GB1580891A

GB1580891A - Process for the production of alkylaryl compounds

Info

Publication number: GB1580891A
Application number: GB16290/76A
Authority: GB
Original assignee: Ciba Geigy AG
Current assignee: Novartis AG
Priority date: 1976-04-22
Filing date: 1976-04-22
Publication date: 1980-12-10
Also published as: BE853789A; FR2348909B1; DE2717781A1; FR2348909A1

Description

(54) PROCESS FOR THE PRODUCTION OF ALKYLARYL COMPOUNDS (71) We CIBA-GEIGY AG., a Swiss Body Corporate, of Basle, Switzerland do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The invention relates to a new process for the production of alkylaryl compounds, as well as to the alkylaryl compounds obtained by means of this process.

The production of alkylaryl ethers and thioethers by reaction of alkali phenolates and thiophenolates with alkyl halides is known. This process is however limited to the available phenols and thiophenols; and as the alkylation of phenols and thiophenols in some cases does not proceed to completion, additional problems are caused. Furthermore, the second reactant, namely the alkyl halide, is not freely available on the market, and in the case of alkoxyalkyl halides they are much more expensive than the starting material required according to the process of the invention.

By the process according to the invention there are obtained, surprisingly, alkylaryl compounds in very high yields. The resulting products have a very high degree of purity, so that, in contrast to the products obtained by the prior processes, they require in most cases no further purification. The reaction conditions are simple, and the course of the reaction is easy to control.

The new process for the production of alkylaryl compounds of the formula

wherein R represent alkyl (C,-C24) which may be branched-chain or straight-chain, optionally substituted aryl or aralkyl, R1 represents H or alkyl (C,-C4), and may be either or both within any one (CHR1)m group, A represents substituted aryl, Y represents 0, S or

whereby in this case R is not present, R2 represents H, optionally substituted alkyl (C1-C6) which may be branched-chain or straight-chain, optionally substituted aryl or aroyl, R3 represents optionally substituted alkyl (Cl-C6) which may be branched-chain or straight-chain optionally substituted aryl, acyl or cycloalkyl or R2 and R3 may together form an alkylene chain (C2-C7), optionally interrupted by other heteroatoms, U represents 0 or S, Z represents an electron-attracting group, particularly the NO2-group, n represents 1 or 2, m represents an integer from 1 to 6 p represents 0 or an integer from 1 to 3, q represents 0 or 1, and t represents 1 or 2, comprises reacting compounds of the formula

in the presence of cations, for example alkali metal and/or ammonium ions, with compounds of the formula X - A - Zn wherein X represents halogen, and can be present one or several times, and the other symbols have the meanings given under formula (1) in a two-phase system, whereby the one phase is water and the other phase consists of the reactant (3) in liquid form or in solution in an organic solvent or solvent mixture immiscible with water, the reactant (2) being present in either or both phases, in the presence of 0.01 to 40 mol. %, relative to the amount of the compound (3), of quaternary ammonium or phosphonium compounds as catalysts, with thorough mixing in an alkaline pH-range.

The radical A of the formula (3) can be substituted by one or more substituents Z.

Suitable substituents Z are, for example: halogen, NO2, alkyl-(C1-C18), alkoxy-(C1-C18), aryloxy, especially phenoxy, CN, CF3, -N=N-aryl, -NH-CO-NH2, NR4R5, SO2R4, SO2NR4Rs, COR4, COOR4 or CONR4R5, whereby R4 and R5 are identical or different, and represent, in particular, H, alkyl-(C1-C12) or aryl, such as phenyl. A represents particularly a benzene or naphthalene radical.

Examples of electron-attracting groups according to the symbol Z are the NO2 and CN group, especially however the NO group.

Mentioned as starting constituent of the formula (2) are alcohols such as n-octanol, nonanol, cetyl alcohol, hexadecanol and tetracosyl alcohol; thiols such as octyl mercaptan and tertiary-dodecyl mercaptan; ethylene glycol-alkyl ether types, such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, ethylene glycol mono-isopropyl ether, ethylene glycol monobutyl ether, ethylene glycol monoisobutyl ether, ethylene glycol monopentyl ether, ethylene glycol monoisoamyl ether, ethylene glycol monohexyl ether, ethylene glycol monoallyl ether; diethylene glycol-alkyl ether types, such as diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol mono-propyl ether or diethylene glycol monobutyl ether, also an alcohol or thiol substituted by an alkoxy, aryloxy or substituted amino group e.g.

1-methoxy-2-propanol, 1-methoxy-3-propanol, 1-methoxy-4-butanol, 1-methoxy-5pentanol, 1-methoxy- 6-hexanol, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, 2-methoxy-ethane- 1-thiol, 2-methoxy-propane-1-thiol, 2-phenoxyethanol, 2-phenoxy-propanol, 2-phenoxy-butanol, 2-dimethyl-amino-ethane-l-thiol, 2dimethylamino-propane-1-thiol, N-(2-hydroxyethyl)-aniline, N-(2-hydroxyethyl)-otoluidine, N- (2-hydroxyethyl)-m-toluidine, N-(2-hydroxyethyl)-p-toluidine, N- (2- hydroxyethyl)-m-chloroaniline, N-(2-hydroxyethyl)-p-chloraniline, N-(2-hydroxyethyl)-m- nitroaniline, N-(2-hydroxyethyl)-m-bromoaniline, N-(2-hydroxyethyl)-m-trifluoromethylaniline, N-(2-hydroxyethyl)-cyclohexylamine, N-(2-hydroxyethyl)morpholine, hydroxyethyl)-piperazine, N-(2-hydroxyethyl)-pyrrolidine, N-(2-hydroxyethyl)-piperidine, N-(2-hydroxyethyl)-benzamide, 2-dimethylaminoethanol, 2-diethylaminoethanol, 3- dimethylamino-1-propanol or N-(2-aminoethyl)-aminoethanol.

The following may be mentioned as examples of compounds of the formula (3) X-A-Zn: 2-chloronitrobenzene, 4-chloro-nitrobenzene, 4-fluoronitrobenzene, 4-bromonitrobenzene, 4-iodonitrobenzene, 2,4-difluoronitrobenzene, 2,4-dichloronitrobenzene, 2,4dinitrochlorobenzene, 2,4-dinitrofluorobenzene, 3,4-dinitrochlorobenzene, 3 ,4-dichloro- nitrobenzene, 2,6-dichloronitrobenzene 2-nitro-5-chloroaniline, 4-nitro-3-chloroaniline, 2-nitro-3 ,5-dichloroaniline, 2-nitro-4 5-dichloroaniline, 2-nitro-5 ,6-dichloroaniline, 2-nitro4-methyl-5-chloroaniline and 2-nitro-4-ethyl-5-chloroaniline.

Catalysts usable according to the invention are quaternary ammonium or phosphonium compounds, such as tetrabutylammonium bromide, tetrabutylammonium chloride, dodecyltrimethylammonium chloride, di-tallow-di-methylammonium chloride, nhexadecyltributylammonium chloride, tetrapropylammonium chloride, nhexadecyltributylphosphonium bromide, benzyltriethylammonium chloride, benzyltributy lammonium bromide, benzyltrihexylammonium bromide, benzyltrioctylammonium bromide, tetrabutylammonium iodide, trioctylmethylammonium chloride, N-octylpyridinium bromide, N-dodecylpyridinium bromide, cyclohexyltriethylammonium bromide ndodecyltriethylammonium bromide, n-octyltributylammonium bromide, nhexadecyltrimethylammonium bromide, n-hexadecyltriethylammonium bromide nhexadecyltripropylammonium bromide, tetrabutylphosphonium chloride, tetraphenylphosphonium bromide, trioctylmethylphosphonium bromide, trioctylethylphosphonium bromide, n-dodecyl-bis-(-hydroxyethyl)-benzylammonium chloride and n-hexadecyl-tri-(ss- hydroxyethyl)-ammonium chloride.

The amount of catalyst used in the process is preferably from 1 to 20. moles %.

It is advantageous if the catalysts are soluble both in water and in the organic phase. The organic phase may contain an organic solvent immiscible with water. Suitable organic solvents immiscible with water are in particular, e.g., aliphatic and aromatic chlorinated hydrocarbons such as carbon tetrachloride, trichloroethylene, especially methylene chloride, chloroform or mono- or dichlorobenzene.

The reaction is performed in simple reaction vessels with reflux condenser and stirrer, or in autoclaves with stirrer, from which follows that the reaction can be performed either under pressure or without pressure.

The reaction temperature varies within a wide range from room temperature to 1200C, and is dependent on the reactivity of the employed constituents. If, for example, in the compound of the formula (2), U represents S, then the reaction can be performed at a temperature between room temperature and 50"C; if however U represents oxygen, then a reaction temperature in the range of from 80 to 1100C is advantageous.

The reaction constituent of the formula (2) is advantageously used in a small stoichiometrical excess; optionally however up to a 50% excess relative to the constituent X-A-Zn.

