=C), 1271 (C-O), but also 963, 832 and 764 cm -1 which are the bending motions always associated with the 2,5-disubstituted furan ring. For the poly (2,5-furan dicarboxylic acid-coglycerol) PHPF and PDGF, the material was analyzed and compared to FT-IR spectrum obtained from the branched polymer recently synthesized by Amarasekara et al. [28].

In the PHPF spectrum, it was possible to observe the characteristic bands of furan-based polyesters located respectively at 1733 (C=O), 1157 and 1276 cm -1 (C-O-C).

Unfortunately, it was impossible for us to detect the presence of the typical -OH vibration bands. On the other side, all representative bands of the furan-based polyesters were effectively present. For PDGF, the bands of -OH vibrations were clearly visible around 3297 cm -1 and all other characteristic bands located at 2955, 1720, 1584 cm -1 , but also 1128 and 1278 cm -1 attributed to the diglycerol moiety. 13 C-and 1 H-NMR spectra of PHPF in DMSO-d6 and (c) 13 C-NMR of PDGF measured in DMSO-d6.

DSC analysis

The DSC thermograms of our synthesized PEF, PHPF, and PDGF were measured (Fig. 5.2). Due to a possible high crystallinity level, the melting point Tm recorded for PEF gave a value a little bit inferior than the normal value of 211 °C generally encountered in the literature [10,15,19], but still superior to 183 °C. This result could be connected to the length of the polyester chain formed during the process. A normal crystallization exotherm was present in the thermogram and the material expressed a cold crystallization temperature Tc at 142 °C. In comparison, PHPF did not show an endothermic peak but rather two strong peaks located at 345 and 379 °C, respectively, in the thermogram. This result could be attributed as the first evidence of a possible modification of the amorphous structure of the material giving later a glassy appearance after a treatment at higher temperatures. For PDGF, the thermogram displayed at temperatures superior to 250 °C, two successive crystallization values of Tc observed at 267 and 322 °C. Curiously, after further warming cycles, a new peak started to appear at 350 °C. It is possible to attribute this phenomenon to degradation or rearrangements of the polymer backbone.

TGA analysis

TGA measurements were recorded for two of our polymeric samples for evaluating the stability of our polymers at the higher temperature in air or under a nitrogen atmosphere (Fig. 5.3). For PEF, the material is quite stable for temperatures above 220 °C, but around 380 °C the material lost about 60% of its total mass. This result is in accordance with literature [10,15,19]. For PHPF, the mechanism appeared to be more complicated. In fact, the glassy black solid already lost around 4% of its mass at 200 °C, but the DTGA curve clearly showed two peaks located at 290 and 380 °C, respectively (Fig. S5.6). The first one could be representative of a partial dehydration of the polyester chain localized on the glycerol moiety followed by structural transformations that could occur at higher temperatures. Finally, both polymers undergo mass variations at temperatures below 400 °C, this result is also in agreement with the above DSC measurements.

XRD and SEM analysis

The crystal structures of PEF and PHPF were estimated by XRD (Fig. 5.4). For PEF, the diffractogram displayed three representative sharp signals observed at 18, 22 and 28°, characteristic of a semi-crystalline material. On the contrary, the glycerolbased PHPF was completely amorphous and did not show a real crystallinity pattern.

Unsurprisingly, PDGF was also an amorphous material and did not display peaks or

EDX analysis

In association with this result the EDX spectrum showed that the purified material was rich in carbon and oxygen, but some traces of cobalt salts remained entrapped inside the material. Conversely, in the PHPF photograph, it is possible to observe larger and entangled structures, unfortunately loaded with more cobalt traces, proven by the corresponding EDX spectrum (Fig. 5.5). This result could be suggested by the presence of a great number of hydroxyl groups present on the surface of the material able to complex a certain amount of the catalyst. In order to determine the sustainability of our processes, EcoScale has been calculated as a rapid metric [38] for the optimized syntheses of FDCA, DEFDC, BHEFDC and BDHPFDC. For the production of the polymers PEF, PHPF and PDGF with undetermined yields and molecular weights the EcoScale was not calculated. The values obtained using the Ecoscale tool allow us to rank our optimized experiments as follow: acceptable reactions conditions for the synthesis of FDCA with a total score of 68; inadequate reaction conditions for the synthesis of DEFDC with a total score of 32;

excellent reaction condition for the synthesis of BHEFDC and BDHPFDC, with total scores of 75 and 81, respectively.

Conclusion

A new process for the synthesis of the diethyl ester of FDCA starting from mucic acid was developed in a one-pot two step procedure furnishing the target diester in 29% yield. Using this platform molecule, two prepolymers were produced by transesterification with ethylene glycol and glycerol and Co(Ac)2•4 H2O as catalyst in 68% and 80% yields, respectively. Then, different kinds of furan-based polyesters were produced using a solvent-free Co(Ac)2•4H2O catalyzed polytransesterification between FDCA diethyl ester and two polyol-derived prepolymers (PEF and PHPF). The glycerol-based linear polyester seems to be subject to some kind of further rearrangement causing reticulation of the material, when heated at temperatures above 370 °C. However, due to the increasing number of hydroxyl groups on the periphery of the material, the viscous resin of PDGF was clearly a water soluble material. This methodology should be extended to other biosourced diols or PTA-based prepolymers to access new copolymers of interest. The resulting linear PHPF and branched PDGF polymers could be also functionalized on their free hydroxyl group for future biological or medicinal applications.

  Pepijn who helped me a lot to draft the first English manuscript of my life. My Chinese friends: Lu, Rui, Zhi, Congcong et al. The first year, we celebrated Chinese New Year together. Thanks to supervisor Prof. Virginie Vidal and all colleagues from the group in Paris, good opportunity to study in Chimie ParisTech, I made lots of excellent friends here, especially Bin, we are tight. Longsheng, Amine, Mohamad, Aymane and Sudipta etc… Of course, I ought to show great gratitude to the selfless love from my parents, Chengrong, Shujun and my sister Mingming. My family was always the exhaustless energy source to me all the time. Another important thing during my PhD is my marriage with Ting in 19/08/2019, the unforgettable moment for me. I love you, my wife, forever. No matter what happen in the future, we can overcome together! You are my sunshine. Thank you for your support and your encouragements, especially when I was homesick. Thank you for trying to understand my work and listening to me when I needed it.

Fig. 0. 1

 1 Fig. 0.1 Major conversion technologies for converting biomass into useful energy carriers. Fig. 0.2 Electric (E) and magnetic (H) field components in microwaves.

Fig. 0. 3

 3 Fig. 0.3The difference between microwave and conventional heating nature.

Fig. 0. 4 Fig. 0. 6

 46 Fig. 0.4The frequency and wavelength of microwave radiation region. Fig. 0.5 The fundamental mechanism of microwave heating: (A) dipole rotation; (B) ionic migration. Fig. 0.6 Two of the small scale dedicated microwave units for scientific applications.

Fig. 0. 7

 7 Fig. 0.7 Reactors used for continuous flow synthesis. Fig. 0.8 Comparison of batch microwave and flow processing (conductive heating).

Fig. 0. 9 Fig. 1 . 1

 911 Fig. 0.9 Different type of laboratory scale continuous flow reactors. Fig. 0.10 Synthesis and application of two platform molecules: Furfural and 5-Hydroxymethylfurfural. Fig. 1.1 Methyl levulinate (ML), α-angelica lactone (AAL), β-angelica lactone (BAL) and 2-methoxy-2-methylfuran (MMF) yields obtained after 5 min batch alcoholysis of 0.2 M furfuryl alcohol (FA) assisted by microwave irradiation in methanol (MeOH) at 150 °C using 50 mg of zeolite catalyst.

Fig. 1 . 2

 12 Fig. 1.2 Effect of hydrodynamic pressurization on ML and BAL yields over 2 h on stream in continuous flow alcoholysis at 170 °C using 200 mg H-ZSM-5-50 and 0.2 M FA in MeOH at 0.2 mL min -1 feed rate.

Fig. 1 . 3

 13 Fig. 1.3 Effect of FA load in MeOH and flow rate on (a) conversion and (b) yield of ML, (c) BAL and (d) MMF, observed in continuous flow alcoholysis at 170 °C and 50 bar using 200 mg H-ZSM-5-50. Fig. 1.4 Evolution the ML yield with the weight hourly space velocity (WHSV, g g -1 h -1 ) at different flow rates, as observed in continuous flow alcoholysis at 170 °C and 50 bar using 200 mg H-ZSM-5-50.

Fig. 1 . 5

 15 Fig. 1.5 Effect of reaction temperature on conversion and product yields in continuous flow alcoholysis using 200 mg H-ZSM-5-50 and 1.6 M FA in MeOH at 0.2 mL min -1 feed rate.

Fig. 1 . 6

 16 Fig. 1.6 Operational stability in continuous flow alcoholysis experiments at at 170 °C and 50 bar using 200 mg H-ZSM-5-50 and (a) 1.6 M FA and (b) 0.2 M FA, both in MeOH at 0.2 mL min -1 feed rate. Fig. 1.7 Weight loss observed during thermogravimetric (TGA) analysis from fresh and used H-ZSM-5-50 recovered after continuous flow alcoholysis (170 °C, 50 bar, 0.2 mL min -1 ) using different feed loads of FA in MeOH.

Fig. 1 . 8

 18 Fig. 1.8

Fig. 1 . 9

 19 Fig. 1.9Plausible FA alcoholysis reaction mechanism in HZSM-5-50 catalytic system.

Fig. 2 . 1 Fig. 2 . 2 Fig. 2 . 3 Fig. 2 . 5 Fig. 2 . 6 Fig. 3 . 3

 212223252633 Fig. 2.1 Effect of catalysts and residence time on (a) the GVL yields and (b) on the productivity. Reaction conditions: ML (0.2 M), catalyst (0.88 cm 3 of the CatCart cartridge), 2-PrOH, 130 °C, 20 bar, 0.4 mL min -1 . Fig. 2.2 Effect of reaction temperature on GVL productivity and products yield in continuous flow process. Reaction conditions: ML (0.2 M), 5% Ru/C (330 mg), 2-PrOH, 100-150 °C, 20 bar, 0.4 mL min -1 . Fig. 2.3 Effect of hydrodynamic pressure on GVL productivity and products yield and productivity in continuous flow process. Reaction conditions: ML (0.2 M), 5% Ru/C (330 mg), 2-PrOH, 150 °C, 20-60 bar, 0.4 mL min -1 . Fig. 2.4 Effect of flow rate on GVL productivity and products yield in continuous flow process. Reaction conditions: ML (0.2 M), 5% Ru/C (330 mg), 2-PrOH, 150 °C, 40 bar, 0.2-0.8 mL min -1 . Fig. 2.5 Effect of flow rate and substrate concentration with a constant ML feeding rate on GVL and MHP yields in continuous flow process. Reaction conditions: ML (0.2-0.8 M), 5% Ru/C (330 mg), 2-PrOH, 150 °C, 40 bar, 0.2-0.8 mL min -1 . Fig. 2.6 Operational stability of the catalyst 5% Ru/C in continuous flow alcoholysis of ML. Reaction conditions: ML (0.4 M), 5% Ru/C (330 mg), 2-PrOH, 150 °C, 40 bar, 0.8 mL min -1 . Fig. 3.1 Effect of Na2CO3 amount on HMFCA synthesis. Reaction condition: HMF (37.8 mg), Na2CO3 (0-158 mg) Ag2O (20 mg), 10 mL HPLC water, oil bath 90 ºC under stirring 300 rpm, 8.1 wt% H2O2 aqueous with flow rate 0.2 mL min -1 during 1 h. Fig. 3.2 Effect of catalyst amount on HMFCA synthesis. Reaction condition: HMF (37.8 mg), Na2CO3 (126.4 mg), Ag2O (0-25 mg), 10 mL HPLC water, oil bath 90 ºC under stirring 300 rpm, 8.1 wt% H2O2 aqueous with flow rate 0.2 mL min -1 during 1 h. Fig. 3.3 Effects of temperature and reaction time on HMFCA synthesis. Reaction condition: HMF (37.8 mg), Na2CO3 (126 mg), Ag2O (20 mg), 10 mL HPLC water, oil bath 90 or 120 ºC under stirring 300 rpm, 8.1 wt% H2O2 aqueous with flow rate 0.1-2 mL min -1 during 6-120 min.

Fig. 3 . 4

 34 Fig. 3.4 Effects of H2O2 concentration on HMFCA synthesis. Reaction condition: HMF (37.8 mg), Na2CO3 (126 mg), Ag2O (20 mg), 10 mL HPLC water, oil bath 90 ºC under stirring 300 rpm, 0-10.6 wt% H2O2 aqueous with flow rate 0.2 mL min -1 during 60 min.

Fig. 3 . 5 Fig. 3 . 7

 3537 Fig. 3.5

Fig. 3

 3 Fig. 3.8 SEM-mapping micrographs of the fresh catalyst (A-D) and the spent catalyst after the batch (E-H) and the continuous flow reaction (J-M).

Fig. 3

 3 Fig. 3.9 TEM micrographs of the fresh catalyst (A) and the spent catalyst (B) and the continuous flow reaction (C). Insets: size distribution histograms based on TEM images (100 nanoparticles).

Fig. 3

 3 Fig. 3.10Plausible HMF oxidation mechanism in Ag2O-H2O2 catalytic system.

Fig. 4 . 1

 41 Fig. 4.1 Catalyst screening experiments. Reaction conditions: HMF (37.8 mg, 0.3 mmol), Na2CO3 (31 mg, 0.3 mmol), catalysts (25 mg) in water (5 mL), 2 min under MW (30 W) and then addition of aqueous H2O2 (6.5 wt %) with a flow rate of 1 mL min -1 during 10 min under MW (8 W).

Fig. 4

 4 Fig. 4.2 HMF conversion, FFCA, DFF and FDCA yields versus reaction time. Reaction conditions: HMF (37.8 mg, 0.3 mmol), Na2CO3 (31 mg, 0.3 mmol), catalysts (25 mg) in water (5 mL), 2 min under MW (30 W) and then addition of aqueous H2O2 (6.5 wt %) with a flow rate of 0.1-10 mL min -1 during 1-60 min under MW (8 W).

Fig. 4 . 3

 43 Fig. 4.3 Optimization of HMF oxidation to FDCA via FFCA under microwave-batch conditions. Fig. 4.4 HMF conversion and FFCA, DFF, FDCA yield at different reaction times. Reaction conditions: HMF (37.8 mg, 0.3 mmol), Na2CO3 (31 mg, 0.3 mmol), catalysts (25 mg), air flow (3 mL min -1 ) in water (15 mL), 80 °C.

Fig. 4 . 5

 45 Fig. 4.5 Optimization of HMF oxidation to FDCA via FFCA with air flow. Reaction conditions: HMF (37.8 mg, 0.3 mmol), Na2CO3 (31 mg, 0.3 mmol), catalysts (25 mg), air flow (3 mL min -1 ) in water (15 mL), 80 °C, 6 h and then addition of NaOH (95.9 mg, 2.4 mmol) in the presence of air flow (3 mL min -1 ), 80 °C, 2-20 h. Fig. 4.6 N2 adsorption-desorption isotherms of fresh and spent catalysts.

Fig. 4

 4 Fig. 4.7X-ray diffractograms of the fresh and spent samples.

Fig. 5 . 1

 51 Fig. 5.1(a)13 C-NMR spectrum of PEF in DMSO-d6; (b,d)13 C-and 1 H-NMR spectra of

Fig. 5 . 2 DSC

 52 Fig. 5.2

Fig. S1. 1

 1 Fig. S1.1 Illustration of the ThalesNano TM Phoenix equipment used for continuous flow alcoholysis of furfuryl alcohol feedstocks in methanol, ethanol or n-propanol.

Fig. S1. 2

 2 Fig. S1.2 XRD spectra of (a) pristine H-ZSM-5-50, (b) H-ZSM-5-50 used in continuous flow acloholysis (1.6 M FA in MeOH, 170 °C, 50 bar, 0.2 mL min -1 ) and (c) used H-ZSM-5-50 and regenerated by calcination at 500 °C during 4 h. Fig. S2.1 Illustration of the ThalesNanoTM H-Cube Pro™ equipment used for continuous flow of methyl levulinate feedstocks in 2-propanol. Fig. S2.2 NMR of the GVL and methyl 4-hydroxypentanoate(MHP).

Fig. S4. 1

 1 Fig. S4.1 Illustration of the MiniFlow 200SS microwave equipment used for microwave batch of HMF oxidation to FDCA. Fig. S4.2 Illustration of the MiniFlow 200SS microwave equipment used for continuous flow of HMF oxidation to FDCA.

Fig. S5. 1 2D-

 1 Fig. S5.1 2D-NMR sequences of BDHPFDC: COSY ( 1 H-1 H) and HMBC ( 1 H-13 C).

Fig. S5.2 1 H

 1 Fig. S5.2 1 H NMR of PEF in DMSO-d6 after complete polymerization.

Fig. S5.3 1 H

 1 Fig. S5.3 1 H NMR of PDGF after polymerization.Fig. S5.4 Cosy ( 1 H-1 H) spectrum of PDGF. Fig. S5.5 FT-IR spectra of (a) PEF, (b) PHPF and (c) PDGF. Fig. S5.6 TG-DTG curves of (a) PEF and (b) PHPF.

Fig. 0. 1 .

 1 Fig. 0.1. Major conversion technologies for converting biomass into useful energy carriers.

Fig. 0. 2 .

 2 Fig. 0.2. Electric (E) and magnetic (H) field components in microwaves.

Fig. 0. 3 . 4 .

 34 Fig. 0.3. The difference between microwave and conventional heating nature.

Fig. 0. 4 .

 4 Fig. 0.4. The frequency and wavelength of microwave radiation region.

Fig. 0. 5 .

 5 Fig. 0.5. The fundamental mechanism of microwave heating: (A) dipole rotation; (B) ionic

6 .

 6 scientific microwave apparatus are Anton Paar (Monowave), CEM (Discover), Biotage (Initator) and Sairem (Minilabotron 2000). Which are shown in Fig. 0.Anton Paar (Monowave) are capable of heating reactions, in sealed-vessel format, the maximum temperatures can reach to 300 °C. Pressure limits of the glass reaction vessels used are 300 psi (~20 bar) for the Initator and Discover units and 435 psi (30 bar) for the Monowave (Fig. 0.6 a). The CEM Discover (Fig. 0.6 b) can be used accommodating round bottom flasks of up to 125 mL capacity. The equipment utilizes 300 W (Discover), 400 W (Initiator), and 850 W (Monowave) magnetrons. The waveguide design and intellectual property of the units are quite different, though all are very effective at heating reactions. Temperature is generally monitored via an infrared detector located below or alongside the reaction vessel. Alternatively, a fiber-optic probe can be immersed in the reaction vessel by means of a thermowell. Pressure measurement is generally by means of a load cell. Biotage® Initiator (Fig. 0.6 c) represents the latest in microwave synthesis

Fig. 0. 6 .

 6 Fig. 0.6. Four small scale dedicated microwave units for scientific applications.

Fig. 0. 7 .

 7 Fig. 0.7. Reactors used for continuous flow synthesis.

Fig. 0. 8 .

 8 Fig. 0.8. Comparison of batch microwave and flow processing (conductive heating).

ü

  (headspace) batch conditions to a conventionally heated flow regime are highlighted (Fig. 0.8). In this regard, continuous flow processing has a number of significant and inherent advantages when compared to batch reactor technologies in details: Continuous flow processing allows a better of control of reaction conditions.

  pressure meso-fluidic reactors employ heterogeneous catalysts in a continuous flow regime, cartridge based flow devices such as the microwave assisted continuous flow reactor, ThalesNano Phoenix flow reactor and H-Cube Pro™ and shown in Fig. 0.9 have been showed.

Fig. 0. 9 .

