Title of Invention	A PROCESS FOR THE SELECTIVE PREPARATION OF A HYDROXYBENZOIC ACID AND A 4-HYDROXYBENZLDEHYDE AND DERIVATIVES THEREOF
Abstract	The present invention relates to a process for preparing a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde and derivatives thereof, characterized in that a mixture of phenolic compounds, one (A) carrying a formyl or hydroxymethyl group in the 2 position; and the other (B) carrying a formyl or hydroxymethyl group in the 4 position, the formyl or hydroxymethyl group in the 2 position of compound (A) is selectively oxidized to a carboxy group and optionally of a hydroxymethyl group of compound (B) in the 4 position is selectively oxidized to a formyl group thus producing a mixture of a 2-hydroxybenzoic acid and a 4- hydroxybenzaldehyde, in the presence of a catalyst based on palladium and/or platinum and a base employed in a quantity such that the ratio between the number of moles of basic agent and the number of moles of phenolic compounds is in the range 2 to 10.2.

Title of Invention

A PROCESS FOR THE SELECTIVE PREPARATION OF A HYDROXYBENZOIC ACID AND A 4-HYDROXYBENZLDEHYDE AND DERIVATIVES THEREOF

Abstract

The present invention relates to a process for preparing a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde and derivatives thereof, characterized in that a mixture of phenolic compounds, one (A) carrying a formyl or hydroxymethyl group in the 2 position; and the other (B) carrying a formyl or hydroxymethyl group in the 4 position, the formyl or hydroxymethyl group in the 2 position of compound (A) is selectively oxidized to a carboxy group and optionally of a hydroxymethyl group of compound (B) in the 4 position is selectively oxidized to a formyl group thus producing a mixture of a 2-hydroxybenzoic acid and a 4- hydroxybenzaldehyde, in the presence of a catalyst based on palladium and/or platinum and a base employed in a quantity such that the ratio between the number of moles of basic agent and the number of moles of phenolic compounds is in the range 2 to 10.2.

