Title of Invention	PROCESS FOR THE PREPARATION OF A 4-HYDROBENZALDEHYDE AND ITS DERIVATES
Abstract	A process for preparing a 4-hydroxybenzaldehyde and its derivatives The present invention relates to a process for preparing a 4-hydroxybenzaldehyde and its derivatives, characterized in that it consists of selectively oxidising the group in the 2 position with respect to the hydroxyl group to a carboxy group, and the hydroxymethyl group in the 4 position to a formyl group, present in the phenolic compounds in a mixture comprising at least: a phenolic compound (A) carrying formyl and/or hydroxymethyl groups in the 2 and 4 position; a phenolic compound (B) carrying a formyl or hydroxymethyl group in the 4 position; a phenolic compound (C) carrying a formyl or hydroxymethyl group in the 2 position; resulting in a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde, a 4-hydroxybenzaldehyde and a 2-hydroxy-benzoic acid, which then undergoes a decarboxylation operation to produce the 4-hydroxybenzaldehyde and a phenol.

Title of Invention

PROCESS FOR THE PREPARATION OF A 4-HYDROBENZALDEHYDE AND ITS DERIVATES

Abstract

A process for preparing a 4-hydroxybenzaldehyde and its derivatives The present invention relates to a process for preparing a 4-hydroxybenzaldehyde and its derivatives, characterized in that it consists of selectively oxidising the group in the 2 position with respect to the hydroxyl group to a carboxy group, and the hydroxymethyl group in the 4 position to a formyl group, present in the phenolic compounds in a mixture comprising at least: a phenolic compound (A) carrying formyl and/or hydroxymethyl groups in the 2 and 4 position; a phenolic compound (B) carrying a formyl or hydroxymethyl group in the 4 position; a phenolic compound (C) carrying a formyl or hydroxymethyl group in the 2 position; resulting in a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde, a 4-hydroxybenzaldehyde and a 2-hydroxy-benzoic acid, which then undergoes a decarboxylation operation to produce the 4-hydroxybenzaldehyde and a phenol.

Full Text	The present invention concerns a process for the preparation of a 4-hydroxybenzaldehyde and its derivatives. More particularly, the invention concerns the preparation of 3-methoxy-4-hydroxybenzaldehyde and 3-ethoxy-4-hydroxybenzaldehyde, respectively known as vanillin and ethylvanillin. hi French patent application n° 95/06186, a process is described for the preparation of 4-hydroxybenzaldehydes, more particularly vanillin and ethylvanillin. The process described consists of preparing a 3-carboxy-4-hydroxybenzaldehyde then decarboxylating that compound to produce the 4-hydroxybenzaldehyde. According to FRn°95/06186, the 3-carboxy-4-hydroxybenzaldehyde is prepared from one of the compounds given below and mixtures thereof, more an alkyl, alkenyl, alkoxy, hydroxyalkyl, alkoxyalkyl, cycloalkyl or aryl radical, a hydroxyl group, a nitro group, a halogen atom, or a trifluoroethyl group. In that patented process, the starting compound is a bifunctional phenohc compound carrying two functional groups on the aromatic ring in the ortho and para positions which can be a -CHO group and/or a -CH2OH group. Firstly, the ortho group is selectively oxidised to a carboxylic group; the group in the para position is at most oxidised to a formyl group. After elimuiating the carboxy group in the ortho position, a 4-hydroxybenzaldehyde is obtained. Thus vanillin and ethylvanillin can advantageously be prepared using a process which is selective and also highly competitive from an industrial viewpoint as it uses inexpensive reactants. However, in that process it is difficult to obtain a reaction yield (expressed with respect to the starting phenol) of more than 70% as obtaining a high yield of a bifimctional phenolic compound is accompanied by that of a by-product, namely a bis-arylmethane. During our research, we discovered in French application n°96/12479 that a 4-hydroxybenzaldehyde can be prepared from a mixture of monosubstituted 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, and selectively oxidising the formyl or hydroxymethyl group in the 2 position of compound (A) to a carboxy group, and possibly a hydroxymethyl group in the 4 position of compound (B) to a formyl group, thus producing a mixture of a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde from which the latter is separated. an alkyl, alkenyl, alkoxy, hydroxyalkyl, alkoxyalkyl, cycloalkyl or aryl radical, a hydroxyl group, a nitro group, a halogen atom, or a trifluoroethyl group. The disadvantage of that process is that to obtain compounds with formula (DA) or (IIB), by hydroxymethylation of a phenol, it is essential to work with a low degree of conversion of the starting phenol which results in low productivity. Thus the existing processes must be improved in order to have available a process which is of great economic interest which minimises the by-products and can produce a high operating productivity. We have discovered, and this constitutes one aspect of the present invention, a process for the preparation of a 4-hydroxybenzaldehyde and its derivatives, characterized in that it consists of selectively oxidising, to a carboxy group, the group in the 2 position with respect to the hydroxyl group, present in the phenolic compounds in a mixture comprising at least: • a phenolic compoimd (A) carrying formyl and/or hydroxymethyl groups in the 2 and 4 position; • a phenolic compound (B) carrying a formyl or hydroxymethyl group in the 4 position; • a phenolic compound (C) carrying a formyl or hydroxymethyl group in the 2 position; resulting in a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde, a 4-hydroxybenzaldehyde and a 2-hydroxybenzoic acid, which then undergoes a decarboxylation operation to produce the 4-hydroxybenzaldehyde and a phenol which can optionally be recycled. Li a further aspect, the invention provides a starting mixture of phenolic compounds claimed as; the mixture itself, and the mixture obtained after oxidation. Finally, processes for preparing these mixtures constitute further aspects of the mvention. hi the process of the invention, we have discovered that by starting from a mixture of starting compounds as defined above, it is possible to carry out simultaneous intramolecular oxidation (A) and intermolecular oxidation (B + C) since oxidation of the carboxy group takes place preferentially on the hydroxymethyl or formyl group in the ortho position. The process of the invention thus comprises an oxidation step and a decarboxylation step for a 3-carboxy-4-hydroxybenzaldehyde to a 4-hydroxybenzaldehyde and a 2-hydroxybenzoic acid which can produce the phenolic starting compound which can then be recycled; the 4-hydroxybenzaldehyde is then recovered conventionally. The starting substrates used in the process of the invention are mixtures of phenolic compounds, one (A) carrying formyl and/or hydroxymethyl groups in the 2 and 4 positions, the second (B) carrying a formyl or a hydroxymethyl group in the 4 position and the last, (C), in the 2 position. " The term "phenolic compound" means any aromatic compound with an aromatic nucleus which carries a hydroxy group. In the following disclosure of the present invention, the term "aromatic" means the conventional idea of aromaticity as defined in the literature, in particular in "Advanced Organic Chemistry" by Jerry MARCH, 4* edition, John have formulae (DA) to (EC) where Z], Z2 and Z3, which may be identical or different, represent one of the following 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 radical; • a phenyl radical; • a halogen atom, preferably a fluorine, chlorine or bromine atom. The present invention does not exclude the presence of substituents of different natures on the aromatic ring, provided that they do not interfere with the reactions taking place in the process of the invention. The present invention is preferably applicable to compounds with formula (HA) to (HC) where Zi 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; Z and Z3 represent a hydrogen atom; and Yi and Y2 are identical and represent a formyl group or a hydroxymethyl group. Preferred examples of mixtures of phenolic compounds for use in the process of the invention are: • o-hydroxymethylguaiacol, p-hydroxymethylguaiacol and 4,6- ""-di(hydroxymethyl)guaiacol; • o-formylguaiacol, p-formylguaiacol and 4,6-diformylguaiacol; • o-hydroxymethylguetol, p-hydroxymethylguetol and 4,6- di(hydroxymethyl)guetol; • o-formylguetol, p-formylguetol and 4,6-diformylguetol. The process of the invention uses a starting mixture of phenolic compounds which preferably have formula (II). The proportion of each phenolic compound in the mixture depends on the method of their preparation. Preferred mixtures comprise: • 30% to 70% by weight, more preferably 50% to 70%, of a phenolic compound (A); • 30% to 70% by weight, more preferably 50% to 70%, of a mixture of phenolic compounds (B+C). As an indication, the quantities of isomers B and C are approximately equimolar in the mixture. A reaction scheme is given below to facilitate comprehension of the disclosure of the invention without in any way limiting the scope of the invention to the scheme. In the present text, reference will be made to the periodic table published in the "Bulletin de la Societe Chimique de France", n°l (1966). In accordance with the process of the invention, the Yi group in position 2 of phenolic compounds (A) and (C) preferably with formulae (HA) and (IIC) is selectively oxidised to a carboxy group, and a hydroxymethyl group, if present in the 4 position in phenolic compounds (A) and (B) preferably with formulae (IIA) and (IIB), is selectively oxidised to a formyl group. Oxidation is carried out using 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 with formula (II) m 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 Mi selected from metals from group lb and 8 of the periodic classification of the elements, which may optionally contain, as an activator, metals such as cadmium, cerium, bismuth, lead, silver, tellurium or tin. We have surprisingly discovered that if the temperature is increased and the reaction is preferably carried out under pressure or if the quantity of base present during oxidation is increased, group Yi in the 2 position in phenolic compounds (A) and (C), preferably with formulae (HA) and (EC) is selectively oxidised to a carboxy group, and the group located in the 4 position in phenolic compounds (A) and (B), preferably with formulae (DA) and (HB), is at most oxidised to the formyl group.. The catalysts used in the process of the invention are based on a metal from 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 Regarding metals from group lb, copper is preferred. Preferably, platinum and/or palladium catalysts are used, in any available form such as: platinum black, palladium black, platinum oxide, palladium oxide or the noble metal itself deposited on different supports such as carbon black, calcium carbonate, aluminas or activated silicas or equivalent materials. Catalytic masses based on carbon black are particularly suitable. The quantity of catalyst used, expressed as the weight of metal Mi with respect to that of the phenolic compound with formula (II), can vary from 0.01% to 10%, preferably 0.04% to 2%. Further details of the catalysts can be obtained from United States patent US-A-3 673 257, and French patents FR-A-2 305 420 and FR-A-2 350 323. The activator can be selected from all those mentioned in the above patents. Preferably, bismuth, lead and cadmium are used as the free metal or as cations. In the latter case, the associated anion is not critical and all derivatives of these metals can be used. Preferably, bismuth metal or its derivatives is used. An inorganic or organic bismuth derivative can be used in which the bismuth atom has an oxidation number of more than zero, for example 2, 3, 4 or 5. The residue associated with the bismuth is not critical provided that is satisfies this condition. The activator can be soluble or insoluble in the reaction medium. Illustrative examples of activators which can be used in the process of the present invention are: 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, niobate, 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 sahs. Other inorganic or organic compounds are binary compounds of bismuth with elements such as phosphorous or arsenic; heteropolyacids containing bismuth and salts thereof; also aliphatic and aromatic bismuthines. Specific examples are: • oxides: BiO; Bi203; Bi204; BizOj; • hydroxides: Bi(0H)3; • salts of inorganic hydracids: bismuth chloride BiCla; bismuth bromide BiBrs; bismuth iodide Bils; bismuth sulphide BiaSs; bismuth selenide BiiScs; bismuth telluride BiaTes; • salts of inorganic oxyacids: basic bismuth sulphite Bi2(S03)3,Bi203,5H20; neutral bismuth sulphate Bi2(S04)3; bismuthyl sulphate (BiO)HS04; bismuthyl nitrite (BiO)NO2,0.5H2O; 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 BiP04; bismuth pyrophosphate B"iPjOih; bismuthyl carbonate (BiO)2CO3;0.5H2O; neutral bismuth perchlorate Bi(C104)3,5H20; bismuthyl perchlorate (BiO)C104; bismuth antimonate BiSb04; neutral bismuth arsenate Bi(As04)3; bismuthyl arsenate (Bi0)As04,5H20; bismuth selenite 812(8603)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]2Cr207; acid bismuthyl chromate H(Bi0)Cr04; double chromate of bismuthyl and potassium K(Bi0)Cr04; bismuth molybdate Bi2(Mo04)3; bismuth tungstate Bi2(W04)3; double molybdate of bismuth and sodium NaBi(Mo04)2; basic bismuth permanganate Bi202(OH)Mn04; • sahs of aliphatic or aromatic organic acids: bismuth acetate Bi(C2H302)3; bismuthyl propionate (BiO)C3H502; basic bismuth benzoate C6H5C02Bi(OH)2; bismuthyl salicylate C6H4C02(BiO)(OH); bismuth oxalate (C204)3Bi2; bismuth tartrate Bi2(C4H406)3,6H20; bismuth lactate (C6H905)OBi,7H20; bismuth citrate CeHjOvBi; • phenates: basic bismuth gallate C-jUjOjBi; basic bismuth pyrogallate C6H3(OH)2(OBi)(OH). Other inorganic or organic compoimds are also suitable: bismuth phosphide BiP; bismuth arsenide Bi3As4; sodium bismuthate NaBi03; bismuth-thiocyanic acids H2[Bi(BNS)5],H3[Bi(CNS)6] and sodium and potassium salts thereof; trimethylbismuthine Bi(CH3)3, triphenylbismuthine Bi(C6H5)3. Preferred bismuth derivatives for use in the process of 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 group of activators for carrying out the process of the invention is constituted by: bismuth oxides Bi203 and Bi204; bismuth hydroxide Bi(0H)3; neutral bismuth sulphate 812(804)3; bismuth chloride BiCl3; bismuth bromide BiBr3; bismuth iodide Bils; neutral bismuth nitrate Bi(N03)3,5H20; bismuthyl nitrate BiOCNOa); 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 Mi used, can be varied between wide limits. As an example, this quantity can be as low as 0.1% and can attain the weight of metal Mj used, or even exceed it without any problems. More particularly, this quantity is selected so that it provides the oxidation medium with 10 ppm to 900 ppm by weight of activator metal with respect to the phenolic compound with formula (II). hi this respect, higher quantities of activator of the order of 900 ppm to 1500 ppm can naturally be used, but with no great additional advantage. hi the process of the mvention, oxidation is carried out in an aqueous medium containing a basic agent in solution, more particularly ammonium hydroxide, alkaline or alkaline-earth bases, for example hydroxides such as sodium, potassium, lithium and baryte hydroxides; alkaline alkanolates such as sodium or potassium methylate, ethylate, isopropylate or t-butylate, sodium or potassium carbonates or bicarbonates and in general, the salts of alkaline or alkaline-earth bases and weak acids. Thus compounds with formulae (HI) to (V) can be completely or partially in their salt form depending on the quantity of basic agent used. It follows that in these formulae, M, the residue of the base, generally symbolises a hydrogen atom and/or a metallic cation from group (la) or (Ha) or