Elodie Blanco

Qingyi Gu

Julien Couble

Lucile Martin

Thomas Onfroy

Guylène Costentin

Jean-François Paul

Carine Michel

Stéphane Loridant

Acidic Properties of Alkaline-earth Phosphates Determined by an Experimental-Theoretical Approach

Alkaline-earth phosphates efficient in the dehydration of lactic acid to acrylic acid were previously shown to contain a surface mono/dihydrogen phosphate amorphous layer composed by M 2+ cations, P=O and POH groups. In this work, acidic properties of such a layer were determined combining FTIR spectra achieved at the dehydrated state and under water vapor and DFT simulations of non-defective and defective MPOH structure. The FTIR spectra of adsorbed pyridine and lutidine revealed the presence of moderate Lewis acid sites (LAS) and of POH groups interacting by H-bonding without significant protonation. DFT calculations were key to interpret FTIR spectra after adsorption of NH 3 : when solely adsorbed, NH 3 interacts with the LAS on both the nondefective surface and the defective surface while the POH for which H points up towards the gas phase are reoriented downward. Brønsted acid sites (BAS) were shown to form under water vapor. This phenomenon was shown by DFT to arise from a more acidic character of HPO 4 2-species for non-defective surface and casual formation of nondefective surface leading to higher amount of H 2 PO 4 -species, which are more acidic BAS.

INTRODUCTION

Acrylic Acid (AA) is a platform molecule used as a building block to produce acrylate polymers and plastics and currently produced by catalytic oxidation of propylene in large volume (6 Mt/y predicted by 2020). [START_REF] Mäki-Arvela | Production of lactic acid/lactates from biomass and their catalytic transformations to commodities[END_REF][START_REF] Blanco | Valorization of lactic acid and derivatives to acrylic acid derivatives: review of mechanistic studies[END_REF] From both environmental and economical point of view, alternative routes to produce acrylic acid should be developed. Glycerol is a potential renewable raw material to produce acrylic acid by oxidehydration. [START_REF] Sun | Glycerol as a potential renewable raw material for acrylic acid production[END_REF] Yields higher than 50% were obtained on W-V-Nb mixed oxides with hexagonal tungsten bronze structure. [START_REF] Chieregato | One-pot glycerol oxydehydration to acrylic acid on multifunctional catalysts: Focus on the influence of the reaction parameters in respect to the catalytic performance[END_REF][START_REF] Chieregato | Multielement Crystalline and Pseudocrystalline Oxides as Efficient Catalysts for the Direct Transformation of Glycerol into Acrylic Acid[END_REF] Another investigated route is the dehydration of Lactic Acid (LA), a platform molecule used to produce chemical commodities and PLA polymers. [START_REF] Mäki-Arvela | Production of lactic acid/lactates from biomass and their catalytic transformations to commodities[END_REF][START_REF] Blanco | Valorization of lactic acid and derivatives to acrylic acid derivatives: review of mechanistic studies[END_REF][START_REF] Fan | Selective Catalysis of Lactic Acid to Produce Commodity Chemicals[END_REF] Lactic acid is currently yielded by carbohydrates fermentation [START_REF] Mäki-Arvela | Production of lactic acid/lactates from biomass and their catalytic transformations to commodities[END_REF][START_REF] Blanco | Valorization of lactic acid and derivatives to acrylic acid derivatives: review of mechanistic studies[END_REF][START_REF] Fan | Selective Catalysis of Lactic Acid to Produce Commodity Chemicals[END_REF] but can also be obtained by alternative fermentation processes using various substrates [START_REF] Abdel-Rahman | Lactic acid production from lignocellulosederived sugars using lactic acid bacteria: Overview and limits[END_REF][START_REF] Abdel-Rahman | Recent advances in lactic acid production by microbial fermentation processes[END_REF] and by glycerol catalytic dehydrogenation. [START_REF] Auneau | Heterogeneous Transformation of Glycerol to Lactic Acid[END_REF] The global market for lactic acid was 0.75 Mt/y in 2017 and is projected to reach 1.8 Mt/y by 2022. 10 Modified zeolites, sulphates/nitrates, and phosphates were specifically investigated. The best yields were obtained using alkaline earth metal phosphates (up to 85% AA yield) which furthermore are more stable than zeolites. [START_REF] Mäki-Arvela | Production of lactic acid/lactates from biomass and their catalytic transformations to commodities[END_REF][START_REF] Blanco | Valorization of lactic acid and derivatives to acrylic acid derivatives: review of mechanistic studies[END_REF][START_REF] Fan | Selective Catalysis of Lactic Acid to Produce Commodity Chemicals[END_REF] We established correlations between the NH 3 and CO 2 -TPD curves and the AA selectivity using alkaline earth phosphates as catalysts. 11 The catalysts with only weak acid and basic sites were selective and their NH 3 and CO 2 -TPD curves were surprisingly quite similar. Furthermore, the best AA selectivity was obtained for barium orthophosphate, for which the acid to base balance was close to 1. It suggested the participation of acid-base pairs in the mechanism. However, TPD measurements were achieved after pre-treatment at the calcination temperature while water vapor was present in the reaction feed and generated by dehydration. More recently, characterization of the prepared alkaline earth phosphates (including barium orthophosphate) showed the systematic

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The Journal of Physical Chemistry presence of a surface mono/dihydrogen phosphate amorphous (non-crystalline for X-rays and electron diffraction) layer containing POH species. [START_REF] Blanco | Dehydration of ethyl lactate over alkaline earth phosphates: Performances, effect of water on reaction pathways and active sites[END_REF] In situ DRIFT measurements have suggested that formation of POH groups was favored under water vapor and that these species interacted with reactants or reaction products at the reaction temperature.

DFT calculations could help in rationalizing the experimental observations. For instance, Paul and co-workers investigated the LA to AA transformation but on ZrO 2 . [START_REF] Hammaecher | Density functional theory study of lactic acid adsorption and dehydration reaction on monoclinic 011, 01, and 11 zirconia surfaces[END_REF] They identified that on this oxide, the dehydration site is clearly an acido-basic pair, where the acid site Zr 4+ stabilizes the leaving α-OH and the basic O 2-site on zirconia plays the role of proton acceptor. Theoretical studies were also achieved on alkaline earth phosphates but mostly on hydroxyapatites Ca 5 (PO 4 ) 3 (OH) due to their important using in biomaterials. [START_REF] Dorozhkin | Biological and Medical Significance of Calcium Phosphates[END_REF] In the present work, acidic sites of alkaline-earth phosphates catalysts were characterized by NH 3 adsorption followed by IR spectroscopy at the dehydrated state and in the presence of water vapor. The IR spectra were assigned from DFT calculations, which also explained acidic properties determined by NH 3 adsorption. Characterization of acidity was strengthened by adsorption of pyridine and lutidine followed by IR spectroscopy.

METHODS

Catalysts preparation

Barium orthophosphate (labelled BaOP) was prepared by mixing a solution of diammonium hydrogen phosphate (NH 4 ) 2 HPO 4 (Aldrich, 99%) at 0.20 mol.L -1 for which the pH was previously adjusted to 9 adding NH 4 OH (32%vol) and a solution of barium nitrate (Ba(NO 3 ) 2 ) (Aldrich, >99%) at 0.30 mol.L -1 . The latter one was added drop wise while maintaining constant the pH and stirring for 1 h. The precipitate was filtrated off, washed with deionized water, dried at 100 °C and crushed before calcination under air flow at 600 °C for 6 h.

Catalysts characterizations

Analysis of the acidic properties of samples was performed by adsorption-desorption of pyridine and lutidine followed by infrared spectroscopy. Self-supported wafers were placed inside the IR cell and then outgassed under secondary vacuum at 350 °C for 2 h. In the following, the samples were contacted at room temperature with gaseous basic probe via a separate cell containing liquid pyridine or lutidine. The spectra were then recorded following desorption at increasing temperature with a Bruker Vector 22 spectrometer (resolution 2 cm -1 , 64 scans). The reported spectra were obtained after subtraction of the spectrum recorded before probe adsorption.

In situ DRIFT spectra were achieved with a Nicolet 6700 FTIR spectrometer (Thermo Scientific) equipped with Praying Mantis™ High Temperature Reaction Chamber (Harrick, model HVC-DRP-4). The CaF 2 windows used for the experiments were heated at 70-80 °C with external water system to avoid condensation. The effect of water was investigated by flowing 30%H 2 O-He or 30%D 2 O-He at 380 °C after pre-treatment at 380 °C for 30 min under He. Such high water partial pressure was obtained using a saturator heated at 70 °C. The background corresponded to the spectrum of dehydrated KBr.

