PROCESS FOR THE SYNTHESIS OF A CARBOXYLIC DIACID

Abstract

The present invention relates to a process for the synthesis of a dicarboxylic acid, having a 5 or 6-membered heteroaromatic compound optionally comprising an allylic or methylstyrenic function, preferably chosen from 5 or 6-membered heteroaromatic compounds and comprising at least one nitrogen atom. Abbreviated figure: no figure in the abstract

Description

Title of the invention: PROCESS FOR THE SYNTHESIS OF A CARBOXYLIC DIACID Technical field

[0001] The present invention relates to a process for the synthesis of a 5- or 6-membered heteroaromatic dicarboxylic acid optionally comprising an allylic or methylstyrenic function, preferably chosen from 5- or 6-membered heteroaromatic compounds and comprising at least one nitrogen atom. State of the art

[0002] MOFs (Metal-Organic Frameworks) are crystalline porous hybrid materials that result from the association of inorganic building blocks (simple polyhedra, clusters, chains or 3D inorganic arrangements) and organic ligands, mainly anionic donors O (polycarboxylates, polyphosphates) or N (imidazolates, polypyrazolates, polytetrazolates), exclusively connected by strong ionocovalent bonds forming a well-defined three-dimensional network. Several thematic reviews have highlighted the developments made in the design, synthesis and potential applications (catalysis, luminescence, magnetism) of these materials. As porous solids, MOFs also appear to be ideal adsorbents for the storage and separation of gases such as carbon dioxide and dihydrogen, due to their large specific surfaces and their adjustable pore sizes and compositions.

[0003] To increase the number of applications of these MOFs, it is important to innovate on the structure, on the nature of the ligands and the metals involved. For large-scale applications, it is necessary to develop rapid, efficient, economical and eco-compatible syntheses (minimum of steps, minimum of waste, minimum of treatment). Among the recently developed MOFs, the combination associating an aluminum salt and 3,5-pyrazoledicarboxylic acid as ligand (MOF "Al-PDA") has demonstrated exceptional properties for the selective and reversible capture of formaldehyde in environmental conditions, the main pollutant of indoor air, but also the production of fresh water from ambient air. This commercial ligand is prepared by oxidation of 3,5-dimethylpyrazole in the presence of potassium permanganate (KMnO4). However, several points of vigilance on the use of solid KMnO4 (CAS 7722-67-7) on an industrial site are known:

[0004] i. KMnO4 is a drug precursor (category 2B). Registration with the MNCPC (National Mission for the Control of Drug Precursors) is required for quantities above 100 kg.

[0005] ii. KMnO4 is an oxidizing solid, it is therefore necessary to control storage (incompatibilities, detection, extinction) and remain vigilant with regard to the significant risk of fire during implementation.

[0006] iii. KMnO4 is a CMR (suspected for reprotoxicity (R)) and with suspected chronic toxicity to the brain. Control of exposures at the workplace is therefore required.

[0007] iv. KMnO4 is very toxic to aquatic organisms. Discharges and waste must be strictly controlled to prevent it from being released into the natural environment.

[0008] v. In the above-mentioned reaction, a large excess of KMnO4 is required. The quantity of waste to be treated is therefore significant and this implies a significant additional production cost.

[0009] In the context of an industrial application of the MOF "Al-PDA", it is therefore necessary to develop a new green and / or more eco-compatible and economical method for the oxidation of 3,5-dimethyl pyrazole (DMP) to 3,5-pyrazoledicarboxylic acid (PDA), and more generally for the oxidation of a 5- or 6-membered heteroaromatic compound, comprising two methyl groups and optionally comprising an allylic or methylstyrenic function, preferably chosen from 5- or 6-membered heteroaromatic compounds and comprising at least one nitrogen atom. Oxidation is one of the most important reactions in organic synthesis. Generally, strong oxidants such as peroxides (such as hydrogen peroxide), peracids (such as meta-chloroperbenzoic acid), inorganic salts (potassium permanganate, potassium dichromate, etc.) and other high-valent reagents (Dess-Martin periodinane, 2-iodoxybenzoic acid, etc.), are very often used for the oxidation of aromatic alkyl derivatives. In the last decade, heterogeneous catalysts based on metal nanoparticles have also been applied in the oxidation of benzyl C(sp3)-H bonds.

