IE51456B1 - Process for the manufacture of 3-acylazo-propionic acid esters and isomers thereof - Google Patents

Abstract

3-Acylazo-propionic acid esters of the general formula I and isomers thereof (in which R1 represents C1-C6-alkyl and R2 represents alkoxy or amino), suitable as starting materials for the manufacture of 1,2,3-thiadiazole-5- carboxylic acid derivatives, are prepared by a process which comprises reacting an acrylic acid ester of the general formula H2C=CH-COOR1 with a hydrazine derivative of the general formula H2N-NH-CO-R2 to form a 3- acylhydrazino-propionic acid ester of the general formula and oxidizing this ester in an inert solvent with an oxidizing agent.

Description

The present invention ie concerned with ε new process for the manufacture of 3-acylazo-propionic acid esters and also isomers thereof including the isomeric formylacetic acid eBter acylhydrazones thereof.

Processes for the manufacture of formylacetic acid ethyl eBter semicarhazone [V. Wislicenus, H.W. BywaterB, Liebigs Ann. Chem. 356, 50 (1907)] and formylacetic acid ethyl ester ethoxycarbonylhydrazone [R. Raap, R.G. Kicetich, Can» J. of Chem» 46,1057 (1968)] are already known. These compounds can be manufactured by reacting the sodium Balt of the formylacetic acid ester in question with the corresponding hydrazine derivative, which process requires the synthesis and isolation of the formylacetic acid ester sodium salt. The latter can, however, be manufactured only by using complicated and lengthy working procedures and, moreover, only in unsatisfactory yields (German Patent Specification No, 708,513; British Patent Specification No. 568,512).

The problem upon which the present invention is based has therefore been to provide a process that permits the manufacture of 3-acylazo-propionic acid esters and also the isomers thereof in a technically simple manner and in high yields.

This problem is now solved according to the process of the present invention.

The present invention accordingly provides a process for the manufacture of a compound selected from a 3—acylazo51456 propionic acid ester of the general formula I ch2 - CHg - COOi^ (I), N «= N - CO - R2 in which R^ represents a C^-Cg-alkyl group and 5 R2 represents an alkoxy group, preferably a C^-C^-alkoxy group, or an amino group, and isomers thereof of the general formula V CH - CH2 - COOR1 (V), N - NH - CO - R2 in which R^ and Rg have the meanings given above, 10 and of the general formula VI CH = CH - COOR.

(VI), NH - NH - CO - R. in which R^ and Rg have the meanings given above, which comprises reacting an acrylic acid ester of the general formula II C = C - COORj (II), - 4 in which R^ has the meaning given above, with a hydrazine derivative oi the general formula III H2N - NH - CO - fiz (III), in which R2 has the meaning given above, if desired with 5 the use of an inert solvent and/or in the presence of a catalyst, to form a 3-aeylhydrazino-propionic acid ester of the general formula IV CH- - CH- - COOR, I NH - NH - CO - S2 in which R^ ^2 ^e meanings given above, and oxidizing this compound of the general formula IV in an inert solvent with an oxidizing agent.

As alkyl groups there may be mentioned, for example, methyl, ethyl, propyl, isopropyl, n-butyl, sec.-butyl, n-pentyl and n-hexyl groups.

As alkoxy groups there may be mentioned, for example, methoxy, ethoxy, propoxy and butoxy groups.

The process of the present invention thus makes use of readily available starting materials and makes possible a technically simple and safe manufacture of the desired process products in high yields.

Particular embodiments of the process of the present Invention consist in that, the reaction of the acrylic acid ester of the general formula II with the hydrazine derivative of the general formula III is carried out at a temperature within the range of from -20°C to 150°C, preferably within the range of from 0°C to 50°C, and at a pressure within the range of from 1 to 10 atmospheres, preferably at 1 atmosphere, if desired as a base- or acid-catalysed reaction and that approximately equimolar amounts of the acrylic acid ester of the general formula II and of the hydrazine derivative of the general formula III are used, and that the oxidation of the 3-acylhydrazino-propionio acid ester of the general formula IV ie carried out with an oxidizing agent, for example a conventional oxidizing agent, at a temperature within the range of from -20°C to 100°C, preferably from -5°C to 50°C, and that a 3-acylhydrazino-propionio acid ester of the general formula IV is used which is not isolated from the reaction mixture in which It is formed, so that the formation of this ester and the oxidation thereof may be a continuous process.

The process of the present invention is carried out in a technically simple and elegant manner.

The synthesis of the 3-a°ylbydrazino-propionic acid esters of the general formula IV may be carried out according to the process of the present invention starting with an acrylic acid ester of the general formula II and reacting it with an approximately equimolar amount of a hydrazine - 6 derivative of the general formula III in an aqueous medium, in an inert organic eolvent, preferably in an aqueous or alcoholic medium, or, if desired, even using no solvent at all. Advantageously, the acrylic acid ester is added, in portions or diluted with a solvent, for example a C^-C^-alcohol, to a solution of the hydrazine component which is diluted with water or a C^-C^alcohol. In so doing, the mixing ratio of alcohol/water can vary within wide limits, since both alcohol on its own and water on its own can he used. The ratio hy weight of alcohol/water can preferably be 1:1. The reactants may also he added in the reverse order.

The reaction takes place at temperatures of from -20°C to 150°C, preferably from 0°C to 50°C· The pressure can he from 1 to 10 atmospheres, preferably, however, 1 atmosphere. Solvents that are inert with respect to the reactants are, for example, C^-C^-alcohols, for example methanol, dfchanol, propanol, isopropanol, butanol, sec.butanol and tert.-butanol, halogenated hydrocarbons, for example methylene chloride, chloroform and. carbon tetrachloride, aliphatic and aromatic hydrocarbons, for example petroleum ether, pentane, cyclohexane, benzene, toluene and xylene, ethers, for example diethyl ether, tetrahydrofuran, dioxan and ethylene glycol diethyl ether, carboxylic acid nitriles, for example acetonitrile, and carboxylic acid amides, for example dimethylformamide.

The reaction may be carried out advantageously using - 7 a basic or alternatively an acidic catalyst. Ab basic catalysts there are most frequently used alkali hydroxides, alkali alcoholates, tertiary amines, for example triethylamine and Ν,Ν-dimethylaniline, benzyltrialkyl ammonium hydroxides, for example benzyltrimethyl ammonium hydroxide, and dialkylcarhoxylic acid amides, for example dimethylformamide and dimethylacetamide. For the acidic catalysis there may he used sulphuric acid, phosphoric acid, acetic acid, lactic acid and boron trifluoride.

After the reaction has taken place the reaction mixture is worked up, if desired in a maimer known per Be. After any solvent has been removed, the residue is either fractionally distilled under reduced pressure or recrystallized from suitable solvents, for example ketones, alcohols, nitrilee, eaters, ethers and chlorinated hydrocarbons, for example acetone, methanol, ethanol, acetonitrile, ethyl acetate, diisopropyl ether and chloroform. The reaction products are obtained in the form of colourless crystals or as colourless liquids that are stable at room temperatures.

When, however, a continuous process is chosen,-- the reaction product of the general formula IV does not need to be isolated, but can be further processed directly.

The 3-acylazo-propionic acid esters of the general formula I may then be produced according to the process of the present invention by reacting the 3-aeylhydrazinopropionic acid esters of the general formula IV with conventional oxidizing agents in an aqueous medium, or in organic solvents that are inert with respect to the reactants, the oxidizing agents being used either in stoichiometric amounts or in excess.

Advantageously, the oxidizing agent is added, in portions as an aqueous solution or alternatively diluted with a solvent, to a solution of the 3-acylhydrazinopropionic acid ester which is diluted with water or a solvent. The reactants may also be added in the reverse order. This reaction step takes place at temperatures within the range of from -20°C to 100°C, preferably from -5°C to 50°C. The reaction time can be between 0.5 hour and hours depending on the reaction temperature.

The following may be mentioned as solvents that are inert with respect to the reactants : aliphatic and aromatic hydrocarbons, for example cyclohexane, heptane, ligroin, benzene, toluene and xylene, and halogenated hydrocarbons, for example chlorobenzene, methylene chloride, chloroform, carbon tetrachloride and 1,2-dichloroethane.

In the presence of these solvents, further processing can be carried out even with the crude solutions, since these solvents also behave in an inert manner in the following optional steps.

The following may be mentioned as examples of conven25 tional oxidizing agents which correspondingly determine the choice of solvent s nitric acid, potassium dichromate, potassium permanganate, mercury oxide, ammonium nitrate «nd - 9 eodium nitrate, sodium chlorate, chlorine, alkali metal hypochlorites and alkaline earth metal hypochlorites, ammoniacal hydrogen peroxide, iron(lll) chloride, dinitrogen trioxide and lead(IV) oxide.

After the reaction has taken place, the reaction mixture may be worked up in a manner known per se. for example by distilling off the solvent used at a reduced or normal pressure or by extraction, it being possible to use the organic solvents employed in the course of the reaction also as agents for extracting the 3-acylazopropionic acid esters. The extracts may then be worked up in a known manner, for example after euitable drying by distilling off the solvent used at normal or a reduced pressure. In this manner the 3-acylazo-propionic acid esters are obtained in the form of slightly yellowcoloured crystals or oils in an extremely pure form and in very high yields, so that they can be reacted without further purification.

By the oxidation of the 3-acylhydrazino-propionic acid esters of the general formula IV, primary compounds of the structural general formula I are formed as can be seen by examining the nuclear magnetic resonance spectra.

In solution these compounds have the tendency to rearrange to form formylacetic acid ester acylhydrazones of the general formula V - 10 CH - CH2 - COOI^ l (V)’ N - NH - CO - E2 which accordingly represent isomers of the compounds of the general formula I.

The manufacture of the compounds of the general 5 formula V, that is the formylacetic acid ester acylhydrazones, is therefore also included within the scope of the present invention.

The compounds of the general formula V are, on the other hand, in an isomeric equilibrium with compounds of the general formula VI CH = CH - COOB^ (VI), NH - NH - CO - R2 the manufacture of which is therefore also included within the scope of the present invention.

If desired, an irreversible rearrangement of the com15 pounds of the structural general formula I into the isomeric form(s) of the structural formula(e) V and/or VI can be carried out in a controlled manner, which rearrangement is also included within the scope of the process of the present invention.

According to thiB optional step of the process of the - 11 present invention, the 3-acylazo-propionic acid esters of the general formula I are treated with catalysts, optionally using an inert solvent, R^ and Rg having the meanings given above.

One particular embodiment of this process feature consists in that a 3-acylazo-propionic acid ester of the general formula I is rearranged, at a temperature within the range of from -20°C to 50°C, preferably at a temperature vi thin the range of from 0°C to 30°C, to form the acylhydrazone of the formylaeetic acid ester of the general formula V and to form the enhydrazine of the general formula VI.

ThlB reaction may be carried out ueing both acid or lewis acid catalysts and also basic catalysts. The following may be mentioned as examples of acid catalysts : hydrochloric acid, eulphuric acid and nitric acid, HgClg, (NH4)2S04, NH4C1, NH4Br, HgBr2, (CHjJjSiOSOgCFj, SnCl4, BP,ρ-toluenesulphonic acid hydrate, acetic acid and trifluoroacetic acid.

The following may be mentioned as basic catalysts : oxides, hydroxides, alcoholates and carbonates of the alkaline earth metals and alkali metals, ammonia, tertiary amines, for example triethylamine and Ν,Ν-dimethylaniline, and pyridine bases. The isomerization reaction advantageously takes place in an aqueous medium and/or in organic solvents.

The following may be mentioned as inert solvents : - 12 halogenated hydrocarbons, for example methylene chloride, chloroform, 1,2-dichloroethane, carbon tetrachloride and chlorobenzene, aliphatic and aromatic hydrocarbons, for example petroleum ether, pentane, Aeptane, cyclohexane, benzene, toluene and xylene, ethers, for example diethyl ether, tetrahydrofuran, dioxan and diisopropyl ether, end alcohols, for example methanol and ethanol.

The reaction may take place at a temperature within the range of from -20°C to 50°C, preferably at a tempera10 ture within the range of from 0°C to 30°C.

In practice the process is carried out in such a manner that an appropriate catalyst is added to the crude solution of the 3-acylazo-propionic acid ester and. then the reaction products, which are normally solid, are iso15 lated in the form of colourless crystals by filtration, by freezing-out or by removing the solvent. These can be readily recrystalli26d from suitable organic solvents, for example ketones, alcohols, nitriles, esters, ethers and chlorinated hydrocarbons, for example acetone, methanol, ethanol, acetonitrile, ethyl acetate, diisopropyl ether and chloroform, and are stable at room temperature. The compounds are generally, however, produced in such a highly pure form that they can be further reacted in the un-recrystallized state.

The products manufactured according to the process of the present invention represent important starting materials for the manufacture of l,2,3-thiadiazole-5-carbo3ylic acid - 13 derivatives from which valuable plant protecting agents and pest-controlling agents and also pharmaceutical products can be manufactured.

This manufacture of l,2,3-thiadiazole-5-carboxylic acid derivatives of the general formula VII N-C-H II (VII), / C - COCff^ in which Rj has the meaning given above, can be carried out, for example, in a manner known per se by reacting the process products of the general formula(e) V and/or VI with thionyl chloride.

The process of the present invention offers, in addition, a new advantageous method of manufacture for the compounds of the general formula VII, by directly reacting the primarily formed process products of the general formula I with thionyl chloride of the formula SOClg to form the desired products of the general formula VII, as a result of which one step of the process ie avoided (as compared with the reaction of thionyl chloride with compounds of the general formula(e) V and/or VI). This pro20 cess feature is also included within the scope of the process of the present invention.

The synthesis of the l,2,3-thiadiazole-5-oarboxylie acid esters of the general formula VII is carried out in - 14 this case by starting from 3-acylazo-propionic acid esters of the general formula I and reacting them with thionyl chloride. The reaction is carried out at a temperature within the range of from -20°C to 100°C, preferably from -5°C to 50°C. The reaction time can be between 1 hour and 20 hours depending on the reaction temperature.

For the synthesis of the l,2,3-thiadiazole-5-carboxylic acid esters, the reactants can be used in approximately equimolar amounts. Thionyl chloride may, however, alternatively be used in a large excess quasi as a solvent.

Advantageously, however, the molar ratio of the 3acylazo-propionic acid ester to the thionyl chloride used for the reaction is 1ί3. The reaction may also proceed in the presence of solvents that are inert with respect to the reactants. As such solvents there may be mentioned halogenated hydrocarbons, for example methylene chloride, chloroform and carbon tetrachloride, aliphatic and aromatic hydrocarbons, for example petroleum ether, pentane, cyclohexane, benzene, toluene and xylene, ethers, for example diethyl ether, tetrahydrofuran, dioxan, ethylene glycol diethyl ether and diethylene glycol diethyl ether, and esters, for example ethyl acetate.

The 3-acylazo-propionic acid ester, optionally dissolved or suspended in a suitable solvent, is normally added in portions to the thionyl chloride optionally diluted with an organic solvent, but the reactants may also be added in the reverse order. The hydrogen chloride that - 15 is formed during the reaction can be removed continuously from the reaction vessel by means of an inert gaB current or by applying a vacuum.

After the reaction has taken place, the reaction mixture may be worked up in a manner known per Be.

After distilling off the solvent and any excess thionyl chloride, the residue can be fractionally distilled; alternatively, however, any excess thionyl chloride is destroyed with a saturated soda solution, sodium bicarbonate solution, potassium bicarbonate solution or sodium acetate solution or with a sodium hydroxide solution or potassium hydroxide solution or directly with water and the reaction solution is subjected to steam distillation or extraction, it being possible to use the solvents employed in the course of the reaction also as extracting agents. The extracts may then be worked up in a known manner; for example, after appropriate drying and distilling-off of the solvent, the residue is fractionally distilled under a reduced pressure or simply digested with a suitable solvent, for example an aliphatic hydrocarbon, for example pentane, hexane, cyclohexane or petroleum ether.

The l,2,3-thiadiazole-5-oarboxylic acid esters are thus obtained in an extremely pure form and in very high yields, so that they can be further reacted to form the desired end products without being purified. 6 - 16 The following Examples illustrate the invention: Example 1 a) MANTJFACTPRE OF 3-SEMICARBAZIDO-PRQPIONIC ACID ΜΕΤΗΠ, ESTER In a three-necked 2 litre round-bottomed flask equipped with a stirrer, thermometer and reflux condenser having a drying tube, 173.0 g (1.5 moles) of pulverized semicarbazide hydrochloride were suspended in 300 ml of methanol; to this a sodium methoxide solution freshly prepared from 34.4 g (l.5 moles) of sodium and 500 ml of methanol was added dropwise in the course of 10 minutes, the temperature in the flask being kept at between 15°C and 20°C. The reaction mixture was then stirred for a further 15 minutes at 20°C, and then the sodium chloride was filtered off with suction. The filtrate was collected in a three-necked 2 litre round-bottomed flask and 90 ml (1.0 mole) of acrylic a:id methyl ester were added whilst stirring at 20°C in the course of one hour. The mixture was left to stand for 3 days at room temperature, was then filtered again and then the filtrate was concentrated in vacuo at 40°C. 205 g of a yellow oily product was obtained which was then extracted by stirring for a further hour, at room temperature, with 1 litre of ethyl acetate. The undissolved material was filtered off and the filtrate wae then concentrated to 500 ml at 40°C. White crystals were obtained by trituration which were filtered off with suction and dried in vacuo at room temperature until their weight was constant.

Tield: 134.4 g = 83.4% of the theoretical yield.

M.p.: 67 - 69°C. bl) MANUFACTURE OF 3-CARBAMOTLAZO-PROPIONIC ACID METHYL ESTER In a three-necked 1 litre flask equipped with a thermometer and stirrer, 16.1 g (0.1 mole) of 3-semicarbazidopropionic acid methyl ester were dissolved in 100 ml of water and, whilst cooling with ice, 246.0 g (0.3 mole) of an approximately 10% freshly prepared sodium hypochlorite solution were added in the course of 20 minutes, the temperature in the flask being kept at between 5 and 7°C.

After stirring the yellow reaction solution so ohtained for 10 minutes in an ice bath, 85 g of sodium chloride were added and the mixture waB extracted carefully five times, with 400 ml of chloroform each time. The extracts, dried over magnesium sulphate, were concentrated in vacuo at 40°C. A yellow crystalline product was obtained, Tield: 12.9 g = 81.1% of the theoretical yield.

M.p.: 85 - 87°C with decomposition. b2) MANUFACTURE OF 3-CARRAMQTIAZ0-PR0PI0NIC ACID METRTL ESTER In a three-necked 1 litre flask equipped with a stirrer and a thermometer, 16.1 g (0.1 mole) of 3-semicarbazidopropionic acid methyl ester were dissolved in a mixture of 150 ml of water and 10.3 g of approximately 95% sulphuric acid. Whilst cooling with ice, a solution of 9.79 g (0.0333 - 18 mole) of potassium dichromate in 70 ml of water and 13.8 g of approximately 95% sulphuric acid were added dropwise, in the course of 10 minuteB, at a reaction temperature of from 7°C to 10°C, The mixture wae then left to react for a further 10 minuteB and then 20.0 g of solid potassium bicarbonate were added. Yellow crystals separated. The reaction solution was extracted intensively five times, with 300 ml of chloroform each time. The chloroform extracts, dried over magnesium sulphate, were concentrated in vacuo at 40°C. Yellow crystals were obtained.

Yield: 9.0 g = 56.5% of the theoretical yield.

M.p.: 85 - 87°C with decomposition. c) MANUFACTURE OF 3-SEMICARBAZ0N0-FR0PIONIC ACID METHYL ESTER In a three-necked 250 ml flask equipped with a thermometer and a stirrer, 15.9 g (0.1 mole) of 3-carbamoylazo-propionic acid methyl ester were dissolved in. 100 ml of chloroform and 0.5 ml of triethyl amins was added, the temperature in the flask being kept at 30°C by cooling.

The mixture was then stirred for a further hour at room temperature and then the resulting crystalline magma was concentrated to dryness by evaporation in vacuo at 40°C. The residue was digested with 150 ml of diisopropyl ether, filtered with suction and dried in vacuo until its weight was constant.

Yield: 14.5 g = 91.1% of the theoretical yield.

M.p.: 159°C with decomposition. - 19 Example 2 a) MANUFACTURE OF ^-ETHOIYCARBOJiYIRTPRAZINO-PROPIONIC ACID METHYL ESTER In a three-necked 1 litre flask equipped with a stirrer, thermometer and reflux condenser, 114.4 g (1.1 moles) of hydrazinoformic acid ethyl ester were dissolved in 600 ml of ethanol and 90 ml (0.1 mole) of acrylic acid methyl ester were added at 20°C in the course of one hour. The mixture was left to stand for 4 days at. room temperature in a sealed flask and then the reaction solution was concentrated in vacuo at 40°C. The liquid so obtained was distilled in vacuo.

Tield! 111.1 g = 58.4?» of the theoretical yield.

B.p.! 110 - 111°C / 0.1 torr. b) MANUFACTURE Of 3-ETH0XYCARBOMTIA2O-PROPIONIC ACID METHYL· ESTER In a three-necked 250 ml flask equipped with a stirrer and a thermometer, 9·5 β (0.05 mole) of 3-ethoxycarbonylhydrazino-propionic acid methyl ester were dissolved in 50 ml of water and 82 g (0.1 mole) of an approximately 10?ί freshly prepared sodium hypochlorite solution were added in the course of 20 minutes, the temperature in the flask being kept at between 5°C and 7°C. A yellow oil separated. The mixture was then stirred for a further 10 minutes in an ice bath, extracted three times, with 75 ml of chloroform each time, and a yellow viscous oil was obtained after drying over magnesium sulphate and concentrating the chloro51456 -20 form phases by evaporation In vacuo at 40°C.

Yield: 8.7 g = 92.4% of the theoretical yield. n^° s 1.4424. c) MANUFACTURE OF 5-BTH0XYCARB0NYIiBYDRAZ0N0-PR0PI0NIC 5 ACID METHYL ESTER In a three-necked flask equipped with a stirrer and a thermometer, 18.8 g (0.1 mole) of 3-ethoxycarhonylazopropionic acid methyl ester were dissolved in 100 ml of chloroform and 0.5 ml of triethylamine was added at 30°0, during which operation the mixture had to be cooled owing to the exothermic course of the reaction. Stirring was then subsequently carried out for a further hour at room temperature and then the reaction solution was concentrated in vacuo at 40°C. The oil remaining as residue was digested with 50 ml of diisopropyl ether and the crystals so obtained were filtered with suction and dried. Yield: 17.9 g = 95.2% of the theoretical yield.

M.p.: 60 - 61°C.

Example 5 MANUFACTURE OP 3-SEMICARBAZ0N0-PR0PI0NIC ACID METHYL ESTER (continuous) In a three-necked 1 litre flask equipped with a thermometer and a stirrer, 16.1 g (0.1 mole) of 3-semicarbazido-propionio acid methyl ester, prepared as described in Example la), were dissolved in 100 ml of water and, whilst cooling with ice, 141.6 g (0.2 mole) of an approximately 10% freshly prepared sodium hypochlorite solution were 514 5 6 - 21 added in the course of 20 minutes, the temperature in the flask being kept at between 5°C and 7°C. The yellow reaction solution was then stirred for a further 20 minutes in an ice bath, 66 g of sodium chloride were added and then the mixture wae extracted carefully five times, with 400 ml of chloroform each time. The chloroform phases, dried over magnesium sulphate, were concentrated to 100 ml at 40°C in vacuo. 0.5 ml of triethylamine was added to the chloroform solution concentrated to 100 ml, the temperature in the flask being kept at 30°C by cooling.

After stirring for one hour at room temperature, the resulting crystalline magma was concentrated to dyness at 40°C 3jq vacuo. The residue was digested with diisopropyl ether, filtered with suction and dried in vacuo until its weight was constant.

Yield: 12.0 g = 75*5% of the theoretical yield.

M.p.: 158.5 - 159.5°C with decomposition.

Example 4 MANDFACTURB OF 5-ETH0XYCARB0KYLBYDRAZ0N0-PR0PI0HI0 ACID METHYL ESTER (continuous) In a three-necked 500 ml flask equipped with a stirrer and a thermometer, 19.0 g (0.1 mole) of 3-ethoxycarbonylhydrazino-propionic acid methyl ester, prepared as described in Example 2a)., were dissolved in 100 ml of water and 141.6 g (0.2 mole) of an approximately 10% sodium hypochlorite solution were added ia the course of 20 minutes, the temperature in the flask being kept at between 5°C and 7°C. A 1456 - 22 yellow oil separated. The mixture was then stirred for 10 minutes, and extracted three times, with 150 ml of chloroform each time, and the chloroform phase was concentrated to 100 ml after drying over magnesium sulphate. 0.5 ml of triethylamine was added to the chloroform solution concentrated to 100 ml, during which operation the temperature should not exceed 30°C. After subsequent stirring for one hour at room temperature, the reaction solution was concentrated by evaporation in vacuo at 40°0; the oily residue was then digested with 50 ml of diisopropyl ether and the colourless crystals formed were filtered with suction and dried.

Yields 12.9 S = 68,5% of the theoretical yield.

M.p.: 59 - 6l°C.

Example 5 MANUFACTURE OP 5-ETH0XYCARB0NYiaYURAZ0N0-PR0PI0NI0 ACID MBTHYI ESTERIn a three-necked 500 ml flask equipped with a stirrer and a thermometer, 19.0 g (0.1 mole) of 3-ethoxycarbonylhydrazino-propionie acid methyl ester, prepared as described in Example 2a), were dissolved in 150 ml of water and a solution of 9.79 g (0.0333 mole) of potassium dichromate in 70 ml of water and 17.2 g (0.167 mole) of 95% sulphuric acid were added in the course of 15 minutes. The temperature in the flask was kept at between -2°C and 0°C for 30 minutes. The mixture was then extracted twice, with 40 ml of chloroform each time. After drying over magnesium sul51456 - 23 phate, the chloroform solution was concentrated by evaporation in vacuo at 4O°C. The oil remaining bb residue was digested with diisopropyl ether and the resulting crystals were filtered with Buction.

Tield: 12.4 g = 65.9% of the theoretical yield.

M.p.: 57 - 61°C.

Example 6 MANUFACTURE OF 1,2.3-ΤΗΙΑΡΙΑΖΟΕΒ-5-ΟΑΚΒΟΧΤ1ΙΟ ACID METHT1 ESTER In a three-necked 250 ml round-bottomed flask equipped with a stirrer, thermometer and a condenser having an outlet into the fume cupboard, 21.8 ml (0.3 mole) of thionyl chloride were cooled to -10°C and 15.91 g (0.1 mole) of 3-carbamoylazo-propionic acid methyl ester, prepared as described in Example 1 bl) or 1 b2), were added in portions in the course of 15 minutes, the temperature in the flask being kept at between -5°C and 0°C. After the addition had been completed the yellow reaction solution was stirred for a further two hours, while allowing the temperature in the flask to rise slowly to +2°C. The solution was then diluted with 6 0 ml of chloroform and carefully decomposed with 60 ml of a saturated potassium bicarbonate solution, the temperature in the flask being kept at between 10° and 20°C. The chloroform phase was separated off, washed until neutral with 30 ml of a potassium bicarbonate solution, dried over magnesium sulphate and concentrated in vacuo at 40°C. The resulting 514 5 6 - 24 liquid was distilled in a water-jet vacuum. Yield: 11.6 g = 80.5% of the theoretical yield B.p.: 110 - 111°C / 14 torr.

Claims (5)

What we claim is: 1. , in which B^ and B 2 bave the meanings given in claim 1, and/or a compound of the general formula VI given in claim 1, in which B^ and Bg have the meanings given in claim 1, whenever made by the process claimed in any one of claims 20 1 to 21. 31® A l,2,3-thiadia2ole-5-carboxylic acid derivative of the general formula VII given in claim 22, in which B^ - 51 represents a C^-C^-alkyl group, whenever made by the process claimed in any one of claims 22 to 28. 32. A process substantially as hereinbefore described with reference to the examples.

1. A process for the manufacture of a compound selected from a 3-acylazo-propionic acid ester of the general formula I CH 2 - CHg - COO^ (I), N = N - CO - B 2 in which R^ represents a C^-Cg-alkyl group and Rg represents an alkoxy group or an amino group, and isomers thereof of the general formula V CH - CHg - COOR^ (V), N - NH - CO - Rg in which Rj and Rg have the meanings given above, and of the general formula VI CH = CH - COOR^ (VI), NH - NH - CO - Rg in which R^ and Rg have the meanings given above, 15 which comprises reacting an acrylic acid ester of the - 26 general formula II Η H \ I C = C - COOR. (II), ,/ in which R^ has the meaning given above, with a hydrazine derivative of the general formula III 5 H 2 N - HH - CO - R 2 (III), in which Rg has the meaning given above, to form a 3-acyl hydrazino-propionic acid ester of the general formula IV CHg — CHg — COOR^ I (IV), NH - NH - CO - R 2 in which Rj, and Rg have the meanings given above, and io oxidizing this compound of the general formula IV in an inert solvent with an oxidizing agent.

2. A process as claimed in claim 1, wherein Rg represents a C^C^-alkoxy group.

3. A process as claimed in claim 1 or 2, wherein the 15 reaction of the acrylic acid ester of the general formula II with the hydrazine derivative of the general formula III is carried out in an inert solvent.

4. A process as claimed in any one of claims 1 to 3, - 27 wherein the reaction of the acrylic acid eater of the general formula II with the hydrazine derivative of the general formula III is carried out in the presence of a catalyst. 55. A process as claimed in claim 4, wherein the catalyst is a basic or an acidic catalyst. 6. A process as claimed in any one of claims 1 to 5» wherein the reaction of the acrylic acid ester of the general formula II with the hydrazine derivative of the 10 general formula III is carried out at a temperature within the range of from -20°C to 150°C. 7. A process as claimed in claim 6, wherein the temperature is within the range of from 0°C to 50°C. 8. A process as claimed in any one of claims 1 to 7, 15 wherein the reaction of the acrylic acid ester of the general formula II with the hydrazine derivative of the general formula III is carried out at a pressure within the range of from 1 to 10 atmospheres. 9. A process as claimed in claim 8, wherein the 20 pressure is 1 atmosphere. 10. A process as claimed in any one of claims 1 to 9, wherein approximately equimolar amounts of the acrylic acid ester of the general formula XI and of the hydrazine derivative of the general formula III are used. 25 11. A process as claimed in any one of claims 1 to 10, wherein the oxidation of the 3-acylhydrazino-propionie acid ester of the general formula TV is carried out with - 28 a conventional oxidizing agent at a temperature within the range of from -20°C to 100°C. 12. A process as claimed in claim 11, wherein the temperature is within the range of from -5°C to 50°C. 5 13. A process as claimed in any one of claims 1 to 12, wherein the 3-acylhydrazino-propionie acid ester of the general formula IV is not isolated from the reaction mixture in which it is formed, and the formation of this ester and the oxidation thereof is a continuous process,, 10 14. A process as claimed in any one of claims 1 to 13, wherein a resulting compound of the general formula I is rearranged to form a compound of the general formula V and/or a compound of the general formula VI by treatment with a catalyst. 15 15. A process as claimed in claim 14, wherein the catalyst is an acid or a lewis acid. 16. A process as claimed in claim 14, wherein the catalyst is a base, 17. A process as claimed in any one of claims 14 to 16, 20 wherein the rearrangement is carried out in a solvent. · 18. A process as claimed in any one of claims 14 to 17, wherein the rearrangement is carried out at a temperature within the range of from -20°C to 50°C to form a compound of the general formula V and a compound of the general 25 formula VI. 19. A process as claimed in claim 18, wherein the temperature is within the range of from 0°C to 30°C. - 29 20. A process as claimed in claim 1, conducted substantially as described herein. 21. A process as claimed in claim 1, conducted substantially as described in any one of Examples 1 to 5 5 herein. 22. A process as claimed in any one of claims 1 to 13, 20 and 21, wherein a resulting compound of the general formula I is reacted with thionyl chloride of the fbrmula SOC1 2 to form a l,2,3-thiadiazole-5-carboxylic acid deriva10 tive of the general formula VII JT-c - H II I (vii) , N C - COOR. in which R^ represents a C^-Cg-alkyl group. 23. A process as claimed in claim 22, wherein the reaction is carried out at a temperature within the range 15 of from -20°C to 100°C. 24. A process as claimed in claim 23, wherein the temperature is within the range of from -5°C to 50°C. 25» A process as claimed in any one of claims 22 to 24, wherein the molar ratio of the compound of the general 20 formula I to the thionyl chloride used for the reaction is 1 : 326. A process as claimed in claim 22, conducted substantially as described herein. S1456 ~ 30 27. A process as claimed in claim 22, conducted substantially as described in Example 6 herein. 28. A process as claimed in any one of claims 1 to 21, wherein a resulting compound of the general formula V 5 and/or a resulting compound of the general formula VI is/are reacted with thionyl chloride of the formula SOC1 2 to form a 1,2,3-thiadiazole-5-carboxylic acid derivative of the general formula VII H-0 - H (VII), / 0 - COORj^ lo in which represents a C^-Cg-alkyl group. 29. A 3-acylazo-propionic acid ester of the general formula I given in claim 1, in which B^ and Eg bave the meanings given in claim 1, whenever made by the process claimed in any one of claims 1 to 13, 20 and 21. 15 30. A compound of the general formula V given in claim

5. 33. A compound substantially as hereinbefore described with reference to the examples.