JP3196267B2 - Vinyl ether derivative, production method thereof and use thereof - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a vinyl ether derivative useful as an intermediate for pharmaceuticals, agricultural chemicals, fragrances, analytical reagents and the like, a method for producing the same, and a method for producing unsaturated ketoaldehydes using the compound.

[0002]

BACKGROUND OF THE INVENTION The reaction of adding an organolithium compound to a double bond is widely known. However, when trying to apply this reaction to α, β-unsaturated ketones, it is known that the addition of an organolithium compound is favored by the Grignard reaction type 1,2-addition over 1,4-addition. Therefore, it was considered difficult to selectively introduce a substituent at the β-position. On the other hand, as an addition reaction of an α, β-unsaturated ketone to the β-position, a method using lithium and copper instead of a lithium compound is known (Tetrahedron, V.
ol. 33, 1977, p.1105-1112). However, this method requires a strict control of the conditions such as the reaction temperature and the reaction rate, and that the water in the reaction solvent must be strictly removed before use. It was necessary to strictly control the conditions, and this was not always an industrially satisfactory method.

[0003]

SUMMARY OF THE INVENTION The present inventors have developed α, β
For the addition reaction of the unsaturated ketone to the β-position, as a result of various studies, when an organolithium compound obtained by reacting a compound having a specific skeleton with a lithiation agent is used, 1,
It has been found that 4-addition, that is, the addition reaction of the α, β-unsaturated ketone to the β-position occurs selectively, and a vinyl ether derivative can be industrially advantageously obtained. The present inventors have found that the conversion is useful as an intermediate for pharmaceuticals, agricultural chemicals, fragrances, analytical reagents, and the like, and have reached the present invention.

[0004]

That is, the present invention provides a compound represented by the general formula [1]: (Wherein, R ¹ is an alkyl group having 1 to 10 carbon atoms, 6 to 10 carbon atoms)
R ² represents an aryl group having 6 to 15 carbon atoms, an aryl group having 7 to 15 carbon atoms, or an aralkyl group having 7 to 15 carbon atoms;
15 aralkyl group, <br/> also an alkyl group having 1 to 10 carbon atoms or a hydrogen atom, or R ¹ and R ² are bonded to carbon atoms
Represents 2 to 10 alkylene groups. Here, the alkylene group is an OSi (R ⁷ ) ₃ group (where R ⁷ is the same or different)
Or an alkyl group having 1 to 4 carbon atoms) , or an alkoxy group having 1 to 5 carbon atoms or a halogen atom. R ³ has 6 carbon atoms (which may be substituted with an alkoxy group having 1 to 5 carbon atoms or a halogen atom)
Represents an aryl group having from 15 to 15, R ⁴ and R ⁵ each represent a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R ⁶ represents an alkyl group having 1 to 10 carbon atoms. A) a vinyl ether derivative represented by the general formula [2]: (Wherein R3, R4, R5 and R6 have the same meanings as described above), and a lithiating agent is reacted with the alkenylthioether represented by the general formula [3]. (Wherein, R1 and R2 have the same meanings as described above), and a method for producing a vinyl ether derivative by reacting an α, β-unsaturated ketone, and a general formula of reacting the vinyl ether derivative with an oxidizing agent [ 4] (Wherein, R1, R2, R4 and R5 have the same meanings as described above). Hereinafter, the present invention will be described in detail.

[0005] The vinyl ether derivative represented by the general formula [1] is obtained by reacting an alkenyl thioether represented by the general formula [2] with a lithium-forming agent, and then reacting the α, β-unsaturated compound represented by the general formula [3]. It can be obtained by reacting ketones.

R ³ of the alkenyl thioethers [2] is an aryl group which may have a substituent, for example, an alkylphenyl group such as a phenyl group, a tolyl group, an ethylphenyl group and a butylphenyl group, a chlorophenyl group, Halophenyl groups such as fluorophenyl group, methoxyphenyl group, butoxyphenyl group, alkoxyphenyl group such as methylenedioxyphenyl group, naphthyl group, methylnaphthyl group, alkylnaphthyl group such as butylnaphthyl group, chloronaphthyl group, fluoronaphthyl group And methoxynaphthyl group, butoxynaphthyl group, and alkoxynaphthyl group such as methylenedioxynaphthyl group. R ⁴ and R ⁵ are each a hydrogen atom or an alkyl group, for example, a hydrogen atom, a methyl group, an ethyl group, a propyl group, a butyl group, etc., and R ⁶ is an alkyl group, for example, a methyl group, an ethyl group, a propyl group, A butyl group and the like can be mentioned. Specific examples thereof include 1-methoxy-3-phenylthio-1-propene, 1-ethoxy-3-phenylthio-1-propene,
1-propoxy-3-phenylthio-1-propene, 1
-Methoxy-2-methyl-3-phenylthio-1-propene, 1-propoxy-2-methyl-3-phenylthio-1-propene, 1-methoxy-3-methyl-3-phenylthio-1-propene, 1-propoxy -3-methyl-3-p-tolylthio-1-propene, 1-methoxy-
2,3-dimethyl-3-p-chlorophenylthio-1-
Propene, 1-propoxy-2,3-dimethyl-3-p
-Methoxyphenylthio-1-propene, 1-propoxy-2,3-dimethyl-3- (2-naphthylthio) -1
-Propene and the like. The amount is usually 0.5 to 5 times the molar amount of the α, β-unsaturated ketone [3].

