JPS5877878A - Preparation of carbamate compound - Google Patents

Abstract

PURPOSE:To obtain the titled substance having a powerful insecticidal activity with low toxicity to warm-blooded animals, by reacting 2,3-dihydro-2,2-dimethylbenzofuran-7-yl N-methylcarbamate with a novel aminosulfenyl chloride derivative as raw materials. CONSTITUTION:2,3-Dihydro-2,2-dimethylbenzofuran-7-yl N-methylcarbamate is reacted with an aminosulfenyl chloride derivative of formula II (R1 and R2 are X-COOR3 or Y-CN; X and Y are 1-6C alkylene; R3 is 1-8C alkyl except when both X and Y are methylene groups; either one of R1 and R2 represents X- COOR3 or Y-CN, the other represents 1-8C alkyl, benzyl, etc.) in a molar amount of preferably 1-1.2 times of that of the compound of formulaIin the presence of a basic compound to give the aimed compound of formula III. The compound of formula II is novel and synthesized by reacting a compound of formula IV with sulfur monochloride.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for producing a carbamate compound, and further details
゜8-dihydro 2,2-dimethylbenzofuran-7-
yl N -(N,N-disubstituted aminosulfenyl)N
-Regarding a method for producing a methyl carbamate derivative.

Conventionally, certain carbamate compounds have been known to have strong insecticidal activity, and many of these compounds have been put into practical use. However, these highly potent compounds often have the disadvantage of being highly toxic to warm-blooded animals. Among them, 2,3-dihydro-2,2-dimethylbenzofuran-7-yl N-methyl methylcarbamate (common name: carbofuran, hereinafter referred to as "carbollan") is a useful compound with strong insecticidal activity. It is highly toxic to animals and poses problems in use. Considering these factors, it is very meaningful to maintain the insecticidal activity of carbollan and reduce its toxicity to warm-blooded animals.

From this point of view, the present inventors first developed 2,3-dihydro-2,2-dimethylbenzofuran- represented by the following general formula [I] which has strong insecticidal activity and low toxicity to warm-blooded animals.
At first glance, a 7-yl N-(N,N-disubstituted aminosulfenyl)N-methyl mate derivative was found. The present invention provides a novel method for producing a compound represented by the general formula [13].

That is, the present invention relates to the 2,3-dihydro-2,2-dimethylbenzofuran-7-yl N-methylcano;mate represented by the formula E and the general formula E in which R and R2 are the same or different groups -X- C00R8
Or it represents a group -Y-CN. where X and yiic, ~
6 straight chain or branched alkylene group, R8 is CI~8
represents an alkyl group. However, this excludes the case where both X and Y are methylene groups. Also, one of R and R2 is a group -X-CO
OR3 or a group -Y-CN, the other one is a C1-8 alkyl group, a C cycloalkyl group, a benzyl group, a Fe3-6yl group, a substituted benzyl group, a substituted phenyl group, or a group -Z
-R4 may also be indicated. The substituent is a halogen atom, a C alkyl group, or a C1-31-8 alkoxy group. Further, Z is a carbonyl group or a sulfonyl group, R is a C alkyl group, a 4 1-6 phenyl group, a phenyl group having a C1-8 alkyl group or a halogen atom as a substituent, a C5-3 alkoxy group or a phenoxy group shows. 1 is reacted with the aminosulfenyl chloride derivative represented by formula 1 to form a compound of the general formula [wherein R1 and R2 are the same as above]. ] A method for producing a carbamate compound, characterized by obtaining a 2,3-dihydro-2,2-dimethylbenzofuran-7-yl N-(N,N-disubstituted aminosulfenyl)N-methylcarbamate derivative represented by Pertains to.

The reaction between the compound of the formula [old] and the compound of the formula [g] is carried out in the absence of a solvent or in a suitable solvent. Examples of the solvent include halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, ethane dichloride, trichloroethylene, and methyl chloroform, and ethers such as diethyl ether, diethyl ether, dibutyl ether, tetrahydrofuran, and dioxane. be able to. Formula [11
] The ratio of the compound of formula [1] to the compound of formula [1] is not particularly limited and can be appropriately selected within a wide range, but usually the latter is preferably about 1 to 2 times the former by mole. It is preferable to use 1 to 1.2 times the mole of the compound represented by formula [11] and the compound represented by formula [3] in the presence of a basic compound.

Examples of the basic compound that can be used include octa-aryl amines such as triethylamine, tributylamine, dimethylaniline, diethylaniline, and ethylmorpholine, and pyridines such as pyridine, picoline, and lutidine. The amount of the basic compound to be used is sufficient as long as it can capture the hydrogen chloride produced as a by-product in the above reaction, but it is preferably about 1 to 10 times the molar amount of the compound of formula [1]. It is preferable to use 1 to 5 times the molar amount. The reaction proceeds either under cooling, at room temperature, or under heating, but usually at about -20 to 50'C, preferably at 0 to 40'C.
It is better to do it at Further, the reaction time varies depending on the type of basic compound, the amount used, etc., and cannot be determined unconditionally, but is generally about 1 to 20 hours.

The compound of the general formula [2] used as a starting material in the present invention is a novel compound discovered for the first time by the present inventors, and can be produced, for example, by the method shown in Synthesis Method 1 or 2 below.

Synthesis method 1 General formula E In the formula, R1 and R2 are the same as 1 above. It is easily produced by reacting the amine derivative represented by ] with sulfur monochloride or sulfur dichloride.

In formula E, R and R2 are the same as above. ] Even when using sulfur chloride in reaction formula (1), and also when using sulfur dichloride in reaction formula (11), the reaction proceeds in a short time, but in the case of reaction formula (1) Sulfur is liberated. The reaction is the reaction formula (1)
The case of reaction formula (1) and the case of reaction formula (1) proceed under the same reaction conditions.

The reaction between the compound of general formula [Iv] and sulfur monochloride or sulfur dichloride is carried out without a solvent or in a suitable solvent. Examples of the solvent include methyl chloride/, chloroform, carbon tetrachloride, amino dichloride, trichlorethylene, methyl chloroform, etc., nitrogenated hydrocarbons, diethyl ether, dipropyl ether, diptyl ether,
Ethers such as tetrahydrofuran and dioxane, n-
Examples include hydrocarbons such as pentane, n-hexane, n-hebutane, and cyclohexane, and aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene. The ratio of the compound of formula [L] and sulfur monochloride or sulfur dichloride to be used is not particularly limited and can be appropriately selected within a wide range, but usually the latter is 1 to 2 times the former by mole, It is preferable to use 1 to 12 times the mole amount. The reaction between the compound of formula [IV] and sulfur monochloride or sulfur dichloride is preferably carried out in the presence of a basic compound. Examples of the basic compounds used include tertiary amines such as triethylamine, tributylamino, dimethylaniline, diethylaniline, and ethylmorpholine;
Examples include pyridines such as pyridine, picoline, and lutidine. The amount of such basic compound used is:
The amount may be sufficient as long as it can capture the hydrogen chloride produced as a by-product in the above reaction, but it is usually about 1 to 2 times the molar amount, preferably 1-1.5 times the molar amount of the compound of the formula [ffl.

The reaction proceeds either under cooling, at room temperature, or under heating, but usually at about -20°C to 50°C, preferably at -1θ
It is preferable to carry out the reaction at a temperature of 80°C to 80°C. Further, the reaction is completed in about 1 to 2 hours.

Synthesis method 2 In the general formula, R and R2 are the same as above. ] is reacted with sulfur monochloride to form the general formula [wherein RIR2
is the same as above. It is easily produced by obtaining a bisamino disulfide derivative represented by , ] and then chlorinating the resulting compound of general formula EV].

The reactions shown in the reaction formula (set) are carried out without a solvent, in an appropriate solvent, or in a two-layer reaction between a solvent and water.

- As a solvent, for example, methidichloride/, chloroform,
(carbon tetrachloride, dichloroethane, trichloroethylene, methyl chloroform, etc.), rogenated hydrocarbons, ethers such as diethyl ether, siglovir ether, diptyl ether, tetrahydrofuran, dioxane, n-pentane, n-hexane, Examples include hydrocarbons such as n-hebutane and cyclohexane, and aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene. The ratio of the compound of formula [W] and sulfur monochloride in reaction formula (1) is not particularly limited and can be appropriately selected within a wide range, but usually the latter is 0.00% of the former. It is best to use around 5 times the mole.

The reaction of the compound of formula [ffl in reaction formula (1) with sulfur monochloride is preferably carried out in the presence of a basic compound.

As the basic compound used, the amine used as a raw material may be used, and other basic compounds,
For example, tertiary amines such as triethylamine, tributylamine, dimethylaniline, diethylaniline, and ethylmorpholine, and pyridines such as pyridine 1, picoline, and lutidine may be used. On the other hand, when carrying out a two-layer reaction between a solvent and water, caustic soda, caustic potash, sodium carbonate,
Potassium carbonate etc. can be used. The amount of the basic compound to be used may be any amount that can capture the hydrogen chloride produced as a by-product from the above reaction, but it is usually about 1 to 10 times the molar amount of the compound of formula [ff], preferably 1 to 10 times the molar amount of the compound of formula [ff]. It is preferable to use 5 times the molar amount. The reaction proceeds either under cooling, at room temperature, or under heating, but it is usually carried out at about -20°C to 50°C, preferably at -10°C to 80°C. The reaction is completed in about 1 to 2 hours. The general formula obtained in this way [
The bisamino disulfide derivative 4 represented by VJ may be used after purification, or the reaction solution may be washed with water and dried and then used as it is for the next reaction.

The reaction represented by reaction formula (iv) can be carried out without a solvent or in an appropriate manner.
It is carried out in a suitable solvent. As a solvent, use the above reaction formula (-)
All the solvents used in are used. As the chlorinating agent, for example, chlorine, sulfuryl chloride, etc. are used. The proportion of the chlorinating agent to be used is not particularly limited and can be appropriately selected within a wide range, but it is usually about 0.5 to 5 times the mole, preferably 05 to 15 times the mole of the compound of the formula [VJ]. It is better. The reaction proceeds either under cooling, at room temperature, or under heating, but it is usually carried out at about -20 to 50°C, preferably at -1θ°C to 30°C.

The reaction is completed in about 1 to 2 hours.

The compound of the present invention represented by the general formula (IF) obtained above can be easily isolated and purified from reaction mixtures by conventional separation means such as solvent extraction, recrystallization, column chromatography, etc.

The present invention will be explained in more detail with reference to Reference Examples and Examples below.

Reference Example I Production of N-acetyl-N-ethoxycarbonylmethylaminosulfenyl chloride (synthesis method 1).

- Sulfur chloride 2.7F (0.02 mol) is added to tetracarboxylic 85%
0.08 g of N-acetylglycine ethyl ester 2.9F (0.02 mol) l)i was added at 0 to 5°C.

Triethylamine 2.4f (0,024
mol) was added dropwise and stirred for 1 hour. The precipitated crystals were filtered and the mother liquor was concentrated under reduced pressure to obtain an oil. Yield: 8.8 IC yield: 90.5%) NMR of the oil in deuterated chloroform showed the following.

δ, 1.24 ppm (t, 8H), δ, 2.5
2ppm (s, 3H), δ, 4.14ppm (q
, 2H), δ, 4. B 8 pI)m(s, 2
H:).

From NMR, it was confirmed that a slight amount of raw material and bisamino dylphide was formed.

Reference Example 2 Production of N-n-phthyl-N-ethoxycarbonylethylaminosulfenyl chloride (synthesis method 2) - 1.4 g of sulfur chloride <, 0.01 mol 9 was added to carbon tetrachloride 50
Ethyl N-butylaminopropionate 3.5F (0.02 mol) was added dropwise to the solution at 0 to 5°C, and triethylamine 21 (0.02 mol) was further added dropwise thereto. After the addition, the mixture was stirred for a period of time and the reaction solution was washed three times with 5o-e of water. After drying the carbon tetrachloride layer with sodium sulfate, the solution was cooled to 0° C. and stirred again. 1.4 f (0.01 mol) of sulfuryl chloride was added dropwise under cooling, and after stirring at the same temperature for 1 hour, the reaction solution was concentrated under reduced pressure to obtain an oil. NMR of the oil in deuterated chloroform (yield: 4.51 (yield: 918%)) was as follows.

δ, 0.7-2.0 ppm (m, 7H),
δ, 1.26 ppm (L, :jH), δ, 2.7
0 ppm (L, 2H), J, 3.25 ppm (t,
2 old, δ, 8.48 ppm (t, 2H), δ, 4.0
8 ppm (q, 2H), the presence of crab bisamino disulfide was confirmed by NMR.

Example 1 2.3-dihydro-2,2-dimethylbenzofura/-7
-yl N-[N,N-bis(cyanoethyl)aminosulfenyl]N-methylcano(Mate production 2.8-dihydro-2,2-dimethylpenzofura/-7
-il N-metercano (mate 4.4 & (0,02
mol), 8.8 g (0.02 mol) of bis(cyanoethyl)aminosulfenyl chloride and H.

Dissolve 4.7 g of lysine in 35-ff of methylene chloride,
Stirred at 5-30°C for 20 hours. After the reaction, the reaction solution was washed with water, then with diluted hydrochloric acid, and then with water.

The methylene chloride layer was dried over sodium sulfate and then concentrated under reduced pressure to obtain an oil.

Yield: 6.2 IC (Yield: 827 IC) This oily substance contained a small amount of impurities and raw materials, but was mostly the desired product. A portion of the product was purified by silica gel column chromatography to confirm the target product. Penze/:ethyl acetate-4:1 was used as a solvent to obtain an oily substance. NMR of the oil in deuterated chloroform was shown as follows.

δ, 1.43ppm (s, 6H), a, 2.73
ppm (L, 4H), δ, 2.97 ppm (s,
2H), δ, 8.37ppm (s, 3H), δ, 8.4
3ppm (L, 4H), a, 6.5-7.2 ppm
m (m, 3H>, elemental analysis (C, 8H22N403S
= 374.472) Analysis value (H) C: 57.
84 H: 5.81 N: I5.06 calculated value (
H) C: 57.71 H: 592 N: I4.96
From the above results, n was confirmed.

Example 2 2.3-dihydro-2,2-dimethylbenzofuran-7
-yl N-(N-butyl-N-ethoxycarbonyletheraminosulfenyl)N-)f Preparation of carbamate 2.3-dihydro-2,2-dimethylpenzofura/-7
-yl N-methyl carbamate 2.2f (0.01 mol) and N-butyl-N-ethoxycarbonylethylaminosulfenyl chloride 24y (0.01 mol) at 80%
-1 in methylene chloride and cooled to 0°C. 1.2 g (0,012 mol) of triethylamine was added dropwise while stirring, and the mixture was reacted at the same temperature for 2 hours. After the reaction, the reaction solution was washed with water, then with diluted hydrochloric acid, and then with water. After drying the methylene chloride layer, it was concentrated under reduced pressure to obtain an oil. Yield: 84f (yield: 81ch) This oily substance contained a small amount of raw materials and impurities, but was mostly the desired product.

In order to confirm the desired product, the product was purified by silica gel column chromatography to obtain an oily substance (solvent Pe/Zene:ethyl acetate 10:l). NMR of the oil in deuterated chloroform was shown as follows.

a, 0.7-1.8 ppm (m, 10H),
δ, 1.4 1ppm (s, 6H bar δ, 2
．． 4-2.8 ppm (m, 2H), δ, 2.
95 ppm (s, 2H bar δ, 3.33 ppm (s, 3H
), δ, 3.1 to 3.4 ppm (m, 4H bar δ
, 397ppm (q, 2H), δ, 6.6~
7.2 ppm (m, 3H:l.

Elemental analysis (C21H1□N205S = 424.56
9) Analysis value (%) C: 59.01 H near,
38 N: 6.79 Calculated value (chi) C: 59.42
H near, 60 N: confirmed from the results of 6.60 or higher.

Example 3 2.3-dihydro-2,2-dimethylbe/Zofura/-7
-yl N-(N-inpropyl-N-cyanoethylaminosulfenyl)N-)f-Production of h-bamate 2.3-dihydro-2,2-dimethylbenzofurano-7
-yl 2.29 (0.01 mol) of N-methylcarbamate and 1.8 g (0.01 mol) of N-improvil-N-cyanoethylaminosulfenyl chloride were ao
, g of methylene chloride and cooled to 0°C. 1.2 f (0.01 mol) of triethylamine was added dropwise with stirring and reacted for 2 hours at the same temperature. After the reaction, the reaction was washed with water, then with diluted hydrochloric acid, and then with water. The methylene chloride layer was dried and concentrated under reduced pressure to form an oil. I got something.

Yield: 30y (yield: 833%) This oily substance contained a small amount of raw materials and impurities, but most of it contained the target product. A portion of the product was purified by silica gel column chromatography to confirm the target product. Benzene:ethyl acetate-1O:1 was used as a solvent to obtain an oily substance. NMR of the oil in deuterated chloroform was shown as follows.

δ, 1.21 ppm (d, 6H), δ, 1.
43 ppm (s, 6H bar δ, 2.72 ppm (t, 2
H), δ, 3.00 ppm (s, 2H bar δ, 8.0
~3.8 ppm (m, 3H), δ, 3.32 ppm
(s, 3H), δ, 6.6-7.2 ppm (m,
3H), elemental analysis (C18) (25N303S-36
3488) Analysis value (%) C: 5955 H
:6.74 N:1184 Calculated value (%) C:59
49 H: 6.93 N: 1156 This was confirmed from the above results.

Example 4 2.3-dihydro-2,2-dimethylbenzofuran-7
-1ru N-(N-ethoxycarbonyl-N-ethoxycarbonylmethylaminosulfenyl) Production of N-methylcarbamate 2.8-) Hydro-2,2-dimethylbenzofurano = 7
-yl N-methylcarbamate 2.2f″′ (o,
ot mol) and N-ethoxycarbonyl-N-ethoxycarbonylmethylaminosulfenyl chloride 2.4 f
(0.01 mol) and pyridine 3.2f (0.04 mol) were dissolved in chloroform 3 (J, eVC, 20-30
Stirred at ℃ for 24 hours. After the reaction, the reaction solution was washed with water, followed by diluted hydrochloric acid and water, and the chloroform layer was dried and concentrated under reduced pressure to obtain an oil.

Yield 3.4L! (Yield: 79%) This oily substance contained a small amount of raw materials and impurities, but most of it contained the desired product. A portion of the product was purified by silica gel column chromatography to confirm the target product. Benzene:ethyl acetate (4:1) was used as a solvent to obtain an oily substance. NMR of the oil in deuterated chloroform was shown as follows.

δ, 1.17 ppm (t, 6H δ1.44 p
pm (s, 6H), δ, 2.94ppm (s
, 2H), δ, 3.41 ppm (s, 3H bar δ, 4
．． O5ppm (q, 2H), δ4.15 ppm
(q, 2H), δ, 4.41 ppm (s, 2H),
δ, 6.5~? : Oppm (m, 3H)
, elemental analysis C, C,, H26N207S = 426.
499) Analysis value (%) C: 53.46 H: 6
31 N: 6.39 calculated value f%) C: 53.51
H: 614 N: 657 From the above results, it was confirmed.

(that's all)

Claims (1)

[Claims] 2,8-dihydro-2,2-dimethylbenzofuran-7-yl N-methylcarbamate represented by the formula 0 and the general formula E in which R and R2 are the same or different groups -X -■ represents COOR3 or the group -Y-CN. where X and yI
I'ic represents a straight-chain or branched alkylene group of ~6, R
8 represents a C1-8 alkyl group. However, this excludes the case where both X and Y are methylene groups. Also, one of R1 and R represents a group -X -C0OR or a group -Y-CN, and the other one represents a C1-8 alkyl group, a C3-6 cycloalkyl group, a benzyl group, a phenyl group, a substituted benzyl group. , a substituted phenyl group or a group -Z -R4. The substituent is a halogen atom, a C alkyl group, or CI~81
-8 represents an alkoxy group. In addition, 2 represents a carbonyl group or a sulfonyl group, and R4 represents a C1-6 alkyl group, a phenyl group, a phenyl group having a C3~ alkyl group or a halogen atom as a substituent, a C1-8 alkoxy group, or a phenoxy group. . ] is reacted with an aminosulfenyl chloride derivative represented by the general formula [wherein R1 and R2 are the same as above]. ] A method for producing a carbamate compound, characterized by obtaining a 2,8-dihydro-2,2-dimethylbenzofuran-7-yl N-(N,N-disubstituted aminosulfenyl)N-methylcarbamate derivative represented by .