JP2001181236A - Method for producing cyclopropanecarboxylic acid derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a cyclopropanecarboxylic acid derivative expressed by general formula (4) in a better yield. SOLUTION: This method for producing the cyclopropanecarboxylic acid derivative (4) is provided by reacting a diazoacetic acid ester of general formula (1): N2CHOOR1, with an olefin of general formula (2) in the presence of a rhodium catalyst expressed by the formula (3): Rh2(OCOCPH3)4.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a cyclopropanecarboxylic acid derivative.

[0002]

2. Description of the Related Art General formula (4) (Wherein R ² represents a hydrogen atom or a methyl group;
It is - represents a (CH _{2) n} -R ³ or -CH (OR ⁴⁾ _2. Here, R ³ represents a halogen atom, an alkoxy group having 1 to 10 carbon atoms, an acyloxy group having 2 to 10 carbon atoms or an alkoxycarbonyl group having 2 to 10 carbon atoms, and n represents an integer of 0 to 10. R ⁴ represents an alkyl group having 1 to 10 carbon atoms, and two R ⁴ 's may form a ring together. The cyclopropanecarboxylic acid derivative represented by the formula (1) is useful as an intermediate for pharmaceuticals, agricultural chemicals and the like. As a method for producing the cyclopropanecarboxylic acid derivative represented by the general formula (4), for example, ethyl diazoacetate and ethyl vinyl ether are reacted in the presence of a rhodium acetate catalyst to produce ethyl 2-ethoxycyclopropanecarboxylate. Method (Synthesis, 787 (19)
81)) and the like are known, but such a method has a low yield of the desired product and is not always satisfactory from an industrial viewpoint.

[0003]

SUMMARY OF THE INVENTION Under such circumstances,
The present inventors have conducted intensive studies on a method for producing the cyclopropanecarboxylic acid derivative represented by the general formula (4) in a higher yield, and found that the general formula (1) (Wherein R ¹ has the same meaning as described above) and an olefin represented by the general formula (2): (In the formula, R ² and Z represent the same meaning as described above.)
The diazoacetic acid ester represented by the following formula (3) It has been found that the cyclopropanecarboxylic acid derivative represented by the above general formula (4) can be obtained in high yield by reacting in the presence of a rhodium catalyst represented by the formula (1), and the present invention has been accomplished.

[0004]

That is, the present invention provides a compound represented by the following general formula (1): (Wherein R ¹ represents a linear, molecular chain or cyclic alkyl group having 1 to 10 carbon atoms) and a general formula (2) (Wherein R ² represents a hydrogen atom or a methyl group;
It is - represents a (CH _{2) n} -R ³ or -CH (OR ⁴⁾ _2. Here, R ³ represents a halogen atom, an alkoxy group having 1 to 10 carbon atoms, an acyloxy group having 2 to 10 carbon atoms or an alkoxycarbonyl group having 2 to 10 carbon atoms, and n represents an integer of 0 to 10. R ⁴ represents an alkyl group having 1 to 10 carbon atoms, and two R ⁴ 's may form a ring together. The olefin represented by the following formula (3) Wherein the reaction is carried out in the presence of a rhodium catalyst represented by the following general formula (4): (Wherein, R ¹ , R ² and Z have the same meanings as described above).

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. General formula (1) In the formula of diazoacetates represented by R ¹ represents a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms, for example, a methyl group, an ethyl group, an n-propyl group,
Isopropyl group, n-butyl group, isobutyl group, sec
-Butyl group, tert-butyl group, n-pentyl group, n
-Hexyl group, cyclohexyl group, n-octyl group, isooctyl group, n-decyl group, menthyl group and the like. Examples of the diazoacetic esters represented by the general formula (1) include, for example, methyl diazoacetate, ethyl diazoacetate, n-propyl diazoacetate, isopropyl diazoacetate, n-butyl diazoacetate, tert-butyl diazoacetate, and diazoacetic acid. Cyclohexyl, menthyl diazoacetate and the like can be mentioned. The diazoacetic esters represented by the general formula (1) are prepared, for example, by reacting the corresponding aminoacetic esters with a diazotizing agent such as sodium nitrite.

Formula (2) Wherein R ² represents a hydrogen atom or a methyl group, and Z represents-(CH ₂ ) _n -R ³ or-
CH (OR ⁴ ) ₂ . Z is - (CH ₂₎ when representing the _n -R ^3, R ³ represents a halogen atom, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having an acyloxy group or a C2-10 C2-10 , N is 0
Represents an integer of 10 to 10.

[0007] Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom and the like.
Examples of the alkoxy group having 1 to 10 carbon atoms include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-hexoxy, n-
Octoxy groups and the like. Examples of the acyloxy group having 2 to 10 carbon atoms include an acetyloxy group, a propionyloxy group, a butyryloxy group, and the like.

Examples of the alkoxycarbonyl group having 2 to 10 carbon atoms include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl. Group, t
tert-butoxycarbonyl group, n-hexoxycarbonyl group, n-octoxycarbonyl group, benzyloxycarbonyl group and the like.

When Z represents —CH (OR ⁴ ) ₂ , R ⁴
Represents an alkyl group having 1 to 10 carbon atoms, and two R ⁴ 's may form a ring together. Carbon number 1-10
Examples of the alkyl group include a methyl group, an ethyl group, n
-Propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-
Examples include a hexyl group, an n-octyl group, an isooctyl group, and an n-decyl group.

Examples of the substituent Z include a fluorine atom, chlorine atom, bromine atom, iodine atom, chloromethyl group, 2-chloroethyl group, 4-chlorobutyl group, 8-chlorooctyl group, methoxy group, ethoxy group, n -Propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group,
n-hexoxy group, n-octoxy group, methoxymethyl group, methoxyethyl group, ethoxymethyl group, acetyloxy group, propionyloxy group, butyryloxy group, acetyloxymethyl group, propionyloxymethyl group,
Methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, isopropoxycarbonyl group,
n-butoxycarbonyl group, isobutoxycarbonyl group, sec-butoxycarbonyl group, tert-butoxycarbonyl group, n-hexoxycarbonyl group, n-octoxycarbonyl group, benzyloxycarbonyl group,
Methoxycarbonylmethyl group, dimethoxymethylene group,
Diethoxymethylene group, dipropoxymethylene group, ethylenedioxymethyl group, propylenedioxymethyl group,
And a butylene dioxymethyl group.

The olefins represented by the general formula (2) include, for example, vinyl chloride, vinyl bromide, allyl chloride, allyl bromide, 4-chloro-1-butene, 6-chloro-1-hexene, 10- Chloro-1-decene, methyl vinyl ether, ethyl vinyl ether, propyl vinyl ether, vinyl acetate, allyl acetate, vinyl propionate, allyl propionate, methyl acrylate, ethyl acrylate, 1-chloro-2-methylpropene, 1-chloro- 3-methyl-2-butene, 1-ethoxy-2-methylpropene, 1-acetoxy-2-methylpropene, 1
-Acetoxy-3-methyl-2-butene, methyl 3,3-dimethylacrylate, 3,3-diethoxy-1-propene, 2-vinyl-1,3-dioxolan, 2- (2-
Methylpropenyl) -1,3-dioxolane and the like.

The amount of the olefin represented by the general formula (2) is usually 0.8 to 10 times, preferably 0.9 mol, per mol of the diazoacetate represented by the general formula (1).
The molar ratio is up to 5 times, more preferably 1 to 2 times.

According to the present invention, the diazoacetic acid ester represented by the above-mentioned general formula (1) and the olefin represented by the general formula (2) are converted into the following formula (3) The reaction is carried out in the presence of a rhodium catalyst represented by the following formula. As the rhodium catalyst, a commercially available one may be used or one prepared by a known method may be used.
The amount of the rhodium catalyst to be used is generally 0.001 to 1 mol%, preferably 0.005 to 0.5 mol%, more preferably 0.1 to 1 mol%, based on the diazoacetic acid ester represented by the general formula (1). 01 to 0.1 mol%.

This reaction may be carried out without a solvent depending on the type of olefin used, but is usually carried out in the presence of a solvent. Examples of the solvent include aliphatic hydrocarbon solvents such as hexane, heptane and cyclohexane, halogenated hydrocarbon solvents such as dichloromethane and chloroform, and ester solvents such as ethyl acetate, and the amount of the solvent is not particularly limited. However, in consideration of economy, volumetric efficiency, etc., it is practically 100 times or less the weight of the diazoacetate represented by the general formula (1).

[0015] The reaction temperature is usually 0 to 100 ° C.

This reaction is usually carried out in a mixture of an olefin represented by the general formula (2), a rhodium catalyst represented by the formula (3) and, if necessary, a solvent, a diazoacetic acid ester represented by the general formula (1). Are added. The addition of such diazoacetates may be continuous or intermittent. This reaction may be carried out under normal pressure conditions or may be carried out under pressurized conditions. In particular, when using a low boiling point olefin as the olefin represented by the general formula (2), it is practical to carry out the reaction under a pressurized condition.

The above reaction may be carried out in the presence of a dehydrating agent such as molecular sieves and magnesium sulfate. The amount of the dehydrating agent used is not particularly limited, but is usually 0.5 times by weight or less based on the diazoacetic acid ester represented by the general formula (1).

After completion of the reaction, if necessary, insolubles are removed by filtration or the like, and then subjected to a general post-treatment such as distillation or column chromatography to obtain the compound represented by the general formula (4). (Wherein, R ¹ , R ² and Z have the same meanings as described above).

The cyclopropanecarboxylic acid derivative represented by the general formula (4), which is usually obtained, is a mixture of a cis-form and a trans-form. However, the cis-form and the trans-form can be separated by a usual treatment such as distillation. it can.

Examples of the cyclopropanecarboxylic acid derivative represented by the general formula (4) include methyl 2-chlorocyclopropanecarboxylate, ethyl 2-chlorocyclopropanecarboxylate, tert-butyl 2-chlorocyclopropanecarboxylate, Menthyl 2-chlorocyclopropanecarboxylate, methyl 2-bromocyclopropanecarboxylate, ethyl 2-bromocyclopropanecarboxylate,
Tert-butyl 2-bromocyclopropanecarboxylate, menthyl 2-bromocyclopropanecarboxylate, 2
-Methyl (chloromethyl) cyclopropanecarboxylate,
Ethyl 2- (chloromethyl) cyclopropanecarboxylate, 2- (chloromethyl) cyclopropanecarboxylate t
tert-butyl, menthyl 2- (chloromethyl) cyclopropanecarboxylate, methyl 2- (bromomethyl) cyclopropanecarboxylate, ethyl 2- (bromomethyl) cyclopropanecarboxylate, tert-butyl 2- (bromomethyl) cyclopropanecarboxylate Menthyl 2- (bromomethyl) cyclopropanecarboxylate,

Methyl 2- (2-chloroethyl) cyclopropanecarboxylate, ethyl 2- (2-chloroethyl) cyclopropanecarboxylate, tert-butyl 2- (2-chloroethyl) cyclopropanecarboxylate, 2- (2-
Chloroethyl) menthyl cyclopropanecarboxylate, 2
Methyl-(4-chlorobutyl) cyclopropanecarboxylate, ethyl 2- (4-chlorobutyl) cyclopropanecarboxylate, tert-butyl 2- (4-chlorobutyl) cyclopropanecarboxylate, 2- (4-chlorobutyl)
Menthyl cyclopropanecarboxylate, methyl 2- (8-chlorooctyl) cyclopropanecarboxylate, 2- (8
-Chlorooctyl) ethyl cyclopropanecarboxylate,
Tert-butyl 2- (8-chlorooctyl) cyclopropanecarboxylate, menthyl 2- (8-chlorooctyl) cyclopropanecarboxylate,

Methyl 2-methoxycyclopropanecarboxylate, ethyl 2-methoxycyclopropanecarboxylate,
Tert-butyl 2-methoxycyclopropanecarboxylate, menthyl 2-methoxycyclopropanecarboxylate,
Methyl 2-ethoxycyclopropanecarboxylate, ethyl 2-ethoxycyclopropanecarboxylate, tert-butyl 2-ethoxycyclopropanecarboxylate, menthyl 2-ethoxycyclopropanecarboxylate, methyl 2-propoxycyclopropanecarboxylate, 2-propoxy Ethyl cyclopropanecarboxylate, tert-butyl 2-propoxycyclopropanecarboxylate, menthyl 2-propoxycyclopropanecarboxylate, methyl 2-acetyloxycyclopropanecarboxylate, ethyl 2-acetyloxycyclopropanecarboxylate, 2-acetyloxy Tert-butyl cyclopropanecarboxylate, menthyl 2-acetyloxycyclopropanecarboxylate,

Methyl 2- (acetyloxymethyl) cyclopropanecarboxylate, 2- (acetyloxymethyl)
Ethyl cyclopropanecarboxylate, tert-butyl 2- (acetyloxymethyl) cyclopropanecarboxylate, menthyl 2- (acetyloxymethyl) cyclopropanecarboxylate, methyl 2-propionyloxycyclopropanecarboxylate, 2-propionyloxycyclopropane Ethyl carboxylate, tert-butyl 2-propionyloxycyclopropanecarboxylate, menthyl 2-propionyloxycyclopropanecarboxylate, 2-
Methyl (propionyloxymethyl) cyclopropanecarboxylate, ethyl 2- (propionyloxymethyl) cyclopropanecarboxylate, tert-butyl 2- (propionyloxymethyl) cyclopropanecarboxylate, 2
-Menthyl (propionyloxymethyl) cyclopropanecarboxylate, methyl cyclopropane-1,2-dicarboxylate, ethyl 2- (methoxycarbonyl) cyclopropanecarboxylate, tert-butyl 2- (methoxycarbonyl) cyclopropanecarboxylate, 2 Menthyl-(methoxycarbonyl) cyclopropanecarboxylate, 2-
(Ethoxycarbonyl) methyl cyclopropanecarboxylate, ethyl cyclopropane-1,2-dicarboxylate, 2
-(Ethoxycarbonyl) cyclopropanecarboxylic acid t
tert-butyl, menthyl 2- (ethoxycarbonyl) cyclopropanecarboxylate,

Methyl 3-chloro-2,2-dimethylcyclopropanecarboxylate, ethyl 3-chloro-2,2-dimethylcyclopropanecarboxylate, 3-chloro-2,2
Tert-butyl-dimethylcyclopropanecarboxylate, menthyl 3-chloro-2,2-dimethylcyclopropanecarboxylate, methyl 3-chloromethyl-2,2-dimethylcyclopropanecarboxylate, 3-chloromethyl-
Ethyl 2,2-dimethylcyclopropanecarboxylate, 3
Tert-butyl-chloromethyl-2,2-dimethylcyclopropanecarboxylate, 3-chloromethyl-2,2-
Menthyl dimethylcyclopropanecarboxylate, methyl 3-ethoxy-2,2-dimethylcyclopropanecarboxylate, ethyl 3-ethoxy-2,2-dimethylcyclopropanecarboxylate, 3-ethoxy-2,2-dimethylcyclopropanecarboxylate tert-butyl, menthyl 3-ethoxy-2,2-dimethylcyclopropanecarboxylate,

Methyl 3-acetyloxy-2,2-dimethylcyclopropanecarboxylate, 3-acetyloxy-
Ethyl 2,2-dimethylcyclopropanecarboxylate, 3
Tert-butyl acetyloxy-2,2-dimethylcyclopropanecarboxylate, 3-acetyloxy-2,
Menthyl 2-dimethylcyclopropanecarboxylate, 3-
Methyl (acetyloxymethyl) -2,2-dimethylcyclopropanecarboxylate, ethyl 3- (acetyloxymethyl) -2,2-dimethylcyclopropanecarboxylate, 3- (acetyloxymethyl) -2,2-dimethylcyclo Tert-butyl propanecarboxylate, menthyl 3- (acetyloxymethyl) -2,2-dimethylcyclopropanecarboxylate,

2,2-dimethylcyclopropane-1,3
-Dimethyl carboxylate, 3-methoxycarbonyl-
Ethyl 2,2-dimethylcyclopropanecarboxylate, 3
Tert-butyl-methoxycarbonyl-2,2-dimethylcyclopropanecarboxylate, menthyl 3-methoxycarbonyl-2,2-dimethylcyclopropanecarboxylate, 2- (1,3-dioxolan-2-yl) cyclopropanecarboxylic acid Methyl, ethyl 2- (1,3-dioxolan-2-yl) cyclopropanecarboxylate, 2-
Tert-butyl (1,3-dioxolan-2-yl) cyclopropanecarboxylate, menthyl 2- (1,3-dioxolan-2-yl) cyclopropanecarboxylate, 3
Methyl- (1,3-dioxolan-2-yl) -2,2-dimethylcyclopropanecarboxylate, 3- (1,3-
Ethyl dioxolan-2-yl) -2,2-dimethylcyclopropanecarboxylate, tert-butyl 3- (1,3-dioxolan-2-yl) -2,2-dimethylcyclopropanecarboxylate, 3- (1, 3-dioxolane-
2-yl) -menthyl 2,2-dimethylcyclopropanecarboxylate,

Methyl 2- (diethoxymethyl) cyclopropanecarboxylate, ethyl 2- (diethoxymethyl) cyclopropanecarboxylate, tert-butyl 2- (diethoxymethyl) cyclopropanecarboxylate, 2- (diethoxymethyl) ) Mentyl cyclopropanecarboxylate, 3
-(Diethoxymethyl) -2,2-dimethylcyclopropanecarboxylate methyl, 3- (diethoxymethyl)-
Ethyl 2,2-dimethylcyclopropanecarboxylate, 3
And tert-butyl-(diethoxymethyl) -2,2-dimethylcyclopropanecarboxylate and menthyl 3- (diethoxymethyl) -2,2-dimethylcyclopropanecarboxylate.

[0028]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. The analysis was performed by gas chromatography.

Example 1 A reaction vessel was charged with 25 g of heptane and Rh ₂ (OCOCPh ₃ ).
₄ 27mg, Molecular sieves 4A (powder) 1.2
g, 12.9 g of vinyl acetate. Internal temperature 25-30
C. and 38 g of a heptane solution containing 11.4 g of ethyl diazoacetate was added dropwise over 5 hours. After further keeping the temperature for 1 hour, 78.9 g of a solution containing ethyl 2-acetoxycyclopropanecarboxylate was obtained. Content: 20.5% by weight, yield: 94%, cis / trans ratio = 41/59.

Example 2 Example 1 was repeated, except that 10.8 g of ethyl vinyl ether was used in place of 12.9 g of vinyl acetate.
72.3 g of a solution containing ethyl 2-ethoxycyclopropanecarboxylate was obtained. Content: 19.
5% by weight, yield: 89%, cis / trans ratio = 47 /
53.

Example 3 2- (acetoxymethyl) cyclopropanecarboxylic acid was prepared in the same manner as in Example 1, except that 15.0 g of allyl acetate was used instead of 12.9 g of vinyl acetate. 81.9 g of a solution containing ethyl were obtained. Content: 2
0.4% by weight, yield: 90%, cis / trans ratio = 4
1/59.

Example 4 The procedure of Example 1 was repeated, except that 18.2 g of allyl bromide was used instead of 12.9 g of vinyl acetate, to give 2- (bromomethyl) cyclopropanecarboxylic acid. 80 g of a solution containing ethyl were obtained. Content: 15.8% by weight, yield: 61%, cis / trans ratio = 34/66.

Example 5 The procedure of Example 1 was repeated, except that 11.5 g of allyl chloride was used instead of 12.9 g of vinyl acetate, to give 2- (chloromethyl) cyclopropanecarboxylic acid. 74.7 g of a solution containing ethyl were obtained. Content: 19.1
% By weight, yield: 88%, cis / trans ratio = 35/6
5.

Example 6 The procedure of Example 1 was repeated, except that 12.9 g of methyl acrylate was used in place of 12.9 g of vinyl acetate, to give 2- (methoxycarbonyl) cyclopropanecarboxylic acid. 81.6 g of a solution containing ethyl acid were obtained. Content: 15.3% by weight, yield: 72%, cis / trans ratio = 34/66.

Example 7 The procedure of Example 1 was repeated, except that 19.5 g of acrolein diethyl acetal was used instead of 12.9 g of vinyl acetate, to give 2- (diethoxymethyl) cyclopropane. 85. Solution containing ethyl carboxylate
8 g were obtained. Content: 17.7% by weight, yield: 70%, cis / trans ratio = 36/64.

[0036]

According to the method of the present invention, cyclopropanecarboxylic acid derivatives useful as intermediates for pharmaceuticals, agricultural chemicals and the like can be produced in higher yield.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 317/30 C07D 317/30 F-term (Reference) 4G069 AA02 AA06 BA27A BA27B BC71A BC71B BE37A BE37B BE42B CB65 DA02 4H006 AA02 AC28 BA24 BA32 BJ20 BM10 BM71 BM72 BM73 BM74 BP10 BS10 BS20 4H039 CA40 CF10

Claims (1)

[Claims] 1. The general formula (1) (Wherein R ¹ represents a linear, molecular chain or cyclic alkyl group having 1 to 10 carbon atoms) and a general formula (2) (Wherein R ² represents a hydrogen atom or a methyl group;
It is - represents a (CH _{2) n} -R ³ or -CH (OR ⁴⁾ _2. Here, R ³ represents a halogen atom, an alkoxy group having 1 to 10 carbon atoms, an acyloxy group having 2 to 10 carbon atoms or an alkoxycarbonyl group having 2 to 10 carbon atoms, and n represents an integer of 0 to 10. R ⁴ represents an alkyl group having 1 to 10 carbon atoms, and two R ⁴ 's may form a ring together. The olefin represented by the following formula (3) Wherein the reaction is carried out in the presence of a rhodium catalyst represented by the following general formula (4): (Wherein, R ¹ , R ² and Z have the same meanings as described above).