JPH04145060A - Improved process for producing benzene sulfonamide compound - Google Patents

Abstract

PURPOSE:To smoothly and readily produce the subject compound in a high yield without being troubled by the hydrochloride of a base used in the reaction, by reacting a benzene sulfonyl chloride compound with an aniline compound in the presence of a basic compound such as beta-picoline. CONSTITUTION:A benzene sulfonyl chloride compound of formula I (R<1>, R<3> are H, Cl or CH3; R<2> is H, Cl or CF3) is subjected to condensation reaction with an aniline compound of formula II (R<4> is nitro, CF3) in the presence of a basic compound such as beta-picoline or gamma-picoline in an amount of 0.01-1.0 mole based on the aniline compound of formula II, if necessary, in a solvent in a stream of inert gas such as N2 gas at 130-200 deg.C, preferably 140-180 deg.C, preferably for 3-15hr, while the produced hydrogen chloride is immediately removed, away outside the system, thereby industrially profitably and smoothly providing the objective compound of formula III useful as an antimicrobial agent in the field of agricultural chemicals without causing troubles such as pipeline clogging due to the adhesion of hydrochlorides to a condenser, etc.

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention relates to the formula (III) or a trifluoromethyl group, and R4 is a nitro group or a trifluoromethyl group.

The benzenesulfonamide compound of formula (I[l) is a compound useful as a fungicide in the agrochemical field.

[Prior Art and Problems to be Solved by the Invention] It has been known that sulfonamide compounds have a bactericidal effect.

For example, JP-A-58-219159 describes the following formula [wherein X and Y each represent a hydrogen atom or a methyl group, and Z
represents a methyl group, a halogen atom, or a nitro group, and n is 1
It is an integer of ~3. A 3-nitrohenzenesulfonamide-based compound represented by the following is disclosed as a bactericidal agent.

Also, JP-A-61-200959.61-200960.
61-205247.61-205248.61-23
According to Publication No. 3660.61-271270, etc., the formula (
The sulfonamide compound of I[I] is disclosed in the above-mentioned JP-A-58-
It is said to have a more excellent bactericidal effect than the compound described in No. 219159, and is a compound of high industrial value.

The benzenesulfonamide compound is produced by condensing benzenesulfonyl chlorides and anilines, which are equivalent to those used in boat fishing, in the presence of equimolar or more pyridine. In fact, Japanese Patent Publication No. 58-219
159, 3-nitro-4-methyl-N-(2-
As a method for producing chloro-5-nitrophenyl)henzenesulfonamide, 2-chloro-5-nitrophenyl)
5-nitroaniline and an equimolar amount of 3-nitro-4-methylhenzenesulfonyl chloride are condensed under reflux in the presence of an equimolar amount of pyridine. However, in this method, although a relatively expensive base such as pyridine is used in equimolar amounts relative to the reaction substrate, the yield of the desired product is only about 50% or more.

On the other hand, regarding the method for producing the sulfonamide compound of formula (II), the following formula (TV) is described in JP-A-61-205247:
"[In the formula, R' and R" represent a hydrogen atom or a chlorine atom. ]
] The following formula (V) [in the formula,
p, 21rb and R7 represent a hydrogen atom, a chlorine atom or a methyl group. ] has been disclosed, and according to this method, the corresponding benzenesulfonyl chlorides and anilines are condensed in orthodichlorobenzene in the presence of pyridine at a temperature of around 180°C. However, the yield is only about 40-50%.

Thus, for example, the reasons for the low yield in the production of the sulfonamide compound of formula (I Therefore, the basicity of the amino group has decreased, and the reactivity has therefore decreased significantly.

2) The reactivity of 0-chloro-P-nitroaniline, which has a chlorine atom at the 〇-position, is only further reduced, and the chlorine atom at the 〇-position may cause steric hindrance. be.

3) Due to the decrease in reactivity on the aniline side, the condensation conditions become harsher, making it easier to induce side reactions such as decomposition of raw materials.

4) The presence of water in the reaction system induces a hydrolysis reaction of benzenesulfonyl chlorides.

etc.

As a method to improve the condensation reaction yield of anilines and benzenesulfonyl chlorides, which have decreased reactivity, the present inventors first introduced an inert gas such as nitrogen in the presence of an organic basic catalyst. He proposed a method of carrying out the condensation reaction by blowing into the reaction system (Japanese Patent Application Laid-open No. 57565/1983).
.

By this method, the yield of the compound of formula (I[l) could be dramatically improved. For example, in the condensation of 4-chloro3-trifluoromethylbenzenesulfonyl chloride and 2-chloro-4-nitroaniline, the reaction is carried out in 0-dichlorobenzene in the presence of an organic basic catalyst while blowing nitrogen gas into the system. Therefore, the desired 4-chloro-3
-Trifluoromethyl-(2-chloro-4-nitrophenyl)henzenesulfonamide can be produced with a yield of 80% or more.

By the way, in the improved method, as an organic basic catalyst,
Pyridine was considered the most preferred base. In fact, the patent application in question also contains such a statement. Certainly, pyridine remains a preferred base. However, as a result of further detailed study of this condensation reaction, it was found that the use of pyridine as a base poses a problem in industrializing the method. That is, when pyridine is used as a base, crystals of pyridine hydrochloride are formed as the reaction progresses and adhere to the upper part of the reactor and even to a part of the condenser, and the amount gradually increases as the reaction progresses. .

This hydrochloride is not easily dissolved in refluxing solvents, and therefore, if the scale becomes large, it may sometimes cause problems such as condenser clogging, which is one of the problems in industrialization. become. Furthermore, the absolute amount of pyridine as a catalyst in the reaction system decreases, resulting in a decrease in the reaction rate.

Considering the mechanism by which pyridine hydrochloride adheres to condensers, etc., one is that pyridine hydrochloride generated in the reaction system is sublimated and dispersed into the gas phase by the flow of inert gas such as nitrogen. Because the reaction temperature is usually higher than the boiling point of pyridine, the concentration of pyridine in the gas phase is relatively high, and the hydrochloric acid gas and pyridine that have risen from the system It is thought that the lysine hydrochloride reacts with the lysine hydrochloride in the gas phase and becomes fixed.

[Means to solve the problem]

In view of the problems in reaction operation in the condensation reaction under a pyridine catalyst as described above, the present inventors have devised a method that does not reduce the yield of the condensation reaction and does not cause troubles due to the fixation of hydrochloride. We conducted extensive research on basic catalysts.

As a result, it was found that when β-picoline or T-picoline was used as a base, no hydrochloride was observed to adhere to a portion of the capacitor during the condensation reaction, and the reaction itself proceeded more smoothly.

Furthermore, among the picolines, when α-picoline was used as a base, the caking phenomenon of hydrochloride was observed as in the case of pyridine. Such findings were completely unknown in the past, and the present invention was completed by further developing these findings.

That is, the present invention provides compounds of formula (I) [wherein R' and R3 represent a hydrogen atom, a chlorine atom, or a methyl group, and R2 represents a hydrogen atom, a chlorine atom, or a trifluoromethyl group]. benzenesulfonyl chlorides represented by the formula (It) I [wherein R4 represents a nitro group, a cyano group or a trifluoromethyl group]; [In the formula, R1, R2, R3 and R4 are each represented by the formula (I)
and (same as that of (If))], wherein the benzenesulfonamide compound of formula (I) is characterized in that β-picoline or γ-picoline is used as the basic substance. An improved method for producing compounds.

The method of the present invention will be explained in detail below.

Benzenesulfonyl chlorides of formula (I) and formula (I[)
In the condensation reaction with anilines, the proportion of these compounds used is 0.5 to 2 mol, preferably 17 to 1.3 mol, of the compound of formula (II) per 1 mol of the compound of formula (I). If the usage ratio is outside this range, not only will by-products be likely to increase, but it will also be industrially disadvantageous in terms of raw material consumption.

In the method of the present invention, the condensation reaction of the formula (+) compound and the formula (■) compound is usually carried out in a 111f@ medium.

The organic solvent used is not particularly limited as long as it is inert to the reaction, but in order to simplify the method of isolating the desired product after the reaction, toluene, xylene, monochlorobenzene, or O2 is usually used. - Aromatic hydrocarbon or halogenated hydrocarbon solvents such as dichlorobenzene are used. Of course, the condensation reaction proceeds without using any solvent at all, but in this case, depending on the substrate for the reaction, the substrate concentration becomes extremely high, making it easy to induce side reactions such as decomposition.
This may lead to a decrease in yield and quality, and due to problems in handling the condensation mass, it is preferable to use the above-mentioned organic solvents from an industrial perspective. The amount of solvent used is calculated using the formula (
I) The amount is preferably 0.4 parts by weight or more based on the amount of compound 11i. There is no particular restriction on the upper limit of the amount used, but it must be said that using too much will not only lower the substrate concentration and reduce the reaction rate, but will also be industrially disadvantageous in terms of volumetric efficiency. I don't get it. Therefore, usually formula (I)
It is used in an amount of 5 parts by weight or less, more preferably 2 parts by weight or less, per 1 part by weight of the compound.

In the present invention, the condensation reaction is carried out in the presence of a basic catalyst, and the basic catalyst may be β-picoline or T
- It is characterized by the use of picoline,
This prevents troubles caused by fixation of the hydrochloride of the basic substance during the reaction, and also promotes the smooth progress of the reaction, leading to improved yield and quality.

β-picoline or γ-picoline used in the present invention is usually used alone, but it is also possible to use both in combination. If the amount of β-picoline or T-picoline used is too small, its effect as a base will be small and the smooth progress of the reaction will be inhibited, and if it is used in excess, it is practically meaningless. )0 for the compound
．． It is used in a molar ratio of 0.01 to 1.0, preferably 0.1 to 0.5.

In the condensation reaction of the present invention, reaction substrates of formulas (I) and (II)
A compound, a base catalyst, and a solvent if necessary are charged into a reaction vessel, and heated to 130 to 200°C, preferably 140 to 180°C.
It is necessary to forcibly remove the hydrogen chloride generated at this time from the reaction system, and for this purpose, in the present invention, an inert gas is added to the reaction system. Do this by blowing into the liquid.

By introducing this inert gas into the reaction system, the hydrogen chloride produced in the reaction can be quickly removed from the system, promoting the smooth progress of the reaction and resulting in the desired sulfonamide in high yield. The hydrogen chloride produced in the reaction that can produce the compound is β-picoline or T-picoline as a base.
It is thought that a salt is formed with picoline, but this salt is easily decomposed under relatively high temperature conditions, and only hydrogen chloride is thought to be accompanied by an inert gas and removed from the reaction system. Examples of the inert gas include common inert gases such as air, nitrogen, carbon dioxide, helium, and argon, but nitrogen gas is usually used frequently. The amount of inert gas blown cannot be determined uniquely depending on the scale of the reaction, etc., but if it is set within a range that can prevent loss due to significant entrainment of β-picoline or γ-picoline as a base, or solvent. good.

After the reaction, the desired sulfonamide compound of formula (I[l)] can be isolated from the reaction mixture using various methods, examples of which are as follows.

If necessary, the reaction solution is charged with an appropriate amount of the same type of solvent and hot water as used in the condensation reaction, and after cooling to room temperature, the precipitated crystals are collected by filtration to obtain the desired benzenesulfonamides. , this is subjected to column chromatography or recrystallization if necessary.

Examples of the compound of formula (Ill) that can be produced by the method of the present invention include the following benzenesulfonamides.

210 rho N-(2-chloro-4-nitrophenyl)benzenesulfonamide, 3-chloro-N-(2-chloro-4-nitrophenyl)benzenesulfonamide, 4-chloro-N-(2-chloro-4-nitrophenyl) phenyl)benzenesulfonamide, 2,5-dichloro-N-(2-chloro-4-nitrophenyl)benzenesulfonamide, 3
．． 4-cycloN-(2-chloro-4-nitrophenyl)benzenesulfonamide, 2,4.5-)cycloN-(2-chloro4-nitrophenyl)benzenesulfonamide, 2chloro-4-methyl-N -(2-chloro-4-nitrophenyl)benzenesulfonamide, 3
-chloro-4-methyl-N(211:l rho-4-nitrophenyl)benzenesulfonamide, 2-methyl-5-
Chloro-N-(2-chloro-4-nitrophenyl)benzenesulfonamide, 4-methylN-(2-chloro-4
-nitrophenyl)benzenesulfonamide, 2,4-
Dimethyl-N-(2-chloro-4-nitrophenyl)benzenesulfonamide, 3-trifluoromethyl-N
-(2-chloro-4-nitrophenyl)benzenesulfonamide, 3-trifluoromethyl-4-chloro-N-
(2-chloro-4-nitrophenyl)benzenesulfonamide, 2-chloro-5-trifluoromethyl-N-(
2-chloro-4-nitrophenyl)benzenesulfonamide, 2,4-dichloro-5-trifluoromethyl N-
(2-chloro-4-nitrophenyl)benzenesulfonamide, 2-chloro-N-(2-chloro-4-trifluoromethylphenyl)benzenesulfonamide, 3chloro-N-(2-chloro-4-trifluoro methylphenyl)benzenesulfonamide, 4-chloro-N-(2chloro-4-trifluoromethylphenyl)benzenesulfonamide, 2,5-dichloro-N-(2-chloro-4
trifluoromethylphenyl)benzenesulfonamide, 3,4-dichloro-N-(2-chloro-4-trifluoromethylphenyl)benzenesulfonamide, 3-chloro-4-methyl-N-(2-chloro-4 -trifluoromethylphenyl)benzenesulfonamide, 2-methyl-5-chloro-N-(2-chloro-4-trifluoromethylphenyl)benzenesulfonamide, 3-trifluoromethyl-N-(2-chloro-4 -trifluoromethylphenyl)benzenesulfonamide, 3-trifluoromethyl-4-chloro-N-(2-chloro-4-trifluoromethylphenyl)benzenesulfonamide, 2
-Chloro-5-trifluoromethyl-N-(2-chloro-4-trifluoromethylphenyl)benzenesulfonamide, 2,4-dichloro-5-trifluoromethyl-N
(2-chloro-4-trifluoromethylphenyl)benzenesulfonamide and the like.

Furthermore, the benzenesulfonyl chlorides of the compounds used in the present invention, such as 3-trifluoromethyl-4-chlorobenzenesulfonyl chloride, can be obtained by reacting O-chlorobenzene trifluoride with chlorosulfonic acid as follows. The 2-chloroaniline compound of formula (■) is a compound known as a dye intermediate and can be easily produced manually.

〔Effect of the invention〕

According to the method of the present invention, there is no possibility that the hydrochloride of the base used during the condensation reaction will stick to the condenser etc. and cause problems such as clogging the line, and the reaction proceeds smoothly, resulting in high yield. Since it is possible to produce sulfonamide compounds, it is an extremely valuable production method from an industrial perspective.

〔Example〕

Hereinafter, the present invention will be explained in detail with reference to Examples.

Example 1 69.8 g of 4-chloro-3-trifluoromethylhenzensulfonyl chloride in a 5001d four-way flask
(0.25 mol), 2-chloro-4-nitroaniline 4
3.6 g (0,253 mol), β-picoline 4.6
5 g (0.05 mol) and 25 g of xylene were charged, heated to 160°C on an oil bath, and reacted at the same temperature for 10 hours. During this time, nitrogen gas was flowed into the reaction solution at a flow rate of 15I11/min. During the reaction, no solidification of β-picoline hydrochloride was observed in the upper part of the reaction flask or in a part of the condenser, and the reaction proceeded smoothly.

After the reaction, 25 g of xylene was charged into the reaction solution, and 100 g of xylene was added to the reaction solution.
After cooling to ℃, 100 g of warm water was added and crystallization was carried out while stirring and gradually cooling. After cooling to room temperature, the precipitated crystals were suction filtered, washed with water, washed with 50M1 methanol, and dried to give pale yellow 4-chloro-3-trifluoromethyl-N-(2chloro-4- 93.1 g of (nitrophenyl)benzenesulfonamide was obtained.

Yield: 88.7% (vs. 4-chloro-3-trifluoromethylhenzenesulfonyl chloride) The purity of this product was 99.2% as a result of analysis by high performance liquid chromatography.

Example 2 and Comparative Example 1.2 The same procedure as in Example 1 was carried out except that 7-picoline, pyridine or α-picoline was used instead of β-picoline. The results are shown in Table-1.

(Left blank space below) Table 1 Examples 3 to 6 Table 2 shows the results of condensation reactions performed in the presence of β-picoline or T-picoline with various benzenesulfonyl chloride, substituted anilines, and reaction solvents.

During the reaction, nitrogen gas was blown into the system at a rate of 10 to 20 d/min. Also, the isolation of the sulfonamide compound which was produced after the reaction was carried out according to Example 1.

(Margin below)

Claims (1)

[Claims] 1. Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R^1 and R^3 represent a hydrogen atom, a chlorine atom, or a methyl group, and R^ 2 represents a hydrogen atom, a chlorine atom, or a trifluoromethyl group. ] and the benzenesulfonyl chloride represented by the formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, R^4 represents a nitro group or a trifluoromethyl group.) Formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R^1, R^2, R^3 and A method for producing a benzenesulfonamide compound represented by formula (I) and formula (II), respectively, in which R^4 is the same as that of formula (I) and formula (II), characterized in that β-picoline or γ-picoline is used as the basic substance. An improved method for producing a benzenesulfonamide compound of formula (III). 2. The amount of β-picoline or γ-picoline to be used is
The method according to claim 1, wherein the molar ratio to the anilines in I) ranges from 0.01 to 1.0. 3. The method according to claim 1, wherein the reaction is carried out under an inert gas stream.