Dr Romain Tavernier

Dr. Mona Semsarilar
email: mona.semsarilar@umontpellier.fr

Dr. Sylvain Caillol
email: sylvain.caillol@enscm.fr

E D Endocrine

Disruptor Eew

Ipda

Biosourced alternatives to diglycidylether of bisphenol A in epoxy-amine thermosets: a focus on materials properties and endocrine activity

Keywords:

Since 1940s, bisphenol A (BPA) has been used in plastic industry reaching production of 10 million tons in 2022. More than 30 % of the produced BPA is used in the production of epoxy resins. Decades of research has now provided enough evidence that (BPA) has endocrine disrupting activity. Hence, it is an urgent matter to replace the use of BPA in production of epoxy resins. In the past years, considerable effort have been put into finding alternatives to the toxic BPA. However, the diglycidylether bisphenol A (DGEBA) does not only exhibits high polymerization reactivity, but the presence of aromatic rings confers interesting thermos-mechanical resistance to epoxy networks therefrom. Hence, this properties are also expected from potential alternatives to BPA. In this review, first the elements leading to toxicity of BPA is explained and then a thorough account of possible bio-sourced aromatic alternatives to BPA are gathered. The reported synthetic routes to each of these alternatives and their toxicity are described. Also, their use in synthesis of epoxy resins and how the new alternatives influence the mechanical properties are discussed. This is a concise summary of the structure-property and structure-toxicity relationship for possible bio-sourced substitutes of BPA in synthesis of epoxy resins.

Introduction

Epoxy thermosetting resins are an important class of plastics that are used in a wide range of fields such as paints, coatings, composites, electronics, adhesives, construction, wind turbines, etc. The global epoxy resin market size is estimated to worth 11.26 billion dollars by 2026, and it was valued at 7.6 billion dollars in 2019. [START_REF]Epoxy Resins Market Share, Size, Trends, Industry Analysis Report[END_REF] The main application segments of epoxies are paints and coatings, for over 40 % of the total market. The most used epoxy monomer is diglycidylether of bisphenol A (DGEBA), followed by diglycidylether of bisphenol F (DGEBF). The majority of epoxy resins are derived from fossil resources.

The shift toward the use of bioresources for polymer synthesis could be a major move in the reduction of fossil carbon dissemination into the environment. For example, in the field of packaging, more than 80 billion kg are annually produced and originate from fossil resources. [START_REF] Hillmyer | [END_REF] A recent analysis of patent literature shows that there is a growing interest in sustainability in industry. More specifically, the use of bioresources for the production of chemicals, process optimisation that minimize waste or emissions are some of the main source of innovations. 3 In addition with tackling the global challenges for a more sustainable use and production of plastics, the use of bioresources is also a source of innovation, thanks to the diversity of monomer design from naturally available building blocks. 4 Polymer scientists have long been working on biobased epoxy monomers for synthesis of epoxy networks. The use of biobased starting materials is an effective way to reduce the carbon footprint, and it allows to valorise organic wastes, as well as investigating new structures for thermosetting epoxies. The use of biobased materials in itself does not specifically prevent the use of toxic or hazardous compounds, but following the green chemistry principles usually includes the seek for low impacts either on the environment than on health. Epoxy monomers can be obtained from the oxidation of unsaturated compounds (epoxidation of carbon-carbon double bonds), or via the addition of a glycidyl moiety, for example using epichlorohydrin. When converting a double bond to an epoxide moiety, the reaction does not imply the introduction of carbon into the monomer, it is usually carbon neutral (considering only the atoms introduced, and ignoring any use of solvent, catalyst or waste generation). However, the introduction of a glycidyl moiety will involve the addition of carbon into the monomer. But this step does not necessarily involve the introduction of fossil carbon, since commercially available biobased epichlorohydrin can be utilized to target 100 % biobased epoxy monomers. For example, the synthesis of DGEBA using petrosourced BPA and biobased epichlorohydrin will lead to nearly 30 % of carbon originating from renewable resources. Several manufacturers are already selling epoxy formulations that contain a high biobased carbon percentage. 5 Academic scientists however have conceived a wider range of epoxy monomers obtained from biobased compounds, and several reviews have already focused on these monomers. For instance, in 2014, Auvergne et al. published an important review on biobased thermosetting epoxy resins, which covered the whole available literature on biobased epoxy monomers. 6 Since then, other groups also worked on gathering new data from literature, either for a general purpose [7][8][9][10][11] , or for specific applications such as aerospace industry. 12 With a focus on specific starting materials, such as furanics or aromatics, other reviews have gathered valuable information on reported structures. Ng et al. focused their work on aromatic compounds 13 , Wan et al. worked on phenols 14 , Caillol et al. on eugenol 15 , while a very recent paper by Eid et al. highlights the progress made in furanic monomers. 16,17 The use of specific biomass types for synthesis of monomers is also investigated, and especially aromatic-containing biomass such as lignin is an important area of research. [18][19][20][21] Since BPA is not only used as an epoxy precursor, some work of interest on the generation of potential for substitutes for any application can feed the research on thermosetting epoxy resins, for instance, Liguori et al. provided a very complete overview of potential substitutes, focusing on their synthesis. 22 Synthetic tools to obtain functional monomers from biobased furans and phenols have also been reviewed recently by Decostanzi et al.. 23 Finally, it is worth mentioning that in the case of epoxy-amine networks, it is also important to consider the origin of the amine, and especially, the availability of biobased amine is still low. 24,25 In this review, available structures that could replace bisphenol A, or more specifically, DGEBA in the synthesis of epoxy-amine resins are summarized. For this purpose, the initial focus would be on potentially biosourced compounds, and then on phenolic or furanic derivatives, that would be the most relevant structures to replace DGEBA in the synthesis of thermosets. For each compound, the thermoset properties using amine hardeners are discussed and compared with the same network obtained using DGEBA. Further, the available data on their endocrine disruption are compared with the know hazards of BPA.

BPA is used as a monomer in the synthesis of polycarbonate thermoplastics and as monomer precursor in epoxy resins. 26 Thus, environmental BPA contamination mainly comes from leaching from the polymers under specific conditions, depending on the stability of the material. For example, the release of BPA from polycarbonates occurs due to hydrolysis under acidic conditions and upon heating. 27 Similarly, BPA is released from epoxy resins when heated above 100 °C (often during sterilization step). 28,29,30 BPA contamination has also been detected from dental sealants, 31 in house dust and air, 32 as well as in textile. 33

Endocrine activity assays

The toxicity of BPA is due to its similar activity to 17β-oestradiol hormone, a human oestrogen α receptor. 34 This activity is due to the chemical structure of BPA mimicking 17β-oestradiol (Figure 1). Several factors control this similar activity. First is the presence of the two hydroxyl groups ensuring the efficient interaction between the receptor and the potential agonist. The second factor is the size of the receptor and the compound. In order to have a binding inside the receptor's binding site, the compound has to fit inside the receptor pocket. The size of the receptor pocket is 440 Å, while the size of 17β-oestradiol is 245 Å, allowing an adequate fitting. Apart from these factors the distance between the hydroxyl groups as well as the hydrophobic nature of the middle part of the molecule (for example, the two methyl units in BPA) also influence the interactions between the compound and the receptor (Figure 2). 35,36 evaluation of endocrine disruption is not only due to the oestrogen receptor α, 34 but also to other biochemical mechanisms that have influence on the oestrogen binding. 37 The entire steroid metabolism have an effect on the oestrogen binding, since oestradiol belongs to the class of steroids. Hence, any effect on the steroid metabolism could have an effect on the binding in ERα. 38 Figure 3 -Postulated metabolitic pathway of Bisphenol A, reproduced from Chen et al. 39 Usually, regarding in vitro or in vivo bioassays, the compound activity is compared with the activity of the natural hormone, in order to determine a coefficient of activity. In addition, as a control, the activity of the tested compound is also compared to the vehicle, which is the vector used to drive the compound to the receptor. For instance, the vehicle is the solvent in which the compound is solubilised for in vitro testing, or the type of food in which the compound is included for in vivo experiments.

Phenols I. Vanillin

Figure 4 -Chemical structure of vanillin and some simple vanillin derivatives used as epoxy monomer precursors Vanillin (Figure 4) is a natural monophenol, bearing a methoxy moiety and an aldehyde. It is one of the main components of natural vanilla aroma, and it has been produced on a large scale from fossil resources mainly for food industry. Vanillin is also synthesized from bioresources on an industrial scale. 40 As a food additive, its toxicological profile is thus positive, and it has led researcher to study different chemical modification of the compound for the synthesis of epoxy monomers. 41 Vanillin derivatives has been widely used in the literature for the synthesis of epoxy monomers.

Vanillin in itself does not seem to have an impact on the endocrine system. A recent article by Ji et al. has evaluated the activity of vanillin on different receptors, such as ERα, androgen receptor, thyroid receptor and retinoic X receptor β. 42 Vanillin did not show any activity against these receptors, for all the concentrations tested. Vanillyl alcohol (VA) is a vanillin derivative that can be obtained from the reduction of the aldehyde. VA is commercially available since it is used as a flavouring. 43 This aromatic compound contains a methoxy moiety, a phenolic hydroxyl and a primary alcohol, the two latter being the reactive sites for glycidylation. Diglycidylether of vanillyl alcohol (DGEVA, Figure 5) has been synthesized first by Fache et al. as part of a series of monomers obtained from vanillin. 41 Since then, several groups used DGEVA in order to elaborate thermosets, with different hardeners, and some thermomechanical properties are reported in Table 1. Fache et al. studied the curing behaviour of DGEVA with IPDA, and they obtained lower T g (97 °C) than with DGEBA (166 °C). 44 This can be explained by the fact that there is less aromatics in DGEVA compared to DGEBA, and that DGEVA contains a methylene, that can induce more mobility of the chains. The calculated crosslink density is also lower for DGEVA (0.7 mmol•m -3 vs 1.4 mmol•m -3 for DGEBA). Degradation under nitrogen is a one step process for both DGEBA and DGEVA-IPDA thermosets, and the DTG peak corresponding to the degradation happens for both materials around 360 °C, but DGEVA produces more char yield (19 % vs 10 % for DGEBA). 45 The thermosets were compared with DGEBA and DGEBF. DGEVA thermoset displays a T g around 100 °C, compared to the DGEBA system (190 °C). The glass transition temperature of DGEVA cured with IPDA and PACM is thus very close, which is not surprising considering the two amines are based on cyclohexyl moieties, however, the storage moduli are higher for DGEVA and DGEBA cured with PACM than with IPDA. Finally, the degradation of DGEVA-PACM occurs at a lower temperature than with DGEBA, under nitrogen. The char yield is higher for DGEVA thermoset (7 %) than for DGEBA (2 %), following the same trend than DGEVA-IPDA.

Vanillyl alcohol

Ng et al. used DGEVA with dicyandiamide (DICY) for the elaboration of coatings. 46 They used oligo-DGEBA and pure DGEBA for comparison. The cure temperature of the neat mixture of amine and epoxide is 220 °C for both DGEBA types and 210 °C for DGEVA, which are very close. Glass transition temperatures determined for DGEBA material are 146 °C and 93 °C for DGEVA, which is following the same trend than discussed before. The T d5% under nitrogen is 342 °C for DGEBA, and 289 °C for DGEVA, which is slightly lower. However, the char yield is higher for DGEVA (23 %) than for DGEBA (13 %). The adhesion properties of the corresponding coatings performed well with or without adhesion promoter, with an ISO 2409 classification of 0 or 1 on a 5-scale (the lower the value, the higher is the adhesion). Reinforcement of a glass plate was also evaluated by measuring the break strength, and it is higher for DGEVA formulation than for pure DGEBA, but very similar to oligomerized DGEBA.

Tian et al. used DGEVA with the addition of an eugenol-based diepoxide for the elaboration of shape-memory polymers. 47 They used DDM as the curing agent. They obtained T g s between 111 and 124 °C (respectively from DSC and DMA as tan δ peak), as compared to DGEBA/DDM system that reaches 154 °C (from tan δ in the work of Wan et al. 48 ). The storage modulus at 25-30 °C is 2.8 GPa for DGEVA thermoset, that is higher than for DGEBA-DDM material (2.3 GPa). In overall, formulation with the eugenol-based monomers have shown effective shape memory properties, especially using DGEVA as a hard segment, for the induction of phase separation, as evidenced by AFM.

Wang et al. prepared epoxy composites using DGEVA/TETA as the matrix and lignin-containing cellulose nanofibres. They obtained for the neat resin two exothermic signals, with maxima at 113 °C and 167 °C. The two peaks are attributed respectively to the reaction of primary and secondary amines. In the DGEBA/TETA system, only one peak is observed for stoichiometric compositions, with a maximum at 98 °C. 49,50 This two-stage curing behaviour could be attributed to diffusion differences between DGEBA et DGEVA systems, since stoichiometric ratios were applied with DGEVA. A study of TETA/DGEVA ratios vs T g of materials should be of interest. Mechanical properties of cured DGEVA were reported, especially using DMA. Two relaxations were found for DGEVA, with T α of 71 °C and 109 °C, revealing an inhomogeneous network, probably due to two types of crosslinking brought by the amine containing both primary and secondary NH. The storage modulus at 30 °C was found to be 3.7 GPa.

DGEBA cured with TETA presents also two tan δ peaks, but with a maximum contribution of the second peak, which maximum is 142 °C, and the storage modulus at 40 °C is around 4 GPa. 49 Degradation behaviour of DGEVA/TETA has been investigated under nitrogen, and a two-step degradation pathway was found, with a maximum of degradation at 309 °C and a char yield of 16 %. The DGEBA system presents a single-stage degradation with a DTG peak at 372 °C, which shows a better thermal stability. 51 Char yield was not reported for this material, but is believed to be lower than for DGEVA according to the trend observed.

Gnanasekar et al. synthesized a phosphorylated epoxy monomer using vanillin as the precursor. 52 In order to assess the effect of the phosphorylation, they also used DGEVA as a phosphorus-free control. The study was also focused on the use of polyurethane as a toughening agent in the synthesis of epoxy thermosets. DGEVA and the phosphorylated monomer were cured with DETA. DGEVA/DETA properties could then be compared with DGEBA. DMA tests showed a glassy modulus at 30 °C for DGEVA/DETA to be around 3.5 GPa, compared to 2

GPa for the DGEBA network as reported in the literature. 53 The tan δ peak of the DGEVA/DETA network appears around 90 °C, which is slightly lower than that of DGEBA (100 °C). Thermal stability under nitrogen was also assessed. The T d5% of DGEVA/DETA was 247 °C and char yield at 600 °C is 7 %, compared to DGEBA/DETA with a T d5% of 305 °C and a char yield of 8 %. The lower thermal stability could be attributed to the presence of the methoxy moiety, consistently with the other reports from literature. However, the lower char yield is unexpected compare to the other DGEVA networks. However, it is worth mentioning that the low char yield was expected due to the aliphatic structure of the hardener.

In a different work, Gnanasekar et al. used phosphorylated vanillin-based epoxy monomer, with modified graphene oxide as the filler. 54 They also used DGEVA as a phosphorus-free control. The authors report the use of 4,4'-DDS as the hardener, without describing the curing procedure. They determined the glass transition temperature of DGEBA/44DDS using DSC at 108 °C. As a comparison, DGEBA/44DDS network has a T g of 238 °C. 55 Thermal stability under nitrogen was also assessed, and the DGEVA/44DDS showed a T d10% of 251 °C, which is lower than T d5% for DGEBA/44DDS thermosets reported (> 300 °C). Char yield at 600 °C was 7 %, which is lower than when DGEBA is used (approx. 14 %). The global lower performances of DGEVA cured with 44DDS can be attributed to the lower aromatic density, and the presence of a methylene moiety in the structure of the epoxy monomer.

Mauck et al. used a diamine based on furfurylamine with DGEVA in order to get epoxy thermosets. 56 The methylenedifurfurylamine (DFDA) was used to harden several epoxy monomers derived from biophenols. The authors determined the EEW of their synthesized DGEVA at 133 g•eq -1 , slightly lower than the DGEBA used for comparison (190 g•eq -1 ). Thermomechanical properties were evaluated for cured networks. DMA showed that the DGEVA/DFDA has a T α of 81 °C compared to 109 °C for DGEBA/DFDA network. The Young's modulus at 25 °C is 3.7 GPa for DGEVA compared to 2.4 GPa for DGEBA. It is consistent with all other articles discussed herein, DGEVA giving lower T g values and higher stiffness. As expected, the crosslinking density is higher for DGEVA, which is composed on one aromatic ring compared to DGEBA, respectively 3.82 mmol•m -3 vs 2.62 mmol•m -3 .

Regarding thermal stability under inert atmosphere (Ar), DGEVA thermoset degrades earlier than DGEBA, as

shown by the T d5% , namely 304 °C for DGEVA/DFDA compared to 330 °C for DGEBA/DFDA. However, char yield at 600 °C is higher with DGEVA (42 % vs 23 % for DGEBA).

