JP3319225B2 - Method for producing α-cyanobenzyl ester compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing an α-cyanobenzyl ester compound.

[0002]

2. Description of the Related Art Conventionally, aldehydes such as acid halides or acid anhydrides, alkali metal or alkaline earth metal cyanides and 3-phenoxybenzaldehyde have been used in the presence of an inert organic solvent-water in the presence of a phase transfer catalyst. It is known to react in a two-phase solvent to produce the corresponding ester compound (J. Chem. Soc., Vol. 95,
1404 (1909), JP-A-52-142046 and 55
-133349]. In this method, an acid halide or an acid anhydride is added to a mixed solution of cyanide and 3-phenoxybenzaldehyde in the presence of a phase transfer catalyst. In this method, a by-product benzoin ester is produced. There is a problem that the compound is produced in a large amount, the yield of the target compound is low, the purity of the product is at most 90%, and the benzoin ester is contained in an amount of about 2 to 3%. To solve this problem, a method of adding a tertiary amine to the reaction system has been proposed (Japanese Patent Publication No. 5-64137), but this method cannot always be said to have a satisfactory yield. However, good results could not be obtained even in the additional tests performed by the present inventors.

[0003]

SUMMARY OF THE INVENTION
We use 3-phenoxybenzaldehyde as the aldehyde, without using a tertiary amine,
As a result of examining a method for producing a corresponding α-cyanobenzyl ester compound by reacting this with an acid halide or an acid anhydride and a cyanide of an alkali metal or an alkaline earth metal, with high yield, high purity and easily,
The present inventors have found that an α-cyanobenzyl ester compound can be easily obtained with high yield and high purity by reacting under specific reaction conditions, and the present invention has been accomplished.

[0004]

That is, the present invention provides a compound represented by the general formula (2): (Wherein, X represents a halogen atom or —O—CO—R, and R is Is shown. Where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ ,
R ₇ and R ₈ are the same or different and each represent a hydrogen atom or a linear or branched lower alkyl group, and X ′ represents a halogen atom. Reaction of the acid halide or anhydride, 3-phenoxybenzaldehyde and cyanide of alkali metal or alkaline earth metal in an inert organic solvent-water two-phase solvent in the presence of a phase transfer catalyst. A general formula (1) characterized in that an acid halide or acid anhydride and 3-phenoxybenzaldehyde are added together to the reaction system. (Wherein, R has the same meaning as described above)
A method for producing a cyanobenzyl ester compound.

In the acid halide or acid anhydride represented by the general formula (2), which is a raw material of the present invention, the substituents R ₁ to
R ₈ is methyl, ethyl, n-propyl, isopropyl,
a straight-chain or branched lower alkyl group such as sec-butyl, and when a plurality of such substituents are present in the substituent R, these substituents R _{1 to} R ₄ and R _{5 to} R ₆ are often Is the same as above, but may be different depending on the target compound. Examples of such an acid halide or acid anhydride include 2,2,3,3-tetramethylcyclopropanecarboxylic acid chloride (or bromide or iodine) and 2,2,3,3-tetraethylcyclopropanecarboxylic acid chloride ( Or bromide or iodine), 2,2-dimethyl-3- (2,2-
Dichlorovinyl) -cyclopropanecarboxylic acid chloride (or bromide or iodine), 2,2-diethyl-3- (2,2-dichlorovinyl) -cyclopropanecarboxylic acid chloride (or bromide or iodine),
2,2-dichloro-1- (4-ethoxyphenyl) cyclopropanecarboxylic acid chloride (or bromide or iodine), 2,2-dichloro-1- (4-propoxyphenyl) cyclopropanecarboxylic acid chloride (or bromide or iodine) ), Α-isopropyl- (p-
Chlorobenzyl) carbonyl chloride (or bromide or iodine) and acid anhydrides thereof are exemplified. Usually, acid halide is preferably used.

The alkali metal or alkaline earth metal cyanide (hereinafter simply referred to as cyanide) used in the present invention includes, for example, sodium cyanide, potassium cyanide, magnesium cyanide, calcium cyanide and the like. In particular, alkali metal cyanide is preferably used. Examples of the phase transfer catalyst include benzyltrialkylammonium halides (eg, benzyltriethylammonium chloride, benzyltriethylammonium bromide, and benzyltriethylammonium iodide), and tetraalkylammonium halides (eg, chlorinated, brominated or Butylammonium, tetrapropylammonium chloride or bromide or iodide) and the like.

In the present invention, the amount of each raw material used for 3-phenoxybenzaldehyde is 0.95 to 0.95 for the acid halide or acid anhydride represented by the general formula (2).
1.1 mole times, preferably 0.97 to 1.0 mole times, and for cyanide, 1 to 1.5 mole times, preferably 1.
1 to 1.3 mole times, 0.1 to 2 for phase transfer catalyst
Mol%, preferably 0.8 to 1 mol%.

According to the present invention, an alkali metal or alkaline earth metal cyanide, acid halide or acid anhydride and 3-phenoxybenzaldehyde are prepared in the presence of a phase transfer catalyst in an inert organic solvent-water two-phase solvent. Is to react. Here, as the inert organic solvent, toluene, xylene, hexane, heptane, methylene chloride,
A solvent inert to the reaction such as chloroform is exemplified, and the mixing ratio of the organic solvent and water is not particularly limited. In the present invention, it is very important to co-add the acid halide or acid anhydride and 3-phenoxybenzaldehyde to the reaction system. Specifically, in the mixture of the required amount of cyanide and the phase transfer catalyst, , The required amount of acid halide or anhydride and 3-phenoxybenzaldehyde are added together. At this time, the cyanide and the phase transfer catalyst are usually dissolved in water and used as an aqueous solution, and the acid halide or acid anhydride and 3-phenoxybenzaldehyde added together are dissolved in an inert organic solvent. The solution is used as a solution, and an organic solvent solution of each of an acid halide or an acid anhydride and 3-phenoxybenzaldehyde is co-injected into an aqueous solution of a cyanide and a phase transfer catalyst to thereby form an inert organic solvent.
The reaction is carried out in a two-phase water solvent.

In the method of the present invention, when the acid halide or acid anhydride and 3-phenoxybenzaldehyde are co-injected, the co-injection of both raw materials may be started at the same time.
Within 10% by weight of the total amount used, preferably 1 to 5
It is preferred to start the addition of the acid halide or acid anhydride after the addition of the amount by weight of 3-phenoxybenzaldehyde. By performing such co-injection, benzoin condensation of the intermediate cyanohydrin produced by the reaction and the starting aldehyde is prevented, the production of benzoin ester as a by-product is suppressed, and the addition of acid halide or acid anhydride is started. Is retarded from 3-phenoxybenzaldehyde, thereby preventing the reaction of acid halides or acid anhydrides with water or cyanide ions, the reaction with the generated cyanohydrin proceeds preferentially, and high purity α-
Cyanobenzyl ester can be obtained in high yield.
In addition, by performing such co-addition, the reaction proceeds smoothly, the heat generation is constant, and the reaction and temperature control become easy.

The reaction temperature in this reaction is usually -10
C. to 50.degree. C., preferably 0.degree. C. to 20.degree. C., but is not particularly limited to this range, and is determined according to each condition such as the type of raw material and solvent.

[0011]

According to the method of the present invention, the content of by-products such as benzoin ester is extremely low, at most 0.5% or less, the yield is high, and the reaction is easily controlled by the general formula (1). Α-cyanobenzyl ester is obtained, which is very advantageous as an industrial production method of the ester.

[0012]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but it goes without saying that the present invention is not limited thereto.

Example 1 23.53 g (0.48 mol) of sodium cyanide and 1.82 g (0.004 mol) of a 50% aqueous solution of benzyltriethylammonium chloride were dissolved in 91.27 g of water. The aqueous solution was cooled to 5 ° C., and 158.56 g (0.4 mol) of a 50% 3-phenoxybenzaldehyde / toluene solution was dropped into the aqueous solution at 5 ± 3 ° C. at a rate of 0.88 g / min. 2.5 minutes later (corresponding to 1.39% of the total amount used), 37.5% by weight of 2,
Dropping of 169.83 g (0.396 mol) of a 2,3,3-tetramethylcyclopropanecarboxylic acid chloride / toluene solution was started at a rate of 0.94 g / min. After dripping over 3 hours from the start of dripping for each,
The mixture was stirred at the same temperature for 1 hour. After completion of the reaction, 11.92 g of an 11% aqueous sodium carbonate solution and 124.07 g of a 12% aqueous sodium hypochlorite solution were added, and the mixture was stirred at 57 to 60 ° C. for 1 hour. Then, 15.92 g of a 10% aqueous sodium thiosulfate solution was added, and the mixture was washed at 57 to 60 ° C. Thereafter, washing was repeated three times at the same temperature with 56.44 g / time of water.
The obtained toluene layer was concentrated at 120 ° C. and 10 mmHg to obtain 139.21 g of 3-phenoxy-α-cyanobenzyl-2,2,3,3-tetramethylcyclopropanecarboxylic acid ester as a dark brown oil. Yield 99.6%, purity 95.7% The content of benzoin ester in the obtained ester was 0.1%.
37%.

