JPS6039269B2 - Acylketene-S/N-acetal compound and its production method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel acylketene-S.N-acetal and a new method for producing the same, and more specifically, the present invention relates to a novel acylketene-S.N-acetal and a novel method for producing the same. Indicates an atom, lower alkyl group or aryl group.

R3 represents a lower alkyl group, R4 represents a lower alkyl group,
Indicates an aryl group or an aralkyl group. ) and a method for producing the same. In the definition of the general formula (1), the lower alkyl group refers to a straight or branched alkyl group having 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or to rt
-Butyl.

Aryl group refers to a straight or branched alkyl group having 1 to 3 carbon atoms in the aromatic ring, a straight or branched alkoxo group having 1 to 3 carbon atoms, Aryl groups with or without halogen atoms, nitro groups as substituents, such as phenyl.

-, m- or p-tolyl, 4-ethylphenyl, 2
-n-propylphenyl, 4-methoxyphenyl, 3-
Ethoxyphenyl, o-, m- or p-chlorophenyl, p-promphenyl, 3-nitrophenyl or 4-nitrophenyl. Furthermore, an aralkyl group is a linear or branched alkyl group having 1 to 3 carbon atoms in the aromatic ring, or a linear or branched alkyl group having 1 to 3 hydrogen atoms in the aromatic ring. groups, halogen atoms, nitro groups, penzyl groups with or without phenyl groups as substituents, such as penzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 4-ethylbenzyl, 2-isopropylbenzyl, 4-methoxybenzyl, 3-ethoxybenzyl, 2-chlorobenzyl, 3-
Chlorbenzyl, 4-chlorobenzyl, 4-bromobenzyl, 2-nitrobenzyl, 4-nitrobenzyl or 4-phenylbenzyl. The compounds having the general formula (1) obtained by the method of the present invention are all new compounds, and are important compounds as intermediates in the production of heterocyclic compounds such as inxazole and virazole.

For example, a compound having the general formula (1) is ring-closed by reacting with hydroxylamine, and the general formula (wherein R, , R2 and R3 have the same meanings as above) is useful as an intermediate for herbicide production. has.

) can be obtained. Conventionally, regarding the production method of acylketene-S/N-acetal, a) thiocarboxylic acid amide obtained by reacting penzoyl dithioacetic acid methyl ester with pyrrolidine is reacted with allyl bromide in the presence of thallium methoxide to produce 3-allylthio-3
-pyrolyzino-1-phenyl-2-fu.

Method for obtaining Roben-1-one [(Ber.)
Vol. 100, p. 591, 1967], (Tetrahedron
Volume 30, page 1283, 1974), b) aceto vinegar tem
-Butyl ester is reacted with phenylthioisocyanate in the presence of potassium ten-butoxide, then treated with allyl bromide, and then further heated under acidic conditions to obtain 4-allylthio-4-anilino-3-buten-2-one. Method (Tetrahedron Vol. 30, p. 1283, 1974), c) 3,3-dimethylthio-1-phenyl-2-proben-1-one and 2,2-diethoxyethylamine were heated to reflux in ethanol for 2 hours. 3-Methylthio 3-(2,2-diethoxyethylthio)-1-phenyl-2-p. Method for obtaining pen-1-one (Chemical Communications (J.C.S. Chemical)
Comm Plate Jcaticns), page 593, 1973), etc. are known. However, the above conventional method, for example, a)
In this method, amidation is limited to the use of secondary amines, and allylation also increases regioselectivity.
Requires a strong and special base.

The method b) is limited only when a methylene compound activated by two electron-withdrawing groups is used as a starting compound, and in addition, the reaction operation is complicated and the yield is poor. In method c), the reaction progresses easily with ketene mercaptal having two dew-withdrawing groups, but in other cases, as shown in the example, long-term heating,
In some cases, it may be necessary to heat the sealed tube to a high temperature.
Furthermore, when the amine to be reacted has other nucleophilic substituents, such as amine groups, hydroxyl groups, mercapto groups, etc., secondary reactions tend to occur, resulting in the production of by-products. As a result of intensive research into an industrial method for producing acylketene-S.N-acetals having a hydrogen atom on a nitrogen atom, the present inventors have found that, unlike conventional methods, they are less likely to produce by-products and can be produced under mild conditions. We have developed a new method that provides high yields. According to the method of the present invention, the compound having the general formula (1) can be produced as follows.

That is, it can be obtained by reducing a compound having the general formula (wherein R,, R2, R3, R4 and x have the same meanings as described above). In carrying out the method of the present invention, the reaction is easily carried out by contacting the compound having the general formula (0) with a reducing agent in a suitable inert solvent.