Mora et al. synthesized new aromatic-containing amines and cured DGEVA and DGEBA for comparisons. 57 They reported lower thermal stability for all DGEVA-based thermosets (T d5% ) but higher char yields. Glass transitions temperatures and T α were also lowered with DGEVA compared to DGEBA. They also reported the synthesis of nearly full vanillin-based epoxy networks, using an aminated DGEVA as the curing agent with DGEVA, and with DGEBA for comparison. 58 This resulted in lower decomposition temperatures as well as T g / T α but higher char yield for DGEVA. As demonstrated by Noè et al., DGEVA could also be used in photopolymerisation process. However, in such case conversion gets limited by a fast vitrification of the forming coating. 59 Epoxy thermosets based on DGEVA could also be used in manufacturing of composites with cellulose nano-fibres as the filler 60 as well as glass coatings for food contact material. 46 Vanillic acid is the oxidized form of vanillin, where the aldehyde is transformed into a carboxylic acid. This compound gives the flavour of natural vanilla, and is also an artificial flavouring. Diglycidylether of vanillic acid (DGEVAC, Figure 6) is a diepoxy readily obtained from the reaction between vanillic acid and epichlorohydrin. The nucleophilic substitution of the phenolate and the carboxylate can occur at the same time. 41 Another way to obtain this compound is the one pot allylation of the same moieties, followed by epoxidation via the use of mCPBA, or through an enzymatic process. 61 Fache et al. cured DGEVAC with IPDA, and they obtained a glass transition temperature of 152 °C and a T α of 166 °C, these values are slightly lower compared to those reported for DGEBA-IPDA (T g of 166 °C and T α of 182°C). 44 The presence of the ester linkage on the aromatic ring could bring rigidity, compared to the abovementioned DGEVA that contains a methylene instead. It is noteworthy that the T g values are very close, even if the epoxy monomers have very different structure (two aromatic rings for DGEBA compared to only one for DGEBA).

Usually, the T g value increases linearly with the number of aromatic rings in the monomer. It can be observed that rigid structures like ester linkages can be as effective as aromatic density to improve the T g of the epoxy thermosets.

This behaviour is not correlated to the crosslinking density that has been calculated to be 1.4 mmol•m -3 for both DGEVAC and DGEBA materials. In addition, the storage modulus of DGEVAC thermoset was measured at 2.1

GPa, as compared to 1.9 GPa for DGEVA. Thermal stability under nitrogen is however lower for DGEVAC compared to DGEBA. DGEVAC/IPDA degrades in two step, measured at 315 and 370 °C compared to the unique decomposition temperature of DGEVA system, with a peak at 360 °C. This two-step degradation behaviour can be attributed to the earlier rupture of the ester bond. The char yield of DGEVAC thermoset follows the trend observed with DGEVA, since it is higher than for DGEBA (14 % for DGEVAC and 10 % for DGEBA).

No more investigation has been performed on epoxy-amine thermosets with DGEVAC. However, there are examples on the epoxy-anhydride thermosets, such as the use of methylhexahydrophthalic anhydride and the hydrolytic degradation. 62,63 DGEVAC has also been used with nadic methyl anhydride as the curing agent. 64 3. Methoxy-hydroquinone Methydroxyquinone is a commercially available compound, but it can also be obtained from the Dakin oxidation of vanillin, using sodium percarbonate as the oxidizing agent. The aldehyde from vanillin is oxidized into a phenol in mild conditions. The diglycidylether of methoxyhydroquinone (DGEMHY) can be obtained through the glycidylation of both phenolic moieties (Figure 7). It was first prepared by Fache et al. 41 and the curing reaction with IPDA was extensively studied. 44 T g and T α values of 132 °C and 154 °C were reported. DGEBA with the same curing agent gave higher transition temperatures. The calculated crosslinking density was similar to the DGEBA system (1.4 mmol•m -3 ) and in the DGEMHY system (1.3 mmol•m -3 ). The degradation of the thermoset under nitrogen atmosphere resulted in a single step weight loss with a peak at 338 °C, lower than in the case of DGEBA (360 °C). However, the char yield obtained was 20 % at 600 °C compared to 10 % with DGEBA.

Curing of DGEMHY has also been performed with other amines: DA10 is decanediamine, an aliphatic biobased amine obtained from castor oil, vanillylamine is a vanillin-derived amine and BFAA is bisfurfurylamine A, a potentially biobased diamine. 65 DGEMHY cured with the biobased amines shows lower T g values than DGEBAbased thermosets. The aliphatic amine DA10 gave a T g of 74 °C with DGEMHY (98 °C with DGEBA), vanillylamine gave nearly the same T g with DGEMHY (64 °C) and DGEBA (67°C) and BFAA lead to a T g of 111 °C with DGEBA and 85°C with DGEMHY. The aromatic content seems to be the most influential contributor to the T g values of these epoxy thermosets, leading to higher values with DGEBA. The higher decrease regarding DA10

and BFAA with DGEMHY could be due to the presence of the methylene moieties in both amine and epoxy monomers. The lower T g values were obtained for DGEBA and DGEMHY cured with vanillylamine, which could be due to the lower functionality of the amine.

The commercially available DGEBA mainly contains two epoxide moieties, (or as oligomers) with different epoxide contents and chain lengths. DGEMHY has been also studied in its oligomerized form. 66 Fache and co-workers performed a catalytic oligomerization by using triphenylbutylphosphonium bromide, using methoxyhydroquinone with an excess of DGEMHY. Then, the crosslinking of the oligomers was obtained using IPDA as the hardener. A decrease in the T g and T α of the cured samples were observed with the increase of the repeating units. This is due to the higher chain length between two crosslinking nodes. However, the effect of the chain length was counter balanced by the higher aromatic density in the oligomers, which rather limited the increase of the T g and T α values.

Gastrodigenin

Figure 8 -Synthesis of DGEGD by Hernandez et al. 45 Gastrodigenin is a monophenolic compound that can be found in Gastrodia elata, a flower from the Orchidaceae family. This compound is one of the main active ingredients of this plant, and has shown some analgesic effects. 67 The structure of this molecule consist in a phenol bearing a methylenol in para position. The glycidylation of this compound leads to a diepoxy monomer, as shown in Figure 8. Hernandez et al. prepared DGEGD monomer with an EEW of 119 g•eq -1 and used PACM as the hardener. 45 68 The XenoScreen XL YES/YAS assay used in this report is a yeast based in vitro method to assess the activity of compounds both on the ERα receptor and the human androgen receptor.

Bisvanillyls

Figure 9 -Synthesis of bisvanillyl based epoxy monomers according to Savonnet et al. 69 The oxidative coupling of phenolics by enzymatic processes leads to the formation of diphenolic compounds that can help access to difunctional aromatic monomers. 70 The coupling of vanillin, and the reduction of the aldehyde moieties lead to a bisaromatic compound bearing two phenolic hydroxyls and two hydroxymethyl moieties. Thus, a tetra-functional epoxy monomer can be afforded after glycidylation. Savonnet et al. performed the synthesis of tetrafunctional monomer, but also obtained tri and difunctional monomers, by adjusting the ratios of epichlorohydrin in the glycidylation reaction of divanillylalcool (Figure 9). 69 Purification allowed the study of these different monomers, especially upon curing with IPDA.

The three monomers are DiGEDVA (diglycidylether of divallinylalcool), where the two hydroxymethyl moieties are reacted with epichlorohydrin, TriGEDVA with one phenolic moiety reacted, and then the TetraGEDVA, fully reacted. Interestingly, the viscosity at 40 °C shows that the tetrafunctional monomer has the lower viscosity. DMA was also performed, and properties such as the α transition temperatures, the Young's moduli and the crosslinking densities were measured. The T α followed indeed the same trend than T g measured by DSC. The GEDVA epoxy monomers have T α s of respectively 140, 177 and 200 °C with increasing functionality, as compared with DGEBA/IPDA with a T α of 155 °C. In overall, the Young's moduli on the glassy state are higher than for DGEBA, in the range 1.9-2.4 GPa, with the higher for TriGEDVA. On the rubbery state, higher moduli are also measured for the GEDVAs, ranging between 35 and 210 MPa, with values increasing from mono to tetrafunctional.

Interestingly, DGEBA/IPDA give a modulus 35 MPa, similar to DiGEDVA. Crosslinking densities are similar between DGEBA and DiGEDVA networks (namely 9.2 and 9.5 kmol•m -3 ). For the higher functionalities, crosslinking density increases accordingly, with 25 kmol•m -3 for TriGEDVA and 49 kmol•m -3 for TetraGEDVA.

The higher crosslinking densities of tri and tetra epoxy monomers mainly explain the higher mechanical properties observed. Tensile tests performed revealed that GEDVA monomers lead to higher Young's moduli, with increasing value when functionality also increases. However, elongation at break is lower in all cases than the DGEBA network. The rigidity of the monomers with a single carbon-carbon bond attaching the two aromatic rings seems to be detrimental to the elasticity of the network. Thus, DGEBA/IPDA displays an elongation at break of 6.3 % whereas DGEVAS network are between 3.3 and 4.7 %.

The thermal stability under air and under inert atmosphere showed that degradation of GEDVA networks happens at lower temperature than with DGEBA. The presence of the methoxy moieties usually leads to lower degradation temperatures. The T d5% is similar for all networks under air and under nitrogen, in the range 273-292 °C for GEDVAs and around 330 °C for DGEBA. There is no residue at 600 °C under air for all the networks. Under inert atmosphere, the char yield at 700 °C is around 10 % for DGEBA/IPDA, whereas it increases for GEDVAS. Tri and

TetraGEDVA have a char yield around 30 % whereas it is 40 % for DiGEDVA. This is simply explained by the free hydroxymethyl moieties in DiGEDVA. It is known that hydroxymethyl moieties can undergo a novolac-type condensation that could possibly happen during the degradation of the network, finally increasing the char formation.

It is worth mentioning that a biobased amine was also prepared from the difunctional vanillin derivative, and it was used as the hardener in fully vanillin-based epoxy-amine thermosets. 71 This amine was also used to crosslink DGEBA, and quite elevated T g was obtained (176 °C), however lower than DGEVA/44DDS (204 °C). Vanillin and other aromatic aldehydes derivatives were also used in order to synthesize rigid structures using a spiroacetal linker, based on pentaerythritol, a tetra-hydroxyl compound (Figure 10). 72 Different bisphenolic structures were synthesized by Ochi et al. in order to analyse the contribution of methoxy moieties in epoxy thermosets using mechanical and dielectric analyses. 73,74 The monomers cured with DDM show slightly less crosslinking densities than DGEBA, and present alpha transitions very close to the DGEBA-DDM system (around 160 °C). The presence of methoxy moieties have shown to improve impact strength of the materials. However, no more study has been reported in the literature about degradation behaviour or other properties.

Spiro-divanillin

Divanillin spiro erythritol

Figure 11 -Synthesis of DGEVE from vanillin and erythritol, according to Yuan et al. 75 A bisphenol based on vanillin and the sugar substitute erythritol was synthesized by Yuan et al.. 75 The glycidylation leads to a diepoxy monomer (DGEVE, Figure 11), which was then cured with DDS and compared with DGEBAbased thermoset. The high melting temperature of the monomer (245 °C), led the team to heat the formulation at 250 °C prior to a curing step at 180 °C, but the DGEBA-based mixture had the same curing scheme for comparison.

Dynamic mechanical analysis revealed an alpha transition temperature of 184 °C which is close to the DGEBA/DDS formulation (208 °C). This high transition temperatures reveals a very rigid behaviour of the spiro acetal containing monomer. The rubbery plateau is lower for the newly synthesized monomer (11 MPa for the DGEVE monomer and 23 MPa for DGEBA). However, on the glassy plateau, from the published curves, we can observe that the modulus at 0 °C is about 1.5 GPa for DGEBA epoxy, compared to 3 GPa for the methoxycontaining network. The degradation behaviour showed that methoxy-containing material degrades at lower temperature than DGEBA. For instance, under inert atmosphere, the T d5% of DGEBA/DDS is 394 °C whereas it is 343 °C for the DGEVE/DDS network. The char yield is higher with the methoxy-containing network since it nearly triples (34.4 % for DGEVE vs 11.7 % for DGEBA, at 700 °C).

Tensile strength measurements were also performed on both networks. It can be remarked that DGEBA/DDS has a higher elongation at break (7.1 %) than DGEVE/DDS (3.1 %). However, the tensile modulus is higher for DGEVE (3.3 GPa) than for DGEBA network (1.8 GPa). The tensile strength is similar (71-83 MPa). The DGEVE monomer gives a higher hardness to the system, due to the rigid spiro acetal structure. However, the lower elongation at break shows a higher brittleness of the network.

Degradation in aqueous conditions have also been monitored. Indeed, the linker based on acetal moieties can be easily cleaved in acidic conditions. Epoxy film samples were immersed in a mixture of polar organic solvent and water with different mineral acids. Then the time was measured to the point where no observable material was remained. Hydrochloric acid showed the lowest degradation time compared to sulphuric and phosphoric acid.

Regarding the organic co-solvent it was observed that degradation was accelerated when the most polar solvent was used. Degradation time was between 55 and 160 minutes depending on the organic solvent used with 0.1 M HCl at 50 °C. Degradation was also monitored by NMR spectroscopy, and it was observed that the degradation occurred through acidic cleavage of the acetal moiety, leading to regeneration of the aldehyde. The aging of the epoxy resin was also studied using a Xenon test chamber, at a temperature of 60 °C and a humidity of 95 %. Under such conditions the T g of the material did not change significantly after 15 days.

Bisguaiacol F and other guaiacyls and syringyls

Figure 12 -Synthetic scheme of DGEBF synthesis according to Hernandez et al. 45 Coupling of phenolics is an interesting way to access bisphenolic compounds, with a structure close to BPA. 23 The properties of their epoxide derivatives are expected to be close to DGEBA. Hernandez et al. prepared a bisphenol from vanillyl alcohol and guaiacol, another lignin derivative (Figure 12). 45 Reaction was conducted in acidic medium, and purification by column chromatography afforded the desired isomer. After glycidylation, the EEW was determined to be 193 g•eq -1 , a value close to the DGEBA used for comparison (190 g•eq -1 ). The bisguaiacol was cured with PACM, and compared with DGEBA/PACM system. Dynamic mechanical analysis was performed on the networks, and it was observed that DGEBGF gave the higher E' (3.35 GPa) compared to DGEBA (2.37 GPa).

However, the tan δ of the DGEBA network displayed a peak maximum at 158 °C, whereas DGEBGF displayed a peak at 111 °C. DSC confirmed the trend with a measured T g of 149 °C for DGEBA network and 104 °C for DGEBGF. It was observed that the presence of the methoxy moieties in DGEBGF gave higher loss modulus on the glassy plateau, but that the packing of the network was less efficient due to the same methoxy moieties. This could explain both the higher loss modulus and the lower T g in comparison with DGEBA, which does not bear any methoxy. Degradation under nitrogen atmosphere revealed that the DGEBA network started to degrade at a higher temperature than DGEBGF, however the char yield was lower (2.3 % compared to 5.6 % for DGEBGF). The bisguaiacol-based epoxy showed the same trend than all the other vanillin-based monomers, resulting in lower T g but higher thermal stabilities. In a more recent paper, Nicastro et al. synthesized several bisphenols based on vanillic alcohol or syringyl alcohol, condensed with other phenols, 76 using a similar protocol than Hernandez et al.. 45 The condensation on the aromatic ring could happen at different position (ortho, meta, para), depending on the phenol, and the authors obtained mixtures, some of them were purified to obtain pure isomers. Thermomechanical properties evaluated by DMA of the pure isomers and the glycidylated mixtures of isomers (shown in Figure 13) are summarized in Table 2. All the thermosets were prepared using MDA as the hardener. All the thermosets displayed alpha transition temperatures lower than the DGEBA/MDA system, but it should be noted that most of the prepared monomers have higher EEW than DGEBA. A higher oligomerization degree could lower the crosslinking density. It has also been shown that at the rubbery state, the storage modulus decreased as the number of methoxy moieties increased. Koelewijn et al. worked on the synthesis method of bisguaiacol F isomers in order to obtain polycarbonates via copolymerisation of BGF. 77 They also conducted in vitro experiments to assess the human oestrogen receptor α activity of BGF, using two of the BGF isomers, namely 4,4'-BGF et 3-4'-BGF. Comparison was also made with 4-4'-BPF and 4,4'-BPA, and the natural hormone oestradiol. It was shown that BPA and BPF fully activated hERα in a dose-dependent manner, whereas the dose-response curves were only partial for the BGF isomers. The relative oestrogenic efficacy (REE) is an indication of the efficacy of the receptor activation compared to the one of the hormones (that has a REE of 100 %). REE for BPA and BPF were respectively 96 and 126 % showing a similar interaction between the bisphenols and the oestrogen receptor, whereas it was only 48 and 37 % for BGF isomers.

