JPH06271513A - Production of n-tertiary alkyl-substituted aniline analogue - Google Patents

Abstract

PURPOSE:To obtain an N-tertiary alkyl-substituted aniline analogue useful for agrichemicals and medical cares under a relatively low pressure in good yield by reacting an analogue with a tertiary alkyl halide in the presence of an iodide. CONSTITUTION:An aniline analogue of formula I (Y is H, halogen, benzyl, phenoxy, phenylthio) (e.g. 4-chloroaniline) is reacted with a tertiary alkyl halide (e.g. 2-chloro-2-methylpropane) in the presence of an iodide (e.g. sodium iodide) to produce an N-tertiary alkyl-substituted aniline analogue of formula II (e.g. N-t-butyl-4-chloroaniline). The alkylating agent and the iodide are preferably used in molar ratios of 0.9-2.2 and 0.4-2.2, respectively, based on the aniline analogue of formula I. The pressure and the temperature in the reaction are preferably 1-10kg/cm<2>G and 100-140 deg.C, respectively.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention is useful for agricultural chemicals and N.
-A novel method for producing a tertiary alkyl-substituted aniline analog.

[0002]

2. Description of the Related Art N-tertiary alkyl-substituted aniline analogs are disclosed in US Pat.
It is known to have excellent herbicidal activity as described in 2-126155. Also, conventionally, N-third
Secondary alkyl substituted aniline analogs are described in US Pat.
Aniline analogues as described in No. 287
Although it was synthesized by reacting a secondary alkanol (for example, t-butanol), in the presence of an acid such as hydrochloric acid,
Since the reaction is carried out at a temperature close to 0 ° C., a large amount of dehydrated olefin (eg, isobutylene) is generated and a high pressure reaction occurs (10 to 30 kg / cm 2). Further, since water is generated by the reaction and the acid strength is lowered, the reaction is stopped in the middle of the reaction and the yield of the target product is low. Also, US Pat.
No. 2,287, J. Chem. Soc. 1933,
Hickinbottom's method described in 946,
That is, aniline is reacted with t-butyl iodide to give N-
A method for producing t-butylamine has been introduced. However, the tertiary alkyl iodide used is a chemically unstable compound and is relatively expensive.

[0003]

The present invention is based on the conventional N-
The present invention was made in order to solve the above-mentioned problems in the production of a tertiary alkyl-substituted aniline analog, which is lower in pressure than a conventional system for tertiary alkylation with a tertiary alkanol, and It is to provide a method for producing the compound with high yield.

[0004]

DISCLOSURE OF THE INVENTION As a result of intensive studies made by the present inventors in view of the above-mentioned objects, the present inventors have succeeded in developing N at a low pressure and a high yield as compared with the conventional method of alkylating with a tertiary alkanol.
-The present invention has been completed by finding a method for producing a tertiary alkyl-substituted aniline analog. The present invention has the general formula (I):

[0005]

[Chemical 3]

(Wherein Y represents a hydrogen atom, a halogen atom, a benzyl group, a phenoxy group or a phenylthio group) and an aniline analog represented by the general formula (II) RX ... (II) R represents a tertiary alkyl group, and X represents a fluorine atom, a chlorine atom, or a bromine atom.), And a halogenated tertiary alkyl represented by the formula (3) is reacted in the presence of iodide. General formula (III):

[0007]

[Chemical 4]

(Wherein Y and R have the same meanings as described above), and a method for producing an N-tertiary alkyl-substituted aniline analog. In the definition of Y of the compound of the general formula (I) or the general formula (III) of the present invention, examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. The tertiary alkyl group in R of the compound of the general formula (II) or the general formula (III) is
It is a tertiary alkyl group having 4 to 9 carbon atoms, and specific examples thereof include t-butyl group, 1,1-dimethylbutyl group, and 1,1-dimethylhexyl group.

