JP2513483B2 - Method for producing cyanobenzoyl chlorides - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing cyanobenzoyl chlorides useful as a raw material for medicines or a polymer material. More specifically, it relates to a method for producing cyanobenzoyl chlorides which are useful as an intermediate for the production of tranexamic acid, which is useful as a medicine, especially as an antiplasmin agent.

(Prior Art) Conventionally, cyanobenzoyl chloride, for example, produced phthalic acid monoamide or a metal salt thereof from phthalic acid,
Furthermore, a method for producing by reacting with phosphorus oxychloride is known. (See JP-A-52-39649) (Problems to be solved by the invention) However, this method is difficult to amidate only one carboxyl group from phthalic acid,
There are various problems as an industrial method for producing cyanobenzoyl chloride, such as high-purity phthalic acid monoamide being difficult to obtain, and phosphorus oxychloride being difficult to handle must be used.

(Means for Solving the Invention) In view of such problems, the present inventors have conducted earnest studies to obtain a method for industrially producing cyanobenzoyl chloride with high purity and high yield. As a result, it was found that by selectively using trichloromethylbenzamide as a raw material and heating it in the presence of an acid catalyst, hydrolysis of the trichloromethyl group and dehydration reaction of the amide group occur at the same time to produce cyanobenzoyl chloride. The present invention has been completed based on this knowledge.

That is, the present invention has a general formula The general formula characterized by heating trichloromethylbenzamide represented by Is a method for producing cyanobenzoyl chloride.

In the present invention, examples of trichloromethylbenzamides used as a raw material include 2-trichloromethylbenzamide, 3-trichloromethylbenzamide, and 4-trichloromethylbenzamide. Further, these trichloromethylbenzamides can be obtained by reacting trichloromethylbenzoyl chloride with ammonia according to a conventional method.

Examples of cyanobenzoyl chlorides obtained from these trichloromethylbenzamides as starting materials include 2-cyanobenzoyl chloride, 3-cyanobenzoyl chloride, and 4-cyanobenzoyl chloride.

Examples of the acid catalyst used in the present invention include sulfuric acid,
Mineral acids such as trifluoromethanesulfonic acid, organic acids, and Lewis acids such as ferrous chloride, ferric chloride, stannous chloride, stannic chloride, zinc chloride, and aluminum chloride can be used. The amount of the acid catalyst used is the same as in the general formula (I).
0 for the trichloromethylbenzamides represented by.
It is used in a proportion of 1 to 5.0% by weight, preferably 0.5 to 3.0% by weight. In addition, this reaction is usually carried out in a solvent for the purpose of smoothing the reaction, but it may be carried out without solvent. When carrying out the reaction in a solvent, the solvent used is
Specific examples include benzene, toluene, chlorobenzene, chlorotoluene, xylene and other non-reactive inert solvents. The reaction temperature is usually selected in the range of 80 to 200 ° C, preferably 120 to 180 ° C. The desired cyanobenzoyl chloride can be obtained by distilling the obtained reaction mixture according to a conventional method.

(Effect of the invention) The production method of the present invention uses trichloromethylbenzamide as a raw material, and by heating and reacting in the presence of an acid catalyst, hydrolysis and dehydration reactions occur simultaneously in the molecule, and hydrogen chloride gas is generated. This is an industrially excellent production method in which the desired cyanobenzoyl chloride can be obtained in high yield.

The obtained cyanobenzoyl chlorides can be easily hydrolyzed by a conventional method to easily produce cyanobenzoic acid, which can be further converted to tranexamic acid.

(Examples) Hereinafter, the present invention will be described in more detail with reference to Examples.

Reference Example 1 [Production of 4-trichloromethylbenzamide] 25.8 g of 4-trichloromethylbenzoyl chloride was added to a four-necked flask equipped with a stirrer, a thermometer and a reflux condenser.
(0.1 mol) and orthochlorotoluene 50g as solvent
Was charged, and 13 g (0.21 mol) of ammonia water was added at 10 ° C with stirring.
Was added dropwise over 30 minutes, and the reaction was stirred for 1 hour.
After the reaction was completed, the produced crystals were separated by filtration and dried to obtain 23.1 g of 4-trichloromethylbenzamide. The yield was 96.9%.

Example 1 [Production of 4-cyanobenzoyl chloride] 4-trichloromethylbenzamide (16.7 g, 0.07) was added to a four-necked flask equipped with a stirrer, a thermometer and a reflux condenser.
Mol), 0.11 g of ferric chloride and 50 g of orthochlorotoluene as a solvent, and reacted at 160 ° C. for 4 hours. After the reaction is completed, it is distilled under reduced pressure to give a boiling point of 150-151 ℃ / 25mmH.
8.2 g of 4-cyanobenzoyl chloride was obtained. Yield 70.
The purity was 7% and the purity was 99.1%.

Examples 2 to 5 The reaction was performed in the same manner as in Example 1 except that the acid catalyst and the solvent were changed. The results are shown in Table 1.

Example 6 The same reaction as in Example 1 was carried out except that 3-trichloromethylbenzamide was used in place of 4-trichloromethylbenzamide in Example 1 to obtain 8.12 g of 3-cyanobenzoyl chloride. The yield was 70.1%.

Example 7 The reaction was performed in the same manner as in Example 1 except that 2-trichloromethylbenzamide was used instead of 4-trichloromethylbenzamide of Example 1 to obtain 8.09 g of 2-cyanobenzoyl chloride. The yield was 69.8%.

Claims (1)

(57) [Claims] 1. A general formula The general formula characterized by heating trichloromethylbenzamide represented by A method for producing cyanobenzoyl chlorides represented by: