JP2002088023A - Method for producing alcohol and/or hydrocarbon from halogenated hydrocarbon through organic zinc compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing an alcohol useful as a raw material for pharmaceuticals, agrochemicals and other chemicals on an industrial scale by reacting an aldehyde with a haloester, etc., having halogen atom at or beyond the β-position. SOLUTION: The method for producing an alcohol and/or a hydrocarbon comprises the reaction of a halogenated hydrocarbon expressed by general formula X-R (X is a halogen atom; and R is a >=2C alkyl which may have substituent) and having the halogen atom bonded to either one of the carbon atoms of the alkyl chain with metallic zinc in a solvent in the presence of a nitrogen-containing compound and adding an aldehyde expressed by general formula R'-CHO (R' is an aryl group or a heterocyclic group which may have substituent) and a tri-substituted silyl halide to the reaction product.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing alcohols and / or hydrocarbons from halogenated hydrocarbons via an organozinc compound. Further, the present invention relates to a method for producing an organozinc compound from halogenated hydrocarbons.

[0002]

2. Description of the Related Art Numerous reports have been made on the synthesis of hydroxyesters by the reformatsky type reaction between aldehydes and α-haloesters. on the other hand,
When a haloester having a halogen atom beyond the β-position is used as a starting material, it is generally considered that a reformatsky type reaction is difficult.

[0003] Therefore, in the prior art, a method has been proposed in which the reaction proceeds by using a specific catalyst such as copper or titanium. For example, as a method for producing an organozinc compound, complexing with a different metal such as Cu described in "Tetrahedron Letter., 1985, 26, 5559-5562",
There is a method using metal zinc which has been activated in advance by an acid treatment or the like described in “Tetrahedron Letter., 1991, 32, 4909-4912”. That is, both methods require the use of activated metallic zinc.

In the case of synthesizing alcohols using the produced organozinc compound, J. Org. Chem., 1988, May
3,2390-2392 "or metal salts such as CuCN-2LiCl, or" J. Org. Chem., 1988, 53, 1343-134.
It is necessary to further add a metal salt such as (i-PrO) ₃ TiCl described in “4”.

[0005]

However, in the above-mentioned synthesis method, the reaction technique tends to be complicated due to activation of metal zinc and addition of a metal salt, and the cost tends to be high. Moreover, in the conventional reaction, it is necessary to carry out the reaction under relatively severe conditions such as extremely low temperature. For this reason, it is not easy to carry out a method for producing alcohols using haloesters beyond the β-position as a starting material on an industrial scale.

[0006] Alcohols produced by reacting aldehydes with haloesters at positions beyond the β-position are useful as raw materials for pharmaceuticals, agricultural chemicals and other chemicals. The development of a method that can be manufactured with a high demand has been desired.

Accordingly, it is a main object of the present invention to provide a method for producing alcohols and / or hydrocarbons from halogenated hydrocarbons via an organozinc compound on an industrial scale.

[0008]

The inventor of the present invention has conducted intensive studies in order to solve the problems of the prior art.
It has been found that the above object can be achieved by reacting halogenated hydrocarbons under specific conditions, and the present invention has been completed.

That is, the present invention is represented by the general formula XR (where X is a halogen atom, R is an alkyl group having 2 or more carbon atoms and may have a substituent). And, after reacting a halogen atom with a metal zinc in the presence of a nitrogen-containing compound in a solvent, a halogenated hydrocarbon bonded to any carbon atom of the alkyl chain,
General formula R'-CHO (however, R 'is an aryl group or a heterocyclic group, which may have a substituent).
The present invention relates to a method for producing alcohols and / or hydrocarbons by adding an aldehyde represented by the formula (1) and a trisubstituted silyl halide.

The present invention further relates to a compound represented by the general formula XR:
X represents a halogen atom, and R represents an alkyl group having 2 or more carbon atoms which may have a substituent. ) And a halogen atom is bonded to any carbon atom of the alkyl chain by reacting a halogenated hydrocarbon with metallic zinc in the presence of a nitrogen-containing compound in a solvent to form an organic zinc compound. It relates to a manufacturing method.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Production of Organozinc Compound The production method of the organozinc compound of the present invention has the general formula XR
(Where X is a halogen atom, and R is an alkyl group having 2 or more carbon atoms which may have a substituent), and the halogen atom is any carbon atom of the alkyl chain. An organic zinc compound is produced by reacting a halogenated hydrocarbon bonded to a metal zinc in a solvent in the presence of a nitrogen-containing compound.

As the halogenated hydrocarbon, a compound represented by the general formula X
-R (where X is a halogen atom, and R is an alkyl group having 2 or more carbon atoms (preferably 2 to 30, more preferably 2 to 20), which may have a substituent). The indicated compound is used. Further, the halogen atom of this compound is bonded to any carbon atom of the alkyl chain of the above alkyl group. The type of the substituent is not particularly limited as long as it does not have active hydrogen. For example, R ¹ to
Substituents of the kind (alkyl group, ester group, etc.) as shown by R ⁷ can be mentioned.

In the present invention, in particular, the above-mentioned alkyl group R which may have a substituent has the following general formulas a) to d) a) —CH ₂ — (CH ₂ ) ₁ —R ¹ b) —CH ｛ ^{_{(CH 2) m R 2}}} {(CH 2) n R 3} c) -C {(CH 2) o R 4} {(CH 2) p R 5} {(CH
₂ ) _q R ⁶ ｝ d) It is preferably any one of cycloalkyl groups which may have a substituent R ⁷ . Where l
And q represents an integer of 1 to 18, preferably 1 to 10.

The cycloalkyl group is not limited, but usually preferably has about 3 to 18 carbon atoms. For example, a cyclohexyl group, a cyclopentyl group and the like can be mentioned.

R ^{1 to} R ⁷ are not particularly limited as long as they do not have active hydrogen. Specifically, a hydrogen atom, an alkyl group (eg, a methyl group, an isopropyl group, a tert-butyl group, a pentyl group, a cyclopentyl group, a cyclohexyl group, etc.), an alkenyl group (eg, a vinyl group, an allyl group,
Cinnamyl group), alkynyl group (eg, propargyl group), aryl group (eg, phenyl group, naphthyl group, anthranyl group, etc.), heterocyclic group (eg, pyridyl group, thiazolyl group, oxazolyl group, imidazolyl group, furyl group, pyrrolyl) Group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, sulfolanyl group, piperidinyl group, pyrazolyl group, tetrazolyl group, etc.), alkoxy group (for example, methoxy group, ethoxy group, propyloxy group, pentyloxy group, cyclopentyloxy group, xylohexyloxy) Group), an aryloxy group (eg, a phenoxy group), an ester group (eg, a methyl ester group, an ethyl ester group, a propyl ester group, an isopropyl ester group, a tert-butyl ester group, a pentyl ester group, a hexyl ester group, Hexyl ester group, etc.), alkoxycarbonyl group (eg, methyloxycarbonyl group, ethyloxycarbonyl group, butyloxycarbonyl group, etc.), aryloxycarbonyl group (eg, phenyloxycarbonyl group, etc.), acyl group (eg, acetyl group, methylcarbonyl group) Group, ethylcarbonyl group, propylcarbonyl group, pentylcarbonyl group, cyclohexylcarbonyl group, phenylcarbonyl group, pyridylcarbonyl group, etc.), amino group (eg, dimethylamino group, diethylamino group, etc.), amide group (eg, methylcarbonylamino group, Ethylcarbonylamino group, propylcarbonylamino group, etc.), acetal group (eg, dimethylacetal group, diethylacetal group, etc.), halogen group (eg, F-, Cl-, Br-, I-), And the like. In the present invention, among these groups, those having usually about 1 to 18 carbon atoms can be used.

In the present invention, among the groups mentioned above, an alkyl group, an aryl group, an ester group, a cyano group and the like can be preferably used. More preferred are ester groups (particularly those having 2 to 10 carbon atoms).

Specific examples of the halogenated hydrocarbons include 1-iodopentane, 2-iodopentane, 3-iodopentane, 1-bromopentane, 2-bromopentane, 3-bromopentane, iodocyclopentane, and 1-iodopentane. −
Bromoiodopentane, 2-bromoiodopentane, 3
-Bromoiodopentane, 4-bromoiodopentane,
5-bromoiodopentane, 1-bromo-2-iodopentane, 2-bromo-2-iodopentane, 3-bromo-2-iodopentane, 4-bromo-2-iodopentane, 5-bromo-2-iodopentane , 1-bromo-3
-Iodopentane, 2-bromo-3-iodopentane,
3-bromo-3-iodopentane, 1-bromoiodocyclohexane, 2-bromoiodocyclohexane,
Bromoiodocyclohexane, methyl 5-iodopentanoate, methyl 4-iodopentanoate, methyl 3-iodopentanoate, methyl 2-iodopentanoate, methyl 5-bromopentanoate, methyl 4-bromopentanoate, 3-
Methyl bromopentanoate, methyl 2-bromopentanoate, ethyl 5-iodopentanoate, ethyl 4-iodopentanoate, ethyl 3-iodopentanoate, ethyl 2-iodopentanoate, ethyl 5-bromopentanoate, 4-bromo Ethyl pentanoate, ethyl 3-bromopentanoate,
Ethyl 2-bromopentanoate, 5-iodopentanenitrile, 4-iodopentanenitrile, 3-iodopentanenitrile, 2-iodopentanenitrile, 5-bromopentanenitrile, 4-bromopentanenitrile, 3-bromopentanenitrile
Bromopentanenitrile, 2-bromopentanenitrile, 5-iodopentyl acetate, 4-iodopentyl acetate, 3-iodopentyl acetate, 2-iodopentyl acetate, 5-iodopentyldimethylamine, 4-iodopentyldimethylamine, 3- Iodopentyldimethylamine, 2-iodopentyldimethylamine, 5-bromopentyldimethylamine, 4-bromopentyldimethylamine, 3-bromopentyldimethylamine, 2-bromopentyldimethylamine, 5-bromopentyldimethylamine
Iodopentane methyl ether, 4-iodopentane methyl ether, 3-iodopentane methyl ether, 2
-Iodopentane methyl ether, 5-bromopentane methyl ether, 4-bromopentane methyl ether,
3-bromopentane methyl ether, 2-bromopentane methyl ether, 5-iodopentyl diethyl acetal, 4-iodopentyl diethyl acetal, 3-iodopentyl diethyl acetal, 2-iodopentyl diethyl acetal, 5-bromopentyl diethyl acetal, 4 -Bromopentyl diethyl acetal, 3-
Bromopentyl diethyl acetal, 2-bromopentyl diethyl acetal, 1-iodo-4-pentene, 1
-Iodo-3-pentene, 1-iodo-2-pentene,
1-iodo-1-pentene, 1-bromo-4-pentene, 1-bromo-3-pentene, 1-bromo-2-pentene, 1-bromo-1-pentene, 1-iodo-4-pentene, 1- Iodo-3-pentyne, 1-iodo-2-
Pentine, 1-iodo-1-pentyne, 1-bromo-4
-Pentin, 1-bromo-3-pentyne, 1-bromo-
2-pentine, 1-bromo-1-pentyne, benzyl chloride, benzyl bromide, benzyl iodide, 2-iodomethylthiazole, 2-iodomethylimidazole and the like.

In the above b), the group {(CH ₂ ) _m
R ² } and the group {(CH ₂ ) _n R ³ } may be the same as or different from each other. Similarly, in c) above, the group —C {(CH ₂ ) _o R ⁴ } and the group {(CH ₂ ) _p R ⁵ }
And the group {(CH ₂ ) _q R ⁶ } may be the same or different.

The solvent is not particularly limited as long as the halogenated hydrocarbon is uniformly dissolved or dispersed, and examples thereof include ethers, esters, ketone ethers, ketone esters, ester ethers, aromatics, and hydrocarbons. Hydrogen system,
A known organic solvent such as a halogen-based solvent can be suitably used.

Examples of the ether-based solvent include tetrahydrofuran (THF), diethyl ether, dipropyl ether, dibutyl ether, 1,4-dioxane, diglyme, dimethoxyethane (DME), diethyl carbitol, diethyl cellolbu and the like. Examples of the ester solvent include methyl acetate, ethyl acetate, methyl butyrate, ethyl butyrate, methyl propionate, ethyl propionate, and ethyl formate. Examples of the ketone solvent include acetone, acetonylacetone, diisobutyl ketone, diethyl ketone, dipropyl ketone, methyl amyl ketone, methyl butyl ketone, methyl cyclohexanone, methyl dipropyl ketone, methyl ethyl ketone, methyl isobutyl ketone, methyl propyl ketone,
Medisyl oxide and the like. Examples of the ketone ether solvent include acetal etol ether, methyl ethoxyethyl ether and the like. Examples of the ketone ester solvent include ethyl acetoacetate, ethyl pyruvate and the like. Examples of the ester ether solvents include butyl carbitol acetate, butyl cellosolve acetate, carbitol acetate, cellosolve acetate, acetic acid 3
-Methoxybutyl, methyl carbitol acetate, methyl cellosolve acetate and the like. As the aromatic solvent,
For example, benzene, toluene, xylene, decalin, cymene and the like can be mentioned. Examples of the hydrocarbon solvent include petroleum ether, pentane, cyclopentane, hexane, cyclohexane and the like. As the halogen-based solvent,
For example, dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, perchloroethylene, bromoethylene, bromoform, chlorobenzene, bromobenzene,
Dichlorobenzene and the like. One or more of these solvents can be used. In the present invention, THF, toluene and the like are particularly preferable.

The concentration of the above-mentioned halogenated hydrocarbons in the solvent may be appropriately set according to the type of the halogenated hydrocarbons or the solvent to be used.
It may be about mol / l, preferably 0.5 to 1 mol / l.

The nitrogen-containing compound is not limited, but usually a nitrogen-containing organic compound is used. Examples of the nitrogen-containing organic compound include amide compounds, urea compounds, and amine compounds. At least one of these can be used. Examples of amide compounds include N, N
-Dimethylacetamide (DMA), N-methylpyrrolidone (NMP), N, N'-dimethylimidazolinone (DMI), hexamethyl phosphorotriamide (HMP
T), N, N-dimethylformamide (DMF) and the like. As urea compounds, for example, N, N,
N ', N'-tetramethylurea (TMU) and the like. Examples of the amine compound include triethylamine, N, N-dimethylaniline, monoethanolamine, triethanolamine, 1-piperidino-3,3-
Dimethyl-2-butanol (PDB), 1-pyrrolidino-3,3-dimethyl-2-butanol and the like.