In situ FTIR acidity measurements were performed on self-supported pellets (53 mg) with a Nicolet 6700 spectrometer (ThermoScientific) using a homemade stainless steel IR cell reactor specially designed to limit the gas phase contribution (its optical path is 2.2 mm) [START_REF] Chafik | Heat of Adsorption of Carbon Monoxide on a Pt/Rh/CeO 2 /Al 2 O 3 Three-Way Catalyst Using in-Situ Infrared Spectroscopy at High Temperatures[END_REF] and NH 3 as probe molecule. This IR cell allowed the study of adsorbed species in the range 20-450 °C under gas flow rates (200 mL.min -1 in the present study) of gas mixtures at atmospheric pressure such as x% NH 3 /y% H 2 O/He with x and y in the ranges 0-1% and 0-3% respectively. The amount of H 2 O Page 7 of 53

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The Journal of Physical Chemistry was controlled using a saturator/condenser system as described previously. [START_REF] Giraud | Experimental Microkinetic Approach of De-NOx by NH 3 on V 2 O 5 /WO 3 /TiO 2 Catalysts. 4. Individual Heats of Adsorption of Adsorbed H 2 O Species on Sulfate-Free and Sulfated TiO 2 Supports[END_REF] BaOP pellet was pretreated at 380 °C under 20%O 2 -He for 1 h and then He. NH 3 adsorption equilibrium was followed at 2%NH 3 upon heating and cooling between RT to 200 °C. The AEIR (Adsorption Equilibrium InfraRed spectroscopy) method was used to determine individual NH 3 heats of adsorption from the evolution of the IR band area of each adsorbed X ads species with the increase in T a in isobaric conditions. The experimental curve θX exp = f(T a ), with θ corresponding to the coverage of sites, was compared to the one obtained from the Temkin model assuming localized adsorbed species.

Adjustment of the theoretical curve to the experimental data provides E x (1) and E x (0), the heats of adsorption at high and low coverages of the X ads species, respectively. The accuracy of the method to determine NH 3 heats of adsorption has been evidenced for TiO 2 support and V 2 O 5 /WO 3 /TiO 2 catalysts. [START_REF] Giraud | Experimental Microkinetic Approach of De-NOx by NH 3 on V 2 O 5 /WO 3 /TiO 2 Catalysts. 1. Individual Heats of Adsorption of Adsorbed NH 3 Species on a Sulfate-Free TiO 2 Support Using Adsorption Isobars[END_REF][START_REF] Giraud | Experimental Microkinetic Approach of De-NOx by NH 3 on V 2 O 5 /WO 3 /TiO 2 Catalysts. 2. Impact of Superficial Sulfate and/or V x O y groups on the Heats of Adsorption of Adsorbed NH 3 Species[END_REF][START_REF] Giraud | Experimental Microkinetic Approach of De-NOx by NH 3 on V 2 O 5 /WO 3 /TiO 2 Catalysts. 3. Impact of Superficial WO z and V x O y /WO z Groups on the Heats of Adsorption of Adsorbed NH 3 Species[END_REF] Acidity measurements in presence of water vapor [START_REF] Buniazet | Unravelling water effects on solid acid catalysts: Case study of TiO 2 /SiO 2 as a catalyst for the dehydration of isobutanol[END_REF] were achieved at adsorption equilibrium flowing 1%NH 3 -3%H 2 O-He mixture upon heating and cooling between RT and 200 °C.

DFT Computational details

Density functional theory (DFT) calculations were carried out using the Vienna ab initio simulation package (VASP). [START_REF] Kresse | Efficient iterative schemes for ab initio total-energy calculations using a plane-wave basis set[END_REF][START_REF] Kresse | Efficiency of ab-initio total energy calculations for metals and semiconductors using a plane-wave basis set[END_REF][START_REF] Kresse | Ab initio molecular dynamics for liquid metals[END_REF] The exchange and correlation terms were obtained by the Perdew-Burke-Ernzerhof form of Generalized Gradient Approximation (GGA-PBE) functional. [START_REF] Perdew | Generalized Gradient Approximation Made Simple[END_REF] The core electrons were kept frozen and a projector-augmented wave (PAW) method was used to substitute the core electrons. [START_REF] Kresse | From ultrasoft pseudopotentials to the projector augmented-wave method[END_REF] A cut-off energy of 550 eV of the plane wave basis set was used to describe the valence electrons. The bulk optimization would reach the convergence when the energy was converged to 1×10 -6 eV and the forces were smaller than 0.01 eV/Å with a k-point mesh of 5×2×5. For optimization of the slab, the same energy convergence criterion was used and

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The Journal of Physical Chemistry the convergence criterium on the forces was set to 0.03 eV/Å. The k-point mesh was adapted to the super cell size using a mesh of 5×5×1 k-points. Frequencies were computed within the harmonic approximation. Gibbs free energies were derived using those frequencies, and for the molecules using the perfect gas and rigid rotator approximations.

Based on the previous characterizations of the BaOP catalyst 11,[START_REF] Blanco | Dehydration of ethyl lactate over alkaline earth phosphates: Performances, effect of water on reaction pathways and active sites[END_REF] and on the fact that Ca and Ba are expected to have similar properties being both alkaline-earth elements, we selected the Brushite, a well-known layered calcium hydrogen orthophosphate dihydrate, [START_REF] Curry | Crystal Structure of Brushite, Calcium Hydrogen Orthophosphate Dihydrate: A Neutron-diffraction Investigation[END_REF][START_REF] Hirsch | Infrared Absorption Spectrum of Brushite from First Principles[END_REF][START_REF] Schofield | The role of hydrogen bonding in the thermal expansion and dehydration of brushite, di-calcium phosphate dihydrate[END_REF] to model the amorphous layer lying over the catalyst crystallites. In solution, Brushite forms thin hexagonal platelet. [START_REF] Hirsch | Infrared Absorption Spectrum of Brushite from First Principles[END_REF][START_REF] Kumta | Nanostructured calcium phosphates for biomedical applications: novel synthesis and characterization[END_REF] Since the (010) surface corresponds to the basal plane of the platelets, it is expected to be the most stable and have a very low surface energy. In order to define a model of this surface, the cutting plane was located in the middle of the gap between two layers. The number of water molecule was kept equal to the number in the solid. Using this choice, the surface is created cutting only hydrogen bonds. Two other planes perpendicular to the basal plane were studied: the (100) and the (001) in order to model the edges of the platelets. The two surfaces have been defined without breaking any P-O or O-H bonds, in order to reduce their surface energies. For the three surfaces, symmetric and stoichiometric slabs were used with a vacuum layer of 15.14 Å to avoid the interaction between the slabs. The computed surface energies for (001), (010) and (100) were 0.047 eV/Å 2 , 0.016 eV/Å 2 and 0.032 eV/Å 2 respectively, confirming the greater stability of the The IR spectroscopy was modelled by accurately determining the vibrational spectrum of a system. We used the density functional perturbation theory in our study to determine the Hessian matrix, and finally obtain the wavenumber of every vibration mode. [START_REF] Baroni | Green's-Function Approach to Linear Response in Solids[END_REF] Within this framework, the overtones are not simulated and the influence of the temperature on the vibration wavenumbers is not included. We determined the scaling factor between experimental wavenumbers and DFT ones using NH 3 and H 2 O as a reference and we obtained 0.98 for the stretching vibration modes and 1.00 the for bending ones as shown in Table S1 of Supplementary material. Scaling down some wavenumbers to improve the quality of the prediction obtained within the harmonic approximation allows us to partially recover anharmonicity effects. [31][32][33] The good agreement with the experimental spectra confirms that this factor established on gas phase spectra of water and ammonia is still valid for adsorbed species.

RESULTS

Characterization of the dehydrated and hydrated state

The main structural and textural properties of BaOP catalyst have been previously described. 11 Shortly, it contained mostly crystalline Ba 3 (PO 4 ) 2 and its specific surface area was 8.9 m 2 .g -1 .