As the reducing agent used in the reaction, any reducing agent that is normally used in reduction reactions can be used without particular limitation, but reducing agents that produce so-called nascent hydrogen are preferred, such as tin,
Combinations of metals such as iron, zinc and zinc amalgam with acids such as chlorine, sulfuric acid and acetic acid; combinations of metals such as sodium, sodium amalgam, magnesium, magnesium amalgam, zinc, iron and water with water, etc. Also, metal hydride compounds such as sodium borohydride, potassium borate hydride, lithium borate hydride, trimethoxylithium aluminum hydride, rt-ptoxylithium aluminum hydride, and lithium aluminum hydride: primary chloride Examples include low-valent metal compounds such as tin, ferrous sulfate, ferrous hydroxide, and titanium trichloride; and combinations of methylbutane and various amines.
The solvent used in the reaction is not particularly limited as long as it is not involved in this reaction, and includes, for example, water; lower alcohols such as methanol, ethanol, or isopropanol; and ethers such as ethyl ether, tetrahydrofuran, dioxane, or dimethoxyethane. Types: halogenated hydrocarbons such as methyl chloride, chloroform or trichloroethane; aromatic hydrocarbons such as benzene, toluene or xylene; organic acids such as acetic acid or propionic acid and mixed solvents of these solvents, etc. can give. The reaction is carried out using a stoichiometric amount of reducing agent, but an excess amount (approximately 1
．． Preference is given to using a reducing agent of 1 to 1.3 somole. The reaction temperature is not particularly limited, and the reaction is usually carried out at room temperature, but the reaction may proceed at higher or lower temperatures. Note that the reaction is accelerated by overflowing, so sometimes about 40~
It may also be carried out by heating to 6,000 ℃. The time required for the reaction varies mainly depending on the type of raw material compound, reaction temperature, etc., but is usually 0.5 to 1 instant. After completion of the reaction, the target compound of the method of the invention is recovered from the reaction mixture by conventional methods.

For example, it can be obtained by separating insoluble matter from the reaction mixture in a furnace and removing the solvent from the furnace solution under reduced pressure.If necessary, it can also be purified by a conventional method such as a recrystallization method. Furthermore, the above formula (
The compound having (b) is a new compound and can be produced, for example, by the following series of reactions.

(In the formula, R,, R2, R3, R4 and X have the same meanings as in the preceding and Jikomono, and M represents a metal atom.

) Each step will be explained below. The first step is a step of producing a compound having the above general formula (N), in which the compound having the above general formula (m) is added preferably at least 1 molar amount.
This is achieved by contacting with 1 to 2.0 molar equivalents of phosgene or 0.5 molar equivalents or more, preferably 0.5 to 1.0 molar equivalents, of trichloromethoxycarbonyl chloride.

The reaction is preferably carried out in the presence of a solvent. The solvent to be used is not particularly limited as long as it does not participate in this reaction, but it is preferably a solvent that dissolves the starting compound (m), such as aromatic hydrocarbons such as benzene, toluene or xylene; methylene chloride; Halogenated hydrocarbons such as ethylene dichloride, trichloroethylene or o-dichlorobenzene; good ethers such as ethyl ether or tetrahydrofuran are used. The reaction temperature is not particularly limited as long as it does not decompose the product, and the reaction is usually carried out at room temperature, but the reaction can be further accelerated by flooding. The time required for the reaction varies depending on the raw material compound, reaction temperature, etc., but is usually 1 to 2 hours.
It is 4 hours. After the reaction is completed, the target compound is collected from the reaction mixture by a conventional method.

For example, if the target compound is precipitated as a crystalline substance, it can be obtained by filtering it, or if it is in a solution state, it can be obtained by distilling off the solvent. The crude target compound can also be purified by conventional methods such as recrystallization.
The second step is a step of producing a compound having the general formula m), in which the compound having the general formula (V) is used in an equimolar to slightly excess amount to the compound having the general formula (W), and the compound having the general formula (W) is inactivated. This is achieved by bringing the two into contact in a solvent. The metal atom represented by M in the general formula (V) is not particularly limited as long as it forms a metal mercaptide, but alkali metals and alkali metals such as sodium, potassium, and calcium are preferred. be.

This metal mercaptide may be produced in the present reaction system, or may be produced and isolated in advance. Inert solvents used include, for example, methanol, ethanol, n
- lower alcohols such as propanol or tert-butanol; aromatic hydrocarbons such as benzene or toluene; halogenated hydrocarbons such as methylene chloride or trichlorethylene; ethers such as tetrahydrofuran or dioxane; Examples include nitriles such as pionitrile or penznitrile; amides such as dimethylformamide or dimethylacetamide; and mixed solvents of these solvents; particularly preferred are polar solvents such as methanol, tetrahydrofuran, acetonitrile, etc. . The reaction temperature is not particularly limited, and the reaction is usually carried out at room temperature. The time required for the reaction varies depending on the type of raw material compound and the reaction temperature, but is usually about 1 to 3 hours. After the reaction is complete,
The target compound is collected from the reaction mixture by conventional methods.

For example, if the target compound precipitates from the reaction system, it is collected in a furnace, or if it is not precipitated, the reaction mixture is concentrated, and the filtered product or residue is redissolved in a solvent such as methylene chloride to remove impurities. After removing the solvent, it can be obtained by distilling off the solvent, or by adding a nonpolar solvent such as hexane, benzene, or ethyl ether and collecting the precipitate in a furnace. It can be used as it is as a raw material compound solution for the next step without purification. The third step is a step of producing inxazoline-3-thione having the general formula (W), which can be easily produced by bringing the isoxazolium salt having the general formula (W) into contact with an inorganic or organic sulfur compound. carried out.

The reaction involves dissolving or suspending a compound having the general formula (W) in an inert solvent, and preparing an alkali metal sulfide salt such as sodium bisulfide or potassium bisulfide; an alkali metal sulfide such as sodium sulfide or potassium sulfide; Alkali metal salts of thiosulfate such as sodium thiosulfate and potassium thiosulfate; alkali metal salts of xanthate such as sodium xanthate and potassium xanthate; thioureas such as thiourea and thioamides such as thioacetamide, etc. Add inorganic or organic sulfur compounds or
Alternatively, the sulfur-containing compound may be dissolved or suspended in a solvent, and a compound having the general formula (W) may be added thereto.

Although the reaction proceeds stoichiometrically with equivalent amounts of both reagents, it is preferable to use an excess of the sulfur-containing compound.

The solvent used is not particularly limited as long as it does not participate in this reaction, but preferably water; lower alcohols such as methanol or ethanol; ketones such as acetone or methyl ethyl ketone; ethyl ether, tetrahydrofuran or dioxane. Ethers such as; nitriles such as acetonitrile or propionitrile, and mixed solvents of these solvents are used. The reaction temperature is not particularly limited, and the reaction is usually carried out at room temperature, but the reaction can proceed at temperatures higher or lower. The time required for the reaction is usually about 0.5 to 3 hours. After the reaction is completed, the target compound is collected from the reaction mixture by a conventional method.

For example, if the target compound precipitates as a crystalline substance, it can be filtered out in a furnace, or if it is in a solution form, the solvent can be removed, the residue can be dissolved in a strong solvent that is miscible with water, and after washing with water, the solvent can be evaporated. If necessary, it can be further purified by conventional methods such as recrystallization, vacuum distillation, chromatography, etc. The fourth step is a step of producing a compound having the general formula (b),
This is achieved by bringing the compound having the general formula (W) into contact with a halogen compound having the general formula (skin) in the presence of a solvent. Although the reaction proceeds stoichiometrically in equimolar amounts, it is preferable to use an excess of the halogen compound (Yanagi).

In addition, when the reactivity of the halogen compound used is weak, iodides such as sodium iodide, potassium iodide, and lithium iodide can be added.Especially when the halogen compound is a chloride compound, the above-mentioned The addition of iodide is suitable for accelerating this reaction. The solvent used is not particularly limited, but includes, for example, hydrocarbons such as cyclohexane, benzene or toluene; halogenated hydrocarbons such as methylene chloride, ethylene dichloride trichlorethylene or o-dichlorobenzene; methanol, ethanol, Lower alcohols such as isopropanol or n-butanol; ethers such as ethyl ether, tetrahydrofuran or dioxane;
Ketones such as acetone or methyl isobutyl ketone; Nitriles such as acetonitrile, propionitrile or penznitrile; Esters such as methyl acetate or ethyl acetate; Furthermore, the above general formula (skin)
C. Gen compounds and the like can be used. The reaction temperature is not particularly limited, and is carried out at a relatively low temperature, preferably from room temperature to about 4,030 ℃. The time required for the reaction is usually 5 to 2 hours. After the reaction is completed, the target compound is collected from the reaction mixture by a conventional method.

For example, when the target compound is obtained as a precipitate, it is collected in a furnace, or when it is dissolved, the solvent is distilled off under reduced pressure, and a solvent such as ethyl ether, benzene, or toluene is added to the residue. However, in this series of methods, it can be used as a raw material compound solution for the next step without isolation and purification. Furthermore, in the second step, by combining the compound having the general formula (machi) with a free mercaptan and various amines and reacting the same, the method of the present invention can be carried out without isolating the compound having the general formula (b). It is also possible to obtain the target compound (1).

Next, the method of the present invention will be explained in more detail with reference to Examples and Reference Examples, but the present invention is not limited thereto.

Example 1 3-Methylamino-3-phenylthio-1-phenyl-2-proben-1-one ■ 2-Methyl-3-phenylthio-5-phenyl isoxazolium chloride 3.
After suspending 0.0 μl in 50 μl of tetrahydrofuran, 0.65 μl of zinc powder was added and incubated at room temperature for 1 hour.

After finishing the reaction, the insoluble matter was separated from the reaction mixture in a furnace, the solvent was removed from the furnace liquid under reduced pressure, and the residue was subjected to silica gel column chromatography (eluent: n-hexane-acetone=
30:1) to obtain 1.18 ml of the desired compound as white needles with a melting point of 123-124 qo. (Yield 44.4%) Elemental analysis value (%) C, illusion, calculated value as 5NOS C, 71.34: day, 5.61: N, 5.
20: S, 11.90 actual measurement value C, 71.66: day, 5
．． 59; N, 5.45: S, 12.19■ 2-Methyl-3-phenylthio-5-phenyl isoxazolium chloride After suspending 9 of 304 in benzene 5M, 9 of thiophenol 220 and n-dibutylamine 14
2-9 was added and incubated at room temperature for 30 minutes.

After completing the test, the reaction mixture was washed with water, dried over anhydrous sodium sulfate, the solvent was removed, and the resulting residue was subjected to silica gel thin layer chromatography (developing solvent: n-hexane-acetone: 3:1). Further purification yields the target compound 233-9
I got it. (Yield 86.6%) The following compound was produced according to the method of Example 1 above.

3-methylamino-3-phenylthio-3-phthene-2
-one, melting point 81°C 3-methylamino-3-p-tolylthio-3-buten-2-one, melting point 117-11800 3-methylamino-3-p-chlorophenylthio 3-one
Buten-2-one, melting point 129-13000 3-methylamino-3-penzylthio 3-phthene-2
-one, melting point 75-760○ 3-methylamino-3-benzylthio-1-phenyl-2-proben-1-one, melting point 105-10600 3-methylamino-3-p-tolylthio-1-phenyl-2-proben-1-one, melting point 83-84°C 3-methylamino -3-p-chlorophenylthio-1-
Phenyl-2-proben-1-one, melting point 107~
10 is ○Example 2 3-methylamino-3-ethylthio-3-butene-2-
After suspending 0.5 parts of 3-ethylthio-2.5-dimethylisoxazolium oxide in 5 parts of benzene, 0.22 parts of ethanethiol and 0.18 parts of triethylamine were added, and the mixture was stirred at room temperature for 15 hours. did.

After washing, the reaction mixture was purified with water, dried over anhydrous sodium sulfate, the solvent was removed, and the residue was washed with silica gel.
Purified by column chromatography (eluent: n-hexane-acetone = 30:1), with a melting point of 48.6-5.
0.18% of the target compound in the form of pale yellow platelets having a molecular weight of 0.18% was obtained. (Yield 64.2%) Elemental analysis value (%) C7 days,
Calculated value as 3NOS C, 52.80: Sun, 8.23
;N, 8.80;S, 20.13 Actual value C, 53.5
0; Sun, 8.54; N, 8.20: SI9.58 ■ 3
After suspending 1.0 volume of ethylthio 2,5-dimethylisoxazo IJumodide and 0.22 volume of zinc powder in 4 parts of dichloromethane, 2 parts of acetic acid was added and the mixture was allowed to stand at room temperature for 3 minutes.

After the reaction was completed, the residue was removed from the reaction mixture, washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography (eluent: n-). The product was purified with xane-acetone (30:1) to obtain 0.46 g of the target compound. (Yield 82.1%) Reference Example 1 After dissolving 62.2 units of 3-chloro-2,5-dimethylisoxazolium chloride 2,5-dimethyl-4-isoxazolin-3-one in 500 units of dehydrated benzene. Then, 65.0 μl of liquefied phosgene was added and incubated at room temperature for 1 hour.

After the reaction was completed, the precipitate was collected in a furnace, washed with benzene, and then dried to obtain 87.1 kg of white crystals of the target compound having a melting point of 122 to 123 qo. (Yield 94.1%
) Elemental analysis value (%) Calculated value as C5 day 7CI2NO C, 35.74: day, 4.20; N, 8.34: CI
, 42.20 actual value C, 34.49; day, 4.39:
N, 7.76; CI, 42.36 The following compound was produced according to the method of Reference Example 1 above.

3-chloro-2-methylisoxazolium. lido,
Melting point 152-154℃ 3-chloro-2-ethyl-5
-Methylisoxazolium chloride, melting point 10
5-109pm 3-chloro-2-8-fromethyl-5-methylisoxazolium chloride, melting point 166-16900 3-chloro-2-methyl-5-ethylisoxazolium chloride, melting point 48-500○ 3-chlor-2 ,4,5-trimethyl isoxazolium chloride, melting point 75-78qO 3-chloro-2-methyl-5-phenyl isoxazolium chloride, melting point 122-1250○ 3-chloro-2-ethyl-5-phenyl isoxazo Lium chloride, melting point 111-11500 3-chloro-2-methyl benzisoxazolium chloride, melting point 75-83°C 3-chloro-2-p-nitrobenzy-5-methylisoxazolium chloride, melting point 115-11600 3-chloro-2-methylbenzisoxazolium chloride, melting point 115-11600 2-p-methylbenzyl-5-methylisoxazolium chloride, melting point 101-103°C 3-chloro-2-p-chlorobenzyl-5-methylisoxazolium chloride, melting point 96-98qO 3-chloro-2-p-methylbenzyl 5-phenyl-isoxazolium chloride, melting point 68-77
003-Chloro-21 p-nitrobenzyl-5-phenyl isoxazolium chloride, melting point 80-870
0 3-chloro-2-p-chlorobenzyl-5-phenyl isoxazolium chloride, melting point 75-790○ 3-chloro-2-benzylisoxazolium chloride, melting point 77-81°C 3-chloro-2-benzyl-5- Methylisoxazolium chloride, melting point 76-80°C 3-chloro-2-benzyl-5-ethyl isoxazolium chloride, oil 3-chloro-2-benzyl-5-n-propylisoxazolium chloride, oil 3-chloro-2-benzyl -4,5-dimethylisoxazolium chloride, melting point 48-50 3-chloro-2-penzyl-benzisoxazolium chloride, melting point 98-9900 3-chloro-2-penzyl-5-phenyl isoxazolium Chloride, melting point 82-900○ 3-chloro-2-allylisoxazolium chloride,
Melting point 92-94003-chloro-2-aryl-5-
Phenyl isoxazolium chloride, melting point 86~
88qO 3-Chlor-2-allyl benzisoxazolium chloride, melting point 66-69qO Reference example 2 3-chloro-2-n-propyl-5-phenyl isoxazolium chloride 2-n-propyl-5-phenyl After dissolving 1.5 parts of 4-isoxazolium-3-one in 100 parts of dehydrated benzene, 0.8 parts of trichloromethoxycarbonyl chloride was added and the mixture was stirred immediately at room temperature for 1 hour.

After the completion of the reaction, the precipitate precipitated was collected in a furnace, washed with benzene, and then dried to obtain 1.6 kg of white crystals of the target compound having a melting point of 61-M°C. (Yield 82.0%) Elemental analysis value (%) C, 2 days, calculated value as 3CI2NO C,
55.83: Sun, 5.08: N, 5.43: CI, 27
．． 47 actual measurement value C, 55.80: day, 5.37: N, 5
．． 06; CI, 27.10 The following compound was produced according to the method of Reference Example 2 above.

3-Chlor-2-isopropyl-5-methylisoxazolium chloride, melting point 96-98qO 3-chloro-2-ally-5-methylisoxazolium chloride, melting point 75-770 3-chloro-2-n-butyl-5-methyliso Oxazolium chloride, oil 3-chloro-21n-f.

Lopyl-5-methylisoxazolium chloride, melting point 41-4300 3-k.

2-isopropyl-5-phenyl isoxazolium chloride, melting point 133-134°C 3-chloro-2-n-octyl-5-phenylisoxazolium chloride, oil 3-chloro-2-n dodecyl-5- Phenyl isoxazolium chloride, oily substance 3-chloro-2-n-cetyl-5-phenylisoxazolium chloride, oily substance Reference example 3 2-penzyl-5-phenyl-4-isoxazoline-3-thione■ 2-penzyl-3-chloro-5-phenyl isoxazolium chloride 1.2 parts water 10 parts
Sodium 1.0% dissolved in 70% water at room temperature
Added evening.

After 30 minutes, the precipitated crystals were taken out of the oven, washed with water, dried, and recrystallized from benzene to obtain the desired compound in the form of pale yellow needles having a melting point of 121-1220.

(Yield 89.5%) Elemental analysis value (%) C, 6 days, 30
Calculated value as NS C, 71.88: day, 4.90: N
, 5.24: S, 11.99 actual measurement C, 72.14:
Day, 4.78:N, 5.12:S, 12.03■ Add 2-
0.53 g of pendyl-3-chloro-5-phenylisoxazolium chloride was added, and the mixture was heated under reflux for 2 hours.

After cooling, the precipitated crystals were separated in a furnace and washed with acetone. The furnace liquid and washing liquid were combined and concentrated under reduced pressure. The residue was filtered with silica gel.
Subjected to column chromatography, n-hexane-a.
Purified using setone = 3:1 as eluent, melting point 121-1
0.4 yen of the target compound in the form of pale yellow needle crystals having 2〆○ was obtained. (Yield 87.0%) ■ 2-benzyl-3-chloro-5-phenyl isoxazolium chloride 0.67
Dissolve the liquid in 5 parts of water and add 0.4 parts of sodium thiosulfate at room temperature.
Added one evening.

After 30 minutes, ethyl ether was added for extraction, the extract was purified with water, dried over anhydrous sodium sulfate, the solvent was distilled off from the extract, and the resulting residue was recrystallized from benzene. 0.49 g of the target compound in the form of pale yellow needles having a temperature of 122° C. was obtained.

(Yield 84.5%) The following compound was produced according to the method of Reference Example 2 above.

2-Methyl-4-isooxazoline-3-thione, melting point 76-770 2-benzyl-4-isoxazoline-3-thione, melting point 82-83qO 2,5-dimethyl-4-isooxazoline-3-thione, melting point 9430 2-benzyl-5- Methyl-4-isoxazoline-3
-thione, melting point 91-920 21p-methylbenzyl-5-methyl-4-isoxazoline-3-thione, melting point 97-98°C 21p-chlorobenzyl-5-methyl-4-isoxazoline-3-thione, melting point 102- 10300 2-p nitrobenzyl-5-methyl-4-isoxazoline-3-thione, melting point 133-134q0 2-benzy-4,5-dimethyl-4-isoxazoline-3-thione, melting point 81.5-80 2-benzyl-5- n-propyl-4-isoxazoline-3-thione, n-honeyl 1.5995 2-methyl-5-ethyl-4-isoxazoline-3-
Thione, n volume 1-5196 2-Methyl-5-n-bropyr-4-isoxazoline-3-thione, nza 1-5684 2-Methyl-5-phenyl-4-isoxazoline-3
-thione, melting point 120-12100 2-benzylbenziisoxazoline-3-thione, melting point 105-106°C 2-aryl-5-phenyl-4-isoxazoline-3
-thione, melting point 80-8100 2-allyl-4-isooxazoline-3-thioso, n-back 1-5889 2-allylbenziisoxazoline-3-thione, n-yoi 1.6460 2-allyl-5-methyl-isoxazoline- 3-thione, n dorsal. 5 1.5825 2-p-methylbenzyl-5-phenyl-4-isoxazoline-3-thione, melting point 137-13900 2-p-chlorobenzyl-5-phenyl-4-isoxazoline-3-thione, melting point 115-11600 2-isopropyl-5-phenyl -4-Isoxazoline-3-thione, melting point 77-7800 2-ethyl-5-phenyl-4-isoxazoline-3
-thione, melting point 97-9800 2-ethyl-5-methyl-4-isoxazoline-3-thione, melting point 43-44q○ Reference example 4 2-methyl-3-phenylthio-5-phenyl isoxazolium chloride sodium methoxide 3 Thiophenol 7.1 after dissolving .52 methanol in 30 methanol
Then, 15.0 mg of 2-methyl-3-chloro-5-phenylisoxazolium chloride was added and left to stand at room temperature for 3 hours. The insoluble matter was taken up in the furnace, and the solvent was removed from the furnace liquid under reduced pressure. After removing the crab, add methylene chloride to the residue,
The insoluble matter was separated again by the furnace, and the furnace liquid was concentrated to about 1/3.

Next, ether was added, and the precipitated crystals were collected in a furnace, washed with ether, and then dried to obtain 12.40 g of the target compound in the form of a white powder having a melting point of 110 to 113 mm. (Yield 62.
6%) Elemental analysis value (%) C. 6th, calculated value as 4CINOS C, 63.26; day, 4.64; N, 4.6
1: S, 10.55; CI, 11.67 Actual value C, 6
3.43; Sun, 4.69; N, 4.57; S, 10.3
2; CI, 11.39 The following compound was produced according to the method of Reference Example 4 above.

2,5-dimethyl-3-(4-chlorophenylthio)isoxazolium chloride, melting point 46-4700 2,5-dimethyl-3-phenylthio isoxazolium chloride, oil 2-methyl-3-benzylthio-5-isoxa Zolium chloride, melting point 133-13500 2,5-dimethyl-3-(p-tolyl)isoxazolium chloride, oil 2,5-dimethyl-3-pendylthioisoxazo 1"
Um chloride, oil 2-Methyl-3-allylthio-5-phenylisoxazolium chloride, melting point 142-14400 2-methyl-3-n-butylthio-5-phenylisoxazolium chloride, melting point 78-80°C 2-Methyl-3-methoxycarbonylmethylthio-5-phenyl isoxazolium chloride, melting point 146
~14700 Reference Example 5 2-Methyl-3-ethylthio-5-methylisoxazolium After dissolving 20 parts of 2,5-dimethyl-4-isoxazoline-3-thione in 60 parts of acetone, 48 parts of ethyl iodide was dissolved.
．． The mixture was added for 3 nights and then left to stand at room temperature for 2 hours.

After completion of the reaction, the precipitated crystals were collected in a furnace, washed with ether and dried to obtain 43.07 g of the target compound in the form of a white powder having a melting point of 106-100. (Yield 97.6%) Elemental analysis value (%) Calculated value as C7 days, 2JNOS C,2
9.49:Sun, 4.24:N, 4.90:S, 11.2
4: J, 44.50 actual measurement value C, 29.37: day, 4.
19:N, 4.99:S, 11.23; J, 44.49
The following compound was produced according to the method of Reference Example 5 above.

2-Benzy-3-allylthio 5-phenyl isoxazolium bromide, 100-10100 2,5-dimethyl-3-benzylthioisoxazolium 1"
Bromide, melting point 87-880○ 2-penzyl-3-pro/delgylthio-5-phenylisoxazolium bromide, melting point 117-11
900 2-ethyl-3-ethoxycarbonylmethylthio isoxazolium bromide, melting point 133-1340
0 2-Methyl-3-benzylthio-5-phenylisoxazolium bromide, melting point 152-15300 2-benzyl-3-ethylthio-5-methylisoxazolium iodide, melting point 86-8800 2-methyl-3-ethylthio-5- Phenyl isoxazolium bromide, melting point 185-187
00 2-Methyl-3-ethoxycarbonylmethylthio-5-
Phenyl isoxazolium bromide Melting point 139
~140q0 2-benzyl-3-pendylthio-5-phenyl isoxazolium bromide, melting point 145-146°C 2-benzyl-3-methylthio-5-phenyl isoxazolium bromide, melting point 126-1270 2-penzyl- 3-Ethylthio-5-phenyl isoxazolium iodide, melting point 119-120q0 3-methylthio-2,5-dimethyl-isoxazolium iodide, melting point 142-14400 2-methyl-3-phenylthio-5-phenyl isoxa Zolium bromide, melting point 174-179q0 2-ethyl-3-methylthio-5-methylisoxazolium iodide, melting point 149-15000 2-penzyl-3-methylthio isoxazolium bromide, melting point 128-12900 2 -benzyruboxymethylthioisoxazolium bromide, melting point 131-13
○ 2-benzyl-5-n-broby-3-ruboxymethylthioisoxazolium bromide, melting point 137
~13900 2-p-Methylbenzyl-5-methyl-3-carboxymethylthio isoxazo1''um Furo melting point 13
4-135CC2-p-chlorobenzyl-5-methyl-
3-carboxymethylthio isoxazolium furomide, melting point 135-1360○ 2-p-nitrobenzyl-5-methyl-3-carboxymethylthio isoxazolium furomide, melting point
133-13700 2-Benzy-4,5-dimethyl-3-carboxymethylthioisoxazolium bromide, melting point 121
~12300 2-penzyl-5-methyl-3-(1-carboxymethylthio)isoxazolium bromide, melting point 83
~8500 2-penzyl-5-phenyl-3-(1-hydroxyethylthio)isoxazolium furomide, melting point 1
03-10500 2-benzyl-5-phenyl-3-(1-benzylbenzylthio)isoxazolium furomide, melting point
145-146°C 2-Penjiru 3. Ruboxymethylthiobenzisoxazolium.

Mido, melting point 133-13400 2-penzyl-3-ethoxycarbonylmethylthioisoxazolium bromide, melting point 126-1280
○ 2-penzyl-3-(1-ethoxycarbonylbenzylthio)isoxazolium bromide, melting point 99~
10000 2,5-dimethyl-3-ethoxycarbonylmethylthio isoxazolium bromide, melting point 96-9
9°C 2-allyl-5-methyl-3-ethoxycarbonylmethylthioisoxazolium bromide, melting point 1
23-12400 2-penzyl-5-phenyl-3-ethoxycarbonylmethylthio isoxazolium chloride, melting point
86-89qO 2-Methyl-5-phenyl-3-ethoxycarponylmethylthioisoxazolium chloride, melting point 14
0-14 is 0 2-benzyl-5-methyl-3-(1-ethoxycarbonylmethylthio)isoxazolium bromide, melting point
76-780 ○ 2-benzyl-5-phenyl-3-(1-ethoxycarbonylmethylthio) isoxazolium bromide, melting point 92-94 ○ 2-penzyl-5-phenyl-3-(1-ethoxycarbonylbenzylthio) bromide, melting point 95 ～9ge○ 2-penzyl-3-cyanomethylthio isoxazolium iodide, oil 2-benzyl-5-methyl-3-cyanomethylthio isoxazo1'um iodide, oil 2-benzyl-5-phenyl-3-cyanomethylthio
Isoxazolium iodide, melting point 113-11
5q0 2-penzyl-3-carbamoylmethylthioisoxazolium iodide, oil 2-penzyl-5-methyl-3-carbamoylthioisoxazolium iodide, melting point 123-1260
0 2-Methyl-5-phenyl-3-allylthioisoxazo IJum chloride, melting point 142-14400 2-benzyl-5-phenyl-3-ph.

□/Gurgylthioisoxazolium bromide, melting point 117-11 or 0 2-benzyl-5-phenyl-3-allylthioisoxazolium bromide, melting point 100-10100 Reference example 6 3-methylamino-5-methylisoxazo- -'Re3
-Methylamino-3-ethylmercapto-3-buten-2-one 1.0# dissolved in 20 parts of methanol, 0.65 parts of hydroxylamine hydrochloride dissolved in 5 parts of water, and then 85% potassium hydroxide 0.0 parts. A mixture of 62 liters of water was added and the mixture was allowed to stand at room temperature for 4 hours.

After clearing, the reaction mixture was neutralized with IN hydrochloric acid solution and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, the solvent was removed from the extract under reduced pressure, and the residue was purified with silica gel. Purification by thin layer chromatography (developing agent: benzene-ethanol 5:1) yielded 0.70 g of the target compound having a melting point of 62-65 qo.
(Yield 100.0%) Elemental analysis value (%) C5 is N20
Calculated value as C, 53.56: day, 7.19; N, 2
4.98 Measured value C, 53.42: Sun, 7.12; N, 24.7
9 Reference Example 7 3-Methylamino-5-methyl-1-phenylpyrazole 3-methylamino-3-ethylthio-3-butene-2
After 0.7 hours of hydrazine and 0.48 hours of phenylhydrazine were mixed with 10 M of ethanol at room temperature for 1 hour, the solvent was removed from the reaction mixture under reduced pressure, and the residue was purified by silica gel column chromatography (Ayade). agent: n-hexane-acetone = 3:1) and purified to form an oil (n color 5 1
．． 0.68 ml of the target compound (5905) was obtained.

(Yield 82.9%) Elemental analysis value (%) C,. day, 3N
Calculated value as 3 C, 70.56: day, 7.00; N,
22.44 Measured value C, 69.37; Sun, 7.32; N, 21.6
2

Claims (1)

[Claims] 1 Formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R_1 represents a hydrogen atom or a lower alkyl group, R_2 represents a hydrogen atom, a lower alkyl group, or an aryl group. R_3 represents a lower an acylketene-S/N-acetal compound having an alkyl group, and R_4 represents a lower alkyl group, an aryl group, or an aralkyl group. 2 Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 represents a hydrogen atom or a lower alkyl group, R_2 represents a hydrogen atom, a lower alkyl group, or an aryl group. R_3 represents a lower alkyl group, and R_4 represents a lower alkyl group, aryl group, or aralkyl group, and X represents a halogen atom. , R_1, R_2, R_3 and R_4 have the same meaning as described above.) A method for producing an acylketene-S.N-acetal compound.