PROCESS FOR THE PRODUCTION OF LEUCO TRIARYL METHANE COMPOUNDS

Abstract: A process for the production of a compound of formula which comprises reacting a compound of formula or a mixture of the compounds (2a) and (2b) with a compound ZH having an active hydrogen atom, under acidic conditions, wherein X and Y are the same or different and each represents an aromatic carbocyclic radical having an unsubstituted or substi­ tuted amino group in the para position to the indicated bond, or a heterocyclic radical, and Z represents an aryl radical of formula wherein R₁, R₂, R₃ and R₄, each independently of the other, represent hydrogen, hydroxy, halogen, cyano, nitro, C₁-C₁₂-­ alkyl, C₂1-C₁₂-alkoxy, C₂-C₈-alkoxyalkyl, cycloalkyl, aralkyl, aryl, aryloxy, or substituted alkyl, cycloalkyl, aralkyl or aryl, or amino or substituted amino, or a sulphonic acid group or derivates thereof, V represents oxygen, sulphur or imino and T₁ and T₂ indepen­ dently represent hydrogen, C₁-C₁₂-alkyl, C₂-C₁₂-alkenyl, aryl, aralkyl, and T₁ is also amido or ureido, or T₁ and T₂ together with the nitrogen atom which links them, represent a five- or six-­ membered heterocyclic radical. Preferably Z contains at least one water-solubilising group, e.g. -SO₃M, wherein M is hydrogen, ammonium or alkali metal.

Description: Process for the production of leuco triaryl methane compounds The present invention relates to the production of leuco triaryl methane compounds. More particularly it relates to a process for the production of leuco triaryl methane compounds which, on oxidation, form a dyestuff. Accordingly, the invention provides a process for the production of a compound of the formula EMI1.1 wherein X and Y may be the same or different and each represents an aromatic carbocyclic radical having an unsubstituted or substituted amino group in the para-position to the indicated bond, or a heterocyclic radical, and Z represents an aryl radical of formula EMI1.2 wherein R1, R2, R3 and R4 each independently of the other, represent hydrogen, hydroxy, halogen, cyano, nitro, C 1-C12-alkyl, Cl-Cl2alkoxy, C2-C8-alkoxyalkyl, cycloalkyl, aralkyl, aryl, aryloxy, or substituted alkyl, cycloalkyl, aralkyl or aryl, or amino or sub stituted amino, or a sulphonic acid group or derivatives thereof such as a sulphonic acid metal salt, sulphonic acid ester or sulphonic acid amide group. Preferably the aryl radical Z contains at least one watersolubilising group e.g. SO3M wherein M is hydrogen, ammonium or a metal which will give a water soluble salt such as an alkali metal e.g. sodium or potassium. The process of the present invention comprises reacting a compound of formula EMI2.1 or a mixture of the compounds -(2a) and (2b) with a compound ZH having an active hydrogen atom, under acidic conditions, wherein X, Y and Z have the meanings given above, and V represents oxygen, sulphur or imino and T1 and T2 independently represent hydrogen, C1-C12-alkyl, C2-C12-alkenyl, aryl or aralkyl, and T1 may also represent amido or ureido, or T1 and T2 together with the nitrogen atom which links them represent a five- or six-membered, preferably saturated, heterocyclic radical. As an aromatic carbocyclic radical, X and Y may be an amino-substituted phenyl radical of formula EMI2.2 wherein R5 and R6 independently represent hydrogen, C1-C12-alkyl, C2-C8-alkoxyalkyl, cycloalkyl, aralkyl, aryl or substituted alkyl, cycloalkyl, aralkyl or aryl, or together represent methylene groups linked to form a heterocyclic ring which may optionally be interrupted by an oxygen, sulphur or nitrogen atom, such as pyrrolidino, piperidino, morpholino, thiomorpholino or piperazino, and R7 and R8 independently represent hydrogen, hydroxy, halogen, cyano, nitro, C1-C4-alkyl, C1-C4alkoxy, C2-C8-alkoxyalkyl, cycloalkyl, aralkyl, aryloxy, arylamino, aryl or a carboxylic acid, carboxylic ester or carboxylic amide group. R5to R8 may also include a water-solubilising group, e.g. S03M or a sulphonic acid ester or amide