Full Text	The present invention concerns a process for the preparation of a 2-hydroxybenzoic acid and of a 4-hydroxybenzaldehyde and derivatives thereof from a mixture of two phenolic compounds, one carrying a fonnyl or hydroxymethyl group in the 2 position, and the other carying a fonnyl or hydroxymethyl group in the 4 povion. The invention also concerns the preparation of a 4 hydroxybenzaldehyde from said mixture. The invention more particularly concerns the preparation of 3~methoxy-4-hydroxybenzaldehyde and of 3-ethoxy-4-hydroxybenzaldehyde, respectively known as "vanillin" and ethylvauilliii". French patent application no. 95/06186 describes a process for the preparation of 4-hydroxyben.zaldehydes. and more particularly of vanillin and of ethylvanillin. The process described consists of preparing a 3-carboxy-4~hydroxybenzaldehyde, then of decarboxylation of said compound, thereby producing 4-hydroxybenzaldehyde. 3-carboxy 4-hydroxyben^aldehyde is prepared according to FR no. 95/06186 from one of the compounds. a?i 1 mixtures thereof, having more particularly die following formulae (Ha), (lib), (Ik) and (lid) shown below: where, in said formulae: M represents a hydrogen atom and/or a metal cation from group (la) or (Ha), or an ammonium cation, Zj, Z> and Z , which may he identical or different, represent a hydrogen atom, an alk;.i, alketiyl, alkoxy, hydroxyalkyl, alkoxyalkyl, cycloalkyl, or aryl radical, a hydroxy group, a nitro group, a halogen atom, or a trifluoromethyl group. The patented process starts with a bi-functional phenolic compound carrying on the aromatic ring two functional groups of the hydroxy groi:;.>, which can be a -CHO group and/or a -CH2OH group, at the ortho and para positions. Firstly, the group in the ortho position is selectively oxidised to the carboxy proup; the group in the para position being at the most oxidised to the formyl group. Thus, after eliminating die carboxy group in the ortho position, 4-hydroxybenzaldehyde ■ is obtained. Vanillin and ethytvanJMn are advantageously obtained according to a selective process but one which is also highly competitive industrially as it uses less expensive reactants. As a result of research, the applicant has found that it is possible a start with a mixture of monosubstitukd phenolic compounds. A process was found, and is object of the present invention, for the preparation of a 2-hydroxybenz.oic acid and a 4-hydroxybenzaldehyde and derivatives thereof, which is characterised in that in a mixture of phenolic compounds, one (A) carrying a formyl or hydroxymethyl group in the 2 position, and the other (B) carrying a formyl or hydroxymethyl group in the 4 position, the formyl or hydroxynvthyj group in the 2 position of compound (A) is selectively oxidised to a carboxy group and optionally a hydroxymethyl group of compound (B) in the 4 position is selectively oxidised to a formyl group, thus producing a mixture of a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde; In a successive step, the 4-hydroxybenzaldehyde is separated from the reaction medium. A first variation of the invention consists of separating the 4-hydroxybenzaldehyde from the 2-hydroxybenzoic acid by pH controlled extraction of aldehyde. Another variation of the invention consists of decarboxylation of only the 2-hydroxybenzoic acid ia the mixture obtained, producing the injih1 phenolic compound which can then be recycled; the 4-hydroxybenzaldehyde is then recovered in a conventional manner. According to the present invention, it was found that when starting with a mixture of phenolic molecules, one carrying hydroxymethyl or formyl groups in the ortho * position of the hydroxy! group and the other carrying a hydroxymethyl or fonuyl group in the para posr.:,on of the hydroxy group, oxidation to a carboxy group preferably takes place on the hydroxymethyl or formyl group carried by the (A) molecule, substituted in the ortho position. The term "phenolic compound" denotes any aromatic compound with an aromatic ring which carries a hydroxy group. In the following description of the present invention, the term "aromatic" denotes the conventional idea of aromaticity as defined in the literature, particularly in "Advanced Organic Chemistry" by Jerry MARCH, 4th edition, John Wiley and Sons, 1992, pp. 40 ff Thus, a mixture (II) of phenolic compounds is used, more particularly with the following formulae: where, in said formulae (IIA) and 110): Yt and Y2, which may be identical or different, represent one of the following groups: - a -CHO group, . a -CHX)H group, Zlf Z2 and Z3, which may be identical or different, represent a 1 ydrogen atom, an atkyl, alkenyl, alkoxy, hydroxyalkyl, alkoxy alky 1, cycl.oal.kyl, or aryl radical, a hydroxy group, a nitro group, a halogen atom7 or a trifluoromethyl group. Particularly suitable compounds for use in. the process of the invention have formulae (IIA) and (113) where Zu Z, and Z3, which may be identical or different, represent one of the following atoms or groups: a hydrogen atom, a linear or branched alkyl radical containing 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, a linear or branch aUcenyl radical containing 2 to 12 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyl or allyl, a lineal' or branched alkoxy radical containing 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, such as a methoxy, ethuvy, propoxy, isopropoxy, tutoxy, isobutoxy, see-butoxy or tert-butoxy radical, a phenyl radical, a halogen atom, preferably a fluorine, chlorine or bromine atom. The present invention does not exclude the presence on the aromatic cycle of substituents of a different nature, provided that they do not interfere with the reactions taking place \A the process of the invention. The present invention is preferably applicable to compounds with the formulae (HA) and (IIB) where Zt represents a hydrogen atom or a linear or branched alkyl or alkoxy radical containing 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms; Z2 and Z3 represent a hydrogen atom; and Yx and Y2 are identical and represent a formyl group or a hydroxymethyl group. Examples of preferred mixtures of phenolic compounds which can be used in the process of the invention are, inter alia: 1 - o-hydrQxymethylphenol and p-hydroxymethylphenol, o-hydroxymeihylguaiacol and p-hydroxymethylguaiacol, o-formylguaiiicol and p-fonnylguaiacol, o-hydroxymethylguetol and p-hydroxymethylguetol, o-formylgue£ol and p-formylguetoL According to the process of the invention, a mixture of phenolic compounds having preferably formula (II) is used as the starting compound. The proportion of each hydroxymethylated or formylated phenolic compound in the mixture depends on how they are prepared. By way of an example, the proportion of each isomer can vary greatly, for example from 10 to 90% by weight, and more preferably between 30 and 70%. The reaction scheme of the process according to the invention is given below to facilitate comprehension of the disclosure of the invention, without in any way binding the scope of the invention to said scheme. where, in said formulae (I) to (IV): Y, and Y2y which may be identical or different, represent one of the following groups: . a -CHO group, . a -CH2OH group, M represents a hydrogen atom and/or a metal cation from group (la) or (Ha) of the periodic classification, or an ammonium cation, Zj, Z2 and Z3 have the meanings given above. In the present text, references are made hereinafter to the periodic classification of the elements as published in the "Bulletin de la Society Chimique de France", no. 1 (1966). In accordance with the process of the invention, the Y, group in position 2 of a phenolic compound (A) having preferably the formula (HA), is selectively oxidised to a carboxy group, and optionally a hydroxy methyl group in the 4 position of a phenolic compound (B) preferably having the formula (IIB), is selectively oxidised to a formyl group. Oxidation is effected by molecular oxygen or a gas containing molecular oxygen, generally in the presence of a catalyst. A preferred oxidation method consists of oxidising a mixture of phenolic compounds having the formula (II) in the liquid phase using molecular oxygen or a gas containing molecular oxygen, in an aqueous medium comprising a basic agent, m the presence of a catalyst based on a metal M, selected from metals from group lb and 8 of the periodic classification of the elements, optionally comprising as an activator metals such as cadmium, cerium, bismuth, lead, silver, tellurium or tin. According to the invention, it was discovered in a totally unexpected manner that if the temperature was increased and the reaction was preferably carried out under pressure, or if the quantity of the base present during oxidation was increased, the formyl and/or hydroxymethyl groups in the 2 position of molecule (A) were selectively oxidised to a earboxy group, and the group in the 4 position of molecule (B) was at the most oxidised to a formyl group. The catalysts used in the process of the invention axe based on a metal from the group lb and 8 of the periodic classification. Examples of catalysts based on a metal from group 8 of the periodic classification are nickel, ruthenium, rhodium, palladium, osmium, iridium, platinum and mixtures thereof. Of the metals from group lb, copper is preferred. Preferably, platinum and/or palladium catalysts are used, taken from all the available forms such as, for example: platinum black, palladium black, platinum oxide, palladium oxide, or the noble metal itself, deposited on different supports such as carbon black, calcium carbonate, activated aluminas and silicas, or equivalent materials. Catalytic masses based on carbon black are particularly suitable. The quantity of catalyst to be used, expressed as the weight of metal M] with respect to that of the mixture of phenolic compounds with formula (II) can vary from 0.01 to 10%, and preferably 0.04 to 2%. Further details of the catalysts can be obtained from US-A-3 673 257, FR-A-2 305 420 and FR-A-2 350 323. ' An activator is preferably used in the catalysts employed in the process of the invention. The activator can be elected from all those mentioned in the above patents. Bismuth, lead and cadmium, in the form of the free metal or as cations, are preferably used. In the latter case, the associated anion is not critical and all derivatives of these metals can be used. Preferably, bismuth metal m derivatives thereof is used An inorganic or organic bismuth derivative of bismuth can be used, in which the bismuth atom has an oxidation number greater than zero, for example 2, 3, 4 or 5. The residue associated with the bismuth is not critical once it satisfies this condition. The activator can be soluble or insoluble in the reaction medium. Illustrative compounds of activators which can be used in the process according to the present invention ate: bismuth oxides; bismuth hydroxides; salts of inorganic hydracids such as: bismuth chloride, bromide, iodide, sulphide, selenide or telluride; salts of inorganic oxyacids such as: bismuth sulphite, sulphate, nitrite, nitrate, phosphite, phosphate, pyrophosphate, carbonate, perchlorate, antimonate, arsenate, selenite or selenate; and salts of oxyacids derived from transition metals such as: bismuth vanadate, mobate, tantalate, chromate, molybdate, tungstate or permanganate. Other suitable compounds are the salts of aliphatic or aromatic organic acids such as: bismuth acetate, propionate, benzoate, salicylate, oxalate, tartrate, lactate, or citrate; and phenates such as: bismuth gallate or pyrogallate. These salts and phenates can also be bismuthyl salts. Other inorganic or organic compounds which can be used are binary compounds of bismuth with elements such as phosphorous or arsenic; heteropolyacids containing bismuth and salts thereof; and aliphatic and aromatic bismuthines are also suitable. Specific examples are: oxides: BiO; Bi203; Bi204; Bi205, hydroxides: Bi(OH)3, salts of inorganic hydracids: bismuth chloride BiCl3; bismuth bromide BiBr3; bismuth iodide Bil3; bismuth sulphide Bi2S3; bismuth selenide Bi2Se3; bismuth telluride Bt2Te3, salts of inorganic oxyacids; basic bismuth sulphite Bi2(SO3VBi203,5H20; neutral bismuth sulphate Bi2(S04)3; bismuthyl sulphate (BiO)HS04; bismuthyl nitrite (BiO)N02,0.5H20; neutral bismuth nitrate Bi(N03)3, 5H20; double nitrate of bismuth and magnesium 2Bi(N03)3>3Mg(N03)2>24H20; bismuthyl nitrate (BiO)N03; bismuth phosphite (Bi2(P03H)3,3H20; neutral bismuth phosphate 3i,P04; bismuth pyrophosphate Bi4(P207)3; bismuthyl carbonate (BiO)2CO3,0,5H:0; neutral bismuth perchlorate Bi(C104)3,5H20; bismuthyl perchlorate (BiO)C104; bismuth antimonate BiSb04; neutral bismuth arsenate Bi(As04)3; bismuthyl arsenate (BiO)As04,5H20; bismuth selenite Bi2(Se03)3, salts of oxyacids derived from transition metals: bismuth vanadate BiV04; bismuth niobate BiNb04; bismuth tantalate BiTa04; neutral bismuth chromate Bi2(Cr04); bismuthyl dichromate [(BiO)2]Cr207; acid bismuthyl chromate H(BiO)Cr04; double chromate of bismuthyl and potassium K(BiO)Cr04; bismuth molybdate Bi2(Mo04)3; bismuth tungstate Bi3(W04)3; double molybdate of bismuth and sodium NaBi(Mo04)2; basic bismuth permanganate Bi202(OH)Mn04, salts of aliphatic or aromatic organic acids: bismuth acetate Bi(C2H302)3; bismuthyl propionate (BiO)C3H502; basic bismuth benzoate CJl5C02Bi((M)2\ bismuthyl salicylate C6H4C02(BiO)(OH); bismuth oxalate (C2C)4)3Bi2; bismuth tartrate Bi2(C4H406)3,6H20; bismuth lactate (C6H905)OBi,7H20; bismuth citrate QH^Bi, phenates: basic bismuth gallate C,H7OjBi; basic bismuth pyrogaltate C6H3(pH)2(OBi)(01I). Other suitable inorganic or organic compounds are: bismuth phosphide BiP; bismuth arsenide Bi3A.s4; sodiumbismuthate NaBi03; bismuth-tliiocyanic acids H2[Bi(BNS)5], H3[Bi(CNwS)6] and sodium and potassium salts thereof; trimethyIbismuthine Bi(CH3)3 , triphenylbismuthine Bi(CeH5)3. The bismuth derivatives * hich are preferably used in the process according to the invention are; bismuth oxides; bismuth hydroxides; bismuth or bismuthyl salts of inorganic hydracids; bismuth or bismuthyl salts of inorganic oxyacids; bismuth or bismuthyl salts of aliphatic or aromatic organic acids; and bismuth or bismuthyl phenates. A particularly suitable gsoup of activators for implementing the process of the invention is constituted by: bismuth oxides Bi203 and Bi204; bismuth hydroxide Bi(OH)3; neutral bismuth sulphate Bi2(S04)3; bismuth chloride BiCl3; bismuth bromide BiBr3; bismuth iodide Bil3; neutral bismuth nitrate Bi(NOs)3,5H20; bismuthyl nitrate BiO(N03); bismuthyl carbonate (BiO)2CO3,0.5H2O); bismuth acetate Bi(C2H302)3; and bismuthyl salicylate C6H4C02(BiO)(OH). The quantity of activator used, expressed as the quantity of metal contained in the activator with respect to the weight of metal M, used, can vary between wide limits. For example, this quantity can be as little at 0.1 % and can reach the weight of metal Mi used, or even exceed it without any problems. More particularly, this quantity is selected so that it provides the oxidation medium with 10 to 900 ppm by weight of activator metal with respect to the mixture of phenolic compounds having the formula (II). In this respect, higher quantities of activator, of the order of 900 to 1500 ppm, can naturally be used, but with no significant additional advantage. * According to the process of the invention, oxidation is carried out in an aqueous medium containing a basic agent in solution, and more particularly ammonium hydroxide, alkaline or alkiline-earth bases, for example hydroxides such as sodium, potassium, lithium and barite hydroxide; alkaline alkanolates such as sodium or potassium methylate, ethylate, isopropylate and tert-butylate, sodium or potassium carbonates or biearbonates, and in general, the salts of alkaline or alkaline-earth bases and weak acids. Thus, the compounds with formula (III) and (IV) can be completely or partially turned into salts depending on the quantity of basic agent used. It follows that in said formulae, M symbolises a hydrogen atom and/or a metal cation from group (la) or (Ila), or an ammonium cation. Sodium or potassium hydroxide is used for reasons of economy. The proportion of inorganic base to be used can be between 0.5 to 10 moles, preferably between 1 and 4 moles, and still mors preferably between 2 and 4 moles of inorganic base per mole of phenolic compounds with formula (II). The concentration by weight of the mixture of phenolic compounds with formula (II) in the liquid phase is usually between 1% and 60%, preferably between 2% and 30%. In practice, one manner of implementing the process consists of bringing the solution comprising the mixture of phenolic compounds with formula (II), the basic agent, the catalyst based on metal Ml( and any activator, into contact wiili molecular oxygen or a gas containing molecular oxygen, for example air, in the pioportions indicated above. Atmospheric pressure can be used, but it is preferable to work under a pressure of between 1 and 20 bar. The mixture is then stirred at the desired temperature until a quantity of oxygen corresponding to that necessary for transforming the hydroxymethyl or formyl group of the compound (A) into a carboxy group, and optionally the hydroxymethyl group of the compound (B) into a formyl group, has been consumed. The temperature of the reaction to be used varies according to the thermal stability of the products to be prepared. In accordance with the invention, the temperature is preferably selected in a temperature range going from 30°C to 200°C, preferably between 40°C and 160°C. The skilled person will adapt the temperature according to the reaction conditions (in particular the quantity of base, nature of the metal M,f pressure and stirring). It has been found, in particular, that the lower the temperature, the- greater the quantity of basic agent which must be used. By way of examples, the preferred conditions for the preferred metals, platinum and palladium, will be given. For platinum, as the temperature selected is between 100°C and 160°C, the quantity of base to be used is advantageously between 1 and 3 moles per mole of phenolic compounds with formula (II). In the case of palladium, the temperature can be selected between 30°C and 200gC, preferably between 30°C and 15G°C, and for this latter range, the quantity of base is preferably 2 to 4 moles per mole of phenolic compounds. Thus, the quantity of base has to be sufficient to oxidise the Yl group, in the ortho position, to a carboxy group. It is determined by the skilled person according to the temperature and the metal selected. At the end of the reaction* which preferably lasts between 30 minutes and 6 hours, 2-hydroxybenzoic acid which can be partially or totally in its salt form, and preferably has formula (III), and a 4-hydroxybenzaldehyde preferably having formula (IV), can be recovered. After any necessary ceding, the catalytic mass is then separated from the reaction medium, for example by filtration. 