KR840000497B1 - Method for production of acylhydrazones of formyl-acetic acid ester - Google Patents

Abstract

HCH2CO2R1 (I; R=C1-4 alkoxy or NH2; R1 = C1-6 alkyl) were prepd. Thus, 9.8g propionate ethyl ester was added dropwise over 5 min to 11.15g semicarbazide hydrochloride, 10.0g KHCO3, 10mL H2O, and 10mL ethanol, and the mixt. was warmed for 4 hr at 30oC to give 93.5% fromylacetate ethyl ester semicarbazon (3-semicarbazono-propionate ethyl ester) (I; R=NH2; R1=Et). Also prepd. was I (R=EtO; R1=Et).

Description

Method for preparing acylhydrazone of formyl acetate ester

The present invention relates to a novel process for preparing acylhydrazone of formyl acetate esters which is important as starting material in the preparation of 1,2,3-thiadiazole derivatives.

Formyl acetic acid ethyl ester semicarbazone [W. Wislicenus, H.W. Bywaters, Liebigs Ann. Chem. 356, 50 (1907)] and formyl acetic acid ethyl ester ethoxycarbonyl hydrazone [R. Reap, R.G. Micetich, Can. J. of Chem. 46, 1057 (1968) is already known in the literature. According to these references, these two compounds are obtained by a process for the reaction of the sodium salt of the formyl acetate ester in question with the corresponding hydrazine derivative.

This method requires the synthesis and separation of formyl acetate sodium salt. However, this method can be manufactured only through a complicated and time-consuming process, and furthermore, the yield is not satisfactory [D.R.P. 708,513, British Patent Specification 568,512, US Patent Specification 2,394,255, and Deschel, Helv. Chim. Acta. 35, 1587 (1952).

One method (L. Beer and P. Halbig, DRP 708,513) condenses formic acid esters and ethyl acetate with sodium alcoholate in an autoclave reactor, which is prepared by reacting excess alcohol with carbon monoxide under pressure. do.

Considering the low yield and cost of equipment (pressurization), this method is not suitable for economic and commercial reasons. The yields shown in the literature are not reproducible.

According to another method (E.H. Northey, British Patent No. 568,512 and United States Patent No. 2,394,255), formic acid esters and ethyl acetate are condensed with alcohol-free sodium alcohol-rate using carbon monoxide under pressure.

This method is also not suitable for industrial production because of the pressurization reaction and the low yield.

Third method [W. Deus-chel, Helv. Chim. Acta. 35, 1587 (1952) is a condensation of a mixture of ethyl acetate and formic acid with an alcohol free sodium alcoholate prepared from powdered sodium and etheric alcohol. Because of the use of sodium suspensions in ether and low yields, the method is only limited to laboratory scale and is very unsuitable for industrial production.

Therefore, the present invention is based on this problem, a process for preparing acylhydrazone of formyl acetate ester with no problem and having a high yield by removing formyl acetate sodium salt in only one step as an intermediate step and It is to provide a method suitable for commercially preparing the material.

This problem was solved according to the method of the present invention.

Accordingly, the present invention reacts the propiolic acid ester of the following general formula (II) with a hydrazine derivative of the following general formula (III) in the presence of water or an organic solvent to acylhydrazone of the formyl acetate ester of the following general formula (I) It provides a method of manufacturing.

In the above general formula

R ₁ represents an alkyl group having 1 to 6 carbon atoms

R ₂ represents an alkoxy group, preferably an alkoxy group having 1 to 4 carbon atoms, or an amino group.

The process of the present invention allows the use of readily available starting materials and the technically simple and harmless production of the desired product in high yield.

Synthesis of acylhydrazone of general formula (I) starting with propiolic acid ester of general formula (II) is preferably carried out in an aqueous medium, in an organic solvent or a mixture of water and organic solvent, preferably in an aqueous or alkoxy medium. It is preferable to carry out by reacting equimolar amounts of hydrazine derivatives of the general formula (III). Advantageously the propiolic acid ester is added in small amounts to water or a solution of the hydrazine component diluted with 1-4 alcohols, or alternatively diluted with a solvent such as, for example, 1-4 alcohols. Here, the alcohol / water mixing ratio can be varied within a wide range, while only alcohol and water may be used. The weight ratio of alcohol / water is preferably 1: 1. Addition of the reactants may also be performed in the reverse order. The reaction takes place in the range of 20 ° C to 100 ° C, preferably 0 ° C to 50 ° C.

Referenced as C1-4 alcohols are, for example, methanol, ethanol, propanol, isopropanol, butanol, secondary-butanol and tert-butanol.

After the reaction has taken place, the generally solid reaction product can be separated into colorless crystals by filtration, freezing precipitation or removal of the solvent. These products can be readily recrystallized with suitable organic solvents such as ketones, alcohols, nitriles, esters, ethers and chlorinated hydrocarbons such as, for example, acetone, methanol, ethanol, acetotrile, ethyl acetate, diiso-propyl ether and chloroform. It is stable at room temperature. The mixture is generally obtained in pure form which can be further reacted in the recrystallization step.

The preparation products of the present invention are commercially useful starting materials used in the preparation of fungicides such as 1,2,3-thiadiazole-5-carboxylic acid derivatives and 1,2,3-thiadiazol-5-yl-urea. .

The following examples illustrate the invention.

Example 1

Preparation of formyl acetic acid ethyl ester semicarbazone (3-semicabazono-propionic acid ethyl ester).

In a three-necked 100 ml round flask equipped with a stirrer and a thermometer, 11.15 g (0.1 mol) of semicarbazide hydrochloride was dissolved in 10 ml of water, to which 10.0 g (0.1 mol) of potassium bicarbonate was added and the whole was 10 ml of ethanol. Dilute with. To this was added dropwise 9.8 g (0.1 mol) of propiolic acid ethyl ester over 5 minutes. The reaction temperature is maintained at about 30 [deg.] C. for 4 hours during which the crystalline magma of the bath is formed slowly. After overnight setting the mixture is cooled in an ice bath and diluted with 10 ml of water. The crystals obtained by suction filtration are washed with water in 10 ml and dried in vacuo at 40 ° C. until weight is contained.

Yield: 16.2 g = 93.5% of theory

Melting Point: 147 to 148 ° C

TLC: eluent = ethyl acetate / chloroform 1: 1

R _f value: 0.110

Elemental Analysis: Calculation: C 41.62% H 6.40% N 24.26%

Found: C 41.70% H 6.40% N 23.89%

Example 2

Preparation of formyl acetic acid ethyl ester ethoxycarbonylhydrazone (3-ethoxycarbonylhydrazono-propionic acid ethyl ester).

41.6 g (0.4 mol) of hydrazinoformate ethyl ester is dissolved in 120 ml of ethanol in a three-neck 250 ml round flask equipped with a stirrer and a thermometer, and 39.2 g (0.4 mol) of propiolic acid ethyl ester is added thereto. As a result, the temperature is raised to 30 ° C., which is maintained for 3 more hours. After overnight standing at room temperature the mixture is evaporated under vacuum at 40 ° C. The yellow oil residue crystallizes when polished. The crystals are ground with a mixture of 60 ml of isopropyl ether and 60 ml of cyclohexane, filtered off with suction, washed with 100 ml of cyclohexane and dried under vacuum at room temperature until the weight is constant.

Yield: 71.2 g = 88.0% of theory

Melting Point: 64 ~ 66 ℃

TLC: eluent = ethyl acetate / chloroform 1: 1

R _f value: 0.360

Elemental Analysis: Calculation: C 47.52% H 6.98% N 13.86%

Found: C 47.21% H 6.77% N 14.08%

Claims (1)

A process for preparing acylhydrazone of formyl acetic acid ester of the following general formula (I) characterized by reacting the propiolic acid ester of the following general formula (II) with a hydrazine derivative of the following general formula (III),

In the above general formula R ₁ represents an alkyl group having 1 to 6 carbon atoms R ₂ represents an alkoxy group or an amino group.