The amount of the nitrogen-containing compound to be used can be appropriately set according to the kind of the halogenated hydrocarbon to be used and the like. What is necessary is to make it 2 mol times.

Known or commercially available metal zinc can be used. The higher the purity of the metallic zinc, the better. Usually, the purity is 90% or more, particularly 99% or more. Although the shape of the metallic zinc is not particularly limited, it is usually desirable to use the metallic zinc in a powder form. In particular, metallic zinc powder of about 100 to 500 mesh can be suitably used.

The amount of the metal zinc to be reacted with the halogenated hydrocarbon may be appropriately set according to the type and amount of the halogenated hydrocarbon used, and is usually equimolar to the halogenated hydrocarbon used. An amount or more may be used.

The reaction conditions can be appropriately changed depending on the kind of the halogenated hydrocarbon used and the like. The reaction temperature may be usually about 0 to 80 ° C. Further, the above reaction is preferably performed with stirring. In general, the above reaction causes the reaction system to change to a bluish white turbid solution state, so that the formation of the organozinc compound can be inferred from the change in the form. Also, take a sample of the reaction system,
This is hydrolyzed with an acid, and the production rate can be confirmed by gas chromatography analysis or the like. When the reaction system is heated, the heating of the reaction system may be stopped when the reaction is completed, and the reaction system may be cooled to room temperature.

The organozinc compound obtained by the method of the present invention is
The compound can be used as a starting material for synthesizing another compound as it is in the solvent. This organic zinc compound is useful as a raw material for producing pharmaceuticals, agricultural chemicals, and the like, in addition to chemicals such as alcohols and hydrocarbons. 2. Production of Alcohols and / or Hydrocarbons The production method of alcohols or hydrocarbons of the present invention is obtained by the general formula XR (where X is a halogen atom, R is an alkyl group having 2 or more carbon atoms and And a halogen atom bonded to any carbon atom of the alkyl chain in a solvent in the presence of a nitrogen-containing compound. After reacting with metal zinc, an aldehyde represented by the general formula R'-CHO (where R 'is an aryl group or a heterocyclic group which may have a substituent) and trisubstitution It is intended to produce alcohols and / or hydrocarbons by adding a type silyl halide.

That is, in the above-mentioned method for producing an organic zinc compound, a halogenated hydrocarbon is reacted with metallic zinc, and then the above aldehyde and trisubstituted silyl halide are further added. Therefore, the method of reacting halogenated hydrocarbons with metallic zinc may be the same as the above-described method for producing organometallic zinc.

In the present invention, as described above, the reaction system after reacting the halogenated hydrocarbon with the metal zinc has the general formula R'-CHO (where R 'is an aryl group or a heterocyclic group, Aldehydes which may have a substituent.) And trisubstituted silyl halides are added.

As the aldehyde, a compound represented by the general formula R'-CHO (where R 'is an aryl group or a heterocyclic group which may have a substituent) is used. good.

Here, R ′ is an aryl group (eg, phenyl group, naphthyl group, anthranyl group, etc.), a heterocyclic group (eg, pyridyl group, thiazolyl group, oxazolyl group, imidazolyl group, furyl group, pyrrolyl group, pyrazinyl group). Group, pyrimidylnyl group, pyridazinyl group, sulfolanyl group, piperidinyl group, virazolyl group, tetrazolyl group, etc.). The number of carbon atoms of R 'may be generally about 1 to 18.

Further, these R's may have a substituent. As the substituent, for example, a halogen group (F—, C
1-, Br-, I-), an alkyl group (for example, a methyl group,
Ethyl group, propyl group, isopropyl group, butyl group, te
rt-butyl group, etc.), acyl group (eg, acetyl group, ethylcarbonyl group, propylcarbonyl group, etc.), amino group (eg, dimethylamino group, diethylamino group, etc.), cyano group and the like. R ′ may have one or more of these substituents. When it has two or more substituents, they may be the same or different.

Specific examples of the above aldehyde include, for example, benzaldehyde, 4-tolualdehyde, 3-tolualdehyde, 2-tolualdehyde, 4-chlorobenzaldehyde, 3-chlorobenzaldehyde, 2-chlorobenzaldehyde, 4-bromobenzaldehyde, -Bromobenzaldehyde, 2-bromobenzaldehyde, 4-
Anisaldehyde, 3-anisaldehyde, 2-anisaldehyde, 4-cyanobenzaldehyde, 3-cyanobenzaldehyde, 2-cyanobenzaldehyde, 1-
Formylnaphthalene, 2-formylnaphthalene, 1-formylanthracene, 2-formylanthracene, 3-
Formyl anthracene, 2-formyl pyridine, 3-formyl pyridine, 4-formyl pyridine, 2-formyl quinoline, 3-formyl quinoline, 4-formyl quinoline, 5-formyl quinoline, 6-formyl quinoline, 7
-Formylquinoline and the like.

The addition amount of the aldehyde may be usually equimolar or more than the amount of the halogenated hydrocarbon used.

The trisubstituted silyl halides include:
It suffices that the silicon atom is bonded to one halogen atom and the rest is substituted by three substituents. The three substituents may be the same or different from each other. 3
As the substituted silyl halide, those obtained by any of the production methods can be used, and commercially available products can also be used.

Particularly, in the present invention, the trisubstituted silyl halide is represented by the following general formula:

[0037]

Embedded image

(However, X is a halogen atom, and R ^{8 to} R ¹⁰ are the same or different and each represents an alkyl group or an aryl group).

Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a tert-butyl group, a pentyl group, a hexyl group, a cyclopentyl group and a cyclohexyl group. Examples of the aryl group include a phenyl group, a naphthyl group, and an anthranyl group. The alkyl group or the aryl group usually has about 1 to 18, preferably 1 to 6, carbon atoms. Further, the alkyl group or the aryl group may have a substituent such as a methyl group or an ethyl group.

As the trisubstituted silyl halide, specifically, trimethylsilyl chloride (TMSCl), dimethyl tert-butylsilyl chloride, dimethylphenylsilyl chloride, trimethylsilyl bromide, trimethylsilyl iodide and the like can be used.

The amount of the trisubstituted silyl halide to be added may be generally about 1 to 10 times, preferably 1.5 to 3 times, the amount of the halogenated hydrocarbon used.

The above aldehyde and trisubstituted silyl halide are added to the reaction system. In this case, the aldehyde and the trisubstituted silyl halide may be added at the same time, or one of them may be added first. After both additions are completed,
Stirring is usually continued at a temperature of about 0 to 80 ° C. for about 1 to 18 hours, and then hydrolysis is performed. The hydrolysis may be performed according to a known method, for example, by adding an aqueous solution of a salt such as an aqueous solution of saturated ammonium chloride as needed. Next, the reaction product may be extracted with a solvent such as ethyl acetate according to a known extraction method.

The extracted reaction product is optionally washed, and if necessary, purified, to finally obtain alcohols and / or hydrocarbons. The alcohol is usually represented by the general formula R'CH (OH)
The alcohol represented by R ¹ is obtained. Further, as the above-mentioned hydrocarbons, hydrocarbons having a structure corresponding to a form in which alcohols (the above-mentioned OH) represented by the above-mentioned general formula are dehydrated are usually obtained. That is, hydrocarbons having a C ＝ C bond formed by dehydration of OH together with adjacent hydrogen can be obtained.

In the method of the present invention, only the above-mentioned alcohols or only hydrocarbons can be produced by appropriately controlling the reaction conditions (reaction temperature, reaction time, etc.).
Similarly, a mixture in which both are mixed can be obtained. In general, for example, if the reaction temperature is increased or the reaction time is lengthened, the dehydration reaction is promoted. Therefore, such an operation can increase the production rate of hydrocarbons.

The above-mentioned alcohols and hydrocarbons are useful as intermediates for pharmaceuticals, liquid crystals, catalysts and other chemicals, and are subjected to various reactions such as substitution, elimination, alkylation, etc. Arbitrarily design
Can be manufactured.

[0046]

According to the production method of the present invention, organozinc compounds and alcohols can be produced relatively easily and efficiently. That is, 1) it can be used as it is without activating the metal zinc, and 2) relatively mild reaction conditions can be adopted as compared with the conventional method, so that it can greatly contribute to production on an industrial scale.

The alcohols and the like obtained by the production method of the present invention are useful as intermediates for pharmaceuticals, agricultural chemicals and other chemicals, and can be expected to be applied to the production of these products.

[0048]

EXAMPLES Examples and comparative examples are shown below to further clarify the features of the present invention. However, the scope of the present invention is not limited to the scope of the examples.

In each of the examples, alcohols and hydrocarbons produced via an organozinc compound were treated with ¹ H-
Confirmed by NMR, ¹³ C-NMR and HC COSY.

Example 1 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate,
The mixture was heated and stirred at 60 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 8
77 mg of benzaldehyde was added, and the mixture was stirred as it was for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude methyl 6-hydroxy-6-phenylhexanoate. This crude product was purified by silica column chromatography to give 643 mg (yield 7).
(0%) of methyl 6-hydroxy-6-phenylhexanoate.

Example 2 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate,
The mixture was heated and stirred at 60 ° C. for 1 hour. Next, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 1.161 g of 4-chlorobenzaldehyde were added, and the mixture was stirred as it was for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline, and crude 6-hydroxy-6- (4-
Methyl chlorophenyl) hexanoate was obtained. This crude product was purified by silica column chromatography to give 61
5 mg (58% yield) of methyl 6-hydroxy-6- (4-chlorophenyl) hexanoate was obtained.

Example 3 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate,
The mixture was heated and stirred at 60 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 1.161 g of 3-chlorobenzaldehyde were added, and the mixture was stirred as it was for 18 hours.

Thereafter, saturated ammonium chloride was added to terminate the reaction, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline, and crude 6-hydroxy-6- (3-
Methyl chlorophenyl) hexanoate was obtained. This crude product was purified by silica column chromatography to give 61
5 mg (58% yield) of methyl 6-hydroxy-6- (3-chlorophenyl) hexanoate was obtained.

Example 4 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate,
The mixture was heated and stirred at 60 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 1.161 g of 2-chlorobenzaldehyde were added, and the mixture was stirred as it was for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline, and crude 6-hydroxy-6- (2-
Methyl chlorophenyl) hexanoate was obtained. This crude product was purified by silica column chromatography,
1 mg (67% yield) of methyl 6-hydroxy-6- (2-chlorophenyl) hexanoate was obtained.

Example 5 A stirrer and zinc powder (99% purity) were charged into a 50-ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate,
The mixture was heated and stirred at 60 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 9
33 mg of 4-tolualdehyde was added, and the mixture was stirred as it was for 4 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline, and crude 6-hydroxy-6- (4-
Tol) methyl hexanoate was obtained. The crude product was purified by silica column chromatography to obtain 576 mg (yield 59%) of methyl 6-hydroxy-6- (4-tolu) hexanoate.

Example 6 A stirrer and zinc powder (99% purity) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, 4 ml of THF, 479 mg of N, N-dimethylacetamide and 1.0 g of methyl 5-iodopentanoate were added, and the mixture was heated with stirring at 60 ° C. for 1 hour. Next, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 1.083 g of 4-cyanobenzaldehyde were added, and the mixture was stirred as it was for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline, and crude 6-hydroxy-6- (4-
Methyl (cyanophenyl) hexanoate was obtained. This crude product was purified by silica column chromatography,
1 mg (49% yield) of methyl 6-hydroxy-6- (4-cyanophenyl) hexanoate was obtained.

Example 7 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate,
The mixture was heated and stirred at 60 ° C. for 1 hour. Next, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 1.124 g of 4-anisbenzaldehyde were added, and the mixture was stirred as it was for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude methyl 6- (4-anis) -6-hexenoate. The crude product was purified by silica column chromatography, and 533 mg (yield 53
%) Of methyl 6- (4-anis) -6-hexenoate.

Example 8 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, 4 ml of THF, 479 mg of N, N-dimethylacetamide and 1.0 g of methyl 5-iodopentanoate were added, and the mixture was heated with stirring at 60 ° C. for 1 hour. Next, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 1.124 g of 3-anisbenzaldehyde were added, and the mixture was stirred as it was for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline, and crude 6-hydroxy-6- (3-
Anis) methyl hexanoate was obtained. The crude product was purified by silica column chromatography to give 250 mg
(Yield 24%) of 6-hydroxy-6- (3-anis)
Methyl hexanoate was obtained.

Example 9 A stirrer and zinc powder (purity: 99%) were charged into a 50-ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate,
The mixture was heated and stirred at 60 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride, 93
Add 3 mg of 4-Tolbenzaldehyde and add 1
Stir for 8 hours.

Thereafter, saturated ammonium chloride was added to terminate the reaction, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude methyl 6- (4-tolu) -6-hexenoate. This crude product was purified by silica column chromatography, and 451 mg (50% yield).
Of methyl 6- (4-tolu) -6-hexenoate.

Example 10 A stirrer and zinc powder (purity: 99%) were charged into a 50-ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, 4 ml of THF, 479 mg of N, N-dimethylacetamide and 1.0 g of methyl 5-iodopentanoate were added, and the mixture was heated with stirring at 60 ° C. for 1 hour. Next, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 1.233 g of 4-N, N-dimethylaminobenzaldehyde were added, and the mixture was stirred as it was for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous solution of sodium sulfite and saturated saline to obtain crude methyl 6- (4-N, N-dimethylaminophenyl) -6-hexenoate. This crude product was purified by silica column chromatography to obtain 362 mg (yield 33%) of methyl 6- (4-N, N-dimethylaminophenyl) -6-hexenoate.

Example 11 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, 4 ml of THF, 545 mg of N-methylpyrrolidone and 942 mg of ethyl 5-iodopropionate were added, and the mixture was heated with stirring at 60 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 877 mg of benzaldehyde were added.
Stirred for hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous solution of sodium sulfite and saturated saline to obtain crude ethyl 4-hydroxy-4-phenylbutanoate. This crude product was purified by silica column chromatography to give 103 mg (yield 12
%) Of ethyl 4-hydroxy-4-phenylbutanoate.

Example 12 A stirrer and zinc powder (purity: 99%) were charged into a 50-ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of ethyl 5-iodobutanoate.
The mixture was heated and stirred at 0 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 87
7 mg of benzaldehyde was added and the mixture was stirred as it was for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude ethyl 5-hydroxy-5-phenylpentanoate. This crude product was purified by silica column chromatography, and 414 mg (yield 4
(5%) of ethyl 5-hydroxy-5-phenylpentanoate.

Example 13 A stirrer and zinc powder (purity: 99%) were charged into a 50-ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, 4 ml of THF, 479 mg of N, N-dimethylacetamide and 1.116 g of ethyl 6-iodohexanoate were added, and the mixture was heated with stirring at 60 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 877 mg of benzaldehyde were added, and the mixture was stirred for 18 hours.

Thereafter, saturated ammonium chloride was added to terminate the reaction, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude ethyl 7-hydroxy-7-phenylheptanoate. The crude product was purified by silica column chromatography to obtain 507 mg (yield 4).
9%) of crude ethyl 7-hydroxy-7-phenylheptanoate.

Example 14 A stirrer and zinc powder (purity: 99%) were charged into a 50-ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 819 mg of iodopentane.
The mixture was heated and stirred for hours. Then, after cooling to room temperature, 89
8 mg of trimethylsilyl chloride and 877 mg of benzaldehyde were added, and the mixture was stirred for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude 1-phenylhexanol. This crude product was purified by silica column chromatography to obtain 552 mg (75% yield) of 1-phenylhexanol.

Example 15 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 523 mg of benzyl chloride.
For 1 hour. Then, after cooling to room temperature,
898 mg of trimethylsilyl chloride and 877 m
g of benzaldehyde was added and the mixture was stirred as it was for 18 hours.

Thereafter, saturated ammonium chloride was added to terminate the reaction, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude 1,2-diphenylethanol. This crude product was purified by silica column chromatography, and 147 mg (18% yield) of 1,2-
Diphenylethanol was obtained.

Example 16 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, 4 ml of THF, 479 mg of N, N-dimethylacetamide and 1.0 g of methyl 5-iodopentanoate were added, and the mixture was heated with stirring at 60 ° C. for 1 hour. Then, after cooling to room temperature, 1 ml of trimethylsilyl chloride and 877 mg of benzaldehyde were added, and 18
Stirred for hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude methyl 6-hydroxy-6-phenylhexanoate. This crude product was purified by silica column chromatography to obtain 597 mg (yield 6).
5%) of methyl 6-hydroxy-6-phenylhexanoate was obtained.

Example 17 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, 4 ml of dichloromethane, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate were added, and the mixture was heated with stirring at 60 ° C. for 1 hour. Then, after cooling to room temperature, 1 ml of trimethylsilyl chloride and 877 mg of benzaldehyde were added, and 18
Stirred for hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude methyl 6-hydroxy-6-phenylhexanoate. The crude product was purified by silica column chromatography, and 478 mg (yield 5
2%) of methyl 6-hydroxy-6-phenylhexanoate.

Example 18 A stirrer and zinc powder (purity: 99%) were charged into a 50-ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, 4 ml of toluene, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate were added, and the mixture was heated and stirred at 60 ° C for 1 hour. Then, after cooling to room temperature, 1 ml of trimethylsilyl chloride and 8 ml
77 mg of benzaldehyde was added and the mixture was stirred for 1 hour.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude methyl 6-hydroxy-6-phenylhexanoate. This crude product was purified by silica column chromatography, and 533 mg (yield 5
8%) of methyl 6-hydroxy-6-phenylhexanoate.

Example 19 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate,
The mixture was heated and stirred at 60 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 8
77 mg of benzaldehyde was added, and the mixture was stirred as it was for 4 days.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude methyl 6-phenyl-6-hexenoate. This crude product was purified by silica column chromatography, and 565 mg (yield 65%) of 6
-Methyl phenyl-6-hexenoate was obtained.

Example 20 A stirrer and zinc powder (purity: 99%) were charged into a 50 ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, 4 ml of toluene, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate were added, and the mixture was heated and stirred at 60 ° C for 1 hour. Next, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 877 mg of benzaldehyde were added, and the mixture was stirred at 80 ° C. for 4 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline to obtain crude methyl 6-phenyl-6-hexenoate. This crude product was purified by silica column chromatography, and 464 mg (yield 55%) of 6
-Methyl phenyl-6-hexenoate was obtained.