4-hydroxybenzaldehyde will be recovered from the reaction medium. A first method for treatment of die reaction medium consists of pH controlled extraction of the 4-hydroxybenzaldehyde. To this end, the reaction medium is placed in contact with an organic solvent able to extract aldehyde. A solvent is chosen which is non-miscible with water. Examples of solvents suitable for the invention are, in particular, ketones such as methylethylketone, methylisobutylketone, cylcohexanone; esters such as ethyl acetate, isopropyl acetate, butyl acetate; ether oxides such as diethylether, diisopropylether, methyl-tert-butylether, ethyl-tert-butylether, di-n-butylether; heavy alcohols (containing preferably at least 4 atoms of carbon) such as butanol, hexanol, octanol, cyclohexanol; aliphatic hydrocarbons such as n-pentane, hexane, heptane and cyclohexane; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane; aromatic hydrocarbons such as toluene, xylenes; halogenated aromatic hydrocarbons such as monoehlorobenzene, dichlorobenzene, and mixtures thereof. The reaction medium is thus placed in contact with the reaction solvent, generally at one volume of solvent per volume of medium. 1 or more extractions can be carried out. for example 5, and more preferably 1 to After, or at the same time as the addition of the solvent, the pH is returned to between 4 and 9 by adding a protonic acid of inorganic origin, preferably hydrochloric acid or sulphuric acid such as, for example, trifluoromethanesulphonic acid or methanesulphomc acid. The concentration of the acid is immaterial and commercially available forms are preferably used. The aqueous and organic phases are separated. The aqueous phase comprises 2-hydroxybenzoic acid in salt form. The organic phase comprises 4-hydroxybenzaldehyde which is perhaps then recovered according to conventional techniques, particularly by distillation. The aqueous phase can be treated by carrying out decarboxylation of the 2-hydroxybenzoic acid obtained, the description of which is set out in detail in the second variation, which allows regeneration of the starting phenolic compound which can then be recycled. According to a second variation of the process of the invention, at the end of the reaction producing 2-hydroxybenzoic acid partially or completely in its salt form, and 4-hydroxybenzaldehyde, a decarboxylation reaction is carried out un the reaction medium. This is effected by acidifying the resulting medium by adding a protonic acid of inorganic origin, particularly those previously described, until a pH of less than or equal to 3 is obtained. The reaction medium is heated to a temperature varying, for example, between 120°C and 3509C, and preferably between 150°C and 220°C, The process is preferably carried out under the autogenous pressure of the readmits. Al the end of the reaction, the reaction medium is cooled between 20°C and 80°C. A two-phase medium is obtained, constituted by an organic phase comprising on the one hand 4-hydroxyb;izaldehyde, preferably with formula (IV) and the starting phenolic compound w (h formula (I), and on the other hand a saline aqueous phase The organic and aqueous phases are separated and the 4-hydroxybenzaldehyde is ' recovered from the eiganic phase using conventional separation techniques, for example by extraction using a suitable solvent and then by distillation. Reference may be made to the description of the first variation. In accordance with the; process of the invention, the mixture used is of two phenolic compounds, one carrying a formyl or hydroxymethyl group in the 2 position, and the other carrying a txrmyl or hydroxymethyl group in the 4 position. in said formulae, Mu Zt, Z2 and Z3 have the meanings previously described. The mixtures of phenolic compounds to which the process according to the invention can be applied are generally known products which can be prepared by various methods of organic synthesis. Thus, mixtures with formula (Ila^ and (Ilbj) can be obtained by a process of hydroxymethylation of a phenol by condensation thereof with formaldehyde or a formaldehyde generator in an aqueous phase in the presence of an alkaline or alkaline earth base. More precisely, there is- an unsubstituted phenol on the ortho and para positions with respect to the hydroxy group, with the general formula (I): in which Z,, Z2 and Z} have the meanings previously described. Examples of phenoU with formula (I) which may act as a starting point tor the synthesis of compounds with formula (II) are phenol, pyrocatechin, guaiacol, guetol, 5 3-methoxyphenol, 3-ethoxyphenol, 3-isopropoxy phenol, 3-t-butoxyphenol, m-cresol and o-cresol. r The conditions selected for this hydroxymethylation step are those taught by the prior art listed hereinafter: see in particular H.G. PEER, Rec. Trav. Chim. Pays-CD Bas [Netherlands] IP 825-835 (1960); GB-A-774 696, GB-A-751 845; EP-A-165; J.H. FREEMAN, J. Am. Chem. Soc. 74 6 257-6 260 (1952) and 76 2080-2087 (1954); H.G. PEER, Ret. Trav. Chim. Pays-Bas [Netherlands] 7£ 851-863 (195V); H. EULER et al Arkiv fur Chem. 13 1-7 (1939); P. CLAUS et al Monath. Chem. 103 1178-11293 (1972). Formaldehyde or any formaldehyde generator can be used such as, for example, trioxane or paraformaldehyde used as linear paraformaldehydes of any degree of polymerisation, preferably containing 8 to 100 (CH20) units-Formaldehyde can be used in the form of an aqueous solution of non-critical concentration. It can vary between 20 and 50% by weight; preferably commercial solutions are used which have a concentration of about 30 to 40% by weight. The quantity of formaldehyde expressed as moles of formaldehyde per mole of phenol can vary between wide limits. The formaldehyde/phenol molar ratio can vary between 0.5 and 2 0, and preferably between 0.5 and 1.5. The quantity of base present in the hydroxymethylation medium, expressed as the number of moles of base/phenolic hydroxy group of die phenol to be hydroxymethylated, can vary between broad limits. In general, this ratio, which is variable depending on the nature of the base, can vary between 0.1 and 2, and preferably between 0.5 and 1.1. The base used can be one of those cited above for the oxidation phase. The use of alkaline hydroxides in aqueous solution is particularly convenient. In general, the hydroxymethylation step is carried out at a temperature between 0 and 100°C, preferably between 20 and 70°C. The process is preferably carried out under the pressure which is autogenous for the reactants to avoid any possible losses of paraformaldehyde, which may be gaseous at the temperatures used. Preferably, the reaction is carried out under a controlled atmosphere of inert gases such as nitrogen or noble gases, for example argon. The reaction time can be very variable. It is usually between 30 minutes and 24 hours, preferably between 4 hours and 8 hours. In practice, the reaction is readily carried out by placing the phenol and formaldehyde, and any base, in the equipment, then stirring and heating the reaction mixture to the temperature desired for the time required to complete the reaction. The order of introduction of the reactants is not critical and can thus be different. A mixture of phenolic compounds with formula (Ila^ and (IIbt) is obtained. The compounds with formula (IIa2) and (IIb2) can be prepared by oxidation of hydroxymethylated phenolic compounds with formula (Ila,) and (Ilb^, by oxidation with molecular oxygen or a gas containing molecular oxygen, in an alkaline aqueous phase in the presence of a catalyst based on a metal from group 8 of the periodic classification, preferably platinum and palladium, optionally containing metals such as cadmium, cerium, bismuth, lead, silver, tellurium or tin as an activator, Such processes have been described in US-A-3 673 257, FR-A-2 305 420, and in FR-A-2 350 323. If necessary, the pH ot the solution is brought to a value between 8 and 13 by optional addition of an alkaline or earth-aUkaline base. The optimum pH value depends on the nature of the hydroxymethylated phenols. For example, in die case of a platinum catalyst, the quantity of base to be used is advantageously between 1 and 3 moles per mole of hydroxymethylated r>henolic compounds, and between 0.5 and 2 in the case of a palladium catalyst. The temperature of the oxidation reaction is between 10°C and 60°C, and preferably between 20°C and 50°C. More specifically again, the process according to the present invention is very suitable for the preparation of compounds with formula (IIa2) and (llb2) from phenolic compounds with formula (Ila^ and (Ilbi) resulting from the first step, by molecular oxygen or a gas containing molecular gas in the presence of a catalyst based on a metal from group 8 of the periodic classification, optionally containing a metal such as those urad as an activator, without intermediate separation of the hydroxymethylated phenolic compounds. It appears particularly advantageous for industry to implement the process according to the present invention using compounds with formula (Ha2) and (IIb2) obtained by a two-step process comprising: hydroxymethylation of a phenol in an aqueous medium in the presence of an alkaline or earth-alkaline base, by formaldehyde or a formaldehyde generator, producing a mixture of hydroxymethylated phenolic compounds, one hydroxymethylated in the 2 position, the other in the 4 position, and oxidation, without intermediate separation, of phenolic compounds obtained by molecular oxygen or a gas containing molecular oxygen in an alkaline aqueous phase in the presence of a catalyst based on a metal from group 8 of die periodic classification, with optionally as an activator, a metal such as those previously listed. A supplementary importance of the process of the invention is that it allows the use of mixtures of phenolic compounds directly produced from the preceding steps of hydroxymethylation and optionally of oxidation. As previously mentioned, the process of the invention is particularly suitable for the preparation of vanillin a d of ethylvanillin from a mixture of phenolic compounds obtained by hydroxymefnylation of guaiacol or of guetol. Thus, vanillin can be prepared by selective oxidation of the hydroxymethyl group in the 2 position of compound (A) of a mixture of phenolic compounds, o-hydroxymethylguaiacol (A) and p-hydroxymethylguaiacol (B), to thecarboxy group, and of the hydroxymethyl group of compound (B) in the 4 position to the formyl group, thus producing a mixture of a 2-hydroxy-3-methoxybenzoic acid and vanillin, then of recovering the latter. Another variation consists of selective oxidation of the formyl group in the 2 position of compound (A) of a mixture of phenolic compounds, o-formylguaiacol (A) and p-formylguaiaccl (B), to the carboxy group, thus producing a mixture of a 2-hydroxy-3-methoxybenzoic acid and vanillin, then of recovering the latter. With regard to the preparation of ethylvanillin, in accordance with the invention, the hydroxymethyl group ir. the 2 position of compound (A) of a mixture of phenolic compounds, o-hydrox:.\nethylguaiacoi (A) and p-hydroxymethylguaiacol (B) is selectively oxidised to the carboxy group, and the hydroxymeuiyl group of compound (B) in the 4 position to the formyl group, thus producing a mixture of a 2-hydroxy-3-ethoxybenrioic acid and ethylvanillin, then of recovering the latter. Another variation is i:i the fact that in a mixture of phenolic compounds, o-formylguetol (A) and p-formylguetol (B)> there is selective oxidation of the formyl group in the 2 position of compound (A) to the carboxy group, thus producing a mixture of a 2-hydrox>-3-ethoxybenzoic acid and ethylvaniUto, then of recovering the latter. Examples of implementations of the invention will be given below. These examples are given by way of illustration are in no way limiting. In the examples, the degree of conversion and the yield obtained is defined. The degree of converson (DC) corresponds to the ratio between the number of moles of substrate trans formed and the number of moles of substrate used. The yield (YY) corresponds to the ratio between the number of moles of product formed and the number of moles of substrate used. The yield (YTvanjjlin) corresponds to the ratio between the number of moles of vanillin formed and the number of moles of guaiacol transformed in the sequence. In the examples, the abbreviations are: o-hydroxymethylguaiacol = OMG p-hydroxymethylguaiacol = PMG o-vanillin - 3-methoxy-2-hydroxyhenzaldehyde = OVA p-vanillin = 3-methoxy-4-hydroxybenzaldehyde = PVA o-vanillic acid - 2-hydroxy-3-methylbenzoic acid = AOV p-vanillic acid = 4-hydroxy-3-methy!benzoic acid = APV EXAMPLES Example 1: In this example, a mixture of o-hydroxymethylguaiacol and p-hydroxymethylgua'iacol is oxidised, 2700 g of an aqueous solution containing 28.5 g of o-hydroxymethylguaiacol (OMG) and 33.72 g of p-hydroxymethylguaiacol (PMG) and 148 g of sodium carbonate is introduced into a pressurised 3.91 autoclave provided with an automatic exhaust turbine. This aqueous solution is the product of condensation of guaiacol on fonnol in an aqueous base solution, and prepared as described in the prior art (particularly according to example 4 m US 4 351 962). 0.54 g of bismuth trioxide and 22 g of palladium catalyst, deposited on charcoal in an amount of 3% by weight of metal, is added to this reaction mixture. The reaction mixture is stirred at 1500 rpm and the temperature thereof increased to 45C in nitrogen. A pressure of 3 bar is established and air introduced into the reaction medium at a rate of 300 g/h. The reaction mixture is kept under these conditions for 6 hours. The reaction mixmre is cooled and the pressure returned to atmospheric pressure, then the catalyst is filtered. The reaction medium is then analysed using high performance liquid chromatography. The results obtained are as follows; DC OMG - 100% % YY o-vanillin YYo-vanillic « 93% DC PMC 100% YYp-vanillin ■'- 89% YY p-vanjllic acid = 7% Examination of these results shows that o-vanillin was selectively oxidised, compared to p-vanillin. Example 2 In this example, a mixoire of o-vanillin/p-vanillin is oxidised. 50.26 g of o-vanillin, 49.88 g of p-vanillin, 2003 g of water and 142.5 g of an aqueous solution of 30% by weight of sodium carbonate is introduced into a 3.91 autoclave provided with an automatic exhaust turbine. 22 g of palladium catalyst, deposited on charcoal in an amount of 3 % by weight of metal* and 0.96 g of bismuth trioxide is added to the reaction mixture. The mixture is stirred at 1500 rpm and the temperature thereof is increased to 1406C in nitrogen. A pressure of 13 bar is established and aix introduced at a rate of 300 g/h for 15 minutes. The reaction mixture is pooled and the pressure returned to atmospheric pressure, then the catalyst is filtered. The reaction medium is then analysed using high performance liquid * chromatography. ' The results obtained are is follows: DC o-vanillin « 100% YY o-vanillic acid - 90% DC p-vanillin =* 20% YY p-vanillic acid =16% This clearly demonstrates the selectivity of the oxidation. Example 3 Example 2 is repeated, but using a platinum catalyst. 50.5 g of o-vanillin, 50.1 g of p-vanillin, 2003 g of water and 142.5 g of an aqueous solution of 30% by weight of sodium carbonate is introduced into a 3,91 autoclave provided with an automatic exhaust turbine. 22 g of platinum catalyst, deposited on charcoal in an amount of 5% by weight of metal, and 1.5 g of bismuth trioxide is added to this reaction mixture. The mixture is stirred at 1500 rpm and the temperature thereof increased to 140°C in nitrogen. A pressure of 13 bar is established and air introduced at a rate of 300 g/h for 30 minutes. The reaction mixture is cooled and the pressure returned to atmospheric pressure, then the catalyst is filtered. The reaction medium is then analysed using high performance liquid chromatography. ' ' The results obtained are is follows: DC o-vanillin - 100% YY o-vanillic acid - 89% DC p-vanillin = 15% YY p-vanillic acid = 12% This also clearly demonstrates the selectivity of the oxidation. CLAIMS 1. A process for the preparation of a 2-hydroxybenzoic acid and a 4- hydroxybenzaldehyde and derivatives thereof, characterised in that in a mixture ot phenolic compounds, one (A) carrying a formyl or hydroxymethyl group in the 2 position, and the other (B) carrying a formyl or hydroxymethyl group in the 4 position, the formyl or hydroxymeihyl group in the 2 position of compound (A) is selectively oxidised to a carboxy group and optionally a hydroxymethyl group of compound (B) in the 4 position is selectively oxidised to a formyl group, thus producing a mixture of a 2-hydroxybenzoic acid and a 4-hydroxybemaldehyde. where, in said formulae (IIA) and (IIB): - Yl and Y2. which may be identical or different, represent one of the following groups: . a -CHO group . a -CH2OH group, - Zv Z2 and Z3, which may be identical or different, represent a « hydrogen atom, an alkyl, alkenyl, allcoxy, hydroxyalkyl, alkoxyalkyl, cycloalkyl, or aryl radical, a hydroxy group, a nitro group, a halogen atom, or a trit'luoromethyl group. 3, A process according to one of claims 1 and 2, characterised in that the phenolic compounds have formula (IIA) and (IIB), where Zu Z2 and Z3> which may De identical or different, represent one of the following atoms or groups: , a hydrogen atom, . a linear or branched alkyl radical containing 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, • a linear or branched alkenyl radical containing 2 to 12 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyl or allyl, . a linear or branched alkoxy radical containing 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, such as a methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy or tert-butoxy radicals, • a phenyl radical, . a halogen atom, preferably a fluorine, chlorine or bromine atom. A process axording to one of claims 1 to 3, characterised in that the phenolic compounds have the formulae (IIA) and (IIB), where Zx represents * hydrogen atom or a linear or branched alkoxy radical containing 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms; Z2 and Z3 represent a hydrogen atom; and Yj and Y2 are identical and represent a formyl group or a hydroxymethyl group. A process according to one of claims 1 to 4, characterised in that the mixture of phenolic compounds having formula (II) is: - o-hydroxymethylphenol and p-hydroxymethylphenol, - o-hydroxymethylguaiacol and p-hydroxymethylguaiacol, - o-formylguaiacol and p-formylguaiacol, - o-hydroxymethylguetol and p-hydroxymethylguetol, - o-formyJguetol and p-formylguetol. A process according to one of claims 1 to 5, characterised in that a mixture of phenolic compounds having the formula (II) is oxidised in the liquid phase using molecular oxygen or a gas containing molecular oxygen, in an aqueous medium comprising a basic agent, in the presence of a catalyst based on a metal M, selected from metals from group lb and 8 of the periodic classification of the elements, optionally comprising as an activator metals such as cadmium, cerium, bismuth* lead, silver, tellurium or tin. A process according to claim 6, characterised in that the catalyst is based on copper, nickel, ruthenium, rhodium, palladium, osmium, iridium, platinum or mixtures thereof; said catalyst being preferably based on platinum and/or palladium. A process according to one of claims 6 and 7 characterised in that the platinum and/or palladium catalyst is provided in the form of platinum black, palladium black, platinum oxide, palladium oxide, or the noble metal itself, deposited on different supports such as carbon black, calcium carbonate, activated aluminas and silicas, or equivalent materials preferably carbon black. A process according to one of claims 6 to 8, characterised in that the quantity of catalyst to be used, expressed as the weight of metal Mx with respect to that of the phenolic compound with formula (II) can vary from 0.01 to 10%, preferably from 0,04 to 2%. A process according to one of claims 6 to 9, characterised in that the activator is an inorganic or organic bismuth derivative selected from the group of: bismuth oxides; bismuth hydroxides; bismuth or bismuthyl salts of inorganic hydracids, preferably the chloride, bromide, iodide, sulphide, selenide or telluride; bismuth or bismuthyl salts of inorganic oxyacids, preferably the sulphite, sulphate, nitrite, nitrate, phosphite, phosphate, pyrophosphate, carbonate, perchlorate, antimonate, arsenate, selenite or selenate; bismuth or bismuthyl salts of aliphatic or aromatic organic acids, preferably the acetate, propionate, salicylate, benzoate, oxalate, tartrate, lactate, or citrate; and bismuth or bismuthyl phenates, preferably the gallate or pyrogallate. A process according to claim 10, characterised in that the bismuth derivative is selected from the group of: bismuth oxides; Bi203 and Bi204; bismuthhydroxide Bi(OH)3; bismuth chloride BiCl3; bismuth bromide BiBr3; bismuth iodide Bil3; neutral bismuth sulphate Bi2(S04)3; neutral bismuth nitrate Bi(N03)3,5H20; bismuthyl nitrite (BiO)N02,0.5H20; bismuthyl carbonate (BiO)2CO3,0.5K2O; bismuth acetate Bi(C2H3Oj)3 and bismuthyl salicylate C6H4C02(BiO)(OH). A process according to one of claims 6 to 11, characterised in that the quantity of activator is selected so that the medium contains: at least 0.1 % by weight of metal activator with respect to the weight of metal M{ used, and 10 to 900 ppm by weight of metal Mi with respect to the phenolic compounds with formula (II). A process according to one of claims 6 to 12, characterised in that the oxidation reaction is carried out within a temperature range of 30°C to 200°C, preferably between 40°C and 160°C. A process according to one of claims 6 to 13, characterised in that a pressure of 1 to 20 bar is used. A process according to one of claims 1 to 14, characterised m that the oxidation is carried out in an aqueous medium containing, in solution, a basic agent, preferably sodium or potassium hydroxide, in a quantity such that it represents 0.5 to 10 moles, preferably 2 to 4 moles of inorganic base per mole of phenolic compounds with formula (II). A process according to one of claims 1 to 15, characterised in that the temperature is selected to be between 30°C and 200°C, preferably between 40°C and 160°C. A process according to claim 16, characterised in that when using a platinum catalyst, the temperature is selected to be between 100°C and 160°C; the quantity of base to be used being between 1 and 3 moles per mole of phenolic compounds with formula (II). A process according to claim 16, characterised in that when using a palladium catalyst, the temperature is selected to be between 30 C and 200°C, preferably between 30°C and 150°C; the quantity of base to be used being between 2 and 4 moles per mole of phenolic compounds with formula (II). Process according to claim 1 to 18, characterised in that the 4-hydtoxybenzaldehyde is extracted with controlled pH. Process according to claim 19, characterised in that the extraction solvent is selected from ketones, preferably methylethylketone, methylisobutylketone, cylcohexanone; esters, preferably ethyl acetate, isopropyl acetate, butyl acetate; ether oxides, preferably diethylether, diisopropyle&her, methyl-tert-butylether, ethyl-tert-butylether, di-n-butylether; heavy alcohols, preferably butanol, hexanol, octanol, cyclolxexanol; aliphatic hydrocarbons, preferably n-pentane, hexane, heptane and cyclohexane; halogenated aliphatic hydrocarbons, preferably dichloromethane, dichloroethane; aromatic hydrocarbons, preferably toluene, xylenes; halogenated aromatic hydrocarbons, preferably monochlorobenzene, dichlorobenzene, and mixtures thereof. A process according to claim 19, characterised in that the pH is returned to between 4 and 9 prior to the addition of the solvent or simultaneously by the addition of a protonic acid of inorganic origin, preferably hydrochloric acid or sulphuric acid, and that the aqueous and organic phases are separated. A process according to claims 1 to 21, characterised in that the 2-hydroxybenzoic acid, which can be partially or completely in its salt form, is dccarboxylated. A process according to claim 22, characterised in that the 2-hydroxyber&oic acid has the general formula (II): where, in said formula (II): - M represents a hydrogen atom and/or a metal cation from group (la) or (Ila) or an ammonium cation, - Zu Z2, Z3 have the meanings given in claims 2 to 4. A process according to one of claims 22 and 23, characterised in that said acid is decarboxylated by adding a protonic acid of mineral origin, preferably hydrochloric acid or sulphuric or an organic acid to the reaction medium until a pH less than or equal to 3 is obtained. A process according to one of claims 22 to 24, characterised in that the reaction medium is heated to a temperature between 120aC and 350°C, preferably 150°C to 220°C, and after cooling, the 4-hydroxybenzaldehyde is separated, which preferably has the formula where, in said formulae: - M represents a hydrogen atom and/or a metal cation from group (la) or (Ila) or an ammonium cation, - ZH Z2, Zx have the meanings given in claims 2 to 4. A process according to claim 26, characterised in that a mixture ol formula (Ila) and (IIbt) is obtained by a process of hydroxymcthylation of a phenol by condensation thereof with formaldehyde oi a formaldehyde generator in an aqueous phase in the pir.cnce of an alkaline or earth alkaline base. A process according to claim 27, characterised in that the starting phenol is an unsubstituted phenol at the ortho and para positions with respect to the hydroxy group, with the general formula (I): in which Zlt 2^, Z3 have the meanings given in claims 2 to 4. A process according to claim 28, characterised in that the phenol with formula (I) is phenol, pyrocatechin, guaiacol, guetol, 3-methoxyphenol, 3-ethoxyphenol, 3-isopropoxyphenol, 3-t-butoxyphenol, m-cresol and o- cresol. A process according to one of claims 27, characterised in that formaldehyde or any formaldehyde generator is used, preferably trioxane or paraformaldehyde used as linear paraformaldehydes of any degree of polymerisation, preferably containing 8 to 100 (CH20) units. A process according to claim 27, characterised in that the formaldehyde/phenol molar ratio can vary between 0.5 and 2.0, and preferably between 0.5 and 1.5. A process according to claim 27, characterised in that the quantity of base present in the hydroxymethylation medium, expressed as the number of moles of base/phenolic hydroxy group of the phenol to be hydroxymethylsted, varies between 0.1 and 2, and preferably between 0.5 and 1.1. A process according to claim 27, characterised in that the hydroxymethylation temperature is between 0 and 100°C and preferably between 20 arcl 70 °C. A process according to claim 27, characterised in that the phenol and formaldehyde, and any base, is placed in the equipment, then, while stirring, the reaction mixture is heated to the temperature desired for the time required to obtain a mixture of phenolic compounds with formulae (HaOandaib;;. A process according to claim 27, characterised in that a mixture of compounds wth formulae (Ilaj) and (IIb2) is obtained by oxidation of hydroxymethyiated phenolic compounds with formulae (Ila^ and (Ilbj), by oxidation using molecular oxygen or a gas containing molecular oxygen in an alkaline aqueous phase in the presence of a catalyst based on a metal from group 8 of the periodic classification, preferably platinum and palladium, optionally containing metals such as cadmium, cerium, bismurh, lead, silver, tellurium or tin as an activator A process according to claim 35, characterised in that the pH of the solution is broaght to a value between 8 and 13 by optionally adding an alkaline or earth alkaline base. A process according to claim 35, characterised in that the temperature of the oxidation reaction is between 10°C and 60°C, and preferably between 20°C and 50°C. A process according to claim 26, characterised by the fact that a mixture of phenolic compounds with formulae (HaO and lib) is obtained by a two-step procen;; comprising: hydroxymcthylation of a phenol in an aqueous medium in the presence of ai alkaline or earth-alkaline base by formaldehyde or a formaldehyde generator producing a mixture of hydroxy methylated phenolic compounds, one hydroxymethylated in the 2 position, the other in the 4 position, and oxidation, widiout intermediate separation, of phenolic compounds obtained by molecular oxygen or a gas containing molecular oxygen in an alkaline aqueous phase in the presence of a catalyst based on a metal from group 8 of the periodic classification, possibly as an activator, this metal being such as those previously listed. A process for the preparation of vanillin according to one of claims 1 to 38, characterised in that the hydroxymethyl group in the 2 position of compound (A) of a mixture of phenolic compounds, o-hydroxymethylf;uaiacol (A) and p-hydroxymethylguaiacol (B), is selectively oxidised to a carboxy group, and the hydroxymethyl group of compound (B) is selectively oxidised to a formyl group, thus producing a mixture of a 2-hydroxy-3-methoxybenzoic acid and vanillin, and the latter is then recovered. A process for the preparation of vanillin according to one of claims 1 to 38, characterised in that the formyl group in the 2 position of compound (A) of a mixture of phenolic compounds, o-formylguaiacol (A) and p- formylguaiaco: (B), is selectively oxidised to a carboxy group, thus producing a nvxture of a 2-hydroxy-3-methoxybenzoic acid and vanillin, and the latter n then recovered. 41. A process for the preparation of ethyl vanillin according to one of claims 1 to 38, characterised in that the hydroxymethyl group in the 2 position of compound (A) of a mixture of phenolic compounds, o- hydroxymethylguetol (A) and p-hydroxymethylguetol (B), is selectively oxidised to a carboxy group, and the hydroxymethyl group of compound (B) in the 4 position is selectively oxidised u a formyl group, thus producing a mixture of a 2-hydroxy-3-ethoxybenzoic acid and ethylvanillin, and the latter is then recovered. 42. A process for riie preparation of ethylvanillin according to one of claims 1 to 38, characterised in that the formyl group in the 2 position of compound (A» of a mixture of phenolic compounds, o-foimylguetol (A) and p-formylguetol (B), is oxidised to a carboxy group, thus producing a mixture of a 2-hydroxy-3-ethoxybenzoic acid and ethylvanillin, and the latter is then recovered. 43. Use of the process described in one of claims 1 to 38 for the preparation of vanillin and ethylvanillin. A process for the preparation of a 2-hydroxybenzoic acid substantially as herein described and exemplified.