Examples of the lithiating agent include n-butyllithium, t-butyllithium, sec. Alkyl lithium such as -butyl lithium, and the amount thereof is usually 1.1 to alkenyl thioethers [2].
It is not more than molar times. The reaction between the alkenyl thioethers [2] and the lithium agent is usually performed in the presence of a solvent. Examples of such a solvent include ethyl ether, tetrahydrofuran, dimethoxyethane, dioxane, hexamethylphosphoric triamide, hexane, heptane and the like. Inert solvents can be mentioned, which are used alone or as a mixture. The reaction is usually carried out with helium, argon,
The reaction is carried out under an inert gas stream such as nitrogen.The reaction is usually carried out by dropping the alkenyl thioethers [2] solution into the alkenyl thioethers [2] solution or dropping the alkenyl thioethers [2] solution into the lithiation agent solution. Done. The reaction temperature is usually from -100 to -10C.

After the reaction of the alkenyl thioethers [2] with the lithiation agent, the resulting reaction solution is usually subjected to α, β-unsaturated ketones without further isolating the vinyl ether derivative [ 1] is obtained.
The reaction is usually performed under an inert gas stream of helium, argon, nitrogen or the like.

Α, β-unsaturated ketones used [3]
R ¹ is an alkyl group which may have a substituent, an aryl group which may have a substituent or an aralkyl group which may have a substituent, for example, a methyl group, an ethyl group, and a butyl group. Alkyl groups such as methoxymethyl group, ethoxymethyl group, ethoxyethyl group, alkoxyalkyl group such as butoxybutyl group, chloromethyl group, fluoroethyl group, haloalkyl group such as chlorobutyl group, phenyl group, tolyl group, ethylphenyl Group, alkylphenyl group such as butylphenyl group, chlorophenyl group, halophenyl group such as fluorophenyl group, methoxyphenyl group, butoxyphenyl group, alkoxyphenyl group such as methylenedioxyphenyl group, naphthyl group, methylnaphthyl group,
Alkylnaphthyl group such as butylnaphthyl group, chloronaphthyl group, halonaphthyl group such as fluoronaphthyl group, methoxynaphthyl group, butoxynaphthyl group, alkoxynaphthyl group such as methylenedioxynaphthyl group, benzyl group,
Phenylethyl group, phenylpropyl group, phenylalkyl group such as diphenylethyl group, tolylmethyl group, ethylphenylethyl group, alkylphenylalkyl group such as butylphenylmethyl group, methoxyphenylmethyl group,
Alkoxyphenylalkyl groups such as ethoxyphenylethyl, butoxyphenylethyl, methylenedioxyphenylmethyl, halophenylalkyl such as chlorophenylmethyl, fluorophenylethyl, naphthyl, naphthylethyl, naphthylpropyl, diphenyl Naphthylalkyl groups such as naphthylethyl group, alkylnaphthylalkyl groups such as methylnaphthylmethyl group, ethylnaphthylethyl group and butylnaphthylmethyl group, methoxynaphthylmethyl group, ethoxynaphthylethyl group, butoxynaphthylethyl group, methylenedioxy Examples thereof include an alkoxynaphthylalkyl group such as a naphthylmethyl group, and a halonaphthylalkyl group such as a chloronaphthylmethyl group and a fluoronaphthylethyl group. R ² is an aryl group which may have a substituent, an aralkyl group which may have a substituent, an alkyl group which may have a substituent or a hydrogen atom, for example, a hydrogen atom, methyl Group, ethyl group, alkyl group such as butyl group, methoxymethyl group, ethoxymethyl group, ethoxyethyl group, alkoxyalkyl group such as butoxybutyl group, chloromethyl group,
Haloalkyl groups such as fluoroethyl group and chlorobutyl group, phenyl groups, tolyl groups, alkylphenyl groups such as ethylphenyl group and butylphenyl group, halophenyl groups such as chlorophenyl group and fluorophenyl group, methoxyphenyl group, butoxyphenyl group, and methylene group Alkoxyphenyl group such as dioxyphenyl group, naphthyl group, methylnaphthyl group, alkylnaphthyl group such as butylnaphthyl group, chloronaphthyl group, halonaphthyl group such as fluoronaphthyl group, methoxynaphthyl group, butoxynaphthyl group,