The para-para orientation of 4,4'-BGF showed a higher activity compared to the 3-4' isomer, which confirmed that the para-para orientation is an important criterion. The lower concentration needed for a given effect, called EC 50 was 1.3•10 -11 M for the 17β-E2 compared to 6.6•10 -7 M for BPA and as high as 9.4 and 8.7•10 -5 M for 4,4' and 3,4'

isomers respectively. This means that a higher amount of BGF is required to activate the receptor. Overall, BGF isomers showed 426-457 times lower affinity than BPA. These results are promising, as they are consistent with previous reports using other evaluation methods. 78 Peng et al. also performed in vitro testing on bisguaiacol F isomers. 79 Since the synthesis of bisguaiacol could generate isomer mixtures, they determined the ratios of isomers that were obtained from the condensation of vanillyl all bisguaiacols, the % RME2 that illustrates the normalized EA was lower than for BPA or BPF, in at least one cell line. The only exception was for one meta-para isomer which would require further investigations.

Amitrano et al. designed a study using molecular docking in order to study the influence of methoxy groups on the calculated binding affinity of bisphenols with the ERα receptor. 81 The authors evaluated several structures that could be derived from lignin, bisphenols bearing one or two methoxies on each aromatic ring. The influence of the bridging unit between the phenols was also studied, and the orientation of methoxy substitution on the ring. Their results suggest that methoxies do have an influence on the interaction between the bisphenols and the receptor via steric hindrance. However, the effect was especially significant when at least two methoxies were attached to one of the phenols, when there was no substitution on the bridging methylene. The authors also suggest that bulky substituents on the bridging unit have also an influence on the affinity with the receptor, likely due to the steric hindrance, especially when the phenols were substituted. Both methoxy substitution on the phenol and bulky groups on the bridging unit are the key parameters to possibly prevent interaction with ERα. The substitution orientation (ortho, meta, para) do not have a significant influence for bulky monomers, i.e. containing 2 methoxies on one phenol ring. However, when containing one methoxy on each phenol ring, the results were consistent with the reported in vitro tests by Peng and co-workers. 79 Some guaiacyl and synringyl bisphenolic compounds were evaluated by Hong et al. with intention to predict the oestrogen activity of a set of compounds using an in silico model, based on available data from the literature. 82 In this work, p,p'-BGF, p,p'-BGS (from Figure 14), and another bisguaiacol having one methoxy group on one of the ortho position, with a dimethyl-substituted bridging unit i.e. Bisguaiacol A (also reported in Amitrano et al. 81 ) were evaluated and their biding affinity predicted. From this three monomers, p,p'-BGS and bisguaiacol A were predicted as non-binder to the receptor. Bisguaiacol F (p,p'-BGF) was predicted to be binder to the receptor, but with a moderate confidence (probability to be binder is lower than 80 %). The quantitative binding affinity calculated for this latter bisphenol was slightly lower than BPA. This result is in accordance with the reported in vitro data described before. If bisguaiacol F do show an activity in vitro, as described e.g. in Koelewijn et al., the real-life concentration needed would be higher than for BPA, thus the ED potential would be lower. 77

Cyclopentanone bisvanillin

Figure 15 -Synthesis of DGEBPO and DGEBP from vanillin, according to Mogheiseh et al. 83 Shibata and Ohkita synthesized a divanillin-based monomer by an aldol condensation between two equivalents of vanillin and cyclopentanone (Figure 15), and used phenolic hardeners in order to generate epoxy-phenol thermosets. 84 More recently, Mogheiseh et al. used this divanillin-based monomer, and synthesized a slightly modified epoxy-phenol. 83 They formed an oxime by the reaction of the ketone with hydroxylamine. The compound containing two vanillin moieties and the oxime could be glycidylated, adding three glycidylether moieties. They used several hardeners, some containing hydroxyls, among them the biobased decanediamine (DA10). The fully cured material with the amine was characterized using infrared spectroscopy, gel content, mechanical and thermal properties. The glass transition temperature of the system DGEBPO/DA10was 102 °C and the alpha transition measured by DMA was 109 °C. For comparison, DGEBA/DA10 thermoset has a T g of 98 °C and T α of 97 °C according to Ménard. 85 The thermoset based on DGEBPO displayed a storage modulus of 1.7 GPa compared to 1.0 GPa for DGEBA/DA10, due to the more rigid structure of DGEBPO that is brought by the cyclopentenedione link between the two aromatic rings, and the higher epoxy functionality. The same trend is observed at the rubbery state with a modulus of 93.0 MPa for DGEBPO based material, compared with 23.2 MPa for DGEBA/DA10. In terms of thermal stability under inert atmosphere, the T d5% of DGEBPO material was 313 °C, which is slightly lower than DGEBA/DA10 (337 °C). This trend is often observed with methoxy-containing monomers such as vanillin-based compounds. Char yield at 700 °C was determined for the cured materials and DGEBPO, displaying 2.5 % compared to 5.2 % for DGEBA/DA10. Usually, it was observed that vanillin-based epoxides give higher char yields, and this result could be explained by a lower contribution to char formation of the cyclopentenedione link between the aromatics, even if the higher functionality of the monomer could lead to a better stability as compared to the difunctional DGEBA.

II.

Syringaldehyde Syringaresinol

Figure 16 -Synthesis of epoxy monomer of Syringaresinol from Syringaldehyde according to Janvier et al. 86 Syryngaresinol is a natural polyphenol found in some plants, but in very low yields. However, researchers have developed several catalytic and biocatalytic processes to afford multigram scale of this antioxidant. 87 Access to large quantities of this natural molecule has led to its use as an epoxy precursor, after glycidylation (Figure 16). Janvier et al. performed the synthesis of this diepoxide, and then studied the network properties with different hardeners such asDA10, IPDA and DIFFA. 86 The IPDA/SYR network displayed a T g of 126 °C, which is slightly lower than DGEBA. The α transition temperature of the SYR network was 157 °C (as compared to 166 °C for DGEBA/IPDA.

The glassy modulus (measured at 50 °C) of SYR/IPDA was 758 MPa while with DGEBA the value was 783 MPa.

The moduli and transition temperatures were similar to each-other, indicating that even if the crosslinking density was expected to be lower for the SYR network (due to a higher molecular weight between the crosslinks), the rigidity brought by the bicyclic linkage counterbalanced the effect on the network. At the rubbery plateau, the DGEBA network displayed a modulus of 16 MPa, compared to 12 MPa for the SYR network. The presence of a higher density of aromatics in DGEBA lead to a higher modulus.

When cured with DA10, the SYR network displayed a T g of 73 °C, compared to the DGEBA network reported by DGEBA, E2 and an isosorbide-based bisferulate described later in this review. 86 The activity relatively to the human hormone were plotted for all the compounds tested, at 10 -8 M. It was shown that the new epoxy monomers and the corresponding diols did not show any oestrogenic activity, since they display the activity corresponding to the vehicle (Figure 17). In addition, no dose-response was observed in the concentration range 10 -13 to 10 -5 M. Glycidylether of gallic acid was prepared by allylation of the carboxylic acid and the subsequent epoxidation of the allylic double bonds (Figure 18). 90 Aouf et al. performed the oxidation using two methods, the first using mCPBA and the second one using Oxone in milder conditions. However, the Oxone method gave lower yield of the tetraepoxide compared with the mCPBA method. GEGA was cured with IPDA using a mixture of the trifunctional and tetrafunctional monomers, with a mean of 3.8 epoxy per monomer. The thermoset properties were compared with the DGEBA/IPDA system. Dynamic mechanical analysis showed a T α of 233 °C for GEGA, much higher than for DGEBA (160 °C). This higher transition can be explained by the higher crosslinking density of GEGA, due to a higher functionality and the lower molecular weight compared to DGEBA. The temperature of 5 % degradation of the material under inert atmosphere (T d5% ) is 300 °C for GEGA and 350 °C for DGEBA. The lower thermal stability of GEGA is probably due to the presence of the ester bond. However, the char yield at 600 °C was 23 % for GEGA and 8 % for DGEBA. The higher crosslinking and aromatic density brought by GEGA lead to a higher stability and char formation at high temperature, compared to DGEBA.

III. Gallic acid

In the work of Tarzia et al., curing of GEGA was performed using IPDA and Jeffamine D230, which is a polypropylene-oxide based diamine. 89 They observed by DSC comparable curing exotherms with both amines (488 J•g -1 with Jeffamine and 531 J•g -1 with IPDA). They also observed similar peak temperatures (respectively 94 and 90 °C). The glass transition temperature after curing at 150 °C was also measured by DSC. systems. The tensile strength for epoxides cured with IPDA was higher with GEGA than with DGEBA. The opposite trend was observed for both epoxides cured with Jeffamine. It seems that the DGEBA systems can be subjected to more plastic deformation than GEGA systems. This is confirmed by the global higher percentage of elongation at break. The GEGA systems were more brittle due to the crosslinking density.

In a study screening 253 industrial chemicals, gallic acid was evaluated for its activity against androgen receptor.

The results indicated that this compound does not have any activity against the AR. 93 Unexpectedly, some studies report a protective effect of gallic acid on the toxicity induced by BPA. For example, a recent study by Trivedi et al. showed in vitro that the addition of gallic acid reduced the toxicity induced by BPA, especially on red blood corpuscle. 94 IV.

Protocatechuic acid

Figure 19 -Synthesis of TGEPA from protocatechuic acid, according to Aouf et al. 90 Protocatechuic acid is a catechol bearing a carboxylic acid moiety. It is a natural polyphenol found in seeds such as chia, canola or sunflower, or in fruits and berries such as mangosteen. 95 It has also been demonstrated that protocatechuic acid can be obtained from glucose, via microbial fermentation. 96,97 The glycidylation reaction of protocatechuic acid was first performed by Aouf et al. in a paper describing the effect of different substituents of natural phenols on the reaction of glycidylation. 90 No thermosetting polymers were prepared from this study, but recently, Chen et al. prepared crosslinked networks with DDM as the hardener. 98 It has to be noted that the trifunctional epoxy monomer can also be obtained by allylation and subsequent oxidation of the double bonds. 99 Chen et al. performed non-isothermal curing kinetics using Kissinger's method in order to assess the activation energies of the TGEPA/DDM system. Using five different heating rates, the authors measured an E α of 54 kJ•mol -1 compared to 57 kJ•mol -1 for DGEBA/DDM system, reported before with the same method. 100 The slightly more favourable activation energy was attributed to the presence of the ester moiety that could activate one of the glycidyl residue. The alpha transition determined by DMA for TGEPA/DDM was not observed by the tan δ peak before 250 °C, which is quite higher than DGEBA/DDM, which T α was measured at 189 °C. The storage modulus of the TGEPA network was higher than DGEBA (respectively 1.9 GPa vs 1.6 GPa) at room temperature, and it is explained by the rigid structure of the monomer compared to DGEBA. It has also to be noted that the single aromatic ring of the new monomer prepared by the authors could also lead to a higher aromatic density in the network, and thus, a higher rigidity. The very high T g was also confirmed by the measurement of coefficient of thermal expansion, determined by thermal dilatometry. Using this method, T g was measured to be 176 °C for DGEBA/DDM compared to 221 °C for TGEPA/DDM, which is coherent with previous characterizations. Finally, regarding thermal stability under nitrogen atmosphere, the T d5% of TGEPA network was 321 °C, lower than for DGEBA (364 °C), as often observed with monomers containing esters. However, the char yield measured at 1000 °C was 16 % for the DGEBA network, compared to 28 % for TGEPA network, showing a better charring ability, probably due to the high aromatic density of the network. 3,4-dihydroxybenzoic acid (protocatechuic acid) is considered as a human metabolite resulting from the exposure to parabens. 101 Parabens are well known preservatives that are also suspected of endocrine disruption. However, so far they have not been evaluated as endocrine disruptors.

V. Ferulic acid

Ferulic acid is a phenolic compound that can be found in bagasse, wheat and rice brans or beetroot pulp. It is composed of an aromatic phenolic ring bearing a methoxy moiety in ortho position, and an α,β-unsaturated carboxylic acid in para position. This compound that can be extracted from non-edible agricultural waste. 88 1. Bisferulates with alkyl ester linker Maiorana et al. synthesized an ester of ferulic acid by an acidic esterification with ethanol. The obtained ester was subsequently reduced in the same pot, using Pd/C and dihydrogen at ambient temperature and pressure. This ester was then used as a starting material for transesterification reactions using a lipase in order to obtain di or trifunctional derivatives with different linkages. The diols utilized were ethanediol, propanediol, butanediol and hexanediol (all linear) as shown in Figure 20. 102 Ménard et al. used the same method using isosorbide, butanediol and butanediamine to obtain bisferulates, and glycerol was used to obtain a trifunctional compound. 88 The corresponding esters or amides were then subjected to glycidylation, in order to obtain the corresponding epoxy monomers. Thermosets were prepared with different amines, and compared with DGEBA systems in each case.

Three amines were used as hardeners, namely IPDA (cycloaliphatic), DA10 (aliphatic) and difurfurylamine A (DIFFA) obtained from the condensation of furfurylamine with acetone. They compared the viscosity of the epoxies at 25 °C, and calculated the flow activation energy. They showed that the temperature dependence of the viscosity for the bisferulates were similar to DGEBA. A linear correlation was observed for the storage moduli at 25 °C when it was plotted against the diol length. The storage moduli were reduced as the length of the linker increased. This is mainly due to the increased chain mobility in the thermoset.

The glassy moduli of the bisferulates based networks were in the range 2300-3500 MPa, while the value for DGEBA network is 2640 MPa (close to the C4 bisferulate (Figure 21)). Regarding the α transition of the networks and the loss moduli peaks, a slight decrease was observed as the linker length increased (Figure 22). This is consistent with the increase in chain mobility as the number of carbons in the linker increased. However, for all the bisferulates diepoxides, the transitions were observed at lower temperatures, in the range 40-70 °C as compared to DGEBA (higher transition around 170 °C). The degradation behaviour of all the thermosets was also investigated under nitrogen. It was observed that longer linkers resulted in higher T d5% , with an increase from 300 to 331 °C for C2 to C6 diols. The onset of degradation was slightly higher for DGEBA network, however in the same range of temperature. Similar thermal resistance indicates similar thermal stability and suitability of the thermoset for same type of applications. It can also be noted that the char yields were higher for bisferulates (shorter chains gave higher char yields). As mentioned previously, the methoxy-containing monomers are more prone to increase the char formation. However, the increase in alkyl carbon content decreases the char formation, mainly due to the lower density of the aromatics and the crosslinking.

The hydrolytic degradation of the networks was studied in alkaline conditions at 60 °C), providing interesting information regarding the possible chemical recycling of the thermosets, and also the possible leaching of the compounds. The cured samples were immersed in an alkaline media at 60 °C and their weight was monitored as a function of time (Figure 23). This figure shows that the DGEBA does not degrade even after 50h, whereas the degradation kinetics for ester containing materials have a linear correlation with the linker size. Shorter alkyl chains degrade faster since the hydrophilicity of shorter chains are higher as confirmed by contact angle measurements. The C4 linker containing epoxide was also cured with DA10 and DIFFA by Ménard and co-workers. 88 It could be observed that the use of aliphatic hardeners with the C4 monomer gave a slightly less stable material with T d5% of 314 °C for IPDA and DA10, compared to the use of DGEBA as the epoxide (respectively 331 and 337 °C). With DIFFA however, the thermal stabilities were comparable with DGEBA (306 °C for the bisferulate and 301 °C for DGEBA). It seems that the crosslinking density of the DGEBA-DIFFA is responsible for the lower thermal stability.

Char yields were higher with all the hardeners with bisferulates, the highest values were obtained with DIFFA as the hardener for all the networks. The glass transition temperatures for all networks based on the C4 bisferulates were nearly one third of the ones obtained with DGEBA, for all hardeners (due to lower crosslinking densities). DMA measurements showed that the alpha transitions followed a similar trend. The glassy modulus of C4 bisferulate was the same as the DGEBA when DA10 was used as the hardener. The elastic modulus of bisferulate network with DA10 however was half of the value obtained for DGEBA (10.8 MPa vs 23.2 MPa). It seems that the rigidity of the monomers is comparable at T < T g , whereas at T > T g , the molecular motion is responsible (for bisferulate), probably due to the lower crosslinking density, and the presence of a linear alkyl chain (inducing free rotations). For the networks obtained with DIFFA, the glassy modulus is higher for DGEBA (2.1 GPa) than for the bisferulate (1.75 GPa), probably due to the higher aromatic density with DGEBA. Over the glass transition temperature, similar trends with DA10 was observed.

Maiorana et al. performed screening of the EA of the n-alkyl bisferulates before glycidylation. Comparison between EA was performed using the natural oestrogen, BPA, BPS and DGEBA (Figure 24). 102 The assay conducted was a measure of the activity of the ERα. While BPA and BPS showed 60 % activity compared to the hormone E2, the nalkyl bisferulates did not show a significant activity compared to DGEBA or the vehicle. No dose-response effect was measured in the studied concentration range. In the work of Ménard et al., butanediamine was used as a linker for the synthesis of a bisferulate, which glycidylation affords a diepoxy monomer (Figure 25). After curing with DA10, IPDA and DIFFA, properties of the networks were evaluated against DGEBA systems. With DA10, the T d5% are respectively 297 °C for the bisferulate and 337 °C for DGEBA, which shows a better stability for the network that did not contain amide bonds. It was also observed that the stability of the ester-containing network was higher, which was unexpected since amide bond is considered thermally more stable. Char yield of the BDFAmide network was 18.2 % compared to 5.2 % for DGEBA. The T g of the amide containing thermoset was 69 °C, which was lower than for DGEBA (98 °C). This can be due to a lower crosslinking density. It was also observed that the amide containing network has a higher T g than the ester pendant (33 °C), probably due to the hydrogen-bonding ability of the amide moiety. Mechanical properties of the material were not evaluated due to the high melting point of the monomer. The measured T g was 75 °C, half the value of DGEBA network. The IPDA/BDFAmide system lead to a T d5% of 282 °C (lower than DGEBA at 331 °C). The char yield was 18.2 %, higher than that of DGEBA (10.2 %). It can be noted that the char yield for IPDAcured amide bisferulate was similar to DA10-cured network. The cycloaliphatic or linear aliphatic amine did not seem to have an influence on the char formation. The low thermal stability could most probably be due to incomplete curing.

Finally, the use of furfurylic diamine DIFFA led to a T d5% of 271 °C versus 301 °C for DGEBA, and a char yield of 23.7 % (14.8 % with DGEBA). The use of a furan-containing hardener increased the char yield globally, but it decreased the thermal stability as compared to the aliphatic amines (char formation is promoted by aromatic containing moieties, such as DIFFA). The T g of 74 °C was similar to IPDA and DA10. The presence of furan rings should increase the rigidity; however, the crosslink density was decreased dueto the structure of the DIFFA. The bisferulate based on isosorbide linker synthesized by Ménard et al. also provided insight into the properties of bisferulate-based epoxides (Figure 26). 88 With all three hardeners, isosorbide-bisferulate networks had lower thermal stabilities (lower T d5% ) compared to DGEBA, but higher char yield due to the presence of the methoxy moiety. Glass transition temperature and alpha transition temperatures were also lower than DGEBA. Comparing with the other bisferulates, the T g was lower than the amide linker, but higher than the linear ester linker (C4). But the glassy moduli with DA10 and IPDA were lower for DGEBA networks. The bicyclic linker provided significant higher rigidity to the networks, although the effect was counterbalanced by the crosslinking density when DIFFA was used, resulting in similar modulus (around 2.0 GPa). At T > T g , the elastic modulus was lower for all the networks with the bisferulate than with DGEBA. Even if the bicyclic structure of isosorbide linker conferred an important rigidity, it seems that at high temperature, it does not impact the mobility of the chains in order to the elastic modulus high (also confirmed by the relatively low alpha transitions temperatures).

Bisferulate with isosorbide linker

The endocrine activity of the bisferulate and its glycidylether derivative was assessed. 86 The activity of the bisferulates at 10 -8 M was comparable to the one of the vehicle, meaning that the diol and the epoxy monomer did not show any specific activity. In addition, no dose-response activity was observed in a concentration range between 10 -13 and 10 -5 M. Using glycerol as the linker between ferulate residues, Ménard et al. also provided data about the behaviour of a trifunctional monomer in different networks (Figure 27). 88 The glycerol-based triferulate GTF gave lower thermal stabilities than for DGEBA for all hardeners, but higher char yields. The higher crosslinking and aromatic density did not increase the thermal stability, mainly due to the presence of the fragile ester linkages, but as expected the higher aromatic density did improve the char formation. Glass transition and α transitions were also lower with the glycerol-based monomer than with DGEBA with all the hardeners, namely 58 °C for DIFFA, 54 °C for DA10 and 73 °C for IPDA (glass transition) compared with respectively 92, 98 and 150 °C for DGEBA. The same trend was observed for T α . Mechanical properties revealed different trends. With IPDA as the hardener, DGEBA and GTF had the same glassy modulus (1.7 GPa) and the elastic modulus was lower for GTF (16.4 MPa vs 21.0 MPa for DGEBA). With DA10, the glassy modulus was higher for GTF (2.4 GPa vs 1.0 GPa) whereas the elastic modulus was almost the same (around 23-24 MPa). With DIFFA, the glassy modulus was 1.7 GPa for GTF while with DGEBA it was 2.1 GPa. The elastic modulus was very low for GTF (7.9 MPa), while it was 21.2 MPa for DGEBA.

Trifunctional ferulic ester epoxy monomer

It seems that in the case of DIFFA, increasing the crosslinking density improves the rigidity at the glassy plateau, but not too beneficial for temperatures above T α . Ferulic acid was also used to synthesize other diepoxides, based on a glycerol linker, but with the addition of a fatty ester chain. The variation of the length of this fatty acid residue allowed Hollande et al. to study the influence of hydrophobic properties on the degradation in acidic aqueous environment, and on the endocrine receptor activities of the bisphenols (which is discussed later in this review). 103 All the monomers were denoted GDFxEPO with x corresponding to the number of carbon of the fatty side chain (Figure 28). The monomers cured with DA10 led to T g between 3 and 5 °C. As a comparison, the C4 bisferulate by Ménard et al. led to a T g of 33 °C, and DGEBA/DA10 of 98 °C. 88 The addition of a fatty acid side-chain led to a dramatic decrease of the T g , as the side-chain acts as a plasticizer. The same trend was observed with the other hardeners: DIFFA cured GDFxEPOs led to T g between 11 and 16 °C as compared to 32 °C for the C4 bisferulate and 92 °C for the DGEBA. For the IPDA-based networks, the T g of the GDFxEPOs were between 18 and 23 °C, 51 °C for the C4 bisferulate and 150 °C for DGEBA. For all the GDFxEPO, the char yields obtained range between 7 and 17 %, the highest obtained for DIFFA cured monomers.

Bisferulate ester with side-chain containing linker

These values were very close to the char yields obtained with DGEBA. Usually, the presence of the methoxy on phenols tend to increase the char yields, but the presence of the fatty acid esters lower the aromatic density in the networks, decreasing the char formation. Thus, the decrease in alkyl content increases the char in ferulic acid based monomers with phenolic methoxy groups, it. The opposite phenomena is observed for DGEBA networks, since there is no phenolic methoxy or long alkyl chains present in the structure. However, regarding degradation temperatures (especially T d5% ), it was observed that for the GDFxEPOs, temperatures of 280 to 310 °C were measured (300-330 °C for DGEBA). The fatty chains-containing bisferulates had slightly lower thermal stabilities compared to the same networks with DGEBA. In overall, the plasticizing effect of the alkyl chains led to similar thermal stabilities, with lower T g values as compared to DGEBA networks.

Regarding the wettability and degradation in aqueous acidic conditions, all the thermosets were evaluated by measuring the contact angle, and the weight loss during incubation in 3 M HCl aqueous solution at 60 °C, up to 50 h. It was observed that, for all hardeners used, the water contact angle increased as the length of the fatty chain increased. All the contact angles were measured between 60 and 90°, showing poor affinity with water. Hydrolytic degradation was however faster for the shorter fatty acid chains. Complete degradation was observed for GDFxEPO with x=10 after 50 h. No comparison with DGEBA was performed. And under alkaline conditions, barely any degradation was observed for DGEBA/IPDA . 102 The work of Hollande et al. also focused on the determination of oestrogenic affinity of the prepared bisferulates. 103 Two other hormone receptors were also tested, namely PXR, a steroid receptor and AR, an androgen receptor. The concentrations tested were in the range 10 -14 to 10 -5 M. At these concentrations, an oestrogen receptor activity was recorded for the E2 hormone, and for BPA. No significant activity was observed for the GDFx (Figure 29). At higher concentration, 10 -5 M, no abnormal receptor activity was measured for all the GDFx as well as other receptors (PXR and AR). Also no antagonist activity of the GDFx was recorded for all the receptors. Diglycidylether of resorcinol (RDGE, Figure 30) is a diepoxy monomer that has been widely reported in the literature. It is composed of a monoaromatic phenolic compound, bearing two substituted phenolic hydroxyls, leading to the diepoxide. This monomer has found a large range of applications, and appears in several patents. The specific position of the two phenolic moieties of resorcinol gives high reactivity to the monomer. However, resorcinol, that is the parent compound of the diglycidylether of resorcinol, has only been evaluated since 2016 as regards to endocrinal disruption activity. It seems that resorcinol may have an effect on thyroid. 104 Recently, the French health agency ANSES (Agence nationale de sécurité sanitaire alimentation, environnement, santé), has recommended its classification as a SVHC for its endocrine disruption properties. 105 Since March 2022the EU regulation commission has added RDGE to the list of carcinogenic and mutagenic substances. 106 Resorcinol based diepoxy monomer and its homopolymer, are used in all kinds of applications given the existence of more than 1200 patents and 350 research journal articles. Among these articles, only a few of them give qualitative data about thermosetting epoxy, cured with standard amine hardeners. For example, Mattar et al. used HMDA and obtained thermosets with a T g of 80 °C and a T α of 110 °C. 107 The modulus at the glassy plateau was 2.5

VI. Resorcinol

GPa, and at the rubbery plateau, it was 20.52 MPa. The presence of the aromatic ring inside the network led to relatively high transition temperatures. As a comparison, DGEBA/HMDA network showed an alpha transition at 118 °C and the E' at the rubbery state was 27.4 MPa. 108 The close values between DGEBA and resorcinol diglycidylether showed that the higher crosslink density with the resorcinol gave close thermomechanical properties to DGEBA thermoset, even if less aromatics were in the monomer structure. In a study evaluating the effect of the geometry of the monomer in epoxy-amine networks, Riad et al. prepared several thermosets using resorcinol diepoxy, cured with several aniline derivatives. 109 They obtained high T g with monoaromatic diamines, between 129 and 148 °C. They also obtained a glass transition temperature of 175 °C with a diamine containing two benzene rings in its structure. The rigidity of this latter hardener, and the higher aromatic density of the obtained network leads to higher T g . As mentioned earlier resorcinol and its derivatives are not recommended and are considered as endocrine disruptor.

VII. Phloroglucinol

Figure 31 -Synthesis of PTGE according to Ménard et al. 85 Phloroglucinol is a biobased phenolic compound bearing 3 phenolic hydroxyls. The structure of phloroglucinol can be found in tannins. 110 This phenolic compound is also a widely used drug, especially for the symptomatic treatment of abdominal pain. 111 The glycidylation reaction leads to a triepoxy monomer (Figure 31), containing generally oligomers, due to the high reactivity of the phenol. More than 70 patents mention the use of PTGE (phloroglucinol triglycidyletherin fiber-reinforced composites for medical prosthesis, binder for cork composites, anti-fouling membranes and adhesives.

Ménard et al. used PTGE cured with several amine hardeners, and compared the thermomechanical properties with and without the addition of a flame retardant. 85 The three curing agent used were DA10, DIFFA and IPDA. The glass transition temperature of PTGE/IPDA network was 177 °C, compared to 157 °C for DGEBA/IPDA. This can be explained by the higher functionality of the epoxy monomer, leading to higher T g via limiting the chain mobility in the network. Thus, despite the lower number of aromatic rings in the epoxy monomer compared to DGEBA, the T g value is higher. Similar trend was observed when the two other curing agents were used. The PTGE/DIFFA network has a T g of 134 °C, whereas the DGEBA/DIFFA network has a T g of 92 °C, and the PTGE/DA10 network has a T g of 137 °C, compared to 98 °C for DGEBA/DA10. 88 The thermal stability of PTGE/IPDA was however lower under nitrogen, with a T d10% of 306 °C compared to 369 °C for DGEBA/IPDA. The lower aromatic content of the monomer may explain the reported lower stability. Char formation was higher for PTGE networks compared to DGEBA. The higher crosslinking density seems to be beneficial for the char formation using this epoxy monomer. It can also be noted that without any fire-retardant additives, the PTGE networks display lower heat release rate.

However, the lower thermal stability of all the networks lead to fuel gas emissions at temperatures lower than for DGEBA/IPDA thermoset (around 300 °C versus nearly 400 °C for DGEBA/IPDA). Phloroglucinol is known to have an effect on human health since it is widely used as an anti-abdominal pain medication. 111 However, some studies suggest the phloroglucinol to be potentially disruptor of thyroid receptors. 112 More studies are required to verify the effect of this compound on the endocrine system. Levulinic acid is a biobased compound that can be obtained from cellulose. It is a linear carboxylic acid containing a methyl ester moiety. The condensation of two equivalents of phenol with the ester leads to a diphenolic compound that is very similar to BPA, but instead of having two methyl moieties between the aromatic rings, the linker is composed of a methyl and a carboxylic acid terminated alkyl chain. After esterification, Maiorana et al. obtained several monomers with different length of side chain esters (Figure 32). 113 The glycidylation of these different diphenols led to several monomers noted DGEDPMe for methyl, DGEDPEt for ethyl, and two others with butyl (Bu) and pentyl (Pt) side chains. The viscosities of the pure monomers were measured and compared to DGEBA, at 25 °C. All the monomers displayed higher viscosities (12 to 792 Pa•s), compared to DGEBA (4 Pa•s). The methyl ester monomer had the highest viscosity (792 Pa•s), with several orders of magnitude above all the other esters ( 12to 63 Pa•s), probably due to a higher oligomerisation degree, evidenced by a higher deviation of the EEW compared to the other esters. It was also mentioned that from ethyl ester, viscosity decreases with the increased chain length.

VIII. Diphenolic acid

All the monomers were cured with IPDA and compared with DGEBA. The glass transition temperatures (from the peak of loss modulus) decreased as the alkyl chain increased, from 158 °C (DGEDPMe) to 86 °C (DGEDPPt), and were lower than for DGEBA (165 °C). Storage moduli were measured at 25 °C. For the methyl ester, this was higher than for DGEBA (2640 MPa for DGEBA and 3278 MPa for DGEDPMe). For all the other monomers, the storage moduli were lower, and decreased with the increase in the chain length. Tensile properties were also measured. Higher tensile strength were measured for the esters between Me and Bu, and it was similar between Pt and DGEBA thermosets. Strain at break was higher with Et and Pt (respectively 9.3 and 11 %), lower for Me (4.6 %) and similar with Bu (8.3 %), compared to DGEBA/IPDA (8.7 %). From these mechanical properties, it can be seen that the presence of the methyl ester does not act as a plasticizer, contrary to longer alkyl chains, as it is shown by storage moduli and T g decreasing with the increase in the ester length. The different behaviour of the methyl ester derivative was mainly due to the presence of triglycidylated products. During the synthesis of the monomer, the formation of a carboxylate resulted in addition of some epichlorohydrin on the carboxylate residue in addition to the phenols. The presence of trifunctional epoxide monomer, led to an increase of the mechanical properties. This can also explain the lower elongation at break, due to a more tightly crosslinked network, hence the brittleness. The thermal stabilities of the networks were also assessed. The T d10% were measured. These were similar for all the esters, ranging from 361 to 363 °C, and slightly lower than for DGEBA (378 °C). Char yields were similar for all the materials considered, between 10 and 13 %. These results show that the mechanical properties are very similar for all the esters, and very close to DGEBA in the case of the methyl ester. as depicted in Figure 33. 114 Complex viscosities of formulations at 90 °C were determined, and it was shown that the viscosity of the Me and Et esters increased faster than all the other formulations, including DGEBA. The induction time in the rise of viscosity was longer for Bu and Pt, but lower than for DGEBA. However, once the viscosity started to rise for DGEBA, the rate of the increase was faster for DGEBA than for the Pt and Bu esters. Moreover, a slower rate of viscosity increase was observed for the pentyl ester. These data in addition with the kinetic studies, lead to the conclusion than the pentyl ester monomer could be a good substitute for DGEBA for infusion moulding applications, whereas the high reactivity of the methyl ester monomer (also containing trifunctional monomers) could be interesting for adhesive applications, for which a fast reaction time is required. McMaster et al. cured these monomers with IPDA, in addition to a propyl ester monomer, and evaluated their dielectric properties. 115 Interestingly, they found that the propyl ester has a high dielectric constant (5.26 at 0.05 Hz), higher than the Bu and Et esters, and especially higher than DGEBA. The DGEDPMe has higher dielectric constants, but as already mentioned earlier, the thermomechanical properties are less consistent. The thermomechanical properties of the DGEDPPr were also measured, with a T g of 129 °C, strain at break of 8.3 % and tensile strength of 58 MPa. These epoxy thermosets could be used as structural capacitors. Gao et al. studied the DGEDPMe cured with DDM. 116 They measured a T g of 153 °C for DGEDPMe/DDM, compared to 164 °C for DGEBA/DDM. The thermal stabilities of the thermosets were also quite similar under air, especially with the measure of the temperature at the onset of degradation which was 315 °C for DGEBA and 310 °C for DGEDPMe. The residual weight at 700 °C was slightly higher for DGEDPMe (2.7 % compared to 0.1 % for DGEBA). Impact strength, tensile strength and elongation at break were also very similar between both epoxy networks. Regarding flame retardant properties, the heat release rate peak was lower for DGEDPMe (520 kW•m -²) compared to DGEBA (711 kW•m -²), but the total heat release was similar, as well as smoke emission parameters (such as average smoke production rate, total smoke release or average CO production rate) were determined. Up to now the diphenolic acid based epoxy monomers have mainly been used in composites with different type of fillers such as cellulose nanocrystals. 117 Some reports have described the endocrine activity of the diphenolic acid derivatives, with R=H. Some research articles have concluded that diphenolic acid did not present any activity over several receptors, such as oestrogen receptor or androgen receptor. 118 However, some others in silico research suggest that diphenolic acid could be a weak ERα agonist. 119 More studies are required to assess the complete toxicological profile of this bisphenol. None of the ester derivatives have been evaluated for potential endocrine activity.

IX. Triphenols

Figure 34 -Synthetic scheme and structures for the obtention of triphenol epoxy monomers from Zhao et al. 53 Zhao et al. used the condensation of aromatic aldehydes on phenols in order to obtain several triphenols, bearing methoxies (Figure 34). 53 From all the synthesized triphenol, they used four of them for glycidylation reactions, and obtained triepoxy monomers. Curing was performed with DETA, and thermomechanical properties were measured.

All the formulations presented low temperature reactivity, as monitored by DSC. For all the monomers, the curing exotherm started around 40 °C with a peak around 80 °C. The obtained networks were characterized using DMA and TGA (Table 3. All the results were compared to DGEBA thermoset, using the same amine hardener. As expected, alpha transitions temperatures were higher compared with DGEBA. Indeed, the higher rigidity of the monomers, due to their structures and aromatic densities, led to higher transition temperatures. Plus, the use of trifunctional monomers usually give higher transition temperatures and higher glassy moduli, due to a high crosslink density. The presence of methoxies lowered the values of transition and Young moduli. Thermal stability was also affected by the presence of the methoxy moieties. As expected, increasing the methoxy content, reduced the thermal stability. BPA-based thermoset in the absence of such methoxies, degrade at higher temperatures. Char yield however was higher for the triphenolic monomer based epoxides. The increase in char yields could be attributed to the increase in the aromatic density (compared to DGEBA). Surprisingly, the increase in methoxy functionality did not lead to an increase in char yield. In this case, the reduction of char yield with increasing methoxy content could be attributed to a lower crosslinking density. The steric hindrance brought by the methoxy groups may have a higher effect on the network structure, leading to reduced mechanical properties, compared to the doping effect on the char yield, as char formation is also highly dependent on the crosslinking density.

Tensile tests of these thermosets, and all the triphenol-based networks displayed similar maximum stress (74.9-80.0 MPa), and elongation at break of 2.55-2.68 %. As a comparison, DGEBA/DETA network showed a maximum stress of 62.2 MPa and elongation at break of 3.56 %. The triphenol networks showed a higher rigidity and a higher brittleness, due to the crosslinking density. The only evaluated compound, M 0 (under commercial name of Tactix 742. 120 ) did not show any strong activity on the receptor in competitive binding assay against ERα. 121 .

None of the other triphenol compounds have been evaluated so far. The work of Hong et al. predicts the binding affinity of a triphenol compound where the three phenols bear a methoxy group on the ortho position. 82 The compound has been predicted to be an ERα binder, with a moderate prediction confidence. However, the model could not calculate the quantitative affinity, since the monomer did not fit the receptor in the molecular docking calculations. The authors thus concluded that it is unlikely that this monomer would have a real affinity for the receptor. Eugenol is a natural phenol, one of the main constituents of clove oil. Its structure is a phenol bearing a methoxy moiety and an allyl moiety (Figure 35). It can also be obtained from the enzymatic hydrolysis of lignocellulose. It is used in perfumes, as food additive as well as in pharmaceutics. 122 Eugenol can be easily modified to obtain diepoxy monomers, and its derivatives have been used as a starting compound, for the synthesis of thermoset polymers.

X. Eugenol

Endocrine activity of eugenol has been assessed especially in the context of the use of essential oils that have gained a growing interest in the past years. Howes et al. looked at the activity of eugenol on the oestrogen and androgen receptors, using enzymatic tests( modified enzymes expressing the human receptors). 123 In this work, eugenol did not show any activity against the androgen receptor. However, it did show an activity on the oestrogen receptor, but at high concentration compared to the E2 hormone. It also showed an activity towards a competitive displacement bioassay, at high concentration (10 4 to 10 5 higher than 17 β-oestradiol). Overall, eugenol showed an anti-oestrogenic activity. A triepoxy can be obtained from eugenol, by a multi-step process, as depicted in Figure 36. 124,125 First, eugenol is reacted with allyl bromide, leading to the allylation of the phenol moiety. Then, a Claisen rearrangement can be performed via a thermal activation. The allyl moiety grafted onto the phenol is rearranged into an allyl moiety, but on the ortho position of the aromatic ring. The further allylation of the now free phenolic moiety leads to a triallyl monomer, since eugenol is naturally bearing an allyl moiety on para position. The oxidation of the three allyl moieties leads to a triepoxy monomer (triepoxy eugenol (TEE)). Santiago et al. used this trifunctional monomer in order to make thermosets, with IPDA and Jeffamine D400 as the hardeners. 126 The results were also compared with the corresponding DGEBA networks.

Tri-epoxy-eugenol

With Jeffamine as hardener, the TEE displayed a T g of 59 °C, which is slightly higher than with DGEBA (T g = 50 °C). With IPDA, a more rigid hardener, the T g of TEE was 174 °C. These high T g values are mainly because the trifunctional TEE monomer, leading to highly crosslinked networks. This effect is favoured with the rigid diamine IPDA, compared to the use of the polypropylene-based Jeffamine. Dynamic mechanical analysis showed a similar trend. The Young's modulus at the rubbery state were 12 MPa for DGEBA/Jeffamine, 35 MPa for TEE/Jeffamine, 45 MPa for DGEBA and 214 MPa for IPDA. Tensile tests showed that the elongation at break was lower for the TEE networks as compared to DGEBA. The higher crosslinking density resulted in brittle material as the elasticity was reduced.

As observed with methoxy-containing monomers, degradation temperatures of TEE networks were lower than for DGEBA networks, under nitrogen. Using Jeffamine as the hardener, DGEBA network had a T d5% of 354 °C, whereas the value for the TEE network was 314 °C. The same trend was observed with IPDA, with 348 °C for DGEBA, and 317 °C for TEE. However, the char yield was higher with TEE, thanks to the higher crosslinking density, and the contribution of the methoxy groups to the char formation. The obtained char yield were 7.6 % for DGEBA/Jeffamine and 15.4 % for TEE/Jeffamine, while with IPDA, the DGEBA had a char yield of 9.6 % as compared to 23.5 % when using TEE. demethylation, in order to generate another phenolic hydroxyl, from the methoxy moiety. 127 The glycidylation of this catechol derivative leads to a diepoxy monomer (Figure 37). The authors studied the curing reaction of the diepoxy monomer with DETA, used dihydroeugenol or the catechol derivative as catalysts, and prepared composites using nanoclay. They obtained low temperature curing, with fast kinetics, with a full conversion observed by DSC.

Dihydroeugenol diepoxy

For example, 100 % conversion was obtained in less than 60 minutes. Post curing at 95 °C was however performed to ensure complete curing. DMA performed on the cured networks revealed a T α of 40 °C, which is much lower than the reported data for DGEBA (100 °C). The Young's modulus of the DGEDHEO/DETA was 175 MPa, which is quite low, compared to the value reported for DGEBA/DETA (2 GPa). The lower transition temperature and lower modulus could be due to the low aromatic density with a mono-phenolic compound, where the propyl moiety act as a plasticizer in the network, but also causes steric hindrance. Thermal properties were evaluated by TGA, with a T d5% of 190 °C, and a char yield of 3 % at 500 °C under nitrogen. These low values can be explained by the use of an aliphatic amine, leading to a low aromatic content in the network. As a comparison, DGEBA-DETA thermosets gave T d5% of 305 °C and a char yield of 8 %. 53 The epoxy-amine network with DGEDHEO has been used as a matrix forming material in composites containing nanoclay as filler. 127 3. Bis-eugenyls with a methylene linker In a study, Zhao and Abu-Omar used two dimers obtained from dihydrogeunol. 128 First, dimerization of dihydroeugenol leads to a bisphenol, which glycidylation results in a diepoxy monomer (DDHE, Figure 388). The product from o-demethylation of dihydroeugenol, after dimerization, leads to a biscatechol compound, which after glycidylation results in a tetra-epoxy monomer (TDHEO, Figure 38). Both monomers were cured with DETA. DMA showed a T α of 70 °C for the DDHE/DETA network, and of 84 °C for the TDHEO/DETA network. The difference between the alpha transitions of both thermoset can mainly be explained by the higher functionality of the TDHEO network. Compared to DGEBA/DETA ( T α = 100 °C) these transitions are lower. 53 This is explained especially by the effect of the propyl moiety, which can either induce a plasticizing effect, or a steric hindrance in the network. In addition, the Young's moduli at the glassy state were 551 MPa for DDHE compared to 1441 MPa for TDHEO, indicating the important effect of the crosslinking density on the mechanical properties. The calculated crosslinking densities were 1.39 mol•dm -3 for DDHE and 3.28 mol•dm -3 for TDHEO (2 GPa for the DGEBA/DETA network) which are higher than for both of the eugenol-derived networks. Regarding thermal stability under inert atmosphere, both TDHEO and DDHE thermosets had comparable T d5% , respectively 245 and 235 °C, and between 10 and 11 % char yields. DGEBA/DETA network had a better thermal stability, with a T d5% of 305 °C and a char yield of 8 %. As evidenced often, the presence of the methoxy moieties lowers the degradation temperatures, but increases the char formation. Koelewijn et al. synthesized different bisphenols from lignin derivatives, in order to further synthesize polycarbonates and cyanate ester resins. 129 These bisphenols were mainly guaiacol derivatives, which were coupled in meta position. Among all monomers investigated in their work, the m-m'-4-n-propylguaiacol corresponded to the bisphenol based on dihydroeugenol reported by Zhao and Abu-Omar. 128 The different bisphenols were evaluated in vitro, and compared with BPA and the E2 hormone. Results using E2 as the reference showed that the synthesized bisphenol has a lower induction potential (maximum 0.67 relative to E2), and at higher concentrations (around 10 -6

M compared to 10 -11 M for E2). These preliminary results should be confirmed by more type of bioassays, as well as in vivo experiments.

Bis-eugenyl with aromatic ether spacer

Figure 39 -Synthesis of dieugenyl monomer DEU-EP from Wan et al. 48 A diepoxy monomer was synthesized by Wan et al. using a dichloroxylylene, reacted with the phenol. 48 This led to an etherified dieugenyl, containing an additional aromatic cycle. The epoxidation of the allyl bond of eugenol residues was then performed using mCPBA, in order to afford the diepoxidized monomer DEU-EP (Figure 39).

Curing was performed using diaminodiphenylmethane hardener (DDM) and was compared with the DGEBA/DDM system. The curing was followed by DSC, and the crosslinking took place after successive melting of the hardener, and the diepoxy monomer. The peak maxima of the heat flux rate was nearly at the same temperature, i.e. 161 °C with DGEBA and 164 °C with DEU-EP. Isothermal curing kinetics revealed that, even if the total enthalpy of the curing reaction was close in both systems, a longer curing time was necessary to obtain 100 % conversion at 140 °C for eugenol-based monomer. This can be explained by a higher steric hindrance due to the presence of the methoxy moieties from eugenol residues. The mechanical properties were also investigated and compared, with a tan δ peak at 154 °C with DGEBA/DDM, and 114 °C with DEU-EP network. Even if the eugenol-based monomer had a higher aromatic density, the crosslink density of the material was lower, as the ether bond of the linker between eugenyls allowed a better motility of the chains, compared to DGEBA network. The crosslinking density was calculated to be 2285 mol•m -3 for DGEBA and 1346 mol•m -3 for DEU-EP, confirming the hypothesis. However, the storage moduli at the glassy plateau revealed that the dieugenyl epoxy network was more rigid and stiff at 30 °C, with values of 362 MPa for DEU-EP/DDM, and 257 MPa for DGEBA/DDM. At temperatures lower than the T α the interaction between the polymer chains in the network seem to have a stronger effect, accompanied by the aromatic density.

Regarding the thermal stabilities, a slightly lower thermal stability was observed for the dieugenyl-based network.

For the eugenol-based network, the T d5% under nitrogen was 341 °C (compared to 379 °C for DGEBA). The char yield was higher than with DGEBA (38 % as compared to 18 %). Flammability tests were also performed using a microscale combustion calorimeter, with a total heat release of 16 kJ•g -1 for dieugenyl network and 27 kJ•g -1 for DGEBA/DDM. The peak temperature of heat release rate was similar, attained at 410 °C for DGEBA, compared to 406 °C for eugenol containing network. However, the peak heat release rate was 447 W•g -1 for DGEBA network, compared to 201 W•g -1 for the DEU-EP thermoset. In general, the eugenol-based diepoxy network had lower flammability, even if degradation happens at slightly lower temperature. Horizontal burning tests of the eugenolbased network showed that they were able to self-extinguish after burning for 10 seconds. This value for the DGEBA network was above 60 seconds. Wan et al. used a biseugenyl with an aromatic linker, based on the terephthalic acyl chloride (Figure 40). 130 They used 33DDS in order to obtain epoxy-amine thermosets and compared the results with the DGEBA network with the same hardener. They measured an alpha transition temperature of 168 °C with the dieugenyl monomer, and 174 °C with DGEBA. The storage moduli at 30 °C were 3.5 GPa for TPEU-EP and 2.7 GPa for DGEBA. The higher rigidity of the eugenyl monomer increased the storage modulus, due to the higher aromatic density and the rigidity of the ester bonds. The rubbery modulus however was lower for the dieugenyl (10.59 MPa) compared to DGEBA network (19.53 MPa). This could be due to the influence of the crosslinking density, since it was 900 mol•m -3 for TPEU-EP and 1640 mol•m -3 for DGEBA. The rigidity brought by the aromatic rings and the ester bonds of the eugenyl monomer had more influence at low temperatures, especially because of the intermolecular interactions, that could be broken at higher temperatures. At the rubbery state, the lower crosslinking density and the breaking of the intermolecular interactions between chains allowed a better molecular motility. Regarding the thermal stability, it was observed that under nitrogen and under air, the eugenyl-based thermoset degraded at lower temperatures compared to DGEBA (T d5% under nitrogen were respectively 338 °C and 394 °C, and 337 and 387 °C under air).

Bis-eugenyl with aromatic ester spacer

This lower degradation temperature is probably due to the presence of methoxy groups on the eugenyl residues, as well as the thermally labile ester bonds. For the eugenyl-based network the char yield under nitrogen was 32 % (14 % for DGEBA).

Burning behaviors of the thermosets were also investigating, using microscale combustion calorimetry and limiting oxygen index evaluation. The LOI of the DGEBA thermoset was 23.5 compared to 26.8 for the TPEU-EP network, demonstrating a lower flammability with the eugenol. However, even if the total heat release was lower (14.9 kJ•g -1 compared to 24.9 kJ•g -1 for DGEBA), as well as lower peak heat release rate for eugenyl (123 W•g -1 compared to 383 W•g -1 for DGEBA). The peak temperature of the heat release was 376 °C for the dieugenyl, compared to 415 °C for DGEBA network. The fact that the eugenyl thermoset degraded at lower temperature could explain the lower peak temperatures. The flammability and the thermal stability of the eugenol containing network were lower compared to DGEBA.

6. Bis-eugenyls with alkyl ester or furanic ester spacers Biseugenyls have been synthesized by Chen et al.. 131 They synthesized four monomers by reacting two equivalents of eugenol with diacyl chlorides, in order to obtain dieugenyls with different spacers. The obtained monomers respectively contained ethyl ester, butyl ester and hexyl ester spacers, and finally a furfuryl ester spacer (Figure 41).

They performed a self-curing reaction, using catalyst, with DDM as the amine hardener. For the amine-cured networks, they obtained T g of 118 °C, 99 °C and 91 °C for the monomers containing the C2, C4 and C6 spacers, and a higher T g of 169 °C with the furfuryl ester spacer (higher than the 164 °C for DGEBA reported by Gao et al. 116 ).

Both the furan rings and the ester bonds bring about rigidity to the network. On the contrary, the alkyl spacers resulted in lower T g values that were decreased with the increasing length of the alkyl chain. These results are in line with the DMA results, where T α of 139 °C, 120 °C and 112 °C were obtained for the C2, C4 and C6 monomers respectively. These values are lower compared to the values reported by Wan et al. for the DGEBA/DDM system(T α = 154 °C). 48 The furan-containing monomer had an alpha transition temperature of 181 °C, higher than DGEBA, probably due to higher rigidity. The rubbery plateau was also measured for the networks. Values of 15 and 21 MPa were obtained for the alkyl containing thermosets, and 36 MPa for the furan-containing network. Regarding the thermal stability, the T d5% of the different alkyl containing networks were in the range of 350-368 °C and 341 °C for the furan containing system. The char yields varied in the range of 20-25 % for the alkyl-containing thermosets, and 28 % when furan was used. The global thermal stability was thus slightly lower than DGEBA/DDM system, reported by Wan. 48 Dielectric constants were also measured for all the thermosets, at ambient temperature at1 GHz.