Chemical and XPS analyses showed sub-stoichiometric Ba/P ratios (1.38 and 1.28, respectively instead of 1.5 for stoichiometric Ba 3 (PO 4 ) 2 ) that could be ascribed to the presence of either small amount of crystalline -Ba 2 P 2 O 7 11 and a phosphorus rich amorphous (non-crystalline) phase which does not diffract either by X-rays and electron diffractions. The latter phase was shown to correspond to a surface layer containing POH species and lying over Ba 3 (PO 4 ) 2 crystallites. [START_REF] Blanco | Dehydration of ethyl lactate over alkaline earth phosphates: Performances, effect of water on reaction pathways and active sites[END_REF] It could be either a stoichiometric BaHPO 4 or a mixture of mono and dihydrogen phosphate with a general formula Ba (1-x) (HPO 4 ) 1-2x (H 2 PO 4 ) 2x .

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The Journal of Physical Chemistry bands between 1850 and 2050 cm -1 corresponded to overtones of (P=O) vibrations which are located around 1000 cm -1 . [START_REF] Cheng | FTIR Study on incorporation of CO 2 into calcium hydroxyapatite[END_REF] The band at 3660 cm -1 was ascribed to (PO-H) stretching vibrations of free surface species by analogy with deficient hydroxyapatites. [START_REF] Blanco | Dehydration of ethyl lactate over alkaline earth phosphates: Performances, effect of water on reaction pathways and active sites[END_REF] The broad band located around 3190 cm -1 corresponded to (PO-H) stretching vibrations as observed for alkaline earth hydrogen phosphates. [START_REF] Trchova | Study of Host-Guest Interactions in Intercalate Zr(HPO 4 ) 2 •2CH 3 CH 2 OH using a Combination of Vibration Spectroscopy and Molecular Simulations[END_REF][START_REF] Koleva | Infrared and Raman studies of manganese dihydrogen phosphate dihydrate, Mn(H 2 PO 4 ) 2 .2H 2 O. Part II: Region of the internal OH group vibrations[END_REF][START_REF] Frost | Vibrational spectroscopy of synthetic archerite (K,NH 4 )H 2 PO 4and in comparison with the natural cave mineral[END_REF][START_REF] Frost | A Raman spectroscopic study of the mono-hydrogen phosphate mineral dorfmanite Na 2 (PO 3 OH)•2H 2 O and in comparison with brushite[END_REF] This large difference of wavenumber could arise from the effect of hydrogen bonds in bulk hydrogen phosphates leading to weakening of PO-H bonds and stretching vibrations at lower wavenumbers. However, the absorbance of the (PO-H) band at 3660 cm -1 was increased evidencing formation of additional POH species. This phenomenon could arise from hydrolysis of the weak amount of -Ba 2 P 2 O 7 leading to BaHPO 4 . Note that the  bending mode of chemisorbed H 2 O at 1600-1630 cm - 1 39,40 was not observed showing such species was not present at the surface of BaOP sample.

Isotopic labelling achieved under 30%D 2 O-He at 380 °C led to a shift of the bands at 3660 and 3190 cm -1 to 2700 and 2390 cm -1 , respectively while the framework vibrational bands at 1850-2050 cm -1 remained unchanged. These shifts are close to the ones expected for deuteration of OH groups considering harmonic oscillator (ratios of 0.74 and 0.75, respectively instead of 0.73).

Modelling of the surfaces and influence of the water amount

The Brushite structure was built based on the neutron single crystal diffraction study [START_REF] Curry | Crystal Structure of Brushite, Calcium Hydrogen Orthophosphate Dihydrate: A Neutron-diffraction Investigation[END_REF] The calculated cell parameters of a =5.98 Å, b = 15.14 Å and c = 6.24 Å, are in good agreement with the experimental ones (a exp = 5.80 Å, b exp = 15.13 Å, c exp = 6.32 Å). [START_REF] Curry | Crystal Structure of Brushite, Calcium Hydrogen Orthophosphate Dihydrate: A Neutron-diffraction Investigation[END_REF] A detailed description of the brushite structure can be found in the Hirsch's work. [START_REF] Hirsch | Infrared Absorption Spectrum of Brushite from First Principles[END_REF] The (010) surface of Brushite is the most stable surface computed (see computational details).

As shown in Figure 3, the top of this surface is covered with eight water molecules per unit cell.

We will consider later this as a complete monolayer of water, θ(H 2 O)=1 ML. One can distinguish two orientations: (i) water marked W a is perpendicular to the surface, 2.55 Å far away from the nearest Ca 2+ atom, and gives a H bond to the O of HPO 4 2-and accepts an H bond from another water molecule nearby (ii) the other water, W b , is parallel to the surface, closer to Ca 2+ with a distance of 2.47 Å and is also involved in a H bond network, donating to HPO 4 2-and to W a . This highly hydrated surface can be easily dehydrated raising the temperature. The fully hydrated surface as cleaved from the bulk structure has a water coverage of θ(H 2 O)=1 ML, which corresponds to eight water molecules per unit cell. We considered various coverages in water, θ(H 2 O)=1 ML, 7/8 ML, 1/8 ML and 0 ML, as shown in Figure 3. To start, we generated a structure with a lower coverage of θ(H 2 O)=7/8 ML removing one water molecule. The structure with W b deleted is -20 kJ.mol -1 more stable than the one where W a is deleted, thus only the surface with W b deleted is shown in Figure 3. Next, we built a weakly hydrated surface, keeping only one water (W a ), reaching a coverage of θ(H 2 O)=1/8 ML. Finally, a fully dehydrated surface was also computed (θ(H 2 O)=0 ML), where the eight water molecules exposed at the external surface were deleted but the ones inside and in the bottom layers were still preserved. The relative stability of these surfaces as function of the temperature under 1 atm pressure of water is shown in Figure 4. When the temperature is lower than 116 °C, the surface prefers to be covered with water. At 116 °C, the surface starts to dehydrate, one W b is desorbed and the exposed surface has a coverage of θ(H 2 O)=7/8 ML. This temperature threshold for dehydration is consistent with the experimental one (80 °C) found by Dosen et al. [START_REF] Dosen | Thermal decomposition of brushite, CaHPO 4 •2H 2 O to monetite CaHPO 4 and the formation of an amorphous phase[END_REF] With an increase in the temperature, the dehydration keeps proceeding and at 187 °C, a coverage of θ(H 2 O)=1/8 ML is reached and when the temperature is higher than 251 °C, the surface is totally dehydrated. It should also be noted that the surface energy becomes negative when the temperature is higher than 310 °C, which means that a dehydration of the bulk should occur. Such transformation to CaHPO 4 (Monetite) [START_REF] Dorozhkin | Biological and Medical Significance of Calcium Phosphates[END_REF] was not further investigated since the purpose was to build a model of the exposed facet of the BaOP catalyst. However, these temperatures of complete dehydration of the surface and of likely bulk dehydration are consistent with experimental observations where the transformation to Monetite is complete between 200 and 220 °C. [START_REF] Dosen | Thermal decomposition of brushite, CaHPO 4 •2H 2 O to monetite CaHPO 4 and the formation of an amorphous phase[END_REF] Based on the above discussion, it is clear that at the reaction temperature of 380 °C (which is also the IR spectrum recording temperature), the most favorable surface is the dehydrated surface. For experiments performed under 30%H 2 O-He, we will include one water molecule to probe the impact of the modifications induced by the change of atmosphere and consider the

