JP2647635B2 - Process for producing β-phenylthio-γ-butyrolactone - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a physiologically active compound useful as an antibacterial, bactericidal and insecticide in the fields of medicine and agriculture and horticulture.
The present invention relates to a novel process for producing β-phenylthio-γ-butyrolactone used in the synthesis of phenylthio-2-butene-4-olides.

[0002]

2. Description of the Related Art A method for producing β-phenylthio-γ-butyrolactone is described in M. Watanabe, K .; Shi
rai and T.R. Kumamoto: Bullet
in of The Chemical Society
of Japan. Vol. 52 (11). 331
8-3320 (1979).

[0003] According to this document by Watanabe et al., An example of a method for producing β-phenylthio-γ-butyrolactone can be represented by the following reaction formula.

[0004]

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[0005] The above-mentioned production method is specifically performed as follows.

In a nitrogen stream, a hexane solution of butyllithium is added dropwise to a solution of thiophenol in tetrahydrofuran, for example, at -50 ° C., and the mixture is stirred for 15 minutes. This produces a lithium salt of thiophenol.

The above mixture containing the lithium salt of thiophenol is added to a solution of 2-butene-4-olide and phenol in tetrahydrofuran at, for example, -50 ° C. over a period of 10 minutes or more, and the mixture is further stirred for 1 hour. . Thereafter, the mixture is warmed to room temperature, washed with a 10% aqueous sodium carbonate solution to remove phenol, and extracted with ether. After drying the ether layer with sodium sulfate, the organic solvent is evaporated and the oily substance obtained is subjected to column chromatography with benzene to obtain β-phenylthio-γ-butyrolactone.

The above-mentioned production method has problems that butyllithium and tetrahydrofuran are expensive and that the phenol used for proceeding the above-mentioned reaction must be removed after the reaction, which complicates the process. doing.

[0009]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems of the conventional method, and to obtain novel β-phenylthio-γ-butyrolactones by a simple reaction process in a high yield. It is to provide a simple manufacturing method.

[0010]

According to the present invention, the expression

[0011]

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The 2-butene-4-olide of the formula HS-R (IV) wherein R represents a phenyl group optionally substituted by a substituent selected from the group consisting of halogen and lower alkyl. Characterized by reacting thiols of the formula with an organic base

[0013]

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[Wherein R has the meaning described above]
A process for preparing phenylthio-γ-butyrolactone is provided.

When R is a substituted phenyl group, examples of the substituent include halogen such as Cl, Br, F and I, and methyl, ethyl, n-propyl, iso-propyl,
n-butyl, iso-butyl, sec-butyl, ter
Lower alkyl such as t-butyl can be exemplified.

An example of a specific method of the present invention is as follows. That is, 2-butene-4- of formula (III)
Using an oride, a 2-butene-4-olide / benzene solution is added dropwise to a benzene solution of thiophenol and triethylamine under a stream of an inert gas such as nitrogen or argon, and the mixture is stirred and reacted at room temperature for 1 hour. After diluting the reaction solution with benzene, the benzene layer is treated with 10% hydrochloric acid and then washed with saturated saline. The benzene layer is dehydrated with anhydrous magnesium sulfate. The benzene layer is separated and purified by silica gel column chromatography, and the solvent is removed by evaporation to obtain 91% of 3-phenylthio-γ-butyrolactone (II).

Examples of the above organic base include, for example, benzene solutions of tertiary amines such as trimethylamine, triethylamine and trihexylamine. Examples of the inert organic solvent used for the reaction include aromatic hydrocarbons such as benzene and toluene;
Examples thereof include HF, dimethoxyethane, ethyl ether and a suitable mixture thereof.

The reaction is carried out at room temperature and does not require any particular heating or cooling. Preferably, a temperature condition of 10 to 30 ° C. can be exemplified. The amount of the tertiary amine used in the reaction can be appropriately selected, and examples thereof include an amount of about 1 to about 1.2 mol based on the compound of the formula (III). The amount of the R-SH thiol compound of the formula (IV) can also be appropriately selected, for example, about 1 to about 2 mol based on the compound of the formula (III).
Further, the amount of the solvent to be used can also be appropriately selected, and for example, the amount of the solvent to be used is about 30 to about 100 times by volume based on the compound of the formula (III).

The β-phenylthio-γ-butyrolactone of the formula (II) obtained by the present invention is oxidized and then subjected to a pummeler rearrangement reaction.

[0020]

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The 3-phenylthio-2-butene-4-olides of the present invention can be produced. As the oxidizing agent used for oxidizing the compound of the formula (II), m-chloroperbenzoic acid, sodium periodate, hydrogen peroxide and the like can be used.

Further, trifluoroacetic anhydride, acetic anhydride and the like can be used as reagents used in the Punmerel rearrangement reaction.

[0023]

According to the present invention, the novel β-phenylthio-γ-
In the process for producing butyrolactone, the starting materials used are inexpensive, the process is simple, and the target compound can be easily obtained in a high yield comparable to the conventional process, as compared with the conventionally known process.

[0024]

【Example】

Example 1 (a) Synthesis of compound (II) β-phenylthio-γ-butyrolactone In a nitrogen stream, thiophenol (R: phenyl) 0.6 was used.
50 g (5.9 mmol) and 0.510 of triethylamine
g (5.0 mmol) was dissolved in 15 ml of benzene, and a solution of 0.420 g (5.0 mmol) of 2-butene-4-olide in 5 ml of benzene was added dropwise to the solution, and the mixture was stirred at room temperature for 1 hour and reacted. Was done. 50m of benzene in the reaction solution
After diluting the mixture, the benzene layer is washed with 10% hydrochloric acid and then with a saturated saline solution. The benzene layer was dehydrated and dried with anhydrous magnesium sulfate. After the benzene was removed by evaporation, the residue was dissolved in benzene and separated and purified by silica gel column chromatography.

Β-phenylthio-γ-butyrolactone
0.88 g, 91% bp. 151-2 ° C./3 mmHg mp. 51-52 ° C (recrystallized from 2-propanol) (b) Synthesis of compound (I) 3-phenylthio-2-butene-4-olide In a nitrogen stream, 1.94 g of β-phenylthio-γ-butyrolactone (10 Mmol) in 50 ml of dichloromethane
And cooled to −50 ° C. A solution of 1.90 (11 mmol) of metachloroperbenzoic acid (m-CPBA) dissolved in 30 ml of dichloromethane was gradually added dropwise thereto, and the mixture was stirred at -50 ° C for 1 hour to carry out a reaction. After completion of the reaction, the reaction solution is washed with a saturated sodium hydrogen carbonate solution,
Further, it was washed with a 10% aqueous solution of sodium thiosulfate. After the dichloromethane layer was dehydrated and dried over anhydrous magnesium sulfate, the solvent was removed by evaporation to obtain a sulfoxide compound. The following pungmerel rearrangement reaction was performed without purifying this sulfoxide compound.

The above sulfoxide compound was treated with 8.40 g (40 mmol) of trifluoroacetic anhydride in a nitrogen stream.
And a catalytic amount of p-trienesulfonic acid (about 20 mg) were dissolved in 10 ml of toluene, and the mixture was stirred at 30 to 35 ° C. for 2 hours to carry out a reaction, and then heated to 60 to 70 ° C. for 2 hours 3
The mixture is stirred for 0 minutes to complete the Punmeler rearrangement reaction. After the completion of the reaction, the mixture was concentrated under reduced pressure.
The benzene layer was washed with a 5% aqueous sodium hydrogen carbonate solution, and then dried over anhydrous magnesium sulfate. After the benzene was removed by evaporation, the residue was separated and purified by silica gel column chromatography using a mixed solvent of benzene and ether (2: 1).

1.63 g of 3-phenylthio-2-butene-4-olide, 85% yield, mp. 46-48 ° C (recrystallized from petroleum ether) Elemental analysis: C ₁₀ H ₈ O ₂ S Calcd: C: 62.50, H: 4.20, S: 16.67 Found: C: 62.45, H: 4.37, S: 16.71 Table 1 shows other characteristics.

Examples 2 to 4 Instead of thiophenol (R: phenyl) of the compound of formula (IV), p-tolylthiol (R: p-methylphenyl), p-chlorothiophenol (p-chlorophenyl) and p-t Except for using -butylthiophenol (R: pt-butylphenyl), the procedure of Example 1 was followed to obtain the compounds shown in Table 1. Other physical data are also shown in Table 1.

[0029]

[Table 1]

 ──────────────────────────────────────────────────続 き Continuing from the front page (56) References References of Polymers, 32 (7), (1975), Tomohiko Asahara, “Selective polyaddition reaction of P-aminothiophenol and maleic anhydride”, p. 452-3 SYNTHESIS, 9, (1976), ISAO, KUWAJIMA, "QUA TERNARY FLUORIDE-C ATALYZED CONJUGATE ADDITION OF THIOL S TOC = C DOUBLE BONDS." 602-4

Claims (1)

(57) [Claims] (1) Formula (1) Of 2-butene-4-olide of the formula Wherein R represents a phenyl group which may be optionally substituted with a substituent selected from the group consisting of halogen and lower alkyl; and a trialkyl having 1 to 6 carbon atoms in each alkyl moiety. A compound characterized by reacting in the presence of at least one amine [Wherein R has the above-mentioned meaning] The process for producing β-phenylthio-γ-butyrolactones described in the above.