GB1565849A

GB1565849A - Process for the production of substituted anilines

Info

Publication number: GB1565849A
Application number: GB4772976A
Authority: GB
Original assignee: Ciba Geigy AG
Current assignee: Novartis AG
Priority date: 1975-11-17
Filing date: 1976-11-16
Publication date: 1980-04-23
Also published as: CH625500A5

Abstract

Aniline derivatives of the formula <IMAGE> in which R denotes hydrogen, C1-C4-alkyl, or C1-C4-alkyl which is substituted by C1-C2-alkoxy and R1 denotes hydrogen or methyl, are prepared by reacting an enamine of the formula <IMAGE> in which X denotes a methylene group, oxygen or a direct bond, with an alpha , beta -unsaturated aldehyde of the formula R1-CH=CH-CHO (III> at temperatures between -30 and 150 DEG C followed by heating of the reaction mixture obtained at temperatures between 100 and 400 DEG C in the presence of a hydrogen-transferring catalyst and in the presence of ammonia or an amine of the formula R-NH2 (IV). The aniline derivatives of the above formula are valuable intermediates for the preparation of pesticides.

Description

(54) PROCESS FOR THE PRODUCTION OF SUBSTITUTED ANILINES (71) We, CIBA-GEIGY AG, a Body Corporate organised according to the laws of Switzerland, 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 present invention provides a process for the production of aniline derivatives of the formula I

wherein R represents hydrogen, C1-C4-alkyl or C1-C4-alkyl substituted by C1-C2- alkoxy, and R, represents hydrogen or methyl.

Substituted anilines of the formula I can be used as intermediates for producing halogenoacetanilides, which for their part, by virtue of their biological action, can be employed for the regulation of plant growth and for the control of phytopathogenic fungi. Such halogenoacetanilides and their use for the regulation of plant growth and their use for the control of phytopathogenic fungi are described in British Patents Nos.

1,422,4731,445,378 and 1,448,810.

It is known that aromatic amines can be produced from corresponding phenols by reaction with ammonia in the presence of a hydrogen-transfer catalyst and in the presence of small amounts of the cyclohexanone that corresponds to the phenol (see DT-OS 2,208,827, British Patent Specification No. 1,344,574). A disadvantage of this process is that it is necessary to use aromatic starting materials, which are expensive as a result of the growing scarcity of aromatic raw materials.

There is also known from the US Patent Specification No. 3,857,892 a process in which 2,3,6-trialkylphenols are produced from aliphatic starting materials by reacting an a,13-unsaturated aldehyde with a dialkylketone in the presence of a base to form the corresponding 2,3,6-trialkyl-2cyclohexenone and this product is dehydrogenated in the presence of a hydrogen-transfer catalyst. This process however gives satisfactory yields only for 2,3,6-trialkylphenols, whilst in an analogous process 2,6-dialkylphenols are obtained only in moderate yield. This process is therefore able to provide alkylphenols as starting materials for the production of aromatic amines only to an inadequate degree.

The present invention provides a process that makes possible, in'a simple manner and in good yields, the production of aniline derivatives of the formula I from aliphatic starting materials.

According to the present invention, an aniline derivative of the formula I is produced by a process which comprises reacting an enamine of the formula:

wherein X represents a methylene group, an oxygen atom or a direct bond, at a temperature of between -300C and 150 C with an a,p-un satu rated aldehyde of the formula: R1-CH=CII-CHO (III) wherein R, has the above-mentioned meaning; and subsequently heating the reaction product obtained to a temperature of between 100 and 400"C in the presence of a hydrogen-transfer catalyst and in the presence of an amine of the formula IV R-NH2 (IV) wherein R has the meaning given under formula I.

The reaction of an enamine of the formula II with an a!,-unsaturated aldehyde of the formula III can be performed in an inert solvent, for example, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aliphatic hydrocarbon such as hexane, a chlorinated aliphatic hydrocarbon such as methylene chloride, chloroform, carbon tetrachloride or 1 ,2-dichloroethane, an aromatic hydrocarbon such as benzene or toluene or a lower alkanol such as methanol, ethanol, propanol or isopropanol.

Preferably, however, the reaction is carried out in the absence of a solvent. The dehydrogenation in the presence of an amine of the formula IV can be performed in an aqueous medium, or in an organic solvent for example an ether such as tetrahydrofuran or dioxane, or an aromatic hydrocarbon such as benzene or toluene.

Suitable hydrogen-transfer catalysts are, in particular, platinum and palladium, especially palladium on charcoal.

After the reaction of an enamine of formula II with an cu,p-unsaturated aldehyde of formula III an anhydrous acid, e.g.

hydrogen chloride, sulphuric acid, phosphoric acid, a sulfonic acid, for example p-toluenesulfonic acid or methanesulfonic acid, a carboxylic acid, for example acetic acid, or an anhydrous salt of an amine of formula IV with for example, one of the afore-mentioned acids can be advantageously added to the reaction mixture in order to promote conversion of the immediate product of the reaction between the enamine and the unsaturated aldehyde into a second intermediate from which the desired final product is obtained either directly or via the cyclohexenone of formula V below.

An advantageous embodiment of the process of the invention comprises reacting an enamine of the formula II with a,- unsaturated aldehyde of the formula III, and then converting the reaction product (optionally after treatment with an anhydrous acid or salt in the manner just described) by the addition of acid into a 2cyclohexen-l-one of the formula V

wherein R1 has the meaning already defined, which is then converted by further reaction with an amine of the formula IV, in the presence of a hydrogen-transfer catalyst, into an aniline of the formula I.

The acid employed can be, in particular, hydrogen chloride or sulphuric acid. The acid can be used in anhydrous form or in the form of an aqueous solution.

Another advantageous embodiment of the process of the invention comprises reacting an enamine of the formula II with an a,p-unsaturated aldehyde of the formula III and then converting the reaction product (optionally after treatment with an anhydrous acid or salt in the manner described above) into the aniline of formula I by reaction with an amine of the formula IV followed by dehydrogenation, in the presence of a hydrogen-transfer catalyst, to obtain an aniline of the formula I.

A third advantageous modification of the process of the invention comprises a procedure whereby first an enamine of the formula II is reacted with an excess of the a,-unsaturated aldehyde of the formula III; unreacted ,-unsaturated aldehyde of the formula III and solvent present are removed; and the resulting product is immediately reacted with an aqueous solution of an amine of the formula IV in the presence of a hydrogen-transfer catalyst. In this modification, the excess of a"B- unsaturated aldehyde can be up to 1.5 moles per mole of enamine of the formula II. The reaction is preferably performed in the absence of solvent.

It is advantageous to perform the final reaction with the amine of the formula IV and dehydrogenation under pressure in the presence of an inert gas and/or of a hydrogen-acceptor. A suitable inert gas is, in particular, nitrogen, and suitable hydrogen-acceptors are, for example, olefins such as propylene, or carbonyl compounds such as acetone, methylethylketone, cyclohexanone or ketones formed during the reaction such as 2,6-dimethyl-cyclohexanone or 2,6dimethylcyclohexenone. It is further advantageous to interrupt the dehydrogenation one or several times and to pass nitrogen through the reaction vessel in order to remove hydrogen and to carry out the dehydrogenation in the presence of nitrogen. The amount of inert gas is so regulated that an initial pressure of 5 to 25 bars is created in the reaction vessel.

When the final reaction with the amine of the formula IV and the dehydrogenation are carried out in an organic solvent, the final products of the formula I can be obtained, after separation of the catalyst, by evaporating off the solvent and distilling the residue. When carrying out the final reaction with the amine of the formula IV and dehydrogenation in an aqueous medium, the end products can be advantageously isolated from the reaction mixture by extraction with a suitable solvent, such as ether or methylene chloride. The final products of the formula I are then obtained from the extract by evaporating off the solvent and processing the residue by distillation.

The process of the invention is particularly suitable for the production of 2,6-dimethylaniline and N-alkyl- or N alkoxyalkyl-2,6-dimethylanilines. The process according to the invention provides a simple means of obtaining aromatic intermediates from aliphatic starting materials.

The process of the invention is further illustrated by the following Examples.

Example I a) 2,6-dimethyl-cyclohex-2-en-l-one 26.1 g (0.168 mole) of N-(3-pent-2-enyl) morpholine is slowly added dropwise to a solution, cooled to 0 , of 16.8 g (0.3 mole) of freshly distilled acrolein in 150 ml of dioxane, the temperature rising to SOC.

After completion of the addition, stirring is maintained for half an hour with ice cooling, and the mixture is then allowed to stand overnight. The solvent is afterwards evaporated off and the oil obtained as residue is dissolved in 120 ml of 20% aqueous hydrochloric acid. On stirring of the acidified solution at room temperature, there precipitates an oil which, after one to two days' stirring, is taken up in ether. The aqueous phase is extracted a further five times with ether. The combined ether phases are dried over magnesium sulphate and the ether is distilled off. There is obtained 18.5 g of crude 2,6-dimethyl-cyclohex-2-en- 1-one in the form of oil, which yields, after distillation in a water-jet vacuum, 15.0 g of 2,6-dimethyl-cyclohex-2-en- l-one (72% of theory); b.p. 6l-630C/l0 Torr.

The N-(3-pent-2-enyl)-morpholine used as starting material is produced as follows: 87.0 g (1 mole) of morpholine and 129.3 g (1.5 moles) of diethyl ketone are placed into a pear-shaped flask fitted with a Soxhlet attachment. The Soxhlet, in which there is provided a tube containing about 200 g of molecular sieve 4A, is then filled up to approximately half a centimetre from the overflow level with diethyl ketone. The contents of the flask are subsequently refluxed for 300 hours at a bath temperature of 150"C. After cooling, the combined liquids from Soxhlet and flask are concentrated at 400C bath temperature in a rotary evaporator. The oily residue is distilled in a water-jet vacuum to yield 84.8 g (550/ of theory relative to the morpholine used) of N-3-pent-2-enyl)-morpholine; b.p.

88-900C/10 Torr.

b) 2,6-dimethylaniline A solution of 19.7 g (0.158 mole) of 2,6 dimethylcyclohex-2-en-l-one in 180 ml of conc. ammonia is heated, after the addition of 4.0 g of palladium on charcoal (5%), in a hydrogenating autoclave for 4 hours at 280290 C, whereby a pressure of 20 bars is established, and is then maintained under these conditions for 5 hours. Cooling and pressure release are then carried out; the contents are again heated for about 5 hours and the pressure is again released. In order to effect the complete removal of hydrogen, the procedure of heating and pressure release is carried out in all three times. An addition is then made of 150 ml of ether and the catalyst is filtered off. The filter residue is washed three times alternately with 100 ml of ether and water, respectively. The mother liquor is extracted, after separation of the ether phase, five times with 150 ml of ether each time. The combined ether phases are dried over magnesium sulphate. After the ether has been distilled off, there remains 17.0 g of crude 2,6-dimethylaniline, from which is obtained, by distillation in a water-jet vacuum, 12.0 g (63% of theory) of pure 2,6-dimethylaniline; b.p. 103"C/18 Torr.

Example 2 2,6-Dimethyl-cyclohex-2-en- 1-one 19.6 g (0.35 mole) of freshly distilled acrolein is added dropwise at a maximum of 50"C, with ice-cooling, to a solution of 27.8 g (0.2 mole) of N-(3-pent-2-enyl)-pyrrolidine in 50 ml of benzene. After completion of the addition, the mixture is stirred overnight at room temperature; it is subsequently heated for 2 hours at 50--550C and then concentrated by evaporation. T-he oil remaining is dissolved in 250 ml of 20% hydrochloric acid and the solution is stirred overnight. Extraction is then performed five times with ether; the combined extracts are dried over magnesium sulphate and the ether is distilled off. The crude 2,6 dimethyl-cyclohex-2-en-l-one remaining is purified by vacuum distillation. There is obtained 14.8 g (60% of theory) of 2,6dimethyl-cyclohex-2-en-l-one, b.p. 62 64"C/10 Torr.

The N-(3-pent-2-enyl)-pyrrolidine used as starting material is produced as follows: 584 g of pyrrolidine and 126.7 g of diethyl ketone are placed into a pear-shaped flask fitted with Soxhlet attachment. In the Soxhlet there is contained 200 g of molecular sieve A4. The mixture is boiled for 170 hours at 1500C bath temperature, and subsequently concentrated in a rotary evaporator. The residue obtained is distilled in a water-jet vacuum. There is obtained 142 g (70An of theory) of N-(3-pent-2-enyl)pyrrolidine, b.p. 800C/18 Torr. With the use of excess diethyl ketone, it is possible to attain a yield of 94%.

Example 3 a) 2,3,6-trimethyl-cyclohex-5-en- 1-one 15.4 g (0.22 mole) of crotonaldehyde is added dropwise at room temperature, without external cooling, to a solution of 27.8 g (0.2 mole) of N-(3-pent-2-enyl)pyrrolidine in 50 ml of anhydrous dioxane, with the temperature rising to 500C and again falling. The mixture is stirred overnight and subsequently heated for 2 hours at 50"C. The oil obtained after the solvent has been evaporated off is dissolved in 250 ml of 205/, hydrochloric acid, with the temperature rising to 400 C. After 2 days' stirring at room temperature, the mixture is extracted four times with ether; the combined ether extracts are dried over magnesium sulphate and the ether is evaporated off. The oil remaining is distilled in vacuum. There is obtained 4.3 g (15 /n of theory) of 2,3,6-trimethyl-cyclohex-5-en- 1 - one; b.p. 61"C/10 Torr.

b) 2,3,6-Trimethylaniline 5.0 g (0.0362 mole) of 2,3,6-trimethyl-5cyclohexen-l-one, 50 ml of conc. ammonia and 1.0 g of palladium on charcoal (5An) are heated in a hydrogenating autoclave under nitrogen for 11 hours at 280--2900C; the initial pressure of the nitrogen is 20 bars, and after one hour and after 6 hours the mixture is cooled and the nitrogen is changed. An addition is made to the cooled mixture of 100 ml of ether; the catalyst is filtered off, and subsequently washed five times witii 100 ml of ether each time. The ether layer is separated from the mother liquor, and the aqueous layer is extracted five times with 50 ml of ether each time. The combined ether extracts are dried over magnesium sulphate and the ether is distilled off. There is obtained 5.0 g of crude 2,3,6-trimethylaniline, which yields, after distillation in vacuo, 4.0 g (80% of theory) of 2,3,6-trimethylaniline; b.p. 102"C/10 Torr.

Example 4 a) N - (2 - Methoxyethyl) - 2,6 dimethylcyclohex - 2 - en - 1 - one imine 38.8 g (0.25 mole) of N-(3-pent-2-enyl)morpholine is slowly added dropwise at 0 to a solution of 25.1 g (0.448 mole) of freshly distilled acrolein in 175 ml of dioxane, with the temperature rising to 50C. After 16 hours subsequent stirring, the solvent is evaporated off in vacuo. There remains 29.0 g of an oil which, after the addition of 37.5 g (0.5 mole) of 2-methoxyethylamine, is boiled for 30 hours at a bath temperature of 130"C.

The mixture is afterwards distilled to yield 1.5 g of N - (2 - methoxyethyl) - 2,6 dimethyl - cyclohex - 2 - en - 1 - one - imine; b.p. 1240C/15 Torr (33% of theory).

b) N-(2-methoxyethyl)-2,6-dimethylaniline 8.0 g of N - (2 - methoxyethyl) - 2,6 dimethylcyclohex - 2 - en - 1 - one - imine (0.0442 mole), 100 ml of dioxane, 40.0 g of propylene and 1.0 g of palladium on charcoal (5%) are heated in a hydrogenating autoclave for 24 hours at 120--130"C. After cooling, the catalyst is filtered off and washed on the filter twice with ether. After concentration of the mother liquor by evaporation, there is obtained 6.6 g of crude N - (2 - methoxyethyl) - 2,6 dimethylaniline, which yields, by distillation in high vacuum, 3.5 g (45in of theory) of pure N - (2 - methoxyethyl) - 2,6 dimethylaniline; b.p. 49"C/0.1 Torr.

Example 5 N-(2-Methoxyethyl)-2,6-dimethylaniline 2.0 g (0.0161 mole) of 2,6 - dimethyl cyclohex - 2 - en - 1 - one, 50 ml of toluene, 1.8 g (0.024 mole) of 2-methoxyethylamine and 0.5 g of palladium on charcoal (5%) are heated with a starting pressure of 17 bars (7 bars propylene and 10 bars nitrogen) for 10 hours at 1800C. After cooling, the catalyst is filtered off and the filter residue is washed with ether and toluene. The solvent is evaporated off to leave 1.0 g of crude N - (2 methoxyethyl) - 2,6 - dimethylaniline, from which is obtained, by distillation in high vacuum, (0.4 g (13% of theory) of pure N (2 - methoxyethyl) - 2,6 - dimethylaniline which distilled at 61620C/0.l Torr.

Example 6 2,6-Dimethylaniline 15.1 g (0.93 mole) of N - (3 - pent - 2 enyl) - morpholine is slowly added dropwise to 9.75 g (0.174 mole) of freshly distilled acrolein with ice-cooling being applied; there occurs a temperature rise from 100C initially to 1 100C. After completion of the addition, stirring is maintained for 15 hours and the excess acrolein is afterwards distilled off. There remain behind 20.0 g of an oil, which is heated with 150 ml of concentrated aqueous ammonia and 4.0 g of palladium on charcoal (5%) at a pressure of 20 bars (nitrogen) for 24 hours at 280- 290"C; heating is carried out firstly for about 5 hours with subsequent cooling and exhausting and reheating; cooling, exhausting and reheating are subsequently performed every 5 hours. An addition of 300 ml of ether is then made to the mixture and the catalyst is filtered off. The filter residue is washed four times with 100 ml of ether each time. After separation of the ether phase from the mother liquor, the aqueous phase is extracted five times with 150 ml of ether each time; the combined ether extracts are dried over magnesium sulphate and the ether is distilled off. The resulting crude 2,6-dimethylaniline is purified by vacuum distillation to yield 4.2 g (35% of theory) of 2,6-dimethylaniline; b.p.

103"C/18 Torr.

Example 7 2,6-Dimethylaniline 12.9 g (0.23 mole) of freshly distilled acrolein is added dropwise at room temperature to a solution of 27.8 g (0.2 mole) of N - (3 - pent - 2 - enyl) pyrrolidine in 50 ml of absolute benzene, with the temperature rising to a maximum of 50"C. After completion of the addition, the mixture is stirred for 2 hours at room temperature. It is subsequently boiled for 15 hours at about 110"C bath temperature in a water-separator. The oil obtained after evaporating off the solvent is heated for 18 hours with 100 ml of anhydrous dioxane, 10.0 g of ammonia, 50.0 g of propylene and 5.0 g of palladium on charcoal (5%) at 12() 1300C under a pressure of 47 bars (nitrogen). After the addition of 100 ml of ether, the catalyst is filtered off and washed three times with ether. The oil obtained after removal of the solvent by evaporation is distilled in vacuo. There is obtained 4.5 g (20% of theory) of 2,6-dimethylaniline, b.p.

103"C/18 Torr, and as by-products 1.9 g (8% of theory) of 2,6 - dimethyl - cyclohex - 2 en - 1 - one, b.p. 62--640C/17 Torr, and 2.4 g (10% of theory) of 2,6-dimethylcyclohexanone.

Example 8 N-methyl-2,6-dimethylaniline 14.0 g (0.25 mole) of acrolein is added dropwise at 25 to 300C to 23.3 g (0.15 mol) of N - (3 - penten - 2 - yl) - morpholine. The mixture obtained is stirred for 15 hours at 25"C and subsequently, for further 15 hours at 50"C. The mixture is then transferred into an autoclave and after addition of 400 ml of a 40 ,i, by weight aqueous solution of methylamine and 10.0 g of palladium on charcoal (5%), the whole is heated under a nitrogen pressure of 50 bars for 5 hours at 280 to 290"C. Subsequently the catalyst is separated off by filtration and washed with ether. The filtrate is extracted several times with ether, the combined extracts are dried over magnesium sulphate and the ether is distilled off. Water is then added to the residue and the whole is acidified by addition of hydrochloric acid. The acid solution obtained is extracted with ether and the extract is discarded. Sodium bicarbonate is added to the acid solution until the mixture shows alkaline reaction and the whole is again extracted with ether.

The extract is dried over sodium sulphate and the ether is distilled off. N - methyl 2,6 - dimethylaniline is obtained by distillation of the residue at 0.1 Torr.

Example 9 2,6-Dimethylaniline 8.4 g (0.15 mol) of acrolein is added dropwise to a solution of 23.3 g (0.15 mol) of N - (3 - penten - 2 - yl) - morpholine in 100 ml of methylene chloride. After addition of the acrolein the mixture is stirred for 15 hours at 250C and subsequently for further 15 hours at 500C. Then 12.0 g (0.225 Mol) of ammonium chloride are added and the solvent is distilled off. The residue is transferred into an autoclave and after addition of 400 ml of concentrate aqueous ammonia and 10.0 g of palladium coal (5%) the whole is heated under a nitrogen pressure of 50 bars for 15 hours at 280- 290"C. The catalyst is then filtered off and washed with ether. The filtrate is extracted several times with ether. The extracts are combined and dried over magnesium sulphate and the ether is distilled off. The residue (14.2 g; 79% of theory) is distilled at a pressure of 15 torr. There is obtained 6.7 g (37% of theory) of 2,6-dimethylaniline, b.p.

94--98"C/15 Torr.

The fraction boiling between 60 and 90"C contains 2,6-dimethylcyclohexanone and 2,6-dimethyicyclohexenone. After addition of ammonia and a dehydrogenation catalyst these products can be converted into 2,6dimethylaniline, as described above. The morpholine which is also present in the fraction boiling between 60 and 90"C can be reused for the preparation of N - (3 penten - 2 - yl) - morpholine.

Example 10 N-(2'-Methoxyethyl)-2,6-dimethylaniline 14.0 g (0.25 mol) of acrolein is added dropwise at a maximal temperature of 35"C to a solution of 23.3 g (0.15 mol) of N - (3 penten - 2 - yl) - morpholine in 100 ml of anhydrous dioxane. The mixture obtained is stirred for 15 hours at 250C and thereafter for further 15 hours at 500C. The solvent is distilled of and the residue is transferred into an autoclave and, after addition of a solution of 200 ml of 2-methoxyethylamine in 200 ml of water and 10.0 g of palladium on charcoal (5%) the whole is heated under a nitrogen pressure of 50 bars for 11 hours at 280290 C. The catalyst is then separated by filtration and washed with ether. After separation of the ethereal layer the filtrate is extracted several times with ether. The extracts are combined and dried over magnesium sulphate and the ether is distilled off. The residue is distilled in vacuo. The fraction boiling between 30 and 63"C at 0.4 torr is mixed with water and acidified by addition of hydrochloric acid.

The resulting solution is extracted with ether and the extract is discarded.

Subsequently sodium bicarbonate is added to the aqueous solution until an alkaline reaction is reached and the whole is again extracted several times with ether. The extracts are combined and dried over magnesium sulphate and the ether is evaporated. N - (2 - methoxyethyl) - 2,6 dimethylaniline is obtained as an oily residue.

Example 11 N-(2'-Methoxyethyl)-2,6-dimethylaniline 14.0 g (0.25 mol) of acrolein is added dropwise to a solution of 23.3 g (0.15 mol) of N - (3 - penten - 2 - yl) - morpholine in 100 ml of chloroform. The mixture obtained is stirred for 15 hours at room temperature and then for further 15 hours at 500C.

Thereafter the solvent is distilled off and the residue is transferred into an autoclave and, after addition of a solution of 200 ml of 2methoxyethylamine in 200 ml of benzene and 10.0 g of palladium coal (5%) the whole is heated under a nitrogen pressure of 50 bars for 15 hours at 280--2900C. The solvent is then evaporated and water is added to the residue. The whole is acidified by addition of hydrochloric acid. The solution obtained is extracted with. ether and the extract is discarded. Subsequently sodium bicarbonate is added to the aqueous solution until alkaline reaction is reached and the whole is again extracted several times with ether. The extracts are combined and dried over magnesium sulphate and the ether is distilled off. The residue (40.1 g) is distilled in vacuo at 0.4 torr. There is obtained 7.5 g (28% of theory) of N - (2' methoxyethyl) - 2,6 - dimethylaniline.

Example 12 2,6-Dimethylaniline 14.0 g. (0.25 mol) of acrolein is added dropwise at maximal temperature of 40"C to a solution of 23.3 g (0.15 mol) of N - (2 penten - 2 - yl) - morpholine in 100 ml of anhydrous chloroform. The mixture is stirred for 15 hours at 250C and then for further 15 hours at 500C. Thereafter the solvent is distilled off and the residue is transferred into an autoclave and, after addition of 400 ml concentrated aqueous ammonia and 10.0 g of palladium coal (5An) the whole is heated under a nitrogen pressure of 50 bars for 15 hours at 280 to 2900 C. Subsequently the catalyst is separated by filtration and washed with ether. After separation of the ethereal layer the filtrate is extracted several times with ether. The extracts are combined and dried over magnesium sulphate and the ether is distilled of. The residue (22 g) is distilled in vacuo. There is obtained 6.5 g (35An of theory) of 2,6-dimethylaniline, b.p. 94 96"C/15 torr.

WHAT WE CLAIM IS: 1. A process for the production of an aniline derivative of the formula:

wherein R represents hydrogen, C1-C4-alkyl or C1-C4-alkyl substituted by C1-C2-alkoxy, and R, represents hydrogen or methyl, which comprises reacting an enamine of the formula:

wherein X represents a methylene group, an oxygen atom or a direct bond, at a temperature of between -30"C and 150"C with an ,-unsaturated aldehyde of the formula: R1-Cll-CH-CHO (III) wherein R1 represents hydrogen or methyl; and subsequently heating the reaction product obtained to a temperature of between 100 and 400"C in the presence of a hydrogentransfer catalyst and in the presence of an amine of the formula IV R-NH2 (IV) wherein R has the meaning given under formula I.

2. A process according to Claim 1, wherein the reaction of an enamine of the formula II with an a,p-unsaturated aldehyde of the formula III is performed in the absence of a solvent.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. a nitrogen pressure of 50 bars for 11 hours at 280290 C. The catalyst is then separated by filtration and washed with ether. After separation of the ethereal layer the filtrate is extracted several times with ether. The extracts are combined and dried over magnesium sulphate and the ether is distilled off. The residue is distilled in vacuo. The fraction boiling between 30 and 63"C at 0.4 torr is mixed with water and acidified by addition of hydrochloric acid. The resulting solution is extracted with ether and the extract is discarded. Subsequently sodium bicarbonate is added to the aqueous solution until an alkaline reaction is reached and the whole is again extracted several times with ether. The extracts are combined and dried over magnesium sulphate and the ether is evaporated. N - (2 - methoxyethyl) - 2,6 dimethylaniline is obtained as an oily residue. Example 11 N-(2'-Methoxyethyl)-2,6-dimethylaniline 14.0 g (0.25 mol) of acrolein is added dropwise to a solution of 23.3 g (0.15 mol) of N - (3 - penten - 2 - yl) - morpholine in 100 ml of chloroform. The mixture obtained is stirred for 15 hours at room temperature and then for further 15 hours at 500C. Thereafter the solvent is distilled off and the residue is transferred into an autoclave and, after addition of a solution of 200 ml of 2methoxyethylamine in 200 ml of benzene and 10.0 g of palladium coal (5%) the whole is heated under a nitrogen pressure of 50 bars for 15 hours at 280--2900C. The solvent is then evaporated and water is added to the residue. The whole is acidified by addition of hydrochloric acid. The solution obtained is extracted with. ether and the extract is discarded. Subsequently sodium bicarbonate is added to the aqueous solution until alkaline reaction is reached and the whole is again extracted several times with ether. The extracts are combined and dried over magnesium sulphate and the ether is distilled off. The residue (40.1 g) is distilled in vacuo at 0.4 torr. There is obtained 7.5 g (28% of theory) of N - (2' methoxyethyl) - 2,6 - dimethylaniline. Example 12 2,6-Dimethylaniline 14.0 g. (0.25 mol) of acrolein is added dropwise at maximal temperature of 40"C to a solution of 23.3 g (0.15 mol) of N - (2 penten - 2 - yl) - morpholine in 100 ml of anhydrous chloroform. The mixture is stirred for 15 hours at 250C and then for further 15 hours at 500C. Thereafter the solvent is distilled off and the residue is transferred into an autoclave and, after addition of 400 ml concentrated aqueous ammonia and 10.0 g of palladium coal (5An) the whole is heated under a nitrogen pressure of 50 bars for 15 hours at 280 to 2900 C. Subsequently the catalyst is separated by filtration and washed with ether. After separation of the ethereal layer the filtrate is extracted several times with ether. The extracts are combined and dried over magnesium sulphate and the ether is distilled of. The residue (22 g) is distilled in vacuo. There is obtained 6.5 g (35An of theory) of 2,6-dimethylaniline, b.p. 94 96"C/15 torr. WHAT WE CLAIM IS:

1. A process for the production of an aniline derivative of the formula:

3. A process according to Claim I or 2,

wherein an anhydrous acid or an anhydrous salt of an amine of formula IV is added to the reaction mixture after the reaction of an enamine of formula II with a unsaturated aldehyde of formula III.

4. A process according to Claim 3, wherein anhydrous hydrogen chloride, sulphuric acid, phosphoric acid, p-toluenesulfonic acid, methanesulfonic acid, acetic acid or an anhydrous salt of the amine of formula IV with one of the afore-mentioned acids is added to the reaction mixture after the reaction of an enamine of formula II with a a,p-unsaturated aldehyde of formula Ill.

5. A process according to any one of Claims 1 to 4, wherein after an enamine of the formula II has reacted with an X unsaturated aldehyde of the formula III the reaction product obtained is converted by the addition of an acid into a 2-cyclohexen I-one of the formula:

wherein R1 has the meaning given under formula I; and this is subsequently converted by reaction with an amine of the formula IV, in the presence of a hydrogen-transfer catalyst, into an aniline of the formula I.

6. A process according to any one of Claims 1 to 4, wherein the reaction product formed by reaction of an enamine of the formula II with an a,X3-unsaturated aldehyde of the formula III, is reacted with an amine of the formula IV, and the product formed is subsequently dehydrogenated in the presence of a hydrogen-transfer catalyst, to obtain an aniline of the formula I.

7. A process according to any one of Claims 1 to 6, wherein the reaction with an amine of the formula IV is performed in an aqueous medium or in the presence of an organic solvent.

8. A process according to Claim 1 or 2, wherein an enamine of the formula II is reacted with an excess of the cr,ss- unsaturated aldehyde of the formula III; unreacted a,ss-unsaturated aldehyde of the formula III and solvent present are removed; and the resulting product is immediately reacted with an aqueous solution of an amine of the formula IV, in the presence of a hydrogen-transfer catalyst, to obtain an aniline of the formula I.

9. A process according to any one of Claims 1 to 8, wherein the final reaction with the amine of the formula IV and dehydrogenation are performed under pressure in the presence of an inert gas and/or in the presence of a hydrogenacceptor.

10. A process according to Claim 1 substantially as described in any one of the foregoing Examples 1 to 12.

11. An aniline derivative of the formula I as defined in Claim 1 when produced by the process claimed in any of Claims 1 to 10.