JPH0374224B2 - - 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-(nitylthio)-1,3-thiazine is reacted with 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, the method for producing a heterocyclic compound having a nitromethylene group in the side chain using a cyclic dithiocarbamate as a starting material requires a very long and complicated reaction process, and also uses methylated raw materials. In the step of reacting with alkyl nitroacetate, methyl mercaptan, which causes a bad odor, is generated, so this method cannot necessarily be said to be industrially satisfactory.

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 () (However, in the formula, X ¹ and X ² represent the same or different halogen atoms, and Y represents a hydrogen atom, a halogen atom, or a lower alkyl group.) In the presence of a base, the general formula () (In the formula, R represents an alkyl group, a cycloalkyl group, an aralkyl group, an alkenyl group, or an alkynyl group, and n represents 2, 3 or 4.) If so, it is very industrially advantageous to use the general formula () (In the formula, Y represents a hydrogen atom, a halogen atom, or a lower alkyl group, R represents an alkyl group, a cycloalkyl group, an aralkyl group, an alkenyl group, or an alkynyl group, and n represents 2, 3, or 4.) The present inventors have discovered that it is possible to produce a heterocyclic compound having a nitromethylene group in the side chain, as shown in the figure, and have completed the present invention.

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-dihalonitroethylene 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 and Y include any of chlorine, bromine, fluorine and iodine. Alternatively, X ¹ , X ² 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-dichloronitroethylene, 2,2-dibromonitroethylene,
2,2-difluoronitroethylene, 2,2-diiodonitroethylene, 1-methyl-2,2-dichloronitroethylene, 1-ethyl-2,2-dichloronitroethylene, 2-bromo-2-chloronitroethylene , 1-methyl-2-bromo-2-
Chloronitroethylene, 1-ethyl-2-bromo-2-chloroethylene or 2-chloro-2-
2,2-dihalonitroethylenes such as fluoronitroethene; and 1,2,2-trichloronitroethylene, 1,2,2-tribromonitroethylene, 1-bromo-2,2-dichloronitroethylene, 1-chloro-2-bromo-2-chloronitroethylene or 1,2-dichloro-2-
Examples include 1,2,2-trihalonitroethylenes such as bromonitroethylene.
Among these, 2,2-dichloronitroethylene, 1,2,2-trichloronitroethylene, and 1-alkyl-2,2-dichloronitroethylene are particularly useful because they are industrially easily available compounds. .

These 2,2-dihalonitroethylene compounds can be easily synthesized by known methods. For example, in the case of the above-mentioned 2,2-dihalonitroethylenes, the reaction between 2,2-dihaloethylene and nitronium halide, and in the case of the above-mentioned 1,2,2-trihalonitroethylenes, 1,2, 2
- It can be easily synthesized by the reaction of trihaloethylene and nitric acid.

The 1-N substituted aminoalkanethiol compound represented by the above general formula (), which is the other raw material in the present invention, is an industrially available compound. In the general formula (), the alkyl group represented by R is an alkyl group having 1 to 12 carbon atoms such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl. can be mentioned. As a cycloalkyl group,
Examples include those having 5 to 12 carbon atoms such as cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl and cyclododecyl. Examples of aralkyl groups include benzyl groups and phenethyl groups; examples of alkenyl groups include those having 3 to 5 carbon atoms, such as allyl, butenyl, and pentenyl;
Furthermore, examples of the alkynyl group include those having 3 to 5 carbon atoms, such as propargyl, butynyl, and pentynyl.

A typical example is 1-methylamino-2-
Ethanethiol, 1-methylamino-3-propanethiol, 1-methylamino-4-butanethiol, 1-ethylamino-2-ethanethiol,
1-ethylamino-3-propanethyl, 1-
Ethylamino-4-butanethiol, 1-propylamino-2-ethanethiol, 1-propylamino-3-propanethiol, 1-propylamino-4-butanethiol, 1-isopropylamino-3-propanethiol, 1- Butylamino-
3-propanethyl, 1-pentylamino-3
-propanethol, 1-hexylamino-3-
Propanethiol, 1-octylamino-3-propanethiol, 1-decylamino-3-propanethiol, 1-dodecylamino-3-propanethiol, 1-cyclohexylamino-2-ethanethiol, 1-cyclohexylamino-3-propane Thiol, 1-cyclohexylamino-4
-butanethiol, 1-cyclooctylamino-
3-propanethiol, 1-cyclododecylamino-3-propanethiol, 1-benzylamino-2-ethanethiol, 1-benzylamino-3
-propanethyl, 1-benzylamino-4-
Butanethiol, 1-allylamino-ethanethiol, 1-allylamino-3-propanethiol, 1-allylamino-4-butanethiol, 1
-propargylamino-2-ethanethiol, 1-
Examples include propargylamino-3-propanethiol. These 1-N-substituted aminoalkanethiol compounds are usually 0.5 to 1 mole of the 2,2-dihalonitroethylene compound.
10 mol, preferably 1 to 5 mol can be used.

In addition, the bases used in the present invention include alkali metal alcoholates such as sodium methoxide, sodium ethoxide, 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 can be used in an amount of usually 2 mol or more, preferably 2.0 to 5 mol, per 1 mol of the 2,2-dihalonitroethylene compound used.

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-dihalonitroethylene compound and the 1-N substituted 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-N substituted aminoalkane thiol compound and a base are reacted in advance in a solvent to convert a thiol compound into a thiolate compound, and then in the solution It can also be carried out by a method of adding a 2,2-dihalonitroethylene compound to the 2,2-dihalonitroethylene compound. However, to a solution in which a 1-N-substituted aminoalkanethiol compound is dissolved in a solvent, a solution in which a 2,2-dihalonitroethylene compound and a base are separately dissolved in a solvent is gradually added, sometimes in portions. By employing this method, the desired product can be obtained 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 represented by the above general formula () having a nitromethylene group in its side chain can be obtained in high yield. For example, when 1-methylamino-2-ethanethiol is used as the 1-N substituted aminoalkanethiol compound,
Thiazolidines such as 3-methyl-2-(nitromethylene)-1,3-thiazolidine and 3-methyl-2-(nitro, chloromethylene)-1,3-thiazolidine; also 1-ethylamino-3-propanethyl When using tetrahydro-3-
Ethyl-2-(nitromethylene)-1,3-thiazine, tetrahydro-3-ethyl-2-(nitro,
Thiazines such as chloromethylene)-1,3-thiazine; and 1-cyclohexylamino-4-
When butanethiol is used, hexahydro-3-cyclohexyl-2-(nitromethylene)-
1,3-thiazepine, hexahydro-3-cyclohexyl-2-(nitro, chloromethylene)-1,
Thiazepines such as 3-thiazepine; can be produced respectively.

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 dichloromethane.
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-dihalonitroethylene compound used.

Example 1 5.0 g of 1-methylamino-3-propanethiol and 0.8 g of caustic soda were added to 40 ml of methanol, stirred, and completely dissolved.
Cooled to ℃. While stirring this solution, add a solution of 1.6 g of caustic soda dissolved in 25 ml of methanol and 2,2-dichloronitroethylene.
A solution of 2.8 g diluted in 20 ml of methanol was mixed with 50
After slowly dripping at the same time over a few minutes, approximately 8℃
The reaction was carried out at a temperature of 1 hour. After the reaction, neutralize to pH 7 with 3N-hydrochloric acid aqueous solution, then add 60ml of water,
Extraction was carried out four times with 50 ml of methylene chloride. The extract was concentrated to give 3.38 g of tetrahydro-3-methyl-2-(nitromethylene)-1,3-thiazine (yield: 97
%) was obtained.

Example 2 An experiment was conducted in the same manner as in Example 1, except that 11.6 g of a 28 wt % methanol solution of sodium methoxide was used in addition to caustic soda. the result,
3.41 g (yield 98%) of tetrahydro-3-methyl-2-(nitromethylene)-1,3-thiazine was obtained.

Example 3 1-ethylamino-3-propanethyl instead of 1-methylamino-3-propanethyl
The experiment was conducted in the same manner as in Example 1, except that 5.6 g was used. As a result, tetrahydro-3-ethyl-2-(nitromethylene)-1,3-thiazine
3.65g (yield 97%) was obtained.

Example 4 An experiment was carried out in the same manner as in Example 3, except that 3.4 g of caustic potash was used instead of caustic soda. As a result, tetrahydro-3-ethyl-2-
3.66 g (yield 97%) of (nitromethylene)-1,3-thiazine was obtained.

Example 5 An experiment was carried out in the same manner as in Example 1, except that 6.3 g of 1-isopropylamino-3-propanethiol was used instead of 1-methylamino-3-propanethiol. As a result, tetrahydro-3
-isopropyl-2-(nitromethylene)-1,3
- 3.92 g (yield 97%) of thiazine was obtained.

Example 6 An experiment was carried out in the same manner as in Example 1, except that 8.3 g of 1-n-hexylamino-3-propanethiol was used instead of 1-methylamino-3-propanethiol. As a result, tetrahydro-3
-n-hexyl-2-(nitromethylene)-1,3
- 4.68 g (yield 96%) of thiazine was obtained.

Example 7 An experiment was carried out in the same manner as in Example 1, except that 8.2 g of 1-cyclohexylamino-3-propanethiol was used instead of 1-methylamino-3-propanethiol. As a result, tetrahydro-
3-cyclohexyl-2-(nitromethylene)-
4.69 g (yield 97%) of 1,3-thiazine was obtained.

Example 8 Potassium methoxide was used instead of caustic soda.
An experiment was conducted in the same manner as in Example 7, except that 14.0 g of a 30 wt% methanol solution was used. the result,
Tetrahydro-3-cyclohexyl-2-(nitromethylene)-1,3-thiazine 4.70 g (yield 97
%) was obtained.

Example 9 An experiment was conducted in the same manner as in Example 1, except that 8.6 g of 1-benzylamino-3-propanethiol was used instead of 1-methylamino-3-propanethiol. As a result, 4.75 g (yield 95%) of tetrahydro-3-benzyl-2-(nitromethylene)-1,3-thiazine was obtained.

Example 10 1-allylamino-3-propanethiol in place of 1-methylamino-3-propanethiol
The experiment was conducted in the same manner as in the example except that 6.2 g was used.

As a result, tetrahydro-3-allyl-2-
3.84 g (yield 96%) of (nitromethylene)-1,3-thiazine was obtained.

Example 11 An experiment was conducted in the same manner as in Example 1, except that 6.1 g of 1-propargylamino-3-propanethiol was used instead of 1-methylamino-3-propanethiol.

As a result, tetrahydro-3-propargyl-
2-(nitromethylene)-1,3-thiazine 3.76g
(yield 95%).

Example 12 Instead of 2,2-dichloronitroethylene,
An experiment was conducted in the same manner as in Example 1, except that 4.6 g of 2,2-dibromonitroethylene was used.

As a result, tetrahydro-3-methyl-2-
3.36 g (yield 96%) of (nitromethylene)-1,3-thiazine was obtained.

Example 13 Instead of 2,2-dichloronitroethylene,
An experiment was conducted in the same manner as in Example 1, except that 3.5 g of 1,2,2-trichloronitroethylene was used.

As a result, tetrahydro-3-methyl-2-
(nitro, chloromethylene)-1,3-thiazine
3.97g (yield 95%) was obtained.

Example 14 1-ethylamino-3-propanethyl instead of 1-methylamino-3-propanethyl
The experiment was conducted in the same manner as in Example 13, except that 5.6 g was used.

As a result, tetrahydro-3-ethyl-2-
(nitro, chloromethylene)-1,3-thiazine
4.18g (yield 94%) was obtained.

Example 15 An experiment was carried out in the same manner as in Example 13, except that 8.2 g of 1-cyclohexylamino-3-propanethiol was used instead of 1-methylamino-3-propanethiol.

As a result, 5.31 g (yield 96%) of tetrahydro-3-cyclohexyl-2-(nitro, chloromethylene)-1,3-thiazine was obtained.

Example 16 An experiment was carried out in the same manner as in Example 13, except that 8.6 g of 1-benzylamino-3-propanethiol was used instead of 1-methylamino-3-propanethiol.

As a result, tetrahydro-3-benzyl-2-
(nitro, chloromethylene)-1,3-thiazine
5.41 g (yield 95%) was obtained.

Example 17 1-allylamino-3-propanethiol instead of 1-methylamino-3-propanethiol
The experiment was conducted in the same manner as in Example 13, except that 6.2 g was used.

As a result, tetrahydro-3-allyl-2-
(nitro, chloromethylene)-1,3-thiazine
4.46g (yield 95%) was obtained.

Example 18 An experiment was conducted in the same manner as in Example 13, except that 6.1 g of 1-propargylamino-3-propanethiol was used in place of 1-methylamino-3-propanethiol.

As a result, tetrahydro-3-propargyl-
4.37 g (yield 94%) of 2-(nitro,chloromethylene)-1,3-thiazine was obtained.

Example 19 1-methylamino-2-ethanethiol instead of 1-methylamino-3-propanethiol
The experiment was conducted in the same manner as in Example 1, except that 4.3 g was used.

As a result, 3-methyl-2-(nitromethylene)
2.88 g (yield 90%) of -1,3-thiazolidine was obtained.

Example 20 1-methylamino-4-butanethiol instead of 1-methylamino-3-propanethiol
The experiment was conducted in the same manner as in Example 1, except that 5.6 g was used.

As a result, hexahydro-3-methyl-2-
(nitromethylene)-1,3-thiazepine 3.38g
(yield 90%).

Claims (1)

[Claims] 1 General formula () (However, in the formula, X ¹ and X ² represent the same or different halogen atoms, and Y represents a hydrogen atom, a halogen atom, or a lower alkyl group.) In the presence of a base, the general formula () (In the formula, R represents an alkyl group, a cycloalkyl group, an aralkyl group, an alkenyl group, or an alkynyl group, and n represents 2, 3 or 4.) The general formula () is characterized by (In the formula, Y represents a hydrogen atom, a halogen atom, or a lower alkyl group, R represents an alkyl group, a cycloalkyl group, an aralkyl group, an alkenyl group, or an alkynyl group, and n represents 2, 3, or 4.) A method for producing a heterocyclic compound having a nitromethylene group in a side chain.