JPS6048978A - Method for producing a heterocyclic compound having a nitromethylene group in the side chain - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

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, JP-A-50-151882 proposes that tetrahydro-2-tromethylene)-1,3-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, the above-mentioned publication discloses the following method for producing tetrahydro-2-tromethylene 11,3-thiazines.

First, tetrahydro-0-1,3-deazine-2-thione is methylated with methyl halide, and the resulting tetrahydro-
2-(Methylthio)-1,3-thiazine is reacted with an alkylnitroacetate in the presence of zinc ions to give an alkylnitro(tetrahydro-1,3-thiazin-2-ylidene)acetate, which is then reacted in the presence of a base. After hydrolysis, the mixture is decarboxylated to produce the desired product, tetrahydro-2-(tromethylene)-1,3-thiazine.

As seen in this example, the method for producing heterocyclic compounds having a nitromethylene group in the side chain using cyclic dithiocarbamate esters as a starting material requires a very long (complicated) reaction process, and also involves the use of methylated raw materials. In the step of reacting nitroacetate 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 21-lomeburene group in its side chain. As a result, 2゜2. 2-1~Rehalo-1-nitroethane compound in the presence of a base in a solvent, general formula (II) H,N-(CI-12))1-8H・(Jr) (where n is 2 .3 or 4) 1-
If it is reacted with an aminoalkanediol compound, it is very industrially advantageous to react with the general formula (i) (wherein Y represents a hydrogen atom, a halogen atom or a lower alkyl 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 represented by the following formula, 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.

2 represented by the above general formula (I), which is a raw material of the present invention,
In the 2.2-trihalo-1-nitroethane compound,
The halogen atoms represented by ×1, X2, X3, and Y may be any of chlorine, bromine, fluorine, and iodine; It may be an atom.

Examples of the 5-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-t-dichloro-1-nitroethane, 2-bromo-2,2-dichloro-1-nitroethane, 2-chloro-2,2-dibromo-1-nitroethane, 2-bromo-2,2-dichloro-1-nitroethane, .2-dichloro-2-iodo-1-nitroethane, 2-chloro-2,2-short-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-short-1-nitroethane, 2,2-dibromo-2-fluoro-1 -nitroethane, 2-bromo-2,2-difluoro-1-nitroethane, 2,2.2-tribromo-nitroethane, 2.2
．． 2-triiodo-1-nitroethane, 2.2.2-t
-Refluor□-1-nitroethane, 1-methyl-2,'
2.2-Trichloro-1-nitroethane, 1-ethyl-
2゜-〇- 2.2-Trichloro-1-nitroethane, 1-methyl-
2-Bromo-2,2-dichloro-1-nitroethane, 1
-Ether-2-bromo-2,2-dichloro-1-troethane and the like 2.2. lt-limulo-1-nitro-1-nitroethane and 1,2,2,2-tetrachloro-
1-nitroethane, 1-bromo-2,2,2-t-dichloro-1-nitroethane, 2-bromo-1,2,2-t
-dichloro-1-nitroethane, 1,2-dibromo-2
゜2-Dichloro-1-nitroethane, 2,2-dibromo-1,2-dichloro-1-nitroethane, 1-chloro-
2,2,2-1-dibromo-1-nitroethane, 2-chloro-1,2,2-tribromo-1-nitroethane, 1
, 2.2.2-tetrahalo-1-nitroethane such as 2.2.2-tetrabromo-1-nitroethane. Among these, 2,2.2-t- is particularly useful because it is an industrially easily available compound.
Dichloro-1-nitroethane, 2.2.2-t-dibromo-1-nitroethane and 1,2,2.2-tethane compounds can be easily synthesized by known methods. For example, in the case of the above-mentioned 2.2.2-trihalo1]-1-nitroethanes, the reaction of 2.2-dihaloethylene with 21-stium halide, and the above-mentioned 1,2.2.2-tetrahalo1 - In the case of nitroethanes, reaction with 1,2,2-triheroethylene, dinitrogen tetroxide [1],
can be easily synthesized by

The 1-aminoalkanethiol compound represented by the above general formula (■), which is the other [Fl in the present invention ('J), is an industrially available compound, and specific examples thereof include , 1-amino-2-ethanediol, 1-amino-3-propanediol and 1-amino-4-butanediol.These 1-aminoalkanethiol compounds are 1-
Usually 0.5 to 10 per mole of the ditroethane compound
It is possible to use moles, preferably 1 to 5 moles.

In addition, the bases used in the present invention include alkali metal alcoholides such as sodium methoxide, sodium ethoxide, potassium methoxide, or potassium ethoxide; alkali metal water such as sodium hydroxide and potassium hydroxide; Oxide; calcium hydroxide,
Alkaline earth metal hydroxides such as barium hydroxide or magnesium hydroxide are useful. These bases are usually 3 moles or more per mole of the 2,2,2-1-dihalo-1-nitroethane compound used.
Preferably, 3.5 to 6 moles can be used.

The reaction in the present invention is carried out in a solvent. The solvent to be used is one in which both raw materials and the base are dissolved at the same time.
Furthermore, any substance that is inert to the reaction is useful.

Specific examples thereof include lower aliphatic alcohols such as methanol, ethanol, i-propanol, n-propanol, i-butanol or n-butanol, water, dimethyl sulfoxide, acetonitrile, and dimethyl holmamide. can. 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 base is added to a solution in which both raw materials are dissolved in a solvent, or a 1-aminoalkanethiol compound and a base are reacted in advance to convert a diol compound into a thiolate compound, and then added to the m solution. 2.2.2-1-Rimuro 1-nitroethane compound addition method can also be carried out. However, 2.2.2-t-
By employing a method in which solutions in which the Limulo 1-nitroethane compound and the base are separately dissolved in a solvent are added gradually, sometimes in portions, the desired product can be obtained in an even higher yield.

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

Thus, in the side chain represented by the above general formula (II), 21-
A peterocyclic compound having a romethylene group can be obtained in high yield. That is, when 1-amino-2-ethanediol is used as the 1-aminoalkanethiol compound, 2-nitromethylene)-1,3-thiazolidine and 2-nitromethylene)-1,3-deacylidine are used as the 1-aminoalkanethiol compound. Deacylidines such as: Also, when 1-amino-3-propanethol is used, tetrahydro-2-
Tromethylene)-1,3-thiazine, tetrahydro-
Thiazines such as 2-nitromethylene)-1,3-thiazine; and when 1-amino-4-butanethiol is used, hexahydro-2-nitromethylene)-1,3-thiazebin; Thiazepines such as 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 filtration, concentration, extraction, or recrystallization. A specific example will be described next. 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 a known 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. In addition, the yield of the target product in each case is 2°2.2-1 ~
Based on lihalo-1-2-1-loethane compound.

Example 1 8.1 q of 1-amino-3-propanethiol and 5.09 q of caustic soda were added to 50111C of methanol and stirred to completely dissolve, and then the mixture was cooled to 0°C. Add 2.2.2-1- into this solution while stirring.
5.4 g of dichloro-1 nitroloethane to 20 g of methanol
The solution diluted to m0 was slowly added dropwise over 15 minutes, and then the reaction was carried out for 1 hour. During this time, heat was generated, but the liquid temperature was maintained at 10°C or less (approximately 8°C). After the reaction, the reaction mixture was neutralized to pH 7 with a 6N aqueous hydrochloric acid solution, then 50 nl of water was added, and extraction was performed four times with 100 ml of dichloromethane.

The extract was concentrated and tetrahydro-2-nitromethylene)-1,3-thiazine 2.91111 (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 instead of 5.0 (l) of caustic soda. 2-<nitromethylene)-1,3-thiazine 3.19! ] (Yield 65.9%) was obtained.

Example 3 A 281#t% methanol solution of sodium methoxide was used in place of 5.0 g of caustic soda, and 1-amino-
An experiment was conducted in the same manner as in Example 1, except that the amount of 3-propanethiol used was changed to 5.5 g. As a result, tetrahydro-2-to-13-romethylene)-1,3-thiazine 2.7Ba (yield: 5
7.4%).

Example 4 Caustic soda5. An experiment was carried out in the same manner as in Example 1, except that a 30W [% methanol solution of 29.2% potassium methoxide] was used instead of Og.

As a result, tetrahydro[]-2- to nitromethylene)-
1,3-thiazine 3.21! J (yield 66.3%) was obtained.

Example 5 8.19 g of 1-amino-3-propanethiol was added to 50 nl of methanol and stirred to completely dissolve, and then the mixture was cooled to 0°C. 5. Caustic soda is added to this solution while stirring. After dropping about 1/3 of the solution of Og dissolved in methanol 40mC, add about 2/3 of the remaining solution.
amount and 2゜2.1-trichloro-1-nitroethane 5
．． A solution prepared by diluting 4° with 20 nl of methanol was slowly added dropwise over a period of 50 minutes. During this time, keep the liquid temperature below 10℃ (
The temperature was maintained at approximately 8°C. After 14 hours of reaction, post-treatment was carried out in the same manner as in Example 1.
4.20 o of -lahydro-2-(di-heromethylene)-1,3-deazine (yield 86.8%) was obtained.

Example 6 5.0 g of caustic soda was added to methanol <o
An experiment was carried out in the same manner as in Example 5, except that 28 wt% sodium methoxide in methanol solution 24.1 () was used instead of the solution dissolved in mρ.
4.25 (yield: 87.8%) of tetrahydro-2-tromethylene)-1,3-thiazine was obtained.

Example 7 The amount of 1-amino-3-propanethiol used was 4.19
The experiment was carried out in the same manner as in Example 5, except that .

As a result, tetrahydro-2- to tromethylene)-1,
3.50 g (yield 72.3%) of 3-thiazine was obtained.

Example 8 Caustic potash 7. OQ methanol 60m
An experiment was conducted in the same manner as in Example 5, except that a solution dissolved in f2 was used. As a result, 4.18 g of tetrahydro-2-totromethylene)-1,3-deazine (yield 86
．． 3%).

Example 9 2.2.2-t-lichloro1-21 to loethane 5°4
An experiment was conducted in the same manner as in Example 5, except that 9.5 g of 2.2.2-1-ribromo-1 to nitroethane was used instead of 2.2.2-1-ribromo-1 to nitroethane. The result was 4.150 (yield 84.
4%).

Example 10 2.2.Instead of 2-trichloro-1-nitroethane,
1,2.2.2-te1~lacloro1-nitroethane6
, 5g was used, and the experiment was conducted in the same manner as in Example 5. As a result, te 1-lahydro-2-toro, chloromethylene l-2,3-thiazine 4. , Og (yield 81
．． 0%) was obtained.

Example 11 An experiment was carried out in the same manner as in Example 4, except that 6.9 g of 1-amino-2-ethanediol was used instead of 1-amino-3-propanethyl.

As a result, 3.200 (yield: 72.4%) of 2-tromethylene)-1,3-thiazolidine was obtained.

Example 12 An experiment was conducted in the same manner as in Example 5, except that 9.3 g of 1-amino-4-butanethiol was used instead of 1-amino-3-propanethiol.

As a result, hexahydro-2- to tromethylene)-1,
3-thiazepine 4.47! J (yield 84.9%) was obtained.

Patent applicant Ube Industries Co., Ltd. 17-

Claims (1)

[Claims] General formula (I) ×1 <wherein the formula, ? and Shio represent the same or different halogen atoms, and Y represents a hydrogen atom, a halogen atom, or a lower alkyl group. ) 2,2,2-trihalo-1-nitroethane compound represented by the general formula (i) 82N-(CI-12)n-8H·(II) (where n in the formula is 2.3 or 4)) (wherein Y represents a hydrogen atom, a halogen atom, or a lower alkyl group). , n is 2.3 or 4), and has a nitromethylene group in its side chain.