JPH0552313B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention is based on the general formula (In the formula, R ¹ represents a cyclic or chain alkenyl group which may have a substituent or an alkyl group having an ether group, R ² and R ³ are each the same or different, and are hydrogen atoms or lower alkyl and R ⁴ represents a phenyl group or a tolyl group.) γ-(Arenesulfonylmethyl)-γ
-Relating to butyrolacrone derivatives. The γ-(arenesulfonylmethyl)-γ-butyrolactone derivatives represented by the general formula () provided by the present invention are (2E, 4E, 6E, 8E)- 3,7-
Dimethyl-9-(2,6,6-trimethyl-cyclohexenyl)-2,4,6,8-nonatetraenoic acid (vitamin A acid), (2E, 4E, 6E, 10E,
14E)-3,7,11,15-tetramethyl-2,4,
6,10,14-hexadecapentenoic acid, (2E,
4E, 6E, 8E)-3,7-dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,
All-trans forms of polyenoic acids such as ethyl 4,6,8-nonatetraenoate (etretinate) and (2E,4E)-11-methoxy-3,7,11-trimethyl-2,4- useful as an insect growth regulator It is useful as an intermediate for the synthesis of all-trans isomers of dieno acids such as isopropyl dodecadienoate (methoprene). [Prior art] Conventionally, (2E, 4E, 6E, 8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoic acid (vitamin A acid), (2E, 4E, 6E, 10E, 14E) −
3,7,11,15-tetramethyl-2,4,6,
10,14-hexadecapentenoic acid, (2E,4E)-
11-methoxy-3,7,11-trimethyl-2,4
- All-trans isomers of polyenoic acids such as isopropyl dodecadienoate (methoprene) are produced by the following method. (1) Method using Wittig reaction (Refer to Special Publication No. 36-16023) (Refer to Japanese Patent Application Laid-Open No. 140949/1983) (Refer to JP-A-56-140949) (2) Method of using sulfone and 4-halogeno-2-alkenoic acid as raw materials (Refer to JP-A-56-140949) (3) Method using aldehyde and propene-1,3-dicarboxylic acid ester as raw materials [The Journal of Organic Chemistry]
[See Chemistry] Volume 40 (1975), pages 1 to 7.] [Problems to be solved by the invention] The above-mentioned conventional method does not require the use of all-trans isomer or This method is not necessarily satisfactory from the viewpoints of high stereoselectivity to all-trans isomer of polyenoic acid ester, high yield of target polyenoic acids, and ease of operation. Therefore, the object of the present invention is to provide a novel polyenoic acid which can be easily produced with good yield from easily available industrial raw materials, and which can be easily derived from all-trans forms of polyenoic acids with high stereoselectivity and good yield. The objective is to provide compounds that are [Means for Solving the Problems] According to the present invention, the above object is achieved by providing a γ-(arenesulfonylmethyl)-γ-butyrolactone derivative represented by the general formula (). R ¹ , R ² , R ³ and
Let's explain R ⁴ in detail. R ¹ represents a cyclic or chain alkenyl group which may have a substituent or an alkyl group having an ether group. Examples of such cyclic alkenyl groups include 1-cyclohexenyl group, 2,6,6-trimethyl-1-cyclohexenyl group, etc., and examples of chain alkenyl groups include vinyl group, allyl group, 1-cyclohexenyl group, etc. -propenyl group, isopropenyl group, 2-methyl-1-
Propenyl group, 1-pentenyl group, 1-undecenyl group, 2,6-dimethyl-1,5-heptadienyl group, 2,6,10-trimethyl-1,5,9-
Examples of the alkyl group include undecatrienyl group, and examples of the alkyl group include methyl group, ethyl group, propyl group, pentyl group, hexyl group, heptyl group,
Examples include 2,6-dimethylheptyl group. The substituents that the chain alkenyl group may have are:
For example, cyclic alkenyl groups such as cyclohexenyl group and trimethylcyclohexenyl group; phenyl group, tolyl group, xylyl group, methoxyphenyl group, methoxytrimethylphenyl group, methylenedioxyphenyl group, hydroxyphenyl group, etc. A phenyl group which may have at least one substituent selected from the group consisting of a lower alkyl group, a lower alkoxyl group, a methylenedioxy group and a hydroxyl group; an aromatic heterocyclic group such as a furyl group and a pyridyl group; be. Chain alkenyl groups having such substituents include 2-methyl-4-(2,6,
6-trimethyl-1-cyclohexenyl)-1,
3-butadienyl group, 2-methyl-4-phenyl-1,3-butadienyl group, 2-methyl-4-
(4-methoxy-2,3,6-trimethylphenyl)-1,3-butadienyl group, 2-methyl-4
-(3,4-methylenedioxyphenyl)-1,3
-butadienyl group, 4-(p-hydroxyphenyl)-2-methyl-1,3-butadienyl group, 2
-Methyl-4-(2-furyl)-1,3-butadienyl group, 2-methyl-4-(3-pyridyl)-1,
Examples include 3-butadienyl group. Examples of the ether group include methoxy group, ethoxy group,
Methylenedioxy group, ethylenedioxy group, trimethylenedioxy group, tetrahydropyran-2-
Examples include yloxy group. Such alkyl groups having an ether group include 2-(tetrahydropyran-2-yloxy)ethyl group, 7-(tetrahydropyran-2-yloxy)heptyl group, 2,6-dimethyl-6-methoxybutyl group,
Examples include 1,3-dioxolan-2-ylmethyl group. R ² and R ³ are the same or different and represent a hydrogen atom; or a lower alkyl group such as a methyl group, an ethyl group, a propyl group, a butyl group, and R ⁴ represents a phenyl group or a tolyl group. The γ(arenesulfonylmethyl)-γ-butyrolactone derivative represented by the general formula () can be easily produced, for example, by the following method. (In the formula, R ¹ , R ² , R ³ and R ⁴ are as defined above, and R ⁵ represents a lower alkyl group.) That is, in the arenesulfone derivative represented by the general formula (), the arenesulfone Organolithium compounds such as butyllithium and phenyllithium in an amount of about 0.5 to 1.2 molar equivalents relative to the derivative; bases such as Grignard reagents such as ethylmagnesium bromide and methylmagnesium chloride in tetrahydrofuran,