 9 Fig. 0.9. Different type of laboratory scale continuous flow reactors.

  The MiniFlow TW 200SS (Fig.0.9 a) is a device that offers the ability to work with multiple microwave reactors, easy to use and specifically designed to work with very small sample amounts or low load samples. The versatility of the MiniFlow 200SS allows it to adapt to all the needs of the laboratory. Also, it is a didactic device that allows the user to know and understand the principle of microwave technology associated with chemistry, as well as the components related to operation.The Phoenix Flow Reactor™ (Fig.0.9 b) is an easy to use reactor designed for high temperature (up to 450 °C temperature capability) and high pressure reactions (1-100 bar), three different system packages are available with additional modules, reactions can be performed in a loop homogeneously or with a range of different cartridges heterogeneously enabling the synthesis of novel compounds in a parameter space not achievable with standard laboratory equipment. The H-Cube Pro™ (Fig. 0.9 c) is the new standard for hydrogenation. This instrument enables safe hydrogenation in flow at high pressures. Quick reactions can be performed without solid catalyst handling or H2 gas cylinders. The H-Cube Pro™ provides a wide temperature range and the ability to adjust the amount of H2 helps to solve selective transformations. It offers great hydrogen production for high throughput, wider temperature capability including active cooling for more selective reactions, and a graphical interface with real time reaction monitoring/data logging and method storage capabilites. Above all, how to realize biomass based compounds with high valuable conversion under both microwave heating method and continuous flow regime are my majority subject. The biomass downstream products from lignocellulosic materials, such as the furan compounds, since they are considered to have especially highly potential for the production of chemicals and fuels. Furfural (FF) and 5-hydroxymethylfurfural (HMF) as the most important and popular platform compounds which can be further transformed to more biomass based downstream products that have various industrial applications (Fig. 0.10).

Fig. 0. 10 .

 10 Fig. 0.10. Synthesis and application of two platform molecules: Furfural and 5-

Scheme 1 . 1 .

 11 Scheme 1. 1. Production of biomass derived alkyl levulinates via (a) esterification of levulinic acid,

Fig. S 1 . 1

 11 in the Supporting Information), connected to a HPLC pump to supply a continuous feed of a 0.1-1.6 M FA solution in MeOH, EtOH or n-PrOH. A 70 mm CatCart cartridge (0.88 mL empty volume) was packed with 200 mg catalyst by applying vacuum suction at the bottom of the cartridge.

) 1 . 4 . Results and discussion 1 . 4 . 1 .

 14141 Catalyst screeningTwo commercial FAU zeolites (H-Y-5.2 and H-Y-60) and two commercial MFI zeolites (H-ZSM-5-30 and H-ZSM-5-50) were tested as solid acid catalysts for the alcoholysis of furfuryl alcohol (FA) feedstocks in methanol (MeOH), aiming to reach high methyl levulinate (ML) yields.In order to distinguish the catalytic performance in FAU and MFI, Brønsted, Lewis acidity and porosity analysis were performed by titration experiment and nitrogen adsorption/desorption experiments. It is assumed that DMPY (2,6-dimethylpyridine) selectivity titrates Brønsted sites (methyl groups hinder coordination of nitrogen atoms with Lewis acid sites) while PY (pyridine) adsorbs both on Brønsted and Lewis acidity.

Fig. 1 . 1 .

 11 Fig. 1.1. Methyl levulinate (ML), α-angelica lactone (AAL), β-angelica lactone (BAL) and 2-

Fig. 1 . 2 .

 12 Fig. 1.2. Effect of hydrodynamic pressurization on ML and BAL yields over 2 h on stream in

(Fig. 1 .

 1 3 c).

Fig. 1 . 3 .

 13 Fig. 1.3. Effect of FA load in MeOH and flow rate on (a) conversion and (b) yields of ML, (c) BAL

Fig. 1 .

 1 3 d) started to build up, showing the kinetic limitations (for the fixed catalyst amount of 200 mg). The empiric relations between the product yield and the weight hourly space velocity (WHSV) at increasing FA load and increasing flow rate are illustrated in Fig. 1.4.

  (g) to which FA is fed; it allows to compare the activity of different catalysts having different loads in continuous flow. The results showed that the ML yield increases with the FA concentration until a certain breaking point between 0.8 and 1.6 M. Further experiments are required to optimize the flow rate in function of the feedstock load more exactly. Feed solutions of 0.8 and 1.6 M FA correspond with MeOH-FA molar ratios of 29 and 13, respectively. In comparison, previously reported batch results

Fig. 1 . 4 .

 14 Fig. 1.4. Evolution the ML yield with the weight hourly space velocity (WHSV, g g -1 h -1 ) at different

Fig. 1 . 5 .

 15 Fig. 1.5. Effect of reaction temperature on conversion and product yields in continuous flow alcoholysis using 200 mg H-ZSM-5-50 and 1.6 M FA in MeOH at 0.2 mL min -1 feed rate.

1. 4 . 5 .Fig. 1 . 6 .

 4516 Fig. 1.6. Operational stability in continuous flow alcoholysis experiments at 170 °C and 50 bar using

Fig. 1 . 7 .

 17 Fig. 1.7. Weight loss observed during thermogravimetric (TGA) analysis from fresh and used H-ZSM-5-50 catalyst recovered after continuous flow alcoholysis (170 °C, 50 bar, 0.2 mL min -1 ),

Fig. 1 . 8 .

 18 Fig. 1.8. Comparison of catalytic activity in continuous flow alcoholysis of 0.2 M FA in MeOH (170 °C, 50 bar, 0.2 mL min -1 ), using 200 mg of (a) fresh H-ZSM-5-50. (b) spent H-ZSM-5-50

Fig. 1 . 9 .

 19 Fig. 1.9. Plausible FA alcoholysis reaction mechanism in HZSM-5-50 catalytic system.

Scheme 2 . 1 .

 21 Scheme 2.1. Production of biomass-derived GVL from cellulose (in green) and hemicellulose (in blue) via AL as a common intermediate.

  Pro TM Flow Reactor ThalesNano TM , Hungary (FigureS2.1), connected to a HPLC pump to supply a continuous feed of ML (0.2-0.8 M) in 2-PrOH, 70 mm CatCart cartridge (0.88 mL empty volume) was packed with 330 mg catalyst by applying vacuum suction at the bottom of the cartridge. The total flow through volume (including feed, reactor and product sections) was 6 mL. First, pure 2-PrOH was pumped through the system and then the feed was changed to the ML feedstock. The flow was continued until the temperature (100-150 °C) and hydrodynamic pressurization (0-50 bar) of the reactor module were reached. Then, in function of the flow rate (0.2-0.8 mL min -1 ), the reaction proceeded during a certain time (12-50 min) before collecting the first sample (time zero). Further samples were collected after regular time intervals.

Fig. 2 . 1 .

 21 Fig. 2.1. Effect of catalysts and residence time on (a) the GVL yields and (b) on the productivity. Reaction conditions: ML (0.2 M), catalyst (0.88 cm 3 of the CatCart cartridge), 2-PrOH, 130 °C, 20 bar, 0.4 mL min -1 .

  2.2). Whatever the temperature, ML furnished two main compounds: GVL and MHP (see in Fig. S2.2 NMR results)

  ?>"L">S (Z,$/ W ℎ ) b.

Fig. 2 . 2 .

 22 Fig. 2.2. Effect of reaction temperature on GVL productivity and products yield in continuous flow process. Reaction conditions: ML (0.2 M), 5% Ru/C (330 mg), 2-PrOH, 100-150 °C, 20 bar, 0.4 mL min -1 .

  With a higher pressure (60 bar vs 40 bar), no apparently changes of GVL and MHP yields were observed. From the point of energy conservation, the pressurization was set as 40 bar for the following optimization reactions.

Fig. 2 . 3 .

 23 Fig. 2.3. Effect of hydrodynamic pressure on GVL productivity and products yield and productivity in continuous flow process. Reaction conditions: ML (0.2 M), 5% Ru/C (330 mg), 2-PrOH, 150 °C, 20-60 bar, 0.4 mL min -1 .

(

  in batch reactor. b microwave-assisted reaction (300 W) in batch reactor. c conventional heating in continuous flow reactor. d residence time/min.

Fig. 2 . 6 .

 26 Fig. 2.6. Operational stability of the catalyst 5% Ru/C in continuous flow alcoholysis of ML. Reaction conditions: ML (0.4 M), 5% Ru/C (330 mg), 2-PrOH, 150 °C, 40 bar, 0.8 mL min -1 .

  catalyst 5% Ru/C for the production of γ-valerolactone (GVL) in continuous flow from either levulinic acid (LA) or alkyl levulinates (AL). After the investigation of methyl levulinate (ML) experiment parameters (reaction temperature, pressure, flow rate, starting material concentration), the optimization condition was at ML (0.4 M) in 2-PrOH, 5% Ru/C (330mg), 150 °C, 40 bar, flow rate=0.8 mL min -1 . Feedstock were fully GVL Yield(%) MHP Yield(%)converted with 85% GVL yield, and 13% methyl 4-hydroxypentanoate (MHP) yield, with the highest productivity is 0.99 mol g -1 h -1 . Effect of the nature of the AL experiments showed the lactonization were facilitated with shorter AL alkyl chains.Finally, 5% Ru/C shows good stability in 9 h cycle experiments.The catalytic upgrading of 5-hydroxymethylfurfural (HMF), an important biobased platform chemical, is of great interest. In this work, we report the selective oxidation of HMF to 5-hydroxymethyl-2-furancarboxylic acid (HMFCA) employing Ag2O, a relatively cheap and commercially available catalyst, to achieve an impressive HMFCA yield of 98 % (60 min, 90 ºC). Various reaction parameters including type of catalyst, base, quantities of base and catalyst, reaction temperature in function of reaction time as well as hydrogen peroxide concentration have been optimized.

Fig. 3 . 1 .

 31 Fig. 3.1. Effect of Na2CO3 amount on HMFCA synthesis. Reaction condition: HMF (37.8 mg), Na2CO3 (0-158 mg) Ag2O (20 mg), 10 mL HPLC water, oil bath 90 ºC under stirring 300 rpm, 8.1 wt% H2O2 aqueous with flow rate 0.2 mL min -1 during 1 h.

Fig. 3 . 2 .

 32 Fig. 3.2. Effect of catalyst amount on HMFCA synthesis. Reaction condition: HMF (37.8 mg), Na2CO3 (126.4 mg), Ag2O (0-25 mg), 10 mL HPLC water, oil bath 90 ºC under stirring 300 rpm, 8.1 wt% H2O2 aqueous with flow rate 0.2 mL min -1 during 1 h.

  HMFCA yield increased gradually from around 50% to around 70% at 90 ºC and then reached quantitative values in 1 h, remaining stable even a couple of additional hours later. As can be predicted, HMF conversion and HMFCA yield increased faster at 120 ºC in the function of reaction time. HMF conversion and HMFCA yield could reach completion in only 24 min. The selectivity of HMFCA by using both temperature values showed the same stability trend. Temperature and time variables did not display a considerable effect on HMFCA selectivity.