an ammonium cation. Sodium or potassium hydroxide is used for reasons of economy. The proportion of inorganic base to be used can be in the range 0.5 to 10 moles, preferably in the range 1 to 4 moles, more preferably in the range 2 to 4 moles, of inorganic base per mole of phenolic compounds with formula (11). The concentration by weight of the mixture of phenolic compounds with formula (II) in the liquid phase is usually in the range 1% to 60%, preferably in the range 2% to 30%. In practice, one implementation of the process consists of bringing the solution comprising the mixture of phenolic compounds with formula (H), the basic agent, the catalyst based on metal Mi, and any activator into contact with molecular oxygen or a gas containing molecular oxygen in the proportions indicated above. Atmospheric pressure can be used, but it is preferable to operate at a pressure of 1 to 20 bar. The mixture is then stirred at the desired temperature until a quantity of oxygen has been consumed which corresponds to that necessary to transform the hydroxymethyl group or formyl group of compounds (A) and (C) into a carboxy group, and the hydroxymethyl group, if present in compounds (A) and (B), into a formyl group. The reaction temperature to be used depends on the thermal stability of the products to be prepared. In accordance with the invention, the temperature is preferably selected so as to be in the range 30°C to 200°C, preferably in the range 40°C to 160°C. , The temperature can be adapted to the reaction conditions by the skilled person(in particular the quantity of base, nature of metal Mi, pressure and stirring). In particular, it has been discovered that the lower the temperature the higher must be the quantity of basic agent used. Examples of preferred conditions in the case of preferred metals platinum and palladium will now be given. For platinum, the temperature can be between 60°C and 160°C, the quantity of base to be used is advantageously in the range 1 to 3 moles per mole of phenolic compounds with formula (11). For palladium, the temperature can be between„3Q°C and 200°C, preferably between 30°C and 150°C, and for the latter interval, the quantity of base is preferably 2 to 4 moles per mole of phenolic compounds. The quantity of base must be sufficient to oxidise the Yi group in the position ortho to the carboxy group. It is determined by the skilled person depending on the temperature and the selected metal. At the end of the reaction, which preferably takes 30 minutes to 6 hours, a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde preferably with formula (HI), a 4-hydroxybenzaldehyde preferably with formula (V) and a 2-hydroxybenzoic acid preferably with formula (IV) are recovered: the compounds can be partially or totally in their salt form. After any necessary cooling, the catalytic mass and the reaction mass are separated, for example by filtering. In a second step of the process of the invention, the reaction medium undergoes a decarboxylation reaction. This is carried out by acidifying the resulting medium by adding a protonic mineral acid, preferably hydrochloric acid or sulphuric acid or an organic acid such as trifluoromethanesulphonic acid or methanesulphonic acid, to obtain a pH 3 or less. The concentration of acid is immaterial and preferably, commercially available concentrations are used. The reaction medium is heated to a temperature of between 120°C and 350 °C, preferably between 150°C and 220°C. The process is preferably carried out under autogenous pressure of the reactants. At the end of the reaction, the reaction medium is cooled to between 20°C and 80°C. A two-phase medium is obtained constituted by an organic phase comprising the 4-hydroxybenzaldehyde preferably with formula (VI) and the starting phenolic compound with formula (I), and also a saline aqueous phase. The organic and aqueous phases are separated and the 4-hydroxybenzaldehyde is recovered jfrom the organic phase using conventional separation techniques, for example extraction using an appropriate solvent (for example methylisobutylketone or isopropyl ether), or by distillation. The improved process of the mvention starts with a mixture of two phenolic compounds, one carrying a formyl or hydroxymethyl group in the 2 and 4 The mixtures of phenolic compounds, to which the process of the invention can be applied, are prepared by a process which constitutes a further aspect of the invention. Thus mixtures of phenolic compounds with formulae (Ilai) to (IIci) can be obtamed by a process for hydroxymethylating a phenol by condensing it with formaldehyde or a formaldehyde generator in an aqueous phase in the presence of and alkaline or alkaline-earth base, so that the phenol conversion is at most 95% optionally followed by an oxidation step. Examples of phenols with formula (I) which can act as a starting point for the synthesis of compounds with formula (II) are guaiacol, guetol, 3-methoxyphenol, 3-ethoxyphenol, 3-isopropoxyphenol, 3-t-butoxyphenol, m-cresol and p-cresol. The conditions selected for carrying out this hydroxymethylation step are those recommended by the prior art listed below: cf in particular H. G. PEER, Rec. Trav. Chim. Netherlands 79, 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, Rec. Trav. Chim. Netherlands 78 851-863 (1959); H. EULER et al, Arkiv flir 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 trioxane or paraformaldehyde used as linear paraformaldehydes of any degree of polymerisation, preferably containing 8 to 100 (CH2O) units. Formaldehyde can be used as an aqueous solution in a concentration which is not critical. It can be in the range 20% to 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 be between 1.0 and 4.0, preferably between 1.0 and 2.5. 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 hydroxymethylated, can vary between wide limits. In general, this ratio, which varies depending on the base, can be between 1.0 and 4.0, preferably between 0.9 and 2.0. The base used may be one of those cited above for the oxidation step. Aqueous solutions of alkaline hydroxides are particularly suitable. In general, the hydroxymethylation step is carried out at a temperature in the range 0°C to 100°C, preferably in the range 20°C to 70°C. The process is preferably carried out at a pressure which is autogenous for the reactants to avoid any paraformaldehyde losses which may be gaseous at the temperatures used. Preferably, the reaction is carried out in a controlled atmosphere of inert gas such as nitrogen or a noble gas, for example argon. The reaction time can readily be determined by the skilled person depending on the desired degree of conversion of the starting phenol and taking into account the necessity to minimise by -products such as bis-arylmethane. It is usually between 15 minutes and 4 hours, preferably between 1 hour and 3 hours. The degree of conversion of phenol is controlled by different parameters (temperature, duration, quantity of reactants). It is advantageously in the range 60% to 95%, preferably in the range 80% to 95%. In practice, the reaction is readily carried out by charging the phenol and formaldehyde, and any base into the apparatus, then stirring and heating the reaction mixture to the desired temperature 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 (Elai) to (IIci) is obtained. Compounds with formula (Ilai) to (nc2) can be prepared by oxidising hydroxymethylated phenolic compounds with formula (Ilai) to (IIci), by oxidising using molecular oxygen or a gas containing molecular oxygen, in an aqueous alkaline phase, in the presence of a catalyst based on a metal from group 8 of the r periodic table, preferably platinum or 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 FR-A-2 350 323. If necessary, the pH of the solution can be raised to a value in thejange„8, to 13 by optional addition of an alkalme or alkaline-earth base. The optional value i of the pH depends on the natiire of the hydroxymethylated phenols. The temperature of the oxidation reaction is between 10°C and 100°C, preferably between 20°C and 60°C. More specifically again, the process of the present invention is suitable for the preparation of compounds with formulae (na2) to (nc2) from phenolic compounds with formulae (Ilai) to (IIci) resulting from the first step, using molecular oxygen or a gas containing molecular oxygen, in the presence of a catalyst based on a metal from group 8 of the periodic table, optionally containing a metal such as those used as an activator, without intermediate separation of the hydroxymethylated phenolic compounds. From an industrial viewpoint, it is particularly advantageous when carrying out the process of the present invention to use compounds with formula (na2) to (nc2) obtained by a two-step process comprising: • hydroxymethylation of a phenol in an aqueous medium in the presence of an alkaline or alkaline-earth base using formaldehyde or a formaldehyde generator, resulting in a mixture of hydroxymethylated phenolic compounds, one being hydroxymethylated m the 2 and 4 positions and the two others being hydroxymethylated in the 2 or in the 4 position; • and oxidation, without intermediate separation, of the phenolic compounds obtained using molecular oxygen or a gas containing molecular oxygen, in an 6 aqueous alkaline phase in the presence of a catalyst based on a metal from group 8 of the periodic table, and optionaliy, a metal such as those cited above, acting as an activator. An additional advantage of the process of the invention is that it allows mixtures of phenolic compounds issuing directly from the preceding hydroxymethylation and optional oxidation steps to be used. As mentioned above, the process of the invention is particularly suitable for the preparation of vanillin and ethylvanillin from a mixture of phenolic compounds obtained by hydroxymethylation of guaiacol or guetol. Thus vanillin can be prepared by selectively oxidising a mixture of phenolic compounds, 4,6-di(hydroxymethyl)guaiacol (A), p- hydroxymethylguaiacol (B) and o-hydroxymethylguaiacol (C) at the hydroxymethyl group in the 2-position of compounds (A) and (C) to a carboxy group, and the hydroxymethyl group in the 4 position in compounds (A) and (B) to a formyl group, resulting in a mixture of 3-carboxy-4-hydroxy-5-methoxybenzaldehyde, vanillin and 2-hydroxy-3-methoxybenzoic acid which, after decarboxylation, produces vanillin and guaiacol which can be recycled. A variation consists of selectively oxidising a mixture of phenolic compounds, 4,6-di(formyl)guaiacol (A), p-formylguaiacol (B) and o-formylguaiacol (C) at the formyl group in the 2-position of compounds (A) and (C) to a carboxy group, resulting in a mixture of 3-carboxy-4-hydroxy-5- methoxybenzaldehyde, vanillin and 2-hydroxy-3-methoxybenzoic acid which, after decarboxylation, produces vanillin and guaiacol which can be recycled. Ethylvanillin is prepared by the process of the present invention by selectively oxidising a mixture of phenolic compounds, 4,6-di(hydroxymethyl)guetol (A), p-hydroxymethylguetol (B) and o- hydroxymethylguetol (C) at the hydroxymethyl group in the 2-position of compounds (A) and (C) to a carboxy group, and the hydroxymethyl group in the 4 position in compounds (A) and (B) to a formyl group, resulting m a mixture of 3- carboxy-4-hydroxy-5-ethoxybenzaldehyde, ethylvanillin and 2-hydroxy-3-ethoxybenzoic acid which, after decarboxylation, produces ethylvanillin and guetol which can be recycled. A further variation consists of selectively oxidising a mixture of phenolic compounds, 4,6-di(formyl)guetol (A), p-fonylguetol (B) and oformylguetol (C) at the formyl group in the 2-position of compounds (A) and (C) to a carboxy group, resulting in a mixture of 3-carboxy-4-hydroxy-5-ethoxybenzaldehyde, ethylvanillin and 2-hydroxy-3-ethoxybenzoic acid which, after decarboxylation, produce vanilling and guaiacol which can be recycled. Examples of implementations of the invention will now be given. These examples are given by way of indication and are in no way limiting. The degree of conversion and the yield obtained are defined in the examples. The degree of conversion (TT) corresponds to the ratio between the number of moles of substrate transformed and the number of moles of substrate used. The yield (RR) corresponds to the ratio between the number of moles of product formed and the number of moles of substrate used. The yield (RTyaniiiin) corresponds to the ratio between the number of moles of vanillin formed and the number of moles of guaiacol transformed in the sequence. The following abbreviations are used in the examples: • o-hydroxymethylguaiacol = OMG • p-hydroxymethylguaiacoi = PMG • o-vanillin = 3-methoxy-2-hydroxybenzaldehyde = OVA • p-vanillm = 3-methoxy-4-hydroxybenzaldehyde = PVA • o-vanillic acid = 2-hydroxy-3-methoxybenzoic acid = AOV • p-vanillic acid = 4-hydroxy-3-methoxybenzoic acid = APV • 4,6-di(hydroxymethyl) guaiacol = DMG • 4,3-(diformyl)guaiacol = DFG • o-carboxyvanillin = OCVA • 4,6-(dicarboxy)guaiacol = DCG. EXAMPLE 1 1. Condensation step The following was charged into a 2 litre reactor provided with a mechanical stirrer and a temperature regulation means: • 152 gof guaiacol; • 249 g of an aqueous 30% formol solution; • 49.2 g of caustic soda; • 872 gof water. The reaction medium was kept at 45°C for 1 hour then cooled and analysed using high performance liquid chromatography. The reaction balance was as follows: • guaiacol conversion = 90% • o-hydroxymethyl guaiacol (OMG) yield = 15% • p-hydroxymethyl guaiacol (PMG) yield = 18% • 4,6-di(hydroxymethyl) guaiacol (DMG) yield = 83% The sum of the upgradable products was 93%. 2. Oxidation step The reaction medium was then diluted with 1500 g of water and 148 g of caustic soda. The reaction medium was then introduced into a 3.9 litre autoclave provided with a self exhausting turbine. 