The arenesulfone derivative is treated in an inert solvent such as an ether solvent such as diethyl ether or dimethoxyethane; or a hydrocarbon solvent such as toluene or hexane at a temperature in the range of about -78°C to about 50°C. By reacting about 0.5 to 1.2 molar equivalents of the formyl ester derivative represented by the general formula () at a temperature in the range of about -78°C to about 0°C, the hydroxyester derivative represented by the general formula () can be obtained. A catalytic amount of the hydroxyester derivative represented by the general formula () thus obtained is
- In the presence of an acid such as toluenesulfonic acid, sulfuric acid, or a strongly acidic ion exchange resin, in an inert solvent such as benzene or toluene, the reaction is heated to about 70°C to about 150°C, resulting in the reaction represented by the general formula (). A γ-(arenesulfonylmethyl)-γ-butyrolactone derivative can be produced. The γ-(arenesulfonylmethyl)-γ-butyrolactone derivative represented by the general formula () can be produced, for example, in the all-trans form of the polyenoic acid represented by the general formula () with high stereoselectivity and good yield by the following method. be guided by. (In the formula, R ¹ , R ² , R ³ and R ⁴ are as defined above.) That is, the γ-(arenesulfonylmethyl)-γ-butyrolactone derivative represented by the general formula () is combined with the γ- (Arenesulfonylmethyl)-γ
- about 2 to 20 molar equivalents of potassium t-butoxy, potassium methoxy to the butyrolactone derivative,
By treatment with a base such as an alkali metal alcoholate or hydroxide such as potassium hydroxide, the all-trans form of polyenoic acid represented by the general formula () can be obtained. This reaction is preferably carried out in an inert solvent, such as an alcoholic solvent such as t-butyl alcohol;
Hydrocarbon solvents such as toluene and cyclohexane are used. It is also preferred that the reaction be carried out at a temperature in the range of about 0°C to about 80°C. Further, the all-trans form of the polyenoic acid represented by the general formula () can be easily induced into the all-trans form of the corresponding polyenoic acid ester by reacting with alcohol. The esterification reaction is carried out, for example, in the presence of about 1.0 molar equivalent of N,N'-dicyclohexycarbodiimide and a catalytic amount of 4-(dimethylamino)pyridine and/or its hydrochloride based on the all-trans isomer of the polyenoic acid. The process is preferably carried out in an inert solvent at a temperature ranging from about 0°C to about 50°C. Examples of such inert solvents include halogenated hydrocarbon solvents such as dichloromethane dichloroethane and chloroform; aromatic hydrocarbon solvents such as benzene and toluene; ether solvents such as diethyl ether and tetrahydrofuran; and esters such as ethyl acetate. A system solvent or the like is used. [Examples] The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples. Example 1 (3-methyl-2-butenyl) under nitrogen atmosphere
In a solution consisting of 1.05 g (5 mmol) of phenyl sulfone and 10 ml of tetrahydrofuran, a concentration of 15 g/100
2.56 ml (6 mmol) of butyllithium in hexane was added dropwise at -30°C, and after 1 hour, the reaction mixture was cooled to -78°C and 0.65 g (5 mmol) of ethyl 4-oxobutyrate and 2 ml of tetrahydrofuran were added. A solution consisting of was added dropwise. After finishing dropping,
After continuing stirring at −78° C. for an additional 0.5 hour, the reaction mixture was poured into dilute hydrochloric acid and extracted with diethyl ether. The ether extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and then low-boiling substances were distilled off under reduced pressure. The crude 4-hydroxy-
Ethyl 7-methyl-5-benzenesulfonyl-6-octenoate was dissolved in 10 ml of benzene, a catalytic amount of p-toluenesulfonic acid was added, and the mixture was heated under reflux for 4 hours. The resulting reaction solution was washed successively with aqueous sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, and then low-boiling substances were distilled off under reduced pressure. By separating and purifying the obtained residue using silica gel column chromatography, 1.21 g of 7-methyl-5-benzenesulfonyl-6-octen-4-olide having the following NMR spectrum was obtained (yield: 82 %). NMR spectrum (60MHz) δ ^TMS _CCl4 : 1.29 (br.s, 3H); 1.69 (br.s, 3H); 2.18-2.54 (m, 4H); 3.82-4.24 (m, 1H); 4.82-5.27 (m , 2H); 7.30-7.88 (m, 5H) Examples 2-3 In Example 1, 5 mmol each of 2-dodecenyl phenyl sulfone or 2-(1,3-dioxolan-2-yl)ethyl phenyl sulfone was used instead of 5 mmol of (3-methyl-2-butenyl) phenyl sulfone. 5-benzenesulfonyl-6-hexadecen-4-olide or 6-benzenesulfonyl-6-hexadecen-4-olide or 6-
(1,3-dioxolan-2-yl)-5-benzenesulfonyl-4-hexanoid was obtained. Table 1 shows the yield and NMR spectrum of each γ-(arenesulfonylmethyl)-γ-butyrolactone derivative.