θ(H 2 O)=1/8ML coverage.
As the amorphous layer lying over Ba 3 (PO 4 ) 2 crystallites of the BaOP catalyst could be a phase with a general formula Ba (1-x) (HPO 4 ) 1-2x (H 2 PO 4 ) 2x (see above), a defective surface was also constructed with a cationic vacancy and completed with two H + . The most favorable structure of this defective surface is shown in Figure 5. The two additional H + are added on two HPO 4 2- yielding two H 2 PO 4 -groups. One of the additional H points down, forming an H bond with another HPO 4 2-deeper in the surface. This orientation is labeled H down . The other additional H points up towards the gas phase and is labeled H up . No other stable configuration can be found with the two additional H + pointing downward. The adsorption of water is not stronger on this Ca 2+ vacancy than on the non-defective surface (adsorption energy of -84 kJ.mol -1 vs. -82 kJ.mol -1 respectively). To determine if the presence of the H up pointing toward the gas phase appears as typical of the presence of a Ca 2+ vacancy, we also investigated the likeliness of finding such an orientation in the non-defective fully dehydrated surface. The corresponding results are collected in Table 1. The most stable structure is Config 1, with four H down , already discussed and shown in Figure 3. With one H up , Config 2 is only 11 kJ.mol -1 higher in energy, which corresponds to a Boltzmann probability of 0.15 at the working temperature of 380 °C. However, with four H up , Config 3 is much less stable and is clearly very unlikely at this temperature. In other words, the presence of H up cannot be attributed only to the presence of Ca 2+ vacancy but is also related to thermal effects that favor the re-orientation of the PO-H bond. These two orientations (up and down) have a clear spectroscopic signature, with distinct (PO-H) stretching vibrations. In the non-defective dehydrated surface, the free PO-H up is found to vibrate around 3690 cm -1 while the PO-H down vibrations are red-shifted to the 3100-3200 cm -1 range due to their involvement in strong H-bonds with internal HPO 4 2-as shown in Table 1. In a defective surface, the vibration of free PO-H up is around 3660 cm -1 and two vibrations of PO-H down are around 3220 cm -1 (Figure 5). These two computed wavenumbers are in agreement with the observations reported in Figure 1 with two bands at 3660 and 3190 cm -1 identified as P-OH vibrations. However, in the defective surface, several PO-H down ) wavenumbers are much lower (3041 cm -1 , 2748 cm -1 and 2424 cm -1 ) due to the change of the environment induced by the deletion of one Ca 2+ atom and the addition of two more protons on the HPO 4 2-groups leading to H 2 PO 4 -.

They could explain the large width of the band at 3190 cm -1 (see Figure 1) tailing to 2400 cm -1 .

This would imply that the surface of the BaOP catalyst was a defective hydrogen phosphate and hence contained H 2 PO 4 -species.

To further confirm the interpretation of the in situ DRIFT spectra of BaOP at 380 °C under He but also under 30%H 2 O-He and 30%D 2 O-He (Figure 1), we also considered the case with 1/8 ML of water (see Figure 4 and the corresponding discussion). The increase of the band at 3660 cm -1 in presence of water cannot be attributed to water itself since the δ bending mode of chemisorbed H 2 O at 1600-1630 cm -1 39,40 was not observed. However, all attempts to increase the amount of P-OH exposed thanks to water dissociation failed, on both the non-defective dehydrated and the defective surfaces. The only stable structure was obtained in the case of the non-defective surface (as shown in Figure S1) but it is 167 kJ.mol -1 less stable than when water is not dissociated.

Since the increase of the band at 3660 cm -1 cannot be attributed to water itself or to the increase of the number of POH by water dissociation, we checked if the stability of the P-OH up could be increased by the presence of a chemisorbed water molecule: as shown in Table S2, turning one P-OH down into a P-OH up costs 9 kJ.mol -1 , which is very close to the 11 kJ.mol -1 that was needed in absence of water (Table 1): the effect is not significant. Finally, we inferred that it could be related to hydrolysis of the small amount of -Ba 2 P 2 O 7 present in the BaOP catalyst leading to BaHPO 4 formation and to an increase in the concentration of cationic vacancy in the hydrogen phosphate layer lying over Ba 3 (PO 4 ) 2 crystallites, which would be favored by water. For BaHPO 4 , the hydrolysis reaction is proposed to occur according to:

BaHPO 4 + H 2 O => Ba (1-x) (HPO 4 ) 1-2x (H 2 PO 4 ) 2x +xBa 2+ + 2xOH -
Note that similar dissolution processes were reported in the liquid phase [START_REF] Lagno | Supersaturation-Controlled Synthesis of Dicalcium Phosphate Dihydrate and Nanocrystalline Calcium-Deficient Hydroxyapatite[END_REF][START_REF] Wang | Calcium Orthophosphates: Crystallization and Dissolution[END_REF] and could be more favorable for sub-stoichiometric brushite containing cationic vacancies.

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The Journal of Physical Chemistry 20

Acidity measurements by IR spectroscopy

The FTIR spectrum of pyridine adsorbed on BaOP plotted in Figure S2 (supplementary material) contained bands at 1614, 1592, 1574, 1489 and 1441 cm -1 which were attributed to pyridine coordinated to Lewis acid sites (LAS) or in H-bonding. [START_REF] Busca | The surface acidity of solid oxides and its characterization by IR spectroscopic methods. An attempt at systematization[END_REF][START_REF] Busca | Spectroscopic characterization of the acid properties of metal oxide catalysts[END_REF] Observation of two 8a vibrational modes at 1614 and 1592 cm -1 revealed the presence of two different coordination sites.

Considering their shifts compared to pyridine in liquid phase (1583 cm -1 ), they were attributed to moderate Lewis acid and H-bonding sites, respectively. The three other bands corresponded to 8b, 19a and 19b modes, respectively. [START_REF] Busca | The surface acidity of solid oxides and its characterization by IR spectroscopic methods. An attempt at systematization[END_REF][START_REF] Busca | Spectroscopic characterization of the acid properties of metal oxide catalysts[END_REF] The absence of band around 1540-1550 cm -1 typical of pyridinium cations indicated the absence of Brønsted acid sites able to protonate pyridine.

As pyridine (pKa=5.2) could be too weak to react with BAS, adsorption-desorption of lutidine (pKa=6.6) was followed by FTIR. Spectra recorded at different desorption temperatures are plotted in Figure 6. At room temperature, bands were observed at 1601, 1580, 1472 and 1455 cm -1 which were attributed to the 8a, 8b, 19a and 19b vibrational modes of lutidine coordinated to LAS or in Hbonding [START_REF] Oliviero | 2,6-Dimethylpyridine as a probe of the strength of Brønsted acid sites: study on zeolites. Application to alumina[END_REF][START_REF] Onfroy | Quantitative IR characterization of the acidity of various oxide catalysts[END_REF] while the negative (PO-H) band at 3673 cm -1 revealed structural modifications of POH up species that could arise from interaction between POH up species and lutidine. It was not possible to know if the broad band around 3200 cm -1 and attributed to POH down was affected because of superimposition of (CH 3 ) and (CH) stretching vibrations of lutidine. The 8a mode of lutidine is very sensitive to the adsorption mode and its small shift compared to the liquid phase (+7 cm -1 ) was typical of H-bonded species. The 8a mode of lutidinium cations located at 1640-1655 cm -1 was not observed showing that POH species were not able to protonate lutidine.

Increasing the desorption temperature, the bands of H-bonded lutidine disappeared in parallel to the negative (PO-H) band confirming their interdependence. The steric hindrance of methyl groups of lutidine could explain such molecule did not probe moderated LAS contrarily to pyridine. [START_REF] Onfroy | Quantitative IR characterization of the acidity of various oxide catalysts[END_REF] The in situ FTIR spectra recorded at adsorption equilibrium of NH 3 are shown on Figure 7 from 120 to 7 °C. They all contain one band at 1630 cm -1 , numerous bands between 3200 and 3400 cm -1 and a negative band at 3670 cm -1 . They disappeared above 200 °C in good agreement with TPD measurements. Comparison between the evolutions of the experimental coverage and the one calculated using the Temkin model (Figure S3) led to adsorption heat values of E 0 = 65 kJ.mol -1 and E 1 = 48 kJ.mol -1 . Such low values were typical of weak adsorption sites. 17 We also established the relative stability of various ammonia surface concentrations as function of the temperature using ab initio thermochemistry (see Figure S4). When T < 145 °C, the coverage of NH 3 was θ(NH 3 )=1 ML (one ammonia per surface phosphate). It decreased to 1/2 ML from 145 °C to 162 °C. Above 162 °C, the surface was predicted to be bare, with no ammonia, in agreement with our experimental observations. To sustain the attribution of the bands and identify the corresponding sites, we show the most important predicted wavenumbers obtained on the dehydrated surfaces with a coverage of θ(NH 3 )=1/4 ML in Figure 8. The ones obtained with a higher coverage, such as 1/2 ML, were found similar (see Table S3). 2. Color-coding: grey for calcium, red for oxygen, green for phosphorus, blue for nitrogen and yellow for hydrogen, except surface H up, which is marked in white.

The negative band at 3670 cm -1 indicated that POH up species are modified by adsorbed NH 3 .