Fig. 3 . 3 .

 33 Fig. 3.3. Effects of temperature and reaction time on HMFCA synthesis. Reaction condition: HMF (37.8 mg), Na2CO3 (126 mg), Ag2O (20 mg), 10 mL HPLC water, oil bath 90 or 120 ºC under stirring 300 rpm, 8.1 wt% H2O2 aqueous with flow rate 0.1-2 mL min -1 during 6-120 min.

Fig. 3 . 4 .

 34 Fig. 3.4. Effects of H2O2 concentration on HMFCA synthesis. Reaction condition: HMF (37.8 mg), Na2CO3 (126 mg), Ag2O (20 mg), 10 mL HPLC water, oil bath 90 ºC under stirring 300 rpm, 0-10.6 wt% H2O2 aqueous with flow rate 0.2 mL min -1 during 60 min.

Entries 9 -

 9 12 displayed the continuous flow reaction under 90 ºC with the same catalyst amount (20 mg) in absence of oxidizing agent (considering the corrosive behavior of aq. H2O2 under high temperature for the H-Cube continuous flow reactor).

Fig. 3 . 5 .

 35 Fig. 3.5. Stability test of Ag2O. Reaction condition: HMF (37.8 mg), Na2CO3 (126 mg), Ag2O (20 mg), 10 mL HPLC water, 90 ºC in oil bath under 300 rpm stirring, 8.1 wt% H2O2 aqueous with flow rate 0.2 mL/min during 60 min. HMF, Na2CO3 and H2O2 aqueous were adjusted to recovered catalyst.

Fig. 3 . 6 .

 36 Fig. 3.6. XRD patterns of the fresh and spent catalyst, after the batch and continuous flow reaction.

  Particularly, C 1s XPS region of the samples displayed three contributions associated with C-C/C = C (ca. 284.6 eV), C=O (ca. 285.5-286.0 eV) and COO-(ca. 288.0-288.5

Fig. 3 . 7 .

 37 Fig. 3.7. Deconvoluted XPS spectra of the fresh catalyst (A-C) and the spent catalyst after the batch (D-F) and the continuous flow reaction (G-I).

Fig. 3 . 8 .

 38 Fig. 3.8. SEM-mapping micrographs of the fresh catalyst (A-D) and the spent catalysts after the

Fig. 3 . 9 .

 39 Fig. 3.9. TEM micrographs of the fresh catalyst (A) and the spent catalyst (B) and the continuous flow reaction (C). Insets: size distribution histograms based on TEM images (100 nanoparticles).

Fig. 3 . 10 .

 310 Fig. 3.10. Plausible HMF oxidation mechanism in Ag2O-H2O2 catalytic system.

  solution) and (ii) Ag2O reduction after reaction. Three strategies for catalyst regeneration were investigated. The first method was based on a thermal treatment of the reused catalyst (rinsed with DMSO, acetone and deionized water) at 60 o C overnight.The recycling result showed 87% HMF conversion and 85% HMFCA yield. Such data indicated an incomplete Ag 0 oxidation process or the presence of residual humins. The second strategy was based on the calcination of the recycled catalyst (washing by deionized water, DMSO and acetone) at 400 o C during 4 h in Maffle furnace. The recycling experiments showed only 20% of HMFCA yield, demonstrating that Ag2O will be totally decomposed at 400 o C. Thus, employment of high calcination temperatures was not a suitable method for Ag2O regeneration. The third attempt was to immerse the recycled catalyst (40 mg, after washing by deionized water, DMSO and acetone) into 3 mL of 8 wt% aq. H2O2 under stirring for 2 hours. The recycling experiment showed 93 % HMF conversion and 87% HMFCA yield. The result suggested that by using aqueous H2O2, just a partial silver oxidation could be accomplished. The presence of humins on the surface also hindered catalyst regeneration. Additional experiments will be conducted in due course for an optimum regeneration of the catalytic system.

  Oxidation of 5-hydroxymethylfurfural (HMF) towards 2,5-furandicarboxylic acid (FDCA) was successfully performed under microwave-assisted heating, using hydrogen peroxide (H2O2) as oxidant agent and various Ru based materials as catalytic systems. Particularly 5% Ru/C, a relatively cheap and commercially available catalyst, achieved an impressive FDCA yield of 88% in only 30 min under microwave batch conditions. The reaction was performed in two steps, adding a weak (Na2CO3) and strong base (NaOH) successively. Various reaction parameters such as reaction time, type of base, base amount, temperature, catalyst loading as well as hydrogen peroxide concentration have been optimized. The optimum conditions were employed in order to accomplish the reaction under air atmosphere, exhibiting 84% FDCA yield in 22 h.

Scheme 4 . 1 .

 41 Scheme 4.1. Different pathways for the production of FDCA starting from LCB.

4. 4 . 1 . MW batch for the production of FDCA 4 . 4 . 1 . 1 .

 414411 Catalyst screening

Fig. 4 . 1 . 4 . 4 . 1 . 2 . 4 . 2 .

 41441242 Fig. 4.1. Catalysts screening experiments. Reaction conditions: HMF (37.8 mg, 0.3 mmol), Na2CO3(31 mg, 0.3 mmol), catalysts (25 mg) in water (5 mL), 2 min under MW (30 W) and then addition of aqueous H2O2 (6.5 wt %) with a flow rate of 1 mL min -1 during 10 min under MW (8 W).

4. 4 . 1 . 6 .Fig. 4 . 2 .

 41642 Fig. 4.2. HMF conversion, FFCA, DFF and FDCA yields versus reaction time. Reaction conditions: HMF (37.8 mg, 0.3 mmol), Na2CO3 (31 mg, 0.3 mmol), catalysts (25 mg) in water (5 mL), 2 min under MW (30 W) and then addition of aqueous H2O2 (6.5 wt %) with a flow rate of 0.1-10 mL min - 1 during 1-60 min under MW (8 W).

4 . 4 . 1 . 7 .

 4417 reaction was rate-limiting step. Effect of base amount for the second step production of FDCA

Scheme 4 . 3 .FDCAFig. 4 . 3 .

 4343 Scheme 4.3. Microwave-assisted oxidation of HMF to FDCA via FFCA in batch reactor.

  and Yield (%) Reaction time and base amount FDCA Yield FFCA Yield HMF Conv. reaction time from 50 min to 25 min.

Fig. 4 . 4 .

 44 Fig. 4.4. HMF conversion and FFCA, DFF, FDCA yield at different reaction times. Reaction conditions: HMF (37.8 mg, 0.3 mmol), Na2CO3 (31 mg, 0.3 mmol), catalysts (25 mg), air flow (3 mL min -1 ) in water (15 mL), 80 °C.

Fig. 4 . 5 .

 45 Fig. 4.5. Optimization of HMF oxidation to FDCA via FFCA with air flow. Reaction

Fig. 4 . 6 .

 46 Fig. 4.6. N2 adsorption-desorption isotherms of fresh and spent catalysts.

Scheme 5 . 1 .

 51 Scheme 5.1. Different ways for the production of 2,5-furandicarboxylic acid starting from lignocellulose.

  On the other hand, from a technical point of view, except the very classical

  = CH 2 CH 2 ) PHPF (R = CH 2 CHOHCH 2 ) PDGF (R = CH 2 CHOHCH 2 OCH 2 CHOHCH 2 ) OH R n

3 .

 3 Scheme 5.3. Synthesis of BHEFDC starting from DEFDC in the presence of Co(Ac)2 under microwave radiation.

Scheme 5 . 4 .

 54 Scheme 5.4. Synthesis of BDHPFDC starting from DEFDC in the presence of Co(Ac)2 under microwave radiation.

Scheme 5 . 5 .

 55 Scheme 5.5. Synthesis of PEF in the presence of Co(Ac)2.

Scheme 5 . 6 .

 56 Scheme 5.6. Synthesis of PHPF in the presence of Co(Ac)2.

  5.1c).The 1 H-NMRs of this product material are also given (Fig.S5.3). According to the results displayed in the COSY spectrum of BDHPFDC, some similarities can be found with spectra obtained from a sample of PDGF in DMSO-d6. Located in the center part of the corresponding spectrum grid four signals around 4.5 ppm in both directions form a square and are Co(Ac) 2 (12 mol%) furan rings bound to diglycerol through a primary alcohol ester made of CH2 groups (Fig.S5.4). Besides, at 3.6 and 5.1 ppm, there are two signals rather characteristic of furan moieties bonded with a secondary alcohol group that corresponds to the -CH-group of the diglycerol. Those results are evidence of the nonlinear nature of the formed PDGF polymer.

Fig. 5 . 1 .

 51 Fig. 5.1. (a) 13 C-NMR spectrum of PEF in DMSO-d6; (b,d)13 C-and 1 H-NMR spectra of PHPF in DMSO-d6 and (c)13 C-NMR of PDGF measured in DMSO-d6.

Fig. 5 . 2 .

 52 Fig. 5.2. DSC thermograms of (a) PEF, (b) PHPF and (c) PDGF after quenching their melted solution with liquid N2. Heating and cooling rate was 10 °C/min.

Fig. 5 . 3 .

 53 Fig. 5.3. TGA traces curves of PEF and PHPF.

  XRD analysis. FE-SEM observations of PEF powder morphology displayed some kind of fibrous and apparently porous network.

Fig. 5 . 4 .

 54 Fig. 5.4. XRD diffractograms and SEM images of synthesized (a) PEF and (b) PHPF.

Fig. 5 . 5 .

 55 Fig. 5.5. EDX spectra of (a) PEF and (b) PHPF.

1 .

 1 Fig. S1.1. Illustration of the ThalesNano TM Phoenix equipment used for continuous flow alcoholysis of furfuryl alcohol feedstocks in methanol, ethanol or n-propanol.

Fig. S1. 2 .

 2 Fig. S1.2. XRD spectra of (a) pristine H-ZSM-5-50, (b) H-ZSM-5-50 used in continuous flow acloholysis (1.6 M FA in MeOH, 170 °C, 50 bar, 0.2 mL min -1 ) and (c) used H-ZSM-5-50 and regenerated by calcination at 500 °C during 4 h.

Fig. S2. 2 .

 2 Fig. S2.2. NMR of the GVL and methyl 4-hydroxypentanoate(MHP).

-

Chapter S4 .Fig. S4. 1 .