[Table] Examples 4 to 16 Under a nitrogen atmosphere, a hexane solution of butyllithium at a concentration of 15 g/100 ml was added to a solution consisting of 5 mmol of an arenesulfone derivative in which R ¹ is a group shown in Table 2 and R ⁴ is a phenyl group in the general formula () and 10 ml of tetrahydrofuran. ml (butyl lithium 6 mmol) [4.7 ml (butyl lithium 11 mmol) only in the case of Example 16] was added dropwise at -30°C, and 1
After an hour, the reaction mixture was cooled to -78 DEG C. and a solution consisting of 0.65 g (5 mmol) of methyl 3-methyl-4-oxobutyrate and 2 ml of tetrahydrofuran was added dropwise. After the dropwise addition was completed, stirring was continued for an additional 0.5 hour at -78°C, and then the reaction mixture was poured into diluted hydrochloric acid and extracted with diethyl ether. The ether extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and then low-boiling substances were distilled off under reduced pressure. The resulting residue was dissolved in 10 ml of benzene, and a catalytic amount of p-toluenesulfonic acid was added (5.01 mmol in the case of Example 14 only).
of p-toluenesulfonic acid) was heated to reflux for 4 hours. The resulting reaction mixture was washed successively with aqueous sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, and then low-boiling substances were distilled off under reduced pressure. By separating and purifying the obtained residue using silica gel column chromatography, in each general formula (), R ¹ is a group shown in Table 2 and R ²
A γ-(arenesulfonylmethyl)-γ-butyrolactone derivative in which is a methyl group, R ³ is a hydrogen atom, and R ⁴ is a phenyl group was obtained. Table 2 shows the yield and FD mass spectrum of each γ-(arenesulfonylmethyl)-γ-butyrolactone derivative.

【table】

〔Effect of the invention〕

As is clear from the above examples, the γ-(arenesulfonylmethyl)-γ-butyrolactone derivative of the present invention represented by the general formula () can be easily produced in good yield from readily available industrial raw materials. can. Furthermore, γ-(arenesulfonylmethyl)-γ- represented by the general formula () of the present invention
As is clear from the above reference examples, butyrolactone derivatives can be easily derived into all-trans isomers of polyenoic acids with high selectivity and good yield.

Claims (1)

[Claims] 1. General formula (In the formula, R ¹ represents a cyclic or chain alkenyl group which may have a substituent or an alkyl group having an ether group, R ² and R ³ are each the same or different, and are hydrogen atoms or lower alkyl and R ⁴ represents a phenyl group or a tolyl group.) γ-(Arenesulfonylmethyl)-γ
-Butyrolactone derivatives.