JPH01319468A - Production of thiazolecarboxylic acid chlorides - Google Patents

Abstract

PURPOSE:To obtain the present compound of a raw material for medicine and agricultural chemical in short reaction time without treatment of by-product by using a catalyst in reaction of thiazole-carboxylic acids with phosgene or trichlroromethylchloroformate. CONSTITUTION:Thiazolecarboxylic acids (e.g., thiazole-5-carboxylic acid) expressed by formula I (R1 is H, halogen, lower alkyl, lower alkoxy or lower alkyl substituted by halogen or lower alkoxy group; R2 is H, lower alkyl or lower alkyl substituted by halogen or lower alkoxy group) is reacted with phosgene or trichloromethylchloroformate, in the presence of a catalyst, preferably using the latter compound of 1.0-5.0mol based on 1mol compound expressed by formula I in a solvent such as benzene to provide the compound expressed by formula II. As the above-mentioned catalyst, N,N-dimethylformamide, etc., is preferably used at an amount of 0.1-1wt.% based on the compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for producing thiazolecarboxylic acid chlorides useful as raw materials for medicines, agricultural chemicals, etc.

[Conventional technology]

Conventional methods for producing thiazolecarboxylic acid chlorides include a method using thionyl chloride (Journal of Chemical Society (J, C, S), 1
945.601), (Journal of Heterocyclic Chemistry (J, HeLerocyclic
c cell, ), 22.1621 (I985))
or a method using oxalyl chloride (Journal of the Chemical Society (J, C, S,), Perkin 1.159, (I982))
It has been known.

[Problem to be solved by the invention]

In the above method using thionyl chloride, since side reactions occur in the case of 2-alkylthiazole carboxylic acids, it is necessary to maintain the reaction temperature at an extremely low temperature, and the number of solvents is also limited. Moreover, the yield is extremely low even under such reaction conditions.

On the other hand, when raw materials other than 2-alkylthiazole carboxylic acids are used, thionyl chloride reacts extremely violently with the raw material thiazole carboxylic acids, making it difficult to control the reaction B. Additionally, when this occurs, it generates intense heat and generates large amounts of corrosive sulfur dioxide gas. For this reason, there are problems in the industrial production method, such as the need for equipment and complicated labor to process the large amount of sulfur dioxide gas produced as a by-product. Also,
Since oxalyl chloride is expensive, it is uneconomical to use it industrially. Moreover, when a catalyst is not used, the reaction time becomes longer.

The present invention shortens the reaction time by using a catalyst,
The objective is to obtain thiazolecarboxylic acid chlorides with high purity and high yield without processing by-products.

[Means and effects for solving the problem] In order to achieve the above object, the present inventors have conducted intensive studies on the above problem, and as a result, the present inventors have determined that thiazole carboxylic acids are combined with phosgene or trichloromethyl chloroformate in the presence of a catalyst. The present invention was completed by discovering a method for producing the reaction.

That is, -Momona (H (wherein, R1 is hydrogen, a halogen atom, a lower alkyl group,
thiazolecarboxylic acids represented by a lower alkoxy group or a lower alkyl group substituted with a halogen atom or a lower alkoxy group, R2 represents hydrogen, a lower alkyl group, or a lower alkyl group substituted with a halogen atom or a lower alkoxy group; (hereinafter referred to as thiazole carboxylic acids) with phosgene or trichloromethyl chloroforme in the presence of a catalyst, -
Thiazolecarboxylic acid chlorides (hereinafter referred to as thiazolecarboxylic acid chlorides) represented by the linear formula (II) (wherein R+ and Rz are the same as in general formula (I)).

).

This is a method for producing thiazole carboxylic acid chlorides, wherein the catalyst is selected from N-substituted amides, N-substituted formamides, organic bases, or phosphoramides.

Next, the present invention will be explained in detail.

Examples of thiazolecarboxylic acids include thiazole-5-carboxylic acid, 2-methylthiazole-5-carboxylic acid, 2-ethylthiazole-5-carboxylic acid, 2-i
so-propylthiazole-5-carboxylic acid, 2-n-
Propylthiazole-5-carboxylic acid, 2-n-butylthiazole-5-carboxylic acid, 2-1so-butylthiazole-5-carboxylic acid, 2-sec-butylthiazole-5-carboxylic acid, 2-tert-butylthiazole -5-carboxylic acid, 2-n-pentylthiazole-5-
Carboxylic acid, 2-n-hexylthiazole-5-carboxylic acid, 2-fluorothiazole-5-carboxylic acid, 2-
Chlorothiazole-5-carboxylic acid, 2-bromothiazole-5-carboxylic acid, 2-iodothiazole-5-carboxylic acid, 2-methoxythiazole-5-carboxylic acid,
2-Ethoxythiazole-5-carboxylic acid, 2-(n-
propoxy)thiazole-5-carboxylic acid, 2-(i
so-propoxy)thiazole-5-carboxylic acid, 2-
Chloromethylthiazole-5-carboxylic acid, 2-trichloromethylthiazole-5-carboxylic acid, 2-fluoromethylthiazole-5-carboxylic acid, 2-trifluoromethylthiazole-5-carboxylic acid, 2-bromomethylthiazole-5 -carboxylic acid, 2-iodomethylthiazole-5-carboxylic acid, 2-(β,β,β-trifluoroethyl)thiazole-5-carboxylic acid, 2-methoxymethylthiazole-5-carboxylic acid, 2-ethoxymethyl Thiazole-5-carboxylic acid, 4-methylnaazole-5-carboxylic acid, 4-ethylthiazole-5-carboxylic acid, 4-4so-propylthiazole-5-carboxylic acid, 4-〇-propylthiazole-5-carboxylic acid acid, 4
-n-butylthiazole-5-carboxylic acid, 4-iso
-butylthiazole-5-carboxylic acid, 4-sec-butylthiazole-5-carboxylic acid, 4-tart-butylthiazole-5-carboxylic acid, 4-n-pentylthiazole-5-carboxylic acid, to 4-n- xylthiazole-5-carboxylic acid, 4-chloromethylthiazole-5-
Carboxylic acid, 4-trichloromethylthiazole-5-carboxylic acid, 4-fluoromethylthiazole-5-carboxylic acid, 4-trifluoromethylthiazole-5-carboxylic acid, 4-bromomethylthiazole-5-carboxylic acid,
4-iodomethylthiazole-5-carboxylic acid, 4-(
β,β,β-trifluoroethyl)thiazole-5-carboxylic acid, 4-methoxymethylthiazole-5-carboxylic acid, 4-ethoxymethylthiazole-5-carboxylic acid, 2,4-dimethylthiazole-5-carboxylic acid acid, 2
．． 4-diethylthiazole-5-carboxylic acid, 2.4-
Di(topropyl)thiazole-5-carboxylic acid, 2,
4-di(iso-propyl)thiazole-5-carboxylic acid, 2.4-di(n-butyl)thiazole-5-carboxylic acid, 2.4-di(iso-butyl)thiazole-5-carboxylic acid, 2 , 4-di(sec-butyl)thiazole-5-carboxylic acid, 2,4-di(terL-
butyl)thiazole-5-carboxylic acid, 2,4-di(
n-pentyl)cyano'-5-carboxylic acid, 2.4
- di(n-hexyl)thiazole-5-carboxylic acid,