Example 2 Instead of 2,2,3,3-tetramethylcyclopropanecarboxylic acid chloride / toluene solution, 2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropanecarboxylic acid chloride / Toluene / n-heptane solution 11
Except for using 5.46 g (content 80.4% by weight, 0.408 mol), the reaction and post-treatment were carried out in the same manner as in Example 1 to give 3-phenoxy-α-cyanobenzyl-2,2-dimethyl-3. 166.02 g of-(2,2-dichlorovinyl) cyclopropanecarboxylic acid ester was obtained. Yield 99.7%, purity 97.3% The content of benzoin ester in the obtained ester was 0.3%.
05%.

COMPARATIVE EXAMPLE 1 An aqueous solution prepared by dissolving 23.53 g (0.48 mol) of sodium cyanide and 1.82 g (0.004 mol) of a 50% aqueous benzyltriethylammonium chloride solution in 91.27 g of water and 50% 37.5% by weight of 2,2,3 in a mixture consisting of 158.56 g (0.4 mol) of a phenoxybenzaldehyde / toluene solution.
The same procedure as in Example 1 was followed, except that 169.83 g (0.396 mol) of a 3-tetramethylcyclopropanecarboxylic acid chloride / toluene solution was added dropwise at a rate of 0.94 g / min over 3 hours. 136.29 g of α-cyanobenzyl-2,2,3,3-tetramethylcyclopropanecarboxylic acid ester was obtained. Yield 97.5%, purity 92.3% The content of benzoin ester in the obtained ester was 2.
93%.

Comparative Example 2 2,2,3,3-Tetramethylcyclopropanecarboxylic acid chloride / toluene solution having a concentration of 37.5% by weight 16
To 9.83 g, 2.97 g of tri-n-butylamine (0.
016 mol) and 64 mg (0.2 mmol) of tetra-n-butylammonium bromide, and the reaction was carried out in the same manner as in Comparative Example 1 except that the reaction temperature was changed from -2 ° C to 0 ° C. The reaction did not proceed. The composition of each component in the reaction mass was 61.3% for 3-phenoxy-α-cyanobenzyl-2,2,3,3-tetramethylcyclopropane carboxylate and 0.25% for benzoin ester. 3-phenoxybenzaldehyde in the reaction was 29.0%.

Claims (4)

(57) [Claims] 1. The general formula (2) (Wherein, X represents a halogen atom or —O—CO—R, and R is Is shown. Where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ ,
R ₇ and R ₈ are the same or different and each represent a hydrogen atom or a linear or branched lower alkyl group, and X ′ represents a halogen atom. The reaction of the acid halide or acid anhydride, 3-phenoxybenzaldehyde and cyanide of an alkali metal or alkaline earth metal in an inert organic solvent-water two-phase solvent in the presence of a phase transfer catalyst ,
An acid halide or an acid anhydride and 3-phenoxybenzaldehyde are added to the reaction system together to give a compound of the general formula (1) (Wherein, R has. As defined above) to produce the α- cyanobenzyl ester compound represented by the
Method, wherein 1 to 5% by weight of the total
Enoxybenzaldehyde is added first and then
Addition of acid halide or acid anhydride represented by the formula (2)
Starting the process for producing an α-cyanobenzyl ester compound. 2. The cyanide is an alkali metal cyanide.
The α-cyanobenzyl ester compound according to claim 1,
Manufacturing method. 3. The method according to claim 1, wherein the alkali metal cyanide is sodium cyanide.
3. The α according to claim 2, wherein the α is potassium or potassium cyanide.
-A method for producing a cyanobenzyl ester compound. 4. A phase transfer catalyst comprising a benzyl trihalide.
The α-cyano according to claim 1, which is alkylammonium.
A method for producing a benzyl ester compound.