JPS60116675A - Production of heterocyclic compound having nitromethylene group on side chain - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as agricultural chemicals, pharmaceuticals, perfumes, etc., with simple reaction step, in high yield, by reacting a 2,2,2-trihalo-1-nitroethane compound with a 1-N-substituted-aminoalkanethiol compound. CONSTITUTION:The objective compound of formula III can be produced by reacting the 2,2,2-trihalo-1-nitroethane compound of formula I (X<1>-X<3> are halogen; Y is H, halogen or lower alkyl) with the 1-N-substituted-aminoalkanethiol compound of formula II (R is alkyl, cycloalkyl, aralkyl, alkenyl or alkynyl; n is 2-4) preferably in a solvent such as methanol, etc. in the presence of a base such as NaOH, etc. at <=100 deg.C, preferably at -10-+50 deg.C for 0.5-10hr. The compound is produced economically in an industrial scale from the industrially available raw materials, without producing methylmercaptan which is an obstacle to the industrial practice.

Description

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

Heterocyclic compounds having a nitromethylene group in their side chains have uses such as agricultural chemicals, medicines, and fragrances. For example, 71 pieces! In Publication No. 151882/1977, l(1:
, tetrahydro-2-totromethylene)-],]3-thiazi/ has been proposed to exhibit excellent activity as a pistil, such as an insecticide or acaricide.

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 materials11.

For example, the publication No. H discloses the method described below as a method for producing tetrahydro-2-tromethylene)-1,3-thiazines.

Tetrahydro-1,3-thiazine-2-thione is methylated with methyl halide, and the resulting tetrahydro-2-(methylthio)-1,3-thiazine is reacted with argyl nitroacetate in the presence of zinc ions. to obtain alkyl nitro(tetrahydro-1,3-thiazin-2-ylidene) acetate (1), which was then hydrolyzed in the presence of one group and decarboxylated to give the desired product, tetrahydro-2=tromethylene) -1. , 3-thiazines are produced.

As seen in this example, cyclic dithiocarbamine monoesters are the starting material. fl (11 The method for preparing a heterocyclic compound having a nitromethylene group in the chain is 9 reaction steps).
In the step of reacting with 1-alkyl nitroacetate, methyl mercaptan, which causes a bad odor, is generated. It is not necessarily possible to create a method that is industrially satisfactory.

The present inventors conducted extensive research with the aim of developing a method for producing heterochemical compounds having a nitromethylene group in the side chain in a commercially efficient manner.The results of the research were , 2 represented by the general formula (1) (in the formula, χ1.X2 and χ3 represent the same or different halogen atoms, and Y represents a hydrogen atom, a halogen atom, or a lower alkyl group), 2
．． 2-) Dissolve the dihalo-1-nitroethane compound in
Q port 1: l in the presence of base.

General formula (n) HN -rcH2), -8H...(Il)1( (wherein Rjd represents an alkyl group, a cycloalkyl group, an aralkyl group, an alkenyl group, or an alkynyl group, and n is 2. 1-N represented by 3-straddle 4)
to be reacted with a substituted aminoalkanethiol compound;
Very industrially advantageous.

General formula (11) " (In the formula, Y represents a hydrogen atom, a halogen atom, or a lower alkyl group, and R represents an alkyl group, a cycloalkyl group,
It is represented by an aralkyl group, an alkenyl group, or an alkynyl group, where n is 2.3 to 4.
! The present invention has been completed based on the fact that it is possible to produce a heterological compound having a nitromethylene group at l'tf4.

The present invention provides + J-, , Ne compared to the known method.
The process is extremely simplified, and there is no by-product of methyl mercaptan, which is an obstacle to practical implementation, and the desired product can be obtained in high yield.

In the 2.2-)dihalo-1-nitroethane compound represented by the above general formula (t), which is the main feature of the present invention, Xl, χ2. The halogen atoms represented by X3 and Y may be any of chlorine, bromine, fluorine and iodine, and xl, x2, y3 and Y may be the same halogen atom or different halogen atoms. good. Examples of the lower alkyl group represented by the rounded Y include alkyl groups having 1 to 4 carbon atoms such as methyl, ethyl, propyl, and butyl.

The concrete hair is kl as 11: , 2, 2.2-)
Dichloro-1-nitroethane, 2-bromo-2,2-cyclo-1-nitroethane, 2-chloro-2,2-cyfuromo-1-nitroethane, 2,2-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- Sifuromo-2-iodo-1-nitroethane, 2-bromo-2,2-short-1
-nitroethane, 2,2-dibromo-2-fluoro-]
-] Nitroethane, 2-bromo-2,2-difluoro-1-nitroethane.

2.2.2-1-ribromo=1-nitroethane, 2,
2,2-triiodo-1-nitroethane, 2,2.2-
) Lifluoro-1-nitroethane, l-methyl-2,
2゜2-) IJ chloro-1-nitroethane, ],
-]ethyl-2.2.2-)dichloro-l-nitroethane, 1-methyl-2-bromo-2,2-dichloro-1
2.2.2-) such as -nitroethane, 1-ethyl-2-bromo-2,2-dichloro-1-nitroethane, etc.) o -1-nitroethane and 1,2,2- .2-tetrachloro-1-nitroethane, 1
-Bromo 2.2.2-Trichloro-1-nitroethane, 2-bromo'l, 2.2-)dichloro-1-nitroethane.

1,2-dibromo-2,2-dichloro-1-nitroethane, 2,2-dibromo-1,2-7chloro-1-nitroethane, 1-chloro-2,2,2-) IJ Furomo-1-di 1,2,2,2-tetrahalo-1-nitroethane, such as troethane, 2-chloro-1,2,2-)lipromo-1-nitroethane, 1,2,2.2- f dorathromo-1-nitroethane There are many types. Among these, from the industrially easily available compounds, 2.2.2-trichloro-1-nitroethane + 2+2+2, ) ') fromo-1-nitroethane and 1,2,2.2. -tetrachloro-1-
Nitroethane is useful.

The 2,2.2-, 1-IJ halo 1-nitroethane compound can be easily synthesized by a known method. For example, above 2, 2.2-) Gino Law 1
- In the case of nitroethanes, the reaction of 2,2-dino-loethylene with nitronium halide, and the above-mentioned 1,2,
In the case of 2゜2-tetrahalo-1-nitroethanes.

1.2.2-) It can be easily synthesized by reaction with lyhaloethylene, dinitrogen tetroxide, and a halogen.

The other raw material in the present invention is the general formula (Il
) in ', )l. The 1-N substituted aminoalkanethiol compound is a commercially available arsenic compound. In the general formula (■), the alkyl group represented by R is methyl, ethyl, and propyl.

Mention may be made of alkyl groups having 1 to 12 carbon atoms, such as phther, pentyl, hexyl, heptyl, octyl, nonyl, tesyl, undecyl and dodecyl. Cycloalkyl groups include cyclohentyl, cyclohexyl, and cycloheptyl.

cyclooctyl, cyclononyl, cyclodecyl.

5 carbon atoms such as cycloundecyl and cyclododecyl
-12 can be mentioned.

Aralkyl groups include benzyl and phenethyl groups, and alkenyl groups include allyl,
1. Examples include those having 3 to 5 carbon atoms, such as butenyl and pentenyl. Furthermore, as an alkynyl group,
3 carbon atoms such as propargyl, butynyl and pentynyl
-5 can be mentioned.

Typical examples include l-methylamino-2-ethanethiol, 1-methylamino-5-propanethiol,
-Methylamino-4-butanethiol, 1-ethyceamino-2-ethanethiol.

l-ethylamino-3-propanethiol, 1-ethylamino-4-butanethiol, 1-propylamino-2
-ethanethiol, l-propylamino-3-propanethiol, ■-propylamino-4-butanethiol,
l-Isopropylamide/-3-furopanthiol, l
-butylamino-3-propanethyl, l-pentylamino-3-propanethyl, l-hexylamino-
3-propanethiol, l-octylamino-3-propanethiol, 1-decylamino-3-propanethiol, 1-dodecylamino-3-propanethiol, 1-
Cyclohexylamino-2-ethanethiol, l-cyclohexylamino-3-propanethiol, l-cyclohexylamino-4-butanethiol, 1-cyclooctylamino-3-propanethiol, 1-cyclododecylamino-3- Propanethiol, 1-benzylamino-2-ethanethiol, l-benzylamino-3-furopanithiol, l-benzylamino-4-butanethiol, ■-allylaminoethanethiol, l-allylamino-3-propanethiol .

Examples include 1-allylamino-4-butanethiol, 1-propargylamino-2-ethanethiol, 1-propargylamino-3-propanethiol, and Nato. These 1-N Aoyagi aminoalkane thiol compounds ir
j, 2,2.2-) iM usually 0.5 to 10 mol per 1 mol of IJ-no-rho l-nitroethane compound,
From 1 to 5 moles of the active ingredient can be used.

Examples of the bases used in the present invention include sodium methoxide, sodium ethoxide, potassium methoxide, and alkali metal alcolades such as potassium ethoxide; alkali metal alcoholides 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 as 2,2.2-) dinohero1
- Usually 3 mol or more per 1 mol of the ditroethane compound.

Good luck υ23. O to 6 moles can be used.

The reaction in the present invention is carried out in a solvent.
As a solvent for iIH, 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 alcohols such as methanol, ethanol, i-7'' lovanol, η-propanol, ]-butanol or n-butanol, water, dimethyl sulfoxide, acetonitrile, and dimethyl formamide. Among these, from the viewpoint of industrial implementation, it is particularly preferable to use lower aliphatic alcohols as the solvent.

2, 2.2-) Rehalo-1-=to which can be linked to the present invention.

There is no need to place any particular restrictions on the method of contacting the ethane compound with the +INi#-converted aminoalkanethiol compound.

For example, a base is added to a solution in which both raw materials are dissolved in a solvent, or a 1-N substituted aminoalkanethiol compound and a compound are reacted in advance in a solvent.

After converting the thiol compound into a thiolate compound.

It can also be carried out by the method of adding 2.2.2-trihalo-1-nitroethane compound into the solution. However, in a solution of a 1-N-substituted aminoalonithiol compound in a solvent, 2,2.2-)dihalo-1-
By employing a method in which a solution in which the nitroethane compound and the u11 group are separately dissolved in a solvent is gradually added, sometimes in portions, 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 1'00°C or lower, preferably at a temperature of -10 to 50°C, for 0.5 to 10 hours, preferably 1 to 5 hours.

Thus, it is represented by the above general formula (1). A heterocyclic compound having no nitromethylene group in the side chain can be obtained in high yield. For example, when 1-methylamino-2-ethanethiol is used as the 1-N substituted aminoalkanethiol compound, 3-methyl-2- to tromethylene)-1,3-thiazolidine, 3-mesol-2- to thiazolidines such as 1,3-thiazolidine; and when 1-ethylamino-3-propanethyl is used (d2.tetrahydro-3-ethyl-2-totromethylene) -1,3- Thiazin.

Thiazines such as tetrahydro-3-ethyl-2-nitro, chloromethylene)-1,3-thiazine; further 1
When using -cyclohexylamino-4-butanethiol, hexahydro-3-cyclohexyl-2-(
d) C1 methylene) -1,3-thiazepine, hexahydro-3-cyclohexyl-2-nitro, chloromethylene) -1,3-thiazepine.

After the reaction is completed, the target product is isolated and purified by filtration and condensation.

This can be easily carried out by appropriately employing operations such as extraction or M'lr crystal. The specifics-
An example is given below. After the reaction was completed without stirring, the reaction solution was neutralized with an aqueous mineral acid solution, and the neutralized solution was diluted with water.

Extract with an organic solvent such as dichloromethane. The purified target product can be isolated by removing the liquid from the extract and recrystallizing the resulting crude crystals.

Next, an example of the present invention will be described. In addition, the yield of the target product in each case is 2°2.2-2.
) dihalo-1-nitroethane IB combination'th standard.

Example 1 Methanol JLOml! To the solution, 5.07 g of l-methylamino-3-bropanethiol and 0.07 g of caustic soda were added and stirred for complete dissolution, and then the mixture was cooled to 0°C. 11 Cl of this bath liquid was mixed with a solution of 2.22 ml of caustic soda dissolved in 25 ml of methanol, and 3.57 ml of dichloro-1-nitroethane diluted with 20 ml of methanol. This solution was slowly added dropwise at the same time over a period of 50 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 reaction.

3N-,1', @ Neutralized to pH'7 with an acid aqueous solution 9 Then, 60ml of water was added, and extraction was performed 4 times with 50ml of salt (methylene).The extract was concentrated and tetrahydro-3-methyl- 2-tromethylene) -1,3-thiazine 3.2
7 g (yield: 94 g) were obtained.

Example 2 28% of sodium methoxide was added to caustic soda.
except that wt% methanol solution 15.47 was used.

An experiment was conducted in the same manner as in Example 1. the result.

Tetrahydro-3-methyl-2-tromethylene) -
1,3-thiazine 3.31f' (yield: 95%) was obtained.

￥ Kai is Ita 113 ■-methylamino-3-propanethiol di-
An actual Mk was carried out in the same manner as in Example 1, except that 5.62% of ethylamino-3-propanethiol was used. the)
As a result, tetrahydro-3-ethyl-2-totromethylene)-'1,3-thiazine a, 53r (yield 94%) was obtained.

Example 4 An experiment was carried out in the same manner as in Example 3, except that caustic potash 4.42° was used instead of caustic soda.

As a result, 3.54 f (yield: 9%) of tetrahydro-3-ethyl-2-tromethylene)-1,3-thiazine was obtained.

Example 5 Instead of 1-methylamino-3-propanethiol, 1
-isopropylamino-3-propanethyl 6.32
The experiment was conducted in the same manner as in Example 1, except that .

As a result, tetrahydro-3-isopropyl-2-totromethylene)-1,3-thiazine z, 5oy (yield 9
4%).

Example 6 Instead of 1-methylamino-3-propanethiol, 1
-n-hexylamino-3-propanethol 8.3v
The experiment was conducted using the same procedure as in Example 1. As a result, tetrahydro-3-n-hexyl-2-totromethylene)-1,3-thiazine a, 54r (yield 9
3%).

Example 7 In place of 1-methylamino-3-propanethiol, l
-cyclohexylamino-3-pQ JZ-thiol 8
．． The experiment was conducted in the same manner as in Example 1, except that No. 22 was used. As a result, tetrahydro-3-cyclohexyl-
2-tromethylene)-1,3-thiazine4. ．． 55y
(yield 94%).

Example 8゜3Q of potassium methoxide in place of caustic soda
Lol? , methanol solution, (8, except that 'i'f was used.

An experiment was conducted in the same manner as in Example 7. the result.

4.6 or (yield: 95%) of tetrahydro-3-cyclohexyl-2-tromethylene)-1,3-thiazine was obtained.

Example 9 Instead of 1-methylamino-3-propanethiol, l
An experiment was carried out in the same manner as in Example 1, except that 8.62% of -benzylamino-3-propanethiol was used. As a result, tetrahydro-3-benzyl-2-totromethylene)-1,3-thiadiy4.61f/(II sol ratio 92%)
) was obtained.

Example 10 l- in place of 1-methylamino-3-propanethyl
An experiment was conducted in the same manner as in Example 1, except that allylamino-3-propanethiol 6.2f was used.

As a result, 3.72% of tetrahydro-3-allyl-2-(tromethylene)-1,3-thiazine was obtained (yield: 93%).

Example 11゜In place of 1-methylamino-3-propanethiol, 1
-Propargylamino-3-propanethol 6.12
An experiment was conducted using the same procedure as in Experiments 1 and 11.

As a result, tetrahydro-3-propargyl-2-totromethylene)-1,3-thiazine: 5.65f (yield 9
Section 2) was obtained.

Example 12 ■-Methylamino-3-propanethol,]
-] Methylamino-2-ethanethiol 43! /'
, i. The experiment was conducted in the same manner as in Example 1 using a real buoy, except that .

As a result, 3-methyl-2- to tromethylene)-1,3
-thiazolidine 2.822 (yield 88%) was obtained.

Example 13 ■-Methylamino-3-propanethiol was replaced with 1
An experiment was conducted in the same manner as in Example 1, except that 5.62 kg of -methylamino-4-butanethiol was used.

As a result, hexahydro-3-methyl-2-tromethylene)-1,3-thiazepine 3.23f (yield 86)
I got it.

Example 14 Instead of 2,2.2-trichloro-1-nitroethane,
2-promo2.2-)chloro-1-nitroethane4.
In addition to using 42, 11. An experiment was conducted in the same manner as in Example 1.

As a result, 3.2 oy of tetrahydro-3-methyl-2-tromethylene)-1,3-thiazine (yield: 94%)
I got it.

Patent applicant Ube Industries Co., Ltd.

Claims (1)

[Claims] General formula (1) (In the formula, χ1. Alkyl group 7y is shown. ) in a solvent in the presence of a base. General formula (n) (wherein R represents an alkyl group, cycloalkyl group, aralkyl group, alkenyl group or alkynyl group,
n indicates 2.3 dimensions or 4. ) can be stolen l −N
It is characterized by reacting with a substituted aminoalkanethiol compound. General formula (11) (wherein Y represents a hydrogen atom, 7 halogen atoms, or a lower alkyl group, R represents an alkyl group, a cycloalkyl group,
Aralkyl group, alkenyl group (represents an alkynyl group, n represents 2, 3 or 4). llj A method for producing a heterocyclic compound having a nitromethylene group.