2.4-di(chloromethyl)thiazole-5-carboxylic acid, 2,4-di(fluoromethyl)thiazole-5
-carboxylic acid, 2,4-di(trifluoromethyl)thiazole-5-carboxylic acid, 2,4-di(trichloromethyl)thiazole-5-carboxylic acid, 2,4-di(
bromomethyl)thiazole-5-carboxylic acid, 2.4-
Di(iodomethyl)thiazole-5-carboxylic acid, 2
．． 4-di(β,β,β-trifluoroethyl)thiazole-5-carboxylic acid, 2゜4-di(methoxymethyl)thiazole-5-carboxylic acid, 2,4-di(ethoxymethyl)thiazole-5 -Carboxylic acid, 2-methyl-
4-ethylthiazole-5-carboxylic acid, 2-methyl-
4-iso-propylthiazole-5-carboxylic acid, 2
-Methyl-4-n-propylthiazole-5-carboxylic acid, 2-methyl-4-n-butylthiazole-5-carboxylic acid, 2-methyl-4-1so-butylthiazole-
5-carboxylic acid, 2-methyl-4-sec-butylthiazole-5-carboxylic acid, 2-methyl-4-tart-
Butylthiazole-5-carboxylic acid, 2-methyl-4-
Lopentylthiazole, 5-carboxylic acid, 2-methy/
L/-4-Q-hexylthiazole-5-carvone L
2-Methyl-4-chloromethylthiazole-5-carboxylic acid, 2-methyl-4-fluoromethylthiazole-
5-carboxylic acid, 2-methyl-4-trifluoromethylthiazole-5-carboxylic acid, 2-methyl-4-trichloromethylthiazole-5-carboxylic acid, 2-methyl-
4-bromomethylthiazole-5-carboxylic acid, 2-methyl-4-iodomethylthiazole-5-carboxylic acid,
2-Methyl-4-(β,β,β-trifluoroethyl)
Thiazole-5-carboxylic acid, 2-methyl-4-methoxymethylthiazole-5-carboxylic acid, 2-methyl-4
-ethoxymethylthiazole-5-carboxylic acid, 2-ethyl-4-methylthiazole-5-carboxylic acid, 2-ethyl-4-n-propylthiazole-5-carboxylic acid,
2-ethyl-4-1so-pro and lunaazole-5-carboxylic acid, 2-ethyl-4-dobutylthiazole-5-
Carboxylic acid, 2-ethyl-4-fluoromethylthiazole-5-carboxylic acid, 2-ethyl-4-trifluoromethylthiazole-5-carboxylic acid, 2-ethyl-4-chloromethylthiazole-5-carboxylic acid, 2 -Ethyl-
4-methoxymethylthiazole-5-carboxylic acid, 2-
iso-propyl-4-methylthiazole-5-carboxylic acid, 2-iso-propyl-4-ethylthiazole-
5-carboxylic acid, 2-iso-propyl-4-n-propylthiazole-5-carboxylic acid, 2-1so-propyl-4-n-butylthiazole-5-carboxylic acid, 2-
iso-propyl-4-fluoromethylthiazole-5
-carboxylic acid, 2-iso-propyl-4-trifluoromethylthiazole-5-carboxylic acid, 2-1so-propyl-4-chloromethylthiazole-5-carboxylic acid, 2-iso-propyl-4-medoxymethyl Thiazole-5-carboxylic acid, 2-n-propyl-4-methylazole-5-carboxylic acid, 2-n-propyl-4-ethylthiazole-5-carboxylic acid, 2-n-propyl-
4-iso-propylthiazole-5-carboxylic acid, 2
-n-propyl-4-n-butylthiazole-5-carvone! , 2-n-propyl-4-fluoromethylthiazole-5-carboxylic acid, 2-n-propyl-4-trifluoromethylthiazole-5-carboxylic acid, 2-n-propyl-4-methoxymethylthiazole-5- Carboxylic acid, 2-tert-butyl-4-methylthiazole-5
-carboxylic acid, 2-tert-butyl-4-ethylthiazole-5-carboxylic acid, 2-tert-butyl-4-
n-propylthiazole-5-carboxylic acid, 2-ter
t-Butyl-4-trifluoromethylthiazole-5-
Carboxylic acid, 2-tert-butyl-4-methoxymethylthiazole-5-carboxylic acid, 2-fluoro-4-methylthiazole-5-carboxylic acid, 2-fluoro-4-
Ethylthiazole-5-carboxylic acid, 2-fluoro-4
-n-propylthiazole-5-carboxylic acid, 2-fluoro-4-iso-propylthiazole-5-carboxylic acid, 2,fluoro-4-n-butylthiazole-5-carboxylic acid, 2-fluoro-4-tert -butylthiazole-5-carboxylic acid, 2-fluoro-4-trifluoromethylthiazole-5-carboxylic acid, 2-fluoro-
4-(β,β2β-trifluoroethyl)thiazole-
5-carboxylic acid, 2-chloro-4-methylthiazole-
5-carboxylic acid, 2-chloro-4-ethylthiazole-
5-carboxylic acid, 2-chloro-4-1so-propylthiazole-5=carboxylic acid, 2-chloro-4-topropylthiazole, 5-carboxylic acid, 2-chloro-4-n-
Butylthiazole-5-carboxylic acid, 2-chloro-4-
n-hexylthiazole-5-carboxylic acid, 2-chloro-4-methoxymethylthiazole-5-carboxylic acid, 2
-Chloro-4-chloromethylthiazole-5-carvone M, 2-chloro-4-trifluoromethylthiazole-
5-carboxylic acid, 2-bromo-4-methylthiazole-
5-carboxylic acid, 2-bromo-4-n-propylthiazole-5-carboxylic acid, 2-bromo-4-n-pentylthiazole-5-carboxylic acid, 2-iodo-4-methylthiazole-5-carboxylic acid , 2-iodo-4-ethylthiazole-5-carboxylic acid, 2-methoxy-4-methylthiazole-5-carboxylic acid, 2-methquine-4-ethylthiazole-5-carboxylic acid, 2-methoxy-4-
iso-propylthiazole-5-carboxylic acid, 2-methoxy-4-n-propylthiazole-5-carboxylic acid, 2-methoxy-4-sec-butylthiazole-5-
Carboxylic acid, 2-methoxy-4-trifluoromethylthiazole-5-carboxylic acid, 2-methoxy-4-methoxymethylthiazole-5-carboxylic acid, 2-chloromethyl-4-methylthiazole-5-carboxylic acid, 2 -chloromethyl-4-ethylthiazole-5-carboxylic acid, 2
-Chloromethyl-4-nitylthiazole-5-carboxylic acid, 2-chloromethyl-4-n-butylthiazole-5
-carboxylic acid, 2-chloromethyl-4-chloromethylthiazole-5-carboxylic acid, 2-chloromethyl-4-trichloromethylthiazole-5-carboxylic acid, 2-chloromethyl-4-(β, β, β= trifluoromethyl)
Thiazole-5-carboxylic acid, 2-trifluoromethyl-4-methylthiazole-5-carboxylic acid, 2-trifluoromethyl-4-ethylthiazole-5-carboxylic acid, 2-trifluoromethyl-4-fluoromethylthiazole -5, carboxylic acid, 2-trifluoromethyl-4-
(β.

β,β-trifluoromethyl)thiazole-5-carboxylic acid, 2-trifluoromethyl-4-methoxymethylthiazole-5-carboxylic acid, 2-methoxymethyl-4-
Methylthiazole-5-carboxylic acid, 2-methoxymethyl-4-ethylthiazole-5-carboxylic acid, 2-methoxymethyl-4-1so-propylthiazole-5-carboxylic acid, 2-methoxymethyl-4-tart-butyl Thiazole-5-carboxylic acid, 2-methoxymethyl-4
-trifluoromethylthiazole-5-carboxylic acid, 2
-methoxymethyl-4-methoxymethylthiazole-5
-carboxylic acids, etc., but are not necessarily limited to these.

Since the reaction of the present invention is carried out in a solution or suspension state, it is preferably carried out in a solvent.

Any solvent may be used as long as it is inert to the reaction.

For example, aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, and dioxane; Examples include, but are not limited to, hydrocarbons, and it is also possible to mix these solvents and use them as the reaction solvent.

The catalysts used in the present invention include N,N-dimethylformamide, N-methylformanilide, N-formylpiperidine, N-formylmorpholine, N,N-dibenzylformamide, N-methyl-N-ethylformamide, N-
-Propyl-N-n-butylformamide, N.

N-G-o-)ruylformamide, N,N-G-P-
Formamides such as tolylformamide, N,N-dibenzylformamide, N-formylpiperazine, N-formylpyrrolidine, N-formylimidazolidine, N,N-dimethylacetamide, N,N-di-n-propylacetamide, N , N-di-1so-propylacetamide, N,N-diethylpropionamide, N,N
-Amides such as dimethylbutyramide and N-methylacetanilide, organic bases such as pyridine, picoline, N,N-dimethylaniline, N,N-diethylaniline, triethylenediamine, and triethylamine, and phosphoramides such as hexamethylphosphoramide These include, but are not limited to.

The amount of the catalyst to be used is 0.000% relative to the thiazole carboxylic acids.
05 to IO% by weight, preferably 0.1 to 1% by weight. When the amount of catalyst is small, the reaction progresses slowly, and when it is large, the purity of the produced thiazolecarboxylic acid chloride is reduced.

It is efficient that the amount of the solvent added is 0.5 to 101, preferably 0.8 to 42, per mole of the thiazole carboxylic acid.

The amount of phosgene or trichloromethyl chloroformate added to thiazole carboxylic acids is preferably 0.5 to 10.0 mol, preferably 1.0 to 5.0 mol, per 1 mol of thiazole carboxylic acids.

The reaction temperature can be between room temperature and the boiling point of each solution.

When blowing phosgene into a solution of thiazole carboxylic acids, the reaction time is 1 to 20 hours, preferably 2 to 8 hours under heating and reflux.

Further, when trichloromethyl chloroformate is added dropwise to a solution of thiazole carboxylic acids, the time is 1 to 20 hours, preferably 2 to 8 hours under heating and reflux.

After the reaction is completed, thiazolecarboxylic acid chlorides can be easily obtained by concentrating the filtrate.

If unreacted thiazolecarboxylic acid remains, thiazolecarboxylic acid chloride can be obtained by separating it by filtration and concentrating the filtrate.

The obtained thiazolecarboxylic acid chlorides can be used in pharmaceuticals,
It can be used in the next step as an intermediate for agricultural chemicals without any purification.

The purity analysis of this thiazole carboxylic acid chloride is
By gas chromatography.

The preferred implementation 111m of the present invention is as follows.

A reactor equipped with a thermometer, a stirrer, and an AM device is charged with phosgene or trichloromethyl chloroformate into a solution or suspension containing a predetermined amount of thiazole carboxylic acids, a predetermined catalyst, and a specific solvent. The mixture is added dropwise and the reaction is carried out under reflux at a predetermined temperature for a predetermined time.

After the reaction is completed, the desired thiazolecarboxylic acid chloride can be obtained by filtering the reaction solution and a-condensing the filtrate.

In addition, 41i! The distillate from the reaction system can be recovered as a solvent.

〔Example〕

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

Example 1 15.7 g (0.1 mol) of 2,4-dimethylthiazole-5-carboxylic acid was added to toluene Loom e in a 300 ml Mitsuro flask! After adding 0.1 g of N,N-dimethylformamide, 1.0 g of phosgene was added under heating under reflux.
After the completion of the reaction, the reaction solution was filtered and the solution a was condensed to give 17
．． 2 g of 2°4-dimethylthiazole-5-carboxylic acid chloride was obtained. The purity was 97.5% and the yield was 98.0%.

Example 2 In the same apparatus as in Example 1, 10.7 g (0.06 mol) of 2-chloro-4-methylthiazole-5-carboxylic acid was suspended in 200 ml of butyl acetate, and 0.7 g (0.06 mol) of 2-chloro-4-methylthiazole-5-carboxylic acid was suspended in 200 ml of butyl acetate. 15.8 g (0.08 mol) of trichloromethyl chloroformate was added dropwise for 4 hours under heating under reflux.After the dropwise addition was complete, stirring was continued for an additional 2 hours.After the reaction was complete, the reaction solution was filtered and the filtrate was condensed to obtain 12.1 g of 2-chloro-4-methylthiazole-5-carboxylic acid chloride. The purity was 98.5% and the yield was 96.9%.

Example 3 In the same apparatus as in Example 1, 2-trifluoromethyl-4
-Methylthiazole-5-carboxylic acid 4.2 g (0,0
2 mol) of chlorobenzene 100mj! After adding 0.04 g of pyridine and adding 9.9 g (0.05 mol) of trichloromethyl chloroformate dropwise for 5 hours under heating and refluxing, after the completion of the 6 dropwise addition, and after the completion of the 0 reaction under PiL control for an additional 2 hours, The reaction solution was filtered and the filtrate was filtered to obtain 4.5 g of 2-trifluoromethyl-4-methylthiazole-5-carboxylic acid chloride. Purity 98.7%, yield 9
Example 4 In the same apparatus as in Example 1, 10.4 g (0.06 mol) of 2-methoxyl 4-methylthiazole-5-carboxylic acid was added to 150 ml of tetrahydrofuran, and N
, 0.02 g of N-dimethylacetamide was added, and 1.0 g of phosgene was added under heating under reflux. Blowing was carried out for 4.5 hours at a flow rate of I N/h (0.23 mol).
After stirring for 0 hours, the reaction solution was filtered and the filtrate was filtered.
The mixture was condensed to obtain 10.8 g of 2-methoxy-4-methylthiazole-5-carboxylic acid chloride. Purity 96.2%,
The yield was 93.9%.

Example 5 In the same apparatus as in Example 1, 2-methylthiazole-5-
10.0 g (0.07 mol) of carboxylic acid to 10 g of xylene
Suspended in 0s+f, triethylenediamine 0.03g
was added, and under heating and reflux, phosgene was blown in at a flow rate of 930 m/h for 6 hours (0.25 mol). After the blowing was finished, the mixture was further stirred for 2 hours. 10.5 g of 2-methylthiazole-5-carboxylic acid chloride was obtained. Purity 96.0%,
The yield was 92.8%.

Example 6 In the same apparatus as in Example 1, 4-methylthiazole-5-
7.2 g (0.05 mol) of carboxylic acid was added to toluene Loo.
Hexamethylphosphoramide 0.02
After the completion of the reaction, the reaction solution was filtered. The filtrate was concentrated to obtain 8.0 g of 4-methylthiazole-5-carboxylic acid chloride. The purity was 99.2% and the yield was 99.0%.

Comparative Example 1 2.4-dimethylthiazole-5-carboxylic acid 15.7
g (0.1 mol) was suspended in 30 hl of ethyl ether and 8 g of pyridine (0.1 mol), and 12 g (0.1 mol) of thionyl chloride was added dropwise over 45 minutes at -3°C. After completion of the reaction. , filter, ijF! m Schiff, 2g of 2.
4-dimethylthiazole-5-carboxylic acid chloride was obtained. The purity was 85% and the yield was 35%.

Comparative Example 2 In the same apparatus as in Example 1, 15.7 g (0.1 mol) of 2,4-dimethylthiazole-5-carboxylic acid was suspended in toluene room N, and 1.5 g of phosgene was added under heating to reflux.
It was blown in for 5 hours at a flow rate of 31.7 hours (0.29 mol). After the reaction was completed, the residue was filtered off and the filtrate was a-condensed. As a result,
7.2 g of 2,4-dimethylthiazole-5-carboxylic acid chloride was obtained. Purity 96.9%, yield 41.0%
Met.

〔Effect of the invention〕

According to the method of the present invention, the reaction time can be shortened, the reaction can be easily controlled Tj, and the desired product can be obtained with high purity and high yield without treating by-products.

Furthermore, the highly purified thiazolecarboxylic acid chlorides obtained can be used in the next step as intermediates for pharmaceuticals, agricultural chemicals, etc. without additional purification operations, and this is an industrially useful method.

Patent applicant: Mitsui Toatsu Kagaku Co., Ltd. Procedural Report (spontaneous) July 1, 1989 Commissioner of the Japan Patent Office Yoshi 1) Moon Tsuyoshi l, Indication of the case Patent Application No. 150183 1988 2, Invention Name: Process for producing thiazolecarboxylic acid chlorides 3, Relationship with the case of the person making the amendment Patent applicant address: 3-2-5-4 Kasumigaseki, Chiyoda-ku, Tokyo Number of claims increased by amendment: 0 5, amendment Part 6 of the detailed description of the invention in the subject specification, Contents of amendment (I) After "-" in the second line of page 20 of the specification (
2) Insert 3.85 (311, S) J of “-・was” on page 20, line 13 of the specification.

(3) "...was..." on page 21, line 3 of the specification.
), 8.15 (III, S) Insert J.

(4) Insert "[-, j)" on page 21, line 13 of the specification.

(5) Insert the following ``Examples 7, 8, and 9J between page 21, line 13 and line 14 of the same page of the specification.

Example 7 30 shots! 18.8 g (0.11 mol) of 2-methyl-4-ethylthiazole-5-carboxylic acid was added to a three-way flask of 150 ml of toluene. , 0.1 g of N,N-dimethylformamide was added, and while heating under reflux, phosgene was blown in at a flow rate of 1.517 hours for 4 hours (0,2
After completion of the reaction, the reaction solution was filtered and the filtrate was concentrated to give 20.3 g of 2-methyl-4-ethylthiazole-5-
Carboxylic acid chloride was obtained. Purity 98.0%, yield 9
7.5% (811, ), 2.46 (311,
S), 3.06 (211,q, J.
mol) was suspended in 15 ml of toluene, 0.1 g of N,N-dimethylacetamide was added, and 1.5 f! of phosgene was added under heating under reflux. After the reaction was completed, the reaction solution was filtered and the filtrate was concentrated to obtain 16.1 g of 2-ethyl-4-methylthiazole-5-carboxylic acid. Obtained chloride. Purity 98.2%
, yield was 96.9%, 811 steps, 2.62 (31
1,3), 2.93 (2111q, J= II 11.
) Example 9 2-propyl-4-
Methylthiazuru-5-carboxylic acid 15.0g (0°0
8 mol) in xylene Loom N, N,N
-Add 0.05g of dimethylformamide and heat under reflux to reduce the amount of phosgene to 1.54! After completion of the reaction, the reaction solution was filtered and the filtrate was concentrated to obtain 16.2 g of 2-propyl-4-methylthiazole-5-carboxylic acid chloride. Ta. Purity 97.
3%, yield 98.2%, t, J = 711. , 1.
80 (2H, m, J=711.), 2.72 (3H,
S).

Claims (1)

[Claims] 1. General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) (In the formula, R_1 is hydrogen, a halogen atom, a lower alkyl group, a lower alkoxy group, or a halogen atom or lower alkoxy a lower alkyl group substituted with a group, R_2 is hydrogen,
Indicates a lower alkyl group or a lower alkyl group substituted with a halogen atom or a lower alkoxy group. General formula (II) characterized by reacting thiazole carboxylic acids represented by ) with phosgene or trichloromethyl chloroformate in the presence of a catalyst ▲There are mathematical formulas, chemical formulas, tables, etc. , R_1 and R_2 are the same as in general formula (I).) A method for producing thiazolecarboxylic acid chloride. 2. The method according to claim 1, wherein the catalyst is selected from N-substituted amides, N-substituted formamides, organic bases, or phosphoramides.