Full Text

The present invention concerns a process for the preparation of a 2-hydroxybenzoic acid and of a 4-hydroxybenzaldehyde and derivatives thereof from a mixture of two phenolic compounds, one carrying a fonnyl or hydroxymethyl group in the 2 position, and the other carying a fonnyl or hydroxymethyl group in the 4 povion.
The invention also concerns the preparation of a 4 hydroxybenzaldehyde from said mixture.
The invention more particularly concerns the preparation of 3~methoxy-4-hydroxybenzaldehyde and of 3-ethoxy-4-hydroxybenzaldehyde, respectively known as "vanillin" and ethylvauilliii".
French patent application no. 95/06186 describes a process for the preparation of 4-hydroxyben.zaldehydes. and more particularly of vanillin and of ethylvanillin.
The process described consists of preparing a 3-carboxy-4~hydroxybenzaldehyde, then of decarboxylation of said compound, thereby producing 4-hydroxybenzaldehyde.
3-carboxy 4-hydroxyben^aldehyde is prepared according to FR no. 95/06186 from one of the compounds. a?i 1 mixtures thereof, having more particularly die following formulae (Ha), (lib), (Ik) and (lid) shown below:

where, in said formulae:
M represents a hydrogen atom and/or a metal cation from group (la) or (Ha), or an ammonium cation,
Zj, Z> and Z , which may he identical or different, represent a hydrogen atom, an alk;.i, alketiyl, alkoxy, hydroxyalkyl, alkoxyalkyl, cycloalkyl, or aryl radical, a hydroxy group, a nitro group, a halogen atom, or a trifluoromethyl group.
The patented process starts with a bi-functional phenolic compound carrying on the aromatic ring two functional groups of the hydroxy groi:;.>, which can be a -CHO group and/or a -CH2OH group, at the ortho and para positions.
Firstly, the group in the ortho position is selectively oxidised to the carboxy proup; the group in the para position being at the most oxidised to the formyl group. Thus,
after eliminating die carboxy group in the ortho position, 4-hydroxybenzaldehyde
■
is obtained.
Vanillin and ethytvanJMn are advantageously obtained according to a selective process but one which is also highly competitive industrially as it uses less expensive reactants.

As a result of research, the applicant has found that it is possible a start with a mixture of monosubstitukd phenolic compounds.
A process was found, and is object of the present invention, for the preparation of a 2-hydroxybenz.oic acid and a 4-hydroxybenzaldehyde and derivatives thereof, which is characterised in that in a mixture of phenolic compounds, one (A) carrying a formyl or hydroxymethyl group in the 2 position, and the other (B) carrying a formyl or hydroxymethyl group in the 4 position, the formyl or hydroxynvthyj group in the 2 position of compound (A) is selectively oxidised to a carboxy group and optionally a hydroxymethyl group of compound (B) in the 4 position is selectively oxidised to a formyl group, thus producing a mixture of a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde;
In a successive step, the 4-hydroxybenzaldehyde is separated from the reaction medium.
A first variation of the invention consists of separating the 4-hydroxybenzaldehyde from the 2-hydroxybenzoic acid by pH controlled extraction of aldehyde.
Another variation of the invention consists of decarboxylation of only the 2-hydroxybenzoic acid ia the mixture obtained, producing the injih1 phenolic compound which can then be recycled; the 4-hydroxybenzaldehyde is then recovered in a conventional manner.
According to the present invention, it was found that when starting with a mixture of phenolic molecules, one carrying hydroxymethyl or formyl groups in the ortho * position of the hydroxy! group and the other carrying a hydroxymethyl or fonuyl group in the para posr.:,on of the hydroxy group, oxidation to a carboxy group preferably takes place on the hydroxymethyl or formyl group carried by the (A) molecule, substituted in the ortho position.

The term "phenolic compound" denotes any aromatic compound with an aromatic ring which carries a hydroxy group.
In the following description of the present invention, the term "aromatic" denotes the conventional idea of aromaticity as defined in the literature, particularly in "Advanced Organic Chemistry" by Jerry MARCH, 4th edition, John Wiley and Sons, 1992, pp. 40 ff
Thus, a mixture (II) of phenolic compounds is used, more particularly with the following formulae:

where, in said formulae (IIA) and 110):
Yt and Y2, which may be identical or different, represent one of the following groups: - a -CHO group, . a -CHX)H group,
Zlf Z2 and Z3, which may be identical or different, represent a 1 ydrogen atom, an atkyl, alkenyl, alkoxy, hydroxyalkyl, alkoxy alky 1, cycl.oal.kyl, or aryl radical, a hydroxy group, a nitro group, a halogen atom7 or a trifluoromethyl group.
Particularly suitable compounds for use in. the process of the invention have formulae (IIA) and (113) where Zu Z, and Z3, which may be identical or different,

represent one of the following atoms or groups: a hydrogen atom,
a linear or branched alkyl radical containing 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl,
a linear or branch aUcenyl radical containing 2 to 12 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyl or allyl, a lineal' or branched alkoxy radical containing 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, such as a methoxy, ethuvy, propoxy, isopropoxy, tutoxy, isobutoxy, see-butoxy or tert-butoxy radical, a phenyl radical, a halogen atom, preferably a fluorine, chlorine or bromine atom.
The present invention does not exclude the presence on the aromatic cycle of substituents of a different nature, provided that they do not interfere with the reactions taking place \A the process of the invention.
The present invention is preferably applicable to compounds with the formulae (HA) and (IIB) where Zt represents a hydrogen atom or a linear or branched alkyl or alkoxy radical containing 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms; Z2 and Z3 represent a hydrogen atom; and Yx and Y2 are identical and represent a formyl group or a hydroxymethyl group.
Examples of preferred mixtures of phenolic compounds which can be used in the process of the invention are, inter alia:
1 - o-hydrQxymethylphenol and p-hydroxymethylphenol,
o-hydroxymeihylguaiacol and p-hydroxymethylguaiacol, o-formylguaiiicol and p-fonnylguaiacol, o-hydroxymethylguetol and p-hydroxymethylguetol, o-formylgue£ol and p-formylguetoL

According to the process of the invention, a mixture of phenolic compounds having preferably formula (II) is used as the starting compound.
The proportion of each hydroxymethylated or formylated phenolic compound in the mixture depends on how they are prepared.
By way of an example, the proportion of each isomer can vary greatly, for example from 10 to 90% by weight, and more preferably between 30 and 70%.
The reaction scheme of the process according to the invention is given below to facilitate comprehension of the disclosure of the invention, without in any way binding the scope of the invention to said scheme.

where, in said formulae (I) to (IV):
Y, and Y2y which may be identical or different, represent one of the
following groups:
. a -CHO group,
. a -CH2OH group,
M represents a hydrogen atom and/or a metal cation from group (la) or
(Ha) of the periodic classification, or an ammonium cation,
Zj, Z2 and Z3 have the meanings given above.
In the present text, references are made hereinafter to the periodic classification of the elements as published in the "Bulletin de la Society Chimique de France", no. 1 (1966).
In accordance with the process of the invention, the Y, group in position 2 of a phenolic compound (A) having preferably the formula (HA), is selectively oxidised to a carboxy group, and optionally a hydroxy methyl group in the 4 position of a phenolic compound (B) preferably having the formula (IIB), is selectively oxidised to a formyl group.
Oxidation is effected by molecular oxygen or a gas containing molecular oxygen, generally in the presence of a catalyst.
A preferred oxidation method consists of oxidising a mixture of phenolic compounds having the formula (II) in the liquid phase using molecular oxygen or a gas containing molecular oxygen, in an aqueous medium comprising a basic agent, m the presence of a catalyst based on a metal M, selected from metals from group lb and 8 of the periodic classification of the elements, optionally comprising as an activator metals such as cadmium, cerium, bismuth, lead, silver, tellurium or tin.
According to the invention, it was discovered in a totally unexpected manner that if the temperature was increased and the reaction was preferably carried out under

pressure, or if the quantity of the base present during oxidation was increased, the formyl and/or hydroxymethyl groups in the 2 position of molecule (A) were selectively oxidised to a earboxy group, and the group in the 4 position of molecule (B) was at the most oxidised to a formyl group.
The catalysts used in the process of the invention axe based on a metal from the group lb and 8 of the periodic classification.
Examples of catalysts based on a metal from group 8 of the periodic classification are nickel, ruthenium, rhodium, palladium, osmium, iridium, platinum and mixtures thereof. Of the metals from group lb, copper is preferred.
Preferably, platinum and/or palladium catalysts are used, taken from all the available forms such as, for example: platinum black, palladium black, platinum oxide, palladium oxide, or the noble metal itself, deposited on different supports such as carbon black, calcium carbonate, activated aluminas and silicas, or equivalent materials. Catalytic masses based on carbon black are particularly suitable.
The quantity of catalyst to be used, expressed as the weight of metal M] with respect to that of the mixture of phenolic compounds with formula (II) can vary from 0.01 to 10%, and preferably 0.04 to 2%.
Further details of the catalysts can be obtained from US-A-3 673 257, FR-A-2 305 420 and FR-A-2 350 323.
' An activator is preferably used in the catalysts employed in the process of the invention.
The activator can be elected from all those mentioned in the above patents. Bismuth, lead and cadmium, in the form of the free metal or as cations, are

preferably used. In the latter case, the associated anion is not critical and all derivatives of these metals can be used. Preferably, bismuth metal m derivatives thereof is used
An inorganic or organic bismuth derivative of bismuth can be used, in which the bismuth atom has an oxidation number greater than zero, for example 2, 3, 4 or 5. The residue associated with the bismuth is not critical once it satisfies this condition. The activator can be soluble or insoluble in the reaction medium.
Illustrative compounds of activators which can be used in the process according to the present invention ate: bismuth oxides; bismuth hydroxides; salts of inorganic hydracids such as: bismuth chloride, bromide, iodide, sulphide, selenide or telluride; salts of inorganic oxyacids such as: bismuth sulphite, sulphate, nitrite, nitrate, phosphite, phosphate, pyrophosphate, carbonate, perchlorate, antimonate, arsenate, selenite or selenate; and salts of oxyacids derived from transition metals such as: bismuth vanadate, mobate, tantalate, chromate, molybdate, tungstate or permanganate.
Other suitable compounds are the salts of aliphatic or aromatic organic acids such as: bismuth acetate, propionate, benzoate, salicylate, oxalate, tartrate, lactate, or citrate; and phenates such as: bismuth gallate or pyrogallate. These salts and phenates can also be bismuthyl salts.
Other inorganic or organic compounds which can be used are binary compounds of bismuth with elements such as phosphorous or arsenic; heteropolyacids containing bismuth and salts thereof; and aliphatic and aromatic bismuthines are also suitable.
Specific examples are:
oxides: BiO; Bi203; Bi204; Bi205,
hydroxides: Bi(OH)3,
salts of inorganic hydracids: bismuth chloride BiCl3; bismuth bromide