Thus, the adsorption of NH 3 was considered on the Config 2 of the non-defective surface (see Table 1), which presented some POH up species, and on the defective surface. In both cases, the interaction with the BAS (the POH up ) and the LAS (Ca 2+ in our model that stands for Ba 2+ in the BaOP catalyst) were considered. The corresponding adsorption energies are provided in Table 2. With a low adsorption energy (-48 kJ.mol -1 ), the adsorption on the BAS (structure A) is less likely than on the LAS of the dehydrated non-defective surface (structure B, -89 kJ.mol -1 ). The contrast between these two site types is likely to be reduced since here we modeled Ba 2+ by a stronger LAS, namely Ca 2+ . On the defective surface, it was the opposite situation with an adsorption on the LAS (structure D, -84 kJ.mol -1 ) less stabilizing than on the BAS (structure C, -118 kJ.mol -1 ), a difference that is expected to be even stronger for the weak LAS Ba 2+ . In this defective case, the adsorbed NH 3 even captured

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Conversely, the generation of NH 4 + from the proton transfer from HPO 4 2-to NH 3 was found to be very unlikely on the non-defective dehydrated surface with an adsorption energy much weaker than the non-dissociative adsorption (-12 kJ.mol -1 vs. -89 kJ.mol -1 , Figure S5).

The experimental spectra contained one band at 1630 cm -1 typical of Lewis coordination and/or H-bonding ((NH 3 ) vibration). [START_REF] Giraud | Experimental Microkinetic Approach of De-NOx by NH 3 on V 2 O 5 /WO 3 /TiO 2 Catalysts. 1. Individual Heats of Adsorption of Adsorbed NH 3 Species on a Sulfate-Free TiO 2 Support Using Adsorption Isobars[END_REF] This vibration mode is doubly degenerated in free NH 3 but nonsymmetric environment slightly split the band in the computed spectra. It was predicted to be not sensitive to the type of interaction since it was computed at 1630, 1611 cm -1 when NH 3 was Hbonded to P-OH up (Figure 8A) and at 1639, 1609 cm -1 when NH 3 was in interaction with a LAS (Figure 8B andD). The (NH 3 ) stretching vibrations were more sensitive to the adsorption site.

The symmetric mode was strongly red-shifted (3227 cm -1 ) when NH 3 was in interaction with the LAS on the non-defective surface (Figure 8B) compared with cases where it was in interaction with the same site on the defective surface (3303 cm -1 , Figure 8D) or H-bonded to PO-H up of the non-defective surface (3304 cm -1 , Figure 8A). The asymmetric vibrations were all found in a range of 3380-3470 cm -1 . All these bands were compatible with the experimental observation of a rather complicated 3200-3400 cm -1 spectral range with bands at 3396, 3375, 3300, 3241 and 3214 cm -1 superimposed to an asymmetric broad one (Figure 7). The first two were attributed to  asym (NH 3 )

vibrations and the third one to  sym (NH 3 ). Note that  asym (NH 3 ) vibrations are doubly degenerated for free NH 3 (E mode). Observation of two  asym (NH 3 ) bands and one  sym (NH 3 ) band implies a symmetry lowering compared to C 3v . Attribution of the two last bands at 3241 and 3214 cm -1 was

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The Journal of Physical Chemistry not obvious since it could either correspond to overtones of  asym (NH 3 ) and to  1 (NH 4 + ) vibrations [START_REF] Zecchina | Vibrational Spectroscopy of NH 4 + Ions in Zeolitic Materials: An IR Study[END_REF][START_REF] Plaza | Optical spectroscopy of the NH 4 + internal vibrations in the orthorhombic phase of NH 4 MF 3 (M is Mn, Zn) perovskites[END_REF] but also to  sym (NH 3 ) with NH 3 in interaction with the Lewis site on the nondefective surface (3227 cm -1 , Figure 8B) or to (PO-H) vibrations of POH down species. As these bands were kept upon heating to 120 °C while   (NH 4 + ) at 1475 cm -1 49,50 disappeared above 7 °C, attribution to  1 (NH 4 + ) was ruled out.

Observation of broad band tailing to 2400 cm -1 strongly suggested higher contribution of (PO-H) vibrations due to POH down . Indeed, some POH down vibrations were predicted to be red-shifted by the NH 3 absorption with bands shifting from 3169 to 3139 cm -1 for instance (see Figure 8A).

In addition, the presence of Ca 2+ vacancies in the defective structure would also yield to the observation of vibrations as low as 2583 cm -1 related to the presence of H 2 PO 4 -species (Figure 8D). Last, when NH 3 was H bonded directly to PO-H up (Figure 8A), the PO-H up ) band at 3691 cm -1 shifted down to 2439 cm -1 due to the strong H-bond. This corresponds to a zone where a small absorbance was seen in the experimental spectra. The orientation of the PO-H up was also affected in the case of an interaction of NH 3 with the LAS, despite the lack of direct interaction. It rotated from up to down, inducing a strong red shift of PO-H up ) from 3691 to 3105 cm -1 and the red shift of the three PO-H down ) to 3100-3200 cm -1 as shown in Figure 8B and D. This is in line with the experimental observations regarding the disappearing of the band at 3670 cm -1 and the broad band in the range of 2800-3200 cm -1 . Finally, the band at 3241 cm -1 could correspond to the  sym (NH 3 ) vibration of NH 3 adsorbed on the LAS of the non-defective surface while the shoulder at 3214 cm -1 would be assigned to changes in the POH down signature. Attribution of the bands 3241 and 3214 cm -1 to two different species (adsorbed NH 3 and POH down , respectively) was confirmed by the change of their relative intensity with the temperature (Figure 7).

The negative shoulder observed at 3715 cm -1 only on the spectrum recorded to 7 °C (below RT) was assigned to (H 2 O) due to traces of physisorbed water leading to the spontaneous reaction: [START_REF] Giraud | Experimental Microkinetic Approach of De-NOx by NH 3 on V 2 O 5 /WO 3 /TiO 2 Catalysts. 4. Individual Heats of Adsorption of Adsorbed H 2 O Species on Sulfate-Free and Sulfated TiO 2 Supports[END_REF][START_REF] Giraud | Experimental Microkinetic Approach of De-NOx by NH 3 on V 2 O 5 /WO 3 /TiO 2 Catalysts. 4. Individual Heats of Adsorption of Adsorbed H 2 O Species on Sulfate-Free and Sulfated TiO 2 Supports[END_REF] NH 3 + H 2 O ads  (NH 4 + ) ads + OH - ads Such reaction which did occur only at 7 °C also explained observation of the bending   (NH 4 + ) and   (NH 4 + ) vibrations bands at 1475 and 1685 cm -1 , respectively. [START_REF] Zecchina | Vibrational Spectroscopy of NH 4 + Ions in Zeolitic Materials: An IR Study[END_REF][START_REF] Plaza | Optical spectroscopy of the NH 4 + internal vibrations in the orthorhombic phase of NH 4 MF 3 (M is Mn, Zn) perovskites[END_REF] The latter one is observed by IR only when symmetry of NH 4 + cations is lower than T d . [START_REF] Zecchina | Vibrational Spectroscopy of NH 4 + Ions in Zeolitic Materials: An IR Study[END_REF][START_REF] Plaza | Optical spectroscopy of the NH 4 + internal vibrations in the orthorhombic phase of NH 4 MF 3 (M is Mn, Zn) perovskites[END_REF] DFT computations provided another possible explanation on NH 4 + formation. Indeed, traces of physisorbed water at low temperature could increase the amount of Ca 2+ vacancies (see section 3.2), which promotes the formation of NH 4 + . Their presence was predicted on the defective surface, with strong adsorption energy of -118 kJ.mol -1 (Table 2). The computed NH 4 + vibration bands were split by the environment. By comparison with the observed ones (1475 and 1685 cm -1 ), two bands were found to be the major ones (1465 and 1679 cm -1 , see Figure 8C).

To sum up, the interaction of NH 3 with the POH groups by H-bonding without significant protonation of the non-defective surface could not be discarded based on the infrared signature.

However, it was found to be less likely based on energetic consideration since it had the weakest adsorption energy (Table 2). Even upon interaction with the LAS, the PO-H up ) band was found to disappear due to the re-orientation of the PO-H bond downward. Bands at 3396-3375, 3300, 3241 and 3214 cm -1 were attributed to degenerated  asym (NH 3 ) ,  sym (NH 3 ) of NH 3 in interaction with the LAS of the defective surface,  sym (NH 3 ) of NH 3 in interaction with the LAS of the nondefective surface and to PO-H down ) respectively. The broad band tailing at 2400 cm -1 was due to the reorganization of the PO-H down upon adsorption.