0.54 g of bismuth trioxide and 22 g of a palladium catalyst deposited on carbon black in a proportion of 3% by weight of metal were then added. Stirring was started at a rate of 1500 rpm and the temperature of the reaction medium was raised to 45°C under nitrogen. It was then placed under a pressure of 3 bars and air was introduced into the reaction medium at a rate of 300 g/h. The reaction medium was held under these conditions for 6 houis. The reaction mediimi was cooled and the pressure was reduced to atmospheric pressure then the catalyst was filtered. The reaction medium was then analysed by high performance liquid chromatography. The yields were as follows (for the complete sequence): • TT guaiacol = 92% • ortho series • RR o-hydroxymethyl guaiacol (OMG) = 0% • RRorthovanillin(OVA) = 1% • RR orthovanillic acid (AOV) = 14% • para series • RR p-hydroxymethylguaiacol (PMG) = 0% • RR vanillin (PVA) = 16% • RR para-vanillic acid (APV) = 1% • di series • RR 4,6-di(hydroxymethyl) guaiacol (DMG) = 0% • RR 4,6-(diformyI) guaiacol (DFG) = 1% • RR orthocarboxyvanillin (OCVA) = 47% • RR 4,6-(dicarboxy) guaiacol (DCG) = 10% The sum of the yields of the upgradable products (guaiacol + OAV + PVA + APV + OCVA + DCG) was 87%. 3. Decarboxylation of reaction mixture 199.91 g of this reaction mixture was neutralised with 16.69 g of 92% sulphuric acid and introduced into a 300 ml autoclave provided with a turbine and a temperature regulation system. The reaction medium was heated to 175°C for 3 hours under autogenous pressure then cooled and measured using liquid chromatography. The vanillin yield and the guaiacol conversion were as follows: • TT guaiacol = 76%/initial guaiacol RR vanillin = 61%/initial guaiacol, i.e., RT vanillin = 80% • EXAMPLE 2 1. Condensation step The following was charged into a 2 litre reactor provided with a mechanical stirrer and a temperature regulation means: • 133 g of guaiacol; • 202 g of an aqueous 30% formol solution; • 145 g of an aqueous 30% caustic soda solution; • 480 g of water. The reaction medium was kept at 47°C for 0 h 50 then cooled 290 g of an aqueous 30% caustic soda solution was added. It was analysed using high performance liquid chromatography. The reaction balance was as follows: • guaiacol conversion = 97% • o-hydroxymethyl guaiacol (OMG) yield = 10% • p-hydroxymethyl guaiacol (PMG) yield = 12% • 4,6-di(hydroxymethyl) guaiacol (DMG) yield = 70%) • (OMG + DMG + PMG) yields = 92% The sum of the RT yields of the upgradable products was 95%). 2. Oxidation step The reaction medium was then diluted with 1230 g of water The reaction medium was introduced into a 3.9 litre autoclave provided with a self exhausting turbine. 0.54 g of bismuth trioxide and 34.5 g of a platinum catalyst deposited on carbon black in a proportion of 2% by weight of metal were then added. Stirring was started at a rate of 950 rpm and the temperature of the reaction medium was raised to 70°C under nitrogen. It was then placed under a pressure of 4 bars and air was introduced into the reaction medium at a rate of 200 g/h. The reaction medium was held under these conditions for 5 hours. The reaction medium was cooled and the pressure was reduced to atmospheric pressure then the catalyst was filtered. The reaction medium was then analysed by high performance liquid chromatography. The yields were as follows (for the complete sequence): • TTguaiacol = 97% • ortho series • RR o-hydroxymethyl guaiacol (OMG) = 0% • RR orthovanillin (OVA) = 1% • RR orthovanillic acid (AOV) = 6% • para series • RR p-hydroxymethylguaiacol (PMG) = 0% • RR vanillin (PVA) = 9% • RR para-vanillic acid (APV) = 2% • di series • RR 4,6-di(hydroxymethyl) guaiacol (DMG) = 0% • RR 4,6-(diformyl) guaiacol (DFG) = 1% • RR orthocarboxyvanillin (OCVA) = 54% • RR 4,6-(dicarboxy) guaiacol (DCG) = 6% The sum of the yields of the upgradable products (guaiacol + OAV + PVA + APV + OCVA + DCG) was 80%. 3. Decarboxylation of reaction mixture 150 g of this reaction mixture was neutralised with 15 ml of 10 mol/1 sulphuric acid and introduced into a 300 ml autoclave provided with a turbine and a temperature regulation system. The reaction medium was heated to 175°C for 2 hours under autogenous pressure then cooled and measured using liquid chromatography. The vanillin yield and the guaiacol conversion were as follows: • TT guaiacol = 91%/initial guaiacol • RR vanillin = 52%/initial guaiacol, i.e., RT vanillin = 57% WE CLAIM: 1. A process for preparing a 4-hydroxybenzaldehyde and its derivatives, characterized in that it consists of selectively oxidising the group in the 2 position with respect to the hydroxyl group to a carboxy group, and the hydroxymethyl group in the 4 position to a formyl group, present in the phenolic compounds in a mixture comprising at least: a phenolic compound (A) carrying formyl and/or hydroxymethyl groups in the 2 and 4 position; a phenolic compound (B) carrying a formyl or hydroxymethyl group in the 4 position; a phenolic compound (C) carrying a formyl or hydroxymethyl group in the 2 position; resulting in a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde, a 4-hydroxybenzaldehyde and a 2-hydroxy-benzoic acid, which then undergoes a decarboxylation operation to produce the 4-hydroxybenzaldehyde and a phenol. 2. The process as claimed in claim 1, wherein the reaction is carried out in the presence of a base and a catalyst based on a metal Ml selected from 1b and 8 metals, resulting in a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde, a 4-hydroxybenzaldehyde and a 2-hydroxybenzoic acid, which then undergoes a decarboxylation operation by heating to produce the 4-hydroxybenzaldehyde and a phenol which can be recycled. 3. The process as claimed in claim 1 or claim 2, wherein the mixture of phenolic compounds has general fonnula (II): in which, in formulae (IIA) to (IIC): Y1 and Y2, which may be identical or different, represent one of the following groups: a -CHO group; a -CH2OH group; Z1 Z2 and Z3 which may be identical or different, represent a hydrogen atom, an alkyl, alkenyl, alkoxy, hydroxyalkyl, alkoxyalkyl, cycloalkyl or aryl radical, a hydroxy group, a nitro group, a halogen atom, or a trifluoromethyl group. 4. The process as claimed in one of claims 1 to 3, wherein the phenolic compounds have formulae (IIA) to (IIC) where Z1 Z2 and Z3- which may be identical or different, represent one of the following 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 radical; a phenyl radical; a halogen atom, preferably a fluorine, chlorine or bromine atom. 5. The process as claimed in one of claims 1 to 4, wherein the phenolic compounds have formulae (IIA) to (IIC) where Zj 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 Yi and Y2 are identical and represent a formyl group or a hydroxymethyl group. 6. The process as claimed in one of claims 1 to 5, wherein the mixture of phenolic compounds with formula (11) is; o-hydroxymethylguaiacol, p-hydroxymethylguaiacol and 4,6- di(hydroxymethyl)guaiacol; o-formylguaiacol, p-formylguaiacol and 4,6-diformylguaiacol; o-hydroxymethylguetol, p-hydroxymethylguetol and 4,6-di(hydroxymethyl)guetol; o-formylguetol, p-formylguetol and 4,6-diformylguetol. 7. The process as claimed in one of claims 1 to 6, wherein a mixture of phenolic compounds with 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 M1 selected from metals from group lb and 8 of the periodic classification of the elements, which catalyst may contain, as an activator, metals such as cadmium, cerium, bismuth, lead, silver, tellurium or tin. 8. The process as claimed in claim 7, wherein the catalyst is based on copper, nickel, ruthenium, rhodium, palladium, osmium, iridium, platinum and mixtures thereof, said catalyst preferably being based on platinum and/ or palladium. 9. The process as claimed in claim 7 or claim 8, wherein the platinum and/or palladium based 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, aluminas or activated silicas or equivalent materials, preferably carbon black. 10. The process as claimed in anyone of claims 7 to 9, wherein the quantity of catalyst used, expressed as the weight of metal Mi with respect to that of the phenolic compound with formula (II), can vary from 0.01 % to 10%, preferably 0.04% to 2%. 11. The process as claimed in claims 7 to 10, wherein the activator is an organic or inorganic bismuth derivative selected from the group formed by: 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. 12. The process as claimed in claim 11, wherein the bismuth derivative is selected from the group formed by: bismuth oxides BiaOs and 81264; bismuth hydroxide Bi(0H)3; bismuth chloride BiCb; bismuth bromide BiBrs; bismuth iodide Bila; neutral bismuth sulphate 812(804)3; neutral bismuth nitrate 8i(N03)3,5H20; bismuthyl nitrate BiOCNOs); bismuthyl carbonate (BiO)2CO3,0.5H2O; bismuth acetate Bi(C2H302)3 and bismuth salicylate C6H4CO2 (BiO)OH. 13. The process as claimed in anyone of claims 7 to 12, wherein 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 Mi used, and 10 to 900 ppm by weight of metal Ml with respect to the mixture of phenolic compounds with formula (II). 14. The process as claimed in anyone of claims 7 to 13, wherein the oxidation reaction is carried out within a temperature range of 30°C to 200°C, preferably between 40°C and 160°C. 15. The process as claimed in anyone of claims 7 to 14, wherein a pressure of 1 to 20 bar is used. 16. The process as claimed in anyone of claims 7 to 15, wherein 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 1 to 4 moles, more preferably 2 to 4 moles, of inorganic base per mole of phenolic compounds with formula (II). 17. The process as claimed in claim 14, wherein when a platinum catalyst is used, the temperature is between 60°C and 160°C; the quantity of base used is in the range 1 to 3 moles per mole of phenolic compounds with formula (II). 18. The process as claimed in claim 14, wherein when a palladium catalyst is used, the temperature is between 30°C and 200°C, preferably between 30°C and 150°C; the quantity of base used is in the range 2 to 4 moles per mole of phenolic compounds with formula (II). 19. The process as claimed in anyone of claims 1 to 18, wherein the reaction medium obtained comprising 45 a 3-carboxy-4-hydroxybenzaldehyde, a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde, completely or partially in their salt form, undergoes decarboxylation. 20. The process as claimed in claim 19, wherein the acids to be decarboxylated have the following formula: wherein, said formulae (III) and (IV): M represents a hydrogen atom and/or a metallic cation from group (la) or (Ila), or an ammonium cation; Z1Z2 and Z3 have the meanings given in claims 3 to 5. 21. The process as claimed in claim 20, wherein said acid is decarboxylated by adding to the reaction medium a protonic acid of inorganic origin, preferably hydrochloric acid or sulphuric acid or an organic acid, until a pH of no more than 3 is obtained. 22. The process as claimed in anyone of claims 20 to 22, wherein the reaction medium is heated to a temperature between 120°C and 350°C, preferably 150°C to 220°C and after cooling, the 4-hydroxybenzaldehyde is separated which preferably has the following formula (VI): in which formula (VI): Z1 "Z2 and Z3 have the meanings given in claims 3 to 5. 23. A reaction medium comprising a 3-carboxy-4-hydroxybenzaldehyde, a 2- hydroxybenzoic acid and a 4-hydroxybenzaldehyde, completely or partially in their salt form prepared by the process as claimed in any one of the preceding claims. 24. The process as claimed in claim 23, wherein it consists of selectively oxidising, in accordance with the process defined in one of claims 1 to 17. 25. A process for preparing a mixture of phenolic compounds as claimed in claim I comprising the step of hydroxymethylating a phenol by condensing it with formaldehyde or a formaldehyde generator in an aqueous phase in the presence of an alkaline or alkaline-earth base such that the degree of phenol conversion is at most 95%, optionally followed by an oxidation step. 26. The process as claimed in claim 25, wherein the degree of phenol conversion is 60% to 95%, preferably 80% to 95%. 27. The process as claimed in claim 25 or claim 26, wherein the starting phenol is a phenol which is not substituted in the ortho and para positions with respect to the hydroxy 1 group, with general formula (I): 29. The process according to claim 28, wherein the phenol with formula (I) is guaiacol, guetol, 3-methoxyphenol, 3-ethoxyphenol, 3-isopropoxyphenol, 3-t- butoxyphenol, m-cresol, or o-cresol. 30. The process as claimed in anyone of claims 25 to 29, wherein formaldehyde or any formaldehyde generator is used, preferably trioxane or para-formaldehyde, used in the form of linear polyformaldehydes with any degree of polymerisation, preferably containing 8 to 100 (CH2O) units. 31. The process as claimed in claim 30, wherein the formaldehyde/phenol molar ratio is between 1.0 and 4.0, preferably between 1.0 and 2.5. 32. The process as claimed in claim 25, wherein the quantity of base present in the hydroxymethylation medium, expressed as the number of moles of basel phenolic hydroxy group of the phenol to be hydroxymethylated, is between 1.0 and 4.0, preferably between 0.9 and 2.0, 33. A process according to claim 25, wherein the hydroxymethylation temperature is in the range 0°C to 100°C, preferably in the range 20°C to 70°C. 34. The process as claimed in claim 25, wherein the duration of the hydroxymethylation reaction is between 15 minutes and 4 hours, preferably between 1 hour and 3 hours. 35. The process as claimed in claim 25, wherein the phenol and the formaldehyde and the optional base are charged into the apparatus, then the reaction mixture is heated to the desired temperature with stirring, for the period necessary to carry out the reaction until a mixture of phenolic compounds is obtained. 36.The process as claimed in claim 1, wherein the phenol obtained is recycled. 37. A process for preparing a 4-hydroxybenzaldehyde and its derivatives substantially as herein described and exemplified.

Full Text

The present invention concerns a process for the preparation of a 4-hydroxybenzaldehyde and its derivatives.
More particularly, the invention concerns the preparation of 3-methoxy-4-hydroxybenzaldehyde and 3-ethoxy-4-hydroxybenzaldehyde, respectively known as vanillin and ethylvanillin.
hi French patent application n° 95/06186, a process is described for the preparation of 4-hydroxybenzaldehydes, more particularly vanillin and ethylvanillin.
The process described consists of preparing a 3-carboxy-4-hydroxybenzaldehyde then decarboxylating that compound to produce the 4-hydroxybenzaldehyde.
According to FRn°95/06186, the 3-carboxy-4-hydroxybenzaldehyde is prepared from one of the compounds given below and mixtures thereof, more

an alkyl, alkenyl, alkoxy, hydroxyalkyl, alkoxyalkyl, cycloalkyl or aryl radical, a hydroxyl group, a nitro group, a halogen atom, or a trifluoroethyl group.

In that patented process, the starting compound is a bifunctional phenohc compound carrying two functional groups on the aromatic ring in the ortho and para positions which can be a -CHO group and/or a -CH2OH group.
Firstly, the ortho group is selectively oxidised to a carboxylic group; the group in the para position is at most oxidised to a formyl group. After elimuiating the carboxy group in the ortho position, a 4-hydroxybenzaldehyde is obtained.
Thus vanillin and ethylvanillin can advantageously be prepared using a process which is selective and also highly competitive from an industrial viewpoint as it uses inexpensive reactants.
However, in that process it is difficult to obtain a reaction yield (expressed with respect to the starting phenol) of more than 70% as obtaining a high yield of a bifimctional phenolic compound is accompanied by that of a by-product, namely a bis-arylmethane.
During our research, we discovered in French application n°96/12479 that a 4-hydroxybenzaldehyde can be prepared from a mixture of monosubstituted 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, and selectively oxidising the formyl or hydroxymethyl group in the 2 position of compound (A) to a carboxy group, and possibly a hydroxymethyl group in the 4 position of compound (B) to a formyl group, thus producing a mixture of a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde from which the latter is separated.

an alkyl, alkenyl, alkoxy, hydroxyalkyl, alkoxyalkyl, cycloalkyl or aryl radical, a hydroxyl group, a nitro group, a halogen atom, or a trifluoroethyl group.

The disadvantage of that process is that to obtain compounds with formula (DA) or (IIB), by hydroxymethylation of a phenol, it is essential to work with a low degree of conversion of the starting phenol which results in low productivity.
Thus the existing processes must be improved in order to have available a process which is of great economic interest which minimises the by-products and can produce a high operating productivity.
We have discovered, and this constitutes one aspect of the present invention, a process for the preparation of a 4-hydroxybenzaldehyde and its derivatives, characterized in that it consists of selectively oxidising, to a carboxy group, the group in the 2 position with respect to the hydroxyl group, present in the phenolic compounds in a mixture comprising at least:
• a phenolic compoimd (A) carrying formyl and/or hydroxymethyl groups in the 2 and 4 position;
• a phenolic compound (B) carrying a formyl or hydroxymethyl group in the 4 position;
• a phenolic compound (C) carrying a formyl or hydroxymethyl group in the 2 position;
resulting in a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde, a 4-hydroxybenzaldehyde and a 2-hydroxybenzoic acid, which then undergoes a decarboxylation operation to produce the 4-hydroxybenzaldehyde and a phenol which can optionally be recycled.
Li a further aspect, the invention provides a starting mixture of phenolic compounds claimed as; the mixture itself, and the mixture obtained after oxidation.
Finally, processes for preparing these mixtures constitute further aspects of the mvention.
hi the process of the invention, we have discovered that by starting from a mixture of starting compounds as defined above, it is possible to carry out simultaneous intramolecular oxidation (A) and intermolecular oxidation (B + C) since oxidation of the carboxy group takes place preferentially on the hydroxymethyl or formyl group in the ortho position.
The process of the invention thus comprises an oxidation step and a decarboxylation step for a 3-carboxy-4-hydroxybenzaldehyde to a 4-hydroxybenzaldehyde and a 2-hydroxybenzoic acid which can produce the phenolic starting compound which can then be recycled; the 4-hydroxybenzaldehyde is then recovered conventionally.

The starting substrates used in the process of the invention are mixtures of
phenolic compounds, one (A) carrying formyl and/or hydroxymethyl groups in the
2 and 4 positions, the second (B) carrying a formyl or a hydroxymethyl group in
the 4 position and the last, (C), in the 2 position.
" The term "phenolic compound" means any aromatic compound with an
aromatic nucleus which carries a hydroxy group.
In the following disclosure of the present invention, the term "aromatic" means the conventional idea of aromaticity as defined in the literature, in particular in "Advanced Organic Chemistry" by Jerry MARCH, 4* edition, John

have formulae (DA) to (EC) where Z], Z2 and Z3, which may be identical or different, represent one of the following 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 radical;

• a phenyl radical;
• a halogen atom, preferably a fluorine, chlorine or bromine atom.
The present invention does not exclude the presence of substituents of different natures on the aromatic ring, provided that they do not interfere with the reactions taking place in the process of the invention.
The present invention is preferably applicable to compounds with formula (HA) to (HC) where Zi 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; Z and Z3 represent a hydrogen atom; and Yi and Y2 are identical and represent a formyl group or a hydroxymethyl group.
Preferred examples of mixtures of phenolic compounds for use in the process of the invention are:
• o-hydroxymethylguaiacol, p-hydroxymethylguaiacol and 4,6- ""-di(hydroxymethyl)guaiacol;
• o-formylguaiacol, p-formylguaiacol and 4,6-diformylguaiacol;
• o-hydroxymethylguetol, p-hydroxymethylguetol and 4,6-
di(hydroxymethyl)guetol;
• o-formylguetol, p-formylguetol and 4,6-diformylguetol.
The process of the invention uses a starting mixture of phenolic compounds which preferably have formula (II).
The proportion of each phenolic compound in the mixture depends on the method of their preparation.
Preferred mixtures comprise:
• 30% to 70% by weight, more preferably 50% to 70%, of a phenolic compound
(A);
• 30% to 70% by weight, more preferably 50% to 70%, of a mixture of phenolic
compounds (B+C).
As an indication, the quantities of isomers B and C are approximately equimolar in the mixture.
A reaction scheme is given below to facilitate comprehension of the disclosure of the invention without in any way limiting the scope of the invention to the scheme.

In the present text, reference will be made to the periodic table published in the "Bulletin de la Societe Chimique de France", n°l (1966).
In accordance with the process of the invention, the Yi group in position 2 of phenolic compounds (A) and (C) preferably with formulae (HA) and (IIC) is selectively oxidised to a carboxy group, and a hydroxymethyl group, if present in the 4 position in phenolic compounds (A) and (B) preferably with formulae (IIA) and (IIB), is selectively oxidised to a formyl group.
Oxidation is carried out using 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 with formula (II) m 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 Mi selected from metals from group lb and 8 of the periodic classification of the elements, which may optionally contain,

as an activator, metals such as cadmium, cerium, bismuth, lead, silver, tellurium or tin.
We have surprisingly discovered that if the temperature is increased and the reaction is preferably carried out under pressure or if the quantity of base present during oxidation is increased, group Yi in the 2 position in phenolic compounds (A) and (C), preferably with formulae (HA) and (EC) is selectively oxidised to a carboxy group, and the group located in the 4 position in phenolic compounds (A) and (B), preferably with formulae (DA) and (HB), is at most oxidised to the formyl group..
The catalysts used in the process of the invention are based on a metal from 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 Regarding metals from group lb, copper is preferred.
Preferably, platinum and/or palladium catalysts are used, in any available form such as: platinum black, palladium black, platinum oxide, palladium oxide or the noble metal itself deposited on different supports such as carbon black, calcium carbonate, aluminas or activated silicas or equivalent materials. Catalytic masses based on carbon black are particularly suitable.
The quantity of catalyst used, expressed as the weight of metal Mi with respect to that of the phenolic compound with formula (II), can vary from 0.01% to 10%, preferably 0.04% to 2%.
Further details of the catalysts can be obtained from United States patent US-A-3 673 257, and French patents FR-A-2 305 420 and FR-A-2 350 323.
The activator can be selected from all those mentioned in the above patents. Preferably, bismuth, lead and cadmium are used as the free metal or as cations. In the latter case, the associated anion is not critical and all derivatives of these metals can be used. Preferably, bismuth metal or its derivatives is used.
An inorganic or organic bismuth derivative can be used in which the bismuth atom has an oxidation number of more than zero, for example 2, 3, 4 or 5. The residue associated with the bismuth is not critical provided that is satisfies this condition. The activator can be soluble or insoluble in the reaction medium.
Illustrative examples of activators which can be used in the process of the present invention are: 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, niobate, 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 sahs.
Other inorganic or organic compounds are binary compounds of bismuth with elements such as phosphorous or arsenic; heteropolyacids containing bismuth and salts thereof; also aliphatic and aromatic bismuthines.
Specific examples are:
• oxides: BiO; Bi203; Bi204; BizOj;
• hydroxides: Bi(0H)3;
• salts of inorganic hydracids: bismuth chloride BiCla; bismuth bromide BiBrs; bismuth iodide Bils; bismuth sulphide BiaSs; bismuth selenide BiiScs; bismuth telluride BiaTes;
• salts of inorganic oxyacids: basic bismuth sulphite Bi2(S03)3,Bi203,5H20; neutral bismuth sulphate Bi2(S04)3; bismuthyl sulphate (BiO)HS04; bismuthyl nitrite (BiO)NO2,0.5H2O; 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 BiP04; bismuth pyrophosphate B"iPjOih; bismuthyl carbonate (BiO)2CO3;0.5H2O; neutral bismuth perchlorate Bi(C104)3,5H20; bismuthyl perchlorate (BiO)C104; bismuth antimonate BiSb04; neutral bismuth arsenate Bi(As04)3; bismuthyl arsenate (Bi0)As04,5H20; bismuth selenite 812(8603)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]2Cr207; acid bismuthyl chromate H(Bi0)Cr04; double chromate of bismuthyl and potassium K(Bi0)Cr04; bismuth molybdate Bi2(Mo04)3; bismuth tungstate Bi2(W04)3; double molybdate of bismuth and sodium NaBi(Mo04)2; basic bismuth permanganate Bi202(OH)Mn04;
• sahs of aliphatic or aromatic organic acids: bismuth acetate Bi(C2H302)3; bismuthyl propionate (BiO)C3H502; basic bismuth benzoate C6H5C02Bi(OH)2;

bismuthyl salicylate C6H4C02(BiO)(OH); bismuth oxalate (C204)3Bi2; bismuth
tartrate Bi2(C4H406)3,6H20; bismuth lactate (C6H905)OBi,7H20; bismuth
citrate CeHjOvBi; • phenates: basic bismuth gallate C-jUjOjBi; basic bismuth pyrogallate
C6H3(OH)2(OBi)(OH).
Other inorganic or organic compoimds are also suitable: bismuth phosphide BiP; bismuth arsenide Bi3As4; sodium bismuthate NaBi03; bismuth-thiocyanic acids H2[Bi(BNS)5],H3[Bi(CNS)6] and sodium and potassium salts thereof; trimethylbismuthine Bi(CH3)3, triphenylbismuthine Bi(C6H5)3.
Preferred bismuth derivatives for use in the process of 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 group of activators for carrying out the process of the invention is constituted by: bismuth oxides Bi203 and Bi204; bismuth hydroxide Bi(0H)3; neutral bismuth sulphate 812(804)3; bismuth chloride BiCl3; bismuth bromide BiBr3; bismuth iodide Bils; neutral bismuth nitrate Bi(N03)3,5H20; bismuthyl nitrate BiOCNOa); 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 Mi used, can be varied between wide limits. As an example, this quantity can be as low as 0.1% and can attain the weight of metal Mj used, or even exceed it without any problems.
More particularly, this quantity is selected so that it provides the oxidation medium with 10 ppm to 900 ppm by weight of activator metal with respect to the phenolic compound with formula (II). hi this respect, higher quantities of activator of the order of 900 ppm to 1500 ppm can naturally be used, but with no great additional advantage.
hi the process of the mvention, oxidation is carried out in an aqueous medium containing a basic agent in solution, more particularly ammonium hydroxide, alkaline or alkaline-earth bases, for example hydroxides such as sodium, potassium, lithium and baryte hydroxides; alkaline alkanolates such as sodium or potassium methylate, ethylate, isopropylate or t-butylate, sodium or

potassium carbonates or bicarbonates and in general, the salts of alkaline or alkaline-earth bases and weak acids.
Thus compounds with formulae (HI) to (V) can be completely or partially in their salt form depending on the quantity of basic agent used. It follows that in these formulae, M, the residue of the base, generally symbolises a hydrogen atom and/or a metallic cation from group (la) or (Ha) or an ammonium cation.
Sodium or potassium hydroxide is used for reasons of economy. The proportion of inorganic base to be used can be in the range 0.5 to 10 moles, preferably in the range 1 to 4 moles, more preferably in the range 2 to 4 moles, of inorganic base per mole of phenolic compounds with formula (11).
The concentration by weight of the mixture of phenolic compounds with formula (II) in the liquid phase is usually in the range 1% to 60%, preferably in the range 2% to 30%.
In practice, one implementation of the process consists of bringing the solution comprising the mixture of phenolic compounds with formula (H), the basic agent, the catalyst based on metal Mi, and any activator into contact with molecular oxygen or a gas containing molecular oxygen in the proportions indicated above.
Atmospheric pressure can be used, but it is preferable to operate at a pressure of 1 to 20 bar.
The mixture is then stirred at the desired temperature until a quantity of oxygen has been consumed which corresponds to that necessary to transform the hydroxymethyl group or formyl group of compounds (A) and (C) into a carboxy group, and the hydroxymethyl group, if present in compounds (A) and (B), into a formyl group.
The reaction temperature to be used depends on the thermal stability of the products to be prepared.
In accordance with the invention, the temperature is preferably selected so as to be in the range 30°C to 200°C, preferably in the range 40°C to 160°C. ,
The temperature can be adapted to the reaction conditions by the skilled person(in particular the quantity of base, nature of metal Mi, pressure and stirring). In particular, it has been discovered that the lower the temperature the higher must be the quantity of basic agent used.
Examples of preferred conditions in the case of preferred metals platinum and palladium will now be given. For platinum, the temperature can be between 60°C and 160°C, the quantity of base to be used is advantageously in the range 1

to 3 moles per mole of phenolic compounds with formula (11). For palladium, the temperature can be between„3Q°C and 200°C, preferably between 30°C and 150°C, and for the latter interval, the quantity of base is preferably 2 to 4 moles per mole of phenolic compounds.
The quantity of base must be sufficient to oxidise the Yi group in the position ortho to the carboxy group. It is determined by the skilled person depending on the temperature and the selected metal.
At the end of the reaction, which preferably takes 30 minutes to 6 hours, a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde preferably with formula (HI), a 4-hydroxybenzaldehyde preferably with formula (V) and a 2-hydroxybenzoic acid preferably with formula (IV) are recovered: the compounds can be partially or totally in their salt form.
After any necessary cooling, the catalytic mass and the reaction mass are separated, for example by filtering.
In a second step of the process of the invention, the reaction medium undergoes a decarboxylation reaction.
This is carried out by acidifying the resulting medium by adding a protonic mineral acid, preferably hydrochloric acid or sulphuric acid or an organic acid such as trifluoromethanesulphonic acid or methanesulphonic acid, to obtain a pH 3 or less.
The concentration of acid is immaterial and preferably, commercially available concentrations are used.
The reaction medium is heated to a temperature of between 120°C and 350 °C, preferably between 150°C and 220°C.
The process is preferably carried out under autogenous pressure of the reactants.
At the end of the reaction, the reaction medium is cooled to between 20°C and 80°C.
A two-phase medium is obtained constituted by an organic phase comprising the 4-hydroxybenzaldehyde preferably with formula (VI) and the starting phenolic compound with formula (I), and also a saline aqueous phase.
The organic and aqueous phases are separated and the 4-hydroxybenzaldehyde is recovered jfrom the organic phase using conventional separation techniques, for example extraction using an appropriate solvent (for example methylisobutylketone or isopropyl ether), or by distillation.

The improved process of the mvention starts with a mixture of two phenolic compounds, one carrying a formyl or hydroxymethyl group in the 2 and 4

The mixtures of phenolic compounds, to which the process of the invention can be applied, are prepared by a process which constitutes a further aspect of the invention.
Thus mixtures of phenolic compounds with formulae (Ilai) to (IIci) can be obtamed by a process for hydroxymethylating a phenol by condensing it with formaldehyde or a formaldehyde generator in an aqueous phase in the presence of and alkaline or alkaline-earth base, so that the phenol conversion is at most 95% optionally followed by an oxidation step.

Examples of phenols with formula (I) which can act as a starting point for the synthesis of compounds with formula (II) are guaiacol, guetol, 3-methoxyphenol, 3-ethoxyphenol, 3-isopropoxyphenol, 3-t-butoxyphenol, m-cresol and p-cresol.
The conditions selected for carrying out this hydroxymethylation step are those recommended by the prior art listed below: cf in particular H. G. PEER, Rec. Trav. Chim. Netherlands 79, 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, Rec. Trav. Chim. Netherlands 78 851-863 (1959); H. EULER et al, Arkiv flir 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 trioxane or paraformaldehyde used as linear paraformaldehydes of any degree of polymerisation, preferably containing 8 to 100 (CH2O) units.
Formaldehyde can be used as an aqueous solution in a concentration which is not critical. It can be in the range 20% to 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 be between 1.0 and 4.0, preferably between 1.0 and 2.5.
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 hydroxymethylated, can vary between wide limits. In general, this ratio, which varies depending on the base, can be between 1.0 and 4.0, preferably between 0.9 and 2.0. The base used may be one of those cited above for the oxidation step. Aqueous solutions of alkaline hydroxides are particularly suitable.
In general, the hydroxymethylation step is carried out at a temperature in the range 0°C to 100°C, preferably in the range 20°C to 70°C.
The process is preferably carried out at a pressure which is autogenous for the reactants to avoid any paraformaldehyde losses which may be gaseous at the temperatures used.
Preferably, the reaction is carried out in a controlled atmosphere of inert gas such as nitrogen or a noble gas, for example argon.
The reaction time can readily be determined by the skilled person depending on the desired degree of conversion of the starting phenol and taking

into account the necessity to minimise by -products such as bis-arylmethane. It is usually between 15 minutes and 4 hours, preferably between 1 hour and 3 hours.
The degree of conversion of phenol is controlled by different parameters (temperature, duration, quantity of reactants). It is advantageously in the range 60% to 95%, preferably in the range 80% to 95%.
In practice, the reaction is readily carried out by charging the phenol and formaldehyde, and any base into the apparatus, then stirring and heating the reaction mixture to the desired temperature 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 (Elai) to (IIci) is obtained.
Compounds with formula (Ilai) to (nc2) can be prepared by oxidising hydroxymethylated phenolic compounds with formula (Ilai) to (IIci), by oxidising using molecular oxygen or a gas containing molecular oxygen, in an aqueous alkaline phase, in the presence of a catalyst based on a metal from group 8 of the r periodic table, preferably platinum or 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 FR-A-2 350 323.
If necessary, the pH of the solution can be raised to a value in thejange„8,
to 13 by optional addition of an alkalme or alkaline-earth base. The optional value i of the pH depends on the natiire of the hydroxymethylated phenols.
The temperature of the oxidation reaction is between 10°C and 100°C, preferably between 20°C and 60°C.
More specifically again, the process of the present invention is suitable for the preparation of compounds with formulae (na2) to (nc2) from phenolic compounds with formulae (Ilai) to (IIci) resulting from the first step, using molecular oxygen or a gas containing molecular oxygen, in the presence of a catalyst based on a metal from group 8 of the periodic table, optionally containing a metal such as those used as an activator, without intermediate separation of the hydroxymethylated phenolic compounds.
From an industrial viewpoint, it is particularly advantageous when carrying out the process of the present invention to use compounds with formula (na2) to (nc2) obtained by a two-step process comprising:

• hydroxymethylation of a phenol in an aqueous medium in the presence of an
alkaline or alkaline-earth base using formaldehyde or a formaldehyde
generator, resulting in a mixture of hydroxymethylated phenolic compounds,
one being hydroxymethylated m the 2 and 4 positions and the two others being
hydroxymethylated in the 2 or in the 4 position;
• and oxidation, without intermediate separation, of the phenolic compounds
obtained using molecular oxygen or a gas containing molecular oxygen, in an 6
aqueous alkaline phase in the presence of a catalyst based on a metal from
group 8 of the periodic table, and optionaliy, a metal such as those cited above,
acting as an activator.
An additional advantage of the process of the invention is that it allows mixtures of phenolic compounds issuing directly from the preceding hydroxymethylation and optional oxidation steps to be used.
As mentioned above, the process of the invention is particularly suitable for the preparation of vanillin and ethylvanillin from a mixture of phenolic compounds obtained by hydroxymethylation of guaiacol or guetol.
Thus vanillin can be prepared by selectively oxidising a mixture of
phenolic compounds, 4,6-di(hydroxymethyl)guaiacol (A), p-
hydroxymethylguaiacol (B) and o-hydroxymethylguaiacol (C) at the hydroxymethyl group in the 2-position of compounds (A) and (C) to a carboxy group, and the hydroxymethyl group in the 4 position in compounds (A) and (B) to a formyl group, resulting in a mixture of 3-carboxy-4-hydroxy-5-methoxybenzaldehyde, vanillin and 2-hydroxy-3-methoxybenzoic acid which, after decarboxylation, produces vanillin and guaiacol which can be recycled.
A variation consists of selectively oxidising a mixture of phenolic compounds, 4,6-di(formyl)guaiacol (A), p-formylguaiacol (B) and o-formylguaiacol (C) at the formyl group in the 2-position of compounds (A) and (C) to a carboxy group, resulting in a mixture of 3-carboxy-4-hydroxy-5- methoxybenzaldehyde, vanillin and 2-hydroxy-3-methoxybenzoic acid which, after decarboxylation, produces vanillin and guaiacol which can be recycled.
Ethylvanillin is prepared by the process of the present invention by selectively oxidising a mixture of phenolic compounds, 4,6-di(hydroxymethyl)guetol (A), p-hydroxymethylguetol (B) and o- hydroxymethylguetol (C) at the hydroxymethyl group in the 2-position of compounds (A) and (C) to a carboxy group, and the hydroxymethyl group in the 4 position in compounds (A) and (B) to a formyl group, resulting m a mixture of 3-

carboxy-4-hydroxy-5-ethoxybenzaldehyde, ethylvanillin and 2-hydroxy-3-ethoxybenzoic acid which, after decarboxylation, produces ethylvanillin and guetol which can be recycled.
A further variation consists of selectively oxidising a mixture of phenolic compounds, 4,6-di(formyl)guetol (A), p-fonylguetol (B) and oformylguetol (C) at the formyl group in the 2-position of compounds (A) and (C) to a carboxy group, resulting in a mixture of 3-carboxy-4-hydroxy-5-ethoxybenzaldehyde, ethylvanillin and 2-hydroxy-3-ethoxybenzoic acid which, after decarboxylation, produce vanilling and guaiacol which can be recycled.
Examples of implementations of the invention will now be given. These examples are given by way of indication and are in no way limiting.
The degree of conversion and the yield obtained are defined in the examples.
The degree of conversion (TT) corresponds to the ratio between the number of moles of substrate transformed and the number of moles of substrate used.
The yield (RR) corresponds to the ratio between the number of moles of product formed and the number of moles of substrate used.
The yield (RTyaniiiin) corresponds to the ratio between the number of moles of vanillin formed and the number of moles of guaiacol transformed in the sequence.
The following abbreviations are used in the examples:
• o-hydroxymethylguaiacol = OMG
• p-hydroxymethylguaiacoi = PMG
• o-vanillin = 3-methoxy-2-hydroxybenzaldehyde = OVA
• p-vanillm = 3-methoxy-4-hydroxybenzaldehyde = PVA
• o-vanillic acid = 2-hydroxy-3-methoxybenzoic acid = AOV
• p-vanillic acid = 4-hydroxy-3-methoxybenzoic acid = APV
• 4,6-di(hydroxymethyl) guaiacol = DMG
• 4,3-(diformyl)guaiacol = DFG
• o-carboxyvanillin = OCVA
• 4,6-(dicarboxy)guaiacol = DCG.
EXAMPLE 1 1. Condensation step
The following was charged into a 2 litre reactor provided with a mechanical stirrer and a temperature regulation means:

• 152 gof guaiacol;
• 249 g of an aqueous 30% formol solution;
• 49.2 g of caustic soda;
• 872 gof water.
The reaction medium was kept at 45°C for 1 hour then cooled and analysed using high performance liquid chromatography. The reaction balance was as follows:
• guaiacol conversion = 90%
• o-hydroxymethyl guaiacol (OMG) yield = 15%
• p-hydroxymethyl guaiacol (PMG) yield = 18%
• 4,6-di(hydroxymethyl) guaiacol (DMG) yield = 83%
The sum of the upgradable products was 93%. 2. Oxidation step
The reaction medium was then diluted with 1500 g of water and 148 g of caustic soda.
The reaction medium was then introduced into a 3.9 litre autoclave provided with a self exhausting turbine.
0.54 g of bismuth trioxide and 22 g of a palladium catalyst deposited on carbon black in a proportion of 3% by weight of metal were then added.
Stirring was started at a rate of 1500 rpm and the temperature of the reaction medium was raised to 45°C under nitrogen. It was then placed under a pressure of 3 bars and air was introduced into the reaction medium at a rate of 300 g/h. The reaction medium was held under these conditions for 6 houis.
The reaction mediimi was cooled and the pressure was reduced to atmospheric pressure then the catalyst was filtered.
The reaction medium was then analysed by high performance liquid chromatography.
The yields were as follows (for the complete sequence):
• TT guaiacol = 92%
• ortho series

• RR o-hydroxymethyl guaiacol (OMG) = 0%
• RRorthovanillin(OVA) = 1%
• RR orthovanillic acid (AOV) = 14%
• para series
• RR p-hydroxymethylguaiacol (PMG) = 0%
• RR vanillin (PVA) = 16%

• RR para-vanillic acid (APV) = 1%
• di series
• RR 4,6-di(hydroxymethyl) guaiacol (DMG) = 0%
• RR 4,6-(diformyI) guaiacol (DFG) = 1%
• RR orthocarboxyvanillin (OCVA) = 47%
• RR 4,6-(dicarboxy) guaiacol (DCG) = 10%
The sum of the yields of the upgradable products (guaiacol + OAV + PVA + APV + OCVA + DCG) was 87%. 3. Decarboxylation of reaction mixture
199.91 g of this reaction mixture was neutralised with 16.69 g of 92% sulphuric acid and introduced into a 300 ml autoclave provided with a turbine and a temperature regulation system.
The reaction medium was heated to 175°C for 3 hours under autogenous pressure then cooled and measured using liquid chromatography.
The vanillin yield and the guaiacol conversion were as follows:
• TT guaiacol = 76%/initial guaiacol
RR vanillin = 61%/initial guaiacol, i.e., RT vanillin = 80%
•
EXAMPLE 2 1. Condensation step
The following was charged into a 2 litre reactor provided with a mechanical stirrer and a temperature regulation means:
• 133 g of guaiacol;
• 202 g of an aqueous 30% formol solution;
• 145 g of an aqueous 30% caustic soda solution;
• 480 g of water.
The reaction medium was kept at 47°C for 0 h 50 then cooled 290 g of an aqueous 30% caustic soda solution was added. It was analysed using high performance liquid chromatography. The reaction balance was as follows:
• guaiacol conversion = 97%
• o-hydroxymethyl guaiacol (OMG) yield = 10%
• p-hydroxymethyl guaiacol (PMG) yield = 12%
• 4,6-di(hydroxymethyl) guaiacol (DMG) yield = 70%)
• (OMG + DMG + PMG) yields = 92%
The sum of the RT yields of the upgradable products was 95%).

2. Oxidation step
The reaction medium was then diluted with 1230 g of water
The reaction medium was introduced into a 3.9 litre autoclave provided with a self exhausting turbine.
0.54 g of bismuth trioxide and 34.5 g of a platinum catalyst deposited on carbon black in a proportion of 2% by weight of metal were then added.
Stirring was started at a rate of 950 rpm and the temperature of the reaction medium was raised to 70°C under nitrogen. It was then placed under a pressure of 4 bars and air was introduced into the reaction medium at a rate of 200 g/h. The reaction medium was held under these conditions for 5 hours.
The reaction medium was cooled and the pressure was reduced to atmospheric pressure then the catalyst was filtered.
The reaction medium was then analysed by high performance liquid chromatography.
The yields were as follows (for the complete sequence):
• TTguaiacol = 97%
• ortho series

• RR o-hydroxymethyl guaiacol (OMG) = 0%
• RR orthovanillin (OVA) = 1%
• RR orthovanillic acid (AOV) = 6%
• para series
• RR p-hydroxymethylguaiacol (PMG) = 0%
• RR vanillin (PVA) = 9%
• RR para-vanillic acid (APV) = 2%
• di series
• RR 4,6-di(hydroxymethyl) guaiacol (DMG) = 0%
• RR 4,6-(diformyl) guaiacol (DFG) = 1%
• RR orthocarboxyvanillin (OCVA) = 54%
• RR 4,6-(dicarboxy) guaiacol (DCG) = 6%
The sum of the yields of the upgradable products (guaiacol + OAV + PVA + APV + OCVA + DCG) was 80%.
3. Decarboxylation of reaction mixture
150 g of this reaction mixture was neutralised with 15 ml of 10 mol/1 sulphuric acid and introduced into a 300 ml autoclave provided with a turbine and a temperature regulation system.

The reaction medium was heated to 175°C for 2 hours under autogenous pressure then cooled and measured using liquid chromatography.
The vanillin yield and the guaiacol conversion were as follows:
• TT guaiacol = 91%/initial guaiacol
• RR vanillin = 52%/initial guaiacol, i.e., RT vanillin = 57%

WE CLAIM:
1. A process for preparing a 4-hydroxybenzaldehyde and its derivatives,
characterized in that it consists of selectively oxidising the group in the 2 position
with respect to the hydroxyl group to a carboxy group, and the hydroxymethyl
group in the 4 position to a formyl group, present in the phenolic compounds in a
mixture comprising at least:
a phenolic compound (A) carrying formyl and/or hydroxymethyl groups in the 2 and 4 position;
a phenolic compound (B) carrying a formyl or hydroxymethyl group in the 4 position;
a phenolic compound (C) carrying a formyl or hydroxymethyl group in the 2 position; resulting in a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde, a 4-hydroxybenzaldehyde and a 2-hydroxy-benzoic acid, which then undergoes a decarboxylation operation to produce the 4-hydroxybenzaldehyde and a phenol.
2. The process as claimed in claim 1, wherein the reaction is carried out in the
presence of a base and a catalyst based on a metal Ml selected from 1b and 8
metals, resulting in a mixture comprising a 3-carboxy-4-hydroxybenzaldehyde, a
4-hydroxybenzaldehyde and a 2-hydroxybenzoic acid, which then undergoes a
decarboxylation operation by heating to produce the 4-hydroxybenzaldehyde and a
phenol which can be recycled.
3. The process as claimed in claim 1 or claim 2, wherein the mixture of phenolic

compounds has general fonnula (II):

in which, in formulae (IIA) to (IIC):
Y1 and Y2, which may be identical or different, represent one of the following groups:
a -CHO group; a -CH2OH group;
Z1 Z2 and Z3 which may be identical or different, represent a hydrogen atom, an alkyl, alkenyl, alkoxy, hydroxyalkyl, alkoxyalkyl, cycloalkyl or aryl radical, a hydroxy group, a nitro group, a halogen atom, or a trifluoromethyl group.
4. The process as claimed in one of claims 1 to 3, wherein the phenolic compounds have formulae (IIA) to (IIC) where Z1 Z2 and Z3- which may be identical or different, represent one of the following 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 radical;
a phenyl radical;
a halogen atom, preferably a fluorine, chlorine or bromine atom.
5. The process as claimed in one of claims 1 to 4, wherein the phenolic compounds have formulae (IIA) to (IIC) where Zj 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 Yi and Y2 are identical and represent a formyl group or a hydroxymethyl group.
6. The process as claimed in one of claims 1 to 5, wherein the mixture of phenolic compounds with formula (11) is;
o-hydroxymethylguaiacol, p-hydroxymethylguaiacol and 4,6-
di(hydroxymethyl)guaiacol; o-formylguaiacol, p-formylguaiacol and 4,6-diformylguaiacol; o-hydroxymethylguetol, p-hydroxymethylguetol and 4,6-di(hydroxymethyl)guetol; o-formylguetol, p-formylguetol and 4,6-diformylguetol.
7. The process as claimed in one of claims 1 to 6, wherein a mixture of phenolic compounds with 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 M1 selected from metals

from group lb and 8 of the periodic classification of the elements, which catalyst may contain, as an activator, metals such as cadmium, cerium, bismuth, lead, silver, tellurium or tin.
8. The process as claimed in claim 7, wherein the catalyst is based on copper, nickel, ruthenium, rhodium, palladium, osmium, iridium, platinum and mixtures thereof, said catalyst preferably being based on platinum and/ or palladium.
9. The process as claimed in claim 7 or claim 8, wherein the platinum and/or palladium based 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, aluminas or activated silicas or equivalent materials, preferably carbon black.

10. The process as claimed in anyone of claims 7 to 9, wherein the quantity of catalyst used, expressed as the weight of metal Mi with respect to that of the phenolic compound with formula (II), can vary from 0.01 % to 10%, preferably 0.04% to 2%.
11. The process as claimed in claims 7 to 10, wherein the activator is an organic or inorganic bismuth derivative selected from the group formed by: 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.
12. The process as claimed in claim 11, wherein the bismuth derivative is selected from the group formed by: bismuth oxides BiaOs and 81264; bismuth hydroxide Bi(0H)3; bismuth chloride BiCb; bismuth bromide BiBrs; bismuth iodide Bila; neutral bismuth sulphate 812(804)3; neutral bismuth nitrate 8i(N03)3,5H20; bismuthyl nitrate BiOCNOs); bismuthyl carbonate (BiO)2CO3,0.5H2O; bismuth acetate Bi(C2H302)3 and bismuth salicylate C6H4CO2 (BiO)OH.
13. The process as claimed in anyone of claims 7 to 12, wherein 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 Mi used, and 10 to 900 ppm by weight of metal Ml with respect to the mixture of phenolic compounds with formula (II).
14. The process as claimed in anyone of claims 7 to 13, wherein the oxidation reaction is carried out within a temperature range of 30°C to 200°C, preferably between 40°C and 160°C.
15. The process as claimed in anyone of claims 7 to 14, wherein a pressure of 1 to 20 bar is used.
16. The process as claimed in anyone of claims 7 to 15, wherein 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 1 to 4 moles, more preferably 2 to 4 moles, of inorganic base per mole of phenolic compounds with formula (II).
17. The process as claimed in claim 14, wherein when a platinum catalyst is used, the temperature is between 60°C and 160°C; the quantity of base used is in the range 1 to 3 moles per mole of phenolic compounds with formula (II).
18. The process as claimed in claim 14, wherein when a palladium catalyst is used, the temperature is between 30°C and 200°C, preferably between 30°C and 150°C; the quantity of base used is in the range 2 to 4 moles per mole of phenolic compounds with formula (II).
19. The process as claimed in anyone of claims 1 to 18, wherein the reaction medium obtained comprising 45 a 3-carboxy-4-hydroxybenzaldehyde, a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde, completely or partially in their salt form, undergoes decarboxylation.
20. The process as claimed in claim 19, wherein the acids to be decarboxylated have the following formula:

wherein, said formulae (III) and (IV):
M represents a hydrogen atom and/or a metallic cation from group (la) or (Ila), or an ammonium cation; Z1Z2 and Z3 have the meanings given in claims 3 to 5.
21. The process as claimed in claim 20, wherein said acid is decarboxylated by adding to the reaction medium a protonic acid of inorganic origin, preferably hydrochloric acid or sulphuric acid or an organic acid, until a pH of no more than 3 is obtained.
22. The process as claimed in anyone of claims 20 to 22, wherein the reaction medium is heated to a temperature between 120°C and 350°C, preferably 150°C to 220°C and after cooling, the 4-hydroxybenzaldehyde is separated which preferably has the following formula (VI):

in which formula (VI):
Z1 "Z2 and Z3 have the meanings given in claims 3 to 5.
23. A reaction medium comprising a 3-carboxy-4-hydroxybenzaldehyde, a 2-
hydroxybenzoic acid and a 4-hydroxybenzaldehyde, completely or partially in their
salt form prepared by the process as claimed in any one of the preceding claims.
24. The process as claimed in claim 23, wherein it consists of selectively oxidising, in accordance with the process defined in one of claims 1 to 17.
25. A process for preparing a mixture of phenolic compounds as claimed in claim I comprising the step of hydroxymethylating a phenol by condensing it with formaldehyde or a formaldehyde generator in an aqueous phase in the presence of an alkaline or alkaline-earth base such that the degree of phenol conversion is at most 95%, optionally followed by an oxidation step.
26. The process as claimed in claim 25, wherein the degree of phenol conversion is 60% to 95%, preferably 80% to 95%.
27. The process as claimed in claim 25 or claim 26, wherein the starting phenol is a phenol which is not substituted in the ortho and para positions with respect to the hydroxy 1 group, with general formula (I):

29. The process according to claim 28, wherein the phenol with formula (I) is
guaiacol, guetol, 3-methoxyphenol, 3-ethoxyphenol, 3-isopropoxyphenol, 3-t-
butoxyphenol, m-cresol, or o-cresol.
30. The process as claimed in anyone of claims 25 to 29, wherein formaldehyde or
any formaldehyde generator is used, preferably trioxane or para-formaldehyde,
used in the form of linear polyformaldehydes with any degree of polymerisation,
preferably containing 8 to 100 (CH2O) units.
31. The process as claimed in claim 30, wherein the formaldehyde/phenol molar
ratio is between 1.0 and 4.0, preferably between 1.0 and 2.5.
32. The process as claimed in claim 25, wherein the quantity of base present in the
hydroxymethylation medium, expressed as the number of moles of basel phenolic
hydroxy group of the phenol to be hydroxymethylated, is between 1.0 and 4.0,
preferably between 0.9 and 2.0,
33. A process according to claim 25, wherein the hydroxymethylation temperature
is in the range 0°C to 100°C, preferably in the range 20°C to 70°C.

34. The process as claimed in claim 25, wherein the duration of the
hydroxymethylation reaction is between 15 minutes and 4 hours, preferably
between 1 hour and 3 hours.
35. The process as claimed in claim 25, wherein the phenol and the formaldehyde
and the optional base are charged into the apparatus, then the reaction mixture is
heated to the desired temperature with stirring, for the period necessary to carry out
the reaction until a mixture of phenolic compounds is obtained.
36.The process as claimed in claim 1, wherein the phenol obtained is recycled.
37. A process for preparing a 4-hydroxybenzaldehyde and its derivatives substantially as herein described and exemplified.

Documents:

2664-mas-1997 form-6.pdf

2664-mas-1997 petitions.pdf

2664-mas-1997 abstract.pdf

2664-mas-1997 claims duplicate.pdf

2664-mas-1997 claims.pdf

2664-mas-1997 correspondence others.pdf

2664-mas-1997 correspondence po.pdf

2664-mas-1997 description (complete) duplicate.pdf

2664-mas-1997 description (complete).pdf

2664-mas-1997 form-19.pdf

2664-mas-1997 form-2.pdf

2664-mas-1997 form-26.pdf

2664-mas-1997 form-4.pdf

2664-mas-1997 others.pdf

2664-mas-1997 petition.pdf

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Patent Number

203530

Indian Patent Application Number

2664/MAS/1997

PG Journal Number

05/2007

Publication Date

02-Feb-2007

Grant Date

27-Nov-2006

Date of Filing

21-Nov-1997

Name of Patentee

M/S. RHONE-POULENC CHIMIE

Applicant Address

25 QUAI PAUL DOUMER 92408 COURBEVOIE CEDEX,

Inventors:

#	Inventor's Name	Inventor's Address
1	METIVIER PASCAL	29 ALLEE DES FRENES, 69110 SAINTE FOY LES LYON,

PCT International Classification Number

C07C 45/67

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	96 14275	1996-11-22	France