group, which is preferably located at a benzene ring of an aryl, aralkyl, aryloxy or arylamino radical As a heterocyclic radical X and Y may represent a mono- or polycyclic (preferably di- or tricyclic) radical containing a 5- or 6-membered heterocyclic ring containing oxygen, sulphur and/or nitrogen as ring. member, such as a thienyl, furyl, pyrrolyl, pyrazolyl, pyrazolonyl, pyridyl, thiazinyl, oxazinyl, benzothiazinyl, indolyl, indazolyl, benzothiazolyl, benzotriazolyl, naphthotriazolyl, quinolinyl, carbazolyl, phenothiazinyl or phenoxazinyl radical. The mono- or polynuclear heterocyclic radicals may be substituted by one or more of the groups defined for R7 and R8 above. When X and/or Y is a heterocyclic radical, it is preferably one of the formula EMI3.1 wherein Q1 represents hydrogen, C1-C12-alkyl, C2-C12-alkenyl or benzyl and Q2 represents hydrogen, C1-C12-alkyl or aryl, e.g. phenyl, and R7 and R8 have the given meanings. Alkyl groups represented by each of R1 to R8, T1, T2, Q1 and Q2 may be straight or branched chain and are e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, octyl or dodecyl. Alkoxyalkyl represented by each of the radicals R1 to R8 may have 1 to 4 carbon atoms in each part and is preferably ss-methoxyethyl or ss-ethoxyethyl. Q1, T1 and T2 as alkenyl may be for example allyl, 2-methallyl, 2-ethylallyl, 2-butenyl or octenyl. Cycloalkyl within the definition of the R radicals is e.g. cyclopentyl or, preferably, cyclohexyl. An aryl radical represented by each of R and T can be diphenyl, naphthyl or, preferably, phenyl. As aralkyl, R and T may be phenylethyl, phenylpropyl or, preferably, benzyl. When R1 to R6 represent substituted alkyl, cycloalkyl, aralkyl or aryl, the substituent may be one or more halogen, hydroxy, cyano or alkyl and/or alkoxy groups having 1 to 4 carbon atoms. When R1, R2, R3 and R4 represent a substituted amino, the substituents may be alkyl, aryl or aralkyl groups. These aryl or aralkyl groups may contain water-solubilising groups such as -SO3M. A heterocyclic radical formed by the pair of substituents (R5 and R6) and (T1 and T2), together with the nitrogen atom to which said pair is attached, is for example pyrrolidino, piperidino, pipecolino, morpholino, thiomorpholino or piperazino. Z as an aryl radical of formula (la) may be a radical of formula EMI5.1 preferably a radical of the formula EMI5.2 or a radical of the formula EMI5.3 wherein R1, R2, R5, R6 and M are as defined above, Rg is an alkyl or aryl group, mis 1 to 4, preferably 1, and n is 1 or 2. When Z is an aryl radical of formula (lb) it may be a radical of formula EMI5.4 or of formula EMI6.1 wherein R1, R4, R5, R6, M and n are as defined above and R1 is hydrogen or hydroxy. Advantageously, each of R1, R2, R3, R4, R7 and R8 independently represents hydrogen, hydroxy, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy or -S03M, whilst R and R6 are 3 R6 preferably hydrogen, C1-C4-alkyl, C2-C4-alkoxyalkyl, cyclohexyl, benzyl, phenyl, or phenyl or benzyl each substituted by -S03M, wherein M is hydrogen, ammonium or alkali metal. R9 is preferably Cl-C4-alkyl or phenyl. Z is preferably a radical of formula (3a) or (6). T1 and T2 are preferably hydrogen. V is preferably oxygen. The reaction to produce compounds of formula (1) from compounds of formula (2a) or (2b) is carried out under acidic conditions. Any nonoxidising strong inorganic or organic acid may be used, for example hydrochloric, sulphuric, phosphoric, formic, acetic, mono-, di- or trichloroacetic, benzenesulphonic, p-toluene sulphonic or oxalic acid. The acid may be anhydrous or aqueous. The reaction may optionally be carried out in the presence of an alcoholic solvent, e.g. methanol or ethanol. The reaction may be carried out at a temperature from Oo to 100 C, preferably from 800 to 1000C. The compounds of formula (2a) or (2b) may be made by various routes, starting from the basic urea derivative of formula EMI7.1 wherein T1, T2 and V have the given meanings. This