The results were similar for the alkyl containing networks (between 3.03 and 3.08) and 3.10 for the furan-containing thermoset. Dissipation factors varied between 0.019 and 0.022 for all the evaluated thermosets. Comparing to the self-cured epoxy networks with diamine cured networks, showed higher dissipation factors when amine hardeners were used. Zago et al. designed several epoxy monomers derived from vinylphenols (Figure 42). 132 The first vinylphenol used was eugenol bearing a vinyl moiety, attached to the aromatic ring via a methylene. Two other vinyl phenols were obtained from vanillin and syringaldehyde, using the Knoevenagel-Doebner condensation reaction. The aldehyde was converted into a carbon-carbon double bond, leading to a vinyl moiety directly attached to the aromatic ring.

Other vinylphenols

The resulting vinyl phenols, namely 4-vinylguaiacol (from vanillin) and canolol (from syringaldehyde) were glycidylated and finally coupled, by using cross metathesis, in order to obtain diepoxy monomers. However, none of the resulting six diepoxy monomers have so far been used in thermosetting polymers.

These interesting diepoxy monomers were evaluated by computational methods, for their potential ability to bind to the ERα. 132 All the starting monophenols, the glycidylated monophenols, and all the hydrolysed epoxies were evaluated. The molecular docking data revealed that some of the compounds could interact as agonist or antagonist of the receptor. However, when interaction was probable, the dissociation constant calculated, indicated that high concentrations (at least 7 times higher) would be needed to obtain an effective binding (with BPA as the reference).

Thus, it is unlikely that these compounds would have an endocrine activity at relevant environmental concentrations.

However, these data are only computational, and more investigation would be necessary. In addition, in could also be interesting to generate data for the non glycidylated bisphenols, as often considered regarding BPA and DGEBA.

In the work of Hong et al., two of the bisphenols synthesized by Zago et al. were included for prediction of the ERα binding ability. 82 The bisphenol obtained from cross-coupling of eugenol (Eu-Eu), and the compound obtained from the cross-coupling of 4-vinylguaiacol (4VG-4VG) were evaluated. The 4VG-4VG bisphenol was predicted to be a non-binder to the ERα, with a low prediction confidence. The Eu-Eu bisphenol was predicted to be an oestrogen receptor binder. The quantitative affinity that was calculated indicated a higher binding affinity than BPA. These results are consistent with the work of Zago et al., which showed a potential interaction of this compound both as agonist and antagonist of the receptor. 132 However, the prediction by Hong et al. had a low confidence. In vitro testing would provide more data to improve the predictions from in silico model. But these results suggest that such monomer could not meet the criteria for substitution of BPA. When these results are evaluated regarding the work on guaiacyls or syringyls discussed earlier in this paper, the results are rather consistent, especially regarding the influence of methoxy moieties. 81 The presence of methoxies on the phenolic residues do not provide enough steric hindrance to impede the binding to the receptor. The work of Hong et al. also provides prediction for bisphenols that are similar, but which could be obtained from the double-bond reduction of Eu-Eu and 4VG-4VG. The results show that these to hydrogenated bisphenols are predicted to be binder to the ERα. The absence of the double bond lead to an increased affinity with the receptor. The hydrogenated Eu-Eu is predicted to have a higher affinity than BPA, and the prediction to be binder have a high prediction confidence. The hydrogenated 4VG-4VG has a low prediction to be binder, and the quantitative affinity would be lower than BPA. The authors suggest that this result indicates a planar configuration required for the interaction with the receptor. The natural E2 has a planar configuration, and the influence of the double bond would specifically modify the ability of the bisphenol to adopt the planar configuration. Overall, the nature and the length of the bridging unit in bisphenols is also an important parameter, as previously described. 35,36 XI. Magnolol Magnolol is a natural diphenol, extracted from Magnoliae officinalis, bearing two allyl moieties. The glycidylation of the phenolic moieties was performed by Qi et al. in order to obtain a diepoxy monomer (Figure 43), that was subsequently cured with 44DDS. 133 The presence of the allyl moieties could provide the possibility of a second crosslinking via thermal polymerization, within the same temperature range used for the epoxy amine polyaddition.

The DMA tests revealed an alpha transition at the peak of tan δ of 279 °C for DGEM compared to 231 °C for DGEBA/DDS. The Young's modulus of the DGEM at ambient temperature was 3.7 GPa compared to 2.5 GPa for DGEBA. This is mainly explained by a higher crosslinking density of DGEM, due to the further reaction of allyl moieties. The calculated values of crosslinking densities were 3.2 kmol•m -3 for DGEM compared to 2.3 kmol•m -3 for DGEBA/DDS. Flexural strength of both systems was quite similar, around 106-108 MPa, whereas the flexural modulus of DGEM was 3.5 GPa, compared to 2.5 GPa for DGEBA. This reveals the higher rigidity of the DGEM, resulting from the higher crosslinking density. The thermal stability under nitrogen atmosphere was similar for both thermoset, with a T d5% of 402 °C for DGEM compared to 399 °C with DGEBA. This is an interesting result, since usually DGEBA displays a higher thermal stability. The char yield was also higher for DGEM than for DGEBA, with a value of 43 % compared to 15 %. These results show that the tetrafunctional monomer from magnolol give outstanding properties to the epoxy networks. These thermosets also had high temperature resistance, with a lower total heat release. DGEM could self-extinguish after 2.3 seconds, increasing to 4 seconds after a second application of flame. Magnolol is a widely studied pharmacological compound. Generally, it has been used in traditional

Chinese and Japanese medicine and has been considered as a safe compound, with no reported adverse effects. It has antibacterial, anti-inflammatory and antioxidant activities, among others. 134,135 To the best of our knowledge, no endocrine activity has been reported for this compound. Resveratrol is an interesting diphenolic compound that bears three phenolic hydroxyl groups. The glycidylation of those moieties lead to a trifunctional epoxy monomer. Resveratrol can be found in several vegetables, including grapes and more specifically, grape wastes. 137 Garrison et al. performed the synthesis of two resveratrol-based monomers, the first compound was made directly from the resveratrol (GERV), and the second from a hydrogenated form of the resveratrol (GEDRV), that originally bears a double bound between the aromatic rings (Figure 44). 136 They used two hardeners, a commercially available (DDM), and a compound prepared from resveratrol, leading to full resveratrol-based epoxy networks. The alpha transition temperature for GERV/DDM was 285 °C, whereas it was 178 °C for the GEDRV/DDM. For comparison, the DGEBA/DDM network displayed a lower T g of 164 °C. 116 This is mainly explained by the higher crosslinked density from the trifunctional monomers based on resveratrol.

XII. Resveratrol

Thermal stability was also evaluated, under nitrogen and under air. The T d5% of both resveratrol-based thermoset under nitrogen were in the range of 355-358 °C which showed no significant difference between saturated and unsaturated monomers. The DGEBA/DDM network under nitrogen displayed a T d5% of 376 °C, which is slightly higher. 138 The same range of T d5% was observed under air for DGEBA or resveratrol-based networks. The char yield was superior with the unsaturated epoxy resveratrol epoxy monomer (40.5 % vs 26.1 % for saturated), and significantly lower for DGEBA/DDM network (15 %). The higher crosslinking density in the case of resveratrolbased networks improved the char formation. More recently, Tian et al. prepared GERV and used PACM to obtain fully cured networks. 139 In their work, they were able to obtain the monomer with an EEW of 144 g•eq -1 compared to 280 g•eq -1 by Garrison et al.. 136 Tian et al. performed DSC using several heating ramps, but did not fit the data with kinetic models in order to assess the activation energies of the curing reactions. Thermomechanical analysis was performed on cured samples, and the GERV/PACM system showed a T α of 302 °C compared with DGEBA/PACM with a T α of 149 °C. These results were also in agreement with the DMA analysis, giving a T α value of above 300 °C for GERV and 161 °C for DGEBA. The glassy moduli for DGEBA and GERV networks were respectively 2, 4 GPa and 1, 9 GPa at 25 °C, indicating a higher rigidity of DGEBA network. At the rubbery state, the E' for DGEBA was 41 MPa (at 200 °C). E' could not be measured for GERV network at 200 °C but at 300 °C the value was 363 MPa. Tensile properties were also evaluated, 78 MPa for GERV network, and 64 MPa for DGEBA. Tensile strain were respectively 4.5 % for GERV and 3.7 % for DGEBA (quite similar values given the standard error). The authors did not comment about the higher Young's modulus of DGEBA compared to GERV.

The crosslinking density can be considered higher in GERV since it is a trifunctional monomer. However, it does not seem to imply a higher rigidity as it could have been expected. Thermal stability of the networks was assessed by TGA under nitrogen atmosphere. The reported T d5% for GERV/PACM was 320 °C and the T d5% for DGEBA/PACM was 348 °C. This result is in agreement with the work of Garrison et al. which showed that resveratrol-based epoxies have lower thermal stability. 136 The authors did not explain the earlier degradation of resveratrol based network, but it could be because of the carbon-carbon double bond between phenol rings, that may be less stable than the isopropylidene in DGEBA. Char yield at 800 °C was however higher in GERV network (12.4 %) compared to DGEBA (4.2 %), showing that high degrees of crosslinking leads to better thermal stability at high temperature and a better ability to produce char. Non-isothermal degradation kinetics, using Kissinger's model, gave activation energy of 182 kJ•mol -1 for GERV and 181 kJ•mol -1 for DGEBA networks. These results show that there is probably no fundamental difference between the degradation mechanisms of the two thermosets.

Surprisingly, a mixture of DGEBA and GERV cured with PACM showed a significantly higher E α of degradation (222 kJ•mol -1 ). However, the authors did not discuss the reason for obtaining such elevated E α value. Cone calorimetry was used to determine the flame retardancy of the networks (LOI determination and SEM analysis of the pyrolyzed material surfaces). Higher and sharper peak was observed for DGEBA network (2.1 MW•m -2 compared to 1.5 MW•m -2 for GERV). LOI was also higher for DGEBA network (21 % compared to 15.7 % for GERV). These results along with high char yield indicate a better fire resistance of resveratrol-based thermosets.

SEM images of the pyrolyzed materials showed homogeneous char layer in the case of GERV and an irregular surface for the DGEBA.

The evaluation of the dielectric permittivity showed that the DGEBA network had a higher permittivity as compared to GERV. At the range of 10 -10 7 Hz, DGEBA/PACM displayed a permittivity of 4.7-4.1 F/m while GERV/PACM displayed 3.9-3.2 F/m. Generally, resveratrol-based epoxy monomers have very good thermomechanical properties as well as a fair thermal stability, although lower than that of DGEBA. Resveratrol is a compound that is widely studied for its pharmacological properties. It has been associated with protective cardiovascular effect in vitro and in animals. It has also been studied in several clinical trials for its potential effect on cardiovascular diseases, cancer, neurodegenerative or metabolic diseases. It is also sold as a dietary supplement, for its antioxidant activity.

However, a recent review warns that resveratrol is a phytooestrogen. The review collected evidence regarding the activity of resveratrol on the ERα in humen. 140 In this work, Qasem concluded that the effect of resveratrol on the oestrogen receptor is not always reported in studies, since its effect on the endocrine system may arise from repeated exposure.

In the work of Hong et al., resveratrol and dihydroresveratrol were evaluated for their binding affinity with the ERα, using in silico methods. 82 Resveratrol is considered to be a binder to the receptor, with a calculated affinity that is lower than BPA, but slightly higher than BPF. This is consistent with the fact that resveratrol is a phytooestrogen, thus it shows affinity with the oestrogen receptor. However, the calculations for dihydroresveratrol revealed no binding affinity underlining the effect of the bridging unit between the phenol rings. Daidzein is an isoflavone found in soybean biomass. 142 It is used in the food and pharmaceutical industry. The bisphenolic nature of this compound led to its use as a building block for the synthesis of a diglycidylether. Dai et al. performed the synthesis of the monomer (Figure 45), and studied the properties with DDM as the curing agent, and compared it with DGEBA network. 141 Among the different properties studied, it was found that the DGED had an alpha transition of 205 °C with DDM, which was higher than the measured for DGEBA/DDM network (172 °C).

XIII. Flavonoids 1. Daidzein

The Young's modulus at 25 °C was 2.8 GPa (2.4 GPa for DGEBA). These properties are mainly due to the high crosslinking density, which was found to be 6.4 mol•m -3 for DGED as compared to 3.5 for DGEBA/DDM. Other mechanical properties were also measured, such as tensile strength and moduli, and also flexural strength and moduli. In all cases, the thermoset from DGED were superior to DGEBA. Thermal stability under inert atmosphere was lower, since the T d5% for DGED was 335 °C, compared with DGEBA network with a T d5% of 384 °C. The same trend was observed under oxidative atmosphere. This is mainly due to the presence of the heterocycle in the structure of daidzein, which may degrade first. However, regarding the char yield at 800 °C, the DGED had a remarkable superior char formation, 43 % compared to 16 % for DGEBA. The DGED also had low flammability, with a superior LOI of 31.6 % (compared to 24.5 % for DGEBA), and an ability to self-extinguish within 13 seconds. Daidzein is a phytooestrogen, which means it may have the potential to be agonist or antagonist to the oestrogen receptor. 143 It is well known that the consumption of soybean products may interact with the endocrine system, and daidzein is one of the compounds such a kind of effect. More specifically, daidzein is metabolized into equol that has even more activity. But compared to the natural hormone E2, these activities are lower and happen at higher concentrations (Figure 46). 144 It is also important to note that the mode of exposition between the consumption of soy products and the exposition from the use of epoxy thermosets would be very different. The Luteolin is a natural flavonoid that can be found in herbs such as thyme, sage or oregano, in some types of celeries or radicchio, and in lower quantities in beets, Brussel sprouts and lemons. 146 It has shown some anti-microbial activity, anti-inflammatory properties and is considered to have a chemotherapeutic potential. 146 The chemical structure of luteolin is a polyphenol comprising a heterocycle, a resorcinol unit and a pyrocatechol unit. It leads to a compound bearing 4 phenolic hydroxyl moieties (Figure 47). However, only 3 are reactive towards glycidylation since one of the phenolic moieties is blocked by hydrogen-bonding with the carbonyl moiety, as shown by Gao et al.. 145 The glycidylation reaction lead to a trifunctional epoxy monomer named diglycidylether of luteolin (DGEL) in the original publication, but that will be referred to as triglycidylether of luteolin (TGEL) in this article. The monomer was subsequently cured with DDS to afford epoxy thermosets. The curing reaction was first assessed by non-isothermal curing kinetics using Ozawa and Kissinger methods, and compared with DGEBA/DDS system.

Good correlations were obtained with both methods, and DGEBA/DDS showed a lower activation energy than than for the DGEBA network (24.3 kJ•g -1 for TGEL vs 29.1 kJ•g -1 for DGEBA). The heat release capacity of DGEBA network was four times higher than for TGEL (respectively 399 J•g -1 •K -1 and 101 J•g -1 •K -1 ). The LOI value of the TGEL network was 32.5 % whereas it was 27.0 % for DGEBA. Raman spectroscopy showed that TGEL network displays a higher graphitization degree after pyrolysis, which is a desirable property when using charforming material. Decomposition studies showed that DGEBA/DDS could release more aromatic compounds than TGEL/DDS network, indicating that most aromatic compounds stay in the condensed phase. Among all the biological mechanisms of endocrine system, sulfonation of steroids by sulfotransferase enzymes is part of the oestrogenic system. Indeed, the sulfonation of steroids lead to a change in their properties, for instance, oestrogen sulfonates are no longer agonist to the oestrogen receptor. 147 Thus, any activity on these enzymes could affect the endocrine system, and have indirect endocrine disruption potent.

Waring et al. evaluated several phytooestrogen or xenooestrogen as inhibitors to sulfonotransferases. 147 The inhibition potent of several flavonoids were tested on SULT 1A1, and luteolin enzymes showed an IC50 of only 3 nM, but did not show any inhibition activity for SULT 1A3 (a sulfotransferase), at submicromolar scale. It had also no effect on the SULT 2A1 activity. These findings were in agreement with a previous study. 148 In the work of Waring et al. it was shown that for some enzymes, the inhibition potent of flavonoids is several orders of magnitude superior to the synthetic compounds such as alkylphenols or phthalates. 147 The authors noted that for example supplementation with flavonoids may not be universally beneficial, since the addition of exposition to synthetic endocrine disruptors, naturally occurring flavonoids in diet and supplementation may lead to increased risks of cancer. In another work, Nordeen et al. also highlighted luteolin as a multi-functional endocrine disruptor, with a potent progesterone antagonist and oestrogen agonist activity. 149 They assessed the effect of luteolin on the steroid signalling, using T47D cell lines expressing oestrogen and progesterone receptors. The authors also signal out that use of flavonoids supplements could be dangerous for patient with certain type of cancers. Surprisingly, a study described the protective effect of luteolin against bisphenol A toxicity, in drosophila. 150 The protective effect has been partly attributed to the antioxidant properties of luteolin.