Alkoxynaphthyl groups such as methylenedioxynaphthyl group, benzyl group, phenylethyl group, phenylpropyl group, phenylalkyl group such as diphenylethyl group, tolylmethyl group, ethylphenylethyl group, alkylphenylalkyl group such as butylphenylmethyl group, Methoxyphenylmethyl group, ethoxyphenylethyl group, butoxyphenylethyl group, alkoxyphenylalkyl group such as methylenedioxyphenylmethyl group, chlorophenylmethyl group, halophenylalkyl group such as fluorophenylethyl group, naphthyl group, naphthylethyl group, Naphthylalkyl groups such as naphthylpropyl group and dinaphthylethyl group; alkylnaphthylalkyl groups such as methylnaphthylmethyl group, ethylnaphthylethyl group and butylnaphthylmethyl group; Chirumechiru group, an ethoxy naphthyl ethyl group, butoxyethyl naphthyl ethyl group, alkoxyalkyl naphthyl alkyl group such as a methylenedioxy naphthylmethyl group, chloromethyl naphthylmethyl group, Halona border Le alkyl group such as fluoro naphthyl ethyl group, etc., can be exemplified. Further, R ¹ and R ² may be an alkylene group which may have a substituent together, for example, an alkylene group such as an ethylene group, a propylene group, a butylene group, a methylethylene group, and a chloromethylethylene group. Group, ethyl propylene group, alkyl-substituted alkylene group such as dimethylbutylene group, methoxyethylene group, butoxypropylene group,
Chloroethyl propylene group, alkoxy-substituted alkylene group such as diethyl butylene group, trimethylsilyloxyethylene group, t-butyldimethylsilyloxyethylene group, triethylsilyloxypropylene group, t-butyldimethylsilyloxypropylene group, t-pentyldimethylsilyloxy Trialkylsilyloxy-substituted alkylene group such as butylene group, phenyldimethylsilyloxyethylene group, chlorophenyldimethylsilyloxypropylene group, aryldialkylsilyloxy-substituted alkylene group such as methylphenyldimethylsilyloxybutylene group, diphenylmethylsilyloxyethylene group, Diarylalkylsilyloxy-substituted alkylene group such as diphenylethylsilyloxypropylene group, triphenylsilyloxyethyl Triarylsilyloxy-substituted alkylene groups such as tri (chlorophenyl) silyloxypropylene group and tolylsilyloxybutylene group; aralkyl-substituted alkylene groups such as benzylethylene group, phenethylpropylene group and methylphenylmethylbutylene group; ethenyloxyethylene Group, alkenyloxy-substituted alkylene group such as ethenyloxypropylene group, alkoxyalkoxy-substituted alkylene group such as ethoxymethoxyethylene group and methoxymethoxypropylene group, tetrahydropyranyloxyethylene group and tetrahydropyranyl such as tetrahydropyranyloxypropylene group Oxy-substituted alkylene groups and the like can be mentioned. Specific examples thereof include ethyl- (1-propenyl) -ketone, ethoxyethyl- (3-phenyl-1-propenyl) -ketone, and 3-chloropropyl- (4-phenyl-).
1-butenyl) -ketone, phenyl- (1-propenyl) -ketone, p-tolyl- (1-propenyl) -ketone, p-chlorophenyl- (1-butenyl) -ketone,
Phenyl- (4-phenyl-1-butenyl) -ketone,
Phenyl- (2-phenyl-1-ethenyl) -ketone,
p-methoxyphenyl- (3-phenyl-1-propenyl) -ketone, 2-naphthyl- (1-propenyl) -ketone, 2- (6-methylnaphthyl)-[2- (2-naphthyl) -ethenyl]- Ketone, benzyl- (1-pentenyl) -ketone, benzyl- [3- (2-naphthyl)-
1-propenyl) -ketone, p-methylbenzyl- (4
-P-methoxyphenyl-1-butenyl) -ketone, p
-Methoxyphenethyl- (1-propenyl) -ketone,
p-chlorobenzyl- (4-p-chlorophenyl-1-
Butenyl) -ketone, 2-cyclohexenone, 4-ethoxymethoxy-2-cyclohexenone, 4- (t-butyldimethylsilyloxy) -2-cyclohexenone,
-Methyl-2-cyclohexenone, 4- (t-butyldimethylsilyloxy) -2-cyclopentenone, 4-
(Trimethylsilyloxy) -2-cyclopentenone,
4- (phenyldimethylsilyloxy) -2-cyclopentenone, 4- (diphenylmethylsilyloxy) -2
-Cyclopentenone, 4-benzyloxy-2-cyclopentenone, 2-cyclopentenone, 4-tetrahydropyranyloxy-2-cyclopentenone, 4-ethoxymethoxy-2-cyclopentenone, 4-methyl- 2-cyclopentenone and the like can be mentioned.

The reaction is generally carried out by adding an α, β-unsaturated ketone [3] to a reaction solution obtained by reacting the alkenyl thioether [2] with a lithium agent. Examples of the solvent for the reaction include those used for the reaction between the alkenyl thioethers [2] and the lithium agent. The reaction temperature is usually -100 to -10C
It is. After completion of the reaction, the reaction solution is usually charged into ice water, and extraction, concentration, and other operations are performed to obtain a vinyl ether derivative represented by the general formula [1]. If necessary, purification may be performed by column chromatography or the like. it can.

The vinyl ether derivative [1] thus obtained includes, for example, methyl- (3,4-dimethyl-
3-phenylthio-5-methoxy-4-pentenyl)-
Ketone, ethyl- (2,4-dimethyl-3-phenylthio-5-ethoxy-4-pentenyl) -ketone, ethoxyethyl- (2-propyl-3-p-tolylthio-5-
Propoxy-4-pentenyl) -ketone, chloropropyl- (2-benzyl-3-p-chlorophenylthio-3)
-Methyl-5-butoxy-4-pentenyl) -ketone,
Phenyl- (2,3-dimethyl-3-phenylthio-5
-Butoxy-4-pentenyl) -ketone, phenyl-
[2- (6-Methoxy-1-naphthylmethyl) -3-phenylthio-3-methyl-5-methoxy-4-pentenyl] -ketone, phenyl- [2- (6-methoxy-1-
Naphthylmethyl) -3-phenylthio-3-methyl-5
-Methoxy-4-pentenyl] -ketone, p-tolyl-
[2- (6-chloro-2-naphthylmethyl) -3- (2
-Naphthylthio) -3-methyl-5-methoxy-4-pentenyl] -ketone, p-methoxyphenyl- (2-p
-Chlorophenyl-3-phenylthio-5-methoxy-
4-pentenyl) -ketone, p-chlorophenyl- [2
-(2-naphthyl) -3-phenylthio-3-methyl-
5-methoxy-4-pentenyl] -ketone, 2-naphthyl- (2-methoxyethyl-3-phenylthio-3-methyl-5-methoxy-4-pentenyl) -ketone, 2-
Naphthyl- (2-methoxyethyl-3-phenylthio-
3-methyl-5-methoxy-4-pentenyl) -ketone, 2- (6-methylnaphthyl)-(2-chloropropyl-3-phenylthio-3-methyl-5-methoxy-4
-Pentenyl) -ketone, 1- (7-methoxynaphthyl)-(2-phenyl-3-phenylthio-3-methyl-5-methoxy-4-pentenyl) -ketone, 2- (6
-Chloronaphthyl)-(2-p-tolyl-3-phenylthio-3-methyl-5-methoxy-4-pentenyl)-
Ketone, 2- (6-chloronaphthyl)-(3-phenylthio-3-methyl-5-methoxy-4-pentenyl)-
Ketone, 2- (6-chloronaphthyl)-(3-phenylthio-5-methoxy-4-pentenyl) -ketone, benzyl- [2- (2-naphthylmethyl) -3-phenylthio-3-methyl-5-methoxy -4-pentenyl] -ketone, p-ethylbenzyl- [2- (6-methyl-2-
Naphthyl) -3-phenylthio-3-methyl-5-methoxy-4-pentenyl] -ketone, p-propoxybenzyl- [2- (7-methoxy-2-naphthyl) -3-phenylthio-3-methyl-5- Methoxy-4-pentenyl] -ketone, p-chlorobenzyl- [2-p-methoxyphenyl-3- (6-chloronaphthyl) -4-methyl-5-methoxy-4-pentenyl] -ketone, p-chlorobenzyl -[2- (7-methyl-2-naphthylethyl) -3-phenylthio-4-methyl-5-methoxy-
4-pentenyl] -ketone, 2-naphthylmethyl- (2
-P-ethylbenzyl-3-phenylthio-4-methyl-5-methoxy-4-pentenyl) -ketone, (7-methyl-2-naphthylethyl)-(2-p-propoxyphenethyl-3-phenylthio-4- Methyl-5-methoxy-4-pentenyl) -ketone, (6-methoxy-1-)
Naphthylethyl)-(2,4-dimethyl-3-phenylthio-5-methoxy-4-pentenyl) -ketone, (6
-Chloro-2-naphthylethyl)-(2,4-dimethyl-3-phenylthio-5-methoxy-4-pentenyl)
-Ketone, 3- (1-phenylthio-2-methyl-3-
Methoxy-2-propenyl) -cyclopentanone, 3-
(1-Phenylthio-2-methyl-3-methoxy-2-
Propenyl) -cyclohexanone, 4-methyl-3-
(1-Phenylthio-2-methyl-3-methoxy-2-
Propenyl) -cyclopentanone, 4-ethyl-3-
(1-Phenylthio-2-methyl-3-methoxy-2-
Propenyl) -cyclohexanone, 4-ethoxy-3-
(1-Phenylthio-2-methyl-3-methoxy-2-
Propenyl) -cyclopentanone, 4-propoxy-3
-(1-phenylthio-2-methyl-3-methoxy-2
-Propenyl) -cyclohexanone, 4- (t-butyldimethylsilyloxy) -3- (1-phenylthio-
1,2-dimethyl-3-methoxy-2-propenyl)-
Cyclopentanone, 4- (t-butyldimethylsilyloxy) -3- (1-phenylthio-1-methyl-3-methoxy-2-propenyl) -cyclohexanone, 4-trimethylsilyloxy-3- (1-phenylthio-1 ,
2-dimethyl-3-methoxy-2-propenyl) -cyclopentanone, 4-phenyldimethylsilyloxy-3
-(1-phenylthio-1-methyl-3-methoxy-2
-Propenyl) -cycloheptanone, 4-diphenylmethylsilyloxy-3- (1-phenylthio-1,2-
Dimethyl-3-methoxy-2-propenyl) -cyclopentanone, 4-triphenylsilyloxy-3- (1-
Phenylthio-1,2-dimethyl-3-methoxy-2-
Propenyl) -cycloheptanone, 4-triphenylsilyloxy-3- (1-phenylthio-1,2-dimethyl-3-methoxy-2-propenyl) -cyclopentanone, 4-benzyl-3- (1-phenylthio -1,2-
Dimethyl-3-methoxy-2-propenyl) -cyclopentanone, 4-benzyloxy-3- (1-phenylthio-1,2-dimethyl-3-methoxy-2-propenyl) -cyclohexanone, 4-ethenyloxymethoxy -3- (1-Phenylthio-1,2-dimethyl-3-methoxy-2-propenyl) -cyclopentanone, 4-tetrahydropyranyloxy-3- (1-phenylthio-
1,2-dimethyl-3-methoxy-2-propenyl)-
Cyclopentanone, 4-tetrahydropyranyloxy-
3- (1-phenylthio-1,2-dimethyl-3-methoxy-2-propenyl) -cyclohexanone and the like can be mentioned.

The unsaturated ketoaldehyde represented by the general formula [4] can be obtained by reacting a vinyl ether derivative [1] in the presence of an oxidizing agent. Examples of the oxidizing agent include those capable of oxidizing a sulfide to a sulfoxide, such as hydrogen peroxide, t-butyl hydroperoxide, peracetic acid, m-chloroperbenzoic acid, and sodium periodate. Sodium. The amount of the oxidizing agent to be used is usually 1 to 4 moles, preferably 1.5 to 1.5 times the amount of the vinyl ether derivative [1].
It is 3 mole times.

In the reaction, a solvent can be used. Examples of the solvent include acetone, tetrahydrofuran, water, dioxane, dimethoxyethane and the like. These solvents can be used alone or in a mixture. The reaction temperature is usually -20 to 60C, preferably 10 to 35C. The reaction time is usually 3 to 15
About an hour is enough. After completion of the reaction, an unsaturated aldehyde represented by the general formula [4] can be obtained by subjecting to a normal post-treatment operation such as extraction, washing, drying, and concentration, and can be purified by column chromatography or the like, if necessary. it can.