compound may be reacted under acidic conditions with one or two molar equivalents of an aldehyde which is XCHO or YCHO and one or two molar equivalents of a compound XH or YH having an active hydrogen atom, wherein X and Y have the meanings given. Sufficient acid should be used to protonate the amino groups in the radicals X and Y in compounds of formula (2a) or (2b) above. This reaction may be carried out between ambient temperature and 100 C, optionally in the presence of an organic solvent, such as an alcohol, e.g. methanol or isopropanol. Suitable acids include hydrochloric, sulphuric, phosphoric, mono-, di- or trichloroacetic, benzenesulphonic or p-toluenesulphonic acid. For example, p-dimethylaminobenzaldehyde of formula (8) may be reacted with urea and N,N-dimethylaniline in the presence of an acid to form 1,3-bis[(p-dimethylamino-diphenyl)methyl] urea of formula (9) according to the following scheme EMI7.2 EMI8.1 Generally, a mixture of the compound of the formula (9) and of the compound of formula EMI8.2 is obtained. The weight ratio of the compound of formula (9) to the compound of formula (9a) in advantageously between 1:9 to 9:1, preferably between 1:2 to 2:1. It is preferred to use an excess of the active hydrogen compound and tn remove the excess by filtration or steam distillation before reaction with the compound ZH. The benzaldehyde derivatives used in these reaction schemes can be easily prepared by the so-called Vilsmeier-Haack synthesis (Ber. 1927, 60, 119). It is not always necessary to isolate the aldehyde before reacting it with urea and the active hydrogen compound. Compounds of formula (2a), in which X and Y are aromatic carbocyclic radicals, can also be prepared by reacting the urea compound of formula (7) under acidic conditions, optionally in the presence of an organic solvent such as an alcohol or ketone, e.g. methanol, isopropanol or acetone, with a benzhydrolof formula EMI8.3 wherein the benzene rings A and B may be further substituted by one or more substituents selected from halogen, cyano, nitro, C1-C4-alkyl and C C alkoxy and in which each of Rlo, Rill, R12 and R13 independently represents Cl¯Cl2-alkyl, cycloalkyl, aralkyl, aryl, alkoxyaryl, in which the alkoxy group has 2 to 8 carbon atoms, or substituted alkyl, cycloalkyl, aralkyl or aryl. Sufficient benzhydrolmay be used to produce the compound of formula (2a) directly or only enough to react with one NH2-group of the urea may be used. The resulting intermediate may then be reacted with more benzhydrol or with an aldehyde and active hydrogen compound as above to react with the other NH2-group on the urea. Suitable acids include hydrochloric, sulphuric, phosphoric, formic, mono-, di-, trichloroacetic acid, benzenesulphonic, p-toluene sulphonic or oxalic acid. Mineral acids are preferred on cost grounds. The resulting compound of formula (2a) is then reacted under acidic conditions with a compound ZH to produce the compound of formula (1). The resulting leuco compound of formula (1) may be converted into a dyestuff by oxidation in conventional manner. Suitable oxidising agents include sodium or potassium dichromate and sulphuric acid, manganese dioxide, lead (II) dioxide, chloranil, oxygen or air. The oxidation is normally carried out under aqueous conditions, optionally in the presence of an organic solvent such as an alcohol, at a reaction temperature of 20 to 1000C. Since the compounds of formula (2a) and (2b) can readily be isolated in crystalline form from the reaction mixture, the resulting leuco compounds of formula (1) and the dyes produced from them can be obtained in a very pure form. For example, 4,4'-bis-(dimethylamino) benzhydrol (commonly known as Michlervs Hydrol), when prepared by the oxidation route from 4,4'-bis (dimethylamino-diphenyl)-methane, can contain such impurities as the unchanged methane base, tetramethylbenzidine, the corresponding ketone (Michler's ketone) and a hydrol ether. These impurities, however, are