JPS5845413B2 - Method for producing γ,δ-unsaturated-α-oxyvaleric acid esters - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula (wherein R1 is a hydrogen atom, an alkyl group or an aryl group, and R2 is an alkyl group or an aryl group).

) It relates to a method for producing γ/δ-unsaturated monoα-oxyvaleric acid esters.

More specifically, allyltrimethylsilane has the general formula (wherein R1 is a hydrogen atom, an alkyl group, or an aryl group, and R2 is an alkyl group or an aryl group.

α-keto acid ester represented by the general formula (in the formula, the four Xs are the same or different halogen atoms).

) A method for producing γ/δ-unsaturated α-oxyvaleric esters represented by the general formula (I) by reacting in the presence of a titanium compound represented by the formula (I), and then treating the resulting reaction mixture with water. Regarding.

γ-
The δ-unsaturated monoα-oxyvaleric acid esters can be easily converted into the corresponding carboxylic acids (R2=H) by hydrolysis.

Although the γ/δ-unsaturated α-oxyvaleric acid ester and its acid produced by this method have physiological activity by themselves, they can be used to create more complex natural products using unsaturated bonds at the γ/δ-positions. It is a useful synthetic intermediate in that it can synthesize physiologically active substances.

Conventionally, α-oxycarboxylic acid esters have been prepared by reaction of α-keto acid esters with Grignard reagents [for example, J, A, R
e1d, E, E, Turnell J, Chem.

Soc, 1951, 3219) proposed a synthesis method, but additional experiments by the present inventors revealed that when this reaction was carried out using allylmagnesium halide, both the carbonyl group and the ester group were attacked. The reaction that generates glycol is the main reaction, and the target product is hardly obtained (see Reference Example 1.2 below).

According to the method of the present invention, desired γ/δ-unsaturated monoα-oxyvalerate esters can be synthesized in high yield without producing by-products.

Examples of the α-keto acid ester represented by the general formula (n) that can be used in carrying out the present invention include methyl glyoxylate, ethyl glyoxylate, benzyl glyoxylate, phenyl glyoxylate, methyl pyruvate, propyl pyruvate, and pyruvin. A wide range of examples include inbutyl acid, benzyl pyruvate, t-butyl ethylglyoxylate, amyl t-butylglyoxylate, methyl benzoylformate, ethyl penzoylxate, cyclohexyl penzoylxate, and the like.

Allyltrimethylsilane, the other raw material, can be easily synthesized, for example, by reacting allylmagnesium halide with halogenated trimethylsilane.

The present invention requires that it be carried out in the presence of the titanium compound represented by the general formula (I[).

Examples of this titanium compound include titanium tetrachloride, titanium tetrabromide, titanium tetraiodide, titanium tetrafluoride, titanium trichloride-bromide, titanium dichloride and tribromide, etc., but from the viewpoint of availability, Titanium tetrachloride is preferred.

According to the method of the present invention, the α-keto acid ester represented by the general formula (II) and 1.0 to 1.5 equivalents of allyltrimethylsilane are mixed with methylene chloride, chloroform, carbon tetrachloride, ether, benzene, -7 by mixing in an inert solvent such as tetrahydrofuran, xylene, n-hexane, etc.
By heating the mixture to 8°C to room temperature, adding 1/2-1 equivalent of a titanium compound, stirring and mixing, and treating with water after the reaction is complete.
The γ/δ-unsaturated-α oxyvaleric acid ester represented by the general formula (I) can be produced in high yield.

It should be noted that the reaction between allyltrimethylsilane and the α-keto acid ester represented by the general formula (II) is preferably carried out under anhydrous conditions since moisture is disliked.

Hereinafter, the present invention will be explained in more detail with reference to Examples.

Example 1 2.04f (20 mmol) of methyl pyruvate and 3.
42P (30 mmol) of allyltrimethylsilane was added to 2
The mixture was cooled to -78°C in a dry ice-acetone bath, and a solution of titanium tetrachloride in methylene chloride (1 mol) was dissolved in 20 rrLl (
20 mmol) was added dropwise.

After reacting for 30 minutes, it was treated with 2001 rL of water, extracted, dried, concentrated, and distilled to a boiling point of 70°C/22
2.48P (yield: 86%) of γ/δ-unsaturated monoα-oxyα-methyl methyl valerate having a temperature of mmHg was obtained.

Example 2-6 The results shown in Table 1 below were obtained in the same manner as in Example 1.

Reference example 1 1 4.50P (0.05 mol) of propyl pyruvate
001111 in dry ether and cooled in a water bath.

To this solution, 300 Ttl of an ethereal solution of a Grignard reagent prepared from 2.4 ft (0.1 mole) of metallic magnesium and 3.83 P (0.05 mole) of allyl chloride was slowly added dropwise.

After reacting at O-2℃ for 2 hours, hydrolysis with dilute hydrochloric acid,
Extracted with methylene chloride.

After drying the extract with anhydrous calcium chloride, it was concentrated and the product was separated and purified using silica gel chromatography.
x, 72P (yield 20%) of γ/δ-unsaturated-α-oxy-α-methylpropyl valerate was obtained.

Reference Example 2 The reaction was carried out in the same manner as in Reference Example 1 except that the ether solution of propyl pyruvate was added dropwise to the ether solution of allylmagnesium chloride, and post-treatment was performed. No propyl grass acid was obtained.

Claims (1)

[Claims] 1. It is prohibited from reacting allyltrimethylsilane and a keto acid ester of the general formula % in the presence of a titanium compound represented by the general formula, and then treating the resulting reaction mixture with water, A method for producing γ/δ-unsaturated monoα-oxyvaleric acid esters represented by the general formula (wherein R1 is a hydrogen atom, an alkyl group or an aryl group, R2 is an alkyl group or an aryl group, and 4 The number of X's is the same or different halogen atoms.)2 The method according to claim 1, wherein the titanium compound is titanium tetrachloride. 3. The method according to claim 1 or 2, wherein the reaction between allyltrimethylsilane and α-keto acid ester is prohibited from being carried out under anhydrous conditions.