CS224619B2 - Method for producing ester of 3-acylazopropionic acid - Google Patents

Abstract

3-Acylazo-propionic acid esters of the general formula I <IMAGE> 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 <IMAGE> and oxidizing this ester in an inert solvent with an oxidizing agent.

Description

SUMMARY OF THE INVENTION The present invention relates to a novel process for the preparation of 3-acylaza-propionic acid esters and their isomers of acylhydrezones of the locoic acid ester. These compositions are important starting compounds for the preparation of 1,2,3-hiediazole-55-carboxylic acid derivatives from which valuable weed and pest control agents can be prepared, as well as important drugs.

Production of semicarbazone of formyl acetic acid ethyl ester (W. Wislicenus, HW Byureters, Liebigs Ann. Chem. 356, 50 (1907) and ethoxycarbonylhydrazone of formyl acetic acid ethyl ester (R. Reap. RG Micetich, Can. J. of Chem. 46, 1057 (1968)) The preparation of these compounds is based on the reaction of the sodium salt of formylacetic acid with the corresponding hydrazine derivatives, which implies the synthesis and isolation of the sodium salt of formylacetic acid, but this salt is obtained by complicated and time consuming procedures and, moreover, only with unsatisfactory yields. (German patent fi · 708 513; British patent · No · 568 512) ·

SUMMARY OF THE INVENTION It was an object of the present invention to provide a process for the simple production of the Z- _Q- esters of lysvapropionic acid and their isomers with higher yields. The object of the present invention is to provide a process for the preparation of 3-acylazopogopionic acid esters of the general formula I ch ₂ -ch ₂ -cooch _{3 (} e.g.

N = N-CO-R in which

R denotes an ethoxy radical or an amine (a group consisting in reacting a methyl-1-ether of acrylic acid of the formula).

C ₃ -C-COOCH ₃ (II) ^{H / Z} with a hydrazino derivative of formula III

H ₂ N-NH-CO-R (III) wherein

R is as defined above, using. solvent inert to the reactants in the presence of catalysts (basic or acidic); this gives the 3-acylhydrezinoproptonic acid ester of formula IV

CH2-CH2-COOCH3

I 2 2 3

AND

NH ₂ -NH-CO-R (IV) wherein

R has the same meaning as above.

This compound is then oxidized in an inert solvent by the action of oxidizing agents to the desired products of formula (I) above.

Thus, the process of the invention employs readily available starting compounds and allows for the technically simple and safe production of the desired compounds. products at high yields.

The process is preferably carried out such that 'the acrylic ester of the formula ^{11 P} Oneco ^hook reacted with hydrazine derivatives ^and the formula ^P s teptetách ^{111 d} of -20 to 159 ° C, preferably about 0 ^{d d} of 50 ° C and 'pressure of ^{d 0.1 d 1.0} MPE ^h o ^d above them at about ¹ bar, the ^{price P s} onechaj react akvimooární mnotesví acrylic ester of formula II and hydrazine derivative of formula III;

oxidation ester 3-acylhydrθzintprtpiontvé formula IV is carried out by the action of the action of a reagent oxteačníto ^p tepteté s ^ o ^d - ²⁰ to ¹⁰⁰ ° C above ^h o n ^{d of d} of -5 to 5 ⁰ C, the přieemž pouužje ester kyseeiny 3 -ecylay ^d razintprtpiontvé formula IV, which is isolated from the reaction and may be směěl pouužt continuous process.

The process according to the invention is carried out in a technically simple and elegant manner. According to the invention, the synthesis of the 3-acylaydrazine pentionic acid ester of the formula IV is carried out by using acrylic esters of the formula II which are reacted with approximately equimolar amounts of the hydrazine derivative of the formula III in an aqueous medium or in an organic solvent inert to the reactants. but optionally also without the use of any solvent. To a solution of the hydrazine component in water or a C 1 -C 4 alcohol, an acrylic ester is suitably added in portions, optionally diluted with a solvent such as a C 1 -C 4 alcohol.

The ratio of alcohol to water may vary within wide limits; alcohol or water alone may also be used. Preferably, the alcohol / water ratio is 1: 1. The reactants may also be added in reverse order.

Re action ^and di- ^p rov at teptete ^ o ^d - ^{d of 20} to 15 ⁰ C above ^h o n ^e o ^{d d 0 d 0} to 5 ° C. The pressure ^k is from 0.1 to 1 MPe, but preferably 0.1 MPe.

Examples of solvents which are inert to the reactants are alcohols and from 1 to 4 carbon atoms, such as methanol, ethanol, propanol, isopropanol, butanol, sec-butanol, tert-butanol, halogenated hydrocarbons, such as methylene chloride, chloroform and carbon tetrachloride, aliphatic. and aromatic hydrocarbons such as petroleum ether, pentane, cyclohexane, benzene, toluene and xylene, ethers such as diethyl ether, tetrahidrofuran, dioxane, and ethylene glycol diethyl ether, carboxylic acid citriles such as acetonitrile and carboxylic acid amides such as dimethylformamide. The reaction may conveniently be carried out by basic or acid catalysis. The basic catalysts used are, in particular, alkali metal hydroxides, alkali metal alcoholates, tertiary amines such as .alpha., .Alpha., .Delta. iodide, such as benzyltrimetluammonium hydroxide and dialkyl carboxylic acid amides such as dimethylformamide and dimethylecetemide. Sulfuric acid, phosphoric acid, acetic acid, lactic acid and bootifloride can be used as acidic catalysts.

After completion of the reaction, the reaction mixture is optionally worked up in a known manner. After separation of the solvent, the residue is either distilled under reduced pressure or is retarystallized from a suitable solvent such as ketones, alcohols, citriles, esters, ethers and chlorinated hydrocarbons such as acetone, methanol, ethanol, acetic acid, acetic acid ester, dlisopropyl. and chloroform. The reaction products are obtained in the form of colorless crystals or in the form of colorless capsules which are stable at ambient temperatures.

In case you choose! It is appreciated that the reaction product of the formula (IV) must be isolated and can be further processed directly.

The 3-acylazopropionic ester of formula (I) is subsequently prepared by the process according to the invention by reacting the 3-acyltagazinopropionic acid ester of formula (IV) with rapid oxidizing agents in an aqueous medium in the presence of organic solvents inert to the reactants. in excess.

Preferably, the oxidizing agent is added in portions to the solution of the 3-ethylthrayrayin dipropionic acid ester in water or diluted with the solvent in the form of an aqueous solution of the oxidizing agent or also diluted with the solvent. Addition-action components can be performed rovcě ^Z in ^{p p} a governor oi ^R and ^<dd · This reaction hundred ^ n ^P ro ^B i s ^H and ^p ^ a ^ a rotation ^d -20 ^d o! 00 ° C, preferably about ^d - 5 · to 5 ° C. Time ^to rea tion depends on the reaction and it ^ ^ OTE tybuje in the range of 0.5 to 5 ^d him (DIC.

Examples of solvents which are inert to the active ingredients are: aliphatic and aromatic hydrocarbons such as cyclohexane, heptac, ligroic, benzene, toluene and xylene and halogenated hydrocarbons such as hexafluoride, chloroform, tetrachloroethane, and 1,2 -dihhlfrettac.

In the presence of these solvents, it is also possible to process the crude solutions, since these solvents remain inert in subsequent steps.

Examples of quick oxidizing agents that may be used are nitric acid, potassium chromate, potassium malate, potassium chloride, mercuric chloride, ammonium nitrate and sodium nitrate, sodium chloride, chlorine, alkali metal hypochlorite and metals. soil, hydrogen peroxide, iron chloride, nitrous oxide and lead oxide.

After completion of the reaction, the reaction mixture is worked up in a manner known per se, for example by distilling off the solvent used under reduced or atmospheric pressure or by extraction, and the organic solvents used during the reaction can also be used as the 3-acetyl-pentopioic acid ester extraction agent. The extracts can be further worked up in a known manner, for example by distilling off the solvent used at atmospheric or low pressure and drying the product. In this way, the ester of 3-acllazopropylphionic acid is obtained in the form of pale yellow colored crystals or oil in. of excellent purity and very high yield. The product can be used in a longer process without further purification. The oxidation of the 3-acylhydrezinopropionic acid ester of the formula IV results in the formation of an ester. primary compounds of structural formula I as shown by comparison of nuclear resonance spectra.

These compounds have a tendency in solution to switch to the acylhydrazones of the formyl acetic acid ester of formula V

CH-CH-COOR,

I <»>

N-NH-CO-Rg which therefore contaminates the compounds of formula I.

The preparation of the compound of formula (V), i.e. the formyl formic acid ester hydrazones, is therefore also part of the invention.

AND

Compounds of formula (V), on the other hand, are in isomeric equilibrium with compounds of formula (VI)

CH = CH-COOR.

[ ¹ ]

NH-NH-CO-R ₂ which production also belong to the invention.

If desired, the irreversible reaction of the compounds of formula I can be carried out to the isomeric forms of structural formulas V and VI, which further form a further aspect of the invention.

For this purpose, according to the invention, the 3-acylazopropionic acid ester of the formula I is reacted with the catalysts, optionally using an inert solvent. In the formulas, R 1 and R 8 are as defined above.

Mooifikací one of the processing of the process is that the ester a-al-OZO-ojonové Take the formula ^{I d} e at a ^d -20 ^d about 50 ° C, preferably at a temperature from 0-30 ° C, in the acylhyrazone of the phymylacetic acid ester of formula V and the erihadrizine of formula VI.

This reaction can be catalyzed by an acid, in particular a Lewis acid or a base. For example, hydrochloric acid, sulfuric acid and nitric acid, HgClg, (NH4) gSO4, NH4Br, (CH3SiOSOgCFp SnCl3, BF3, p-toluenesulfonic acid hydrate) can be used in the form of an acidic load. , acetic acid and triphenoic acid.

As basic catalysts there is! for example: oxides, hydroxides, alcoholates, alkali earth and alkali metal carbonates, ammonia, tertiary amines such as tertiaryl amine and Ν, Ν-meth-methilane and pyridine bases.

The isomerization reaction is expediently carried out in an aqueous medium and / or in organic solvents.

As inert solvents there may be mentioned: halogenated hydrocarbons such as methyleneiloride, chloroform, 1, Ζ-ϋϋΙΙΓΓΊ π and tetrachloroethane, aliphatic and aromatic hydrocarbons such as petroleum ether, pentane, heptane, cyclohexene, benzene, toluene xylene and chlorobenzene; ethers such as dithyl ether, tetrahydrofuran, dioxane and diisopropyl ether; and alcohols such as methanol and ethanol.

Reafoe robíh ^{p s p} s ^p te ture area, generally ^{p d} s of a temperature between approximately - ²⁰ to ⁵⁰ ° C, preferably at a temperature from 0-30 ° C.

In practice, the crude solution of the 3-acylazopropionic ester is reacted with a corresponding catalyst, followed by generally solid reaction products being collected by filtration, and the product in the form of colorless crystals is obtained by freeze-drying or solvent removal. The crystals obtained are readily crystallized from suitable organic solvents such as ketones, alcohols, litriles, esters, ethers and chlorinated hydrocarbons such as acetone, methanol, ethanol, acetic acid ester, diisopropylspher and chloroform, and are stable at ske These compounds are generally obtained in such high yields that they can be allowed to react further without crystallization.

The products produced by the process according to the invention are important starting compounds for the preparation of 1,2,3-thradizole-5-ear-carboxylic acid derivatives, from which valuable weed and pest control agents can be prepared, as well as important pharmaceuticals.

Preparation of 1,2,3-thradrazole-5-earboyl-acid derivatives of the general formula

N — C-H '

^N -COORi ^S (VID can be carried out, for example, in a known manner by reacting the products of formula V with thionylchloride (R, which is as defined above) ·

Finally, the process according to the invention offers a new advantageous process for the preparation of compounds of the formula VI by reacting the primary compounds of the formula I directly with the hexischloride of the formula SOClg to the desired products of the formula VI, thereby saving one production step. ·

Synthesis of 1,2,3-ester-5-thradrθzol earboxyloué formula VI takes place in the starting compounds in pooužtí forum ester 3-acylazopropionic formula I by reaction with thionyl / lchloridem · ^{R p} is ESPONDING rovádí 's pulse ^{P L rt} c ^h in the range of about ^{d-20 d} Ю0 ° C, preferably from 5 to 50 ° C.

The reaction time is determined in dependence on the reaction temperature! and is from 1 to 20 hours ·

In the synthesis of 1,2,3-α-γ-esters, the reactants can be reacted in approximately equimolar amounts. In addition, however, lhisnyl chloride can be used in large excess and then serves as a false solvent.

Conveniently, however, the 31-cylazopropionic acid ester and the 1-hexylchride will react in a 1: 3 molar ratio.

The reaction may also be carried out in a manner that is inert to the reaction. Suitable solvents include: halogenated hydrocarbons such as methaylene chloride, chloroform and trichlorothorane, aliphatic and aromatic hydrocarbons such as kerosene ,, pentane, cyclohexane, benzene, toluene, and xylene, ethers such as г г г г, trtrahydrsfurrine, dioxane, rtlylrig.ykeSdirtlylrthrг and dirlhylrnglykoldirthylelhrr and esters such as acetic acid ester ·

Generally, the 31acylazopropionic acid ester, optionally also dissolved or suspended in a suitable solvent, is added in portions to thisnyl chloride, optionally diluted with an organic solvent, whereby the order of addition of the reactants can be folded.

Hydrogen chloride produced during the reaction can be continuously removed with a stream of inert gas, possibly under vacuum.

After completion of the reaction, the reaction mixture is worked up in a manner known per se. After removal of the solvent and the excess of the bis-chlorides, the residue can be subjected to fractional distillation; it is also possible to eliminate excess thionyl chloride with a saturated solution of soda, sodium or potassium bicarbonate solution, sodium acetate solution or sodium or potassium hydroxide solution. or directly with water and the solution to be distilled with steam or subjected to extraction, whereby the solvent used can simultaneously serve as the extraction agent during the reaction. The extracts are then treated in a known manner: for example, the residue after drying and distillation of the solvent is subjected to traction filtration under reduced pressure or simply digested using a suitable solvent such as an aliphatic hydrocarbon such as pentane, hexane, cyclohexane or petroleum ether. The 1,2,3-theadeezo-aarboxylic acid ester is obtained in a highly pure form and in a very high yield, so that it can be used in the preparation of the desired end products without further purification.

The following examples serve to illustrate the production method of the invention.

EXAMPLE 1 al Production of 3-tetricrazinopropionic acid

In a 2-L round bottom flask equipped with three tube outlets with stirrer, an epioon and a reflux condenser with a drying tube, 173.0 g (1.5 mol) of powdered solids were suspended in 300 ml of methanol. To this mixture was added dropwise a freshly formed solution of 34.4 g (1.5 moo) of sodium in 500 ml of methanol in the form of meetylsulfonate over 10 minutes. Tyle temperature maintained ^from OV ^and Na in the range of from ¹ 5 to 2 ° C. The reaction mixture was further doiníchávána ^p s ²⁰ ° C for ¹ to ^b 5 minutes to ^ Z tulle evacuated chl.ori sodium ^d. The filtrate tulle was placed in a 2 liter round bottom flask equipped with three outlets and stirred at 20 ° C for one hour with 90 µl. (1.0 mol) acrylic ester. The reaction mixture was allowed to stand at room temperature for 3 days, then refilled again and the filtrate evaporated in vacuo at 40 ° C. 205 g of a yellow oily product were obtained, which was mixed with 1 H-acetic acid ester at ambient temperature for one hour. НеекдпТ mixture Tyl differentiate ^ ^ Ovasi from insoluble ^P U ^S T ^E Joint ^p from ^d and ^f lu ^t .ltrá evaporated at ⁴⁰ ° C in ⁵⁰⁰ ml otyemu. ^R is ozelením zístely Wl ^é crystals Falling edges in vacuo at ambient temperature and dried to constant weight.

Yield: 134.4 g = 83.4% of theory. M.P .: 67 ^and a 69 ° C.

(b) Production of 3-kerramoylapropionic acid ethyl ester

V 1 · lirovvé flask equipped with a three-terminal tepooměrem míchací.em occiput and dissolved 16.1 g (01 mol) of 3-mettylčttčгu sčoi-trrtzi ^d opropinové in 100 ml of water under ice-cooling treated with 24 (6.0 g (0.3 mol) of freshly added 10% sodium hypochlorite solution for 20 minutes, while maintaining the internal temperature at 5 to 7 ° C. The yellow tulle soaked solution obtained after stirring for 10 minutes in an ice bath is allowed to react with 85 g. g 'sodium chloride and extracted five times with peHivě always 4CC ml of chloroform. the extract, dried TORE tent-butyl atým evaporated Pi · ^P 4C ° C in va ^ uu. Zístol ^from Lu ^{characterized} crystalline product.

Yield: 12.9 g = 81.1% of theory. M.P .: ^{8 5-8} ° C for 7 nzUadu.

b2) Manufacture of 3 meetylesteru - trrčool ^r Уtzopripionové

In a 1 liter flask, equipped with three pins with a stirrer and a thermometer, 16.1 g (0.1 mol) of 3-sicocarrazidopropionate meetyl ester were dissolved in a mixture of 150 ml of water and 10.3 g of approximately 95% sulfuric acid. Under ice cooling, tulle over 10 minutes at 7-10 ° C is dropped rlzio- 9.79 g (0.0333 mod ^D vtjchtooιanu potassium in 70 ml of water and 13.8 g of about 95% sulfuric acid, the reaction mixture left a further 10 Tyl After 20 minutes of reaction, 20.0 g of solid potassium hydrogen sulphite were added and the yellow crystals were revealed.

Ί

The reaction solution was extracted five times intensively with 300 ml of chloroform each. The chloroform extract, dried over magnesium sulfate, was evaporated in vacuo at 40 ° C. Yellow crystals were obtained.

Yield: 9.0 g = 56.5% of theory. M.P .: 85 EŽ 87 ° C for extended Ia ^{to d} u.

c) Production of 3-semi meehhlestet ^to arbazoric propionic acid.

^In a round bottom flask and ^p 2 ⁵⁰ t commonly applicable measures Remi tubular development ^dy with a thermometer and stirrer, 15.9 g (0 1 mole _t) meehhlesteru 3- ^to arbamoylazornrinové in 100 mL of chloroform and treated with 0 5 mL of triethylamine was přččemž internal cooling žovÉina u ^ ^p s ³⁰ ° C. Reaction mixture YLA ^b n ^a consequential ječlnu ^of still another hour MIC ^ha to ^p i ^r i warm-up your eye И ^ ^é kana krystaHck slurry scalding ^p s 4 ⁰ C in a vacuum of Suc ^d and ^h.

The residue was digested with 150 ml of diisodate under vacuum to a constant moisture content and dried.

Yield: 14.5 g = 91.1 theory.

Mp: 159 ° ^C with decomposition.

Example 2

e) Preparation of 3-ethoxycarbonylhydrezinoproronic acid methyl ester

In a 3 liter 1 L flask equipped with a stirrer, a thermometer, and a reflux condenser, 114.4 g (1.1 mol) of ethyl ester were dissolved in 600 mL of ethanol and dissolved. one hour reacted with 90 ml (0.1 mol) of acrylic acid, ^p s 2 ° C. The reaction mixture was ^p onechela people in ^the four days ^of the en closed NACE ^{Ž é} ^ REA is the mixture ^{(to mites)} odjpHl vacuum JTI-4 ⁰ ° C. ZIS ^to an ^N paMna ^b YLA ^d estilována in va ^to uu.

Yield: 111.1 g = 58.4% of theory.

Mp. 110-111 ° C ^{/ 13} 33 mmHg.

(b) Production of 3-tert-oxycyclopropyl-azoresorionic acid methyl ester

In a 250 mL 3-mL flask with stirrer and thermometer, 9.5 g (0.08 molar) of 3-tert-oxycarbonyl-trisulphuric acid were dissolved in 50 mL of water and allowed to react for about 20 minutes. 82 g (0.1 mol) of freshly prepared solution of ^10% sodium hypochlorite and ^{BOD from b t} em YLA VNI-tR-maintained between ^5-7 ° C. Odddlil a yellow oil. the product was admixed for 10 minutes in an ice bath, extracted three times with 75 ml of chloroform. After drying propagation sulfate and concentrating in vacuo cУllroloгπlové phase ^p M 4 ^{0 C for} ZIS al bile · ^ 'vis ^the Ozni oil ..

Yield: 8.7 g = 92.4% of theory.

_п Е ° ^{2: 1,} the 4424th

(c) Production of 3-ethoxycarbonyl-hydrazoilorrrine meethyl ester ^; l ^on l ^v é

18.8 g (0.1 mOD ιmeУylθsttru 3-ttУlxykarblnyltzorrlrionlvé were dissolved in a flask provided with three tubular terminals, and tepooměrem stirrer in 100 ml of chloroform and reacted at ³⁰ ° C. ^0.5 ml ^ amine ^rřčt em ^f it was necessary to re-it overlooks direction ^of St. result exothermLcké reaction chladdt. Subsequently, the reaction mixture domíciiána for one ^hour Odin ^'p s • ^ Io · ¹ okoO-I realcční Trituration n ^ JLedn ¹ about ^d hothous ^p s' ⁴⁰ ° C VA in ^the uu. the residual oil «d ^ erovel 50 ml of dimethyl -00 ^ - ^ THERM a. obtained crystals were sucked off and dried.

Yield: 17.9 g = 95.2% of theory.

Mp: 60-61 ° C.

Example 3

Production of 3-semicarbazonopropionic acid methyl ester (continuous)

In a 1 liter flask equipped with three tube outlets, a thermometer and a stirrer, 16.1 g (0.1 mol) of 3-semicarbazidopropionic acid methyl ester was dissolved in 100 ml of water and allowed to react for 20 minutes by stirring and ice-baking. 141.6 g (0.2 mol) of about 10% freshly prepared sodium hypochlorite solution, maintaining the temperature at 5 to 7 ° C. The salted reaction solution was allowed to soak in an ice bath for 20 minutes, allowed to react with 66 g of sodium chloride and finally carefully extracted five times with 400 ml of chloroform each. The chloroform phase, dried over magnesium sulfate, was evaporated in vacuo at 40 ° C to 100 mL. The chloroform solution evaporated to 100 ml was treated with 0.5 ml of triethylamine while maintaining the internal temperature at 30 ° C by cooling. After stirring at ambient temperature for 1 hour, the obtained crystal slurry was evaporated to dryness at 40 ° C under vacuum. The residue was digested with diisopropyl ether, aspirated and dried to constant weight in vacuo.

Yield: 12.0 g = 75.5% of theory.

T. t .; 158.5-159.5 ° C with decomposition.

Example 4

Production of 3-ethoxycarbonylhydrazonopropionic acid methyl ester (continuous)

In a 500 ml flask equipped with three tube outlets with stirrer and thermometer, 19.0 g (0.1 mol) of 3-ethoxycarbonylhydrazinopropionic acid methyl ester was dissolved in 100 ml of water and allowed to react with 141.6 g (0) over 20 minutes. (2 mol) about 10% sodium hypochlorite solution, maintaining the internal temperature in the range of 5 to 7 ° C. A yellow oil precipitated. The reaction mixture was stirred for 10 minutes, extracted three times with 150 ml of chloroform each, and the chloroform phase was concentrated after drying over magnesium sulfate to a volume of 100 ml.

The chloroform solution, concentrated to 100 ml, was treated with 0.5 ml of triethylamine. wherein the temperature did not exceed 30 ° C. After stirring for one hour at ambient temperature, the reaction mixture was evaporated in vacuo at 40 ° C; The oily residue was then digested with 50 ml of diisopropyl ether and the colorless crystals formed were aspirated and dried.

Yield: 12.9 g = 68.5% of theory.

Mp: 59-61 ° C.

Example 5

Production of 3-ethoxycarbonylhydrazonopropionic acid methyl ester

In a 500 mL three-mL flask equipped with a stirrer and thermometer, 19.0 g (0.1 mol) of 3-ethoxycarbonylhydrazinopropionic acid methyl ester was dissolved in 100 mL of water and allowed to react with 9.79 g for 15 minutes. (0.0333 mol) of potassium chromene in 70 ml of water and 17.2 g (0.167 mol) of 95% hydrochloric acid. The internal temperature was maintained at -2 to 0 ° C for 30 minutes. Subsequently, the reaction mixture was extracted twice with 40 ml of chloroform each. After drying over magnesium sulfate, the chloroform solution was evaporated in vacuo at 40 ° C. The oil obtained was digested with diisopropyl ether and the obtained crystals were aspirated.

Severography, n. P., MOST

Price 2,40 Kčs

Yield: 12.4 g = 65.9% of theory.

Mp: 57-61 ° C.

Example 6

Preparation of 1,2,3-thiadiazole-5-carboxylic acid methyl ester

In a round bottom flask with three tubular terminals equipped with stirrer, condenser and tepOmměrem with a turn at the outlet was 21.8 ml (0.3 mol) of thionyl chloride cooled to -10 ° C over ¹ 5 minutes Oneco ^{p h p} o yes amounts to react with ^{15.91 g (MO} J ^ ⁰ meUýlesteru 3-kirbimoolizo ^P ro ^P ion <s, while keeping the internal temperature between -5 and 0 ° C. ^p o ^p utončení of manufacture and ^{d k} u rea yellow tulle ^{the hook} protrudes DIM n ^d MIC other two hours, ^{p Rc CEM} Tyl vnítřrá te ^ ^p omal pivotally raised at 2 ° C. Náslečlně tulle ^extensible from a ^to e ^{of d} en ⁶⁰ ml chlorofomiu and quenched cautiously 60 ml of saturated hydrogeenuiičitanu solution of potassium přčeemž maintaining the internal temperature in the range of ¹⁰ to ^{20 e} C ^and phase ^C hloroformov Tyl separated, washed with 30 ml potassium poly ^d гogečnUliČitiш to neeurální reaction, dried over magnesium sulfate and evaporated in vacuum. 4 ⁰ C . Act of ^T ^ Toná apalina ^to the neck-shield driving after water in ^d ývěvou.

Yield: 11.6 g = 80.5% of theory.

Mp: 110-111 ° C / 1.86 kPa.

Claims (3)

¹ . A process for the preparation of 3-acylazopropionic esters of the formula I C 1 -C 6 -COOC 4 (I) N = N-CO-R in which it is an ethoxy radical or an amino group, characterized in that it is reacted with an acrylic acid of formula II C = C-COOCH ₃ (II) with a hydrezine derivative of formula III HgN-NH-CO-R (III) as defined above, (IV) using an inert solvent and in the presence of a basic or acidic catalyst to form the 3-acylhydrazinopropionic acid ester of formula IV CH _o -CH _o -G00Cbk I ³ NH-NH-CO-R wherein R is as defined above, and this compound is oxidized in an inert solvent by treating the desired products of formula I with an oxidizing agent. 2. Process according to claim 1, characterized in that the reaction of the methyl ester of the acrylic acid of the formula II with the β-hydrazine derivative of the general formula III is carried out at temperatures from -20 to 150 ° C, preferably from 0 to 50 ° C. to 1.0 MPa, preferably at 0.1 MPa, under basic or acid catalysis, using equimolar amounts of methyl ester of acrylic acid of formula IX and a hydrazine derivative of formula III. Process according to Claim 1, characterized in that the oxidation of the 3-acylhydrazinopripionic acid ester of the formula IV is carried out at temperatures from -20 to 100 ° C, preferably from -5 to 50 ° C. Severography, n. P., MOST