JPH0374222B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing a heterocyclic compound having a nitromethylene group in its side chain.

Heterocyclic compounds having a nitromethylene group in their side chains have uses such as agricultural chemicals, medicines, and fragrances. For example, in JP-A-50-151882, tetrahydro-2-(nitromethylene)-1,
It has been proposed that 3-thiazines exhibit excellent activity as agricultural chemicals such as insecticides and acaricides.

Conventionally, many methods for producing heterocyclic compounds having a nitromethylene group in a side chain have used cyclic dithiocarbamate esters, which are easily synthesized and highly reactive substances, as starting materials.

For example, in the above publication, tetrahydro-2
The following method is disclosed as a method for producing -(nitromethylene)-1,3-thiazines.

First, tetrahydro-1,3-thiazine-2-thione is methylated with methyl halide, and the resulting tetrahydro-2-(methylthio)-1,3-thiazine is reacted with an alkyl nitroacetate in the presence of zinc ions, and the alkyl Nitro(tetrahydro-1,3-thiazin-2-ylidene)acetate was obtained, which was then hydrolyzed in the presence of a base and then decarboxylated to obtain the desired product, tetrahydro-2-(nitromethylene)-1,3- Manufacture thiazines.

As seen in this example, cyclic dithiocarbamate esters are used as starting materials. The method for producing heterocyclic compounds having a nitromethylene group in the side chain requires a very long and complicated reaction process, and in the process of reacting the methylated raw material with alkyl nitroacetate, methyl mercaptan, which causes a bad odor, is generated. , etc., cannot necessarily be said to be an industrially satisfactory method.

The present inventors conducted extensive research with the aim of establishing an industrially advantageous method for producing a heterocyclic compound having a nitromethylene group in its side chain. As a result, the general formula () ^{2 , represented} by
2,2-trihalo-1-nitroethane compound,
In the presence of a base in a solvent, 1-aminoalkanethiol represented by the general formula () _H2N- ( _CH2 ) _o -SH...() (in the formula, n represents 2, 3 or 4). If it is reacted with a compound, it is extremely industrially advantageous to form the general formula () (wherein Y represents a hydrogen atom, a halogen atom, or a lower alkyl group, and n represents 2, 3, or 4), and found that it is possible to produce a heterocyclic compound having a nitromethylene group in the side chain, The present invention has now been completed.

In the present invention, the reaction steps are extremely simplified compared to the above-mentioned known methods, there is no by-product of methyl mercaptan which is an obstacle in industrial implementation, and the desired product can be obtained in high yield.

In the 2,2,2-trihalo-1-nitroethane compound represented by the above general formula () which is a raw material of the present invention, the halogen atoms represented by X ¹ , X ² , X ³ and Y include chlorine, bromine, It may be either fluorine or iodine, and X ¹ , X ² , X ³ and Y may be the same halogen atom or different halogen atoms. Examples of the lower alkyl group represented by Y include alkyl groups having 1 to 4 carbon atoms such as methyl, ethyl, propyl, and butyl.

Specific examples include 2,2,2-trichloro-1-nitroethane, 2-bromo-2,2-dichloro-1-nitroethane, 2-chloro-2,2-
Dibromo-1-nitroethane, 2,2-dichloro-2-iodo-1-nitroethane, 2-chloro-
2,2-diiodo-1-nitroethane, 2,2-
dichloro-2-fluoro-1-nitroethane, 2
-Chloro-2,2-difluoro-1-nitroethane, 2,2-dibromo-2-iodo-1-nitroethane, 2-bromo-2,2-diiodo-1-nitroethane, 2,2-dibromo-2-fluoro −
1-nitroethane, 2-bromo-2,2-difluoro-1-nitroethane, 2,2,2-tribromo-1-nitroethane, 2,2,2-triiodo-1-nitroethane, 2,2,2-trifluoro -1-nitroethane, 1-methyl-2,2,2-
Trichloro-1-nitroethane, 1-ethyl-
2,2,2-trichloro-1-nitroethane, 1
-Methyl-2-bromo-2,2-dichloro-1-
Nitroethane, 1-ethel-2-bromo-2,2
2,2,2- such as -dichloro-1-troethane
Trihalo-1-nitro-1-nitroethane and 1,2,2,2-tetrachloro-1-nitroethane, 1-bromo-2,2,2-trichloro-
1-nitroethane, 2-bromo-1,2,2-trichloro-1-nitroethane, 1,2-dibromo-2,2-dichloro-1-nitroethane, 2,2
-dibromo-1,2-dichloro-1-nitroethane, 1-chloro-2,2,2-tribromo-1-
1,2,2, such as nitroethane, 2-chloro-1,2,2-tribromo-1-nitroethane, 1,2,2,2-tetrabromo-1-nitroethane,
Examples include 2-tetrahalo-1-nitroethanes. Among these, 2,2,2- in particular is a compound that is easily available industrially.
Trichloro-1-nitroethane, 2,2,2-tribromo-1-nitroethane and 1,2,2,
2-tetrachloro-1-nitroethane is useful.

