JP2000143649A - Production of 2-chloro-5-chloromethyl-1,3-thiazole - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for industrially and advantageously producing 2-chloro-5-chloromethyl-1,3-thiazole useful as a synthetic intermediate for medicines, agrochemicals, etc. SOLUTION: 3-Chloro-1-isothiocyanato-1-propene is reacted with a chlorinating agent in a polar solvent and a poor solvent for 2-chloro-5-chloromethyl-1,3- thiazole hydrochloride obtained in a reactional liquid is then added thereto to deposit the 2-chloro-5-chloromethyl-1,3-thiazole hydrochloride, which is subsequently separated and neutralized.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing 2-chloro-5-chloromethyl-1,3-thiazole.
2-Chloro-5-chloromethyl-1,3-thiazole produced according to the present invention is useful as a synthetic intermediate for pharmaceuticals and agricultural chemicals, for example, as a synthetic intermediate for insecticides such as hexahydrotriazine compounds ( See Japanese Patent Publication No. Hei 6-776).

[0002]

2. Description of the Related Art 2-Chloro-5-chloromethyl-1,3
As a method for producing thiazole, a method of reacting allyl isothiocyanate with a chlorinating agent (JP-A-63-8363)
No. 079), a method of reacting 2-chloroallyl isothiocyanate with a chlorinating agent (JP-A-4-2348).
No. 64), a method of reacting 3-chloro-1-isothiocyanato-1-propene with a chlorinating agent (see Japanese Patent Application Laid-Open No. Hei 9-110844), and trans-3-chloro-1-isothiocyanato-1-propene. Method for reacting with a chlorinating agent (see JP-A-10-36060)
Etc. are known.

[0003]

However, the above method is a very violent reaction requiring a large excess of the chlorinating agent and a high temperature, and the desired 2-chloro-5-chloromethyl-1,3 Since a plurality of by-products are produced in addition to -thiazole, there is a problem that the purity of the obtained 2-chloro-5-chloromethyl-1,3-thiazole is low. The above method has a problem in that it is difficult to obtain 2-chloroallyl isothiocyanate as a starting material at low cost. In the above method, the raw materials are relatively easy to obtain, but the reaction time is long, the reaction yield and the purity of the obtained product are low, and 2-chloro-5-chloromethyl-1,3 having high purity is obtained. -Purification is indispensable to obtain thiazole. The above process also provides 2-chloro-
5-chloromethyl-1,3-thiazole is obtained,
The purity after distillation and purification is 91.6 to 96.6%, which may be insufficient for use in pharmaceutical and agricultural chemical applications. Thus, an object of the present invention is to produce 2-chloro-5-chloromethyl-1,3-thiazole in a high yield and a high purity under a mild condition by using an inexpensive and easily available raw material. It is another object of the present invention to provide a method for producing the same advantageously.

[0004]

According to the present invention, the above object is achieved by reacting 3-chloro-1-isothiocyanato-1-propene with a chlorinating agent in a polar solvent, and then obtaining the reaction solution. A poor solvent for 2-chloro-5-chloromethyl-1,3-thiazole hydrochloride (hereinafter sometimes simply referred to as a poor solvent) was added to give 2-chloro-5-chloromethyl-
1,3-thiazole hydrochloride is precipitated, and the 2-chloro-5-chloromethyl-1,3-thiazole hydrochloride is separated and neutralized. This is achieved by providing a method for producing 1,3-thiazole.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION As the polar solvent used in the present invention, for example, N, N-dimethylformamide, N, N-dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, hexamethylphosphoric triamide , N-
Amides such as methylpyrrolidone; nitriles such as acetonitrile, propionitrile, butyronitrile; aliphatic or aromatic nitro compounds such as nitromethane, 1-nitropropane, 2-nitropropane, nitrobenzene;
Sulfones such as sulfolane; and sulfoxides such as dimethyl sulfoxide. Among them, N, N-dimethylformamide, N, N-dimethylacetamide, 1,
Preference is given to using 3-dimethyl-2-imidazolidinone, N-methylpyrrolidone, dimethylsulfoxide and acetonitrile, particularly preferably acetonitrile. The amount of the polar solvent used is preferably 0.1 to 10 times by weight, more preferably 0.2 to 2 times by weight, of 3-chloro-1-isothiocyanato-1-propene.

As the chlorinating agent, chlorine or a compound which releases chlorine under the reaction conditions, such as sulfuryl chloride, can be used. The amount of chlorinating agent used is 3-chloro-
Usually, 1-isothiocyanato-1-propene.
A range of 0 to 1.5 equivalents is preferred. When chlorine is used as the chlorinating agent, chlorine gas may be directly blown into the reaction system, or chlorine gas dissolved in a solvent may be used. Examples of solvents used for this purpose include the polar solvents mentioned above.

[0007] The reaction temperature is preferably in the range of -20 to 150 ° C, more preferably in the range of 0 to 100 ° C. The reaction time varies depending on the reaction conditions, but usually 1 to 4 hours is appropriate.

[0008] 2-Chloro-5-chloromethyl-1,3-thiazole produced by the reaction exists as a hydrochloride in the reaction system and is dissolved in the reaction solution. In the present invention,
To precipitate the 2-chloro-5-chloromethyl-1,3-thiazole hydrochloride, 2-chloro-5 was added to the reaction mixture.
It is characterized by adding a poor solvent for -chloromethyl-1,3-thiazole hydrochloride. Examples of poor solvents that can be used for this purpose include methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane,
Halogenated hydrocarbons such as 1,2,2-tetrachloroethane; aliphatic hydrocarbons such as pentane, hexane, heptane and octane; aromatic hydrocarbons such as benzene, toluene and xylene; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane And ethers such as dimethoxyethane; and esters such as methyl acetate, ethyl acetate and butyl acetate. Among them, it is preferable to use a halogenated hydrocarbon such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane, and it is particularly preferable to use 1,2-dichloroethane. . The amount of poor solvent used is
3-chloro-1-isothiocyanato used as a raw material
The range is preferably 0.5 to 50 times, more preferably 1.0 to 10 times the weight of 1-propene.

A poor solvent is added to the reaction mixture to give 2-chloro-5-
The temperature at which chloromethyl-1,3-thiazole hydrochloride is precipitated is preferably in the range of -50 to 100 ° C,
A range of 0 ° C. is more preferred.

[0010] The thus obtained 2-chloro-5-
Separation of chloromethyl-1,3-thiazole hydrochloride from the reaction mixture can be carried out according to a conventional method. For example, after terminating the reaction and cooling to a predetermined temperature, a poor solvent is added to precipitate 2-chloro-5-chloromethyl-1,3-thiazole hydrochloride, followed by filtration, centrifugation or other means. -Chloro-5-chloromethyl-1,3-thiazole hydrochloride is separated off. The separated 2-chloro-5-chloromethyl-1,3-thiazole hydrochloride is optionally washed with the above-mentioned poor solvent, and then neutralized with an aqueous alkali solution such as sodium bicarbonate, sodium carbonate, and sodium hydroxide. To release 2-chloro-5-chloromethyl-1,3-thiazole, extract with an organic solvent, wash the extract with water, dry and concentrate under reduced pressure to obtain the 2-chloro-5-chloro-5-chloromethyl-1,3-thiazole.
Chloromethyl-1,3-thiazole can be isolated. 2-chloro-5-chloromethyl-1,3 obtained
-Thiazole has a purity of 95% or more, and even in a stage where no purification operation is performed, the purity of 2-chloro-5-chloromethyl-1,3-thiazole obtained by performing the purification operation in the conventional production method and Equal or better. If necessary, the purity can be further increased by ordinary purification operations such as distillation under reduced pressure, recrystallization and chromatography.

The starting material, 3-chloro-1-isothiocyanato-1-propene, is prepared by reacting 1,3-dichloropropene with thiocyanate.
Thiocyanato-2-propene is obtained and can be easily obtained by rearranging the obtained 3-chloro-1-thiocyanato-2-propene in the presence of a metal salt such as magnesium chloride, cobalt chloride, cupric chloride and the like. (See JP-A-10-36342). In addition, 1,3-dichloropropene is an inexpensive and readily available compound that is mass-produced as a nematicide.

[0012]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention.

Example 1 3-Chloro-1-isothiocyanato-1-
Propene (44.9 g, 0.336 mol) and 22 ml of acetonitrile were added and cooled to 0 ° C.
Sulfuryl chloride (47.7 g, 0.35
3 mol) was added dropwise over 1 hour. After completion of the dropwise addition, the temperature was raised to room temperature, and the mixture was further stirred for 3 hours. Then, 110 ml of 1,2-dichloroethane was added, and the reaction mixture was cooled to -20C. 2-chloro-5-chloromethyl-precipitated
The 1,3-thiazole hydrochloride was filtered and washed with 20 ml of 1,2-dichloroethane. 62.5 g of the obtained 2-
Chloro-5-chloromethyl-1,3-thiazole hydrochloride was added to 50 ml of water and 100 ml of 1,2-dichloroethane.
The mixture was neutralized by gradually adding 120 g of a 15% aqueous solution of sodium carbonate while keeping the temperature at 0 to 5 ° C., and allowed to stand to separate an organic layer. The aqueous layer was extracted twice with 50 ml of 1,2-dichloroethane, and the extract was combined with the organic layer, washed twice with 100 ml of saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. . When 48.2 g of the obtained concentrate was analyzed by gas chromatography,
It contained 46.3 g of 2-chloro-5-chloromethyl-1,3-thiazole (purity 96.1%, yield 81.9).
%). This concentrate is purified by distillation under reduced pressure, whereby 2-chloro-5-chloromethyl-1,3 having a purity of 98.8% is obtained.
39.8 g of thiazole were obtained (yield 6 after distillation purification).
9.7%).

Example 2 In a reaction vessel, 3-chloro-1-isothiocyanato-1-
Propene (44.9 g, 0.336 mol) and N, N
-22 ml of dimethylformamide was added, cooled to 0 ° C, and sulfuryl chloride (4
(7.7 g, 0.353 mol) was added dropwise over 1 hour.
After completion of the dropwise addition, the temperature was raised to room temperature, and the mixture was further stirred for 3 hours. 2-chloro-precipitated
5-Chloromethyl-1,3-thiazole hydrochloride was filtered and washed with 20 ml of 1,2-dichloroethane. 56.8 g of the obtained 2-chloro-5-chloromethyl-1,3
-Thiazole hydrochloride was poured into a mixed solution of 50 ml of water and 100 ml of 1,2-dichloroethane, and while maintaining the temperature at 0 to 5 ° C, 120 g of a 15% aqueous sodium carbonate solution was added little by little to neutralize the mixture. separated. Water layer 1,
The mixture was extracted twice with 50 ml of 2-dichloroethane, and the extract was combined with the organic layer, washed twice with 100 ml of saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. When 41.9 g of the obtained concentrate was analyzed by gas chromatography, it contained 40.2 g of 2-chloro-5-chloromethyl-1,3-thiazole (purity: 9
5.9%, 71.2% yield). This concentrate is purified by distillation under reduced pressure to give 2-chloro-5 having a purity of 98.4%.
35.1 g of -chloromethyl-1,3-thiazole was obtained (61.2% yield after distillation and purification).

[0015]

Industrial Applicability According to the present invention, 2-chloro-5-chloromethyl-1,3-thiazole can be industrially produced with high purity and high yield under mild conditions using inexpensive and easily available raw materials. It can be advantageously manufactured.

Claims (3)

[Claims] (1) 3-chloro-1-isothiocyanato-1
-After reacting propene with a chlorinating agent in a polar solvent, 2-chloro-5-chloromethyl-1,3
A poor solvent for thiazole hydrochloride was added to precipitate 2-chloro-5-chloromethyl-1,3-thiazole hydrochloride, and then the 2-chloro-5-chloromethyl-1,3 was added.
-A process for producing 2-chloro-5-chloromethyl-1,3-thiazole, comprising separating and neutralizing thiazole hydrochloride. 2. The polar solvent is selected from the group consisting of N, N-dimethylformamide, N, N-dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, N-methylpyrrolidone, dimethylsulfoxide and acetonitrile. The method according to claim 1, wherein: 3. 2-Chloro-5-chloromethyl-1,3
The method according to claim 1, wherein a halogenated hydrocarbon is used as a poor solvent for -thiazole hydrochloride.