not present when a compound of formula (2a) or (2b) is used and do not appear in the leuco compound and in the corresponding dyestuff obtained. A further advantage of the process of the invention is that the compounds of formula (1) are obtained in good yields. In the Examples which follow, the percentages are by weight, unless otherwise indicated. Example 1: 150.g of dibenzylaniline are slowly added to a mixture of 104 g of 98% sulphuric acid and 46.5 g of 20% oleum at 600C. The mixture is then stirred until a solution is obtained. Afterwards 146 g of 65% oleum are added at 600C, the mixture is heated to 750C and stirred at this temperature until disulphonation of the dibenzylaniline is complete. The sulphonation mass is poured intd 840 ml water, then 140 g of sodium carbonate is carefully added and stirred to dissolve. The urea compound of Michlervs hydrol, consisting of a mixture of compounds of formulae (9) and (9a) as filter cake, (equivalent to 120 g of Michler's hydrol 100%), is added at 400C and the volume is adjusted to about 2.3 litres with water. The mixture is heated to 90"C and maintained 1-4 hours at this temperature until the condensation is complete. The condensation mixture is then neutralised to pH 6-6.5 with 200 g of calcium hydroxide at 85-900C and the solution is clarified. The residues are washed with hot water and sucked dry. The combined mother liquor and washings containing the leuco compound are then oxidised using sodium dichromate and sulphuric acid to give, after isolation as a tar, followed by drying, 300 g of concentrated dyestuff having the formula EMI11.1 This compound dyes wool a brilliant violet shade. Example 2: 209 g of 98% sulphuric acid are carefully diluted with 110 g of ice-water and cooled to 200C. 59 g of 2-naphthol-3,6-disulphonic acid and the urea compound of Michler's hydrol (= mixture of compounds of formulae (9) and (9a)) as filter cake (equivalent to 46 g of Michler's hydrol 100%), are added at a temperature below 35"6. The mixture is stirred for 30 minutes and then heated to 800C and kept at 800C for 2-6 hours until the condensation is complete. The mixture is poured into 900 ml of cold water, stirred for 4 hours and then filtered. The filter cake of the leuco compound is washed acid free with cold water, yielding 49 g of a compound of the formula EMI11.2 The leuco compound is then oxidised using manganese dioxide to give the dyestuff of formula EMI12.1 This compound dyes wool a bright green shade. Example 3: 18.5 g of phosphorus oxychloride are slowly added over 3 hours to a mixture of 18 g of dry dimethylformamide and 35.7 g of diethylaniline at 60-65 C. The mixture is stirred for a further hour at 60-650C and then drowned into 50g of ice/water. 7.2g of urea are added to the drowned mass and the mixture is stirred at 500C for 48 hours. The mixture is then added to a mixture of 34.6 g of naphthalene2,7-disulphonic acid in 215 g of water and stirred overnight at room temperature. The pH is then adjusted to 3.5 with sodium hydroxide solution and the whole diluted to 625 ml with water and stirred overnight. The naphthalene-2,7-disulphonic acid addition complex of the mixture of l,3-bis(4,4'-bis-diethylamino-diphenyl-methyl) urea and l-(4,4'-diethylamino-diphenyl-methyl) urea is then filtered off, washed with cold water and dried at 700C in a vacuum oven:yield 46.6 g. This complex is then added at 60-70"C over 20 minutes to 85 g of 14.5% sulphuric acid and the mixture is heated to 1000C, kept for 8 hours at this temperature and drowned into 155 g water. The volume is adjusted to 280 ml with cold water and the mixture is stirred at room temperature to precipitate the leuco compound of the formula EMI13.1 This compound is filtered off and washed acid-free to yield 17 g of leuo compound 100% (by sodium hydroxide titration). The leuco compound is then oxidised with sodium dichromate and oxalic acid to give the dyestuff of formula EMI13.2 which dyes wool a bright green shade.

Claims: WHAT IS CLAIMED IS: 1. A process for the production of a compound of formula EMI14.1 which comprises reacting a compound of formula EMI14.2 or a mixture of the compounds (2a) and (2b) with a compound ZH having an active hydrogen atom, under acidic conditions, wherein X and Y are the same or different and each represents an aromatic carbocyclic radical having an unsubstituted or substituted amino group in the para-position to the indicated bond, or a heterocyclic radical, and Z represents an aryl radical of formula EMI14.3 wherein R1, R2, R3 and R4, each independently of the other, represent hydrogen, hydroxy, halogen, cyano, nitro, C1-C12-alkyl, C1-C12-alkoxy, C -C -alkoxyalkyl, cycloalkyl, aralkyl, aryl, aryloxy, or substituted 28 alkyl cycloalkyl, aralkyl or aryl, or amino or substituted amino, or a sulphonic acid group or a derivative thereof, V represents oxygen, sulphur or imino and T1 and T2 independently represent hydrogen, C1-C12-alkyl, C2-C12-alkenyl, aryl, aralkyl, and T1 is also amido or ureido, or T1 and T2 together with the nitrogen atom which links them represent a five- or six-membered heterocyclic radical. 2. A process according to claim 1, wherein R1, R2, R3, R4 independently represent hydrogen, hydroxy, halogen, cyano, C1-C4-alkyl, C1 -C4- alkoxy, amino, substituted amino or -S03M, wherein M is hydrogen, ammonium or alkali metal. 3. A process according to claim 1 or 2, wherein X and Y independently represent an amino- substituted phenyl radical of formula EMI15.1 wherein R5 and R6 independently represent hydrogen, C1-C12 alkyl, C2-C8 alkoxyalkyl, cycloalkyl, aralkyl, aryl or substituted alkyl, cycloalkyl, aralkyl or aryl, or R and R6 together with the nitrogen 5 atom which links them represent pyrrolidino, piperidino, morpholino, thiomorpholino or piperazino, and R7 and R8 independently represent hydrogen, hydroxy, halogen, cyano, nitro, C1-C4-alkyl, C1-C4-alkoxy, C2-C8-alkoxyalkyl, cycloalkyl, aralkyl, aryl, aryloxy, arylamino, or a carboxylic acid, carboxylic ester or carboxylic amide group. 4. A process according to claim 3, wherein one or more of the substituents R5, R6, R7 and R8 contain a water-solubilising group, especially a -S03M group, wherein M is hydrogen, ammonium or alkali metal. 5. A process according to claim 4, wherein R5 and R6 independently are hydrogen, C -C -alkyl, C2-C4 -alkoxyalkyl, cyclohexyl, benzyl, phenyl, or phenyl or benzyl each substituted by -S03M, wherein M is hydrogen, ammonium or alkali metal. 6. A process according to claim 1, wherein X and Y independently represent an indolyl radical of the formula EMI16.1 wherein Q1 represents hydrogen, C1-C12-alkyl, C2-C12-alkenyl or benzyl, Q2 represents hydrogen, C1-C12-alkyl or aryl, and R7 and R8 independently represent hydrogen, hydroxy, halogen, cyano, nitro, C1-C4-alkyl, C1-C4-alkoxy, C2-C8-alkoxyalkyl, cycloalkyl, aralkyl, aryl, aryloxy, arylamino, or a carboxylic acid, carboxylic ester or carboxylic amide group. 