JPH0222073B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is useful as a synthetic intermediate, such as 5,7-octadien-4-one or 9,11-tridecadien-8-one, which is useful in the production of carotenoids and prostaglandins, etc.
Furthermore, 2,2-di-substituted compounds, which have not been previously described in the literature, exhibit physiological activity by themselves and are expected to be useful as bactericides and insecticides in the fields of medicine, agriculture, and horticulture.
This invention relates to 5-unsubstituted or 2,2-disubstituted-5-alkyl-substituted-2,5-dihydrothiophene-1,1-dioxides and their production method. More specifically, the present invention is based on the following formula () However, in the formula, R ₁ is an alkyl group, preferably C ₁ to C ₁₂
It represents a group selected from the group consisting of an alkyl group, a cyclohexyl group which may be substituted with halogen, and a hydroxyl group, and R ₂ is a hydrogen atom and a lower alkyl group, preferably selected from the group consisting of a C ₁ -C ₄ alkyl group. _R3 represents a group selected from the group consisting of a saturated or unsaturated lower alkyl group, preferably a _C1 to _C4 alkyl group, and a benzyl group optionally substituted with a lower alkyl group. The present invention relates to 2,2-di-substituted-5-unsubstituted or 2,2-di-substituted-5-alkyl-substituted-2,5-dihydrothiophene-1,1-dioxides and methods for producing the same. The present inventors have conducted research on Birch reduction of 2-substituted carbonyl thiophenes. As a result, the following formula (), However, in the formula, R ₁ represents a group selected from the group consisting of an alkyl group, a cyclohexyl group which may be substituted with halogen, and a hydroxyl group, and R ₂ represents a group selected from the group consisting of a hydrogen atom and a lower alkyl group. 2-substituted carbonyl-5-unsubstituted- represented by
Alternatively, a 2-substituted carbonyl-5-alkyl-substituted thiophene is subjected to a reduction reaction in an organic solvent in the coexistence of liquid ammonia and metallic sodium, and the product is treated with ammonium halide, followed by a halogenated alkyl or lower alkyl group. By reacting with an optionally substituted benzyl halide, the following formula (), However, in the formula, R ₁ , R ₂ and R ₃ have the same meaning as above,
5-Unsubstituted- or 2,2-disubstituted-5-alkyl-substituted-2,5-dihydrothiophenes can be produced easily and in good yields, and the compound of formula () is suitable for carotenoids and prostaglans. It is useful as a synthetic intermediate such as 5,7-octadien-4-one or 9,11-tridecadiene-8-one, which is useful for applications such as resins, and also exhibits physiological activity by itself and is used in medicines and agricultural products. Patent application No. 58-49378, filed on the same date by the same applicant, with the title of the invention "2,2-di-substitution", knowing that it is useful as a bactericidal and insecticide in the field of horticulture, etc.
5-Unsubstituted- or 2,2-disubstituted-5-alkyl-substituted-2,5-dihydrothiophenes and their production method.As a result of further research, the present inventors have proposed the above-mentioned 2, which is not described in the conventional literature and can be expressed by the formula ().
2-di-substituted-5-unsubstituted- or 2,2-di-substituted-
It has been discovered that 5-alkyl-substituted-2,5-dihydrothiophene-1,1-dioxides can exist and can be easily synthesized from the compound of formula (). Furthermore, the compound of formula () is useful as an intermediate for the synthesis of 5,7-octadien-4-one or 9,11-tridecadien-8-one, which is useful for uses such as carotenoids and prostaglandins. Moreover, it was found that it is a compound which has not been previously described in any literature, and which exhibits physiological activity by itself and is useful as a bactericidal and insecticide in the fields of medicine, agriculture and horticulture, etc. Therefore, an object of the present invention is to provide a compound of the above formula () and a method for producing the same. The above objects and many other objects and advantages of the present invention will become more apparent from the following description. Examples of the alkyl group in R ₁ of the compound of formula () are methyl, ethyl, propyl (n-,
iso-), butyl (n-, iso-, sec-, tert-),
C ₁ - C ₁₂ such as heptyl, octyl, nonyl, etc.
Preferred examples include alkyl groups. Examples of the cyclohexyl group which may be substituted with halogen include a cyclohexyl group which may be mono- or di-substituted with a halogen atom, such as chloro. The above formula () compound
Examples of the lower alkyl group in R ₂ include the alkyl groups exemplified above for R ₁ , preferably C ₁ to
Examples include C ₄ alkyl groups. or,
Examples of the saturated or unsaturated lower alkyl group in R ₃ of the compound of formula () are methyl, ethyl, propyl, butyl, allyl, butenyl (1
-, 2-, 3-) and the like can be exemplified by C ₁ -C ₄ alkyl groups. Furthermore, examples of the benzyl group which may be substituted with a lower alkyl group in R ₃ include the formula

[Formula] However, in the formula, X and Y are each a hydrogen atom or a lower alkyl group, for example, C ₁
A mono- or di-substituted or unsubstituted benzyl group represented by ˜C ₄ alkyl group can be exemplified. The formula () compound that can be used for producing the formula () compound of the present invention can be obtained by subjecting the formula () compound to a reduction reaction (Birch reduction) in an organic solvent in the coexistence of liquid ammonia and metallic sodium. It can be produced by treating with ammonium halide and then reacting with a benzyl halide optionally substituted with an alkyl halide or a lower alkyl group. Examples of the above-mentioned solvent include lower alcohols such as methanol, ethanol, propanol, and butanol, ethers such as ethyl ether, and tetrahydrofuran, and appropriate mixed solvents thereof, which are used in an anhydrous state. It is good to use it. The reduction reaction is carried out in a solvent such as those exemplified above under refluxing conditions of liquid ammonia, for example, at about -30° to about -35°C.
It can be done with The amount of liquid ammonia used in the reaction can be selected as appropriate, and for example, the amount used may be about 100 to about 250 times the molar amount, more preferably about 150 to about 200 times the molar amount, based on the compound of formula (). . In addition, the amount of metal sodium to be used can be selected as appropriate, for example, about 2% based on the compound of formula ().
Examples of the usage amount include about 3 times the mole, more preferably about 2.2 to about 2.4 times the mole. After the reduction reaction, an alkylation or benzylation reaction can be carried out continuously without taking out the reaction product. The reaction is carried out by treating the product with an ammonium halide such as ammonium chloride, followed by a benzyl halide optionally substituted with an alkyl halide or a lower alkyl group,
For example, it can be carried out by reacting with alkyl bromide or benzyl bromide. The reaction can be carried out under refluxing conditions of liquid ammonia by adding and stirring ammonium halide to the product system, then adding an alkyl halide or benzyl halide such as those exemplified above. The amount of ammonium halide to be used can be appropriately selected, for example, about 1 to about 2 moles, more preferably about 1.1 to about 1.3 moles, based on the compound of formula (). The amount of the alkyl halide or benzyl halide to be used is, for example, about 2.5 to about 5 times the mole, more preferably about 3 to about 3.5 times the mole based on the compound of formula (). A starting compound of formula () can be obtained from a compound of formula () by the method described above. The compound of formula () of the present invention can be produced, for example, by oxidizing the compound of formula () obtainable as described above with an oxidizing agent in an inert organic solvent. The oxidation reaction can be carried out by oxidation treatment using an oxidizing agent under mild oxidation conditions in an inert organic solvent. Examples of the solvent to be used include, for example, methylene chloride and chloroform. The amount used can be selected as appropriate, and for example, the amount used can be about 0 to about 40 times the weight of the compound of formula (). Examples of the oxidizing agent used include relatively mild oxidizing agents such as m-chloroperbenzoic acid and hydrogen peroxide. Although the amount of the oxidizing agent to be used can be selected as appropriate, it may be used in an amount of about 2.0 to about 2.5 mol % based on the compound of formula (). The oxidation reaction temperature and time can be appropriately selected, and examples thereof include a reaction temperature of about 0° C. to room temperature and a reaction time of about 6 to about 12 hours. EXAMPLES Hereinafter, several embodiments of the present invention will be explained in more detail by Examples along with production examples (reference examples) of compounds of formula (). Reference example 12-acetyl-2-benzyl-2,5-
Synthesis of dihydrothiophene: 2.52 g (20 mmol) of 2-acetylthiophene and 4 ml of ethanol in about 100 ml of liquid ammonia,
Add 3 ml of ether and add 1.06 ml of metallic sodium to this.
Birch reduction is carried out by adding g (46 mmol) of strips over 30-40 minutes. After stirring for an additional 60 minutes, add 1.3 g of ammonium chloride and stir well for 30 minutes.
