LU83517A1 - METHOD FOR PRODUCING 3-ACYLAZO-PORPIONIC ACID ESTERS - Google Patents

Description

* *

SCHERING AG

6s - # <3 & !! Ehr RacMtsÄufc P 2214.00

Berlin, l4.o5 «198l»:

METHOD FOR PRODUCING 3-ACYLAZO-I PROPIONIC ACID ESTERS

i + The invention relates to a new process for the preparation of 3-acylazo-propionic acid esters and their isomeric formyl-acetic acid ester acylhydrazones.

Process for the preparation of formyl acetic acid ethyl semicarbazone (V. Wislicenus, H.W. Bywaters, Liebigs Ann.Chem.

! 356, 50 (I9O7) and ethyl formylacetate-ethoxycarbonylhydrazone (R. Raap, R.G. Micetich, Can.J. of Chem. 46, 1057 (1968)) are already known. These compounds are prepared by reacting the sodium salt of the formyl acetic acid ester with the corresponding hydrazine derivatives, which requires the synthesis and isolation of the formyl acetic acid ester, sodium salt. The latter can only be done in! complicated and lengthy work processes can be produced in an unsatisfactory yield f * (DE-PS 708513; GB-PS 568 512).

i f The object of the present invention is therefore to provide a process which is a technically simple preparation of 3-acylazo-propionic acid esters and their isomers in -2- £ board: Br. Herbert Asross. Dr. CtvrgtiEr. S-ilftr · H £ iï-JSrî: er. h * r.ann Fa? * n * 3n «f :: $ SKSR; i43 AS -; - '3E Bviir tS · 65iE ·' 1 Dr.rreic Hennse · Kar: Cttr =. * !; · D :. 5>; rs. ift.re? s * »sr.e» -Ko-sts. Se-iT-y-sr v; T {-. R Banfeia-aa! - · * · .κ «

_2. SCHERING AG

G ** e * 5îhsr RschisÎchuti ’ί! I allowed great yield.

iS This object is achieved according to the invention by a method for; Preparation of 3-acylazo-propionic acid estera of general **

Formula i; · -

Π CH - CH - COOR

| · | 2. ώ- «L

i - i

K = N - CO - R2 I

! : dissolved, in which R ^ is a C ^ -Cg alkylene radical and R0 is an alkoxy radical, preferably a C ^ -C ^ alkoxy radical, or an amino group and is characterized in that m ^ n acrylic acid ester - of the general formula

= C - COOR_ II

h / 1; With. Hydrazine derivatives of the general formula i i- I H0N - NH - CO - R0 III, * optionally using an inert solvent and / or in the presence of catalysts, to give 3-acyl-I hvdrazino-nronionic acid esters of the general formula! \ '’*

! I.

1 CHn - CK0 - COOR1

NH - NH - CO - R IV

\ πηπ sets this · connection. in an inert solvent-- | - X v'Q.’tti.nc: D; .Herüert Axmtt · Dr.S ^ üïip * KtiRMtp. F-cf: SCiKER · »** Ξ-Ε" SS '* J' '· T D. \ tets se Kar Otts. Ii £ fîîe.rrsn & ^? ^ Ic · Dr. W zzt Sff ~: .w »er *. V.?i-\2* Ei.'n-rs-is & B iGC'iX · 'YiÄfa «

SCHERING AG

Often legal protection is oxidized to the desired process products by the action of oxidizing agents, where R_ and R_ have the meaning given above.

Examples of alkyl radicals are methyl, ethyl, *

Propyl, isopropyl, n-butyl, sec.-butyl, n-pentyl, n-hexyl, and others.

Examples of alkoxy radicals are methoxy, ethoxy, propoxy, butoxy and others.

The process according to the invention therefore uses easily accessible starting materials and enables the desired process products to be prepared in high yields in a technically simple and harmless manner.

Particular embodiments of the process according to the invention consist in the reaction of the acrylic acid esters of the formula II with the hydrazine derivatives of the formula III at temperatures from -20 ° C. to 150 ° C., preferably from 0 ° C. to 50 ° C. and under a pressure from 1 to 10 atmospheres, preferably at 1 atmosphere, optionally in a base- or acid-catalyzed reaction, and in that equimolar amounts of the acrylic acid esters of the formula II and the hydrazine derivatives of the formula III are used, that the oxidation of the 3-acylhydrazino-propionic acid esters of -4 - 8 V “4 Vo-ftani: Dr Ke-aeri Asai» · Dr Cftriti * ·. Bft;. · «. - Sîiüs-Jârrer. rtrr.aar? ns-jLtrsrri * · * 3 · D-'ΚΓ i-sriir. e. rz-fri.er £ i asy.

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-4- SCHERING AO

Gsxcïîsîisbar general formula IV with oxidizing agents at temperatures from -20 ° C to 100 ° C, preferably from -5 ° C to 50 ° C, 1st

i takes place and that a 3-acylhydrazino-propionic acid ester of the formula IV is used, which is not * isolated from the reaction mixture and can be used in a continuous procedure.

i

The method according to the invention is carried out in a technically simple and elegant manner.

The synthesis of the 3-acylhydrazino-propionic acid esters of the formula IV is carried out according to the invention starting from acrylic acid esters of the formula II by reaction with approximately equimolar amounts of hydrazine derivatives of the formula III in an aqueous medium, in inert organic solvents, preferably in an aqueous or alcoholic medium, but if appropriate even without using any solvents. Purpose! In some cases, the acrylic acid ester is added in portions or with a solvent such as a C ^ -C ^ -

Alcohol diluted to the solution of the hydrazine component diluted with water or a C 1 -C 4 -alcohol I 'b. Here, the mixture ratio alcohol / water within wide limits! vary by using both alcohol alone and water alone m tx er.

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Can find use. The alcohol / water weight ratio can preferably be 1: 1. The reactants can also be added in the reverse order.

“The reaction takes place at temperatures from -20 ° C to 150 ° C, preferably from 0 ° C to 50 ° C. The pressure can be from 1 to 10 atmospheres, but preferably 1 atmosphere.

Examples of solvents which are inert to the reactants are C 1 -C 4 -alcohols, 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, tetrahydrofuran, dioxane and Äthylenglvcol-dietäthvläther, carbonsitriles such as acetonitrile and carboxamides such as dimethylformamide.

The reaction can advantageously be base-catalyzed or * acid-catalyzed. Alkaline hydroxides, alkali metal alcoholates, tertiary amines such as triethylamine and Κ, Ν-diraethylaniline, benzyltrialkylammonium hydroxides such as, for example, benzyltrimethylamroonium hydroxide and dialkylcarboxamides such as dimethylformamide and dimethyl-6- | serve as basic catalysts “Vo-Eteadh D :. Htrtert Asm »· Pr. & ~ .RtsS * r. Smüiv · Hsas-är ^ er hftmcnn Parins ** «- AS · Γ-T * Se-rr e PçfieS 'S5» r

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• s- SC! iCRING AG

G. sv.oifeBfSor Ss «& iis4wt * acetamid. For acidic catalysis, sulfuric acid, phosphoric acid, acetic acid, lactic acid and boron trifloride are used.

; ii

After the reaction has taken place, the reaction mixture is optionally worked up in a manner known per se. After removing the solvent, the residue is either fractionally distilled under reduced pressure or from suitable solvents such as ketones, alcohols, nitriles, esters, ethers and chlorinated hydrocarbons, such as acetone,

Recrystallized methanol, ethanol, acetonitrile, ethyl acetate, diisopropyl ether, and chloroform. The reaction products are obtained in the form of colorless crystals or as colorless liquids which are stable at room temperature.

However, if a continuous procedure is chosen, the reaction product of the general formula IV need not be isolated, but can be processed directly.

The 3-acylazo-propionic acid esters of the general formula I are then prepared according to the invention by reacting the 3-acylhydrazino-pronionic acid esters of the formula IV with common oxidizing agents in aqueous medium, in organic solvents which are inert to the reactants, the oxidizing agents being used in stoichiometric amounts Amounts as well as used in excess.

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_7_ SCHERING AG

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fZwecJunecessarily - the oxidizing agent is added in portions as an aqueous solution or diluted with a solvent to the diluted with water or a solvent [solution of the 3-acylhydrazinopropionic acid ester. The ! The reactants can also be added in the reverse order. This reaction step takes place at temperatures from −20 ° C. to 100 ° C., preferably from −p C to PO ° C. Depending on the reaction temperature, the reaction time can be between 0.5 hours and 5 hours.

The following may be mentioned as solvents which are inert to the reactants: aliphatic and aromatic hydrocarbons such as cyclohexane, heptane, ligroin, benzene, chlorobenzene,

Toluene and xylene and halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride and 1,2-dichloroethane.

| The presence of these solvents can also be used with the raw solutions, as they are inert in the subsequent steps.

i Examples of common oxidizing agents which accordingly determine the choice of i solvent are:

Nitric acid, potassium dichromate, potassium permanganate, quenk silver oxide, ammonium and sodium nitrate, sodium chlorate, Ü

Chlorj · Alkali and Ercalcali hypochlorites, smmoniakali- Γι '_ w C * · »1 1 3 Vc- ^ tsac: Dr.HerS» t · D'. E-Yr - KïW-v'S'pe ^ · ^ ». Τικιγ PcnrosrirS * :: èSrÆSfNû Αβ g» rilr ® ¢ 0311

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SCHhRïNG AG

öi <r-blahaher R: ’iii-chutx i cal hydrogen peroxide, iron (III) chloride, Distick-: i; ! Trioxide and lead (IV) oxide ·! ; i;

After the reaction, the reaction mixture is worked up in a manner known per se, for example by; i

Distillation of the solvent used under reduced or normal pressure or by extraction, whereby the organic solvents used in the course of the reaction can also serve as extracting agents for the 3-acylazo-propionic acid esters Distill off the solvent used at normal or reduced pressure. In this way, 3 ~ «-cyiazo-propionic acid esters are obtained in the form of pale yellow-colored crystals or oils in excellent purity and in very high yields, so that can be transferred without further cleaning. - - i

When the 3 "A.cvlhvdrazino-t5ronionic acid esters of the formula IV are oxidized, as is evident from studies of the keraresonance spectra, primarily compounds of the structural | formula I.

In solution, these compounds tend to i. "-9- I __ £ V« * tw «Jr Dr.Herbwt Aamit · Dr. Christi» Brum »· h» »s-J2 -? * R Sttisanr. Powssshrjfc; SCrr == ï; t <S AG-IM3XE * riin6ä-? ösKasr »G311 è Dv Η £ 1Γ, Γ! ** 'Γ ** Γ' ΟΒβ« itw.-Rsn »si * is Dr. Hsrt: W: = *. Pars y.sar-Hs! its Se - ::: '- * s «? 17MCK Be» kt *! »H'« ttiKli SV «si8sncsr Mt totgisKsrtts: Dr Sïjsra S ^ vctraraa ^ ar Esr: ir ts.T.SieisiniiAS E * r! .Rror "-L" :. ιοί 7936 X. Sinferafi "10P 4001 I *

-9- SGHB'ÏNG AG

GchfHbEÊûlsr feifeKlwtl j! Formylacetic acid ester acyl hydrazones of the general

Formula CK - CK - COOR.

il Il 2 1

I N - NH - CO - R2 V

·. To rearrange, which consequently represent isomers of the compounds i of formula I.

j The preparation of the compounds of the general formula V, that is to say the forroylacetic acid ester acylhydrazone, is therefore also an object of the present invention.

The compounds of the general formula V, on the other hand, are in an isomeric equilibrium with compounds of the general formula CH = CH - COOR.

i 1! | ri NH - NH - CO - R2 VI, i whose production is therefore also part of the subject of the present invention.

If desired, an irreversible rearrangement of the compounds of structural formula I into the isomeric form of

Structural formula V or VI are carried out purposefully, which is also the subject of the present invention.

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-io- SCHERING AG

According to the invention, for this purpose the 3-acylazc- \ -ronic acid esters of the general formula I with catalysts are optionally used using an inert | 0 treated with solvent, where R, and R0 have the ocige 3edeu $ - il 1 tion.

A particular embodiment of this process feature is that a 3-acylazo-propionic acid ester of the formula I at temperatures from -20 ° C to pO ° C, preferably at 0 ° C to 30 ° C, to the acyl hydrazone of the formyl acetic acid ester of the formula V and is rearranged to enhydrazine of formula VI.

This reaction can be catalyzed by acid or Lewis acid or catalyzed by base.

Examples of acid catalysts are: hydrochloric acid, sulfuric acid and nitric acid, HgCl ^, (NK ^) oS0 ^, NH ^ Cl, NH ^ Br, HgBr ^, (CH ^) ^ iOSOgCF, SnCl ^, BF ^ p-toluene- sulfonic acid hydrate, acetic acid and trifluoroacetic acid.

The following may be mentioned as basic catalysts: oxides, hydroxides, alcohol :: alcoholates, carbonates of the earth alkali and alkali metals, t i 'ammonia, tertiary amines such as triethvlaroin and N.N-Dimethvl- i. * * 7 I anilm and pyridine bases. The isomerization reaction expediently takes place in an aqueous medium and / or in organic solvents.

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_λ1_ fcOHLiiiNG AG

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Inert solvents called sexes: halogenated hydrocarbons, such as methylene chloride, chloroform,; 1,2-dichloroethane and carbon tetrachloride, aliphatic and aromatic hydrocarbons such as petroleum ether,

Pentane, heptane, cyclohexane, benzene, toluene, xylene and chlorobenzene, ethers such as diethyl ether, tetrahydrofuran,

Dioxane and diisopropyl ether and alcohols such as methanol and ethanol.

| j The reaction takes place at room temperatures from -20 C to! 50 ° Ct preferably at 0 ° C to 30 ° C.

In practice, the procedure is such that a suitable catalyst is added to the egg solution of the 3-acylazo-propionic acid ester and then the reaction products, which are generally solid, are isolated by filtration, by freezing out or by removal of the solvent in the form of colorless crystals. These can be made from suitable organic solvents such as ketones, alcohols, nitriles,

Esters, ethereal and chlorinated hydrocarbons such as I * for example acetone, methanol, ethanol, acetonitrile,

Easily recrystallize ethyl acetate, diisopropyl ether and chloroform and are stable at room temperature. In general, however, the compounds are obtained in such a high purity that they can be reacted further without recrystallization.

-12- 1 2 · 2

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_1Ξ_ SCHERING AG

“GswesbKöhsr Sie-drfisdiirtr E> The products manufactured according to the invention represent I important starting products for the production of 1,2,3-. ·; Thiadiazole-5-carboxylic acid derivatives, from which | Valuable pesticides and pesticides as well as pharmaceuticals are made.

j.

This preparation of 1,2,3-thiadiazole-5-carboxylic acid derivatives of the general formula

N-C - H

I! I!

N C - COOR., VII

\ s / can be carried out, for example, in a manner known per se, by using the process products of the general

Formula V with thionyl chloride, where R ^ has the meaning given above.

The method according to the invention additionally opens up a new advantageous production route for the connections? of formula VII, namely by implementing the primarily

T

(Standing process products of the general formula I, the Ï, directly with thionyl chloride of the formula S0Clo to the ·.