Example 21 A stirrer and zinc powder (purity: 99%) were placed in a 50-ml two-necked flask equipped with a Dimroth, and the inside of the flask was dried under reduced pressure and replaced with argon gas. Using a syringe, add 4 ml of THF, 545 mg of N-methylpyrrolidone and 1.0 g of methyl 5-iodopentanoate,
The mixture was heated and stirred at 60 ° C. for 1 hour. Then, after cooling to room temperature, 898 mg of trimethylsilyl chloride and 1.161 g of 4-chlorobenzaldehyde were added, and 6
Stirred at 0 ° C. for 18 hours.

Thereafter, the reaction was terminated by adding saturated ammonium chloride, and the reaction product was extracted with ethyl acetate. The extracted organic layer was washed with a 5% aqueous sodium sulfite solution and saturated saline, and crude 6-hydroxy-6- (4-
Methyl chlorophenyl) hexanoate was obtained. The crude product was purified by silica column chromatography,
3 mg (52% yield) of methyl 6-hydroxy-6- (4-chlorophenyl) hexanoate were obtained.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 229/64 C07C 229/64 253/30 253/30 255/57 255/57 (71) Applicant 000157717 Maru Ryoyu Kagaku Kogyo Co., Ltd. 3-7-1, Tomobuchi-cho, Miyakojima-ku, Osaka-shi, Osaka (72) Inventor Yoshio Ishino 5-428, Imadegawa-kami, Teramachi-dori, Teramachi-dori, Kyoto-shi, Kyoto-shi ) Inventor Takumi Mizuno 6-171 Andodoji-cho, Itami-shi, Hyogo (72) Inventor Toshiyuki Miyata 104-5, Nishino, Sakai-shi, Osaka (72) Inventor Junichi Kobayashi 3-7-12, Tomobuchi-cho, Miyakojima-ku, Osaka-shi, Osaka No. Marubishi Yuka Kogyo Co., Ltd. (72) Inventor Takafumi Kitano 3-12-12 Tomobuchi-cho, Miyakojima-ku, Osaka-shi, Osaka Marubishi Yuka Kogyo Co., Ltd. (72) Akira Ishikawa, Miyakojima, Osaka-shi, Osaka Ward 3-7-12 Marubishi Yuka Kogyo Co., Ltd. F-term (reference) 4H006 AA02 AC22 AC24 BA07 BA53 BJ50 BM72 BN10 BP10 BU46 4H039 CA19 CA60 CA66 CF30

Claims (7)

[Claims] 1. A compound of the general formula XR, wherein X is a halogen atom,
R represents an alkyl group having 2 or more carbon atoms which may have a substituent. ) And a halogen atom is bonded to any carbon atom of the alkyl chain by reacting a halogenated hydrocarbon with metallic zinc in the presence of a nitrogen-containing compound in a solvent; By adding an aldehyde represented by '-CHO (where R' is an aryl group or a heterocyclic group which may have a substituent) and a trisubstituted silyl halide, alcohols and And / or a method for producing hydrocarbons. 2. An alkyl group R which may have a substituent has the following general formulas a) to d): a) -CH _2- (CH ₂ ) ₁ -R ¹ b) -CH ｛(CH ₂ ) _m R ² ｝ ｛(CH ₂ ) _n R ³ ｝ c) -C ｛(CH ₂ ) _o R ⁴ ｝ ｛(CH ₂ ) _p R ⁵ ｝ ｛(CH
₂ ) _q R ⁶ ｝ d) a cycloalkyl group optionally having a substituent R ⁷ (R ^{1 to} R ⁷ represent an ester group, an aryl group, an alkyl group or a cyano group; The method according to claim 1, which is any one of the following. 3. The production method according to claim 1, wherein the nitrogen-containing compound is at least one of an amide compound, a urea compound and an amine compound. 4. A trisubstituted silyl halide represented by the following general formula: (Where X is a halogen atom, R ^{8 to} R ¹⁰ are the same or different and each represents an alkyl group or an aryl group). 5. A compound of the general formula XR, wherein X is a halogen atom,
R represents an alkyl group having 2 or more carbon atoms which may have a substituent. ) And a halogen atom is bonded to any carbon atom of the alkyl chain by reacting a halogenated hydrocarbon with metallic zinc in the presence of a nitrogen-containing compound in a solvent to form an organic zinc compound. How to make. 6. The method according to claim 5, wherein the nitrogen-containing compound is at least one of an amide compound, a urea compound and an amine compound. 7. An alkyl group R which may have a substituent has the following general formulas a) to d): a) -CH _2- (CH ₂ ) ₁ -R ¹ b) -CH ｛(CH ₂ ) _m R ² ｝ ｛(CH ₂ ) _n R ³ ｝ c) -C ｛(CH ₂ ) _o R ⁴ ｝ ｛(CH ₂ ) _p R ⁵ ｝ ｛(CH
₂ ) _q R ⁶ ｝ d) a cycloalkyl group optionally having a substituent R ⁷ (R ^{1 to} R ⁷ represent an ester group, an aryl group, an alkyl group or a cyano group; The production method according to claim 5, which is any one of the following.