Water effect on acidity

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In situ acidity measurements were achieved at adsorption equilibrium under 1%NH 3 -3%H 2 O-He flow and FTIR spectra are plotted in Figure 9. The absorbance value of the  4 (NH 4 + ) band at 1458 cm -1 was strongly increased evidencing a higher Brønsted acidity formed under water vapor. [START_REF] Buniazet | Unravelling water effects on solid acid catalysts: Case study of TiO 2 /SiO 2 as a catalyst for the dehydration of isobutanol[END_REF][START_REF] Giraud | Experimental Microkinetic Approach of De-NOx by NH 3 on V 2 O 5 /WO 3 /TiO 2 Catalysts. 4. Individual Heats of Adsorption of Adsorbed H 2 O Species on Sulfate-Free and Sulfated TiO 2 Supports[END_REF] As the band at 1640 cm -1 could be attributed to either (NH 3 ) and   ) vibrations and as no  asym (NH 3 ) vibrations around 3300-3400 cm -1 were distinguishable from the broad band at 3420 cm -1 due to (H 2 O) of chemisorbed water, the presence of chemisorbed NH 3 species remained questionable. Note that the shoulder observable at 3220 cm -1 above 40 °C could be attributed to  1 (NH 4 + ) vibrations associated with   NH 4 + ) at 1458 cm -1 . [START_REF] Zecchina | Vibrational Spectroscopy of NH 4 + Ions in Zeolitic Materials: An IR Study[END_REF][START_REF] Plaza | Optical spectroscopy of the NH 4 + internal vibrations in the orthorhombic phase of NH 4 MF 3 (M is Mn, Zn) perovskites[END_REF] Finally, the small band at 3692 cm -1 can correspond to (PO-H up ) and to (H 2 O ads ) as already discussed earlier. 2. Color-coding: grey for calcium, red for oxygen, green for phosphorus, blue for nitrogen and yellow for hydrogen, except surface H up which is marked in white.

On the non-defective surface, the presence of a water molecule does not modify the interaction of NH 3 with the LAS site (structure E), which was still found being the most stable adsorption site with adsorption energy of -95 kJ.mol -1 (Table 2). Noticeably, the P-OH up shifts to a P-OH down during this adsorption despite the absence of a direct interaction with NH 3 , yielding to a predicted disappearance of the vibration at 3691cm -1 but with the appearance of a band at 3712 cm -1 related to the elongation of OH in the chemisorbed water. In other words, while the presence of NH 3 was questionable based on the experimental spectrum, it seems rather likely at distance of defective sites since structure E is more stable than the ones yielding to ammonium following a proton transfer from water or the BAS of the surface. Still, co-adsorbed water made the BAS more acidic.

Indeed, interaction of NH 3 with the PO-H up generated NH 4 + (structure F) with adsorption energy of -46 kJ.mol -1 (Table 2), a process strongly facilitated by the presence of water even if it does not participate directly, thanks to an extra stabilizing H bond. On the totally dehydrated surface, the same reactive adsorption yielded only to adsorption energy of -22 kJ.mol -1 . This could explain the increase of the NH 4 + band absorption in presence of ammonia co-fed with water in comparison with ammonia only. Another source of NH 4 + could be the increase of Ca 2+ vacancies promoted by the presence of water (see section 3.2) since NH 3 easily turns into NH 4 + by capturing the proton of the H 2 PO 4 -group close to the Ca 2+ vacancy (structure G), with strong adsorption energy of -108 kJ.mol -1 (Table 2).

CONCLUSIONS

In this work, acidic properties of BaOP catalyst were investigated combining FTIR spectra achieved at the dehydrated state and under water vapour and DFT calculations. Such catalyst efficient for the dehydration of lactic acid to acrylic acid was previously shown to contain a surface mono/dihydrogen phosphate amorphous layer composed by Ba 2+ cations, P=O and POH groups.

Therefore, the surface layer was simulated by non-defective and defective MPOH structure.

Adsorption of pyridine, lutidine and NH 3 at the surface of BaOP catalyst revealed the presence of moderate LAS and of POH groups without significant protonation for the first two probe molecules. Ammonia was found to mainly interact with the LAS on both the non-defective surface and the defective surface while the PO-H up surface groups are reoriented downward. ML. The corresponding adsorption energies are reported in Table 2. Color-coding: grey for calcium, red for oxygen, green for phosphorus, blue for nitrogen and yellow for hydrogen, except surface H up , which is marked in white.

(

  010) surface. The adsorption of the molecules was performed on the top of the most favorable surface (010) surface using a p(2×2) asymmetric slab made of 16 CaHPO 4 •2H 2 O, where the top surface layers, including 8 CaHPO 4 •2H 2 O, were allowed to relax while the bottom 8 CaHPO 4 •2H 2 O were constrained during the geometry optimization.

Figure 1 .

 1 Figure 1. In situ DRIFT spectra of BaOP at 380 °C under He, 30%H 2 O-He and 30%D 2 O-He. The background corresponds to the spectrum of dehydrated KBr (the R reflectance is equal to I/I KBr ).

with a composition of 4 Figure 2 .

 42 Figure 2. Unit cell of the layered structure of the Brushite, containing Ca atoms (grey), O atoms (red), H atoms (yellow) and P atoms (green).

Figure 3 .

 3 Figure 3. Structures of the (010) surface of CaHPO 4 •nH 2 O with different water coverages, θ(H 2 O)=1 ML, 7/8 ML, 1/8 ML and 0 ML. Only half of the surface structure is shown here for simplicity. The two different types of water molecules are marked as W a and W b highlighted by a black circle in the top left structure, which corresponds to the structure obtained as cleaved from the bulk. The H bond network of W a and W b is shown in light blue dashed lines. At 1ML, 8 water molecules are found. At 7/8ML, one W b water has been removed and the black circle indicates its former position. At 1/8ML, only one water molecule remains (W a type) as highlighted by a black circle. Color-coding:grey for calcium, red for oxygen, green for phosphorus and yellow for hydrogen.

Figure 4 .

 4 Figure 4. Surface energy in eV/Å 2 of Brushite (010) surfaces with various coverages (θ(H 2 O)=1 ML, 7/8 ML, 1/8 ML and 0 ML) in water as function of the temperature and under a pressure in water of 1 atm.

Figure 5 .

 5 Figure 5. Computed structure of the defective surface. The Ca 2+ vacancy is shown with a blue circle, the H down with a pink dashed circle and H up with a pink solid circle. The calculated wavenumbers (after rescaling as mentioned in the 2.3 section) of PO-H) vibrations on the first layer are also shown nearby in cm -1 . Color-coding: grey for

Figure 6 .

 6 Figure 6. Evolution of the FTIR spectra of BaOP after adsorption of lutidine at T amb and desorption under vacuum at increasing temperature.

Figure 7 .

 7 Figure 7. Evolution of the IR bands of NH 3 adsorbed species on pre-treated BaOP catalyst recorded under 2%NH 3 -He flow from 120 to 7 °C. The backgrounds correspond to the spectra recorded after pretreatment under He flow at the same temperatures, mass of the pellet 53 mg.

Figure 8 .

 8 Figure 8. Structures (top view) and computed wavenumbers (in cm -1 ) of the (PO-H) stretching vibrations and of the NH 3 or NH 4 + vibrations after the adsorption of NH 3 on the non-defective dehydrated surface (A and B) and on the defective surface (C and D) at a coverage of θ(NH 3 )=1/4 ML. The corresponding adsorption energies are reported in Table2. Color-coding: grey for calcium, red for oxygen, green for phosphorus, blue for nitrogen and yellow for

Figure 9 .

 9 Figure 9. Evolution of the IR bands of NH 3 adsorbed species on pre-treated BaOP catalyst recorded under 1%NH 3 -3%H 2 O-He flow from 172 to 28 °C. The backgrounds correspond to the spectra recorded after pretreatment under He flow at the same temperatures, mass of the pellet 53 mg.

Figure 10 .

 10 Figure 10. Structures and computed wavenumbers (in cm -1 ) of the (PO-H) stretching vibrations, water vibration and of the NH 3 or NH 4 + vibration after the adsorption of NH 3 on the non-defective dehydrated surface (E and F) and on the defective surface (G). The corresponding adsorption energies are reported inTable 2. Color-coding: grey for

Figure 1 :

 1 FIGURES CAPTIONS

Figure 2 :

 2 Figure 2: Unit cell of the layered structure of the Brushite, containing Ca atoms (grey), O atoms

Figure 3 :

 3 Figure 3: Structures of the (010) surface of CaHPO 4 •nH 2 O with different water coverages, θ

Figure 4 :

 4 Figure 4: Surface energy in eV/Å 2 of Brushite (010) surfaces with various coverages (θ(H 2 O)=1

Figure 5 :Figure 6 :

 56 Figure 5: Computed structure of the defective surface. The Ca 2+ vacancy is shown with a blue

Figure 7 :

 7 Figure 7: Evolution of the IR bands of NH 3 adsorbed species on pre-treated BaOP catalyst

Figure 8 :

 8 Figure 8: Structures (top view) and computed wavenumbers (in cm -1 ) of the (PO-H) stretching

Figure 9 :

 9 Figure 9: Evolution of the IR bands of NH 3 adsorbed species on pre-treated BaOP catalyst

Figure 10 :

 10 Figure 10: Structures and computed wavenumbers (in cm-1) of the (PO-H) stretching vibrations,

Figure 8 and

 8 Figure 10. The adsorption of ammonia is given as a successive adsorption after the adsorption of water on structures E, F and G.

Figure1

  Figure1 297x210mm (300 x 300 DPI)

Figure2

  Figure2 117x132mm (300 x 300 DPI)

Figure 3 199x132mm

 3 Figure 3 199x132mm (142 x 142 DPI)

Figure4

  Figure4 226x165mm (300 x 300 DPI)

Figure5

  Figure5 192x78mm (300 x 300 DPI)

Figure7

  Figure7 297x210mm (300 x 300 DPI)

Figure8

  Figure8 191x135mm (300 x 300 DPI)

Figure9

  Figure9 297x210mm (300 x 300 DPI)

Figure10

  Figure10 204x129mm (300 x 300 DPI)

Table 1 .

 1 Influence of the PO-H orientation in the non-defective dehydrated (010) surface of Brushite on the stability at 380 °C and the computed wavenumbers of PO-H), reported after rescaling as mentioned in the 2.3 section.

		Relative energy	Boltzmann	ν(PO-H up )	ν(PO-H down )
	No.	Surface structure*
		/kJ.mol -1	distribution	/cm -1	/cm -1
	Config 1	0	0.84	\	3170, 3161
	Config 2	11	0.15	3691	3200-3133
	Config 3	47	0.0002	3692	\

* H up shown in white and H down shown in yellow.

Table 2 .

 2 Adsorption energy of water and ammonia on the non-defective and defective surface corresponding to the structures shown in Figure8and Figure10. The adsorption of ammonia is given as a successive adsorption after the adsorption of water on structures E, F and G.

				E ads (H 2 O)	E ads (NH 3 )
	Label	Surface	Structure description
				kJ.mol -1	kJ.mol -1
	A	Non-defective	NH 3 is h-bounded to a P-OH up	-	-48
	B	Non-defective	NH 3 is in interaction with Ca 2+	-	-89
	C	Defective	NH 4 +	-	-118
	D	Defective	NH 3 is in interaction with Ca 2+	-	-84
	E	Non defective	NH 3 is in interaction with Ca 2+	-90	-95
	F	Non-defective	NH 4 +	-90	-46
	G	Defective	NH 4 +	-82	-108

Table 2 .

 2 Color-coding: grey for calcium, red for oxygen, green for phosphorus, blue for nitrogen and yellow for hydrogen, except surface H up , which is marked in white.

	Page 40 of 53

Table 1 :

 1 Influence of the PO-H orientation in the non-defective dehydrated (010) surface of Brushite on the stability at 380 °C and the computed wavenumbers of (PO-H), reported after rescaling as mentioned in the 2.3 section.

Table 2 :

 2 Adsorption energy of water and ammonia on the non-defective and defective surface corresponding to the structures shown in

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ACKNOWLEDGEMENTS

This work was supported by French ANR Program Chimie Durable-Industries-Innovation (CD2I) GALAC, a joint project between IRCELYON, UCCS, LC/ENS-Lyon and Novance company. Laurent Piccolo is acknowledged for access to the IR apparatus founded by the project DINAMIC (reference ANR-2011-BS10-009). ACS Paragon Plus Environment The Journal of Physical Chemistry ACS Paragon Plus Environment The Journal of Physical Chemistry

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Notes

The authors declare no competing financial interest.

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Lucile Marin

Prof. Dr Guillaume Force

Dr Vincent Gandon

Emmanuelle Schulz

Dr David Leboeuf
email: dleboeuf@unistra.fr

Aza-Piancatelli Cyclization as a Platform for the Preparation of Scaffolds of Natural and Bioactive Compounds: Application to the Total Synthesis of Bruceolline D

Abstract:

The aza-Piancatelli cyclization is an appealing transformation for the synthesis of 4-aminocyclopentenone building blocks that could be then converted into bioactive aminocyclopentitols; however, while this approach appears promising, total syntheses of natural products featuring the aza-Piancatelli cyclization as a key step are still unprecedented. Here, we disclose our in-depth investigations regarding this reaction in order to access highly complex structures representing the core of some bioactive molecules. The applicability of the cyclization was highlighted by the 3-step total synthesis of bruceolline D. Thus, we anticipate that this work will lay the ground for further applications in the synthesis.

In the last decade, the aza-Piancatelli cyclization has garnered a growing interest because it enables a rapid and efficient pathway to 4-aminocyclopententenone derivatives from biomass-derived furan feedstocks. [START_REF] Piutti | [END_REF] In general, this reaction represents a direct entry to aminocyclitol scaffolds that can be found in numerous bioactive and natural products (Scheme 1). [2] They include pactamycin (antibiotic, antiprotozoal and antiproliferative properties), [START_REF] Argoudelis | For the isolation of pactamycin[END_REF] jogyamycin (antiprotozoal), [START_REF] Iwatsuki | For the isolation of jogyamycin[END_REF] peramivir (antiviral), [START_REF] Mancuso | For the biological activity of peramivir[END_REF] and trehazolin (glycosidase inhibitor). [START_REF] Ando | For the isolation of trehazolin[END_REF] Furthermore, this reaction may also provide a straightforward access to more complex polycyclic targets such as cephalotaxine, [7] bruceolline D [START_REF] Ouyang | For the isolation of bruceolline D[END_REF] and yuehchukene, [9] which embed a cyclopenta [b]indole unit, or gracilamine. [START_REF] Unver | For the isolation of gracilamine[END_REF] Since the pioneering work of Denisov et al. [11] and Read de Alaniz group, [12] we and others have directed efforts towards the preparation of even more densely functionalized targets using the aza-Piancatelli cyclization as a cornerstone. [START_REF] Reddy | For sequential reactions featuring an aza-Piancatelli cyclization[END_REF] For instance, we implemented new strategies for the synthesis of polycyclic structures such as cyclopenta [b]pyrroles, [14] cyclopenta [b]piperazinones [15] and tetrahydrobenzo [b]azepines [16] by pairing the aza-Piancatelli cyclization with a second key transformation, such as hydroamination, annulation or Michael addition. In turn, the studies related to the influence of the substitution pattern of the furan ring on the reactivity has been underexplored. [17] This issue is particularly critical when considering the compounds mentioned above, which bear a multitude of additional functional groups, including heteroatoms on the cyclopentane ring. As a result, the question remains whether the aza-Piancatelli cyclization could be truly useful for the synthesis of such natural and bioactive molecules. In this context, we disclose herein our recent findings to increase the synthetic utility of this reaction by developing (1) a general synthetic approach to install several key functionalities of pactamycin, jogyamycin and peramivir, (2) a simple method to build the cyclopenta [b]indole moiety, which was highlighted by the total synthesis of bruceolline D, and finally (3) an aza-Piancatelli/Diels-Alder/fragmentation reaction sequence to access frameworks of interest. Besides, we provide an overview on the scope and limitations of this reaction, demonstrating that the presence of heteroatoms on the furan ring does not impede the reactivity.

Scheme 1. Aza-Piancatelli cyclization as a platform for natural and bioactive compounds.