The α, β-ketoaldehydes [4] thus obtained include, for example, methyl- (3,4-dimethyl-4-formyl-3-butenyl) -ketone, ethyl-
(2,4-dimethyl-4-formyl-3-butenyl)-
Ketone, ethoxyethyl- (2-propyl-4-formyl-3-butenyl) -ketone, chloropropyl- (2-
Benzyl-3-methyl-4-formyl-3-butenyl)
-Ketone, phenyl- (2,3-dimethyl-4-formyl-3-butenyl) -ketone, phenyl- [2- (6-
Methoxy-1-naphthylmethyl) -3-methyl-4-formyl-3-butenyl] -ketone, phenyl- [2-
(6-methoxy-1-naphthylmethyl) -3-methyl-
4-formyl-3-butenyl] -ketone, p-tolyl-
[2- (6-Chloro-2-naphthylmethyl) -3-methyl-4-formyl-3-butenyl] -ketone, p-methoxyphenyl- (2-p-chlorophenyl-4-formyl-3-butenyl)- Ketone, p-chlorophenyl-
[2- (2-naphthyl) -3-methyl-4-formyl-
3-butenyl] -ketone, 2-naphthyl- (2-methoxyethyl-3-methyl-4-formyl-3-butenyl)
-Ketone, 2-naphthyl- (2-methoxyethyl-4-
(Formyl-3-butenyl) -ketone, (6-methyl-2)
-Naphthyl)-(2-chloropropyl-3-methyl-4
-Formyl-3-butenyl) -ketone, (7-methoxy-1-naphthyl)-(2-phenyl-4-methyl-4-)
(Formyl-3-butenyl) -ketone, (6-chloro-2)
-Naphthyl)-(2-p-tolyl-4-formyl-3-
(Butenyl) -ketone, (6-chloro-2-naphthyl)-
(3,4-dimethyl-4-formyl-3-butenyl)-
Ketone, benzyl- [2- (2-naphthylmethyl) -4
-Methyl-4-formyl-3-butenyl] -ketone, p
-Ethylbenzyl- [2- (6-methyl-2-naphthyl) -4-methyl-4-formyl-3-butenyl] -ketone, p-propoxybenzyl- [2- (7-methoxy-2-naphthyl)- 3-methyl-4-formyl-3-butenyl] -ketone, p-chlorobenzyl- (2-p-methoxyphenyl-3,4-dimethyl-4-formyl-3
-Butenyl) -ketone, p-chlorobenzyl- [2-
(7-methyl-2-naphthylethyl) -4-methyl-4
-Formyl-3-butenyl] -ketone, (2-naphthylmethyl)-(2-p-ethylbenzyl-4-methyl-4
-Formyl-3-butenyl) -ketone, (7-methyl-
2-naphthylethyl)-(2-p-propoxyphenethyl-3-methyl-4-formyl-3-butenyl) -ketone, (6-methoxy-1-naphthylethyl)-(2,4
-Dimethyl-4-formyl-3-butenyl) -ketone, (6-chloro-2-naphthylethyl)-(2,4-
Dimethyl-4-formyl-3-butenyl) -ketone, 3
-(2-methyl-2-formylethenyl) -cyclopentanone, 3- (1-methyl-2-formylethenyl)-
Cyclohexanone, 4-methyl-3- (1-methyl-2
-Formylethenyl) -cyclopentanone, 4-ethyl-3- (2-methyl-2-formylethenyl) -cyclohexanone, 4-ethoxy-3- (1-methyl-2-formylethenyl) -cyclopentanone, 4-propoxy- 3- (2-methyl-2-formylethenyl) -cyclohexanone, 4- (t-butyldimethylsilyloxy)
-3- (1,2-dimethyl-2-formylethenyl)-
Cyclopentanone, 4- (t-butyldimethylsilyloxy) -3- (1-methyl-2-formylethenyl)-
Cyclohexanone, 4-trimethylsilyloxy-3-
(1,2-dimethyl-2-formylethenyl) -cyclopentanone, 4-phenyldimethylsilyloxy-3-
(1-methyl-2-formylethenyl) -cycloheptanone, 4-diphenylmethylsilyloxy-3- (1,
2-dimethyl-2-formylethenyl) -cyclopentanone, 4-triphenylsilyloxy-3- (1,2-
Dimethyl-2-formylethenyl) -cycloheptanone, 4-triphenylsilyloxy-3- (1,2-dimethyl-2-formylethenyl) -cyclopentanone,
4-benzyl-3- (1,2-dimethyl-2-formylethenyl) -cyclopentanone, 4-benzyloxy-
3- (1,2-dimethyl-2-formylethenyl) -cyclohexanone, 4-ethenyloxymethoxy-3-
(1,2-dimethyl-2-formylethenyl) -cyclopentanone, 4-tetrahydropyranyloxy-3-
(1,2-dimethyl-2-formylethenyl) -cyclopentanone, 4-tetrahydropyranyloxy-3-
(2-methyl-2-formylethenyl) -cyclohexanone and the like.

[0015]

The vinyl ether derivative of the present invention [1]
Can lead to unsaturated aldehydes [4], which are useful as intermediates for drugs, pesticides, flavors, analytical reagents and the like. Further, according to the method of the present invention, by using a specific compound called alkenyl thioethers [2], a substituent can be selectively introduced into the β-position of α, β-unsaturated ketones [3], and industrially The vinyl ether derivative [1] can be advantageously produced.

[0016]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the examples.

Example 1 Under a nitrogen stream, 234 mg (1.3 mmol) of 1-methoxy-3-phenylthio-1-propene and 4 ml of tetrahydrofuran were charged into a reactor and cooled to -78 ° C.
Under stirring, 0.59 ml (1.3 mmol) of a 2.2 M solution of t-butyllithium in pentane is added dropwise over 3 minutes. Thereafter, the mixture is stirred at the same temperature for 10 minutes, 0.67 ml (3.9 mmol) of hexamethylphosphorylamide is added, and the mixture is stirred for 1 minute. Then, 2-cyclohexenone 9
6 mg (1.0 mmol) in 1 ml of tetrahydrofuran
Is added dropwise at −78 ° C. over 3 minutes, and the mixture is further stirred at the same temperature for 15 minutes. 2 ml of a saturated aqueous ammonium chloride solution is added to the obtained reaction solution, and the mixture is extracted with 30 ml of ethyl acetate. The obtained organic layer was washed with saturated aqueous ammonium chloride 10
After washing with 10 ml of a saturated saline solution, drying with anhydrous sodium sulfate, and concentration under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solvent: hexane-ethyl acetate (20: 1)].
189 mg of 3- (1-phenylthio-3-methoxy-2-propenyl) -cyclohexanone (71.6% yield)
Get. ^{IR (neat) 1710cm -1 1 HNMR} (C 6 D 6) δ 0.8-2.7 (m, 9H), 3.08 (s, 3H / 2), 3.1
0 (s, 3H / 2), 3.26 (m, 1H), 4.47 (dd, J = 4.39, 12.4Hz, 1
H / 2), 4.59 (dd, J = 4.63, 12.4Hz, 1H / 2), 5.98 (d, J = 1
2.4Hz, 1H / 2), 6.01 (d, J = 12.4Hz, 1H / 2), 7.0-7.4 (m,
5H) MS (m / z) 276 (M ⁺ ) Elemental analysis result by high resolution mass spectrum Found: 276.1194, Calcd for C ₁₆ H ₂₀ O ₂ S, M = 276.1184

Example 2 165 mg of 3- (1-phenylthio-3-methoxy-2-propenyl) -cyclohexanone obtained in Example 1
(0.597 mmol) and 4 ml of dioxane, water 1
of sodium periodate at room temperature.
g (1.402 mmol) is added and stirred for 10 hours. Thereafter, 30 ml of ethyl acetate is added to the reaction solution for extraction. The organic layer is washed twice with 10 ml of a saturated aqueous solution of sodium hydrogencarbonate and once with 10 ml of a saturated saline solution. The obtained organic layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography [developing solvent: hexane-ethyl acetate (10: 1)] to obtain 3- (2-formyl-ethenyl) -cyclohexanone (69 mg, yield 75.9%). IR (neat) 1710, 1682, 1630cm -1 1 HNMR (CDCl 3) δ 0.8-2.7 (m, 9H), 3.08 (s, 3H / 2),
3.10 (s, 3H / 2), 3.26 (m, 1H), 4.47 (dd, J = 4.39, 12.4H
z, 1H / 2), 4.59 (dd, J = 4.63, 12.4Hz, 1H / 2), 5.98 (d, J
= 12.4Hz, 1H / 2), 6.01 (d, J = 12.4Hz, 1H / 2), 7.0-7.4
(m, 5H) MS (m / z) 152 (M ⁺ ) Elemental analysis result by high resolution mass spectrum Found: 152.0848, Calcd for C ₉ H ₁₂ O ₂ , M = 152.0837

Example 3 Under a nitrogen stream, 234 mg (1.3 mmol) of 1-methoxy-3-phenylthio-1-propene and 2 ml of tetrahydrofuran were charged into a reactor, cooled to -78 ° C,
Under stirring, 0.59 ml (1.3 mmol) of a 2.2 M solution of t-butyllithium in pentane is added dropwise over 3 minutes. Thereafter, the mixture is stirred at the same temperature for 10 minutes, 0.67 ml (3.9 mmol) of hexamethylphosphorylamide is added, and the mixture is stirred for 1 minute. Thereafter, a solution obtained by dissolving 0.13 ml (1.0 mmol) of phenyl- (1-propenyl) -ketone in 3 ml of tetrahydrofuran was taken for 3 minutes.
The mixture is added dropwise at 78 ° C, and the mixture is further stirred at the same temperature for 20 minutes. Thereafter, the same post-treatment as in Example 1 was performed, and phenyl- (2-
193 mg (59.3% yield) of methyl-3-phenylthio-5-methoxy-4-pentenyl) -ketone are obtained. ^{IR (neat) 1675, 1632cm -1} 1 HNMR (C 6 D 6) δ 1.11 (m, 4H), 2.7-3.3 (m, 3H), 3.04
(s, 3H), 4.4-4.8 (m, 1H), 6.06 (d, J = 12.7Hz, 1H / 2),
6.14 (d, J = 12.7Hz, 1H / 2), 7.08-8.0 (m, 10H) MS (m / z) 217 (M ⁺ -C ₆ H ₅ S)

Example 4 Phenyl- (2-methyl-3-phenylthio-5-methoxy-4-pentenyl) -ketone 1 obtained in Example 3
08 mg (0.34 mmol) and 4 m of dioxane
1 and 1 ml of water, 300 mg (1.402 mmol) of sodium periodate was added at room temperature, and the mixture was stirred for 9 hours. Thereafter, the same post-treatment as in Example 2 was carried out, and phenyl-
48 mg (yield 69.7%) of (2-methyl-4-formyl-3-butenyl) -ketone are obtained. ^{IR (neat) 1682cm -1 1 HNMR} (CDCl 3) δ 1.22 (d, J = 6.35Hz, 3H), 3.13 (s, 2
H), 3.14 (m, 1H), 6.11 (dd, J = 7.81, 16.1Hz, 1H), 6.8
9 (dd, J = 6.34, 16.1Hz, 1H), 7.1-8.0 (m, 5H), 9.50 (d,
J = 7.81Hz, 1H) MS (m / z) 202 (M ⁺ ) Elemental analysis result by high resolution mass spectrum Found: 202.0995, Calcd for C ₁₃ H ₁₄ O ₂ , M = 202.0994

