JPS61271255A - Production of aniline compound - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for pharmaceuticals, etc., in high yield, by reacting a benzamide compound with an alkali metal hypohalite, etc., in the presence of a phase-transfer catalyst and an alkali. CONSTITUTION:The objective aniline compound of formula II (e.g. 2,6- difluoroaniline) can be produced by reacting a benzamide compound of formula I (X is halogen, trifluoromethyl, nitro or cyano; n is 1-5) with an alkali metal hypohalite (e.g. sodium hypochlorite) or an alkali metal halite in the presence of an alkali (e.g. NaOH, KOH, etc.). In the above process, a phase-transfer catalyst such as benzyltrimethylammonium bromide is used in the reaction. The objective compound can be produced even from a benzamide compound having a phenyl group substituted with an electron-attracting group preventing the influence of the electron-attracting group.

Description

DETAILED DESCRIPTION OF THE INVENTION "Industrial Application Field" The present invention relates to a method for producing anilines useful as intermediates for producing pharmaceuticals, agricultural chemicals, dyes, and the like.

"Prior Art" Conventionally, there has been a reaction in which a benzamide compound is reacted with a hypohalite or halogen salt such as hypochlorite or hypobromite to produce anilines having one less carbon number. Are known. ([New Experimental Chemistry Course 14 Synthesis and Reactions of Organic Compounds■ Shingo Iizumi, (1978), 138
8 pages”, [Chemistry Letters, (1984), 7
(Page 13) "Problems to be Solved by the Invention" In the above reaction, in the case of benzamide compounds in which the phenyl group is substituted with an electron-withdrawing group, anilines can be produced in high yield due to the influence of the electron-withdrawing group. It was difficult to do so. (“Organizational Chemistry 4th Edition,
(19B2), p. 907'') For example, when producing aniline from benzamide, the yield was 90%, whereas when producing P-nitroaniline from P-nitrobenzamide, the yield was 54%. . Therefore, a method for producing corresponding anilines in high yield from benzamide compounds substituted with electron-withdrawing groups has been desired.

"Means for Solving the Problems" In order to solve these problems, the present inventors investigated various methods and found that by using a phase transfer catalyst in the above reaction, the problems of the prior art were solved. We have found that this problem can be solved and have completed the present invention.

That is, the present invention provides a method for forming the general formula (in the formula,
X represents a halogen atom, a trifluoromethyl group, a nitro group or a cyano group, and n represents 1°2.3.4 or 5, provided that when n is 2 or more, each X can be a different group. ) by reacting a benzamide compound represented by the formula with an alkali metal hypohalite or an alkali metal halogenate, a compound represented by the general formula (wherein X and n represent the same meanings as above) is produced. This is a method for producing anilines represented by general formula (I[), characterized in that a phase transfer catalyst is used in the method for producing anilines.

In order to produce the anilines represented by the general formula (I[) according to the method of the present invention, in the presence of an alkali, a benzamide compound represented by the general formula (1) and an equimolar amount or more of hypohalous acid with respect to the benzamide compound represented by the general formula (1) are added. 0.1 mol% of alkali metal salt or alkali metal halide salt to benzamide
It can be produced by carrying out the reaction at -15 to 80°C, preferably 0 to 50°C, in the presence of preferably 1 to 25 mol% of a phase transfer catalyst.

The benzamides used in the present invention are compounds represented by the general formula (1), where X is a halogen atom such as a fluorine atom, a bromine atom, a chlorine atom, or an iodine atom, a trifluoromethyl group, or a nitro group. or a cyano group, and n represents 1.2, 3.4 or 5. However, n
When is 2 or more, each X can be a different group,
Any benzamide compound shown in can be used.

In addition, examples of the alkali metal hypohalite or alkali metal halogen salt used in the present invention include sodium hypochlorite, potassium hypochlorite, sodium hypobromite, potassium hypobromite, and pentachloride. acid sodium,
Potassium chlorite.

Examples include sodium bromite and potassium bromite. Furthermore, according to the following formulas (i) and (ii), for example, an alkali metal hypohalite salt can be used in the reaction system using sodium chloride and sodium chlorite, or sodium hydroxide and chlorine. You can also do it.

(i) MX + MXO□ -) 2MXO (ii
) M OH+ X z −>2 M X
O (in the formula, M represents an alkali metal and X represents a halogen atom) Further, as the phase transfer catalyst used in the present invention, benzyl trialkylammonium salts are used.

Examples include quaternary salts such as benzyltrialkylphosphonium salts, benzyltriphenylphosphonium salts, tetraalkylammonium salts and tetraalkylphosphonium salts, crown ethers, krybutanes, and polyethylene glycols. Specifically, benzyltrimethylammonium bromide, benzyltriethylammonium chloride and bromide, benzyltripropylammonium chloride, benzyltributylammonium chloride, benzyltrihexylammonium chloride, benzyltrioctylammonium chloride, penzyltributylphosphonium bromide, benzyltriphenylphosphonium chloride, tetramethylammonium chloride, tetraethylammonium bromide, tetrapropylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium iodide, tetrahexylammonium bromide 2, tetraoctylammonium chloride, cetyltrimethylammonium chloride, Butyltriethylammonium bromide, lauryltriethylammonium bromide, ethyltributylammonium bromide, isobutyltributylammonium bromide, hexyltributylammonium bromide,
Octyltributylammonium bromide, lauryltributylammonium bromide, methyltrioctylammonium chloride, tetrabutylphosphonium bromide, tributylhexylphosphonium bromide, tributyloctylphosphonium bromide, tetrabutylammonium perchlorate, tetrabutylammonium sulfate,
Examples include benzyl NN-dimethylanisium chloride, N-methylpyridinium bromide, 18-crown-6°crown, dibenzo-18-crown-6, diethylene glycol, and tetraethylene glycol.

The anilines produced by the method of the present invention are compounds represented by the general formula (II), where X is a halogen atom such as a fluorine atom, a bromine atom, a chlorine atom, or an iodine atom, or a trifluoromethyl group. , represents a nitro group or a cyano group, and n represents 1.2.3.4 or 5,
However, when n is 2 or more, X can be a different group.Among the anilines shown in The effect is particularly noticeable in terms of rates. Specifically, 2,
6-dichloroaniline, 3,4-difluoroaniline, 2
．． 4-difluoroaniline, 2-chloro-4-fluoroaniline, 3. 5-'; Fluoroaniline, 3,5-dichloroaniline, 2,4゜6-trifluoroaniline, 2
, 3.4-trifluoroaniline, 3. 5-'; Chloro-4-fluoroaniline, 3.4.5-dichloroaniline, 2-bromo-4-fluoro-5-chloroaniline,
2-chloro-3,5-difluoroaniline, 2.3,4.
5-tetrafluoroaniline, 2,3,4.5-tetrachloroaniline, 2,4-chloro-3,5-dichloroaniline, 2-bromo-3,4,5-trifluoroaniline, 2.4.6- ) IJ dichloro 3-fluoroaniline, 2
, 3.4,5.6-pentafluoroaniline, 2,4.6
-tetrafluoro-3,5-dichloroaniline, 2-bromo-4-chloro-3,5,6-trifluoroaniline, 2
．． 3゜5.6-tetrafluoro-4-chloroaniline, 2
．． 3,4.5-tetrafluoro-6-nitroaniline, 2
-trifluoromethylaniline 94-cyanoaniline and the like.

The alkali used in the present invention is a hydroxide of an alkali metal or an alkaline earth metal, and includes, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, lithium hydroxide, and the like. Further, the amount of the alkali to be used is equal to or more than the amount of the benzamide compound represented by the general formula (I).

Further, in the method of the present invention, the reaction may be carried out using an inert solvent. Examples of the solvent used in this case include n-hexane, pentane, cyclohexane, benzene, toluene, xylene, ethylbenzene, cumene, or butylbenzene. hydrocarbons, halogenated hydrocarbons such as chlorobenzene, chlorotoluene, dichlorobenzene or dichloroethane, and nitrobenzene, acetonitrile.

Examples include benzonitrile and diethyl ether.

"Effects of the Invention" In the method of producing corresponding anilines from benzamide compounds according to the method of the present invention, even in the case of benzamide compounds substituted with electron-withdrawing groups, the desired anilines can be produced without being affected by the electron-withdrawing groups. can now be produced in high yields.

Furthermore, the present invention makes it possible to industrially produce anilines represented by the general formula (II), which are useful as intermediates for the production of benzoylurea-based, maleimide-based pesticides, medicines, or dyes. This is the manufacturing method.

"Example" Next, the present invention will be explained in more detail with reference to Examples.

Example 1 Sodium hydroxide 40 g (1 sol), sodium hypochlorite 39. 5 g (0,53 sol), 4 g (0,0125 sol) of tetrabutylammonium bromide
sol) in 650 g of an aqueous solution containing 0 to 10°C under stirring.
113 g (0.5 sol) of 2,4-difluoro-3,5-dichlorobenzamide was added thereto while maintaining the temperature, the temperature was raised to 80° C. over 1 hour, and the mixture was aged at the same temperature for 1 hour. The reaction product was extracted with toluene, concentrated, and then distilled to obtain 94.0 g of 2,4-difluoro-3.5-dichloroaniline with a boiling point of 118-123° C./20%. The yield was 95%. (Based on 2,4-difluoro-3,5-dichlorobenzamide) Examples 2 to 4 The same procedure as in Example 1 was carried out except that the amount of tetrabutylammonium bromide (indicated by TBAB in the table) was changed. The results are shown in Table 1.

Table 1 Comparative Example Example 1 without using tetrabutylammonium bromide
I did the same thing. As a result, 2,4-dichloro-3,5-
62.4 g of dichloroaniline was obtained. Yield is 63
%Met. (Based on 2,4-difluoro-3,5-dichlorobenzamide) Examples 5 to 8 The type of phase transfer catalyst was changed to tetrabutylammonium perchlorate instead of tetrabutylammonium bromide (indicated as BuJCLO in the table). , tetrabutylammonium sulfate (indicated as Bu-NHSOe in the table), trimethylbenzylammonium chloride IJ F (indicated as PhC in the table)
Hx (CHi) (denoted as JCI) or tetramethylammonium chloride (denoted as M6JC1 in the table)
The same procedure as in Example 1 was carried out except that each of these was used. The results are shown in Table 2.

Table 2 Examples 9 to 17 The benzamide compound of Example 1 was carried out in the same manner as in Example 1, except that the primary hypohalite alkali metal salt (abbreviated as metal salt in the table) and phase transfer catalyst were changed. . The results are shown in Table 3.

Claims (1)

[Claims] In the presence of an alkali, the general formula ▲ includes mathematical formulas, chemical formulas, tables, etc. ▼…………(I) (wherein, (where n represents 1, 2, 3, 4, or 5; however, when n is 2 or more, each X can be a different group.) and an alkali metal hypohalite salt or By reacting with an alkali metal halide salt, the general formula ▲ Numerical formula, chemical formula, table, etc. ▼…………(II) (In the formula, X and n represent the same meanings as above.) A method for producing anilines represented by general formula (II), which comprises using a phase transfer catalyst.