In our initial investigations, we focused on a general route to access the core of pactamycin, jogyamycin and peramivir (Scheme 2). We noticed that all their structures have in common the presence of an oxygen functionality (hydroxymethyl or carboxylic acid) at the same position. In order to perform the aza-Piancatelli cyclization, our first task was to prepare the 2furylcarbinol precursors, which involved the installation of the desired functional groups at the position C3 of the furan ring. We hypothesized that the simplest way to achieve this goal would be to start from the inexpensive 3-furoic acid 1 (~2 €/g). This strategy brings two advantages: (1) the key functional group or its direct precursor would be already present, and ( 2) it is well-documented that the carboxylic acid can serve as a directing group for the regioselective alkylation of furans with aldehydes to rapidly introduce the carbinol moiety. [18] Following this approach, we obtained the 2-furylcarbinol intermediates 3, which were engaged in the next step without further purification. Then, we conducted the selective methylation of the carboxylic acid upon treatment with trimethylsilyldiazomethane to afford the corresponding esters 4 in good to excellent yields over two steps (up to 97%). Finally, the reduction of the ester with LiAlH4 and the subsequent protection of the primary alcohol formed 5 with tertbutyldimethylsilyl chloride (TBSCl) furnished the targeted precursors 6. The protection of this alcohol was required to preclude any direct dehydrative nucleophilic substitution during the reaction.

Preparation of 2-furylcarbinol precursors.

With these precursors in hand, we evaluated their reactivity in the aza-Piancatelli cyclization (Scheme 3). During our previous studies, we developed an efficient promoter system, combining three key components: Ca(NTf2)2 as a catalyst with nBu4NPF6 as an additive in hexafluoroisopropanol (HFIP) as a solvent. [19] This catalytic system allows to work under milder reaction conditions than classic ones, and enables to trigger the reaction with less reactive substrates, including anilines bearing strong electrondonating groups, due to the remarkable ability of HFIP to stabilize carbocation species, to strongly donate hydrogen bonds, in addition to its low nucleophilicity. [20] First, we examined the reaction between 6a and a series of amines (7a-7c). In each case, the 4-aminocyclopentenone was obtained in high yield (up to 95%), with most of the functionalities of jogyamycin being installed. In the same vein, we explored the reactivity of the precursors of peramivir. At the outset, we tested 3b and 3c with p-anisidine 7a under our standard reaction conditions. However, the presence of an electron-drawing group at the C3-position of the furan shutdown the reaction and deactivated completely the alcohol, which remained intact. On the other hand, in the case of the reaction for 6b, the target product 8ba was formed and isolated in 97% yield. With a sight on peramivir, we also conducted the hydrogenation of the cyclopentenone to deliver 9 in 94% yield. Although the identification of the structure of 9 could not be confimred by NMR studies due to the overlap of the signals, NOESY NMR experiments pointed toward the correct arrangement of the substituents (see the Supporting Information for details). Lastly, precursor 6c was subjected to the same reaction conditions with aniline 7d. However, under these conditions, the reaction led only to the decomposition of the substrate. It might be caused by the presence of the benzyl ether that could be deprotected under the reaction conditions. [21] Gratifyingly, switching solvent from HFIP to nitromethane produced compound 8cd in 78% yield, thereby offering an entry point to pactamycin and potential analogues. [22] Scheme 3. Aza-Piancatelli cyclization of 2-furylcarbinols 6a-6c with amines 7a-7d. Structure of 9 tentatively assigned. [a] 6b (1.2 equiv) and 7a (1 equiv).

Another issue that we addressed was the possibility to directly introduce heteroatoms such as oxygen for the synthesis of trehazolin and cephalotaxine or nitrogen for the synthesis of pactamycin and jogyamycin on the furan ring (Scheme 4). To assess such reactivity, we prepared model substrates bearing methoxy or azide functionalities that were easily introduced by direct nucleophilic substitution on 3-bromofuraldehyde, forming the products 6d-e in high yields. Importantly, in contrast with the case mentioned above with a strong electron-withdrawing group, the presence of a strong electron-donating renders the 2furylcarbinol highly reactive and, therefore, not compatible with the standard conditions (with HFIP). In turn, the reaction with nitromethane in place of HFIP provided 8db in 70% yield. Besides, the excellent result obtained for the reaction of azide offers also a plausible alternative to the synthesis of pactamycin. Scheme 4. Influence of the presence of heteroatoms on the aza-Piancatelli cyclization.

Our second objective was to determine whether the aza-Piancatelli could be used to generate cyclopenta [b]indole scaffolds. As a proof of concept, we explored the total synthesis of bruceolline D (Scheme 5). This molecule was isolated in 1994 by the group of Ohmoto from the root wood Brucea mollis Wall. var. tonkinensis Lecomte and is mostly employed in China for the treatment of malaria. [8a] To date, only three total syntheses were described for this molecule. [8c-d] Here, we envisioned an intramolecular aza-Piancatelli cyclization from precursor 11 to deliver bruceolline D. This substrate was rapidly synthesized from commercially available methyl 4-bromofuran-2-carboxylate by addition of methyl Grignard reagent (90% yield) to the ester group and subsequent a Suzuki-Miyaura cross-coupling reaction with 2aminophenylboronic acid 7e (42% yield). However, independent of the solvent employed, the cyclization step did not occur. We only observed the decomposition of 11, which might suggest that the structure is too strained to allow the cyclization. Thus, we changed our approach by performing the aza-Piancatelli cyclization first, which was followed by a Suzuki-Miyaura crosscoupling. First, we studied the cyclization with a model substrate 6f and aniline 7b as a nucleophile. We noticed that the solvent was critical for this transformation because the dehydration of the alcohol occured easily in HFIP or nitromethane, presumably due to the presence of both methyl groups. On the other hand, conducting the reaction in a solvent less prone to H-bonding such as toluene provided the targeted 4-aminocyclopentenone 8fb in 66% yield. [23] Next, we examined the reactivity of 2-furylcarbinol 10 with both 2-aminophenylboronic acid 7e and 2aminophenylboronic acid pinacol ester 7f in toluene. The reaction with the latter formed the cyclization product in higher yield (67% vs 40%). Finally, a Suzuki-Miyaura cross-coupling reaction [24] led to bruceolline D in 48% yield (3 steps, overall yield 29%), demonstrating the synthetic utility of the aza-Piancatelli cyclization.

Scheme 5. Total synthesis of bruceolline D.

Similarly, we sought to exploit the same strategy to access the framework of yuehchukene (Equation 1). While the cyclization reaction worked smoothly, without even requiring the utilization of Ca(NTf2)2 due to the intrinsic acidity of HFIP, all our attempts to achieve the Suzuki-Miyaura cross-coupling reaction failed. At this stage, we do not have specific explanation for this result. Although further optimization studies would be necessary to accomplish this sequence, the approach enabled the construction of the cyclopentane ring of yuehchukene.

Finally, we evaluated the possibility of taking advantage of the alkene moiety of the 4-aminocyclopentenone to implement a Diels-Alder reaction and, thus, build the 5-6-5 aza-tricyclic core of gracilamine in a single step. To fulfil this goal, we prepared an aniline derivative incorporating a furan moiety (7g), which is a well-established diene system for Diels-Alder processes. To our surprise, in contrast with precedent reports, [13f-g] we did not obtain the classic Diels-Alder adduct, forming instead tetrahydro-1Hindene 13 in 90% yield in HFIP (Scheme 6). This reactivity was also extended to 1,3-dienes to furnish the corresponding skeleton 14 in a good yield (65%) under identical reaction conditions. [START_REF]The structural arrangement of compounds 13 and 14 was ascertained by NOESY experiments[END_REF] To account for the formation of such products, we hypothesized that, following the aza-Piancatelli cyclization and the Diels-Alder reaction, the amine might be protonated under the highly acidic reaction conditions and a subsequent Ei elimination would take place. Scheme 6. Aza-Piancatelli/Diels-Alfer/fragmentation reaction sequence.

In conclusion, we have demonstrated that the aza-Piancatelli cyclization could be used successfully to access densely decorated molecules that closely resemble natural and bioactive molecules. It was notably showcased by the concise total synthesis of bruceolline D, which was achieved in 3 steps with 29% overall yield. More importantly, we gained a better insight into the group functional tolerance of this transformation and the influence of solvent on it, which should pave the way for its increasing utilization in total synthesis.

Acknowledgements

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