 S41 Fig. S4.1. Illustration of the MiniFlow 200SS microwave equipment used for microwave batch of HMF oxidation to FDCA.

Fig. S4. 2 .

 2 Fig. S4.2. Illustration of the MiniFlow 200SS microwave equipment used for continuous flow of HMF oxidation to FDCA.

Fig. S5. 2 . 1 H

 21 Fig. S5.2. 1 H NMR of PEF in DMSO-d6 after complete polymerization.

Fig. S5. 3 . 1 H

 31 Fig. S5.3. 1 H NMR of PDGF after polymerization.

Fig. S5. 4 .

 4 Fig. S5.4. Cosy (1H-1H) spectrum of PDGF.

Fig. S5. 5 .

 5 Fig. S5.5. FT-IR spectra of (a) PEF; (b) PHPF and (c) PDGF.

Fig. S5. 6 .

 6 Fig. S5.6. TG-DTG curves of (a) PEF and (b) PHPF.

Table 0

 0

	.1	Commonly used organic solvents classified according to their heating efficiency
		(tan δ) in the microwave field
	Table 0.2	Fundamental information of furfural
	Table 0.3	Fundamental information of 5-hydroxymethylfurfural
	Table 1.1	Acid catalysts reported for the conversion of FA to AL
	Table 1.2	Total specific surface area (SSA), average pore size (APS), total pore volume
		(TPV) and meso/macro pore & external area/ volume of HZSM-5 and H-Y
		zeolites
	Table 1.3	Si/Al ratio and acidic properties of H-ZSM-5 and H-Y zeolites

Table 1 .

 1 4 Effect of alcohol chain length in continuous flow alcoholysis at 170 °C and 50 bar using 1.6 M FA at 0.2 mL min -1 feed rate and 200 mg H-ZSM-5-50

Table 2 .

 2 1 5%Ru/C as catalysts reported for the conversion of LA and AL to GVL

Table 2 .

 2

2

Effect of AL molecular weight as starting material for the production of GVL Table 3.1 Conversion of HMF into HMFCA under different catalysts and bases

Table 3

 3

	.2	Conversion of HMF into HMFCA under different temperatures
	Table 3.3	Comparison between conventional heating, microwave irradiation and
		continuous flow in the oxidation of HMF to HMFCA
	Table 3.4	pH change in pristine and spent Ag2O during different time
	Table 4.1	Activated carbon support Ru catalysts for the conversion of 5-
		hydroxymethyfurfural (HMF) to 2, 5-furandicarboxylic acid (FDCA)
	Table 4.2	Optimization of HMF oxidation to FFCA using 5% Ru/C catalyst
	Table 4.3	Microwave-assisted continuous HMF oxidation to FDCA
	Table 4.4	Catalyst reusability studies and acid-base properties of fresh and spent catalyst
	Table 4.5	Porosity and crystal size data of the fresh and spent catalysts
	Table 4.6	ICP-OES measurement of Ru leaching under different reaction process
	Table 5.1	Dehydration of mucid acid in the presence of acid catalyst for the production of
		FDCA
	Table 5.2	Dehydration of mucid acid in different temperature for the production of FDCA
	Table 5.3	Dehydration of mucid acid in different reaction time for the production of FDCA
	Table 5.4	Production of DEFDC starting from mucic acid in a one-pot two steps reaction

Table 0 .1.

 0

Table 0 . 1 .

 01 Commonly used organic solvents classified according to their heating efficiency (tan δ)

	in the microwave
	High (> 0.5)		Medium (0.1 -0.5)	Low (< 0.1)
	Solvent	tan δ	Solvent	tan δ	Solvent	tan δ
	Ethylene glycol	1.350	2-Butanol	0.447	Chloroform	0.091
	Ethanol	0.941	Dichlorobenzene	0.280	Acetonitrile	0.062
	DMSO	0.825	NMP	0.275	Ethyl acetate	0.059
	2-Propanol	0.799	Acetic acid	0.174	Acetone	0.054
	Formic acid	0.722	DMF	0.161	THF	0.047
	Methanol	0.659	Dichloroethane	0.127	Dichloromethane	0.042
	Nitrobenzene	0.589	Water	0.123	Toluene	0.040
	1-Butanol	0.571	Chlorobenzene	0.101	Hexane	0.020

Table 0 .2. Fundamental information of furfural

 0

	IUPAC name	Furan-2-carbaldehyde	Appearance	Colorless oil
	Other names	Furfural, furan-2-carboxaldehyde, fural, aldehyde furfuraldehyde, 2-furaldehyde, pyromucic	Odor	Almond-like
	Formula	C5H4O2	Density	1.16 g/mL (20 °C)
	CAS Number	98-01-1	Boiling point	162 °C (324 °F; 435 K)
	EINECS Number	202-627-7	Solubility in water	83 g/L
	Molar mass	96.09 g•mol -1	Vapor pressure	2 mmHg (20 °C)
	Melting point	-37 °C (-35 °F; 236 K)	Flash point	60 °C (144 °F; 335 K)
	The first report was in 1821, German chemist Johann Wolfgang Döbereiner first
	discovered FF as a byproduct of formic acid synthesis. The Scottish chemist John
	Stenhouse found that FF could be produced by distilling a wide variety of crop materials,
	including corn, oats, bran, and sawdust, with aqueous sulfuric acid, he also determined
	an empirical formula of (C5H4O2) in 1840. Then, George Fownes named this oil FF in

Table 0 .3. Fundamental

 0

		information of 5-hydroxymethylfurfural
	IUPAC name	5-(Hydroxymethyl)furan-2-carbaldehyde	Appearance	Yellow powder
		5-(hydroxymethyl)-2-furaldehyde, 5-
		(hydroxymethyl)-2-furancarbonal, 5-
	Other names	(hydroxymethyl)-2-furfural, 5-hydroxymethyl-	Odor	chamomile flowers
		2-formylfuran,
	Formula	C6H6O3	Density	1.24 g/mL (25 °C)
	CAS Number	67-47-0	Boiling point	116 °C (1 hPa)
	EINECS Number	200-654-9	Solubility in water	Freely
	Molar mass	126.11 g•mol -1	Vapor pressure	0.005 mmHg (25 °C)
	Melting point	31.5 °C (88.7 °F; 304.65 K)	Flash point 79 °C, closed cup

Table 1

 1

	.1 compares the activity

Table 1 . 1. Acid

 1 catalysts reported for the conversion of FA to AL

	Entry	Catalyst (load, %) a	Conditions	FA (M)	ROH:FA molar ratio	AL yield (%) b	Ref.
		H2SO4 (8)	130 °C, 2 h	0.4	24 (MeOH)	50	[14]
		SO4-ZrO2 (8)	130 °C, 2 h	0.4	24 (MeOH)	73	[14]
		[BMIm-SH][HSO4] (8)	130 °C, 2 h	0.4	24 (MeOH)	94	[14]
		Al-TUD-1 (34)	140 °C, 2 h	0.3	57 (EtOH)	48	[15]
		H3PW12O40 (1.5)	120 °C, 2 h	0.2	60 (EtOH)	63	[16]
		AlCl3 (10)	110 °C, 2 h	0.3	55 (EtOH)	69	[17]
		α-Fe2O3 (3500)	250 °C, 1 h	0.02	745 (EtOH)	73	[18]
		Graphene oxide (25)	120 °C, 2 h	0.3	51(EtOH)	78	[19]
		HCl (39)	120 °C, 2 h	0.2	60 (EtOH)	87	[16]
	10	Amberlyst TM -15 (1.5)	120 °C, 2 h	0.2	60 (EtOH)	88	[16]
	11	[(HSO3-p)2im][HSO4] (12)	110 °C, 2 h	0.4	44 (EtOH)	92	[20]
	12	γ-Fe2O3/H-ZSM-5 (39)	130 °C, 2 h	0.2	55 (2-BuOH)	63	[21]
	13	Amberlyst TM -70 (25)	110 °C, 2 h	0.3	33 (1-BuOH)	68	[4]
	14	CuCl2 (9)	115 °C, 2 h	0.3	35 (1-BuOH)	81	[22]
	15	SBA-15-SO3H (25)	110 °C, 2 h	0.3	33 (1-BuOH)	83	[4]
	a Weight percentage on FA load; b molar percentage

1.3.1. Materials, solvents and reagents

	Furfuryl alchohol (FA, ≥ 98 %), methanol (MeOH, ≥ 99.9 %), ethanol (EtOH, ≥
	99.5 %), n-propanol (n-PrOH, ≥ 99.5 %), methyl levulinate (ML, 99 %), γ-
	valerolactone (GVL, 99 %) and n-decane (≥ 99 %) were purchased from Sigma-Aldrich
	and further used without purification. FA feedstocks of 0.1, 0.2, 0.4, 0.8 and 1.6 M were
	prepared by dissolving 0.993, 1.985, 3.979, 7.936 and 15.882 g FA in 100 mL alcohol
	in a volumetric flask using n-decane (5.0 mg/mL) as external standard. The commercial
	MFI (Mobil type five) zeolites CBV3024E and CBV5524G (H-ZSM-5-30 and H-ZSM-
	5-50 with SiO2/Al2O3 molar ratios 30 and 50, respectively) and FAU (Faujasite) zeolites
	CBV500 and CBV760 (H-Y-5.2 and H-Y-60 with SiO2/Al2O3 molar ratios 5.2 and 60,
	respectively) were purchased from Zeolytes International (USA).

Table 1 . 2 .

 12 Total specific surface area (SSA), average pore size (APS), total pore volume (TPV) and meso/macro pore & external area/ volume of HZSM-5 and H-Y zeolites[35]

	Catalyst		TSSA	APS	TPV	Meso/macro pore & external area (m 2 /g)/volume
		(m 2 g -1 ) a	(nm)	(ccg -1 ) b		(cc/g -1 ) c
	H-ZSM-5-30		350	1.7	0.30		70/0.19
	H-ZSM-5-50		400	1.3	0.26		100/0.13
	H-Y-5.2		570	1.4	0.39		55/0.19
	H-Y-60		790	1.4	0.56		190/0.32
	Catalyst	Si/Al	Total acidity	Brønsted acidity	Lewis acidity	Brønsted
		ratio	(μmol PY g -1 )	(μmol DMPY g -1 )	(μmol DMPY g -1 )	sites (%)
	H-ZSM-5-30	15	237		45		192	19
	H-ZSM-5-50	25	203		41		162	20
	H-Y-5.2	2.6	141		102		39	72
	H-Y-60	30	39		27		12	70

a SSA: Special surface area from N2 sorption at -196 o C, multi-point BET method b Total pore volume at P/P0= 0.99 c Meso/macro pore & external area = TSSA -micropore area (t-plot); Meso/macropore volume = TPV -micropore volume (t-plot) Table

1

.3. Si/Al ratio and acidic properties of H-ZSM-5 and H-Y zeolites

[35]

Table 1 . 4 .

 14 Effect of alcohol chain length in continuous flow alcoholysis at 170 °C and 50 bar using 1.6 M FA at 0.2 mL min -1 feed rate and 200 mg H-ZSM-5-50

			Conversion		Yield (%)
	Entry	Alcohol	(%)	Levulinate a	Angelica lactones	Alkoxymethylfuran b
	1	Methanol (C1)	100	79	21	0
	2	Ethanol (C2)	100	59	23	1
	3	n-Propanol (C3)	100	60	8	2

a methyl/ethyl/n-propyl levulinate; b 2-methoxy/ethoxy/n-propoxy-2-methylfuran.

  to MMF. The further formation of B using two different pathways: way 1 start with intermediate A to release water directly or way 2 start with MMF to release methanol under acidic condition. These two ways are in accordance with the mechanism reported by Maldonado et al.[37]. After elimination in acidic conditions, intermediate B could form compound C through electron shift.

	Then D was formed from C by another water molecular attack the other side of furan
	ring of intermediate C, with further electron and hydrogen shift intermediate F was
	finally formed. Due to unstable enolic structure formed lactone structure BAL and AAL

in our case. Further, after the addition with 1 eq. methanol attacked C=O group with the formation of intermediate G. Intermediate H with enolic structure was formed through C-O bond breaking. Finally the target compound ML was founded in our case.

Another most important intermediate DMOP could be produced by methanol attacking ML through nucleophilic effect. The species (P) with similar structure to DMOP with less stability than DMOP.

Conversion of alkyl levulinates into γ-valerolactone in the presence of Ru/C in continuous flow 2.1. Abstract

	2 mL min -1 , high feed loads
	up to 1.6 M FA were converted efficiently (79 % ML yield), but faced the build-up of
	polyfurfuryl alcohol. The initial activity of the used H-ZSM-5-50 catalyst was restored
	by regeneration at 500 °C. Finally, the alcoholysis in ethanol and n-propanol under
	identical conditions yielded 20 % less alkyl levulinate and similar yield of angelica
	lactones in ethanol, but 13 % less in n-propanol.

Chapter 2.

The present work explored a catalytic transfer hydrogenation process with several supported noble metal on carbon as catalysts for the production of γ-valerolactone (GVL) from methyl levulinates (ML) in iso-propanol (2-PrOH) and the performance of the commercial 5%Ru/C in continuous flow were investigated, GVL yields up to 83% at 150 ºC (40 bar) using a high load (0.4 M ML) feed at 0.8 mL min -1 flow rate. The catalyst productivity (Pr) equal to 0.99 mol g -1 h -1 . Methyl 4-hydroxypentanoate (MHP) were produced as major side product in lower amounts in continuous flow mode. Longterm (9 h) catalyst stability experiment showed good stability under optimum condition.

The yield of GVL obtained from ethyl levulinate (EL), butanol levuliante (BL) and levulinate acid (LA) were ca. 21%, 54% and 26% less than ML in 2-PrOH and Pr were 0.43, 0.73 and 0.48 less respectively. There is no obvious hydrogenation process when changed 2-PrOH to ethanol and 1-butanol.

2.3.1. Materials, solvents and reagents

	Methanol (MeOH, ≥ 99.9%), propan-1-ol (1-PrOH, ≥ 99.5%), propan-2-ol (2-
	PrOH, ≥ 99.5%), ML (99%), GVL (99 %) and n-decane (≥ 99%) were purchased from
	Sigma-Aldrich and further used without purification. ML feedstocks of 0.2, 0.4 and 0.8
	M were prepared by dissolving 2.602 g, 5.204 g and 10.400 g ML in 100 mL

isopropanol in a volumetric flask using n-decane (5.0 mg/mL) as external standard. The commercial 5%Ru/C, 5%Pd/C, 10%Pt/C and 5% Ru/Al2O3 were purchased from Sigma-Aldrich and STEM CHEMICALS further used without purification.

  EHP and BHP were calculated according to the Effective Carbon Number (ECN) method[44], based on the RF and ECN factor of ML (3.75), EL (4.75), BL(6.75)

	and the ECN factor of MHP (4), EHP (5), BHP (7).
	Mass spectra were record on a Hewlett-Packart HP 5973 mass spectrometer via a
	GC/MS coupling with a Hewlett-Packart HP 6890 chromatograph equipped with a
	capillary column HP-5MS (50 m × 0.25 mm i.d. and 0.25 µm film thickness, Alltech
	Part No.31163-01). lonisation was performed by electronic impact (EL, 70 eV). Mass
	spectra are reported as m/z (% of relative intensity).
	BL, methyl 4-hydroxypentanoate (MHP), ethyl 4-hydroxypentanoate (EHP), butanol
	4-hydroxypentanoate (BHP) and LA, n-decane were 3.58 min, 3.39 min, 3.92 min, 5.21
	min, 3.69 min, 4.16 min, 5.44 min, 4.98 min and 2.30 min. respectively. The response
	factors (RF) of ML and GVL relative to a fixed concentration (5.0 mg mL -1 ) of n-decane

GC-FID analysis was performed on a gas chromatograph (HP, 14009 Arcade, New York, United States) coupled with a FID detector equipped with a Supelco 2-8047-U capillary column (15 × 0.25 mm i.d. and 0.25 µm film thickness, Alltech Part No.31163-01). H2 was used as carrier gas at 1 mL min -1 flow rate. The samples were injected directly onto the column using septum-equipped programmable injector (SPI) system. The temperature of the injector was set 250 °C and the oven started at 70 °C, held for 1 min, raised to 250 °C at a rate of 20 °C min -1 , held for 10 min. The ionization mode was FID (70 eV, 300 μA, 250 °C). The identification of the compounds was performed by comparison of the retention times with pure standards and by GC/MS analysis. The solvent delay time was 0.90 min. The retention times of GVL, ML, EL, as internal standard were experimentally determined at 3.62 and 3.01, respectively. The linear regression coefficients of the calibrations were high in all cases (r 2 > 0.99). The RF for MHP, Proton nuclear magnetic resonance ( 1 H NMR) spectra were recorded using a Bruker AC 300 (300 MHz) or a Bruker AC 400 (400 MHz). The chemical shifts are expressed in parts per million (ppm) referenced to residual chloroform (7.26 ppm).

Carbon-13 nuclear magnetic resonance ( 13 C NMR) spectra were recorded using a Bruker AC 300 (75 MHz) or a Bruker AC 400 (100 MHz). The chemical shifts are expressed in parts per million (ppm) relative to the centre line of the triplet at 77.16 ppm for CDCl3

  With a low flow rate (0.2 mL min -1 ), the highest GVL yield was achieved (95% yield) with only 5% MHP. As expected, the decrease of residence time implying by the increase of the flow rate afforded a lower GVL yield (87-92% vs 95%) and a higher MHP yield (6-8% vs 2%). It was obvious that a lower flow rate offered a longer residence time, which favored the reactant contact with the Ru catalyst. In term of productivity, a short residence time with 0.8 mL min -1 flow rate gave a better result compared with a long residence time obtained with 0.2 mL min -1 flow rate (0.551 vs 0.131). Nevertheless, the presence of MHP as side product was a limiting step of the process and required more energy for the work-up and purification. Therefore, the flow rate of 0.2 mL min -1 with only 2-3 % of MHP was choose for the next step of the optimization. Effect of flow rate on GVL productivity and products yield in continuous flow process.Reaction conditions: ML (0.2 M), 5% Ru/C (330 mg), 2-PrOH, 150 °C, 40 bar, 0.2-0.8 mL min -1 .

	10 20,40,60bar ML Conversion 0 5 10 15 80 85 90 95 100 Percentage (%) 0 5 10 15 80 85 90 95 100 Percentage (%) 0.2,0.4,0.8mL/min ML Conversion fully converted. 10 Fig. 2.4.	22 22 20bar GVL Yield 34 20bar MHP Yield Processing capacity (mL) 40bar GVL Yield 46 40bar MHP Yield Pr=0.258 Pr=0.277 Pr=0.279 34 46 0.4mL/min GVL Yield 60bar GVL Yield 58 60bar MHP Yield MHP GVL 58 0.8mL/min GVL Yield 0.8mL/min MHP Yield 0.4mL/min MHP Yield 0.2 mL/min GVL Yield 0.2mL/min MHP Yield Pr=0.551 Pr=0.258 GVL MHP Pr=0.131
		Processing capacity (mL)

Table 2 .1).

 2

	0.2mL/min ,0.8M ML Conversion		0.4mL/min, 0.4M ML Conversion	0.8mL/min, 0.2M ML Conversion
	0.2mL/min, 0.8M GVL Yield		0.4mL/min, 0.4M GVL Yield	0.8mL/min, 0.2M GVL Yield
	0.2mL/min,0.8M MHP Yield		0.4mL/min, 0.4M MHP Yield	0.8mL/min, 0.2M MHP Yield
		100
		95
		90
		85
	Percentage (%)	12 14 80			Pr=0.55
		10
		8
		6
		10	22	34	46	58
				Processing capacity (mL)

Fig. 2.5. Effect of flow rate and substrate concentration with a constant ML feeding rate on GVL and MHP yields in continuous flow process. Reaction conditions: ML (0.2-0.8 M), 5% Ru/C (330 mg), 2-PrOH, 150 °C, 40 bar, 0.2-0.8 mL min -1 .

Selected works describing the production of GVL from LA or AL in the presence of hydrogen source and 5% Ru/C as catalyst in either batch reactor with or without microwave radiation or continuous flow reactor were described (Table

2

.1). CTH using formic acid and 2-PrOH gave not good productivity even the yield of GVL can reach 93% yield (Table

2

.1, entries 1 and 2). It was noteworthy that the use of high concentrated solution of ML (1.4 M vs. 0.43 M) and higher pressure of H2 (30 bar vs.

Table 2 .

