JPS6056689B2 - Production method of cis-2-cycloalkene-1,4-diol - Google Patents

Description

[Detailed description of the invention] The present invention relates to general formula (I) C (CH.

) n(I) (wherein, n represents an integer of 1 or 2).

) is related to a method for producing cis-2-cycloalkene-1,4-diol. Conventionally, as a method for synthesizing cis-2-cycloalkene-1,4-diol related to the present invention, for example, G. O.
henk) etc.
Em, Vol. 68, p. 248, 195:00] reported a synthetic method represented by the following formula.

o:o... (i.e., photo-oxidizes cyclopentadiene to produce 1 as an intermediate,
4-epidioxy-2-cyclopentene is isolated and then reduced with thiourea to synthesize the desired cis-2-cyclopentene-1,4-diol.

According to this known method, the reaction is carried out in two steps: the first step photooxidation reaction is carried out at a low temperature of -100°C to isolate the unstable 1,4-epidioxy intermediate; In two steps, this intermediate is reduced with thiourea to obtain the target compound. Therefore, large-scale synthesis is difficult using this known method due to temperature conditions and other considerations. Furthermore, the present inventor has previously proposed a method of photooxidation in the presence of a reducing agent in one step, which is not performed in conventional synthetic methods, and has filed a patent application.

That is, 1, which is an unstable initial reaction product in many cases,
, 4-epidioxy compound is immediately converted into the corresponding cis-1,4-diol compound by the action of the coexisting reducing agent, so only the target compound can be selectively obtained in high yield under milder conditions than in the above-mentioned known methods. Therefore, we have provided a method that can be synthesized on a large scale. However, there are many points to be improved, such as the yield, and as a result of more detailed study, it was discovered that more favorable results could be obtained by using a thioamide compound, and the present invention was completed.

The compound having the general formula (1) obtained by the method of the present invention is a compound useful as a raw material for the synthesis of 2-cyclopentenone-4-ol, 2-cyclopentene-1,4-dione or prostaglandin derivatives. It is.

According to the method of the present invention, the compound represented by the general formula (1) is obtained by the general formula (where n has the same meaning as defined above).

) is obtained by irradiating a cycloalkane-1,3-diene compound represented by the following formula with light in the presence of oxygen, a sensitizer and a thioamide compound. In carrying out the method of the present invention, the reaction is achieved by photooxidizing the compound represented by the general formula (■) in a solvent in the presence of a thioamide compound.

Singlet oxygen for carrying out the photo-oxidation reaction can be generated by irradiating oxygen gas introduced into a reaction vessel in the presence of a stimulant with various types of visible light. The stimulants used include pigments such as rose bengal, methylene blue, chlorophyll, and hematoporphyrin, and the light sources used include, if necessary, UV rays blocked by Pyrex glass or the like. Examples include incandescent lamps, mercury lamps, sodium lamps, and various halogen lamps. A thioamide compound represented by the formula (■) is used as the thioamide compound that is added at the same time to generate the target diol from the peroxide generated by photooxidation.

(In the formula, R represents hydrogen, an alkyl group having 1 to 4 carbon atoms, or a phenyl group.

) Also, the solvent used in the reaction is not particularly limited as long as it does not affect the reaction, and examples include alcohols such as methanol, ethanol, and isopropanol, and ethers such as diethyl ether, tetrahydrofuran, and dioxane. , ketones typified by acetone, nitriles such as acetonitrile, probionitrile, and butyronitrile, alkyl halides such as methylene chloride, carbon tetrachloride, and carbon disulfide.

Moreover, any mixtures of these solvents can be used if necessary. In addition, combinations of these solvents and thioamide compounds, for example, combinations of thioamide compounds and aprotic solvents suitable for photosensitized oxidation reactions, such as alkyl halides, are effective because the solubility of thioamide is higher than that of thiourea. It has the advantage that not only the amount used can be significantly reduced, but also the reaction time can be significantly shortened.

