JPH0148901B2 - - Google Patents

Description

[Detailed Description of the Invention] The present invention relates to the general formula (In the formula, x represents a halogen atom or a lower alkyl group.) This invention relates to a novel method for producing a compound represented by the formula:

The compound () according to the present invention has the general formula () (In the formula, x has the same meaning as above.) It is a compound useful as an intermediate for producing an excellent acaricide represented by the following formula.

The reaction formula of the production method according to the present invention is as follows.

That is, erythro-2-amino-1-chloro-1
-(4-substituted phenyl)-propane hydrochloride ()
The above compound () is produced by reacting with carbonyl sulfide in a solvent in the presence of a deoxidizing agent. (Reaction formula) Solvents include water, methanol, benzene, chloroform, dichloromethane,
General inert solvents such as, for example, can be used, and as deoxidizing agents, organic bases such as triethylamine, trimethylamine, pyridine, etc., and inorganic bases such as sodium hydroxide, potassium hydroxide, calcium carbonate, etc. can be used.

The reaction is completed at room temperature by bubbling carbonyl sulfide with stirring and then continuing stirring for about 1 hour. After the reaction is completed, the desired product can be obtained in high yield by performing usual operations such as washing with water, drying and distilling off the solvent.

The method for producing compounds () and () is as follows:
(1) Method for synthesizing trans-2-methyl-3-phenylaziridine from norephedrin
Chem, phann, Bull24(5)P1033-1039 (1976) and j.Org.Chem.27P3532 (1962), trans-2-
Erythro from methyl-3-phenylaziridine
Methods for synthesizing 2-amino-1-chloro-1-phenylpropane are described in Tetrahedron 30P2613-21, respectively. However, Erythro-1
No reaction from -substituted phenyl-2-aminopropanol is described. The inventors, 4
When the method described in the above-mentioned literature was applied to the -substituted phenyl derivative, it was found that almost the same reaction conditions could be applied. In addition, when x is a methyl group, when the erythro compound () is reacted with sulfuric acid, a threo-erythro mixed compound () is obtained, but in the ring-closing reaction (reaction formula) with an alkali, either threo-erythro or It has been found that the trans form of the compound () can also be obtained from the compound ().

In producing the compound (), first, as shown in the reaction formula, the compound () is dissolved in water, sulfuric acid is added, and the mixture is reacted with heat to form the sulfuric acid ester (). Next, as shown in the reaction formula, heat in an alkaline aqueous solution such as sodium hydroxide to 80 to 100℃.
A ring-closing reaction is performed to produce aziridine of compound (). Next, the compound () is reacted with hydrochloric acid by a method such as dropping the compound () into an organic solvent saturated with hydrochloric acid to obtain the compound ().

The production method of the present invention has almost no contamination of stereoisomers in each step shown in the reaction formula, and can be said to be an industrially advantageous method with high stereoselectivity.

The structure of the compound was determined from the analysis results of NMR, MASS, IR, etc.

Next, the manufacturing method of the present invention will be explained in more detail with reference to Examples.

Example 1 20 g of erythro-2-amino-1-(4-chlorophenyl)-1-propanol was dissolved in 70 ml of water, 21.9 g of 50% sulfuric acid was added thereto, and the water was distilled off under reduced pressure. 100 ml of benzene was added to the residue, and the mixture was heated under reflux for 5 hours while performing azeotropic dehydration. After the reaction was completed, the mixture was cooled, and the crystals were taken and dried to obtain 28.5 g of the desired product. Yield 99% mp [278-280℃] dec. Example 2 10 g of erythro-2-amino-1-(4-chlorophenyl)-propyl sulfate was suspended in 80 ml of 2N aqueous sodium hydroxide solution and reacted at 90°C for 2 hours. After the reaction was completed, the mixture was cooled and extracted with 80 ml of ether. The ether layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain 6.1 g of the desired product. Yield 97%
n ²² _D 1.5652 Example 3 In a mixed solvent of 100 ml of ether and 1 ml of ethanol,
The mixture was saturated with hydrochloric acid in advance, and a mixture of 6.1 g of trans-2-(4-chlorophenyl)-3-methyl-aziridine and 40 ml of ether was added dropwise at 0°C with stirring.
Stirring was continued for an additional 15 hours at room temperature. After the reaction was completed, the precipitated crystals were collected, washed with ether, and dried to obtain 8.1 g of the desired product. Yield 93% mp [234-237
℃〕dec Example 4 Erythro-2-amino-1-chloro-1-(4
-Chlorophenyl)-propane hydrochloride (2 g) was suspended in 20 ml of benzene, and while stirring, triethylamine was added.
1.8 g of carbonyl sulfide was added thereto, and carbonyl sulfide was then added in excess, followed by continued stirring at room temperature for 1 hour.
After the reaction was completed, it was washed with water, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was recrystallized from benzene to obtain 1.6 g of the target product. Yield 84%mp
[150-152℃] Example 5 Erythro-2-amino-1-chloro-1-(4
-Methylphenyl)-propane hydrochloride (2.2 g) was suspended in 25 ml of benzene, and while stirring, triethylamine was added.
After adding 2.1 g of carbonyl sulfide, excess carbonyl sulfide was added, and stirring was continued for 1 hour at room temperature. After the reaction was completed, the mixture was washed with water, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was recrystallized from benzene to obtain 1.7 g of the desired product. Yield 82% mp [130~
132℃] Example 6 2 g of erythro-2-amino-1-(4-chlorophenyl)-1-chloropropane hydrochloride was added to water-
Suspended in 20 ml of mixed solvent of ethanol (1:1),
2.7 g of 28% caustic soda aqueous solution was added at 0°C.
Next, after an excessive amount of carbonyl sulfide was added, the temperature was raised to 40°C and the reaction was carried out for 1 hour.

After completion of the reaction, pour into ice water, collect precipitated crystals, dissolve these crystals in chloroform, wash with water, dry over anhydrous magnesium sulfate, distill off the solvent, and recrystallize the residue from benzene. object
1.5g was obtained. Yield 80% mp [150-152℃].

Claims (1)

[Claims] 1. General formula (In the formula, x represents a halogen atom or a lower alkyl group.) A general formula characterized by reacting a compound represented by the formula with carbonyl sulfide in an organic solvent in the presence of an acid absorbing agent. A method for producing a compound represented by (in the formula, x has the same meaning as above). 2. The manufacturing method according to claim 1, wherein x is a chlorine atom or a methyl group. 3. The manufacturing method according to claims 1 and 2, wherein the deoxidizing agent is triethylamine. 4 General formula (In the formula, x represents a halogen atom or a lower alkyl group.) In the method for producing a compound represented by: 1 (In the formula, x has the same meaning as above.) is reacted with sulfuric acid to form a sulfuric acid ester (), and then reacted with an alkali, (In the formula, x has the same meaning as above.) A process for producing a compound represented by the formula. 2 Reacting the aziridine () with hydrochloric acid (In the formula, x has the same meaning as above.) A process for producing a compound represented by the formula. 3. A step of reacting the hydrochloride () with carbonyl sulfide in an organic solvent in the presence of a deoxidizing agent to obtain the compound (). A method for producing the compound (), characterized by comprising the above three steps.