JPS603395B2 - Method for producing 1,3-dithio-l-2-ylidene malonic acid esters - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 1,3-dithiol-2-ylidene malonic acid esters.

1,3-dithiol-2-ylidene malonic acid esters are known compounds useful as agricultural and horticultural fungicides and liver disease therapeutic agents.

For example, the following method is known as a method for synthesizing 1,3-dithiol-2-ylidene malonic acid esters using a malonic acid ester derivative as one of the synthetic raw materials: 01 Corresponding 4-hydroxy-1,3-dithiolane A method for dehydrating -2-ylidene malonate ester (JP-A-51-48667) (wherein R and R may be the same or different and represent an organic residue capable of forming an ester.

same as below. ) (2) A method of reacting the corresponding dioxycarbonylketene dimercaptides with cis-1,2-dihalogenoethylene in a polar aprotic solvent (
No. 4-63085) (wherein, M' is an alkali metal atom,
X represents a halogen atom.

) In the method of [1}, the 4-hydroxy-1,3-dithiolane derivative of the starting compound must be separately synthesized using a ketene mercaptide represented by the formula (b') as one of the starting materials.

Therefore, method '1} has the disadvantage that the process is longer than method {2}. On the other hand, the cis-1,2-halogenoethylene used in method '2) is not commercially available as an industrial raw material, so it needs to be specially synthesized, which makes it expensive, and it is also difficult to collect with high purity. There is also the problem of isomerization, and all known methods have room for improvement from a technical or economical point of view. The present inventors have recently discovered that the compound represented by the general formula (b) obtained by the reaction of malonic acid ester and carbon disulfide reacts with 1,1-dihalogenoethylene and undergoes 1,3-dithiol-2 -I learned to give iridenmalonate.

This reaction can be represented diagrammatically as follows:
(In the formula, M represents an alkali metal atom, R and R2 represent a lower alkyl group, and x represents a halogen atom.

). By the way, the compound represented by the general formula (U) can be synthesized by a known method (where R, ,
R2 and M are the same as above. ). General formula (0
) The type of salt of the compound represented by is derived from the type of base used in the reaction of malonic acid ester and carbon disulfide, as is clear from reaction route 4 shown schematically above. In the present invention, any salt that is reactive with 1,1-dihalogenoethylene may be used. Typical salts include dipotassium salt and disodium salt. Other diammonium salts can also be used in the method of the invention. The ester moiety of the compound represented by formula (0) is derived from the malonic acid ester subjected to the reaction (2) above, and can represent a lower alkyl group.

In this case, the two lower alkyl groups may be the same or different. Examples of lower alkyl groups include methyl, ethyl, n-propyl, and isof. Includes lopyl, n-butyl, isobutyl, sec-butyl, tertiary-butyl groups, and the like. Therefore, the formula (
The compounds represented by 0) include, for example, compounds represented by the general formula (b) derived from the following malonate esters: dimethyl malonate, diisopropyl malonate, jetyl malonate. , di-n-propyl malonate, di-n-butyl malonate, diisobutyl malonate, di-tert-butyl malonate, di-t-butyl malonate, methyl ethyl malonate, methyl malonate , isopropylester, methyl malonate, n-
Propyl ester, ethyl malonate, isopropyl ester, methyl malonate, isobutyl ester, ethyl malonate, n-butyl ester, etc. A typical malonate ester is diisopropyl malonate, and therefore typical examples of compounds represented by general formula (b) include: diisoproboxycarbonylketene disodium merca Light yellow crystals with a melting point of 18 qC or more (yellowing) and diisoproboxycarbonyl keran Dibotacium mercaptide Pale yellow crystals that change color while foaming with 102 to 109 qC and turn black and decompose at 300 qC or more Used in the present invention For the 1,1-dihalogenoethylene,
Includes 1,1-dichloroethylene and 1,1-dipromoethylene.

Method '31 of the present invention can be carried out by reacting the compound represented by the general formula (b) with 1,1-dihalogenoethylene.

Although this reaction is an equimolar reaction, more of either reactant may be used. For example, 1,1-dihalogenoethylene is used in an amount of 1 mole of the compound represented by the general formula (0).
It is used in a proportion of ~8 mol, preferably 1-3 mol.

This reaction is carried out in a solvent that does not inhibit the progress of the reaction. Especially organic solvents such as dimethyl sulfoxide,
Preferably, N-methylpyrrolidone, dimethylformamide, dimethylacetamide, hexamethylphosphoric acid amide, sulforane (tetrahydrothiophene-1,1-dioxide), and the like are used. Among them, dimethyl sulfoxide is a good example. In addition, in the present invention, the polar organic solvent has solvent ability even when mixed with water, so
The reaction can also be carried out in polar organic solvents.

The reaction temperature can be set as appropriate, for example, from around 1,000 ℃ to the boiling point of the solvent, but usually from room temperature to 8 ℃.
If you react between 0:00 and 00:00, you can achieve your goal. After the reaction is completed, the target product can be isolated according to a conventional separation method.

For example, the target product can be obtained by extracting the target product from the reaction contents using an appropriate extraction solvent and removing the solvent using an appropriate method. Incidentally, even if the compound represented by the general formula (0) is not particularly isolated, it is possible to directly subject it to the ring-closing reaction as it is in the reaction solution during the synthesis of the compound represented by the general formula (b). It turned out that. This method will be explained below. When malonic acid ester is reacted with carbon disulfide in the presence of a base, the compound represented by the general formula (0) can be obtained almost quantitatively.

The compound represented by the general formula (0) can be obtained in an alkaline aqueous solvent (Japanese Patent Application Laid-Open No. 48-9911 and 50-24265), or in a polar solvent (Japanese Patent Application Laid-Open No. 49-13174). Here, the present invention provides a method for synthesizing 1,3-dithiol-2-ylidene malonate by reacting malonic acid ester with carbon disulfide in the presence of a base and then reacting with 1,1-dihalogenoethylene. It also provides the following.

As the solvent for this reaction, it is convenient to use a polar organic solvent or a mixed solvent system of a polar organic solvent and water. The water in this case generally originates from an aqueous solution of a base. Typical examples of the basic substance include sodium hydroxide and potassium hydroxide, but ammonium bases can also be used. The amount of the base may be about 2 to 3 moles per mole of malonic acid ester. Since the reaction between malonic acid ester and carbon disulfide is an exothermic reaction, it is initially carried out at a temperature below 30°C, and then
The reaction may be carried out at about 0 to 80 oo. Carbon disulfide may be used in a proportion of 0.9 to 1.2 moles per mole of malonic acid ester. The method of the present invention includes, but is not limited to, the following embodiments: ■ Required amounts of malonic acid ester, carbon disulfide, and 1,1-dihalogenoethylene are collectively placed in one container together with a gutter solvent. , A method of reacting by adding the required amount of an aqueous base solution to this:■ Take the required amount of malonic acid ester and carbon disulfide in a polar organic solvent,
A method of reacting by adding an aqueous solution of a base to this and then adding 1,1-dihalogenoethylene alone or dissolved in a polar organic solvent; ■ An aqueous solution of a base to a mixture of the required amount of malonic acid ester and carbon disulfide and then 1,1
A method of reacting by adding a polar organic solvent containing the required amount of -dihalogenoethylene; after the reaction is completed, the desired product may be isolated by the method described above.

The compounds shown below are representative compounds that can be synthesized by the method of the present invention.

EXAMPLES Next, examples will be shown, but the present invention is not limited thereto.

Example 1 18.8 mol of diisopropyl malonate (0.1 mol),
When 7.6 units (0.1 mol) of carbon disulfide is dissolved in 200 units of dimethyl sulfoxide and 40 units (0.25 mol) of a 35% aqueous potassium hydroxide solution is added dropwise at 13 to 17 units,
A pale yellow-red solution containing diisoproboxycarbonylketene dibotacium mercaptide is obtained.

To this solution was added 20 qo of 1,1-dichloroethylene 14.
Add 4 mol (0.15 mol) and slowly lower the temperature to 7 mol after addition.
Raise the temperature to 0°C and allow to react for 30 minutes. After the reaction, the contents were placed in ice water, extracted with benzene, dried over anhydrous magnesium sulfate, and distilled off to remove diisopropyl 1,3
-dithiol-2-ylidene malonate is obtained. Recrystallization from ligroin yields 21.6 ml. Yield 75%, melting point 60.5 qo Example 2 Diisopropyl malonate 18.8 mol (0.1 mol),
7.6 moles (0.1 mol) of carbon disulfide and 14.4 moles (0.15 mol) of 1,1-dichloroethylene were dissolved in 100 moles of dimethyl sulfoxide, and 40 moles (0.25 moles) of 35% potassium hydroxide aqueous solution was dissolved. mol) dropwise.

The reaction was carried out for 30 minutes while maintaining the reaction temperature, which increases due to the reaction heat, at around 60:00. After the reaction is complete, the contents are poured into ice water, extracted with benzene, dried over anhydrous magnesium sulfate, and the benzene is distilled off to obtain the desired product. Recrystallization from n-hexane gives 24.2%. Yield 84% Example 3 Diisopropyl malonate 18.8 mol (0.1 mol),
While cooling 7.6 moles (0.1 mole) of carbon disulfide to below 20°C, 31 moles (0.25 mole) of 45% potassium hydroxide aqueous solution was added.
mol) slowly dropwise.

Claims (1)

[Claims] 1 General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, M represents an alkali metal atom, R_1 and R_
2 represents a lower alkyl group which may be the same or different. ) and 1,1-dihalogenoethylene, the general formula (I)▲mathematical formula,
There are chemical formulas, tables, etc. ▼ (In the formula, R_1 and R_2 are the same as above.) A method for producing 1,3-dithiol-2-ylidene malonate. 2. The manufacturing method according to claim 1, which comprises reacting in a mixed solution of water and a polar organic solvent. 3. The manufacturing method according to claim 2, wherein the polar organic solvent is dimethyl sulfoxide. 4. In the presence of a base, a malonic acid ester represented by the general formula (III) (wherein R_1 and R_2 may be the same or different and represent a lower alkyl group) is reacted with carbon disulfide, and then 1, 1,3-dithiol- represented by the general formula (I), which is characterized by reacting with 1-dihalogenoethylene (there are mathematical formulas, chemical formulas, tables, etc.) (in the formula, R_1 and R_2 are the same as above) Method for producing 2-ylidene malonate. 5. The manufacturing method according to claim 4, which comprises reacting in a mixed solution of water and a polar organic solvent. 6. The manufacturing method according to claim 5, wherein the polar organic solvent is dimethyl sulfoxide. 7. The manufacturing method according to claim 5, wherein the malonic acid ester is malonic acid diisopropyl ester.