The reaction is usually carried out at 0°C to around room temperature, and is particularly preferably carried out at around room temperature. The time required for the reaction varies mainly depending on the reaction temperature, the type of raw material compound, the size of the reaction vessel, as well as the selection of the thioamide compound and solvent, but is approximately 0.5 to 2 hours. After the reaction is completed, the target compound is collected from the reaction mixture according to a conventional method. For example, the target compound can be obtained by distilling off the solvent from the reaction mixture, followed by extraction with water or a suitable organic solvent, washing the extract, and distilling off the solvent from the extract. The target compound thus obtained can be further purified, if necessary, by conventional methods such as vacuum distillation, recrystallization, column chromatography, etc.

Example 1 Cis-2-cyclopentene-1,4-diol Rose Bengal (RO
Se? n? 60m9 and thioacetamide 9y (0.
12 mol) was added to the reaction mixture, oxygen gas was introduced into the reaction mixture for 5 minutes, and then Pyrex (Pyr
ex) 450W high pressure mercury lamp (HanOvi) through glass
679A-36) manufactured by A company is irradiated for 2.5 hours.

During this time, the mercury lamp was cooled with running water.

The temperature of the reaction mixture at this time is around 20-25°C.
After that, the introduction of oxygen gas and irradiation were stopped, the post-reaction liquid was filtered, the solvent was distilled off from the bottom liquid under reduced pressure, and the residue was
After washing the aqueous layer three times with 100 cc of benzene, the water was distilled off from the aqueous layer under reduced pressure, and the residue was distilled under reduced pressure to obtain the desired colorless oil with a boiling point of 100 to 107 C/1.3 mHg. Compound 8.5y (yield 85%, 0.0
85 mol) was obtained. After cooling, this product crystallizes, and when recrystallized from acetone, it becomes crystals with a melting point of 59-60'C. This was mixed with a sample of cis-2-cyclopentene-1,4-diol to confirm its structure. Example 2
~5 Among the operating conditions such as raw materials, reaction, and post-treatment in Example 1, the thioamide compound, molar ratio,
Synthesis was carried out according to Example 1, except for the reaction solvent, reaction temperature, and reaction time.

The synthesis results are shown in Table 1. Example 6 Cis-2-cyclohexene-1,4-diol 1,3-
Cyclohexadiene 6y (0.075 mol) was dissolved in 300 cc of acetone, and methylene blue 100
After adding m9 and thioacetamide 6.9y (0.09 mol), the temperature of the reaction mixture was increased to about 30 ml as in Example 1.
A 450W high-pressure mercury lamp (HanOvia 6
Using a 79A-3 Pyrex filter), irradiate with light for 4 hours while introducing oxygen gas.

After distilling off the solvent under reduced pressure, it was dissolved in 150 cc of water, the aqueous layer was washed three times with 100 cc of benzene, the water was distilled off from the aqueous layer under reduced pressure, and then subjected to vacuum distillation to a boiling point of 105 to 107 pressure C/1.
．． Fraction 6.9y with 3wrInHg (80% yield)
was obtained as the target compound. When this fraction is recrystallized from acetone, white crystals having a melting point of 57-59°C are obtained. This product mixed and melted with the standard product of cis-2-cyclohexene-1,4-diol, and their melting points matched. Example 7 Among the operating conditions such as reaction and post-treatment in Example 6, the second
Synthesis was carried out according to Example 6, except that the thioamide compound, molar ratio, reaction solvent, reaction temperature, and reaction time were used as described in the table.

The results are shown in Table 2.

Claims (1)

[Claims] 1 A cycloalkane-1,3-diene compound represented by the general formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, n represents an integer of 1 or 2.) General formula (I) ▲Mathematical formula, chemical formula,
There are tables, etc.▼(I) Method for producing cis-2-cycloalkene-1,4-diol represented by (in the formula, n represents an integer of 1 or 2). 2 The thioamide compound has the general formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (in the formula, R
represents hydrogen, an alkyl group having 1 to 4 carbon atoms, or a phenyl group. ) The method according to claim 1, wherein the thioamide compound is a thioamide compound represented by: