JP3243875B2 - Method for producing N-propargylglycine derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing an N-propargylglycine derivative useful as an intermediate for producing an insecticide.

[0002]

2. Description of the Related Art An N-propargylglycine derivative represented by the following general formula (4) is used for producing an active ingredient compound of an insecticide described in US Pat. No. 4,176,189. It is known from U.S. Pat. No. 4,827,020 that it is a useful production intermediate, and in this specification, the N-propargylglycine derivative has an N-propargylglycine derivative represented by the following general formula (3). It is described that the compound is obtained by reacting an alkoxycarbonylglycine derivative with propargyl halide in the presence of a base. However, in this production method, the reaction yield is not always sufficiently satisfactory, and further improvement in the yield has been desired.

[0003]

In view of such circumstances, the present inventors have conducted intensive studies to find a more industrially advantageous method for producing an N-propargylglycine derivative. As a result, propargyl was used as a reagent for propargylation. It has been found that the use of mesylate (propargyl methanesulfonate) enables the production of an N-propargylglycine derivative in good yield, and has completed the present invention. That is, the present invention provides a compound represented by the general formula:

Embedded image (Wherein, R and R ′ are the same or different and represent a lower alkyl group (eg, a C1-C4 alkyl group such as a methyl group, an ethyl group, a propyl group, a butyl group, etc.). Is reacted with propargyl mesylate in the presence of a base,
General formula 4

Embedded image (Wherein, R and R ′ have the same meanings as described above.) The present invention provides a method for producing an N-propargylglycine derivative represented by the formula:

In the present invention, examples of the base used include alkali metal hydrides such as sodium hydride and potassium hydride, and alkali metal alkoxides such as potassium tert-butoxide, sodium methoxide and sodium ethoxide (methoxide, methoxide). C1-C4 alkoxides such as ethoxide and tert-butoxide). In the present invention, the reaction is usually carried out with aromatic hydrocarbons such as toluene and benzene, aliphatic hydrocarbons such as hexane and heptane, ethers such as tetrahydrofuran and 1,2-dimethoxyethane, and non-methods such as dimethyl sulfoxide and dimethylformamide. The reaction is carried out in an inert solvent such as a protic polar solvent and a mixture thereof, but it is preferable to use an aromatic hydrocarbon such as toluene from an industrial viewpoint. In the present invention, the use of a phase transfer catalyst as a reaction auxiliary suppresses the generation of by-products and achieves an improvement in purity and yield. Examples of the phase transfer catalyst used include tetrabutylammonium bromide (hereinafter referred to as TBAB), tetrabutylammonium iodide, tetraethylammonium bromide, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, and tetrabutylammonium sulfate. Tertiary amines such as quaternary ammonium salts, tris [2- (2-methoxyethoxy) ethyl] amine, tris (3,6-dioxaheptyl) amine and tris (3,6-dioxaoctyl) amine; And crown ethers such as 18-crown-6 and dicyclohexano-18-crown-6. In the present invention, the reaction is generally carried out in an atmosphere of an inert gas such as nitrogen or argon at a temperature in the range of -30 to 60 ° C over a period of 1 to 40 hours. Usually, the proportion of propargyl mesylate is 1 to 10 mol, the proportion of base is 1 to 1.5 mol, and the amount of the phase transfer catalyst is 0.1 to 1 mol of the compound represented by Chemical formula 3.
It is a ratio of 01 to 0.5 mol. In order to allow the reaction to proceed completely, it is usually desirable to add alcohol as a reaction aid after the other reaction reagents have been added during the reaction. Examples of the alcohol used at this time include C1 to C4 lower alcohols such as methanol, ethanol and propyl alcohol. In order to suppress the generation of impurities due to the transesterification reaction, a compound represented by the general formula 3 is used. It is desirable to use an alcohol having the same alkyl group as R or R ′, more preferably R ′. The amount of the alcohol to be used is generally 0.01 to 1 mol per mol of the compound represented by the general formula (3).
1 mole ratio. After completion of the reaction, the objective is obtained by adding to a method generally used, for example, weakly acidic water having a pH of 2 to 6 (aqueous ammonium chloride solution, dilute hydrochloric acid water, etc.), and separating the resulting organic layer under reduced pressure. N-propargylglycine derivatives can be isolated. Also,
If necessary, it can be further purified by distillation or column chromatography.

[0005]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to the following examples. In addition, all% represent weight%. In addition, all content analyzes were performed by gas chromatography under the following conditions. Column: 2% silicon OV-17, Sumikaso
rb HP (manufactured by Sumika Chemical Analysis Service, Ltd.), diameter 3 mm
× length 1 m, 80-100 mesh Column temperature: 110 ° C Injection and detection temperature: 200 ° C Detection method: FID Carrier gas and its flow rate: nitrogen gas, 30 ml / min Internal standard substance: ethyl cinnamate Example 1 Under nitrogen atmosphere To a suspension of sodium hydride (65.5% oil dispersion) (13.6 g) in toluene (40.0 g) was added a 18.9% N-methoxycarbonylglycine ethyl ester / toluene solution (264.6 g) at 30-35 ° C. .5
It was dropped over time. After keeping the temperature and stirring at the same temperature for 2 hours, TBAB (5.0 g) was added at the same temperature, and the temperature was kept and stirred for 30 minutes. A 50.0% propargyl mesylate / toluene solution (99.9 g) was added dropwise at 0 to 5 ° C over 3 hours.
After keeping the temperature and stirring at the same temperature for 2 hours, the temperature was raised to 20 to 25 ° C., and ethanol (2.50 g) was added dropwise at the same temperature over 10 minutes. After keeping the temperature and stirring at the same temperature for 14 hours, the reaction solution was poured into a solution of ammonium chloride (2.00 g) in cold water (200.0 g). After liquid separation, the toluene layer was concentrated under reduced pressure to obtain 67.66 g of an oily residue. As a result of the content analysis of the residue (8
1.7%), the net yield of N-propargyl-N-methoxycarbonylglycine ethyl ester was 89.5%. Example 2 Under a nitrogen atmosphere, a 18.9% N-methoxycarbonylglycine ethyl ester / toluene solution (30 g to 35 g) was added to a suspension of sodium hydride (65.5% oil dispersion) (13.6 g) in toluene (40.0 g). 264.6g) to 1.5
It was dropped over time. After keeping the temperature and stirring at the same temperature for 2 hours, TBAB (5.0 g) was added at the same temperature, and the temperature was kept and stirred for 30 minutes. A 50.0% propargyl mesylate / toluene solution (99.9 g) was added dropwise at 0 to 5 ° C over 3 hours.
After keeping the temperature and stirring at the same temperature for 2 hours, the temperature was raised to 20 to 25 ° C. After keeping the temperature and stirring at the same temperature for 14 hours, the reaction solution was poured into a solution of ammonium chloride (2.00 g) in cold water (200.0 g). After liquid separation, the toluene layer was concentrated under reduced pressure to obtain 69.57 g of an oily state test. As a result of the content analysis of the residue (7
5.8%), the net yield of N-propargyl-N-methoxycarbonylglycine ethyl ester was 85.3%. Example 3 Under a nitrogen atmosphere, a suspension of sodium hydride (65.5% oil dispersion) (13.6 g) in toluene (40.0 g) was added to a 18.9% N-methoxycarbonylglycine ethyl ester / toluene solution at 30 to 35 ° C. 264.6g) to 1.5
It was dropped over time. The mixture was kept warm and stirred at the same temperature for 2 hours.
A 50.0% propargyl mesylate / toluene solution (99.9 g) was added dropwise at 0 to 5 ° C over 3 hours. After keeping the temperature and stirring at the same temperature for 2 hours, the temperature was raised to 20 to 25 ° C., and ethanol (2.50 g) was added dropwise at the same temperature over 10 minutes. After keeping the mixture at the same temperature for 14 hours and stirring it, ammonium chloride (2.00
g) in cold water (200.0 g). After liquid separation, the toluene layer is concentrated under reduced pressure, and the oily state is checked67.
56 g were obtained. From the result of the residue content analysis (73.6%), N
The pure yield of -propargyl-N-methoxycarbonylglycine ethyl ester was 80.5%. Example 4 Under a nitrogen atmosphere, a suspension of sodium hydride (65.5% oil dispersion) (13.6 g) in toluene (40.0 g) was added to a 18.9% N-methoxycarbonylglycine ethyl ester / toluene solution at 30 to 35 ° C. 264.6g) to 1.5
It was dropped over time. The mixture was kept warm and stirred at the same temperature for 2 hours.
A 50.0% propargyl mesylate / toluene solution (99.9 g) was added dropwise at 0 to 5 ° C over 3 hours. After keeping the temperature and stirring at the same temperature for 2 hours, the temperature was raised to 20 to 25 ° C. After keeping the mixture at the same temperature for 14 hours and stirring it, ammonium chloride (2.00
g) in cold water (200.0 g). After liquid separation, the toluene layer was concentrated under reduced pressure, and the oily state was inspected70.
92 g were obtained. As a result of analyzing the content of the residue (68.92%), the pure yield of N-propargyl-N-methoxycarbonylglycine ethyl ester was 79.1%.

[0006]

According to the present invention, an N-propargylglycine derivative represented by the above general formula 3, which is useful as an intermediate for producing an insecticide, can be produced with high yield.

──────────────────────────────────────────────────続 き Continuation of front page (56) References JP-A-63-238052 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 271/22 C07C 269/06 C07B 61 / 00 300

Claims (3)

(57) [Claims] 1. A compound represented by the general formula: Wherein R and R ′ are the same or different and represent a lower alkyl group, and reacting the N-alkoxycarbonylglycine derivative with propargyl mesylate in the presence of a base. Chemical formula 2 Chemical formula 2 (Wherein R and R ′ have the same meanings as described above). 2. The reaction in the presence of a phase transfer catalyst.
Production method as described. 3. The method according to claim 1, wherein an alcohol is used as a reaction assistant.