XIV. Cardanol and Cardol

epoxy monomer was studied. For DGEBA/DDM network, T g was 179 °C whereas it was 161 °C for DGEBC/DDM, as evaluated using DSC measurements. These similar values and the lower values of DGEBC may be due to modest plasticizing effect of the isopropyls. Thermal stability of the cured networks was assessed using TGA both under air and nitrogen. Under nitrogen, T d5% were 367 and 376 °C for DGEBC and DGEBA cured with DDM. Similar values were obtained when analysis was performed under air. Char yield under nitrogen for DGEBC and DGEBA cured with DDM was 10 -20 % for DGEBA and less than 10 % with DGEBC. It should be noted that, biscarvacrol contains two isopropyl and two methyl groups on the aromatic rings that degrade at lower temperature thus do not contribute towards char formation.

As discussed earlier Hong et al., evaluated a wide set of potential substitutes of BPA for their binding affinity with ERα using an in silico method. 82 This method allowed for the qualitative and quantitative prediction of the binding ability of each compound, as well as the quantitative affinity if considered a binder. The biscarvacrol was part of this set, and it was predicted to be binder. The calculated affinity was 100 times higher than BPA, indicating a strong receptor binder. However, the certitude of the prediction was very low. A diepoxy monomer can easily be obtained from furandicarboxylic acid (FDCA). Several synthesis pathways have been reported to date (Figure 50). The first path involves the allylation of both carboxylic acid moieties. The diallyl is then epoxidized with meta-chloroperbenzoic acid to afford the diepoxy monomer. 155 Two other pathways are also available, as reported by Marotta and co-workers. 156 First, the direct glycidylation of the dicarboxylic acid, reacted with epichlorohydrin. Second, transesterification can be performed on the dimethyl ester of the FDCA, with glycidol, using potassium cyanate as a low toxicity catalyst. Several research articles described the properties of networks with DGEFDCA, using different hardeners. 55 Comparing curing with aromatic amines and polyether amines, the obtained T g values were very similar to the DGEBA networks. In the recent work of Liu et al. the curing of DGEFDCA with DDM showed a higher T α than the equivalent DGEBA, namely 156 °C for the furan-based network, compared to 124 °C. 158 Indeed, higher crosslink densities were obtained with DGEFDCA (1.9 mol•dm -3 ) compared to DGEBA/DDM with 0.3 mol•dm -3 . The higher molecular weight between crosslinks in the DGEBA thermoset led to a higher chain mobility in the network. In addition, hydrogen bonding with the furanic ring, increases the rigidity of the network at low temperatures. Higher crosslinking densities with 33DDS and 44DDS were also measured. Mechanical properties of DGEFDCA cured with DDM were also higher than for DGEBA network, with a storage modulus at the rubbery state (22.3 MPa compared to 2.69 MPa for DGEBA). The networks with 33DDS and 44DDS gave similar results both at glassy and rubbery states. Elongation at break, tensile strength and the shore hardness were slightly better for the furanic based network compared to the DGEBA/DDS systems. The rigidity that is brought by the furan moiety seems to be beneficial for the mechanical properties of the cured thermosets. Mechanical properties for networks with D230 were also investigated. The obtained flexural strength was lower for DGEFDCA thermoset, with a strength of 75 MPa, compared with 121 for DGEBA. The flexural moduli was 2.5 GPa for DGEFDCA/D230 and 2.95 GPa for DGEBA/D230. 155 The flexural tests performed on networks with different hardeners demonstrate that DGEFDCA networks are stiffer and more brittle compared to DGEBA networks. The thermal stabilities of the networks were also evaluated under inert atmosphere. For the D230 networks, the T d5% of DGEFDCA was 267 °C and the char yield 6.8 %, compared to DGEBA/D230 with T d5% of 366 °C and char yield of 4.4 %. The DDM network led to T d5% of 326 °C and char yield of 28.1 % for DGEFDCA. Finally, for DDS cured materials, the T d5% was 324 °C for both 33DDS and 44DDS with DGEFDCA, and respectively 27 and 18 % char yields, compared to 405 and 397 °C for DGEBA/33DDS and DGEBA/44DDS with 20 and 14 % char yields. As discussed earlier, the furan-based thermosets have lower degradation temperatures, but higher char yields. The work of Meng et al. also focused on fire resistance behaviour of the thermosets. They reported that the total heat release of DGEFDCA based networks was lower than DGEBA networks. They also showed that the heat release capacities were lower with the furanic epoxide, namely 132 J•g -1 •K -1 and 222 J•g -1 •K -1 for DGEFDCA/33DDS and DGEFDCA/44DDS respectively (compared to DGEBA/33DDS HRC of 601 J•g -1 •K -1 and DGEBA/44DDS HRC of 516 J•g -1 •K -1 ). These results show that furanic based networks have lower flammability, even if they degrade at lower temperature. The work of Sutton et al. assessed several endocrine activities of furanic compounds. FDCA was thus evaluated in CALUX bioassays, for the determination of endocrine activity on ERα, an androgen receptor, and also a thyroid receptor. 159 FDCA did not show any activity on sexual hormone receptors, but it did show a repression activity on the thyroid TRβ receptor. The activity obtained with 1 gram of nonylphenol was equivalent to the activity of 1700 grams of FDCA, meaning that the compound could have an activity at a high exposure. However, these in vitro tests are not enough to assess the activity of the compound and more studies are required to get reliable results. Diglycidylether of 2,5-furfuryldiol is a monofuranic diepoxy that has been extensively studied (Figure 52), as a substitute for DGEBA. Several articles reported properties of thermoset with different diamine hardeners, such as PACM 161,162 , 4,4'-DDS and 3,3'-DDS 163 , polyethers diamines (commercially known as EDR-148 and EDR-192) 160 , DDM 164 and some furfurylamine derivatives. 161 These studies suggest that the use of DGEFD give lower T g values than DGEBA, but with superior mechanical properties such as higher Young's moduli, higher tensile and flexural strength, lower flammability, higher char yield and lower degradation temperatures. The dynamic mechanical properties of these compounds are summarized in Table 4. As can be de-ducted from these data, the higher glass transition temperatures (or alpha transition) from DGEBA thermoset are probably due to the higher aromatic density brought by the bisphenolic moiety. The rigidity of the network (due to aromatics) is not counterbalanced with higher crosslinking density from DGEFD, due to the lower molecular weight of the monomer. Intermolecular interactions such as pi-stacking may also explain the higher T g with DGEBA, contrary to DGEFD. However, at the glassy state, the Young's moduli were higher for DGEFD, which may be due to the dense packing of the network (crosslinking density) and the intermolecular interactions such as hydrogen bonding brought about by the oxygen of the furan. At the rubbery state, the networks with DDS and DGEFD had higher Young's moduli, most likely due to the packing density of the network, as hydrogen bonding should become very weak at higher temperatures. 163 Regarding the thermal stability of DGEFD thermosets under inert atmosphere, as shown in Table 5 it is clear that the stability of the resins is lower than DGEBA. This is probably due to the presence of the methylene moieties in DGEFD, compared to DGEBA, where the glycidylether is directly attached to the phenol moiety. However, as often observed for thermosets containing furan rings, the char yield is higher in the DGEFD thermosets. 163 They have shown that the DGEFD-based epoxy networks had superior mechanical properties. Both the tensile and flexural strengths were higher for DGEFD than for DGEBA. The shore hardness was also higher in the case of the furan-based epoxy. They reported that the tensile strength of DGEFD cured with 44DDS was comparable to that of polyoxymethylene and Nylon-6. These enhanced mechanical properties were mainly attributed to the hydrogen bonds formed thanks to the heterocycle of DGEFD. The fire resistance of the cured material was also investigated. For example, it was shown than DGEFD cured with both DDS and amine could self-extinguish in 7 seconds. DGEBA-based networks burnt for longer times, where the flame spreading reached 10.2 mm•min -1 for DGEBA/44DDS and 8.5 mm•min -1 for DGEBA/33DDS. The self-extinction of DGEFD thermoset could be explained by the higher char formation due to the presence of the furan rings. The influence of the amine is also very important. In a different work, using polyetheramines as the curing agents (EDR-148 and EDR-192), it shown that DGEFD thermoset could stay ignited for longer times (> 60 s). 160 The flammability was lowered by using the same curing agent with a monomer bearing 2 furan rings. The ability to self-extinguish may probably be influenced by a ratio of furan rings to the alkylether with better resistance to fire with higher loadings of furan rings. In the case of DGEFD/DDS system, the synergy between aromatic and furanic rings led to low flammability. These results were also confirmed by microscale combustion calorimetry. The DGEFD/DDS systems showed lower heat release capacities (121 J•g -1 •K -1 for 33DDS and 179 J•g -1 •K -1 for 44DDS), than for DGEBA (respectively 601 and 516 J•g -1 •K -1 ). The total heat release of the networks with DGEFD were also lower than with DGEBA, precisely 14.9 and 23.6 kJ•g -1 for 33DDS and 44DDS cured materials, compared to 32.3 and 36.4 kJ•g -1

Furanics I. Furan dicarboxylic acid

II. 2,5-furfuryldiol

for DGEBA/33DDS and DGEBA/44DDS networks. In the work of Hong et al., 82 one furan-containing molecule was considered. The furfuryldiol was predicted to be non-binder to the oestrogenic receptor α with a good reliability.

In a recent paper by Sutton et al., several new furfuryldiols were synthesized and their toxicity was assessed. 159 Especially, endocrine activity for several receptor such as human oestrogen receptor α, androgen receptor and a thyroid receptor, were evaluated,. In all the trials, the CALUX bioassays did not show any activity. For ERα activity, no dose-dependent response was seen. Furfuryldiol did not show any potential in vitro endocrine activity. The bisfuranic diepoxy monomer, OmbFdE, was prepared by dimerization of hydroxymethylfurfural (HMF), via a dehydratation reaction. 160 The obtained dialdehyde was then reduced with sodium borohydride to afford the corresponding diol. The glycidylation of the diol led to the formation of the diepoxy monomer (Figure 53). This diepoxy monomer was then cured with different alkylether amines, containing respectively 1 ether linkage (DEGA), 2 ether moieties (also known as EDR-148) and 3 ether moieties (aka EDR-192). Thermomechanical properties were measured, and also fire resistancy was investigated. Comparison with DGEBA was not performed, but data of the network with EDR-148 hardener can be found in the article of Faye et al.. 122 Glass transition temperatures of EDR-148 network with OmbdFdE was 20.6 °C whereas with DGEBA it was 98 °C as obtained by DSC. The presence of numerous alkyl ether linkages in OmbFdE led to higher segmental mobility inside the networks. This is confirmed by the fact that curing OmbFdE with amine containing increasing number of alkylethers, lowers the T g (from 25 to 7 °C). The comparison with the above mentioned DGEFD containing two furan rings showed that the higher content of furan rings results in higher T g values. It seems that even though the use of OmbFdE leads to lower molecular weight between the crosslinks, the T g would still be higher when two furan rings are present as compared to one in the case of DGEFD.

III. Bisfuran with ether linker

Examination of the thermal stability and fire resistance, showed that, T d5% of the cured materials were in the range of 265-291 °C, with the obtained lower temperature for EDR-148 cured monomer. Compared with DGEBA/EDR-148, with a T d5% of 300 °C, the furanic based monomer showed a lower degradation temperature, as often observed.

However, a higher char yield was obtained with OmbFdE, in the range of 18-25 %. This is higher than the case of DGEBA/EDR-148 network with 12 %, and DGEFD with15-21 %. The presence of heterocycles is known to improve the char formation, as evidenced in the case of OmbFdE with 2 furan rings () (compared to one in DGEFD). The presence of these two rings also had an effect on the behaviour of the material in fire. Faster selfextinction was obtained with OmbFdE compared to DGEFD. In addition, the total heat release of OmbFdE/EDR-148 was lower compared to DGEFD (13.7 kJ•g -1 vs 15.6), showing improvement due to the furan loading. In the work of Sutton et al., the endocrine activity of the OmbFdE diol derivative was assessed in vitro, using CALUX testing methods. 159 Several parameters were evaluated such as activity on the ERα, the androgen receptor, and also a thyroid receptor. The diol did not show any activity against the oestrogen α receptor, nor the thyroid receptor.

However, a repression effect on the androgen receptor was observed, but at higher concentrations than the corresponding reference, Flutamide (an androgen repressor drug). These in vitro results are not sufficient to assess the global impact on human health.

Figure 1 -

 1 Figure 1 -Chemical structure of 17β-oestradiol

Figure 5 -

 5 Figure 5 -Synthesis procedure for DGEVA by Fache et al. 41

Figure 6 -

 6 Figure 6 -Reaction scheme for the synthesis of DGEVAC according to Fache et al. 41

Figure 7 -

 7 Figure 7 -Reaction scheme for the synthesis of DGEMHY starting from vanillin according to Fache et al. 41

Figure 10 -

 10 Figure 10 -Synthesis of spirodivanillin according to Mankar et al.. 72 Glycidylation conditions were not reported.

Figure 13 -

 13 Figure13-Bisphenolic epoxy monomers synthesized by Nicastro et al.76

  alcohol and guaiacol, and used these mixtures for the in vitro testing. The two in vitro assays chosen were MCF-7 cell proliferation assay and VM7Luc4E2 TA test. E2 and BPA were used as positive controls. Both assays gave consistent results. Three mixtures testes contained ratios of 3,4-BGF and 4,4-BGF (4,4-BGF being the major one), and one mixture contained the three isomers, with a majority of 2,4-BGF. The results showed that when the mixtures contained a high proportion of 4,4-BGF, or when it contained 2,4-BGF, an increase in the proliferation rate was observed in the MCF-7 assay, indicating an oestrogen affinity. However, the proliferation rate was lower than that of BPA. The mixtures containing higher proportions of 3,4-BGF did not induce MCF-7 cell proliferation. The VM7Luc4E2 test also showed that the high 3,4-BGF containing mixtures had non-detectable EA. The other BGF mixtures did show some EA, but with lower EC 50 values. These results suggest that high 4,4-BGF concentration and 2,4-BGF containing mixtures are moderately active on the oestrogen receptor, but still less active than BPA.

Figure 14 -

 14 Figure 14 -Bisphenols and bisguaiacols used in ERα affinity tests

Figure 17 -

 17 Figure 17 -In vitro evaluation of relative activity of syringaresinol diol (SYR) and diepoxy (SYR-EPO) against HERα by Janvier et al. 86 Comparison were made with BPA, DGEBA. IDF and IDF-EPO are isosorbide-based compounds.

Figure 18 -

 18 Figure 18 -Synthethic patwhays for the synthesis of GEGA, from Tarzia et al. and Aouf et al.89,90

Figure 20 -

 20 Figure20 -Reaction scheme for the synthesis of alkyl bisferulates derived epoxy monomers according to Maiorana et al.102

Figure 21 -

 21 Figure 21 -Young's modulus of bisferulates/IPDA thermosets as a function of the diol spacer length, from Maiorana et al. 102

Figure 22 -

 22 Figure 22 -a) tan δ peaks of alkyl bisferulates based thermosets with IPDA, b) E" peaks and tan δ peak temperatures plotted against the different epoxy structures. EDF = C2, PDF = C3, BDF = C4 and HDF = C6, reproduced from Maiorana et al. 102

Figure 23 -

 23 Figure 23 -Solid fraction as a function of soaking time in alkaline medium for alkyl bisferulate based thermosets, reproduced from Maiorana et al. 102

Figure 24 -Figure 25 -

 2425 Figure 24 -In vitro activity comparison of alkyl bisferulates, from Maiorana et al. 102

Figure 26 -

 26 Figure 26 -Structure of the isosorbide-based bisferulate epoxy monomer by Ménard et al.88

Figure 27 -

 27 Figure 27 -Structure of the trifunctional ferulate ester (GTF) epoxy monomer synthesized by Ménard et al.88

Figure 28 -

 28 Figure 28 -Synthetic pathway for GDFxEPO monomers, by Hollande et al. 103

Figure 29 -

 29 Figure 29 -In vitro activity of the GDFxEPO diols against several hormone receptors by Hollande et al. 103

Figure 30 -

 30 Figure 30 -Structures of Resorcinol and its diglycidylether derivative

Figure 32 -

 32 Figure 32 -Synthesis of diphenolic acid ester based epoxy monomers according to Maiorana et al. 113

Figure 33 -

 33 Figure 33 -Evolution of the complex viscosity as a function of cure time for (a) DGEBA at different temperatures (y-axis linear scale). (b) DGEBA and DGEDP epoxies studied herein at 90 °C cure temperature (y-axis log scale). Reproduced from Patel et al. 114

Figure 35 -

 35 Figure 35 -Structure of eugenol and isoeugenol from cloves, and their reduction to dihydroeugenol. These structures are epoxy monomer precursors.