Next, add 5.0 ml (66.7 mmol) of benzyl bromide,
The reaction is completed with stirring for 60 minutes. All of the above reactions were carried out at liquid ammonia reflux temperature (-30 to -35
°C). After the reaction is complete, ammonia is evaporated, treated with 10% hydrochloric acid, extracted with ether, and neutralized with sodium hydrogen carbonate. After dehydrating the ether solution with anhydrous sodium sulfate, 2-acetyl-2-benzyl-2,5-dihydrothiophene was isolated by column chromatography. Its yield is 73%. The IR, MS, NMR, and elemental analysis values of this substance are shown in Table 1. Reference Example 2 Synthesis of 2-butyryl-2-benzyl-5-butyl-2,5-dihydrothiophene: 2-butyrylthiophene (bp111-112℃/13
mmHg) 23.1 g (0.15 mol) and zinc amargal (metallic zinc 100 g, mercuric chloride 2.0 g, prepared from
(washed with water) in 100 ml of water and 100 ml of concentrated hydrochloric acid,
After boiling and refluxing for 20 hours, it is extracted with benzene, washed with water, and dried over anhydrous sodium sulfate. Remove the solvent and distill under reduced pressure. bp73~80℃/20mmHg
5-butylthiophene is obtained. This 5-butylthiophene was prepared by JR Johnson, GEMay, Org.
2 , 8 (1943), 2-butyryl-5
-Butylthiophene (bp113-114℃/4mmHg)
I got it. 2-butyryl-5-butylthiophene 4.20g
2-butyryl-2-benzyl-5-butyl-2,5-dihydrothiophene was obtained in a good yield of 76% in the same manner as in Reference Example 1 except that (20 mmol) was used. The analytical values are shown in Table 1. Table 1 also shows the results of synthesizing various compounds of formula () in the same manner using various other compounds of formula ().

【table】

【table】

[Table] Example 12-Butyryl-2-benzyl-2,5-
Synthesis of dihydrothiophene-1,1-dioxide 1.23 g (5 mmol) of 2-butyryl-2-benzyl-2,5-dihydrothiophene was dissolved in 40 ml of methylene chloride, and after cooling to 0°C, m ―
After adding 2.16 g (12.5 mmol) of chloroperbenzoic acid and carrying out the reaction with stirring for 3 hours, the reaction was further completed with stirring at room temperature for 24 hours. A small amount of saturated aqueous sodium bisulfite solution is added to the reaction solution to remove excess oxidizing agent, and then added to a saturated aqueous sodium carbonate solution for neutralization, followed by extraction with chloroform. After dehydrating the chloroform solution with anhydrous sodium sulfate, it is separated and purified using column chromatography (silica gel (Wako C-200), benzene petroleum ether system), and the solvent is evaporated to obtain the target product (thermally unstable crystals). isolated. The yield is 86%. The IR, MS, and NMR of this substance are as follows. IR, C=O; 1700cm ^-1 , SO ₂ ; 1105cm ^-1 , 1295
cm ^-1 MS, m/e278 (M ⁺ )214 (M ⁺ -64) NMR,
(CDCl ₃ ) δ: 0.88 (3H, t, J = 3Hz), 1.40~
1.80 (2H, m), 2.12-2.84 (2H, m), 3.12 (2H,
d, J=7Hz), 3.64-3.88 (2H, m), 6.24 (2H,
s), 7.00 to 7.40 (5H, m) Example 2 Synthesis of 2-butyryl-2-benzyl-5-methyl-2,5-dihydrothiophene-1,1-dioxide 2-butyryl-2-benzyl-5- Methyl
1,30 g (5 mmol) of 2,5-dihydrothiophene was dissolved in 40 ml of methylene chloride, and after cooling it to 0°C, 2.16 g (12.5 mmol) of m-chlorobenzoic acid was added, and the mixture was prepared in the same manner as in Example 1. After performing the oxidation reaction, the target substance can be obtained in the form of an oil with a yield of 81%. Its physical properties are: IR:>C=O, 1695cm ^-1 , SO ₂ : 1110cm ^-1 ,
1300cm ^-1 MS: m/, 292 (M ⁺ ), 228 (M ⁺ -64) NMR (CDCl ₃ ): δ: 0.76-1.04 (3H, m),
1.34-1.80 (5H, m), 2.20-2.80 (2H, m), 3.00
~3.34 (1H, m), 3.60 ~ 3.88 (2H, m), 5.90 ~
6.30 (2H, m), 7.00-7.44 (5H, m), Example 3 2-butyryl-2-benzyl-5-butyl-2,5-dihydrothiophene-1,1-dioxide 2-butyryl-2-benzyl -5-butyl-
1.51 g (5 mmol) of 2,5-dihydrothiophene was dissolved in 40 ml of methylene chloride, cooled to 0°C, 2.16 g (12.5 mmol) of m-chloroperbenzoic acid was added, and the same procedure as in Example 1 was carried out. If the reaction is carried out and the product is treated, 84% of the oily target substance can be removed.
obtained with a yield of . Its physical properties are as follows. IR: >C=O1705cm ^-1 , SO ₂ 1115, 1300cm ^-1 MS: m/334 (M ⁺ ), 270 (M ⁺ -64) NMR (CDCl ₃ ): δ: 0.66 to 3.93 (19H, m),
6.03-6.33 (2H, m), 7.20 (5H, s) Example 42-Octanoyl-2,5-dimethyl-
Synthesis of 2,5-dihydrothiophene-1,1-dioxide 2-octanoyl-2,5-dimethyl-2,5
-1.20 g (5 mmol) of dihydrothiophene was dissolved in 40 ml of methylene chloride, and after cooling it to 0°C, 2.16 g (12.5 mmol) of m-chloroperbenzoic acid was added and the same procedure as in Example 1 was carried out. After the reaction, the desired substance can be obtained in the form of an oil with a good yield of 92%. Its physical properties are as follows. IR: > CO1705cm ^-1 , SO ₂ 1115cm ^-1 , 1300cm ^-1 MS: m/272 (M ⁺ ), 208 (M ⁺ -64) NMR (CDCl ₃ ): δ: 0.69 to 2.13 (20H, m),
2.67 (2H, t), 6.03-6.43 (2H, m) 2-acetyl-2-benzyl-2,5-dihydrothiophene, 2-propionyl-2-benzyl-2,5-dihydrothiophene, 2-isobutyl -2-benzyl-2,5-dihydrothiophene,
2-decanoyl-2-benzyl-2,5-dihydrothiophene, 2-cyclohexylcarbonyl-
2-benzyl-2,5-dihydrothiophene, 2
-Butyryl-2-methyl-2,5-dihydrothiophene, 2-butyryl-2-allyl-2,5-dihydrothiophene, 2-butyryl-2-butyl-
If 2,5-dihydrothiophene is oxidized and treated in the same manner as in Example 1, 2-acetyl-2-
Benzyl-2,5-dihydrothiophene-1,1
-dioxide, 2-propionyl-2-benzyl-2,5-dihydrothiophene-1,1-dioxide, 2-isobutyl-2-benzyl-2,5-
Dihydrothiophene-1,1-dioxide, 2-
Decanoyl-2-benzyl-2,5-dihydrothiophene-1,1-dioxide, 2-cyclohexylcarbonyl-2-benzyl-2,5-dihydrothiophene-1,1-dioxide, 2-butyryl-2-methyl -2,5-dihydrothiophene-
1,1-dioxide, 2-butyryl-2-allyl-2,5-dihydrothiophene-1,1-dioxide, 2-butyryl-2-butyl-2,5-dihydrothiophene-1,1-dioxide ,Respectively,
can get.

Claims (1)

[Claims] 1. The following formula () However, in the formula, R ₁ represents a group selected from the group consisting of an alkyl group, a cyclohexyl group which may be substituted with halogen, and a hydroxyl group, and R ₂ represents a group selected from the group consisting of a hydrogen atom and a lower alkyl group. and R ₃ represents a group selected from the group consisting of a saturated or unsaturated lower alkyl group and a benzyl group optionally substituted with a lower alkyl group. Substituted- or 2,2-disubstituted-5-alkyl-substituted-2,5-dihydrothiophene-1,1-dioxides. 2 R ₁ represents a group selected from the group consisting of a C ₁ to C ₁₂ alkyl group, a cyclohexyl group, and a hydroxyl group, and R ₂ represents a group selected from the group consisting of a hydrogen atom and a C ₁ to C ₄ alkyl group. The compound according to claim 1, wherein _R3 represents a group selected from the group consisting of a saturated or unsaturated _C1 - _C4 alkyl group and a benzyl group. 3 The following formula () However, in the formula, R ₁ represents a group selected from the group consisting of an alkyl group, a cyclohexyl group which may be substituted with halogen, and a hydroxyl group, and R ₂ represents a group selected from the group consisting of a hydrogen atom and a lower alkyl group. and R ₃ represents a group selected from the group consisting of a saturated or unsaturated lower alkyl group and a benzyl group optionally substituted with a lower alkyl group. The following formula (), characterized in that substituted- or 2,2-disubstituted-5-alkyl-substituted-2,5-dihydrothiophene is oxidized with an oxidizing agent in an inert organic solvent, However, in the formula, R ₁ , R ₂ and R ₃ have the same meanings as above, 2,2-di-substituted-5-unsubstituted- or 2,2-di-substituted-5-alkyl-substituted-2,5- Method for producing dihydrothiophene-1,1-dioxides.