BiBr3; bismuth iodide Bil3; bismuth sulphide Bi2S3; bismuth selenide
Bi2Se3; bismuth telluride Bt2Te3,
salts of inorganic oxyacids; basic bismuth sulphite Bi2(SO3VBi203,5H20;
neutral bismuth sulphate Bi2(S04)3; bismuthyl sulphate (BiO)HS04;
bismuthyl nitrite (BiO)N02,0.5H20; neutral bismuth nitrate
Bi(N03)3, 5H20; double nitrate of bismuth and magnesium
2Bi(N03)3>3Mg(N03)2>24H20; bismuthyl nitrate (BiO)N03; bismuth
phosphite (Bi2(P03H)3,3H20; neutral bismuth phosphate 3i,P04; bismuth
pyrophosphate Bi4(P207)3; bismuthyl carbonate (BiO)2CO3,0,5H:0;
neutral bismuth perchlorate Bi(C104)3,5H20; bismuthyl perchlorate
(BiO)C104; bismuth antimonate BiSb04; neutral bismuth arsenate
Bi(As04)3; bismuthyl arsenate (BiO)As04,5H20; bismuth selenite
Bi2(Se03)3,
salts of oxyacids derived from transition metals: bismuth vanadate
BiV04; bismuth niobate BiNb04; bismuth tantalate BiTa04; neutral
bismuth chromate Bi2(Cr04); bismuthyl dichromate [(BiO)2]Cr207; acid
bismuthyl chromate H(BiO)Cr04; double chromate of bismuthyl and
potassium K(BiO)Cr04; bismuth molybdate Bi2(Mo04)3; bismuth
tungstate Bi3(W04)3; double molybdate of bismuth and sodium
NaBi(Mo04)2; basic bismuth permanganate Bi202(OH)Mn04,
salts of aliphatic or aromatic organic acids: bismuth acetate Bi(C2H302)3;
bismuthyl propionate (BiO)C3H502; basic bismuth benzoate
CJl5C02Bi((M)2\ bismuthyl salicylate C6H4C02(BiO)(OH); bismuth
oxalate (C2C)4)3Bi2; bismuth tartrate Bi2(C4H406)3,6H20; bismuth lactate
(C6H905)OBi,7H20; bismuth citrate QH^Bi,
phenates: basic bismuth gallate C,H7OjBi; basic bismuth pyrogaltate
C6H3(pH)2(OBi)(01I).
Other suitable inorganic or organic compounds are: bismuth phosphide BiP; bismuth arsenide Bi3A.s4; sodiumbismuthate NaBi03; bismuth-tliiocyanic acids H2[Bi(BNS)5], H3[Bi(CNwS)6] and sodium and potassium salts thereof; trimethyIbismuthine Bi(CH3)3 ,

triphenylbismuthine Bi(CeH5)3.
The bismuth derivatives * hich are preferably used in the process according to the invention are; bismuth oxides; bismuth hydroxides; bismuth or bismuthyl salts of inorganic hydracids; bismuth or bismuthyl salts of inorganic oxyacids; bismuth or bismuthyl salts of aliphatic or aromatic organic acids; and bismuth or bismuthyl phenates.
A particularly suitable gsoup of activators for implementing the process of the invention is constituted by: bismuth oxides Bi203 and Bi204; bismuth hydroxide Bi(OH)3; neutral bismuth sulphate Bi2(S04)3; bismuth chloride BiCl3; bismuth bromide BiBr3; bismuth iodide Bil3; neutral bismuth nitrate Bi(NOs)3,5H20; bismuthyl nitrate BiO(N03); bismuthyl carbonate (BiO)2CO3,0.5H2O); bismuth acetate Bi(C2H302)3; and bismuthyl salicylate C6H4C02(BiO)(OH).
The quantity of activator used, expressed as the quantity of metal contained in the activator with respect to the weight of metal M, used, can vary between wide limits. For example, this quantity can be as little at 0.1 % and can reach the weight of metal Mi used, or even exceed it without any problems.
More particularly, this quantity is selected so that it provides the oxidation medium with 10 to 900 ppm by weight of activator metal with respect to the mixture of phenolic compounds having the formula (II). In this respect, higher quantities of activator, of the order of 900 to 1500 ppm, can naturally be used, but with no significant additional advantage.
* According to the process of the invention, oxidation is carried out in an aqueous medium containing a basic agent in solution, and more particularly ammonium hydroxide, alkaline or alkiline-earth bases, for example hydroxides such as sodium, potassium, lithium and barite hydroxide; alkaline alkanolates such as sodium or potassium methylate, ethylate, isopropylate and tert-butylate, sodium or potassium

carbonates or biearbonates, and in general, the salts of alkaline or alkaline-earth bases and weak acids.
Thus, the compounds with formula (III) and (IV) can be completely or partially turned into salts depending on the quantity of basic agent used. It follows that in said formulae, M symbolises a hydrogen atom and/or a metal cation from group (la) or (Ila), or an ammonium cation.
Sodium or potassium hydroxide is used for reasons of economy. The proportion of inorganic base to be used can be between 0.5 to 10 moles, preferably between 1 and 4 moles, and still mors preferably between 2 and 4 moles of inorganic base per mole of phenolic compounds with formula (II).
The concentration by weight of the mixture of phenolic compounds with formula (II) in the liquid phase is usually between 1% and 60%, preferably between 2% and 30%.
In practice, one manner of implementing the process consists of bringing the solution comprising the mixture of phenolic compounds with formula (II), the basic agent, the catalyst based on metal Ml( and any activator, into contact wiili molecular oxygen or a gas containing molecular oxygen, for example air, in the pioportions indicated above.
Atmospheric pressure can be used, but it is preferable to work under a pressure of between 1 and 20 bar.
The mixture is then stirred at the desired temperature until a quantity of oxygen corresponding to that necessary for transforming the hydroxymethyl or formyl group of the compound (A) into a carboxy group, and optionally the hydroxymethyl group of the compound (B) into a formyl group, has been consumed.

The temperature of the reaction to be used varies according to the thermal stability of the products to be prepared.
In accordance with the invention, the temperature is preferably selected in a temperature range going from 30°C to 200°C, preferably between 40°C and 160°C.
The skilled person will adapt the temperature according to the reaction conditions (in particular the quantity of base, nature of the metal M,f pressure and stirring). It has been found, in particular, that the lower the temperature, the- greater the quantity of basic agent which must be used.
By way of examples, the preferred conditions for the preferred metals, platinum and palladium, will be given. For platinum, as the temperature selected is between 100°C and 160°C, the quantity of base to be used is advantageously between 1 and 3 moles per mole of phenolic compounds with formula (II). In the case of palladium, the temperature can be selected between 30°C and 200gC, preferably between 30°C and 15G°C, and for this latter range, the quantity of base is preferably 2 to 4 moles per mole of phenolic compounds.
Thus, the quantity of base has to be sufficient to oxidise the Yl group, in the ortho position, to a carboxy group. It is determined by the skilled person according to the temperature and the metal selected.
At the end of the reaction* which preferably lasts between 30 minutes and 6 hours, 2-hydroxybenzoic acid which can be partially or totally in its salt form, and preferably has formula (III), and a 4-hydroxybenzaldehyde preferably having formula (IV), can be recovered.
After any necessary ceding, the catalytic mass is then separated from the reaction medium, for example by filtration.

4-hydroxybenzaldehyde will be recovered from the reaction medium.
A first method for treatment of die reaction medium consists of pH controlled extraction of the 4-hydroxybenzaldehyde.
To this end, the reaction medium is placed in contact with an organic solvent able to extract aldehyde.
A solvent is chosen which is non-miscible with water.
Examples of solvents suitable for the invention are, in particular, ketones such as methylethylketone, methylisobutylketone, cylcohexanone; esters such as ethyl acetate, isopropyl acetate, butyl acetate; ether oxides such as diethylether, diisopropylether, methyl-tert-butylether, ethyl-tert-butylether, di-n-butylether; heavy alcohols (containing preferably at least 4 atoms of carbon) such as butanol, hexanol, octanol, cyclohexanol; aliphatic hydrocarbons such as n-pentane, hexane, heptane and cyclohexane; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane; aromatic hydrocarbons such as toluene, xylenes; halogenated aromatic hydrocarbons such as monoehlorobenzene, dichlorobenzene, and mixtures thereof.
The reaction medium is thus placed in contact with the reaction solvent, generally at one volume of solvent per volume of medium.
1 or more extractions can be carried out. for example 5, and more preferably 1 to
After, or at the same time as the addition of the solvent, the pH is returned to between 4 and 9 by adding a protonic acid of inorganic origin, preferably hydrochloric acid or sulphuric acid such as, for example, trifluoromethanesulphonic acid or methanesulphomc acid. The concentration of the acid is immaterial and

commercially available forms are preferably used.
The aqueous and organic phases are separated.
The aqueous phase comprises 2-hydroxybenzoic acid in salt form.
The organic phase comprises 4-hydroxybenzaldehyde which is perhaps then recovered according to conventional techniques, particularly by distillation.
The aqueous phase can be treated by carrying out decarboxylation of the 2-hydroxybenzoic acid obtained, the description of which is set out in detail in the second variation, which allows regeneration of the starting phenolic compound which can then be recycled.
According to a second variation of the process of the invention, at the end of the reaction producing 2-hydroxybenzoic acid partially or completely in its salt form, and 4-hydroxybenzaldehyde, a decarboxylation reaction is carried out un the reaction medium.
This is effected by acidifying the resulting medium by adding a protonic acid of inorganic origin, particularly those previously described, until a pH of less than or equal to 3 is obtained.
The reaction medium is heated to a temperature varying, for example, between 120°C and 3509C, and preferably between 150°C and 220°C,
The process is preferably carried out under the autogenous pressure of the readmits.
Al the end of the reaction, the reaction medium is cooled between 20°C and 80°C.
A two-phase medium is obtained, constituted by an organic phase comprising on the

one hand 4-hydroxyb;izaldehyde, preferably with formula (IV) and the starting phenolic compound w (h formula (I), and on the other hand a saline aqueous phase
The organic and aqueous phases are separated and the 4-hydroxybenzaldehyde is ' recovered from the eiganic phase using conventional separation techniques, for example by extraction using a suitable solvent and then by distillation. Reference may be made to the description of the first variation.
In accordance with the; process of the invention, the mixture used is of two phenolic compounds, one carrying a formyl or hydroxymethyl group in the 2 position, and the other carrying a txrmyl or hydroxymethyl group in the 4 position.

in said formulae, Mu Zt, Z2 and Z3 have the meanings previously described.
The mixtures of phenolic compounds to which the process according to the invention can be applied are generally known products which can be prepared by various methods of organic synthesis.
Thus, mixtures with formula (Ila^ and (Ilbj) can be obtained by a process of hydroxymethylation of a phenol by condensation thereof with formaldehyde or a formaldehyde generator in an aqueous phase in the presence of an alkaline or alkaline earth base.
More precisely, there is- an unsubstituted phenol on the ortho and para positions with respect to the hydroxy group, with the general formula (I):

in which Z,, Z2 and Z} have the meanings previously described.
Examples of phenoU with formula (I) which may act as a starting point tor the synthesis of compounds with formula (II) are phenol, pyrocatechin, guaiacol, guetol, 5 3-methoxyphenol, 3-ethoxyphenol, 3-isopropoxy phenol, 3-t-butoxyphenol, m-cresol and o-cresol.
r
The conditions selected for this hydroxymethylation step are those taught by the prior art listed hereinafter: see in particular H.G. PEER, Rec. Trav. Chim. Pays-CD Bas [Netherlands] IP 825-835 (1960); GB-A-774 696, GB-A-751 845; EP-A-165; J.H. FREEMAN, J. Am. Chem. Soc. 74 6 257-6 260 (1952) and 76 2080-2087

(1954); H.G. PEER, Ret. Trav. Chim. Pays-Bas [Netherlands] 7£ 851-863 (195V); H. EULER et al Arkiv fur Chem. 13 1-7 (1939); P. CLAUS et al Monath. Chem. 103 1178-11293 (1972).
Formaldehyde or any formaldehyde generator can be used such as, for example, trioxane or paraformaldehyde used as linear paraformaldehydes of any degree of polymerisation, preferably containing 8 to 100 (CH20) units-Formaldehyde can be used in the form of an aqueous solution of non-critical concentration. It can vary between 20 and 50% by weight; preferably commercial solutions are used which have a concentration of about 30 to 40% by weight.
The quantity of formaldehyde expressed as moles of formaldehyde per mole of phenol can vary between wide limits. The formaldehyde/phenol molar ratio can vary between 0.5 and 2 0, and preferably between 0.5 and 1.5.
The quantity of base present in the hydroxymethylation medium, expressed as the number of moles of base/phenolic hydroxy group of die phenol to be hydroxymethylated, can vary between broad limits. In general, this ratio, which is variable depending on the nature of the base, can vary between 0.1 and 2, and preferably between 0.5 and 1.1. The base used can be one of those cited above for the oxidation phase. The use of alkaline hydroxides in aqueous solution is particularly convenient.
In general, the hydroxymethylation step is carried out at a temperature between 0 and 100°C, preferably between 20 and 70°C.
The process is preferably carried out under the pressure which is autogenous for the reactants to avoid any possible losses of paraformaldehyde, which may be gaseous at the temperatures used.

Preferably, the reaction is carried out under a controlled atmosphere of inert gases such as nitrogen or noble gases, for example argon.
The reaction time can be very variable. It is usually between 30 minutes and 24 hours, preferably between 4 hours and 8 hours.
In practice, the reaction is readily carried out by placing the phenol and formaldehyde, and any base, in the equipment, then stirring and heating the reaction mixture to the temperature desired for the time required to complete the reaction.
The order of introduction of the reactants is not critical and can thus be different.
A mixture of phenolic compounds with formula (Ila^ and (IIbt) is obtained.
The compounds with formula (IIa2) and (IIb2) can be prepared by oxidation of hydroxymethylated phenolic compounds with formula (Ila,) and (Ilb^, by oxidation with molecular oxygen or a gas containing molecular oxygen, in an alkaline aqueous phase in the presence of a catalyst based on a metal from group 8 of the periodic classification, preferably platinum and palladium, optionally containing metals such as cadmium, cerium, bismuth, lead, silver, tellurium or tin as an activator, Such processes have been described in US-A-3 673 257, FR-A-2 305 420, and in FR-A-2 350 323.
If necessary, the pH ot the solution is brought to a value between 8 and 13 by optional addition of an alkaline or earth-aUkaline base. The optimum pH value depends on the nature of the hydroxymethylated phenols.
For example, in die case of a platinum catalyst, the quantity of base to be used is advantageously between 1 and 3 moles per mole of hydroxymethylated r>henolic compounds, and between 0.5 and 2 in the case of a palladium catalyst.

The temperature of the oxidation reaction is between 10°C and 60°C, and preferably between 20°C and 50°C.
More specifically again, the process according to the present invention is very suitable for the preparation of compounds with formula (IIa2) and (llb2) from phenolic compounds with formula (Ila^ and (Ilbi) resulting from the first step, by molecular oxygen or a gas containing molecular gas in the presence of a catalyst based on a metal from group 8 of the periodic classification, optionally containing a metal such as those urad as an activator, without intermediate separation of the hydroxymethylated phenolic compounds.
It appears particularly advantageous for industry to implement the process according to the present invention using compounds with formula (Ha2) and (IIb2) obtained by a two-step process comprising:
hydroxymethylation of a phenol in an aqueous medium in the presence of an alkaline or earth-alkaline base, by formaldehyde or a formaldehyde generator, producing a mixture of hydroxymethylated phenolic compounds, one hydroxymethylated in the 2 position, the other in the 4 position,
and oxidation, without intermediate separation, of phenolic compounds obtained by molecular oxygen or a gas containing molecular oxygen in an alkaline aqueous phase in the presence of a catalyst based on a metal from group 8 of die periodic classification, with optionally as an activator, a metal such as those previously listed.
A supplementary importance of the process of the invention is that it allows the use of mixtures of phenolic compounds directly produced from the preceding steps of hydroxymethylation and optionally of oxidation.
As previously mentioned, the process of the invention is particularly suitable for the

preparation of vanillin a *d of ethylvanillin from a mixture of phenolic compounds obtained by hydroxymefnylation of guaiacol or of guetol.
Thus, vanillin can be prepared by selective oxidation of the hydroxymethyl group in the 2 position of compound (A) of a mixture of phenolic compounds, o-hydroxymethylguaiacol (A) and p-hydroxymethylguaiacol (B), to thecarboxy group, and of the hydroxymethyl group of compound (B) in the 4 position to the formyl group, thus producing a mixture of a 2-hydroxy-3-methoxybenzoic acid and vanillin, then of recovering the latter.
Another variation consists of selective oxidation of the formyl group in the 2 position of compound (A) of a mixture of phenolic compounds, o-formylguaiacol (A) and p-formylguaiaccl (B), to the carboxy group, thus producing a mixture of a 2-hydroxy-3-methoxybenzoic acid and vanillin, then of recovering the latter.
With regard to the preparation of ethylvanillin, in accordance with the invention, the hydroxymethyl group ir. the 2 position of compound (A) of a mixture of phenolic compounds, o-hydrox:.\nethylguaiacoi (A) and p-hydroxymethylguaiacol (B) is selectively oxidised to the carboxy group, and the hydroxymeuiyl group of compound (B) in the 4 position to the formyl group, thus producing a mixture of a 2-hydroxy-3-ethoxybenrioic acid and ethylvanillin, then of recovering the latter.
Another variation is i:i the fact that in a mixture of phenolic compounds, o-formylguetol (A) and p-formylguetol (B)> there is selective oxidation of the formyl group in the 2 position of compound (A) to the carboxy group, thus producing a mixture of a 2-hydrox>-3-ethoxybenzoic acid and ethylvaniUto, then of recovering the latter.
Examples of implementations of the invention will be given below. These examples are given by way of illustration are in no way limiting.

In the examples, the degree of conversion and the yield obtained is defined.
The degree of converson (DC) corresponds to the ratio between the number of moles of substrate trans formed and the number of moles of substrate used.
The yield (YY) corresponds to the ratio between the number of moles of product formed and the number of moles of substrate used.
The yield (YTvanjjlin) corresponds to the ratio between the number of moles of vanillin formed and the number of moles of guaiacol transformed in the sequence.
In the examples, the abbreviations are:
o-hydroxymethylguaiacol = OMG p-hydroxymethylguaiacol = PMG o-vanillin - 3-methoxy-2-hydroxyhenzaldehyde = OVA p-vanillin = 3-methoxy-4-hydroxybenzaldehyde = PVA o-vanillic acid - 2-hydroxy-3-methylbenzoic acid = AOV p-vanillic acid = 4-hydroxy-3-methy!benzoic acid = APV
EXAMPLES
Example 1:
In this example, a mixture of o-hydroxymethylguaiacol and p-hydroxymethylgua'iacol is oxidised,
2700 g of an aqueous solution containing 28.5 g of o-hydroxymethylguaiacol (OMG) and 33.72 g of p-hydroxymethylguaiacol (PMG) and 148 g of sodium carbonate is introduced into a pressurised 3.91 autoclave provided with an automatic exhaust

turbine.
This aqueous solution is the product of condensation of guaiacol on fonnol in an aqueous base solution, and prepared as described in the prior art (particularly according to example 4 m US 4 351 962).
0.54 g of bismuth trioxide and 22 g of palladium catalyst, deposited on charcoal in an amount of 3% by weight of metal, is added to this reaction mixture.
The reaction mixture is stirred at 1500 rpm and the temperature thereof increased to 45*C in nitrogen.
A pressure of 3 bar is established and air introduced into the reaction medium at a rate of 300 g/h.
The reaction mixture is kept under these conditions for 6 hours.
The reaction mixmre is cooled and the pressure returned to atmospheric pressure, then the catalyst is filtered.
The reaction medium is then analysed using high performance liquid chromatography.
The results obtained are as follows;
DC OMG - 100%
% YY o-vanillin YYo-vanillic « 93%
DC PMC 100%
YYp-vanillin ■'- 89%

YY p-vanjllic acid = 7%
Examination of these results shows that o-vanillin was selectively oxidised, compared to p-vanillin.
Example 2
In this example, a mixoire of o-vanillin/p-vanillin is oxidised.
50.26 g of o-vanillin, 49.88 g of p-vanillin, 2003 g of water and 142.5 g of an aqueous solution of 30% by weight of sodium carbonate is introduced into a 3.91 autoclave provided with an automatic exhaust turbine.
22 g of palladium catalyst, deposited on charcoal in an amount of 3 % by weight of metal* and 0.96 g of bismuth trioxide is added to the reaction mixture.
The mixture is stirred at 1500 rpm and the temperature thereof is increased to 1406C in nitrogen.
A pressure of 13 bar is established and aix introduced at a rate of 300 g/h for 15 minutes.
The reaction mixture is pooled and the pressure returned to atmospheric pressure, then the catalyst is filtered.
The reaction medium is then analysed using high performance liquid * chromatography. '
The results obtained are is follows:
DC o-vanillin « 100%
YY o-vanillic acid - 90%

DC p-vanillin =* 20%
YY p-vanillic acid =16%
This clearly demonstrates the selectivity of the oxidation. Example 3
Example 2 is repeated, but using a platinum catalyst.
50.5 g of o-vanillin, 50.1 g of p-vanillin, 2003 g of water and 142.5 g of an aqueous solution of 30% by weight of sodium carbonate is introduced into a 3,91 autoclave provided with an automatic exhaust turbine.
22 g of platinum catalyst, deposited on charcoal in an amount of 5% by weight of metal, and 1.5 g of bismuth trioxide is added to this reaction mixture.
The mixture is stirred at 1500 rpm and the temperature thereof increased to 140°C in nitrogen.
A pressure of 13 bar is established and air introduced at a rate of 300 g/h for 30 minutes.
The reaction mixture is cooled and the pressure returned to atmospheric pressure, then the catalyst is filtered.
The reaction medium is then analysed using high performance liquid chromatography. '
' The results obtained are is follows:
DC o-vanillin - 100%
YY o-vanillic acid - 89%

DC p-vanillin = 15%
YY p-vanillic acid = 12%
This also clearly demonstrates the selectivity of the oxidation.

CLAIMS
1. A process for the preparation of a 2-hydroxybenzoic acid and a 4-
hydroxybenzaldehyde and derivatives thereof, characterised in that in a mixture ot phenolic compounds, one (A) carrying a formyl or hydroxymethyl group in the 2 position, and the other (B) carrying a formyl or hydroxymethyl group in the 4 position, the formyl or hydroxymeihyl group in the 2 position of compound (A) is selectively oxidised to a carboxy group and optionally a hydroxymethyl group of compound (B) in the 4 position is selectively oxidised to a formyl group, thus producing a mixture of a 2-hydroxybenzoic acid and a 4-hydroxybemaldehyde.

where, in said formulae (IIA) and (IIB):
- Yl and Y2. which may be identical or different, represent one of the
following groups:
. a -CHO group . a -CH2OH group,
- Zv Z2 and Z3, which may be identical or different, represent a
«
hydrogen atom, an alkyl, alkenyl, allcoxy, hydroxyalkyl, alkoxyalkyl,
cycloalkyl, or aryl radical, a hydroxy group, a nitro group, a halogen atom, or a trit'luoromethyl group.
3, A process according to one of claims 1 and 2, characterised in that the

phenolic compounds have formula (IIA) and (IIB), where Zu Z2 and Z3>
which may De identical or different, represent one of the following atoms
or groups:
, a hydrogen atom,
. a linear or branched alkyl radical containing 1 to 12 carbon atoms,
preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl,
butyl, isobutyl, sec-butyl or tert-butyl,
• a linear or branched alkenyl radical containing 2 to 12 carbon atoms,
preferably 2 to 4 carbon atoms, such as vinyl or allyl,
. a linear or branched alkoxy radical containing 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, such as a methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy or tert-butoxy radicals,
• a phenyl radical,
. a halogen atom, preferably a fluorine, chlorine or bromine atom.
A process axording to one of claims 1 to 3, characterised in that the phenolic compounds have the formulae (IIA) and (IIB), where Zx represents * hydrogen atom or a linear or branched alkoxy radical containing 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms; Z2 and Z3 represent a hydrogen atom; and Yj and Y2 are identical and represent a formyl group or a hydroxymethyl group.
A process according to one of claims 1 to 4, characterised in that the mixture of phenolic compounds having formula (II) is:
- o-hydroxymethylphenol and p-hydroxymethylphenol,
- o-hydroxymethylguaiacol and p-hydroxymethylguaiacol,
- o-formylguaiacol and p-formylguaiacol,
- o-hydroxymethylguetol and p-hydroxymethylguetol,
- o-formyJguetol and p-formylguetol.
A process according to one of claims 1 to 5, characterised in that a

mixture of phenolic compounds having the formula (II) is oxidised in the liquid phase using molecular oxygen or a gas containing molecular oxygen, in an aqueous medium comprising a basic agent, in the presence of a catalyst based on a metal M, selected from metals from group lb and 8 of the periodic classification of the elements, optionally comprising as an activator metals such as cadmium, cerium, bismuth* lead, silver, tellurium or tin.
A process according to claim 6, characterised in that the catalyst is based on copper, nickel, ruthenium, rhodium, palladium, osmium, iridium, platinum or mixtures thereof; said catalyst being preferably based on platinum and/or palladium.
A process according to one of claims 6 and 7 characterised in that the platinum and/or palladium catalyst is provided in the form of platinum black, palladium black, platinum oxide, palladium oxide, or the noble metal itself, deposited on different supports such as carbon black, calcium carbonate, activated aluminas and silicas, or equivalent materials preferably carbon black.
A process according to one of claims 6 to 8, characterised in that the quantity of catalyst to be used, expressed as the weight of metal Mx with respect to that of the phenolic compound with formula (II) can vary from 0.01 to 10%, preferably from 0,04 to 2%.
A process according to one of claims 6 to 9, characterised in that the activator is an inorganic or organic bismuth derivative selected from the group of: bismuth oxides; bismuth hydroxides; bismuth or bismuthyl salts of inorganic hydracids, preferably the chloride, bromide, iodide, sulphide, selenide or telluride; bismuth or bismuthyl salts of inorganic oxyacids, preferably the sulphite, sulphate, nitrite, nitrate, phosphite,

phosphate, pyrophosphate, carbonate, perchlorate, antimonate, arsenate, selenite or selenate; bismuth or bismuthyl salts of aliphatic or aromatic organic acids, preferably the acetate, propionate, salicylate, benzoate, oxalate, tartrate, lactate, or citrate; and bismuth or bismuthyl phenates, preferably the gallate or pyrogallate.
A process according to claim 10, characterised in that the bismuth derivative is selected from the group of: bismuth oxides; Bi203 and Bi204; bismuthhydroxide Bi(OH)3; bismuth chloride BiCl3; bismuth bromide BiBr3; bismuth iodide Bil3; neutral bismuth sulphate Bi2(S04)3; neutral bismuth nitrate Bi(N03)3,5H20; bismuthyl nitrite (BiO)N02,0.5H20; bismuthyl carbonate (BiO)2CO3,0.5K2O; bismuth acetate Bi(C2H3Oj)3 and bismuthyl salicylate C6H4C02(BiO)(OH).
A process according to one of claims 6 to 11, characterised in that the quantity of activator is selected so that the medium contains: at least 0.1 % by weight of metal activator with respect to the weight of metal M{ used, and 10 to 900 ppm by weight of metal Mi with respect to the phenolic compounds with formula (II).
A process according to one of claims 6 to 12, characterised in that the oxidation reaction is carried out within a temperature range of 30°C to 200°C, preferably between 40°C and 160°C.
A process according to one of claims 6 to 13, characterised in that a pressure of 1 to 20 bar is used.
A process according to one of claims 1 to 14, characterised m that the oxidation is carried out in an aqueous medium containing, in solution, a basic agent, preferably sodium or potassium hydroxide, in a quantity such that it represents 0.5 to 10 moles, preferably 2 to 4 moles of

inorganic base per mole of phenolic compounds with formula (II).
A process according to one of claims 1 to 15, characterised in that the temperature is selected to be between 30°C and 200°C, preferably between 40°C and 160°C.
A process according to claim 16, characterised in that when using a platinum catalyst, the temperature is selected to be between 100°C and 160°C; the quantity of base to be used being between 1 and 3 moles per mole of phenolic compounds with formula (II).
A process according to claim 16, characterised in that when using a palladium catalyst, the temperature is selected to be between 30 *C and 200°C, preferably between 30°C and 150°C; the quantity of base to be used being between 2 and 4 moles per mole of phenolic compounds with formula (II).
Process according to claim 1 to 18, characterised in that the 4-hydtoxybenzaldehyde is extracted with controlled pH.
Process according to claim 19, characterised in that the extraction solvent is selected from ketones, preferably methylethylketone, methylisobutylketone, cylcohexanone; esters, preferably ethyl acetate, isopropyl acetate, butyl acetate; ether oxides, preferably diethylether, diisopropyle&her, methyl-tert-butylether, ethyl-tert-butylether, di-n-butylether; heavy alcohols, preferably butanol, hexanol, octanol, cyclolxexanol; aliphatic hydrocarbons, preferably n-pentane, hexane, heptane and cyclohexane; halogenated aliphatic hydrocarbons, preferably dichloromethane, dichloroethane; aromatic hydrocarbons, preferably toluene, xylenes; halogenated aromatic hydrocarbons, preferably monochlorobenzene, dichlorobenzene, and mixtures thereof.

A process according to claim 19, characterised in that the pH is returned to between 4 and 9 prior to the addition of the solvent or simultaneously by the addition of a protonic acid of inorganic origin, preferably hydrochloric acid or sulphuric acid, and that the aqueous and organic phases are separated.
A process according to claims 1 to 21, characterised in that the 2-hydroxybenzoic acid, which can be partially or completely in its salt form, is dccarboxylated.
A process according to claim 22, characterised in that the 2-hydroxyber&oic acid has the general formula (II):

where, in said formula (II):
- M represents a hydrogen atom and/or a metal cation from group (la) or (Ila) or an ammonium cation,
- Zu Z2, Z3 have the meanings given in claims 2 to 4.
A process according to one of claims 22 and 23, characterised in that said acid is decarboxylated by adding a protonic acid of mineral origin, preferably hydrochloric acid or sulphuric or an organic acid to the reaction medium until a pH less than or equal to 3 is obtained.
A process according to one of claims 22 to 24, characterised in that the reaction medium is heated to a temperature between 120aC and 350°C, preferably 150°C to 220°C, and after cooling, the 4-hydroxybenzaldehyde is separated, which preferably has the formula

where, in said formulae:
- M represents a hydrogen atom and/or a metal cation from group (la) or (Ila) or an ammonium cation,
- ZH Z2, Zx have the meanings given in claims 2 to 4.
A process according to claim 26, characterised in that a mixture ol formula (Ila) and (IIbt) is obtained by a process of hydroxymcthylation of a phenol by condensation thereof with formaldehyde oi a formaldehyde generator in an aqueous phase in the pir.cnce of an alkaline or earth alkaline base.
A process according to claim 27, characterised in that the starting phenol is an unsubstituted phenol at the ortho and para positions with respect to the hydroxy group, with the general formula (I):

in which Zlt 2^, Z3 have the meanings given in claims 2 to 4.
A process according to claim 28, characterised in that the phenol with formula (I) is phenol, pyrocatechin, guaiacol, guetol, 3-methoxyphenol, 3-ethoxyphenol, 3-isopropoxyphenol, 3-t-butoxyphenol, m-cresol and o-
cresol.
A process according to one of claims 27, characterised in that formaldehyde or any formaldehyde generator is used, preferably trioxane or paraformaldehyde used as linear paraformaldehydes of any degree of polymerisation, preferably containing 8 to 100 (CH20) units.

A process according to claim 27, characterised in that the formaldehyde/phenol molar ratio can vary between 0.5 and 2.0, and preferably between 0.5 and 1.5.
A process according to claim 27, characterised in that the quantity of base present in the hydroxymethylation medium, expressed as the number of moles of base/phenolic hydroxy group of the phenol to be hydroxymethylsted, varies between 0.1 and 2, and preferably between 0.5 and 1.1.
A process according to claim 27, characterised in that the hydroxymethylation temperature is between 0 and 100°C and preferably between 20 arcl 70 °C.
A process according to claim 27, characterised in that the phenol and formaldehyde, and any base, is placed in the equipment, then, while stirring, the reaction mixture is heated to the temperature desired for the time required to obtain a mixture of phenolic compounds with formulae (HaOandaib;;.
A process according to claim 27, characterised in that a mixture of compounds w*th formulae (Ilaj) and (IIb2) is obtained by oxidation of hydroxymethyiated phenolic compounds with formulae (Ila^ and (Ilbj), by oxidation using molecular oxygen or a gas containing molecular oxygen in an alkaline aqueous phase in the presence of a catalyst based on a metal from group 8 of the periodic classification, preferably platinum and palladium, optionally containing metals such as cadmium, cerium, bismurh, lead, silver, tellurium or tin as an activator
A process according to claim 35, characterised in that the pH of the solution is broaght to a value between 8 and 13 by optionally adding an

alkaline or earth alkaline base.
A process according to claim 35, characterised in that the temperature of the oxidation reaction is between 10°C and 60°C, and preferably between 20°C and 50°C.
A process according to claim 26, characterised by the fact that a mixture of phenolic compounds with formulae (HaO and lib*) is obtained by a two-step procen;; comprising:
hydroxymcthylation of a phenol in an aqueous medium in the presence of ai* alkaline or earth-alkaline base by formaldehyde or a formaldehyde generator producing a mixture of hydroxy methylated phenolic compounds, one hydroxymethylated in the 2 position, the other in the 4 position,
and oxidation, widiout intermediate separation, of phenolic compounds obtained by molecular oxygen or a gas containing molecular oxygen in an alkaline aqueous phase in the presence of a catalyst based on a metal from group 8 of the periodic classification, possibly as an activator, this metal being such as those previously listed.
A process for the preparation of vanillin according to one of claims 1 to 38, characterised in that the hydroxymethyl group in the 2 position of compound (A) of a mixture of phenolic compounds, o-hydroxymethylf;uaiacol (A) and p-hydroxymethylguaiacol (B), is selectively oxidised to a carboxy group, and the hydroxymethyl group of compound (B) is selectively oxidised to a formyl group, thus producing a mixture of a 2-hydroxy-3-methoxybenzoic acid and vanillin, and the latter is then recovered.
A process for the preparation of vanillin according to one of claims 1 to 38, characterised in that the formyl group in the 2 position of compound

(A) of a mixture of phenolic compounds, o-formylguaiacol (A) and p-
formylguaiaco: (B), is selectively oxidised to a carboxy group, thus
producing a nvxture of a 2-hydroxy-3-methoxybenzoic acid and vanillin,
and the latter n then recovered.
41. A process for the preparation of ethyl vanillin according to one of claims
1 to 38, characterised in that the hydroxymethyl group in the 2 position
of compound (A) of a mixture of phenolic compounds, o-
hydroxymethylguetol (A) and p-hydroxymethylguetol (B), is selectively
oxidised to a carboxy group, and the hydroxymethyl group of compound
(B) in the 4 position is selectively oxidised u a formyl group, thus
producing a mixture of a 2-hydroxy-3-ethoxybenzoic acid and
ethylvanillin, and the latter is then recovered.
42. A process for riie preparation of ethylvanillin according to one of claims
1 to 38, characterised in that the formyl group in the 2 position of
compound (A» of a mixture of phenolic compounds, o-foimylguetol (A)
and p-formylguetol (B), is oxidised to a carboxy group, thus producing
a mixture of a 2-hydroxy-3-ethoxybenzoic acid and ethylvanillin, and the
latter is then recovered.
43. Use of the process described in one of claims 1 to 38 for the preparation
of vanillin and ethylvanillin.
A process for the preparation of a 2-hydroxybenzoic acid substantially as herein described and exemplified.

Documents:

2277-mas-1997-abstract.pdf

2277-mas-1997-claims duplicate.pdf

2277-mas-1997-claims original.pdf

2277-mas-1997-correspondence others.pdf

2277-mas-1997-correspondence po.pdf

2277-mas-1997-description complete duplicate.pdf

2277-mas-1997-description complete original.pdf

2277-mas-1997-form 1.pdf

2277-mas-1997-form 26.pdf

2277-mas-1997-form 3.pdf

2277-mas-1997-form 4.pdf

2277-mas-1997-pct.pdf

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Patent Number

208257

Indian Patent Application Number

2277/MAS/1997

PG Journal Number

35/2007

Publication Date

31-Aug-2007

Grant Date

20-Jul-2007

Date of Filing

14-Oct-1997

Name of Patentee

RHONE-POULENC CHIMIE

Applicant Address

25 QUAI PAUL DOUMER, 92408 COURBEVOIE CEDEX.

Inventors:

#	Inventor's Name	Inventor's Address
1	DENNIS PHILIPPE,	16 ALLEE DES TROENES, 65150 DECINES.
2	MALIVERNEY CHRISTIAN,	34 RUE RACHAIS, 69007 LYON.
3	METIVIER PASCAL	29 ALLEE DES FRENES, 69110 SAINTE FOY LES LYON.

PCT International Classification Number

C07C323/22

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	9612479	1996-10-14	France