Specific examples of the compound represented by formula (I) include:
Aniline, 2-fluoroaniline, 3-fluoroaniline,
4-fluoroaniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 2-bromoaniline,
3-bromoaniline, 4-bromoaniline, 2-iodoaniline, 3-iodoaniline, 4-iodoaniline,
Examples thereof include 3-benzylaniline, 4-benzylaniline, 2-phenoxyaniline, 3-phenoxyaniline, 4-phenoxyaniline, 2-phenylthioaniline, 3-phenylthioaniline and 4-phenylthioaniline.

Specific examples of the compound represented by the general formula (II) include:
2-chloro-2-methylpropane, 2-bromo-2-methylpropane, 2-chloro-2-methylpentane, 2-
Bromo-2-methylpentane, 2-chloro-2-methylheptane, 2-bromo-2-methylheptane and the like can be mentioned.

Specific examples of the compound represented by the general formula (III) include Nt-butyl-aniline and Nt-butyl-2-.
Chloroaniline, Nt-butyl-3-chloroaniline, Nt-butyl-4-chloroaniline, Nt-butyl-4-bromoaniline, Nt-butyl-4-iodoaniline, Nt -Butyl-4-fluoroaniline, N
-T-butyl-4-benzylaniline, Nt-butyl-2-phenoxyaniline, Nt-butyl-3-phenoxyaniline, Nt-butyl-4-phenoxyaniline, Nt-butyl-2 -Phenylthioaniline, N
-T-butyl-3-phenylthioaniline, Nt-butyl-4-phenylthioaniline, N- (1,1-dimethylbutyl) -aniline, N- (1,1-dimethylbutyl) -2-chloro Aniline, N- (1,1-dimethylbutyl) -3-chloroaniline, N- (1,1-dimethylbutyl) -4-chloroaniline, N- (1,1-dimethylbutyl) -4-bromoaniline, N- (1,1-dimethylbutyl) -4-iodoaniline, N- (1,1-dimethylbutyl) -4-fluoroaniline, N- (1,1-
Dimethylbutyl) -4-benzylaniline, N- (1,
1-dimethylbutyl) -2-phenoxyaniline, N-
(1,1-Dimethylbutyl) -3-phenoxyaniline, N- (1,1-dimethylbutyl) -4-phenoxyaniline, N- (1,1-dimethylbutyl) -2-phenylthioaniline, N- ( 1,1-dimethylbutyl)-
3-phenylthioaniline, N- (1,1-dimethylbutyl) -4-phenylthioaniline, N- (1,1-dimethylhexyl) -aniline, N- (1,1-dimethylhexyl) -2-chloro Aniline, N- (1,1-dimethylhexyl) -3-chloroaniline, N- (1,1-
Dimethylhexyl) -4-chloroaniline, N- (1,
1-dimethylhexyl) -4-bromoaniline, N-
(1,1-dimethylhexyl) -4-iodoaniline,
N- (1,1-dimethylhexyl) -4-fluoroaniline, N- (1,1-dimethylhexyl) -4-benzylaniline, N- (1,1-dimethylhexyl) -2-phenoxyaniline, N- (1,1-dimethylhexyl)
-3-phenoxyaniline, N- (1,1-dimethylhexyl) -4-phenoxyaniline, N- (1,1-dimethylhexyl) -2-phenylthioaniline, N-
Examples thereof include (1,1-dimethylhexyl) -3-phenylthioaniline and N- (1,1-dimethylhexyl) -4-phenylthioaniline.

Examples of iodides include sodium iodide, potassium iodide, ammonium iodide, tetraethylammonium iodide, and the like, with sodium iodide being preferred. In the present invention, a solvent can be used if necessary. Solvents include benzene, toluene, xylene, ethylbenzene, cumene, cymen,
Examples thereof include aromatic hydrocarbons such as naphthalene, aromatic ethers such as anisole and diphenyl ether, and halogenated aromatic hydrocarbons such as chlorobenzene, dichlorobenzene and bromobenzene. Among them, toluene is preferable.

The amount of the compound of the general formula (II) is usually 0.5 to 3. in a molar ratio with respect to the aniline analog of the general formula (I).
The range is 0, and particularly, the range of 0.9 to 2.2 is preferable. The amount of iodide is usually in the range of 0.1 to 3.0 with respect to the aniline analog of the general formula (I), and particularly preferably in the range of 0.4 to 2.2. Although the amount of the solvent can be set arbitrarily, it is preferably in the range of 2 to 20 times the weight of the aniline analog of the general formula (I). The reaction method may be ordinary batch charging, and the reaction can be carried out under either normal pressure or increased pressure, but it is preferable to carry out the reaction at a pressure of 1 kg / cm ² G to 10 kg / cm ² G. The reaction temperature may be usually 60 ° C to 180 ° C, but especially 100 ° C to 1 ° C.
40 ° C. is preferred. After completion of the reaction, the desired product (III) can be obtained by treatment according to a conventional method such as extraction, distillation and chromatography.

[0014]

EXAMPLES The present invention will be described in more detail with reference to examples, but the present invention is not limited to the examples. Example 1 Nt-butyl-4-chloroaniline

[0015]

[Chemical 5]

2.56 g (20 mmol) of 4-chloroaniline, 6.00 g (40 mmol) of sodium iodide, 3.72 g (40 mmol) of 2-chloro-2-methylpropane and 20 ml of toluene were put together in a 50 ml autoclave made of SUS316. The mixture was charged and reacted in an oil bath at 120 ° C. at a reaction pressure of 3 kg / cm ² G for 4 hours. After completion of the reaction, 1N aqueous sodium hydroxide solution was added to adjust the pH of the aqueous layer to 10 or more and then extracted. The toluene layer is concentrated and then separated by silica gel column chromatography (developing solvent: hexane / ethyl acetate = 6/1, Nt-butyl-4-chloroaniline: Rf = 0.4, silica gel: Merck Kieselgel 60). By 1.47
g of Nt-butyl-4-chloroaniline was obtained as a brown oil (40% yield). N-t-butyl-4-chloroaniline: 1H-NMR (CDCl ₃ ): δ1.34 (9H,
s), 6.66 (2H, d, J = 9Hz), 7.10
(2H, d, J = 9 Hz) 2.6 to 3.2 (1H, b
r)

(Examples 2 to 6) Instead of 4-chloroaniline in Example 1, aniline (Example 2), 4-iodoaniline (Example 3), 4-benzylaniline (Example 4), The same reaction was performed using 4-phenoxyaniline (Example 5) and 4-phenylthioaniline (Example 6). As a result, Nt-butylaniline, Nt-butyl-4-iodoaniline, Nt-butyl-4-benzylaniline, Nt-butyl-4-phenoxyaniline, N- which are the desired products were obtained. The yields of t-butyl-4-phenylthioaniline were 33%, 38%, 47% and 7%, respectively.
It was 2% and 78%.

Nt-butylaniline: oily substance 1H-NMR (CDCl ₃ ): δ 1.38 (9H,
s), 2.8 to 3.2 (1H, br), 6.6 to 6.8.
(3H, m), 7.10 (2H, d, J = 7Hz) Nt-butyl-4-iodoaniline: oil 1H-NMR (CDCl ₃ ): δ 1.37 (9H,
s), 6.73 (2H, d, J = 9 Hz), 7.11
(2H, d, J = 9 Hz) 2.6 to 3.0 (1H, b
r) N-t-butyl-4-benzyl aniline: oil _{1H-NMR (CDCl 3):} δ1.32 (9H,
s), 3.88 (2H, s), 6.69 (2H, d, J)
= 8 Hz), 6.99 (2H, d, J = 8 Hz), 7.
23 (5H, m) N- t- butyl-4-phenoxyaniline: oil _{1H-NMR (CDCl 3):} δ1.32 (9H,
s), 6.7 to 7.4 (9H, m), 2.8 (1H, b)
r) N-t-butyl-4-phenylthio aniline: oil _{1H-NMR (CDCl 3):} δ1.38 (9H,
s), 3.46 (1H, br, s), 6.68 (2H,
d, J = 8 Hz), 7.14 (5H, m), 7.28
(2H, d, J = 8Hz)

(Example 7) A reaction was carried out in the same manner as in Example 5, except that 2-chloro-2-methylpentane was used instead of 2-chloro-2-methylpropane. As a result, the desired product, N- (1,1-dimethylbutyl) -4-phenoxyaniline, was obtained in a yield of 38%. N-(1,1-dimethylbutyl) -4-phenoxyaniline: oil _{1H-NMR (CDCl 3):} δ1.42 (6H,
s), 1.48 (2H, t, J = 7Hz), 1.10
(2H, m), 0.89 (3H, t, J = 7Hz),
6.7-7.4 (9H, m), 2.7 (1H, br)

(Comparative Example 1) 50 ml of SUS316
3.28 g of 4-chloroaniline hydrochloride in Toclave
(20 mmol), 14.8 g of t-butanol (200
mmol), and the reaction pressure was 27 at 140 ° C. under an oil bath.
The reaction was performed at kg / cm ² G for 8 hours. After completion of the reaction, 100 ml of ethyl acetate and 100 ml of 1N aqueous sodium hydroxide solution.
And the ethyl acetate layer is concentrated and then separated by silica gel column chromatography (developing solvent: hexane /
Ethyl acetate = 4/1, Nt-butylamino-4-chloroaniline: Rf = 0.4, Silica gel: Merck,
Kieselgel 60) gave 0.55 g of Nt-butyl-4-chloroaniline as a brown oil (yield 15%).

(Comparative Examples 2 to 6) In Comparative Example 1,
Instead of chloroaniline hydrochloride, aniline hydrochloride (Comparative Example 2), 4-iodoaniline hydrochloride (Comparative Example 3), 4-
The same reaction was carried out using benzylaniline hydrochloride (Comparative Example 4), 4-phenoxyaniline hydrochloride (Comparative Example 5), and 4-phenylthioaniline hydrochloride (Comparative Example 6). As a result, Nt-butylaniline and Nt
-Butyl-4-iodoaniline, Nt-butyl-4-
The yields of benzylaniline, Nt-butyl-4-phenoxyaniline and Nt-butyl-4-phenylthioaniline were 18%, 20%, 20%, 45% and 49%, respectively.
%Met.

(Comparative Example 7) In Comparative Example 5, the same reaction was carried out using 2-methyl-2-pentanol instead of t-butanol. As a result, the target product, N-
(1,1-Dimethylbutyl) -4-phenoxyaniline was obtained with a yield of 16%.

(Comparative Examples 8 to 10) In Example 6, sodium iodide was not used, and the reaction temperature was 12 respectively.
0 ° C (Comparative Example 8), 140 ° C (Comparative Example 9), 160 ° C
The same reaction was carried out except that (Comparative Example 10) was used. As a result, the yields of Nt-butyl-4-phenylthioaniline, which was the target substance, were 4%, 17%, and 35%, respectively.

Continuation of the front page (51) Int.Cl. ⁵ Identification number Office reference number FI technical display area C07C 323/33 7419-4H

Claims (1)

[Claims] 1. A compound represented by the general formula (I): (In the formula, Y represents a hydrogen atom, a halogen atom, a benzyl group, a phenoxy group, or a phenylthio group.) And an aniline analog represented by the general formula (II) RX ... (II) (wherein R represents Represents a tertiary alkyl group, and X represents a fluorine atom, a chlorine atom, or a bromine atom), and a halogenated tertiary alkyl represented by the formula (I) is reacted in the presence of an iodide. III): (In the formula, Y and R have the same meanings as described above.) A method for producing an N-tertiary alkyl-substituted aniline analog.