Figure 36 -

 36 Figure 36 -Synthesis of TEE from Guzman et al. 124 and Yoshimura et al. 125

Figure 37 -

 37 Figure 37 -Synthesis of DGEDHEO from Zhao and Abu-Omar 127

Figure 38 -

 38 Figure 38 -Synthetic pathway for the synthesis of DDHE and TDHEO monomers from Zhao and Abu-Omar 128

Figure 40 -

 40 Figure 40 -Synthesis of dieugenyl monomer with aromatic ester spacer from Wan et al. 130

Figure 41 -

 41 Figure 41 -Structures of dieunyl monomers by Chen et al. 131

Figure 42 -

 42 Figure 42 -Reaction pathway for the synthesis of diepoxy monomers from vinylphenols, according to Zago et al. 132 Nomenclature of the monomers corresponds to the different starting vinylphenols, eugenol (Eu), 4-vinylguaiacol (4VG) and canolol (Can).

Figure 43 -

 43 Figure 43 -Synthesis of DGEM according to Qi et al. 133

Figure 44 -

 44 Figure 44 -Synthesis of resveratrol based epoxy monomers, according to Garrison et al. 136

Figure 45 -

 45 Figure 45 -Synthesis of DGED, according to Dai et al. 141

  effect on human health of the ingestion of daidzein and other isoflavones were extensively reviewed by Křížová et al..143

Figure 46 -Figure 47 -

 4647 Figure 46 -In vitro activity of daidzein and E2, adapted from Muthyala et al. 144 2. Luteolin

Figure 51 -

 51 Figure 51 -Several synthesis pathways of DGEFDCA from furandicarboxylic acid

Figure 52 -

 52 Figure 52 -Synthesis of DGEFD according to Meng et al. 160

Figure 53 -

 53 Figure 53 -Synthesis of OmbFdE according to Meng et al. from hydroxymethylfurfural 160

Table 1 -

 1 Thermomechanical properties of DGEVA cured with different amines, from the literature

	Amine	T g or T α (°C)	E' glassy (GPa)	T d5% (°C)	Char yield (%)
	Hardener	DGEBA	DGEVA	DGEBA	DGEVA	DGEBA	DGEVA	DGEBA	DGEVA
	IPDA	166	97	-	-	-	-	10	19
	PACM	190	100	-	-	-	-	2	7
	DICY	146	93	-	-	342	289	13	23
	DDM	154	111 / 124	2.3	2.8	-	-	-	-
	TETA	142	71 & 109*	4	3.7	-	-	-	16
	DETA	100	90	2	3.5	305	247	8	7
	44DDS	238	108	-	-	-	-	14	7
	DFDA	109	81	2.4	3.7	330	304	23	46

* two relaxations are observed by DMA Hernandez et al. used a dicyclohexyl diamine (Amicure), with DGEVA and other vanillin-based epoxides.

Table 2 -

 2 Thermomechanical properties of epoxy thermosets from bisphenols and MDA

Epoxy monomer E' 30 (GPa) E' 200 (MPa) T α (°C) p,p′-BGPDGE

		2.5	46	151
	o,p′-BGPDGE	2.8	22	141
	p,p′-BGSDGE	2.7	33	134
	m,p′-BGSDGE	2.4	28	129
	p,p′-BGMDGE	2.5	26	141
	m,p′-BGMDGE	2.0	15	119
	DGEBA	2.5	46	167

  At the rubbery state, the SYR-DA10 material had a modulus of 14 MPa compared to the reported 23.2 MPa for DGEBA. The lower value obtained is probably due to the lower crosslinking density.Finally, the last hardener used is DIFFA, which lead to a T g of 102 °C and a T α of 108 °C, whereas the DGEBA/DIFFA network had a T g of 92 °C and a T α of 110 °C. These very similar values, show promising results for this epoxy monomer as a substitute for DGEBA. Regarding the rubbery modulus, the SYR network displayed a value of 10 MPa compared to 23.2 MPa for DGEBA. The rigidity brought by the bicyclic linkage does not prevent free rotation once the α transition happened. The global thermal stability of the networks was lower for SYR compared with DGEBA (over 300 °C for DGEBA, and slightly under for SYR, with a difference of approximately 30 °C). The char formation was higher for SYR networks, attaining 29.4 % for DIFFA/SYR at 700 °C.

Ménard et al. with a T g of 98 °C.

88

However, regarding the α transition, the reported DA10/DGEBA value was 97 °C whereas for the SYR network, the T α was 102 °C. The similar values displayed under mechanical investigations lead to the conclusion that the SYR based networks display excellent mechanical properties compared with DGEBA. At the glassy plateau, the values were not comparable for DGEBA and SYR networks since the measurements were not performed at the same temperature (at 50 °C reported by Janvier et al. and at 0 °C reported by

Ménard et al.)

.

Syringaresinol and its glycidylated derivative were evaluated by Janvier et al. against ERα and compared with BPA,

  The IPDA system displayed a T g of 145 °C and the one with Jeffamine was 83 °C. In comparison, from Duchet and Pascault91 , the DGEBA/IPDA system displayed a T g of 156 °C, and the DGEBA cured with Jeffamine D230 had a T g of 80 °C. In the work of Tarzia et al., the glass transition temperatures of GEGA thermosets are very similar to DGEBA thermosets. Compared with the work of Aouf et al. it can be observed that the reported values for IPDA/GEGA were slightly different. Indeed, as a comparison with T g , the alpha transition of IPDA/GEGA from Aouf et al. is 233 °C.89,92 However, in the work of Tarzia et al., the reporting curing procedure at 150 °C was different than the procedure from Aouf et al. which was 30 minutes at 90 °C and then 2 hours at 200 °C. Due to the high functionality of GEGA one could expect that with the same amine, GEGA would lead to higher glass transition temperatures or T α than with DGEBA. It could be deducted that the differences were due to an incomplete curing process from Tarzia et al. since the ratio between trifunctional and tetrafunctional GEGA was reported to be the same. This is also confirmed by the fact that Tarzia et al. observed some residual enthalpy in the 2 nd heating ramp in DSC. Thus, thermosets obtained from GEGA could have similar transitions than with DGEBA only if the thermoset was not fully cured. Regarding the degradation of the cured thermosets, in the work of Tarzia et al. the char yield reported

for IPDA/GEGA was 18 % at 600 °C, which was lower than the one reported by Aouf et al., confirming the incomplete curing process. Regarding tensile tests, DGEBA systems gave lower tensile modulus than GEGA

Table 3 -

 3 Thermal and mechanical properties of thermosets studied by Zhao et al.53

	Epoxy monomer	T α (°C)	E 30 ' (MPa)	T d5% (°C)	Char yield (%)
	M 0	132	2745	257	20
	M 2	125	2598	206	17
	M 2 '	120	2249	218	18
	M 4	118	2477	184	14
	DGEBA	100	2042	305	8

  The thermal stabilities of the networks were evaluated by TGA under nitrogen and air. In both cases, DGEBA/DDS systems showed a higher T d5% (393 °C under N 2 and 374 °C under air), compared to TGEL/DDS (379 °C under N 2 and 346 °C under air), due to an early decomposition of the heterocycle in TGEL. Both networks exhibit similar degradation pathways. Under inert atmosphere, DGEBA/DDS and TGEL/DDS show a single main decomposition step. During this step, the weight loss for DGEBA/DDS was higher than in TGEL/DDS, resulting in a low char yields for DGEBA/DDS, at 700 °C (12 % for DGEBA and 44 % for TGEL). Under oxidative atmosphere, the same trend was observed, with two decomposition steps for all networks, but with a first weight loss at lower temperature for TGEL than for DGEBA. The higher functionality and higher aromatic density of TGEL lead to more char yield under nitrogen, and a delayed decomposition of the material. Several mechanical properties were assessed, such as dynamic mechanical and tensile properties. DMA revealed an alpha transition of 314 °C for TGEL/DDS network, which is a high value, compared to DGEBA/DDS with a T α of 217 °C. The Young's modulus at the glassy plateau at 30 °C were 3.8 GPa for TGEL and 2.7 GPa for DGEBA networks. The high value for TGEL has to be balanced with the fact that a high loss modulus was observed before 100 °C, with a value inferior to 3 GPa at this temperature. The same trend was observed with DGEBA. The rubbery values of Young's modulus were 2.1 GPa for TGEL/DDS and 50 MPa for DGEBA/DDS, illustrating high stiffness of the TGEL. This is in agreement with tensile tests giving lower elongation at break for TGEL (9.5 %) compared to DGEBA (10.8 %), but a higher tensile strength with TGEL compared to DGEBA networks (respectively 69.2 MPa and 57.2 MPa). Surprisingly the crosslinking density of TGEL/DDS network was 1.5 kmol•m -3 whereas it was 2.2 kmol•m -3 for DGEBA/DDS network. This could be due to the high molecular weight of the epoxy monomer, and to its non-symmetric structure, leading to a lower global crosslinking density. Flame retardant properties were extensively evaluated by Gao et al., using microscale calorimetry, LOI tests, TGA-FTIR and Pyrolysis-GC/MS. MCC revealed a lower total heat release for TGEL/DDS

TGEL/DDS (60.7-65.5 kJ•mol -1 for DGEBA/DDS vs 64.8-69.0 kJ•mol -1 for TGEL/DDS). According to the authors, the lower activation energy was mainly due to the high functionality of the monomer.

Table 4 -

 4 Mechanical and thermal properties of DGEFD cured with different amines, and compared with DGEBA

	Amine	T g or T α (°C)	E' glassy (GPa)	E' rubbery (MPa)
	Hardener	DGEBA	DGEFD	DGEBA	DGEFD	DGEBA	DGEFD
	33DDS	184	102	1.9	2.4	17.56	36.15
	44DDS	238	114	1.9	2.7	16.02	24.53
	DEGA	-	13.5	-	-	-	-
	EDR-148	98 / 108 122	13	1.34 122	-	13.2 122	-
	EDR-192	-	7.6	-	-	-	-
	PACM	176	80	2.37	approx. 2.5	-	-
	Epikure W	198	94	-	-	-	-
	DFDA	121	62	approx. 2.5 approx. 3.5	-	-
	DFDA-Me	128	69	approx. 2.5 approx. 3.5	-	-
	DDM	164 116	126 / 149	-	2.4	-	17

Table 5 -

 5 Thermal stability of DGEFD thermosets cured with different amines, and compared with DGEBA Additional properties were also evaluated. Meng et al. characterized mechanical properties via measuring the flexural and tensile strength.

	Amine Hardener	DGEBA	T d5% (°C)	DGEFD	Char yield (%) DGEBA	DGEFD
	33DDS	402		302	20.5	44.1
	44DDS	398		255	13.8	42.3
	DEGA	-		308	-	21
	EDR-148	300 122		314	12 122	19
	EDR-192	-		326	-	15.8
	PACM	336		303	0	6
	Epikure W	-		-	-	-
	DFDA	301		272	<25	40
	DFDA-Me	315		303 / 296*	<25	39 / 2*
	DDM	376 138		296*	15 138	4*
	* under air

M. Fache, E. Darroman, V. Besse, R. Auvergne, S.Caillol and B. Boutevin, Green Chem., 2014, 16, 1987.

Abbreviations

Figure 48 -Cardanol-based polyepoxide commercial monomer NC-514 idealized structure, according to Jaillet et al. 151 Cardanol is an interesting natural phenolic compound, extracted from the cashew nutshell oil, which is a by-product of cashew nut production. This vegetable oil has the advantage of providing biobased aromatics, with alkyl chain, allowing the possibility to design new building blocks, especially for polymers. 152 Cardanol based epoxy resins from Cardolite NC-514 (Figure 48), showed interesting properties. In a paper published by Jaillet et al., its networks with IPDA and Jeffamine were studied. 151 The structural characterization led to the conclusion that NC-514 was mainly composed of diepoxy monomers, with a small percentage of unsaturated compounds. The epoxy structure with cardanol was composed of a phenol ring, with a C15 alkyl chain attached on the meta position. Natural cardanol has unsaturated bonds, which was reacted with phenol in NC-514. This leads to the attachment of another phenol, as a side-group of the alkyl chain. The phenol substitution led to a low unsaturation degree in the formulation. Both phenolic moieties from the natural cardanol, and the pending phenolic side-groups were then substituted by a glycidyl moiety, leading to a difunctional epoxy resin. In this work the EEW was determined around 363 eq•g -1 .

Jaillet et al., studied the formulations of NC-514 with diamine hardeners with higher gel content. Network made using NC-514 and IPDA had a T g of 50 °C (with 90 % gel content). When NC-514/Jeffamine D400 was used the T g was 15 °C (with 90 % gel content). As a comparison, the DGEBA/IPDA network had a T g of 158 °C. Regarding the mechanical properties, a T α of 59 °C was obtained for NC-514/IPDA, and 9 °C for Jeffamine D400/NC-514. DGEBA/IPDA network had a T α of 158 °C and DGEBA/Jeffamine network had a T α of around 50 °C as reported by Soares. 153 The presence of long alkyl chain, especially the pending end chain from cardanol after crosslinking, endows plastifying properties that lead to a low glass transition temperatures to the epoxy network. At the glassy state, a Young modulus of 1.2 GPa for NC514/IPDA and 7 MPa with Jeffamine were recorded (compared to 1.4 GPa for DGEBA/IPDA). The use of polyether-based hardener, Jeffamine, led to a sharp decrease in Young's modulus at the glassy state as compared to when cardanol was used. However, at the rubbery state, the difference of Young's modulus was more pronounced for IPDA based networks, with E' of 19.6 MPa for DGEBA and 3.2 for NC-514 (close to the value of NC-514/Jeffamine, of 2.6 MPa). It could be presumed that at the glassy state, the global network is more affected by the presence of rigid moieties (aromatic rings), and the hardener (for IPDA networks). While at the rubbery state, the presence of alkyl chain results in increased mobility and low crosslinking density.

Besides cardanol, cashew nutshell liquid also contains cardol, which differs from cardanol mainly by bearing an additional phenolic hydroxyl moiety. Carvacrol is a terpenoid phenolic compound that is found in oregano oil, or synthesized from cyclic monoterpenes such as p-cymene. In 2016, Harvey et al. synthesized a bisphenol from carvacrol and a formaldehyde source, trioxane. 154 Garrison and Harvey then used this bisphenol in order to synthesize a diepoxy monomer (diglycidylether of biscarvacrol (DGEBC), Figure 50), and also a diamine. 138 The use of diamine and DDM as hardener with the new

XV. Carvacrol

Conclusion and perspectives

As shown in this review, a lot of epoxy monomer precursors could be derived from biomass feedstock, with a wide range of properties. Some of these new materials show promising results for specific applications, and depending on the targeted properties, some may be suitable to replace DGEBA. However, for some, the starting materials have shown some serious toxicity issues, such as resorcinol. Some others are already known to mimic oestradiol (the natural oestrogen hormone). When selecting a potential BPA substituent, one should be aware of the existing tested precursors for their health hazard. Biobased compounds are seen as promising alternative to replace epoxy monomer precursors. Indeed, the wide range of functionalities available in nature is an infinite source of innovation for polymer chemists. The findings gathered here show that many of structures lead to thermoset properties that are close to DGEBA based systems. A balance in material properties have to be found between thermal or mechanical properties, when trying to remove BPA in epoxy resins. It is unlikely that a universal substitute could be found to replace DGEBA. Indeed, most of the time the potential alternatives to BPA lead to lower mechanical properties.

Hence, the entire formulation must be replaced, and new hardeners should be envisaged. For example, the use of amido-amines instead of amines could allow to restore some mechanical properties. One of the main issues with BPA is not only that it is harmful, but it is also because its constant presence our daily lives, multiplying the chances of exposure to the substance. The diversity of structures offered by bioresources could help to tackle the challenge of BPA elimination, but if for each application a new monomer is required, the profitability will be difficult to attain for industry, however, biorefining is developing opening new routes to obtain bio-sourced compounds. 165 Substitution of harmful chemicals should not focus only on a single side of the problem. Using biomass feedstock does not truly guarantee a sustainable approach. Hence, the use of low environmental impact biomass should be favoured, such as cardanol. Hence, this non-edible natural phenol is a side-products of the production of cashew nut and is not used. Moreover, if left on the soil after cashew harvesting, it could entail adverse effect to the environment. Its production should attain 1Mt/y in the coming years, making this compound a promising starting substance for the replacement of BPA. This review underlines also that using natural compounds to replace petroleum based BPA could also lead to regrettable substitutions. 166,167 For example of the use of phytooestrogens, such as resveratrol or daidzein should be taken with caution when used for the substitution of BPA. To avoid such issues, the development of easily affordable methods to assess the toxicity of compounds are highly desirable. Many research groups are developing such tests. 168 It is also worth mentioning that bio-refining should be performed also with the evaluation of greenhouse gas emissions, to ensure that fossil resources substitution is environmentally viable. The use of life-cycle analysis or other green metrics is also encouraged to determine the environmental performance of the substitution. 169,170 Collaboration between scientists in different fields, and the access to easy-touse tools will improve the impact of the research in this field.