 2 1. 5%Ru/C as catalysts reported for the conversion of LA and AL to GVL

	Entry	Starting material	H source	Temperature
		(M)

Table 2 . 2 .

 22 Effect of AL molecular weight as starting material for the production of GVL a

	Entry	AL	Conv. (%)	GVL yield	AHP yield	Productivity
				(%)	(%) b	(mol g -1 h -1 )
	1	ML	99	85	13	0.99
	2	EL	95	64	31	0.55
	3	BL	94	31	63	0.25
	4	LA	67	59	6 c	0.50
	a Reaction conditions: ML (0.4 M), 5% Ru/C (330 mg), 2-PrOH, 150 °C, 40 bar, 0.8 mL min -1 .

b AHP for alkyl 4-hydroxypentanoate. c 4-hydroxypentanoic acid.

Table 3 . 1 .

 31 Conversion of HMF into HMFCA under different catalysts and bases

	Entry	Catalyst	Base	Time (h)	HMF	HMFCA	HMFCA
					Conv. (%)	Yield (%)	Sel. (%)
	1	------	Na2CO3	1	92	12	13
	2	AgNO3	Na2CO3	1	80	74	92
	3	AgCl	Na2CO3	1	66	58	87
	4	Ag2O	Na2CO3	1	87	80	92
	5	AgO	Na2CO3	1	71	65	91
	6	Ag2O	NaOH	1	>99	61	61
	7	Ag2O	Na2CO3	1	87	80	91.9
	8	Ag2O	NaHCO3	1	28	25	89.2
	9	Ag2O	------	1	12	11	91.6
	Reaction condition: HMF (37.8 mg), catalysts (HMF:Ag x+ =1:0.4 molar), bases (4 eq.), 10 mL HPLC
	water, oil bath 90 ºC under stirring 300 rpm, 8.1 wt% H2O2 aqueous with flow rate 0.2 mL min -1
	during 1h.

Table 3 .

 3

		2. Conversion of HMF into HMFCA under different temperatures
	Entry	Temperature (ºC)	Time (h)	HMF	HMFCA	HMFCA
				Conv. (%)	Yield (%)	Sel. (%)
	1	30	1	55	52	94
	2	60	1	58	56	95
	3	90	1	100	98	98
	4	120	1	100	98	98

Reaction condition: HMF (37.8 mg), Na2CO3 (126 mg), Ag2O (20 mg), 10 mL HPLC water, oil bath 30-120 ºC under stirring 300 rpm, 8.1 wt% H2O2 aqueous with flow rate 0.2 mL min -1 during 1 h.

Table 3 .

 3

		3. Comparison between conventional heating, microwave irradiation and continuous flow
	in the oxidation of HMF to HMFCA
	Entry	Temp. (ºC)	Time	HMF	HMFCA	HMFCA
			(min)	Conv. (%)	Yield (%)	Sel. (%)
	1	90 a	6	47	45	95
	2	90 a	12	69	67	97
	3	90 a	24	79	76	96
	4	90 a	60	100	98	98
	5	87 b	6	52	50	96
	6	88 b	12	88	86	97
	7	90 b	24	99	97	97
	8	92 b	60	100	98	98
	9	90 c	0 d	36	33	91
	10	90 c	30 d	8	5	62
	11	90 c	60 d	6	3	50
	12	90 c	90 d	5	2	40
	Reaction conditions: a) HMF (37.8 mg), Na2CO3 (126 mg), Ag2O (20 mg), 10 mL HPLC water, oil
	bath 90 ºC under 300 rpm stirring, 8.1 wt% aq. H2O2 with flow rate 0.2-2 mL min -1 during 6-60 min.
	b) HMF (37.8 mg), Na2CO3 (126 mg), Ag2O (20 mg), 10 mL HPLC water, microwave 30 W with

stirring 300 rpm, 8.1 wt% aq. H2O2 with flow rate 0.2-2 mL min -1 during 6-60 min. c) HMF (0.01362 M), Na2CO3 (0.05471 M), continuous flow 0.3mL/mL, 20 mg Ag2O, 90°C, 1 bar. d) Time on stream in continuous flow.

Table 3 .

 3 4. pH change in pristine and spent Ag2O during different time

	Entry	Ag2O	0 min	15 min	30 min	45 min	60 min
	1	Pristine	10.83	9.98	10.26	10.47	10.07
	2	Spent	11.08	10.8	10.43	9.97	10.45
	Reaction conditions: Pristine or spent Ag2O (20 mg),HMF (37.8 mg), Na2CO3 (126 mg), water (10
	mL), oil bath 90 ºC under 300 rpm stirring, 8.1 wt% H2O2 aqueous with flow rate 0.2 mL min -1
	during 60 min.

Table 4 . 1 .

 41 Activated carbon support Ru catalysts for the conversion of 5-hydroxymethyfurfural (HMF) to 2, 5-furandicarboxylic acid (FDCA)

	Entry	Catalyst (Ru/HMF molar ratio)	Base	Oxygen Pressure	Time (h)	Tem. ( o C)	Heating method b	HMF Conv. (%)	FDCA Yield (%)	Ref.
	1	Ru/C (0.1)	PH=13	10 bar O2	4	50	CH	98	6.4	[14]
	2	Ru/C (50)	1 eq. NaOH	2 bar O2	5	120	CH	100		[15]
	3	Ru/C (50)	1 eq. K2CO3	2 bar O2	5	120	CH	100		[15]
	4	Ru/C (50)	1 eq. Na2CO3	2 bar O2	5	120	CH	100		[15]
	5	Ru/C (50)	1 eq. HT	2 bar O2	5	120	CH	100		[15]
	6	Ru/C (50)	1 eq. CaCO3	2 bar O2	5	120	CH	100		[15]
	7	Ru/C (100)	----	2 bar O2	10	120	CH	100		[15]
	8	Ru/C (0.1)	1 eq. Na2CO3	35 wt % H2O2	6	75	CH	100		[16]
	9	Ru/C (0.01)	4 eq. NaHCO3	40 bar air	2	100	CH	100		[17]

a Residence time, b Conventional heating (CH), microwave heating (MW).

Table 4 .

 4

	2. Optimization of HMF oxidation to FFCA using 5% Ru/C catalyst
	Entry	Base type	Base	Catalyst	H2O2	Reation	HMF	DFF	HMFCA	FFCA	FDCA
			/eq.	/mg	/wt%	time/min	Conv.	Yield (%)	Yield	Yield (%)	Yield (%)
							(%)		(%)
	1	Na2CO3	1	25	----	10	15	0	0	1
	2	Na2CO3	1	---	6.5	10	2	0	0	0
	3	NaHCO3	2	25	6.5	5	87	24	0	54
	4	NaHCO3	2	25	6.5	10	100	0	0	82
	5	Na2CO3	1	25	6.5	5	100	0	0	83
	6	Na2CO3	1	25	6.5	10	100	0	0	84
	7	NaOH	2	25	6.5	5	100	0	0	65
	8	NaOH	2	25	6.5	10	100	0	0	61
	9	KHCO3	2	25	6.5	5	88	21	0	53
	10	KHCO3	2	25	6.5	10	100	0	0	85
	11	K2CO3	1	25	6.5	5	98	5	0	72
	12	K2CO3	1	25	6.5	10	100	0	0	81
	13	KOH	2	25	6.5	5	100	0	0	70
	14	KOH	2	25	6.5	10	100	0	0	62
	15	Na2CO3	0.5	25	6.5	5	90	21	0	53
	16	Na2CO3	2	25	6.5	5	99	0	0	73
	17	Na2CO3	1	25	3.6	5	98	16	0	72
	18	Na2CO3	1	25	10.7	5	100	0	0	73
	19	Na2CO3	1	12	6.5	5	66	16	0	34
	20	Na2CO3	1	50	6.5	5	100	0	0	84

Table 4 .

 4 1, entry 12: 85% C balance, 81% FFCA selectivity) displayed outstanding results in terms of selectivity and carbon balance. Remarkably, Ru/C catalyst also achieved similar high FFCA yield even after 5 min, by employing Na2CO3 (Table 4.1, entry 5).

	.1, entry 4: 82% C balance, 82% FFCA

4.4.1.5. Effect of catalyst amount for the first step production of FFCA

	Moreover, catalyst amount (Table 4.1, entries 19 and 20) also affected the
	selective oxidation of HMF to FFCA. Higher 5% Ru/C amount (12 mg vs. 50 mg)
	resulted in higher FFCA yield (34% vs. 84%, respectively), and higher HMF conversion
	(66% vs. 100%, respectively). Additionally, 25 mg of catalyst were also employed in
	the same reaction conditions, achieving fully HMF conversion and comparable FFCA
	yield. Therefore, 25 mg of catalyst was selected as the optimum amount, considering
	the balance between cost-efficiency and catalytic performance. As well, the crucial role
	of microwave irradiation was evaluated by performing the reaction under stirring at
	room temperature (Table 4.1, entry 22), only 32% of HMF conversion was achieved,
	with 6% DFF yield and 10% FFCA yield.

Table 4 .

 4

		3. Microwave-assisted continuous HMF oxidation to FDCA
	Entry	MW	Temperature	TOS /min	HMF	FFCA	FDCA	Productivity	STY
		power/W	/ o C		Conv.	Yield	Yield	mmol(FDCA)g(metal) -1 h -1	g(FDCA)L(reactor) -1 h -1
					(%)	(%)	(%)
	1	8	63	20	100	86	7	6.0	5.8
	2	8	66	30	100	86	7	6.0	5.8
	3	8	66	40	100	85	7	6.0	5.8
	4	8	67	50	100	85	6	5.1	4.9
	5	16	83	20	100	58	30	25.9	25.2
	6	16	83	30	100	57	29	25.0	23.9
	7	16	84	40	100	57	29	25.0	23.9
	8	16	85	50	100	57	28	24.1	20.2
	9	32	95	20	100	38	47	40.6	39.5
	10	32	95	30	100	49	44	38.0	37.0
	11	32	96	40	100	39	43	37.1	36.2
	12	32	96	50	100	40	42	36.2	35.3

Table 4 . 4 .

 44 Catalyst reusability studies and acid-base properties of fresh and spent catalyst

	Entry	Catalyst	Acidic	Basic	Total content of	HMF	DFF	FFCA	FDCA
		condition	groups	groups	surface oxides	Conv.	Yield	Yield	Yield (%)
			(mmol/g)	(mmol/g)	[mmol/g]	(%)	(%)	(%)
	1	MW/batch	1.1675	0.6464	1.8139	100	0	83	1
		Fresh
	2	MW/batch	1.0095	0.3975	1.4070	62	13	35	2
		Spent
	3	MW CF	1.1675	0.6464	1.8139	100	0	38	47
		Fresh
	4	MW CF	1.0527	0.3975	1.4502	70	11	40	3
		Spent

Table 4 . 5 .

 45 Porosity and crystal size data of the fresh and spent catalysts

	Entry	Catalyst	Total SSA	Total Pore	Micropore	Meso/macro-pore &
		condition	(m 2 /g) a	Volume	Area	External Surface
				(cc/g) b	(m 2 /g) and volume	Area
					(cc/g) c	(m 2 /g) and volume
						(cc/g) d
	1	Fresh Catalyst	816	0.862	454 / 0.19	362.051 / 0.672
	2	MW/batch	214	0.470	4.2 / 0	210 / 0.470
		Spent
	3	MW CF	694	0.807	312 / 0.131	382 / 0.676
		Spent
	a SSA: specific surface area from N2 sorption at -196 °C (multi-point BET method); b Total pore
	volume at P/Po = 0.99; c. t-plot method; d. Meso/macropore & external area = Total SSA-Micropore
	area; Meso/macropore volume = Total pore volume-Micropore volume (t-plot).

. Products synthesis, analysis and characterization 5.3.3.1. Diethyl furan-2,5-dicarboxylate (DEFDC)

  Other sequences such as COSY ( 1 H-1 H), direct HSQC ( 1 H-13 C) and HMBC long range coupling ( 1 H-13 C) were applied on monomers BHEFDC and PDGF polymers. Chemical shifts (δ) are quoted in parts per million (ppm). Coupling constants are quoted in Hertz. Sometimes, comparison with already described compounds has been used to confirm the NMR peak assignments.

	(FEI) equipped with a microanalysis detector for EDX from Bruker. SEM micrographs
	acquired in secondary electron mode were obtained at low vacuum, 15 Kv accelerating
	voltage and 10 mm working distance.
	XRD experiments were recorded on a X'pert MRD diffractometer (Pan
	Analytic/Philips 40 Kv, 30 mA) using Cu Kα (λ = 0.151418 nm) radiation. Scans were
	High performance liquid chromatography (HPLC), each sample was analyzed performed over a 2θ range from 10 to 80, at step size of 0.018° with a counting time
	separately by means of a Prominence HPLC system (Shimadzu). Unreacted mucic acid per steps of 5 s.
	was detected with a low temperature evaporative light scattering detector (ELSD-LT II)
	and the products concentration was estimated with a UV-Vis detector (SPD-M20A) at 5.3.3
	a wavelength of 265 nm. The column used was a Grace Prevail C18 column (250 × 4.6
	mm 5 μm). The mobile phase was MeOH-water (9:1) solution flowing at rate of 0.5
	mL/min. The column oven temperature was set at 40 °C.
	Differential Scanning Calorimetry (DSC) was conducted on a DSC 8MC apparatus
	(Mettler-Toledo, using aluminium pans. Scans were conducted under nitrogen with a
	heating rate of 10 °C/min in the temperature range of 40-250 °C.
	Thermogravimetric analysis (TGA) was carried out on an Setsys Evolution
	analyzer (ATG Setaram, equipped with an aluminium cell, using aluminium pans to
	encapsulate the samples. Typically, samples were heated at a constant rate of 10 °C/min
	from room temperature up to 550 °C, under a helium flow of 50 mL/min. The thermal
	decomposition temperature was taken at the onset of significant (≥5%) weight loss from
	the heated sample.
	FT-IR (ATR) spectra were recorded on FT-IR 4000 (in a range of 650 to 4000
	cm -1 ).
	FE-Scanning Electron Microscopy (SEM)-Energy Dispersive X-ray Diffraction
	(EDX) analysis of polymer powders was performed on a Quanta FEG 250 instrument

1

H-and

13

C-NMR) spectra were recorded on an Avance III 400 spectrometer (Bruker equipped with a BBFO probe operating at room temperature.

Table 5 . 1 .

 51 Dehydration of mucid acid in the presence of acid catalyst for the production of FDCA

	Entry Acid [Acid] [eq.] Temperature [°C] Time [min] Yield of FDCA [%] a
	1	PTSA	1	160	60	32
	2	PTSA	2	160	60	41
	3	PTSA	3	160	60	36
	4	PTSA	4	160	60	34
	5	PTSA	5	160	60	37
	6	MSA	1	160	60	34
	7	MSA	2	160	60	39
	8	MSA	3	160	60	35
	9	MSA	4	160	60	35
	10	MSA	5	160	60	30
	11	CSA	1	160	60	4
	12	CSA	2	160	60	11
	13	CSA	3	160	60	15
	14	CSA	4	160	60	12
	15	CSA	5	160	60	9
	a The FDCA yield was calculated from liquid chromatography analysis with a calibration curve.

Table 5 . 2 .

 52 Dehydration of mucic acid in different temperature for the production of FDCA The FDCA yield was calculated from liquid chromatography analysis with a calibration curve.

	Entry Acid [Acid] [eq.] Temperature [°C] Time [min] Yield of FDCA [%] a
	1	PTSA	2	140	60	12
	2	PTSA	2	160	60	41
	3	PTSA	2	170	60	28
	4	MSA	2	140	60	15
	5	MSA	2	160	60	39
	6	MSA	2	170	60	25
	a

Table 5 . 3 .

 53 Dehydration of mucic acid in different reaction time for the production of FDCA

	Entry Acid [Acid] [eq.] Temperature [°C] Time [min] Yield of FDCA [%] a
	1	PTSA	2	160	5	8
	2	PTSA	2	160	15	20
	3	PTSA	2	160	30	30
	4	PTSA	2	160	90	40
	5	PTSA	2	160	120	37
	6	MSA	2	160	5	8
	7	MSA	2	160	15	30
	8	MSA	2	160	30	39
	9	MSA	2	160	90	35
	10	MSA	2	160	120	32
	a The FDCA yield was calculated from liquid chromatography analysis with a calibration curve.

Table 5 . 4 .

 54 Production of DEFDC starting from mucic acid in a one-pot two steps reaction

	Entry Temperature [°C] Time [h] Yield of DEFDC [%] a
	1	70	4	15
	2	70	8	23
	3	70	16	29
	4	90	4	27
	5	90	8	29
	6	90	16	30
	a

Acknowledgements

This PhD work was started from 18/10/2016 in the laboratory Transformations Intégrées de la Matière Renouvelable (TIMR, EA4297) of the Université de Technologie de Compiègne (UTC) for 1 year and then in the Institute of Chemistry for Life and Health Sciences of École national supérieure de Chimie de Paris (Chimie

List of Schemes

Furthermore, XRD patterns of fresh and spent 5%Ru/C catalyst were obtained, as shown in Fig. 4.7. The three samples showed two broad diffraction peaks at 24.5º and 44.0º associated to (002) and (100) reflections, respectively. The (002) band is commonly associated to the carbon interlayer-stacking structure, while the (100) peak is attributed to the interlayer reflection of the hexagonal carbon structure. The presence of both peaks confirmed the formation of a disordered carbon material [29]. As well, the three materials exhibited a sharp peak located around 27.5º, which could be assigned to (110) crystallographic plane of ruthenium oxide [30,31]. Additionally, the above mentioned peak centered at 44.0º, could also have a contribution related to (101) plane of metallic ruthenium [30]. Post-characterization XRD analysis of the spent catalysts did not exhibited considerable changes, in comparison with the results obtained for the fresh material. Even if the peak around 44.0º displayed certain shape change, nonconclusive explanation for the observed deactivation could be achieved from XRD analysis. The stabilization of the catalytic performance under the continuous flow operating conditions could be complex involving certain accumulation of carbon entities on the surface of the catalyst, leaching processes as well as stabilization of hydrodynamic conditions.

ICP-OES analysis

General Conclusions

The aim of this PhD work was to explore green methods for the conversion of respectively. Solvent-free regioselective polytransesterification for the production of glycerol-based furanic polyesters were realized under the performance of Co(Ac)2. In all studies, the optimization of green production process was focused on several key points: solvent, activation method, catalysts and reaction regime.

Solvents. Methanol was proved as a suitable medium for the alcoholysis of FA to ML when using zeolite HZSM-5-50 as catalyst. Different type of alkyl levulinates (AL) (ethyl and n-propyl levulinate) can be obtained when using ethanol and n-propanol as solvent. 2-PrOH was used as hydrogen donor in the catalytic transfer hydrogenation process for the synthesis of GVL under 5% Ru/C. There is no obvious hydrogenation process when changed 2-PrOH to ethanol and 1-butanol. For HMF conversion to HMFCA and FDCA part, the greener solvent -water has been used.

Activation method. Microwave irradiation was found to be a good alternative to conventional heating. Thanks to MW, we can achieve 60 % ML and 33 % β-angelica lactone (BAL) yields in only 5 min at 150 °C. And 83 % FFCA yield with fully HMF conversion in only 5 min in MW power equal to 8 W.

Catalysts. During this PhD, the development of greener, durable and efficient catalysts to realize the conversion of bio-based compounds has been employed. (1).

Two FAU zeolites and two MFI zeolites were tested for the catalytic alcoholysis of furfuryl alcohol in methanol. HZSM-5-50 zeolite (SiO2/Al2O3 molar ratio 50) showed the best activity. High feed loads up to 1.6 M FA were also converted efficiently (79 % ML yield), but faced the formation of pore blocking polyfurfuryl alcohols. The initial activity of the spent HZSM-5-50 catalyst was restored by regeneration at 500 °C. (2).

GVL yield (83%) starting from ML in Reaction regime. In parallel, as an alternative to batch reaction, continuous flow reactors, such as H-Cube Pro, Pheonix, microwave continuous flow etc…were also tested. Generally, continuous flow reactions are more efficiency than batch reactions.

Take an example, FF hydrogenation experiments were conducted for 5h in batch, however, in continuous flow, the residence time of the reactant was only several minutes, which significantly improved the target compound productivity. Besides, the hydrogenation selectivity could be controlled by turning the flow rate, and side reaction could be suppressed. Benefit to the exploration of these key points, the advanced results obtained during this PhD study could be summarized as follows: