JPH10167999A - Method for producing bromomethylcyclopropane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for industrially advantageously producing bromomethylcyclopropane having a small amount of impurities while maintaining high selectivity. SOLUTION: Bromomethyl cyclopropane is obtained by brominating cyclopropanemethanol in a hydrocarbon solvent at a temperature of 0 ° C to 40 ° C with a complex of dimethylsulfide and bromine, and then performing a deodorizing treatment. Production method.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing bromomethylcyclopropane, which is useful as a raw material for pharmaceuticals.

[0002]

2. Description of the Related Art As a method for producing bromomethylcyclopropane, a method of reacting phosphorus tribromide with cyclopropanemethanol is known [J. Am. Chem. Soc.
509 (1951)]. In this method, by-product cyclobutyl bromide is 20%, 4-bromo-
6% of 1-butene is formed. Therefore, in order to suppress the formation of such a by-product in which the cyclopropane ring is cleaved, there is known a method of preparing phosphorus tribromide at a low temperature of -80 ° C [J. Am. Chem. , P. 6675 (195
5)). Also, a method using triphenylphosphine-carbon tetrabromide as a brominating agent is known [see J. Org. Chem., 49, 431 (1984)]. A method of brominating cyclopropanemethanol with a bromine-dimethylsulfide complex is also known [JCS Chem. Comm., P. 212 (1973)].

[0003]

However, in the above-mentioned method using phosphorus tribromide or triphenylphosphine-carbon tetrabromide as a brominating agent, these brominating agents are expensive and a large amount of phosphorus is used. Waste is by-produced. Further, regarding the method using a bromine-dimethyl sulfide complex, the purity of the obtained bromomethylcyclopropane is not described. Further, since the bromine-dimethylsulfide complex is separately prepared, isolated and used in advance, the operation is complicated, and it is necessary to use a large excess of the starting material cyclopropanemethanol, and the purification after the reaction is also complicated. Furthermore, since the odor derived from dimethyl sulfide cannot be removed only by ordinary distillation, the method has a problem in industrially implementing the method. Accordingly, an object of the present invention is to provide a method for industrially advantageously producing bromomethylcyclopropane containing few impurities while maintaining high selectivity.

[0004]

According to the present invention, the above object is achieved by brominating cyclopropanemethanol with a complex of dimethylsulfide and bromine in a hydrocarbon solvent at a temperature of 0 ° C to 40 ° C. Thereafter, a deodorizing treatment is performed, which is achieved by providing a method for producing bromomethylcyclopropane.

[0005]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Since a complex of dimethyl sulfide and bromine is a solid, a diluent is required to increase the yield based on cyclopropanemethanol.
Hydrocarbon solvents are used. As the hydrocarbon solvent, a linear, branched or cyclic hydrocarbon such as pentane, hexane, 2-methylbutane, octane, cyclopentane and cyclohexane is used. Particularly, pentane, hexane and the like are preferable. Solvents other than hydrocarbon solvents reduce the selectivity of the reaction.

The amount of dimethyl sulfide used is preferably in the range of 0.4 to 1.0 mol based on 1 mol of cyclopropanemethanol. The amount of bromine used is preferably in the range of 0.4 to 1.0 mol per mol of cyclopropane methanol, and more preferably in the range of 0.5 to 0.8 mol in terms of economy. preferable. The complex of dimethyl sulfide and bromine, prior to the addition of cyclopropanemethanol,
It is prepared by reacting dimethyl sulfide with bromine under cooling in the above-mentioned solvent, and can be subjected to a reaction with cyclopropane methanol as a suspension without isolation.

[0007] The reaction is carried out at a temperature in the range of 0 ° C to 40 ° C, more preferably in the range of 20 ° C to 40 ° C. 40
If the temperature is higher than 0 ° C., the cyclopropane ring tends to open, which is not preferable.

After the completion of the bromination reaction, the desired product can be isolated and purified from the reaction solution by removing the lower layer in which phase separation has occurred, followed by washing and distillation, but the odor derived from dimethyl sulfide is eliminated. Therefore, it is necessary to deodorize before or after distillation.

As the deodorizing operation, methods such as contact with hydrogen peroxide solution and adsorption with activated carbon are used. As the aqueous hydrogen peroxide, for the dimethyl sulfide contained,
A 5-35% strength aqueous solution containing 2-20 molar equivalents of hydrogen peroxide is used and is contacted with bromomethylcyclopropane or a solution thereof for 0.5-10 hours at a temperature of -5-10 ° C. Deodorization is completed. Activated carbon is used in different amounts depending on its adsorptive power, but is added at 0 to 70 ° C. until dimethyl sulfide disappears, and then filtered to complete deodorization.

[0010]

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 95.9 bromine was added to a solution of 37.3 g of dimethyl sulfide in 600 ml of hexane under a nitrogen atmosphere under ice-cooling.
g was added dropwise over 2 hours and further stirred for 1 hour to prepare a suspension of dimethylsulfide-bromine complex. 72.1 g of cyclopropanemethanol was added to this suspension at 25 ° C.
Was added dropwise over 2 hours, and stirring was continued at 25 to 30 ° C. overnight. The resulting reaction mixture was separated to remove the lower layer, and the upper layer was
500 ml of 10% hydrogen peroxide solution was added dropwise at 2 ° C. over 2 hours, and stirring was continued at 0 ° C. for 3 hours. After removing the aqueous layer and washing the upper layer with aqueous sodium bicarbonate, hexane was distilled off and distilled under reduced pressure to remove bromomethylcyclopropane.
1.3 g was obtained (yield 75%).

Example 2 The lower layer of the reaction solution prepared in the same manner as in Example 1 was removed, and the upper layer was washed with aqueous sodium bicarbonate, and about の of hexane was distilled off.
Activated carbon (10 g) was added to the residue, and the mixture was stirred for 4 hours, filtered, concentrated, and distilled under reduced pressure to obtain bromomethylcyclopropane (87.7 g, yield 65%).

[0013]

According to the present invention, there is provided a method for industrially advantageously producing bromomethylcyclopropane containing few impurities while maintaining high selectivity.

Claims (2)

[Claims] 1. Bromomethylcyclopropane, which is obtained by brominating cyclopropanemethanol with a complex of dimethylsulfide and bromine in a hydrocarbon solvent at a temperature of 0 ° C. to 40 ° C. and then performing a deodorizing treatment. Manufacturing method. 2. The process according to claim 1, wherein the complex of dimethyl sulfide and bromine is used in an amount of 0.4 to 1.0 mol per 1 mol of cyclopropanemethanol.