[0010] However, these methods may suffer from certain limitations such as stoichiometric amounts of reactants, waste (inorganic salts, organic by-products, etc.), high temperatures (often a prerequisite for the formation of active catalytic species) and / or low selectivity (side reactions), and consequently low conversions. All these concerns limit the practical and industrial applicability of these processes. Finally, one of the most interesting and cheapest oxidants would be oxygen (O2).

[0011] Molecular oxygen as a non-toxic and inexpensive oxidant has already shown many advantages over other oxidants towards more selective, sustainable and environmentally friendly organic transformations. Oxygenation reactions that use molecular oxygen or ambient air as both oxidant and as an oxygen source provide an efficient route for the synthesis of oxygenated compounds, and have been applied in various applications such as the synthesis of compounds of pharmaceutical interest and the late functionalization of complex molecules. Among the processes known in the literature for oxygenation / oxidation in the presence of molecular oxygen, radical reactions are the most represented.

[0012] Photoinduced redox processes using visible light offer a wide variety of catalytic transformations in organic synthesis, open new perspectives in organic chemistry, and constitute an emerging technology in industry. Recent literature amply demonstrates that this technology is expanding, but there are still opportunities to develop new reactions and introduce new substrates into photoredox reactions. Processes for the photoinduced aerobic oxidation of aromatic alkyls, such as toluene, have thus been developed to access alcohols, aldehydes, ketones and carboxylic acids. However, some of these methods suffer from certain limitations such as low selectivity and / or conversion, including the need for UV light irradiation.Among all the photocatalysts described in the literature, polyoxometalates (POMs), and in particular decatungstate salts, are widely used for their versatility and low cost for hydrogen atom transfer (HAT). In particular, they can allow the CH functionalization of benzylic C(sp3)-H bonds under light irradiation. POMs, and more particularly tetrabutylammonium decatungstate (TBADT), have thus recently been used to oxidize alkyl-aromatic derivatives (such as toluene) under light irradiation in the presence of oxygen.

[0013] There is therefore a need to fill the gaps and drawbacks of the prior art and to provide a method for synthesizing dicarboxylic acid ligands, having a 5 or 6-membered heteroaromatic compound, preferably chosen from 5 or 6-membered heteroaromatic compounds and comprising at least one nitrogen atom which is economical, easy to implement, applicable on an industrial scale, while limiting as much as possible its impact on the operator and on the environment.

[0014] Detailed description of the invention. The invention relates to a process for the synthesis of a compound of formula (I): [Chem 1] in which group A represents a 5- or 6-membered heteroaromatic compound optionally comprising an allylic or methylstyrenic function, preferably chosen from 5- or 6-membered heteroaromatic compounds and comprising at least one nitrogen atom, the -COOH groups being linked to group A via CC bonds, said method comprising a step of photoinduced oxidation of a compound of formula (Ia): [Chem 2] in which A is as above, said photoinduced oxidation being carried out in a reaction medium comprising water, at least one water-miscible organic solvent, at least one acid and a dissolved gas, said gas containing dioxygen or consisting of dioxygen, in the presence of a polyoxometalate (POM).

[0015] Advantageously, a reaction medium consists of water, at least one water-miscible organic solvent, at least one organic or inorganic acid, a dissolved gas, said gas containing dioxygen or consisting of dioxygen, and a polyoxometalate (POM).

[0016] It is to the credit of the inventors to have developed a synthesis of diacid ligands making it possible to solve the problems and drawbacks of the state of the art, in particular from the economic, ecological and safety points of view of the performer. The method according to the invention has in particular the advantage of comprising only one step, not requiring complex implementation.

[0017] The compound of formula (I) may be chosen from the following compounds:

[0018] [Chem.3]

[0019] These compounds are marketed and have proven economic interest.

[0020] The term "heteroaromatic compound" means the definition in the sense of IUPAC: that is to say heterocyclic compounds derived from arenes (aromatic compounds) by replacement of one or more methine (-C=) and / or vinylene (-CH=CH-) functions by tri- or divalent heteroatoms, respectively, so as to maintain the continuous electronic system characteristic of aromatic systems and a certain number of out-of-plane electrons corresponding to the Hückel rule (4n+2).

[0021] Advantageously, the compound / precursor of formula (Ia) may be chosen from compounds in which group A represents a group chosen from furan, pyrrole, thiophene, imidazole, pyrazole, triazole, oxazole, isoxazole, thiazole, isothiazole, pyridine, pyrazine, pyrimidine, pyridazine, oxadiazole and thiadiazole groups. In particular, the compound of formula (Ia) may be chosen from compounds of the following formula: [Chem 4] [Chem 5] [Chem 6]

[0022] The term "photoinduced oxidation" means the oxidation of the -CH3 groups by exposing the reaction mixture to a light source in the presence of oxygen or any oxidant and possibly a catalyst.

[0023] Advantageously, the oxidation may be photoinduced by exposing said reaction mixture to a light source with a wavelength greater than or equal to 240 nm and less than or equal to 800 nm, preferably greater than or equal to 320 and less than or equal to 450 nm and more preferably equal to 365 nm. The power of the light source may be greater than or equal to 1 Watt and less than or equal to 100 Watts, preferably greater than or equal to 1W and less than or equal to 40 Watts and more preferably equal to 18 Watts. The duration of exposure to the light source may be greater than or equal to 1 hour and less than or equal to 96 hours, preferably equal to 72 hours.

[0024] Advantageously, the gas may comprise from 1 to 100% by volume of dioxygen, and is preferably chosen from air and pure dioxygen.

[0025] Advantageously, when implementing the method according to the invention, the gas is partially dissolved. A concentration equilibrium is created between the solution and the atmosphere above the reaction medium. The variation in concentration in the reaction medium is relatively small, because the slight overpressure induced by a balloon is sufficient to maintain constant the concentration of dissolved gas, in particular dissolved oxygen in the reaction medium. The maximum pressure exerted by the gas above the reaction medium can be equal to one atmosphere (1 atm).

[0026] For the purposes of the invention, the term polyoxometalate or POM means an anionic cluster based on an oxo complex of transition metals. In the most common examples, the transition metals at the base of polyoxometalates are V(V) (in which case we will speak of polyoxovanadate), Mo(VI) (polyoxomolybdate), W(VI) (polyoxotungState) and Tc(V,VII) (polyoxotechnetate). There are four main types of structures: the Lindqvist structure, the Anderson structure, the Keggin structure and the Dawson structure. Preferably, the POM is of Keggin structure ([XMi2O40] " ) or Dawson structure ([X2Mi8O62]nG, in which, for example, M is chosen from Mo, V and W and X is chosen from Si, P, S and Ge. The polyoxometalate may be chosen from molybdenum, vanadium, tungsten, niobium, tantalum polyoxometalates. Preferably, it is chosen from decatungstate, polyoxomolybdates and polyoxo-vanadates.

[0027] Advantageously, the polyoxometalate is introduced in the form of a salt. Preferably, the salt is chosen from sodium, lithium, alkaline earth and tetraalkylammonium salts, the alkyl comprising from 1 to 10 carbon atoms, preferably from 1 to 4 carbon atoms and more preferably 4 carbon atoms (for example tetrabutylammonium).

[0028] Advantageously, the water-miscible organic solvent is acetonitrile.

[0029] Advantageously, the organic solvent / water volume ratio may be greater than or equal to 2 / 1 and less than or equal to 1 / 2, preferably the volume ratio is equal to 1 / 1.

[0030] Advantageously, the gas comprising dioxygen can be solubilized in the reaction medium by bubbling, preferably for a duration greater than or equal to 1 and less than or equal to 10 minutes, preferably equal to 5 minutes.

[0031] The acid may be chosen from organic acids, inorganic acids, mixtures of organic acids, mixtures of inorganic acids and mixtures of at least one organic acid with at least one inorganic acid.

[0032] Thus, said acid may be chosen from hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, phosphomolybdic acid, citric acid, acetic acid, trifluoroacetic acid, oxalic acid, ethylenediaminetetraacetic acid and mixtures thereof.

[0033] Preferably, the acid concentration in the aqueous portion of the mixture of solvents is less than or equal to 12M, preferably equal to IM.

[0034] Advantageously, when carrying out the oxidation step, the pH of the reaction medium is less than or equal to 7, and is preferably equal to 0.

[0035] Advantageously, the method according to the invention may further comprise a purification step, for example by crystallization.

[0036] The method according to the invention makes it possible to obtain high yields; it is simple and inexpensive to implement.

[0037] The invention also relates to the use of the product obtained according to the process according to the invention in a process for synthesizing MOFs. Brief description of the figures

[0038] [Fig.l] [Fig.l] represents a 1H-NMR spectrum of 3,5-pyrrazole dicarboxylic acid.