£ £ - J * can convert desired products of formula VII, thereby saving one process step. This feature of the method is also part of the subject of the present report! finding.

«The synthesis of 1,2,3-thiadiazole-5-carboxylic acid esters of _? ·? _ * I

V

" In the

'* S

’»

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-13- SCI ÎËRiMG AG

C-î · «..:: blîs £ sf EcÆËîÆutt

Formula VII is carried out starting from 3-acylazopropionic acid esters of the formula I by reaction with thionyl chloride.

The reaction is carried out at temperatures between -20 ° C. and 100 ° C., preferably between −5 ° C. and 5 ° C. Depending on the reaction temperature, the reaction time can be between 1 hour and 20 hours.

For the synthesis of the 1 »2,3-thiadiazoI-5 ~ carboxylic acid esters, the reactants can be used in approximately equimolar amounts. However, a large excess of thionyl chloride can also be used as a solvent.

However, 3-acylazo-propionic acid esters and thionyl chloride are expediently used in a molar ratio of 1: 3.

The reaction can also proceed in the presence of solvents which are inert to the reactants. The following may be mentioned as such: halogenated hydrocarbons, such as methylene chloride, chloroform and carbon tetrachloride, aliphatic and aromatic hydrocarbons, such as petroleum ether, pentane, cyclo'nexane, benzene, toluene and xylene, ethers, such as diethyl ether, tetrahydrofuran, dioxane, xthylene glycol diethyl ether, and diethyl ether unc esters, like ethyl acetate.

As a rule, the 3-acvlazo-propionic acid ester, optionally also dissolved or suspended in a suitable solvent, is added in portions to the thionyl chloride which may be diluted with organic solvents. Herbert Asmi «· Dr. Chrtsiiar Brunr * Htns-JCrsen Hamann -Gsuihscrtrifr: AG - Sërxr * ¢ 5 * ES 03 ** i Dr-hel! S: ottr MiKea-tfnssarte D: Hort * Jokes' Psssnsa-kontc: 5e - :: r> -V .es: r> r. fce-æ îX «tt

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SGHbßiNG AG

<3-r Γ ^ ί Order can be made. The one during the reaction? hydrogen chloride which forms can be continuously removed by | an inert gas flow or by applying | Vacuum can be removed from the reaction vessel.

| After the reaction is complete, the reaction! - Known ^ worked up.

After the solvent and the excess thionyl chloride have been distilled off, the residue can be fractionally distilled; or else the excess thionyl chloride is destroyed with saturated sodium carbonate solution, sodium or potassium hydrogen carbonate solution, sodium acetate solution or with sodium hydroxide solution or potassium hydroxide solution or directly with water and the reaction solution is subjected to a steam determination or extraction, the solvent used in the course of the reaction also being used as the extractant can serve. The extracts are then worked up in a known manner: in some cases, after the appropriate drying and distilling off of the solvent, the residue is fractionally distilled under reduced pressure or simply with a suitable solvent such as an aliphatic hydrocarbon : substance such as pentane, hexane, cyclohexane or petroleum ether digested.

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80HHRÎNG AG

”Cf ·. . · NbSsfeirr Reg & KÄtAt j

Kan receives εο 1,2,3-thiadiazole-5-carboxylic acid ester in. outstandingly pure form and in very high yields, so that they can be converted to the desired end products without purification.

| The following examples explain how the er; inventive method.

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-16- SCHiiRiNGAG

G liîiVrÂar FsÆ'sîsiuU

Example 1

a) PRODUCTION OF 3-SEMICAR3AZIDO-PROPIONS AUREMETHYL-3 ESTER

I In a triple-tumbled 2 1 round-bottom flask with stirrer, j I thermometer and reflux condenser with drying tube, i 173.0 g ¢ 1.3 mol) of powdered semicarbazide hydrochloride J. suspended in 300 ml of methanol; For this purpose, a sodium methoxide solution freshly prepared from 3¾ ^ ¾ S (l> 5 mol) sodium and I 5OO ml methanol is dropped within 10 minutes! the internal temperature being kept between 15 ° and 20 ° C f o

•becomes. The reaction mixture is at 15 C for 15 minutes

stirred, then the sodium chloride is suctioned off. The filtrate is collected in a triple-tubed 2 1 round-bottom flask and, with stirring at 20 ° C., 90 ml (1.0 mol) of methyl acrylate are added within one hour. The batch remains at room temperature for 3 days, then becomes again

filtered and then the filtrate in vacuo at 40 ° C.

constricted. This gives 205 g of a yellow oily product, which is then 1 hour with 1 1 ethyl acetate at room temperature *! rature is carried out. It is filtered off from the undissolved ij; and the filtrate was then concentrated to 500 ml at 40 ° C.

. By rubbing you get white crystals, which are suctioned off

Iji are dried in vacuo at room temperature to constant weight.

Yield: 134.4 S = 33.45¾ of theory

Mp: 67-69 ° C

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-17- SOI ERiNQ AQ

. Gîv, -iÂKs; - r Rîÿ; ,,.

- bl) PRODUCTION OF 3 - C ARE AMO YL AZO - PRO FIONIC ACID - iBaUXw uni fiw ΊΠI a I »lu. . b ίβ ^ ϊτιι · —îTftin ιι ~ ιί · »γ» —n "T -—-—» - «-». '«'!

MBTHYLESTER

In a triple-tubed 1 1 flask with thermometer and stirrer, 16, 1 g (0.1 mol) of 3-semi-carbazido-propionic acid ethyl ester are dissolved in 100 ml of water and, with ice cooling, 246.0 g (0.3 mol) of an approx. 10% mixture freshly made en sodium hypo-? ! chlorite solution added within 20 minutes, the internal temperature being kept between 5 and 7 ° C.

After stirring for 10 minutes in an ice bath, the yellow reaction solution thus obtained is mixed with 85 g of sodium chloride and carefully extracted five times with 400 ml of chloroform. The extracts dried over magnesium sulfate are concentrated in vacuo at 4 ° C. A yellow crystalline product is obtained.

Yield: 12.9 ε = 81 »1% of theory mp: 85 - 87 ° C decomposition

b2) PRODUCTION OF 3-CARBAM0YLAZ0-PROPIONIC ACID METHYL ESTER

j, in a triple tubed 1 1 flask with stirrer and! 16.1 g (0.1 mol) of 3-senicarbazido: methyl propionate are thermometers in a mixture of 150 ml

Water and 10.3 g of approx. 955% sulfuric acid dissolved.

η p • lü »m 05 m« r ψ + £ Vcreani D :. He-bert AsmitDr. Christ; *? - E-ahr - Harjs-Jiraen htmanr Pctiinsîr.rt! :: SCHERING AG · C-15X äe'Str. 65 - Pstffz ;? £ 5 £ Pi <* * · *? «· *" *: Cm · Or.h «* W; 2 *; YOrmseritr ses Ailffcici'tttratt: Dr. Eeuird v. Ss-.w.-h-rnr«; * »* ·. R -t-t '.- icx · = .---------- ..

_18. SCHERING AG

GêarxüîiaÎïsr Rscs’iiwdhtrfx

With ice cooling, a solution is released within 10 minutes.

Solution from 9.79 s (0.0333 mol) potassium dichromate in 70 ml; §

Water and 13, δ g approx. 95 / iiser sulfuric acid in one! I.

; f drop reaction temperature from 7 ° to 10 ° C. Man

I I

! can react for another 10 minutes and then adds: | v Add 20.0 g of solid ovalium hydrogen carbonate. Yellow crystals separate out. The reaction solution becomes five -i I; times intensively extracted with 300 ml of chloroform. The chloroform extracts dried over magnesium sulfate are concentrated in vacuo at 40.degree. Yellow crystals are obtained. Yield: 9.0 g = 56.5? * Of theory, mp: 85-87 ° C decomposition

c) PRODUCTION OF 3-SEMICAR3AZ0N0-FR0PI0NIC ACID · METHYL ESTER

In a triple-tubed 250 ml flask with thermometer and stirrer, 15.9 U (0.1 mol) of 3-carbamino-propionic acid methyl ester are dissolved in 100 ml of chloroform and with 0.5 ml:! Triethylamine added, the internal temperature being kept at 30 ° C. by cooling. Then I is stirred for a further hour at room temperature and then the crystal slurry formed is evaporated to dryness at 40 ° C. in vacuo. The residue is digested with 15C ml of Biisoororyläther * f, suction filtered and in vacuo to constant weight; -19- ec i «e. · Vo-Mtnd: Dr. Herten Asm! » Br, 3nris'; sr Brun.- · Hsnt-v'ürasr Himann »etanscRrtft: $ SKSR! N6 AG D-10QC Berte £ · rasées ·. £ C31t * D ·· hate »* Ktri CMC MWesientsn ·« Dr. hear; Like «: Ββ, 3 = ·, · βΓΛ.οηκ: Bt'te-West U7S-1K. Senses: »» · iac? Xic i:

SC! - (! ;; RÎNG AG

Ge.ts: iiîtahcr Eesî'ssirft dried.

j Yield: 14.5 S = 91 »19» of theory I mp: 159 ° C decomposition j Example 2! a) PRODUCTION OF 3-ETHOXYCARBONYLHYDRAZINO-PROFIONSAURE-! --------—

! * METHYLESTER

In a triple-tubed 1 1 flask with stirrer, thermometer and reflux condenser, 11.4.4 g (1.1 mol) of ethyl hydrazino-formate are dissolved in 600 ml of ethanol and internally! half an hour with 90 ml (0.1 mol) of methyl acrylate at 20 ° C. The mixture is left to stand in a closed flask for 4 days at room temperature, then the reaction solution is concentrated in vacuo at 40 ° C. The liquid thus obtained is distilled under vacuum, i yield: 111.1 g = 53.4% of theory

Kp .: 110 - 111 ° C / 0.1 Torr

b) PREPARATION OF 3-ÂTH0XYCARB0NÎLAZ0-PROPIONIC ACID METHYLBSTER

In a triple tubed 250 ml flask with stirrer and »

Thermometers are 9.5 S (0.05 mol) 3-Äthoxycarbonylhyörazino-propionsäuremethylester-dissolved in 50 ml ÎTasser and within 20 minutes with 82 g (0.1 mol) of a freshly prepared sodium hypochlorite solution with about 10 O & Lgen, the internal temperature between 5 ° and 7 ° C is maintained. It does not matter -20- Λ oa tr.

”Vc'S'snd - Dr. Berε-about? Aimit · Sr.Sh-iri; «: trjnr Hïris-Jjrper, H * w. * Nr Pasisnsiftriftr SCKERIKG AG - D-? XJC Eerisr £ 5 · 6? β 11 9 Λ. ; «. · I _ a.a. »S, L ·. MfC: W.: · * · _ _____ ·. t- r. »► <.. -r ... r-: U: cnncw ...

, 20th SCHERING AG

Ctesj & tfe & or Rfrs & iîMàui * is a yellow oil. The mixture is stirred for a further 10 minutes in an ice bath, extracted three times with 75 ml of chloroform and, after drying over magnesium sulfate and evaporating the chloroform phases at 40 ° C. in vacuo, a yellow viscous oil is obtained. Yield: 8.7 g = 92.4 / a theor: .s n ^ °: 1.4424

c) PRODUCTION OF 3-ÄTHOXYC ARBONUfLKYDRAZONO -PRORIONIC ACID METHYLESTER

18.8 g (0.1 mol) of ethyl 3-ethoxycarbonylazo-propionate are dissolved in 100 ml of chloroform in a triple-tubed flask with a stirrer and thermometer, and 0.5% of triethylamine are added at 30 ° C., cooling due to the exothermic course of the reaction got to. The mixture is then stirred for a further hour at room temperature and the reaction solution is then concentrated in vacuo at 40.degree. The remaining 01 is digested with 50 ml of diisopropyl ether and the crystals thus obtained are suction filtered and dried.

Yield: 17t9 E = 95t2 # of theory Mp .: 60 - 6l ° C

'Example 3 PREPARATION OF 3-SEMICARBAZQN0-PROPIONIC ACID METHYL ESTER (continuous)

16.1 g (0.1 mol) of 3-semicarbazido-propionr are in a triple-tubed 1 1 flask with thermometer and stirrer. i - iiX - «a É» er e · r- 2 board: Df.Kerbet *, Asmis · Or.Cnrisben Eruhr · '-sr.iuj j: e- t & nî & nr · »esamwirifi: SCHEStNG AG - D-ICK Sertît: SS - Fosfre * ^ Dr. K6MZ Hantsse Kar; Ot »MtSeittensmeie · Dr. hors: Wrie. * a ** »es * -Kents: Seriin-VitK 1 i7MC. Benfcleteeh! 10CM0010

SCHERING AG

6e * Eislv.-r R «& is $ 5fetrtz acidic acid methyl ester dissolved in 100 nl water and 141.6 g (0.2 mol) freshly prepared sodium hypochlorite solution were added within 20 minutes while cooling with ice, the internal temperature between 5 ° C and 7 ° C is maintained. The yellow reaction solution is stirred for a further 20 minutes in an ice bath, mixed with 66 g of sodium chloride and then carefully five times with 400 ml of chloroform; extracted. The chloroform phases dried over magnesium sulfate are concentrated in vacuo at 40 ° C. to 100 ml.

The concentrated chloroform solution to 100 ml is added: ni ~ 0.5 ml triethylamine, the internal temperature being kept at 30 ° C. by cooling. After stirring for one hour at room temperature, the crystal slurry thus obtained is evaporated to dryness in vacuo at 40.degree. The residue is digested with diisopropyl ether, suction filtered and dried in vacuo to constant weight.

Yield: 12.0 g = 75.5 ^ of theory. Mp .: IpS, 5 - 159 »5 ° C decomposition

Example 4> PREPARATION OF 3 -ÄTHOXYCARBONYLIIYDRAZONO -PRO? IOXOIC ACID METHYLESTER (continuous)

19.0 g (0.1 mol) of methyl 3-ethoxycarbonylhydrazino-propionic acid are dissolved in 100 ml of water in a triple-tubed 500 ml flask with stirrer and thermometer and within 20 minutes with 14.6 g (0.2 mol) one approx

-22-? \ 'Γ Vcirsand: Dr. Herder; Asm »- Dr. Cfiristisr Bryhr · -.tmtnr f-artt'rsärift: SDHERrNG AG B-1M0 Berlsr £ S - Psstreöi SB 0311? Dr · »*» · - »» Mi »*« ’*« · * · Br. Harr. Wi ». Si-K.Pisan, «ioc ic

SCHERING AG

"1_e" Giv arider Res & î $: rèiirtz 10% sodium hypochlorite solution is added, the internal temperature being kept between 5 ° and -7 ° C. A yellow oil separates out. The mixture is stirred for a further 10 minutes, extracted three times with 150 ml of chloroform and narrows the i 3

Chloroform phase after drying over magnesium sulfate to 100 ml.