The reaction is performed in an alkaline medium. The alkali constituent can be added, for example, as an aqueous concentrated solution (10 to 50%) before commencement of reaction of the constituent of the formula (2). This water content is sufficient in most cases for the formation of the two-phase system (water/solvent mixture). With the use of highly concentrated alkali liquor, an addition of water is in certain cases necessary. The procedure in detail is as follows: The starting constituent of the formula (2) may be in the form of an aqueous alkali solution or suspension; and the solution or suspension should clearly show an alkaline reaction. This solution is placed into a reaction vessel, whereupon a solution of the reaction constituent X-A-Zn in a solvent immiscible with water is added; the catalyst as defined is then added, and stirring is maintained for a period of up to 10 hours at a temperature of between room temperature and 1200C. The solvent and, if necessary, also unchanged reactants are afterwards removed from the reaction system by means of steam distillation, and can be used again for a new starting mixture; the reaction mixture is subsequently cooled, the precipitated product is filtered off and washed with water until neutral.

A further procedure for performing the reaction according to the invention comprises adding the reaction constituent X - A - Zn to the reaction mixture in the absence of a solvent in which case, the constituent X-A-Zn itself forms the organic phase, e.g. as a melt or together with reactant of formula (2) forms the organic phase.

The starting material X-A-Zn may be added in solid form to the reaction mixture and may be heated to form a melt.

The resulting product of the formula (1) is of the necessary purity for further processing.

The yields are, as a rule, above 70% of theory.

The compounds of the formula (1) produced by the new process are valuable intermediates for pigment, agrochemical or dyestuff synthesis; e.g., in relation to the latter, after prior reduction of the nitro group and possible sulphonation, as diazo component for producing azo dyestuffs.

Compared with the initially described production method using alkyl halides and phenolates, the method of the invention is surprising in that with the hydroxy compounds of the formula (2), or with the alkali or ammonium compounds thereof, there is obtained at the low reaction temperatures of the process according to the invention a very high degree of conversion of the reaction constituents, with the resulting product being moreover obtained in a very pure form.

In the process according to the invention, the reaction is performed in water or in a mixture of water and a solvent immiscible with water; the carrying out of the process is simple and, after processing of the reaction mixture, e.g. by means of steam distillation, a solvent if employed can be used again for the next reaction mixture, to minimise contamination of the environment.

Finally, the advantages of the new process are furthermore reflected in the great simplicity of the technical aspects of the process.

The following Examples illustrate the procedure of the process of the invention without however the process being limited by them. Temperature values are given in degrees Centigrade, and 'parts' (T) denote units of weight.

Example 1 A mixture of 40 ml of a 50% sodium hydroxide solution and 60 ml of ethylene glycol-monomethyl ether is stirred for 15 minutes in a 0.5 litre steel autoclave; there is then added the suspension of 78.8 g of p-chlbronitrobenzene and 9.6 g of the catalyst, tetrabutylammonium bromide, in 150 ml of chlorobenzene. This reaction mixture is maintained for 4 hours, with thorough stirring, at an internal temperature of 100 . After cooling, the reaction product has partially crystallised out. The employed chlorobenzene is separated by means of steam distillation, and is used again for the next reaction mixture.

The solution remaining is cooled with stirring, whereupon there is obtained at 55 to 600 the reaction product of the formula

in the form of a slightly yellow-coloured, coarse crystalline precipitate. The reaction product is washed neutral with water, and dried in vacuo to obtain 82 g of product (= 83% of theory) having a melting point of 79 to 820.

If the procedure is carried out as in Example 1 except that there are used, instead of ethylene glycol monomethyl ether, corresponding amounts of the alcohols or thiol given in Column I of Table I and of the halogenobenzenes shown in Column II, then there are obtained the alkylaryl ethers listed in Column III.

TABLE 1 I II III Ex. Alcohol Halogenobenzene Alkyaryl ether

Continuation of Table 1

TABLE I (cont. .)

Example 25 2.2 g of sodium hydroxide is dissolved in 20 ml of water in a 100 ml round flask fitted with stirrer, thermometer and reflux condenser; there are then added 7.6 g of 2-phenoxyethanol, 7.88 g of p-chloronitro-benzene and 1.33 g of the catalyst, benzyltributylammonium bromide, and the whole mixture is refluxed for 8 hours. After cooling, the reaction product of the formula

is obtained as a light-yellow-coloured precipitate, which is filtered off, washed neutral and dried in vacuo.

Yield: 11.3 g = 87% of theory; m.p.: 83-85 .

With this procedure it is possible to perform the reaction in an aqueous medium without addition of an organic solvent.

