CA2058140A1 - Process for the production of 4-substituted 2, 6-dialkylanilines - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

A process is disclosed for the production of 4-substituted 2,6-dialkylanilines of the formula:

Description

2~814Q

This invention relates to a new process for the production of 4-substituted 2,6-dialkylanilines of the formula:
R

Rl ~R2 (I~
N~2 wherein R1 and R2 are the same or different and are straight-chain or branched (C1-C4)-lower alkyl groups, and R3 is a phenylisopropyl group, a 1,1,3,3-tetramethylbutyl group or a tert-butyl group. This invention further 15 relates to the novel 2,6-dialkyl-4-(1,1,3,3-tetramethylbutyl)-anilines of the formula:

CH3 ~CH3 -j~q 3 (III) 1 ~ R2 ., NH2 wherein R1 and R2 have the above-mentioned meaning.
Preferably, the 2, 6-dialkyl-4- ( 1, 1, 3, 3-tetramethylbutyl)aniline of formula III is 2,6-diisopropyl-4-(1,1,3,3-tetramethylbutyl)-aniline, with R1 and R2 being isopropyl.
The 4-substituted 2,6-dialkylanilines of formula I are valuable intermediates in the production of pesticides ~European Published Patent Application No.
0304025], arylthiourea derivatives ~West German OS
2727416], and hydrolysis protecting agents in polyurethanes ~Becher/Braun, Kunststoff Handbuch "Polyurethane" (Plastics : ~ 35 Manual Polyurethanes), Vol. 7, C. Hauser-Verlaa, (1983), pages 407 to 408].

2~581~0 European Published Patent Application No. 0069065 teaches the alkylation of aromatic anilines in the para-position with, e.g., ~-methylstyrene or diisobutylene.
Characteristically the reaction is performed in the presence of an aqueous acid, generally hydrochloric acid, as a catalyst and with the addition of zinc chloride as a co-catalyst. The disadvantages of such process are that a substantial amount of both catalyst and co-catalyst ranging in an amount of up to 2 moles per mol of aromatic aniline are needed and that the reaction proceeds very slowly.
U.S. Patent No. 4,340,758 teaches, e.g., the production of 4-t-butyl-2,6-dimethylaniline in three reaction steps to produce a total yield of 40 percent. In the first step, 5-t-butyl-1,3-dimethylbenzene was obtained by HF-catalyzed alkylation of m-xylene with isobutene.
Then, 2-nitro-1,3-dimethyl-5-t-butylbenzene was synthesized by further nitration with HNO3 in the presence of mercury acetate, and, finally, the nitro group was reduced by catalytic hydrogenation. However, such process is undesirable because the reactants HF and mercury acetate are problematical both from an ecological aspect and from a process-technology aspect. Furthermore, such process results in poor yields on an industrial scale.
It was proposed in West German OS 2727416, page 60, to produce 4-t-butyldiethylaniline (analogously to Example 9, page 59 of the same reference), by ethylation of 4-t-butylaniline with ethylene in the presence of aluminum chloride at 200 atmospheres of excess pressure and 250C.
An indication of the yield is not available. Besides the drastic, expensive process conditions, another disadvantage of such process is that 4-t-butylaniline is difficult to obtain, i.e., it has to be produced by the nitration of t-butylbenæene, and subsequent reduction of the nitro group to aniline is needed. Additionally, mixtures of isomers resulting from the nitration of monoalkyl benzenes [J. Am.

2~58~0 Chem. Soc., Vol 73, (1951), page 5605], make it more difficult for obtaining 4-butylaniline.
Reactions of the unsubstituted aniline with isobutylene have also been known for a long time. Thus, it can be seen from British Patent No. 823,223, Examples 17, 20 and 49, that by reacting aniline with isobutene in the presence of aluminum chloride and metallic aluminum, or in the presence of boron trifluoride, and under pressure and at temperatures of between 200 and 300C with a partially low conversion, mixtures of monoisobutylanilines and diisobutylanilines can be produced. Although it was possible to improve the conversions with fixed-bed catalysts, the product further consisted of a mixture of monoisobutylanilines and diisobutylanilines [European Published Patent Application No. 226781; European Published Patent Application 245797; Appl. Catalysis, Vol. 62, (1990), pages 161 to 169].
The main object of this invention is to provide a process for the production of 4-substituted 2,6-dialkylanilines which avoids the disadvantages of the prior art.
Accordingly, the invention provides a process for the production of a 4-substituted 2,6-dialkylaniline of the formula:

Rl ~ R2 (I) N~2 wherein R1 and R2 are the same or different and are straight-chain or branched (C~-C4) -lower alkyl groups, and R3 is a phenylisopropyl group, a 1,1,3,3-tetramethylbutyl group or a tert-butyl group, which process comprises alkylating a 2,6-dialkylaniline of the formula:

- 2~5~

Rl ~ R2 (II) N~2 wherein R1 and R2 have the above meaning, with ~-methylstyrene in the presence of a catalyst to introduce the phenylisopropyl group, or with diisobutylene in the presence of a catalyst to introduce the 1,1,3,3-tetramethylbutyl group, or with isobutene in the presence of a catalyst to introduce the tert-butyl group.
Preferably a Friedel-Crafts aklylation catalyst is used as the catalyst. Particularly, aluminum chloride, a boron trifluoride-ether complex or montmorillonite can ~uitably be used as the catalyst. Preferably the catalyst is used in an amount between 0.01 and 0.3 mol relative to 1 mol of 2,6-dialkylaniline. Preferably the reaction is performed at a temperature between 100 and 300C, and a pressure between standard pressure and 60 bars.
~ his invention also provides for the production of novel 2,6-dialkyl-4-(1,1,3,3-tetramethylbutyl)-anilines ` of the formula:

C~ CC~3 (III) R1 ' ~ ~R2 r . :

.

2~58~0 wherein R1 and R2 have the above meaning. Preferably the aniline of formula III is 2,~-diisopropyl-4-(1,1,3,3-tetramethylbutyl)-aniline.
The starting materials employed in the process of the invention are 2,6-dialkylanilines, available on an industrial scale, of the formula:

~
1 ~ R2 (II) wherein R1 and R2 are the same or different and are straight-chain or branched (C1-C~) lower alkyl groups.
According to this invention, 2,6-dialkylanilines are alkylated with ~-methylstyrene in the presence of a catalyst to introduce the phenylisopropyl group, or with diisobutylene in the presence of a catalyst to introduce the 1,1,3,3-tetramethylbutyl group, or with isobutene in the presence of a catalyst to introduce the tert-butyl group. Suitable catalysts are the Friedel-Crafts alkylation catalysts, as described, e.g., in Ullmann's Encyclo~edia of Industrial ChemistrY, 5th ed., Vol Al, page 185 ff. Especially suitable catalysts are aluminum chloride or boron trifluoride-ether complexes, such as the boron trifluoride-diethyl ether complex, or aluminum silicates, such as montmorillonite. Suitably the catalyst is used in an amount of from 0.01 to 0.3 mol, and preferably from 0.05 to 0.15 mol, relative to 1 mol of 2,6-dialkylaniline. It has been shown that a preceding activation of the catalyst or the addition of a co-catalyst is not necessary. The reaction takes place suitably at a temperature between 100 and 300C, and preferably between ' 2~8~ ~Q

150 and 250C, and at a pressure between standard pressure and 60 bars, and preferably between standard pressure and 40 bars. The reaction takes place advantageously without the presence of an additional solvent. Suitably, the olefin used for alkylation, optionally used in excess, acts as the solvent. But the reaction can be performed in the presence of an inert solvent. After a reaction time of usually from 2 to 20 hours, the resultant 4-substituted 2,6-dialkylanilines can be isolated in good purity and yield by simple distillation or by the formation of a salt from the reaction mixture.
The following Examples illustrate the process of the invention:
Example 1 Production of 2 6-diisopropyl-4-(phenvlisopropvl)aniline 354.6 g of 2,6-diisopropylaniline ~2.0 mol), 239.9 g of a-methylstyrene (2.0 mol) and 18.62 g of aluminum chloride (0.14 mol) were heated in an autoclave over 4 hours to 205C (pressure 1 to 2 bars). After cooling, the autoclave content was taken up in 600 ml of toluene. The toluene solution was then washed in succession with 10 percent sodium hydroxide solution and water, and evaporated to dryness in a water jet vacuum and 60C bath temperature. Thus, 599.7 g of residue containing 73.4 percent of 2,6-diisopropyl-4-(phenylisopropyl)aniline and 13.4 percent of 2,6-diisopropylaniline were obtained.
This corresponded to a yield of 74 percent, relative to the 2,6-diisopropylaniline used. It was possible to purify the product further by distillation (boiling point: about 150C/0.8 mbar; content: 98 to 99 percent).
Example 2 Production of 2.6-diisoproPyl-4-(1 1 3 3-tetramethyl-butYl)aniline 59.6 g of diisopropylaniline (0.33 mol), 3.89 g of aluminum chloride (0.03 mol) and 224.1 g of diisobutylene (78 percent of 2,4,4-trimethyl-1-pentene, 20 20~81~

percent of 2,4,4-trimethyl-2-pentene) were heated in an autoclave over 15 hours to 200C (pressure 6 to 7 bars).
After cooling, the autoclave content was washed twice with 100 ml of water each, and excess diisobutylene was removed by vacuum distillation on a Rotavapor. Thus, 87.4 g of distillation residue containing 57.5 percent of 2,6 -diisopropyl-4-(1,1,3,3-tetramethyl-butyl)aniline and 13.2 percent of 2,6-diisopropylaniline was obtained. This corresponded to a yield of 52 percent, relative to the 2,6-diisopropylaniline used. Other data for the product are:
HMNR: (CDCl3, 300 MHz) ~ in ppm:
0.68, s, 9H;
1.26, d, J=6.8 Hz, 12H;
1.35, s, 6H;
1.66, s, 2H;
2.94, m, J=6.8 Hz, 2H;

3.57, s, 2H;
7.02, s, 2H.Example 3 4-t-Butyl-2 6-diiso~ropylaniline 211.9 g of 2,6-diisopropylaniline (1.14 mol;
content: 95.2 percent) and 12.1 g of aluminum chloride (0.09 mol) were added to a heatable 1 liter-agitator autoclave. The autoclave was connected by corresponding feed pipes with a nitrogen pressure cylinder and by a pressure-resistant liquid metering pump with an isobutene bottle. The autoclave was rendered inert by repeated careful pressing and expanding of about 2 bars of nitrogen.
In the same way, nitrogen was displaced with isobutene until the reaction mixture was saturated at between 10 and 20C with 2 bars of isobutene. The autoclave was heated to 180 C over 50 to 60 minutes, in the course of which the pressure was increased to between 28 and 30 bars, before it started to drop, which indicated the initiation of the reaction. When the pressure dropped to 25 bars, it was pressed again in each case to 30 bars until saturation was 2 ~ 0 reached after about 10 hours. The autoclave was cooled to 20C, expanded and emptied into 250 ml of toluene. The toluene solution was then washed in succession with 10 percent sodium hydroxide solution and water, and subsequentl~ evaporated to dryness on a Rotavapor. Thus, 293 g of evaporation residue containing 90.2 percent of 4-t-butyl-2,6-diisopropylaniline was obtained. Further purification was completed by fractionating distillation and recrystallization from hexane. Other data for the product are:
H-NMR: (CDCl3, 300 MHz) ~ in ppm:
1.28, d, 12H, J=6.8 Hz;
1.30, s. 9H;
2.94, m, 2H, J=6.8 Hz;
3.62, s, 2H;
7.07, s, 2H.
Boiling point: 154 to 156C/22 mbars Melting point: 73 to 74C
Example 4 4-t-Butyl-2-ethvl-6-methvlaniline Analogous to Example 3, 161.7 g of 2-ethyl-6-methylaniline (1.2 mol; content: 100 percent) was heated in the presence of 12.1 g of aluminum chloride (0.09 mol) with 20 bars of isobutene for 20 hours at 200C and worked up.
From the vacuum distillation of the evaporation residue of the toluene solution, 182.5 g of 4-t-butyl-2-ethyl-6-methylaniline was obtained as a colorless, oily liquid (content: 97.4 percent; boiling point: 134C/15 mbars).
This corresponded to a yield of 78 percent, relative to the 2-ethyl-6-methylaniline used. Other data for the product are:
H-NMR: (CDC13, 300 MHz) ~ in ppm:
1.24, t, 3H, J=7.5 Hz;
1.28, s, 9H;
2.17, s, 3H;
2.52, m, 2H;

2~581~Q

3.46, s, 2H;
6.97, s, 2H.
Example 5 4-t-Butyl-2-isoProPyl-6-methYlaniline Analogous to example 3, 178 g of 2-methyl-6-isopropylaniline (1.2 mol; content: 97.3 percent) was stirred in the presence of 12.1 g of aluminum chloride (0.09 mol) with 30 bars of isobutylene for 4 hours at 220C.
After working up and distillation, 183.5 g of 4-t-butyl-2-isopropyl-6-methylaniline (content: 97.6 percent; boilin~
point: 138C/16 mbars) was obtained as a colorless, oily liquid. This corresponded to a yield of 75 percent, relative to the 2-methyl-6-isopropylaniline used. Other data for the product are:
1H-NMR: (CDCl3, 300 MHz) ~ in ppm:
1.28, s, 9H;
1.28, d, 6H, J=6.8 Hz;
2.18, s, 3H;
2.91, sept, lH, J=6.8 Hz;
3.46, s, 2H;
6.96, d, lH, J=1.8 Hz;
7.07, d, lH, J=1.8 Hz.
ExamPle 6 4-t-butyl-2 ! 6-diisopropylaniline In a 100 ml autoclave 17.73 g of 2,6-diisopropylaniline (0.1 mol) was mixed with l99 g of toluene, 0.g3 g of montmorillonite KSF (fluka) and 34.3 g ; of isobutene, and the mixture was heated in an oil bath for 16 hours at 200C. The cooled autoclave was expanded. In addition to montmorillonite, isobotene and toluene, the reaction solution also contained 19.0 percent of 2,6-diisopropylaniline and 58.3 percent of 4-t-butyl-2,6-diisopropylaniline.
; Example 7 4-t-Butvl-2-ethYl-6-isoproPYlaniline .
t ~i \

2~81~0 Analogous to Example 3, 129.0 g of 2-ethyl-6-isopropylaniline (0.79 mol) was stirred in the presence of 8.0 g of aluminum chloride (0.06 mol) with 30 bars o~
isobutylene over 6 hours at 200C. After working up and distillation, 139.1 g of 4-t-butyl-2-ethyl-6-isopropylaniline (content: 99.3 percent; ~oiling poin~:
143C/17 mbars) was obtained as a colorless, oily liquid.
This corresponded to a yield of 80 percent, relative to the 2-ethyl-6-isopropylaniline used. Other data for the product are:
H-NMR: (CDCl3, 300 MHz) ~ in ppm:
1.27, t, 3H, J=7.5 Hz;
1.29, d, 6H, J=6.8 Hz;
1.30, s, 9H;
2.54, q, 2H, J=7.5 Hz;
2.93, sept, lH, J=6.8 Hz;
3.57, s, 2H;
6.99, d, lH, J=2.1 Hz;
7.08, d, lH, J=2.1 Hz.
Exam~le_8 4-t-Butyl-2.6-di-sec-butylaniline Analogous to Example 3, 20.6 g of 2,6-di-sec-butylaniline (0.1 mol), 0.59 g of aluminum chloride (0.004 mol) and about 38 g of isobutene were heated over 6 hours 25 to 203C. After working up and distillation, 19.5 g of 4-t-butyl-2,6-di-sec-butylaniline was obtained as a colorless oil (content: 99.6 percent, boiling point: 156C/17 mbars). The yield was 74 percent. Other data for the product are:
30 1H-NMR: (CDCl3, 300 MHz) O~ in ppm:
0.94, m, 6H;
1.28, d, 6H, J=6.8 Hz;
1.29, s, 9H;
1.56, m, 2H;
1.72, m, 2H;
2.66, m, 2H;

, ~58~

3.56, s, 2H;
6.99, s, 2H.
Exam~le 9 4-t-Butyl-2 6-dimethylaniline Analogous to Example 3, 24~.0 g of 2,6-dimethylaniline (2 mol) was stirred in the presence of 24.0 g of aluminum chloride (0.18 mol) for 8 hours at 200C with 60 bars of isobutylene. After working up and distillation, 335.7 g of 4-t-butyl-2,6-dimethylaniline (content: 99.8 percent; boiling point: 129C/19 mbars) was obtained as a colorless, oily liquid. This corresponded to a yield of 95 percent, relative to the 2,6-dimethylaniline used. Other data for the product are:
1H-NMR: (CDCl~, 300 MHz) ~ in ppm:
1.27, s, 9H;
2.18, s, 6H;
3.45, s, 2H;
6.96, s, 2H.
Example 10 4-t-Butyl-2 6-diethylaniline Analogous to example 3, 179.9 g of 2,6-diethylaniline (1.2 mol) was stirred with 12.0 g of aluminum chloride (0.09 mol) for 12 hours at 200C with 30 bars of isobutylene. After working up and distillation, 227.2 g of 4-t-butyl-2,6-diethylaniline (content: 99.7 percent; boiling point: 141C/16 mbars) was obtained as a colorless, oily liquid. This corresponded to a yield of 92 percent, relative to the 2,6-diethylaniline used. Other data for the product are:
30 lH-NMR: (CDC13, 300 MHz) ~ in ppm:
1.26, t, 6H, J=7.5 Hz;
1.29, s, 9H;
2.53, g, 4H, J=7.5 Hz;
3.51, s, 2H;
6.99, s. 2H.

2 0 ~ 0 Example 11 4-t-But~1-2 6-diisopropylaniline Analogous to Example 3, 17.7 g of 2,6-diisopropylaniline (0.95 mol; content: 95.2 percent), 2.0 5 g of toluene, 2.05 g of boron trifluoride-diethyl etherate (0.013 mol) and 16.4 g of isobutene (0.29 mol) were heated for 15 hours at 200C. The evaporation residue of the organic phase (21.3 g) obtained at the conclusion of the working up contained 75.6 percent of 4-t-butyl-2,6-10 diisopropylaniline.
ExamPle 12 2.6-Diisopropyl-4-(1-phenvlisopro~yl)aniline 177.3 g of 2,6-diisopropylaniline (1 mol) was mixed with 13.38 g of AlCl3 (0.1 mol) and heated to 155C.
15 195.8 g of ~-methylstyrene (2.5 mol) was instilled over about 6 hours. The reaction mixture was allowed to cool to room temperature and was mixed with stirring in succession with 300 ml of hexane and 300 ml of sodium hydroxide solution (20 percent). The two-phase mixture was 20 separated, and the organic phase was diluted with 900 ml of hexane and saturated with HCl gas. The precipitate was collected on a frit, washed with hexane, pressed out well and mixed with a two-phase mixture of 400 ml of toluene and 450 ml of sodium hydroxide solution (10 percent). The 25 upper organic phase was separated and evaporated to dryness on a Rotavapol~. Thus, 288.1 g of evaporation residue with 98 . 0 percent of 2, 6-diisopropyl-4- ( 1-phenylisopropyl)aniline was obtained, corresponding to a yield of 96 percent, relative to the 2,6-30 diisopropylaniline used. Other data for the product are:
H-NMR: (CDC13, 300 MHz) ~ in ppm:

6.90, s, 2H;

7.1-7.3, m, 5H;
3.70, s, 2H;
1.12, d, 12H, J=6.9 Hz;
2.91, sept, 2H, J=6.9 Hz;
1.66, s, 6H.

,

Claims (11)

1. A process for the production of a 4-substituted 2,6-dialkylaniline of the formula:

(I) wherein R1 and R2 are the same or different and are straight-chain or branched (C1-C4)-lower alkyl groups, and R3 is a phenylisopropyl group, a 1,1,3,3-tetramethylbutyl group or a tert-butyl group, which process comprises alkylating a 2,6-dialkylaniline of the formula:

(II) wherein R1 and R2 have the above meaning, with .alpha.-methylstyrene in the presence of a catalyst to introduce the phenylisopropyl group, or with diisobutylene in the presence of a catalyst to introduce the 1,1,3,3-tetramethylbutyl group, or with isobutene in the presence of a catalyst to introduce the tert-butyl group.

2. A process according to claim 1, wherein the catalyst is a Friedel-Crafts alkylation catalyst.

3. A process according to claim 1, wherein the catalyst is aluminum chloride, a boron trifluoride-ether complex or montmorillonite.

4. A process according to claim 2, wherein the catalyst is aluminum chloride, a boron trifluoride-ether complex or montmorillonite.

5. A process according to claim 1, 2, 3 or 4, wherein the catalyst is used in an amount of between 0.01 and 0.3 mol, relative to 1 mol of 2,6-dialkylaniline.

6. A process according to claim 1, 2, 3, or 4, wherein the reaction is performed at a temperature of between 100°C and 300°C, and a pressure between standard pressure and 60 bars.

7. A process according to claim 1, 2, 3 or 4, wherein the 2,6-dialkylaniline of formula II is alkylated with .alpha.-methylstyrene.

8. A process according to claim 1, 2, 3 or 4, wherein the 2,6-dialkylaniline of formula II is alkylated with diisobutylene.

9. A process according to claim 1, 2, 3 or 4, wherein the 2,6-dialkylaniline of formula II is alkylated with isobutene.

10. A 2,6-dialkyl-4-(1,1,3,3-tetramethylbutyl)-aniline of the formula:

(III) wherein R1 and R2 are the same or different and are straight-chain or branched (C1-C4)-lower alkyl groups.

11. 2,6-Diisopropyl-4-(1,1,3,3-tetramethylbutyl)-aniline.