[0039] [Fig.2] [Fig.2] represents a 1H-NMR spectrum of 3,5-pyrrazole dicarboxylic acid after purification by crystallization from water.

[0040] [Fig.3] [Fig.3] represents a 1H-NMR spectrum of 3,5-dimethyl pyrazole.

[0041] Example

[0042] The following example illustrates the invention, in a non-limiting manner.

[0043] In a Schlenk tube closed by a septum, 3,5-dimethylpyrazole (48 mg, 0.5 mmol, 1.00 equiv.) and tetrabutylammonium decatungstate (TBADT, 33.2 mg, 0.01 mmol, 0.02 equiv.) are solubilized in a mixture of acetonitrile (1 mL) / aqueous hydrochloric acid solution (1 M HCl, 1 mL). The oxygen is solubilized in the solution by bubbling for 5 minutes. Bubbling was carried out by introducing a needle into the reaction mixture through which the gas escapes and an outlet in the septum to allow bubbling. The reaction mixture thus formed is then topped with an oxygen balloon (to maintain a slight oxygen pressure) and placed under magnetic stirring in front of a violet lamp (wavelength: 365 nm) of 18W for 72 hours. The conversion (92%) to 3,5-pyrrazole dicarboxylic acid (PDA) is calculated by 1H-NMR analysis (see [Fig.l]).

[0044] PDA can be purified by crystallization from water. The reaction crude is dissolved in boiling water. Hydrochloric acid is added until pH = 0 and then the mixture is cooled overnight in a refrigerator to give the product with a yield of 70%. [Fig.2] represents a 1H-NMR spectrum of 3,5-pyrrazole dicarboxylic acid obtained after purification by crystallization from water.

Claims

Claims

1. A process for the synthesis of a compound of formula (I): [Chem 8] in which group A represents a 5- or 6-membered heteroaromatic compound optionally comprising an allylic or methylstyrene function, preferably chosen from 5- or 6-membered heteroaromatic compounds and comprising at least one nitrogen atom, the -COOH groups being linked to group A via CC bonds, said method comprising a step of photoinduced oxidation of a compound of formula Ia: in which A is as above, in a reaction medium comprising water, at least one water-miscible organic solvent, at least one acid and a dissolved gas, said gas containing dioxygen or consisting of dioxygen, in the presence of a polyoxometalate (POM).

2. A method according to claim 1 wherein the compound of formula (Ia) is selected from compounds in which A represents a group selected from furan, pyrrole, thiophene, imidazole, pyrazole, triazole, oxazole, isoxazole, thiazole, isothiazole, pyridine, pyrazine, pyrimidine, pyridazine, oxadiazole and thiadiazole groups.

3. Process according to claim 1 in which the compound of formula (Ia) is chosen from the compounds of the following formula: [Chem 10] [Chem 11] [Chem 13]

4. Method according to any one of the preceding claims, in which the oxidation is photoinduced by exposing said reaction mixture to a light source with a wavelength greater than or equal to 240nm and less than or equal to 800nm, preferably greater than or equal to 320nm and less than or equal to 450nm and more preferably equal to 365nm.

5. Method according to any one of the preceding claims, in which the duration of exposure to the light source is greater than or equal to 1 hour and less than or equal to 96 hours, preferably equal to 72 hours.

6. Method according to any one of the preceding claims, in which the polyoxometalate is chosen from molybdenum, vanadium, tungsten, niobium, tantalum polyoxometalate, preferably chosen from decatungstate, polyoxomolybdates and polyoxovanadates.

7. A method according to any one of the preceding claims, wherein the polyoxometalate is introduced in the form of a salt chosen from sodium, lithium, alkaline earth and tetraalkylammonium salts, the alkyl comprising from 1 to 10 carbon atoms, preferably from 1 to 4 carbon atoms and more preferably 4 carbon atoms.

8. A method according to any preceding claim, wherein the water-miscible organic solvent is acetonitrile.

9. A method according to any one of the preceding claims, wherein the acid is selected from hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, phosphomolybdic acid, citric acid, acetic acid, trifluoroacetic acid, oxalic acid and ethylenediaminetetraacetic acid and mixtures thereof.

10. A method according to any preceding claim, wherein the acid concentration in the aqueous portion of the solvent mixture is less than or equal to 12 M, and is preferably equal to 1 M.

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