Similarly high yields are obtained if 2-phenoxyethanol is replaced by 2-phenoxypropanol or 2-phenoxybutanol, under otherwise the same conditions as those described.

Examples 26-37 If the procedure as described in Example 25 is carried out except that there are used, instead of 2-phenoxyethanol, corresponding amounts of the hydroxy or thiol compounds given in Column 1 of the Table 2, then there are obtained the alkyl-aryl ethers shown in Column II.

TABLE 2 I II Ex Hydroxy or thiol compound Alkylaryl ether

TABLE 2 (cont...)

Example 38 In a 100 ml steel autoclave there are added to the solution of 5.0 g of sodium hydroxide in 20 ml of water 14.4 g of N-(2-hydroxyethyl)-morpholine, 3.2 g of the catalyst, tetrabutylammonium bromide, as well as the solution of 15.75 g of p-chloronitrobenzene in 30 ml of chlorobenzene. After closing of the autoclave, the two-phase mixture is maintained for 8 hours, with good stirring, at a temperature of 100 . After separation of the chlorobenzene by means of steam-distillation, there precipitates, on cooling of the aqueous solution, the reaction product of the formula

in the form of a yellowishly coloured precipitate, which is filtered off, washed neutral and dried in vacuo.

Yield: 19.6 g = 76% of theory.

If the procedure as described in Example 38 is carried out except that there are used, instead of N-(2-hydroxyethyl)-morpholine, corresponding amounts of the hydroxy or thiol compounds given in Column I of the Table 3 and of the halogenobenzenes shown in Column II, then there are obtained the alkylaryl ethers contained in Column III.

TABLE 3 I II III Ex. Hydroxy compound Halogenobenzene Alkyaryl ether

TABLE 3 (cont. .)

Example 50 In a 500 millilitre round-bottomed flask equipped with a mechanical stirrer was placed a mixture of 27.2 g. of 3-phenyl-1-propanol, 160 ml. of aqueous 30% sodium hydroxide and 34.6 g. of 1-chloro-4-nitrobenzene. After adding 7.2 g. of the catalyst benzyltributylammonium bromide, the reaction mixture was heated under reflux at 1120 with vigorous stirring for 8 hours.

Steam distillation of the reaction mixture was then carried out. After 1 litre of distillate had been collected, the mixture was cooled and extracted with toluene. The toluene extract was dried and concentrated under reduced pressure to give 4-(3-phenylpropoxy)-1nitrobenzene.

Claims

Yield: 38.6g. = 75% of theory; m.p.: 76 - 78 WHAT WE CLAIM IS:

1. A process for the production of alkylaryl compounds of the formula

wherein R represent alkyl (Cl-C24) which may be branched-chain or straight-chain, optionally substituted aryl or aralkyl, R1 represents H or alkyl (C1-C4), and may be either or both within any one (CHR1)m group, A represents substituted aryl, Y represents 0, S or

whereby in this case R is not present, R2 represents H. optionally substituted alkyl (Cl-C6) which may be branched-chain or straight chain, optionally substituted aryl or aroyl, R3 represents optionally substituted alkyl (C1-C6) which may be branched-chain or straight-chain optionally substituted aryl, acyl or cycloalkyl or R2 and R3 may tbgether form an alkylene chain (C2-C7), optionally interrupted by other heteroatoms, U represents 0 or S, Z represents an electron-attracting group, n represents 1 or 2, m represents an integer from 1 to 6, p represents 0 or an integer from 1 to 3, q represents 0 or 1, and t represents 1 or 2, comprises reacting compounds of the formula

wherein R. Y, Rl, U. q. m and p are as defined under formula I above, in the presence of cations, with compounds of the formula X-A-Zn wherein X represents halogen, and can be present one or several times, and the other symbols have the meanings given under formula (1) in a two-phase system whereby the one phase is water and the other phase consists of the reactant (3) in liquid form or in solution in an organic solvent or solvent mixture immiscible with water, the reactant (2) being present in either or both phases. in the presence of 0.01 to 40 mol. %, relative to the amount of the compound (3), of quaternary ammonium or phosphonium compounds as catalysts, with thorough mixing in an alkaline pH-range.

2. A process as claimed in claim 1 wherein the cations present in the reaction mixture are alkali metal or ammonium ions.

3. A process as claimed in claim 1 or 2 wherein Z is halogen, nitro, C,-C,s alkyl, C1-C15 alkoxy, aryloxy. CN. CF -N=N-aryl. -NH-CO-NH2, -NR4Rs, SO2R4, SO2NR4R5, COR4, COOR4 or CONR4R wherein R4 and R5 are identical or different and each is H, C1-C12 alkyl or aryl.

4. A process as claimed in claim 3 wherein Z is CN or nitro.

5. A process as claimed in any of the preceding claims wherein A is a benzene or naphthalene radical.

6. A process as claimed in any of the preceding claims wherein the starting material of formula 2) is an alcohol; a thiol; an ethylene glycol-alkyl ether; a diethylene glycol - alkyl ether; or an alcohol or thiol substituted by an alkoxy, aryloxy or substituted amino group.

7. A process as claimed in any of the preceding claims wherein the starting material of formula (3) is 2-chloronitrobenzene, 4-chloronitrobenzene, 4-fluoronitrobenzene, 4bromonitrobenzene, 4-iodonitrobenzene, 2,4-difluoronitrobenzene, 2,4dichloronitrobenzene, 2,4-dinitrochlorobenzene, 2 ,4-dinitrofluorobenzene, 3,4dinitrochlorobenzene, 3 ,4-dichloronitrobenzene, 2,6-dichloronitrobenzene, 2-nitro-5chloroaniline, 4-nitro-3-chloroaniline, 2-nitro-3,5-dichloroaniline, 2-nitro-4,5dichloroaniline, 2-nitro-5,6-dichloroaniline, 2-nitro-4-methyl-5-chloroaniline and 2-nitro-4ethyl-5-chloroaniline .

8. A process as claimed in any of the preceding claims wherein the catalyst is tetrabutylammonium bromide, tetrabutylammonium chloride, dodecyltrimethylammonium chloride, di-tallow-di-methylammonium chloride, n-hexadecyltributylammonium chloride, tetrapropylammonium chloride, n-hexadecyltributylphosphonium bromide, benzyltriethylmonium chloride, benzyltributylammonium bromide, benzyltrihexylammonium bromide, benzyltrioctylammonium bromide, tetrabutylammonium iodide, trioctylmethylammonium chloride, N-octylpyridinium bromide, N-dodecylpyridinium bromide, cyclohexyltriethylammonium bromide, n-dodecyltriethylammonium bromide, n-octyltributylammonium bromide, n-hexadecyltrimethylammonium bromide, n-hexadecyltriethylammonium bromide, n-hexadecyltripropylammonium bromide, tetrabutylphosphonium chloride, tetraphenylphosphonium bromide, trioctylmethylphosphonium bromide trioctylethylphosphonium bromide, n-dodecyl-bis-(-hydroxyethyl)-benzylammonium chloride and n-hexadecyl-tri-(ss-hydroxyethyl) ammonium chloride.

9. A process as claimed in claim 8 wherein the catalyst is benzyl-tributylammonium bromide or tetrabutylammonium bromide.

10. A process as claimed in any of the preceding claims wherein the catalyst is soluble in water and in the organic phase.

11. A process as claimed in any of the preceding claims wherein the organic phase comprises an organic solvent immiscible with water.

12. A process as claimed in claim 11 wherein the organic solvent is an aliphatic or aromatic chlorinated hydrocarbon.

13. A process as claimed in claim 12 wherein the chlorinated hydrocarbon solvent is methylene chloride, chloroform or mono- or dichlorobenzene.

14. A process as claimed in any of the preceding claims wherein the reaction temperature is within the range of from room temperature up to 1200C.

15. A process as claimed in claim 14 wherein U is 0 and the reaction is performed at a temperature in the range of from 80" to 1100C.

16. A process as claimed in any of the preceding claims wherein the starting material of formula (2) is used in a stoichiometric excess of up to 50% relative to reactant X-A-Zn.

17. A process as claimed in any of the preceding claims wherein one phase of the reaction mixture is an aqueous alkaline solution or suspension of starting material (2) and the organic phase is a solution of starting material (3) in an organic solvent immiscible with water.

18. A process as claimed in any of claims 1 to 10 and 14 to 16 wherein the starting material (3) is added to the reaction mixture in the absence of a solvent, so that the constituent X-A-Zn itself, or together with the reactant of formula (2), forms the organic phase.

19. A process as claimed in claim 18 wherein the starting material (3) is added in solid form to the reaction mixture and then heated to form a melt.

20. A process according to any of the preceding claims wherein the amount of catalyst used is from 1 to 20 mol %.

21. A process as claimed in any of the preceding claims wherein, in the product of formula (1). p and t are each 1 and q is zero.

22. A process for the production of a compound of formula (1) substantially as described with reference to any of the Examples.

23. A compound of formula (1) when produced by a process claimed in any of the preceding claims.

Reference has been directed in pursuance of section 9, subsection (1) of the Patents Act 1949, to patent No. 1532684.