These 2,2,2-trihalo-1-nitroethane compounds can be easily synthesized by known methods. For example, the above 2,2,2-trihalo-
In the case of 1-nitroethanes, reaction of 2,2-dihaloethylene with nitronium halide, and in the case of the above-mentioned 1,2,2,2-tetrahalo-1-nitroethanes, reaction of 1,2,2-trihaloethylene It can be easily synthesized by reaction with ethylene, dinitrogen tetroxide, and a halogen.

The 1-aminoalkanethiol compound represented by the above general formula (), which is the other raw material in the present invention, is an industrially available compound, and specific examples include 1-amino-2- Mention may be made of ethanethiol, 1-amino-3-propanethiol and 1-amino-4-butanethiol. These 1-aminoalkanethiol compounds are usually 0.5 to 10 mol per mol of the 2,2,2-trihalo-1-nitroethane compound,
Preferably, 1 to 5 moles can be used.

In addition, the bases used in the present invention include alkali metal alcoholates such as sodium methoxide, sodium oxide, potassium methoxide, or potassium ethoxide; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide. ; hydroxides of alkaline earth metals such as calcium hydroxide, barium hydroxide, or magnesium hydroxide; and the like are useful. These bases are the 2,2,2-trihalo-1-
It can be used in an amount of usually 3 mol or more, preferably 3.5 to 6 mol, per 1 mol of the nitroethane compound.

The reaction in the present invention is carried out in a solvent. Any solvent is useful as long as it can dissolve both raw materials and the base at the same time and is inert to the reaction. Specific examples thereof include lower aliphatic alcohols such as methanol, ethanol, i-propanol, n-propanol, i-butanol, and n-butanol, water, dimethyl sulfoxide, acetonitrile, and dimethylformamide. Among these, from the viewpoint of industrial implementation, it is particularly preferable to use lower aliphatic alcohols as the solvent.

There is no need to place any special restrictions on the method of contacting the 2,2,2-trihalo-1-nitroethane compound and the 1-aminoalkanethiol compound in the present invention.

For example, a method in which a base is added to a solution in which both raw materials are dissolved in a solvent, or a method in which a 1-aminoalkanethiol compound and a base are reacted in advance in a solvent to convert a thiol compound into a thiolate compound, and then 2 , 2,2-trihalo-1-nitroethane compound. However, a solution in which a 2,2,2-trihalo-1-nitroethane compound and a base are separately dissolved in a solvent is gradually added to a solution in which a 1-aminoalkanethiol compound is dissolved in a solvent, sometimes in portions. By employing this method, it is possible to obtain the desired product in an even higher yield.

The reaction of the present invention can be carried out usually at a temperature of 100°C or lower, preferably -10 to 50°C, for 0.5 to 10 hours, preferably 1 to 5 hours.

In this way, a heterocyclic compound having a nitromethylene group in its side chain, represented by the above general formula (), can be obtained in high yield. That is, as a 1-aminoalkanethiol compound, 1-amino-2-
When ethanethiol is used, thiazolidines such as 2-(nitromethylene)-1,3-thiazolidine, 2-(nitro, chloromethylene)-1,3-thiazolidine; or 1-amino-3-propanethyl When using, tetrahydro-2-(nitromethylene)-1,3-thiazine, tetrahydro-2-(nitro, chloromethylene)-
Thiazines such as 1,3-thiazine; further 1-
When using amino-4-butanethiol,
hexahydro-2-(nitromethylene)-1,3-
Thiazepines such as thiazepine and hexahydro-2-(nitro, chloromethylene)-1,3-thiazepine can be produced.

After completion of the reaction, isolation and purification of the target product can be easily carried out by appropriately employing operations such as filtration, concentration, extraction, or recrystallization. A specific example will be described below. First, after the reaction is completed, the reaction solution is neutralized with an aqueous mineral acid solution, the neutralized solution is diluted with water, and then extracted with an organic solvent such as chloroform. The purified target product can be isolated by removing the organic solvent from the extract and recrystallizing the resulting crude crystals.

Next, examples of the present invention will be given. Note that the yield of the target product in each example is based on the 2,2,2-trihalo-1-nitroethane compound used.

Example 1 8.1 g of 1-amino-3-propanethiol and 5.0 g of caustic soda were added to 50 ml of methanol and stirred to completely dissolve them, and then the mixture was cooled to 0°C. Add 2,
A solution prepared by diluting 5.4 g of 2,2-trichloro-1-nitroethane with 20 ml of methanol was slowly added dropwise over 15 minutes, and the reaction was carried out for 1 hour. During this time, heat was generated, but the liquid temperature was kept below 10°C (approximately 8°C). After the reaction, neutralize to pH 7 with 6N aqueous hydrochloric acid, then add 50 ml of water, and add 100 ml of dichloromethane.
Extraction was performed four times. Concentrate the extract and extract tetrahydro-2-(nitromethylene)-1,3-thiazine.
2.91 g (yield 60.1%) was obtained.

Example 2 An experiment was conducted in the same manner as in Example 1, except that 24.1 g of a 28 wt% methanol solution of sodium methoxide was used in place of 5.0 g of caustic soda. As a result, tetrahydro-2-(nitromethylene)-
3.19 g (yield 65.9%) of 1,3-thiazine was obtained.

Example 3 A 28 wt% methanol solution of sodium methoxide was used in place of 5.0 g of caustic soda, and 1-
The amount of amino-3-propanethyl used is 5.5g.
The experiment was carried out in the same manner as in Example 1, except that . As a result, 2.78 g of tetrahydro-2-(nitromethylene)-1,3-thiazine (yield 57.4%)
I got it.

Example 4 An experiment was conducted in the same manner as in Example 1, except that 29.2 g of a 30 wt% methanol solution of potassium methoxide was used in place of 5.0 g of caustic soda. As a result, tetrahydro-2-(nitromethylene)-
3.21 g (yield 66.3%) of 1,3-thiazine was obtained.

Example 5 8.1 g of 1-amino-3-propanethiol was added to 50 ml of methanol and stirred to completely dissolve it, and then the mixture was cooled to 0°C. While stirring this solution, about 1/3 of a solution prepared by dissolving 5.0 g of caustic soda in 40 ml of methanol was added dropwise, and then about 2/3 of the remaining solution and 2,2,2-trichloro- A solution prepared by diluting 5.4 g of 1-nitroethane with 20 ml of methanol was slowly added dropwise over a period of 50 minutes. During this time, the liquid temperature was maintained at 10°C or less (approximately 8°C). After reacting for 1 hour, post-treatment was carried out in the same manner as in Example 1 to obtain tetrahydro-2-
4.20 g (yield: 86.8%) of (nitromethylene)-1,3-thiazine was obtained.

Example 6 5.0g of caustic soda was added to methanol as a base.
An experiment was conducted in the same manner as in Example 5, except that 24.1 g of a 28 wt% methanol solution of sodium methoxide was used instead of the solution dissolved in 40 ml. As a result, tetrahydro-2-(nitromethylene)-
4.25 g (yield 87.8%) of 1,3-thiazine was obtained.

Example 7 The amount of 1-amino-3-propanethiol used
The experiment was conducted in the same manner as in Example 5, except that the amount was changed to 4.1 g. As a result, 3.50 g of tetrahydro-2-(nitromethylene)-1,3-thiazine (yield
72.3%).

Example 8 As a base, 7.0 g of caustic potash was added to 60 g of methanol.
An experiment was carried out in the same manner as in Example 5, except that the solution dissolved in ml was used. As a result, tetrahydro-
2-(nitromethylene)-1,3-thiazine 4.18g
(yield 86.3%).

Example 9 2,2,2-trichloro-1-nitroethane
2,2,2-tribromo-1- in place of 5.4g
An experiment was conducted in the same manner as in Example 5, except that 9.5 g of nitroethane was used. As a result, tetrahydro-2-(nitromethylene)-1,3-thiazine
4.15g (yield 84.4%) was obtained.

Example 10 The experiment was carried out in the same manner as in Example 5, except that 6.5 g of 1,2,2,2-tetrachloro-1-nitroethane was used instead of 2,2,2-trichloro-1-nitroethane. I went. As a result, 4.0 g (yield: 81.0%) of tetrahydro-2-(nitro, chloromethylene)-2,3-thiazine was obtained.

Example 11 Instead of 1-amino-3-propanethiol,
An experiment was conducted in the same manner as in Example 4, except that 6.9 g of 1-amino-2-ethanethiol was used. As a result, 3.20 g (yield 72.4%) of 2-(nitromethylene)-1,3-thiazolidine was obtained.

Example 12 Instead of 1-amino-3-propanethiol,
An experiment was conducted in the same manner as in Example 5, except that 9.3 g of 1-amino-4-butanethiol was used. As a result, hexahydro-2-(nitromethylene)-
4.47 g (yield 84.9%) of 1,3-thiazepine was obtained.

Claims (1)

[Claims] 1 General formula () (However, in the formula, X ¹ , X ² and X ³ represent the same or different halogen atoms, and Y represents a hydrogen atom, a halogen atom or a lower alkyl group.) A nitroethane compound is added to 1 represented by the general formula () _H2N- ( _CH2 ) _o -SH...() (wherein n represents 2, 3 or 4) in a solvent in the presence of a base. - general formula (), characterized by reacting with an aminoalkanethiol compound (In the formula, Y represents a hydrogen atom, a halogen atom, or a lower alkyl group, and n represents 2, 3, or 4.) A method for producing a heterocyclic compound having a nitromethylene group in a side chain.