Example 5 A reactor was charged with 70 mg (0.39 mmol) of 1-methoxy-3-phenylthio-1-propene and 2 ml of tetrahydrofuran under a stream of nitrogen and cooled to -78 ° C.
Under stirring, 0.23 ml (0.39 mmol) of a 1.7 M solution of t-butyllithium in pentane is added dropwise over 3 minutes. Thereafter, the mixture is stirred at the same temperature for 10 minutes, 0.2 ml (1.17 mmol) of hexamethylphosphorylamide is added, and the mixture is stirred for 1 minute. Thereafter, 4- (t-butyldimethylsilyloxy) -2-cyclopentenone 65 mg
(0.3 mmol) in 1 ml of tetrahydrofuran was added dropwise at -78 ° C over 3 minutes, and the mixture was further stirred at the same temperature for 15 minutes. Thereafter, the same post-treatment as in Example 1 was performed to obtain 4- (t-butyldimethylsilyloxy) -3.
98 mg (yield 83.7%) of-(1-phenylthio-3-methoxy-2-propenyl) -cyclopentanone are obtained. ^{IR (neat) 1745cm -1 1 HNMR} (C 6 D 6) δ -0.04 (s, 3H / 2), -0.00 (s, 3H / 2), 0.
02 (s, 3H / 2), 0.06 (s, 3H / 2), 0.92 (s, 9H), 1.2-2.4
(m, 5H), 2.9-3.3 (m, 1H), 3.04 (s, 3H), 3.80 (m, 1H),
4.39 (m, 1H), 5.92 (d, J = 12.4Hz, 1H / 2), 6.15 (d, J = 1
2.4Hz, 1H / 2), 7.0-7.4 (m, 5H)

Example 6 4- (t-Butyldimethylsilyloxy) -3- (1-phenylthio-3-methoxy-2- obtained in Example 5
Propenyl) -cyclopentanone 81 mg (0.206
mmol), 4 ml of dioxane and 1 ml of water, and 200 mg (0.9 mg) of sodium periodate at room temperature.
35 mmol) and stirred for 7 hours. Hereinafter, Example 2
The same post-treatment as described above is carried out to obtain 45 mg of 4- (t-butyldimethylsilyloxy) -3- (2-formylethenyl) -cyclopentanone (81.8% yield). IR (neat) 1745, 1683, 1638cm -1 1 HNMR (CDCl 3) δ 0.06 (s, 6H), 0.88 (s, 9H), 2.0-3.
1 (m, 5H), 4.23 (q-like, J = 6.83Hz, 1H), 6.17 (dd, J = 7.
32, 15.6Hz, 1H), 6.80 (dd, J = 6.83, 15.6Hz, 1H), 9.5
5 (d, J = 7.32Hz, 1H) MS (m / z) 268 (M ⁺ ) Elemental analysis result by high resolution mass spectrum Found: 268.1517, Calcd for C ₁₄ H ₂₄ O ₃ Si, M = 268.1495

Example 7 75 mg (0.39 mmol) of 1-ethoxy-3-phenylthio-1-propene as alkenylthioethers
l) used, 4- (t-butyldimethylsilyloxy)-
The reaction and post-treatment were carried out in the same manner as in Example 5 except that 2-cyclopentenone was dissolved in 3 ml of tetrahydrofuran.
91 mg (yield 74.6%) of-(t-butyldimethylsilyloxy) -3- (1-phenylthio-3-ethoxy-2-propenyl) -cyclopentanone are obtained. ^{IR (neat) 1748cm -1 1 HNMR} (C 6 D 6) δ -0.04 (s, 3H / 2), -0.00 (s, 3H / 2), 0.
03 (s, 3H / 2), 0.07 (s, 3H / 2), 0.93 (s, 9H), 0.94 (t, J
= 6.83Hz, 3H), 1.3-2.7 (m, 5H), 3.28 (q, J = 6.83Hz, 2
H), 3.29-3.9 (m, 2H), 4.40 (m, 1H), 5.6-6.2 (m, 1H),
7.0-7.5 (m, 5H)

Example 8 4- (t-Butyldimethylsilyloxy) -3- (1-phenylthio-3-ethoxy-2- obtained in Example 7
Propenyl) -cyclopentanone 90 mg (0.2 mm
ol), and the reaction and post-treatment were carried out in the same manner as in Example 6 to obtain 4- (t-butyldimethylsilyloxy)-
3- (2-formylethenyl) -cyclopentanone 46
mg (83.6% yield).

Example 9 76 mg of 1-methoxy-2-methyl-3-phenylthio-1-propene as alkenylthioethers
(0.39 mmol), except that the reaction and post-treatment were carried out in the same manner as in Example 5 to obtain 4- (t-butyldimethylsilyloxy) -3- (1-phenylthio-2-methyl-3-
Methoxy-2-propenyl) -cyclopentanone 90m
g (74.4% yield). IR (neat) 1742cm ^{-1 1} HNMR (C ₆ D ₆ ) δ -0.06 (s, 3H / 2), 0.00 (s, 3H / 2), 0.1
3 (s, 3H / 2), 0.21 (s, 3H / 2), 0.89 (s, 9H / 2), 0.98 (s,
9H / 2), 1.67 (s, 3H / 2), 1.88 (s, 3H / 2), 1.9-3.2 (m, 6
H), 2.92 (s, 3H / 2), 2.98 (s, 3H / 2), 4.15 (m, 1H), 5.1
7 (m, 1H / 2), 5.27 (s, 1H / 2), 7.0-7.4 (m, 5H)