7. A process according to claim 1, wherein Z is a radical of formula EMI16.2 wherein R5 and R6 independently represent hydrogen, Cl-Cl2 alkyl, C2-C8 alkoxyalkyl, cycloalkyl, aralkyl, aryl or substituted alkyl, cycloalkyl, aralkyl or aryl, or R5 and R6 together with the nitrogen atom which links them represent pyrrolidino, piperidino, morpholino, thiomorpholino or piperazino, M is hydrogen, ammonium or alkali metal and R1 and R2 are as defined in claim 1. 8. A process according to claim 7, wherein Z is a radical of formula EMI17.1 wherein Rg is alkyl or aryl, m is 1 to 4, n is 1 or 2 and M is as defined in claim 7. 9. A process according to claim 1, wherein Z is a radical of formula EMI17.2 wherein R1 is hydrogen or hydroxy, n is 1 or 2, and R1 and R4 are as defined in claim 1, R5 and R6 independently represent hydrogen, C1-C12 alkyl, C2-C8 alkoxyalkyl, cycloalkyl, aralkyl, aryl or substituted alkyl, cycloalkyl, aralkyl or aryl, or R5 and R6 together with the nitrogen atom which links them represent pyrrolidino, piperidino, morpholino, thiomorpholino or piperazino, M is hydrogen, ammonium or alkali metal. 10. A process according to claim 8 or 9, wherein Z is a radical of formula (3a) or (6). 11. A process according to claim 1 wherein the compounds of formula (2a) and (2b) or a mixture thereof are prepared by reacting a compound of the formula EMI18.1 wherein V, T1 and T2 are as defined in claim 1, under acidic conditions, with one or two molar equivalents of an aldehyde which is X-CH0 or Y-CH0 and one or two molar equivalent of a compound XH or YH, wherein X and Y are as defined in claim 1. 12. A process according to claim 11 wherein p-dimethylamino-benzaldehyde is reacted with urea and N,N-dimethylaniline, in the presence of an acid, to form N-14,4'-dimethylamino-diphenyl-methyl]urea or N,N' -bis [4,4' -dimethyl-amino-diphenyl-methyl]urea or a mixture of these urea derivatives. 13. A process according to claim 1, wherein a compound of formula (2a) is used, wherein each of X and Y is an aromatic carbocyclic radical having an unsubstituted or substituted amino group in the para-position, wherein this compound of formula (2a) is produced by reacting a compound of formula EMI18.2 wherein V, T1 and T2 are as defined in claim 1; under acidic conditions, with a benzhydrol of formula EMI19.1 wherein the benzene rings A and B are unsubstituted or substituted by one or more substituents selected from halogen, cyano, nitro, Cl-C4-alkyl and Cl-C4-alkoxy, and in which R10, Rill, R12 and R13 each independently represent C1-C12-alkyl, cycloalkyl, aralkyl, aryl, alkoxyaryl, in which the alkoxy group has 2 to 8 carbon atoms, or substituted alkyl, cycloalkyl, aralkyl or aryl. 14. The leuco triaryl methane compound obtained according to the process as claimed in any one of claims 1 to 13. 15. The use of the leuco triaryl methane compound, obtained according to the process as claimed in any one of claims 1 to 13, as intermediate for the oxidation to produce a dyestuff.

Inventors: CLARK MALCOLM COLIN DR, HART DERRICK ALEXANDER, CLARK, MALCOLM COLIN, DR., HART, DERRICK ALEXANDER
Applicants: CIBA-GEIGY AG
Application year: 1982
Main classification: C09B11
IPC codes: C09B11