JPH0684369B2 - Method for producing 2- (disubstituted methylene) -1,3-dithiol compound - Google Patents

Description

Detailed Description of the Invention

[0001]

The present invention relates to 2- (disubstituted methylene)-
The present invention relates to a method for producing a 1,3-dithiol compound.

[0002]

2. Description of the Related Art Among sulfur-containing organic compounds, many compounds having physiological activity such as medical and agricultural chemicals and various functional compounds exhibiting specific behaviors against electricity, light and the like are known.
In creating these compounds, various chemically active intermediates are often used. It is already known that 1,3-dithiolium salts, which are a kind of heteroaromatic cation compounds, are highly reactive and lead to many derivatives by reaction with a nucleophilic reagent. 2- (Disubstituted methylene) -1,3-dithiols have already been obtained via 1,3-dithiolium salts. However, in the conventional method, the number of reaction stages is large, and when attempting to produce 2- (disubstituted methylene) -1,3-dithiols having various substituents, the reaction itself depends on the kind of the substituents. Be restricted.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method capable of economically producing a 2- (disubstituted methylene) -1,3-diol compound economically.

[0004]

The present invention has completed the present invention as a result of intensive studies to solve the above problems. That is, according to the present invention, the general formula (1)

[Chemical 3] (In the formula, R ¹ and R ² represent hydrogen or an inert substituent, and R ¹
And R ² may form a ring when the ends are bonded to each other, and a 1,3-dithiol-2-thione compound represented by the general formula (2) R ³ —CH ₂ —R ⁴ (wherein R ₂ ³ and R ⁴ represent an electron-withdrawing substituent) and a reactive methylene compound represented by the general formula (3) characterized by reacting in the presence of a silver salt and a base.

[Chemical 4] (In the formula, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above.)
A method for producing 2- (disubstituted methylene) -1,3-dithiols represented by is provided.

In the general formula (1) representing a 1,3-dithiol-2-thione compound, the substituents R ¹ and R ² represent hydrogen or an inert substituent. As the inert substituent, any group such as an alkyl group, a cycloalkyl group, an aryl group, an arylalkyl group, an alkoxy group, a cyano group, a carbamoyl group, an acyl group or an aroyl group can be used as long as it does not participate in the reaction. Good. The ends of R ¹ and R ² may combine to form a ring. An inert substituent may be further bonded to these substituents.

General formula used as a raw material in the present invention
Several production methods are known for the 1,3-dithiol-2-thione compound represented by (1). As the main one, a method of treating an O-alkyldithiocarboxylic acid β-ketoester obtained from phenacyl halide-xanthogenate with diphosphorus pentasulfide, acetylenes-carbon disulfide-sulfur in the presence of a base. High pressure method, 2-disubstituted amino
There is a method of causing hydrogen sulfide to act on a 1,3-dithiolium salt. Since either method can be used for relatively easy synthesis, a raw material having a desired substituent can be easily obtained.

In the general formula (2) representing an active methylene compound, R ³ and R ⁴ are electron withdrawing substituents,
Examples of such a substituent include a conventionally known one such as a carbamoyl group, an acyl group, an aroyl group, an alkoxycarbonyl group, a cyano group and a nitro group. Further, other inactive substituents may be bonded to these substituents. Specific examples of the active methylene compound include, for example,
Methyl cyanoacetate, malonic acid diester, β-diketones and the like can be mentioned. This active methylene compound is 1 to 2 mol per 1 mol of the 1,3-dithiol-2-thione compound,
It is preferably used in a proportion of 1 to 1.5 mol.

In the present invention, a 1,3-dithiol-2-thione compound and an active methylene compound are reacted in the presence of a silver salt and a base to give the desired 2- (disubstituted methylene) -1,3- A dithiol compound can be obtained. Examples of the silver salt include organic carboxylic acid silver salts, inorganic silver salts such as silver nitrate, silver tetrafluoroborate, and silver perchlorate. Specific examples of the organic carboxylic acid silver salt include silver benzoate, silver acetate, etc., but particularly from the viewpoint of solubility in an organic solvent, it is preferable to use a fluorine-containing organic carboxylic acid silver salt such as CF ₃ COOAg. preferable. The silver salt is used in the reaction system in an amount of 1 to 5 mol, preferably 2 to 3 mol, per 1 mol of the 1,3-dithiol-2-thione compound.

The base may be any base having a basic nitrogen atom in the molecule and includes fatty acid amines, aromatic amines and heterocyclic amines. Specific examples of such a base include triethylamine, N-methylpiperidine, quinoline, 4-dimethylaminopyridine and the like. Generally, a tertiary amine is preferably used as the base. In the reaction system, this base is 2 to 10 mol, preferably 4 to 1 mol, per 1 mol of the active methylene compound.
Used in a proportion of 5 mol.

Next, the reaction in the present invention is represented by the formula as follows. General formula (1) + general formula (2) + 2Ag + → general formula (3) + Ag ₂ S

In the reaction of the present invention, Ag + attacks the thiocarbonyl sulfur atom of the 1,3-dithiol-2-thione compound, and the reaction is initiated by withdrawing this, and a base- It is believed that the carbanion produced by the active methylene compound leads to the product by addition. Therefore, the presence of metal ions, which have a strong affinity for sulfur atoms, is essential for this reaction, with silver ions giving the most favorable results. The reaction is usually sufficient to be heated in a hot water bath, but may be further heated if necessary. In this case, the reaction temperature is 0 to 150.
C., preferably room temperature to 80.degree. In addition, the reaction time is usually 30 minutes to 5 hours, but if necessary, it may take longer. The reaction is usually carried out in an organic solvent, and any solvent can be used as long as it dissolves the components involved in the reaction, but water interferes with this reaction, and therefore it is preferable to carry out the reaction in an anhydrous reaction system. Examples of the organic solvent include acetonitrile, dimethylformamide, pyridine and the like. After completion of the reaction, the produced sulfide is removed by filtration, the filtrate is concentrated under reduced pressure and poured out into water, so that a crude product is often precipitated. Each crude product obtained is recrystallized and purified in the solvent of choice. The fact that the product thus obtained is a 2- (disubstituted methylene) -1,3-dithiol compound means that their melting point, elemental analysis, mass spectrometry (MS), infrared absorption spectrum (I
R) and nuclear magnetic resonance spectrum (NMR).

[0012]

EXAMPLES Next, the present invention will be described in more detail by way of examples. Example 1 To 5 ml of an acetonitrile solution in which 290 mg of 4,5-diphenyl-1,3-dithiol-2-thione and 450 mg of silver trifluoroacetate were dissolved, 120 mg of methyl cyanoacetate and 1 ml of triethylamine were added, and the mixture was heated in a water bath. After heating for 2 hours, the solvent of the reaction solution from which silver sulfide was removed by filtration was distilled off under reduced pressure. The obtained residue was washed with water and recrystallized from acetonitrile to give a melting point of 2
2-Cyano (methoxycarbonyl) methylene at 26-227 ℃
205 mg of -4,5-diphenyl-1,3-dithiol (yield 58%)
Got IR: 2200 (CN), 1676 (C = O), 1454 (C = C), 1307 (CO) cm
^-1 . MS: m / z 351 (M +). The elemental analysis results as C ₁₉ H ₁₃ NO ₂ S ₂ were as follows. Calculated value (%): C, 64.63; H, 3.73; N, 3.99;
S, 18,25 Measured value (%): C, 64.33; H, 3.77; N, 4.10;
S, 17.94

Example 2 4,5-Dimethoxycarbonyl-1,3-dithiol-2-thione 2
Acetonitrile 5 m containing 50 mg and silver nitrate 380 mg
l mg of malonnitrile and 1 ml of triethylamine
Was added, and the mixture was heated in a hot water bath for 0.5 hour, and then the precipitated silver sulfide was filtered off and the filtrate was poured out into water to obtain a crude product. Recrystallized from methanol and purified, melting point
254 mg of 2- (dicyanomethylene) -4,5-dimethoxycarbonyl-1,3-dithiol at 112-113 ℃ (yield 90%)
Obtained. IR; 2953 (CH). 2208 (CN), 1759 (C = O), 1446, 1429 (C
= C), 1263 (CO) cm ^-1 . MS: m / z 282 (M +). NMR: δ = 3.93 (s, -CH 3). The elemental analysis results as C ₁₀ H ₆ N ₂ S ₂ O ₄ were as follows. Calculated value (%): C, 42.55; H, 2.14; N, 9.92; S, 2
2.72 Measured value (%): C, 42.60; H, 2.12; N, 9.94; S, 2
2.82

Example 3 4,5- (Ethylenedithio) -1,3-dithiol-2-thione 23
While stirring 5 ml of a dimethylformamide solution in which 0 mg and 400 mg of silver tetrafluoroborate were dissolved, 200 mg of malonic acid diisopropyl ester and then triethylamine 1
After adding ml, the mixture was heated on a hot water bath for 2 hours, and the reaction solution from which the produced silver sulfide was removed by filtration was poured out into water. The crude product obtained was recrystallized from methanol and had a melting point of 111-112.
2- (diisopropoxycarbonylmethylene) -4,5-
(Ethylenedithio) -1,3-dithiol 130 mg (yield 40
%) Was obtained. IR: 2980 (CH), 1643 (C = O), 1421 (C = C), 173 (CO) cm < ^-1 >.
MS: m / z 378 (M +). The elemental analysis results for C ₁₄ H ₁₈ S ₄ O ₄ were as follows. Calculated value (%): C, 44.42; H, 4.79; S, 33.88 Measured value (%): C, 44.50; H, 4.98; S, 34.51

Example 4 4- (p-chlorophenyl) -1,3-dithiol-2-thione 250
200 mg of ethyl benzoylacetate and then 1 ml of triethylamine were further added while stirring 5 mg of an acetonitrile solution in which 450 mg of silver trifluoroacetate was dissolved. After heating this reaction solution at about 70 ℃ for 2 hours,
The produced silver sulfide was filtered off. When the obtained filtrate was poured out into water, a crude product was deposited. This was recrystallized from ethanol to give 230 mg (yield 57%) of 2-benzoyl (ethoxycarbonyl) methylene-4- (p-chlorophenyl) -1,3-dithiol having a melting point of 161-162 ° C.
IR: 3065 (CH), 2980 (CH), 1668 (C = O), 1402 (C = C),
1263 (CO) cm ^-1 . MS: m / z 402 (M +). NMR: δ = 0.84 (t, CH ₃ CH ₂ O
-), 4.03 (q, CH 3 CH 2 O-), 7.21~7.62 (m, Arom.H). The elemental analysis result as C ₂ H ₁₅ S ₂ O ₃ was as follows. Calculated value (%): C, 59.62; H, 3.75; S, 15.92 Measured value (%): C, 59.69; H, 3.67; S, 15.83

Example 5 4,5-Dimethyl-1,3-dithiol-2-thione 170 mg and 1,3-
Indandione 150 mg was heated with silver trifluoroacetate and triethylamine in an acetonitrile solvent in the same manner as in Example 4, and the obtained crude product was recrystallized from acetonitrile. 1,3-
Dioxoindanylidene) -4,5-dimethyl-1,3-dithiol was obtained almost quantitatively. IR: 1653 (C = O), 1473 (C = C) cm < ^-1 >. MS: m / z 274 (M
+). The results of elemental analysis as C ₁₄ H ₁₀ S ₂ O ₂ were as follows. Calculated value (%): C, 61.29; H, 3.67; S, 23.73 Measured value (%): C, 61.38; H, 3.61; S, 24.00

[0017]

INDUSTRIAL APPLICABILITY Among the 2- (disubstituted methylene) -1,3-dithiols, compounds having nonlinear optical activity and compounds having physiological activity as therapeutic agents for liver diseases are also known.
However, in the conventional method for obtaining them, first,
A two-step reaction was required in which the 3-dithiol-2-thiones were first treated with an alkylating agent such as methyl iodide or dimethyl sulfate, followed by reaction with an active methylene compound. According to the present invention utilizing a silver salt, 1,3-dithiol-2
-The target product can be easily and directly produced from a thione compound, and in this respect, the industrial significance of the present invention is great.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁵ Identification number Internal reference number FI Technical indication location C07B 61/00 300 (72) Inventor Yoichi Taguchi 1-chome Higashi 1-chome, Tsukuba-shi, Ibaraki Industrial Technology Chemical Technology (72) Inventor Toru Tsuchiya 1-1, Higashi, Tsukuba-shi, Ibaraki Industrial Technology Institute, Institute of Chemical Technology (72) Inventor Masahiro Mizuno 1-1-1, East, Tsukuba City, Ibaraki Institute of Chemical Technology, Institute of Industrial Technology

Claims (2)

[Claims] 1. A general formula: (In the formula, R ¹ and R ² represent hydrogen or an inert substituent, and R ¹
And R ² may combine with each other to form a ring), and a 1,3-dithiol-2-thione compound represented by the general formula R ³ —CH ₂ —R ⁴ (wherein R ³ and R 2 ⁴ represents an electron-withdrawing substituent), and is reacted with an active methylene compound represented by the formula (I) in the presence of a silver salt and a base. (In the formula, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above.)
A method for producing 2- (disubstituted methylene) -1,3-dithiols represented by: 2. The method of claim 1, wherein the reaction is carried out in an anhydrous solvent.