The chloroform solution, which is concentrated to 100 ml, is mixed with 0.5 ml of triethylamine, the temperature not to exceed 30 ° C. After stirring for one hour at room temperature, the reaction solution is evaporated in vacuo at 40 ° C; the oily residue is then digested with 50 ml of diisopropyl ether and the colorless crystals formed are suction filtered and dried.

Yield: 12.9 g - 68.5% of theory, m.p .: 59 - 6l ° C

r * Example 5 i I PRODUCTION OF 3 -ÄTHOXYCARBONYLHYDRAZONO-FROFION-r-

ACID METHYLESTER

In a triple tubed 500 ml flask with stirrer and

Thermometers are dissolved 19 * 0 (0.1 mol) 3 "'4 * hoxycarbonylhydrazino-1-propionic acid methyl ester in 150 ml water and iimer- • half a 15 minutes with a solution of 9» 79 £ (0.0333 mol)

Potassium dichromate in 70 ml water and 17 »2 g (0, lb7 mol)! 95% sulfuric acid added. The inside temperature is kept between -2 ° and C ° C for 30 minutes. Then -23- m at ▼ 4; VorstenC: Dr. Herbert Asm! » Dr. ChrisSitr Bruhr. Κκ-ηιητ SCHERîfe'G 4S · D-1ÖX Berîta SS Pwîfa * 55031-s “D :. Hmrz Htim - W Otto M *** · «» · * - Dr. Hart W; se PoniSiea ^ omc: Berk-Who K »« · Ëer.üîe ^ ar-? 0C IX «

_23. SCHhRiNG AG

G ^ stiKch :: Reehistchrfz extracted twice with 40 ml chloroform. After drying over magnesium sulfate, the chloroform solution is evaporated in vacuo at 40 ° C. The remaining 01 is digested with diisopropyl ether and the crystals thus obtained are suction filtered

Yield: 12.4 g = 65.9 ^ of theory. Mp .: 57-6l ° C

EXAMPLE 6 PREPARATION OF VOX 1,2,3-TIIIADIAZOL-5-CARBONIC ACID METHYL ESTER In a triple-tubulated 250 ml round-bottomed flask equipped with a stirrer, thermometer and condenser with discharge into the fume cupboard, 21, S-mi (0.3 mol) of thionyl chloride are cooled to -10 ° C. and 15.91 pounds (0.1 mol) of methyl 3-carbamoylazo-propionate were added in portions within 15 minutes, the internal temperature being kept between -5 ° and 0 ° C. After the addition has ended, the yellow reaction solution becomes two more

Stirred for hours, whereby the internal temperature may slowly rise to +2 C. The mixture is then diluted with 60 ml of chloroform and carefully decomposed with 60 ml of a saturated potassium hydrogen carbonate solution, the internal temperature being kept between 10 ° and 20 ° C. The chloroform phase is separated off, washed neutral with 30 ml of potassium hydrogen carbonate solution, dried over magnesium sulfate and concentrated in vacuo at 40 ° C. The liquid thus obtained becomes -24- m à i board! Dr. harsh; Asm «- Dr. Cbr: si: ïr griinn · hEns-Jb’jer. himann postal address: SCHERING AG D-tOK Berlin fö · PO Box S5B311

t Dr. Heinz Kennst · Kari Site Msteittensaneie · D :. Hora; Jokes- Pestssnecx accounts: Beritn-West Ssr.Rieitra «: 10C10C1C

B e. ·. . - _ _. · Μ · r ~ ui at «μ m

~ 2-'ί- SCHERING AG

Oar.-ssiSahar Reah'xFcfcutz distilled under h'asserstrahl.l% rakuuin.

Yield: 11.6 g = 80.55¾ of theory bp .: 110 - 111 ° C / 1k Torr ji i:. ί:. -25- i:! ! · Ί i i ί rs

Vertta ^ d. Dr. Herbert AsmisDr. Chrtsfcar Eruhn · hans-J ^ ser Hanann Bbstsrissririft * AG - Berlin 6c- ^ oetfecr. 66 0311 s & · '· he «R2 hannse - Kart Otsc Mrtteictenscrwd - Dr. Hers: Witte: ür.-W «: 1175-1S: Eertfc ^ ttah * IX1X10

Claims (2)

1. Process for the preparation of 3-acylazo-propionic acid esters of the general formula 0Ho - CHn - COOR - »! u N = N - CO - n2 I in which a C ^ -Cg alkyl radical and an alkoxy radical, preferably a C ^ -C ^ alkoxy radical, characterized in that acrylic acid esters of the general formula H H I C = C - COOR. H "" 11 with hydrazine derivatives of the general formula H N - NH - CO - R "III £ * M, if appropriate using an inert solvent and / or in the presence of a catalyst, to ♦ 3-Acylhydrazino-propionic acid esters of the general formula CH - CH_ - COOR. i 2 1 NH - NH - CO - R0 IV Am • and these compounds in an inert solution -2c- w- '·? a ♦ £ Mind: Dr. Herbert Asmi »· Dr. Christie 'Bruhr, · Hsns-Jt-per Hsnanr Bost £ h! «IrI {t: SCHERING AG D-130C 5« riir- 65 · Potfissh 65 0311 4 Dr · "e'r" henrtse · Kw * Otto MttMtttenseneie Dr. Herr Witze. Psrsw * ». Korac: 6erür> -WeK 1175-10 :. Sasfcii'öiv WC WO» * __ ».. N.: .. M .________ W. - AM. - _ _ ib> k- .. «ns ^ lvu · nf. C._tiU! TaaU · Vl ifVt AA _, s_ SCHERING AG” Ga “Gfa! Teh®r Legal protection means by action of oxidizing agents to the desired process products: -, where R., and Rn ['1 have the meaning given above. j ·' 2. The method according to claim 1, characterized in that the #r 3 implementation of the acrylic acid ester of the formula XI with the hydrazine derivatives of the formula III at temperatures from -20 C to 150 ° C, preferably from 0 ° C to 50 ° C, and at a pressure of 1 to 10 atmospheres, preferably at 1 ί atmosphere , optionally in a base or acid catalyzed reaction and that equimolar amounts of the acrylic acid esters of the formula II and the hydrazine derivatives of the formula III are used. 3. The method according to claim 1, characterized in that the oxidation of the 3-A-cylhydrazino-propionic acid esters of the general formula IV with common oxidizing agents at temperatures from -20 ° C to 100 ° C, preferably from -5 ° C to 50 ° C , takes place and that a 3-acylhydrazino-propion-! Acid ester of formula IV is used, which is not isolated from the reaction mixture and is implemented in a continuous process. i ’’ 4. Process according to Claims 1 to 3 for the preparation of h compounds of the general formulas j. -27- b I - i. p Ui ! ‘G j £ Vcrstena: Dr. Notches Asrm * · Dr. Siriïtiar Bruhr. Hsns-Jüi-aen ^ e.-nanr »snrssairtf :: SSKSWN6 AS · D-13CC Bert» 6E Pa * S * st> ββ11 I ··:; Dr. Heinz hannse · Kar ’OtK MinMSwraMiB · Df. Ho« S WBM: PSÏWs-ew-Ker- «- BeriirvW«; 1Î75-W .. Benhieteahi 1XÎ051C t · - Vor * if? * R.Ger fl · * · TV Pr-ürn l c ..!. ».. r tr Ce.« Jr * · k '«nrrwk ·· in £ 7niV-rr lOFlQßOC _27_ SCHERING AG Gr ··! î.bSàar Riïshhsdhuîx CK- CH0 - COO ^ N - NH - CO - R2 V and CH = CH - COOR: NH - NH - CO - R2 VI. 5. The method according to claim characterized in that compounds of the general formula CH - CH "- COOR .. j sL £ XN = N - CO - RI are optionally treated with a solvent using catalysts, wherein R_ and R0 - those mentioned above Have meaning. 6. The method according to claim 5, characterized in that a 3-acylazo-propionic acid ester of the formula I at temperatures from -20 ° C to 50 ° C, preferably at 0 ° C to * 30 ° C, to the acylhydrazone of the formyl acetic acid ester of the formula V. and is stored without storage to the enhydrazine of the formula VI. 7. The method according to claim 1 for the production of 1,2,3--2Ö- • S VG? S: anä: Dr. nareert Asmis Dr. Christian Sruhr. - Hans-Jüroer. humer.r Pesisntetirift: SCHERING AS · D-lOK Sarhr. ¢ 5Postbox β50Ϊ 11 i Dr. Heinz HarmsKarl One Mister SaiaiC Dr. Hors * was Possswac-Komc: BerSr-Wasr wwr Banbelsah10010816 -Î r>. c ^ r ... ».. e λ v .. ·. s .. • «rww irm rvs Λ -28- SCHERING AG Gf · ·: -: 5Πώ * Γ Legal protection thiadiazole-5-carboxylic acid derivatives of the general formula N-C - H« II NC - COOR., VII \ / 1 where R1 has the meaning given above. 8. The method according to claim 7, characterized in that compounds of the general formula CH - CH0 - COOR! “N = N - CO - Rn I with thionyl chloride of the formula soci2, where R ^ has the meaning given above. 9. The method according to claim 7, characterized in that * compounds of the general formula CH- CH- - COOR. »2. 1 . l! Reacts N - NH - CO - R_ V with thionyl chloride, where R ^ and R0 have the meaning given above. 10. The method according to claims 1 to 9 for the production of crop protection agents and pesticides and pharmaceuticals. C \ «9 Cb tc ^ ^ \ J Vorstenß: Dr. Herbert AsmisDr. Christiar. Bruhn HK »« JEirßBrt hirnenr Postal address: SCHERING AG D-tQOC Berlin es - PotV * er 650215 2 Dr. hetre hsnn «· Karl Ottc Msttftiiterîssfîèic · Dr. Horst W * tte. · A .-. R ä «. 1 ^ «« e '- ^ u. ,. PoîtscnecK-Kcntc: ae-iîp-Vv »! 1175 * 101. EanKte-tze ^ v 10C10C1C? -Ï YcrSltZenOe * OBZ AL.SlältSretSr Dr. Eoutrc v. SSTWCrtZKCZDer Rer: «*! ® * 'Cammerrha?» *: AG. Bernn. Kftfrtr — ki »tvcnn imtfnnn