Example 10 63 mg of 4- (t-butyldimethylsilyloxy) -3- (1-phenylthio-2-methyl-3-methoxy-2-propenyl) -cyclopentanone obtained in Example 9
(0.154 mmol), and the reaction and post-treatment were carried out in the same manner as in Example 6 to obtain 38 mg of 4- (t-butyldimethylsilyloxy) -3- (2-formyl-2-methylethenyl) -cyclopentanone ( (Yield 88.3%)
Get. IR (neat) 1742, 1682, 1640cm -1 1 HNMR (CDCl 3) δ 0.02 (s, 3H), 0.04 (s, 3H), 0.85
(s, 9H), 1.85 (s, 3H), 1.9-2.9 (m, 4H), 3.34 (m, 1H),
4.23 (q-like, J = 6.83Hz, 1H), 6.28 (d, J = 9.76Hz, 1H),
9.45 (s, 1H) MS (m / z) 282 (M ⁺ ) Elemental analysis result by high resolution mass spectrum Found: 282.1645, Calcd for C ₁₅ H ₂₆ O ₃ Si, M = 282.1651

Example 11 1-methoxy-2,3 as alkenylthioethers
-Dimethyl-3-phenylthio-1-propene 82 m
The reaction and post-treatment were carried out in the same manner as in Example 5 except that g (0.39 mmol) was used, and 4- (t-butyldimethylsilyloxy) -3- (1-phenylthio-1,2-dimethyl-3-methoxy- 116 mg (92% yield) of 2-propenyl) -cyclopentanone are obtained. Top spot IR (neat) 1745 cm ^-1 MS (m / z) 310 (M ⁺ -C ₆ H ₅ SH) ¹ H NMR (C ₆ D ₆ ) δ -0.07 (s, 3H), -0.04 (s, 3H) , 0.90
(s, 12H), 1.25 (s, 3H), 1.6-2.0 (m, 5H), 3.27 (s, 3
H), 4.20 (m, 1H), 5.78 (s, 1H), 7.0-7.5 (m, 5H) Lower spot IR (neat) 1740cm ^-1 MS (m / z) 310 (M ⁺ -C ₆ H ₅ SH ) ¹ HNMR (C ₆ D ₆ ) δ 0.20 (s, 3H), 0.33 (s, 3H), 0.87 (s,
3H), 1.03 (s, 9H), 1.88 (s, 3H), 2.0-2.5 (m, 5H), 2.9
7 (s, 3H), 4.87 (m, 1H), 5.20 (s, 1H), 7.0-7.5 (m, 5H)

Example 12 84 mg of 4- (t-butyldimethylsilyloxy) -3- (1-phenylthio-1,2-dimethyl-3-methoxy-2-propenyl) -cyclopentanone obtained in Example 11 (0.199 mmol), and the reaction and post-treatment were carried out in the same manner as in Example 6 to give 4- (t-butyldimethylsilyloxy) -3- (2-formyl-1,2
-Dimethylethenyl) -cyclopentanone 44 mg (74.5% yield, cis: trans = 43: 57) is obtained. IR (neat) 1745, 1662, 1617cm ^{-1 1} HNMR (CDCl ₃ ) δ 0.00 (s, 3HX43 / 100), 0.05 (s, 3HX5
7/100), 0.08 (s, 3HX57 / 100), 0.13 (s, 3HX43 / 100), 0.8
7 (s, 9HX43 / 100), 0.89 (s, 9HX57 / 100), 1.88 (s, 3HX43
/ 100), 1.94 (s, 3HX57 / 100), 1.95 (s, 3HX43 / 100), 2.2
1 (s, 3HX57 / 100), 2.3-2.9 (m, 5H), 4.35 (m, 1H), 10.2
(s, 1HX57 / 100), 10.3 (s, 1HX43 / 100) MS (m / z) 281 (M ⁺ -CH ₃ )

──────────────────────────────────────────────────の Continuation of the front page (51) Int.Cl. ⁷ identification symbol FI C07F 7/18 C07F 7/18 A (58) Investigated field (Int.Cl. ⁷ , DB name) C07C 323/00 C07C 45 / 00 C07C 49/00 C07C 319/00 C07F 7/00 CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] 1. The general formula [1] (Wherein, R ¹ is an alkyl group having 1 to 10 carbon atoms, 6 to 10 carbon atoms)
R ² represents an aryl group having 6 to 15 carbon atoms, an aryl group having 7 to 15 carbon atoms, or an aralkyl group having 7 to 15 carbon atoms;
15 aralkyl group, <br/> also an alkyl group having 1 to 10 carbon atoms or a hydrogen atom, or R ¹ and R ² are bonded to carbon atoms
Represents 2 to 10 alkylene groups. Here, the alkylene group is an OSi (R ⁷ ) ₃ group (where R ⁷ is the same or different)
Or an alkyl group having 1 to 4 carbon atoms) , or an alkoxy group having 1 to 5 carbon atoms or a halogen atom. R ³ has 6 carbon atoms (which may be substituted with an alkoxy group having 1 to 5 carbon atoms or a halogen atom)
Represents an aryl group having from 15 to 15, R ⁴ and R ⁵ each represent a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R ⁶ represents an alkyl group having 1 to 10 carbon atoms. A) a vinyl ether derivative represented by the formula: 2. The general formula [2] (Wherein, R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above), and a lithiating agent is reacted with the alkenyl thioether represented by the general formula [3]. ^{2. The} method for producing a vinyl ether derivative according to claim 1, wherein an α, β-unsaturated ketone represented by the formula ( ¹ ) is used. 3. A general formula [4] wherein the vinyl ether derivative according to claim 1 is reacted with an oxidizing agent. (Wherein, R ¹ , R ² , R ⁴ and R ⁵ have the same meanings as described above).