IE63469B1 - Process for the preparation of pyrethroide derivatives - Google Patents

Description

’ Process to the preparation of pyrethroide derivatives The invention relates to the preparation of pyrethroide derivatives in a great purity suitable for controlled crystallization.of the general formula (I), in the course of which cyanhydrine of the general formula (II) CN ι is acylated with acid chloride of the general formula (III) (III) A 4682-77 OE/Hoj -2and the cyanhydrine of the general formula (II) is prepared from benzaldehyde of the general formula (IV) (IV) by reacting the seme with alkali-cyanide and water using an amine as catalyst in a way, that in the aqueous solution of alkali-cyanide of 7-9 mol% benzaldehyde uf the general formula (IV) is added iri the presence of 0.150.25 mol equivalents of amine calculated on tho aldehyde and the cyanhydrine of the general formula (II) formed in the reaction mixture is acylated in statu naacens parallel to the formation of cyanhydrine with an acid chloride of the general formula (III) ur with an acid chloride mixture added continuously, controlling tho temperature balance of the reaction in a way, that the acylation should be finished between 0.2-4 hours at a temperature of 80-10°C and the cyparmotrine emulsion obtained is extracted advantageously with en apolar solvent and after distillation of tha solvent the remaining oily product is advantageously isolated from a f 25 alcohol.

In the general formulas -A is a chlorine atom, a bromine atom or a methyl group -3- Y Is a hydrogen, a fluor or a chlorine atom - the wave line means an R respectively S configuration.

The o4-cyano-estera of thB general formula (I) are effective insecticides (Hungarian Pat. Specification No. 170 866).

To their preparation several processes are known. This way from - in given caae suitable substituted phenoxy benzaldehyde with potassium cyanide in the presence of sulphuric acid a cyanhydrine derivative of the general formula (II) was obtained and after purifying the product by extraction it was soylated in the presence of pyridine with acid chlorides of the general formula (III) in benzene at 20°C for 10 hours, thereafter the reaction mixture was subjected to chromatographic analysis (Hungarian Pat. Specification No. 170 866, example 20; Pesticide Sci. 6 (1975) 537).

Disadvantage of the process is, that because of the known inclination of cyanhydrldes to decomposition special storage and reaction circumstances had to be insured to exclude the hydrogen-cyanide generation. To exclude the cyan danger the tosilate of cyanhydrine of the general formula (II) was reacted with the sodium salts of cyclopropane carboxylic acids. Disadvantage is, that - although the cyanhydrine-tosilate ie more stable end an intermediate which can be isolated in a crystalline form - its reactivity is weaker and the re-eaterification takes 5-10 hours at a temperature of about 70°C. -4Thus in the course of the reaction 5-20¾ of decomposition products are formed, firstly due to the decomposition of the cypermetrine formed (Specification of the EU. Patent No. 67461).

The cyanhydrine intermediate is excluded (eliminated) too in a way, that the suitable benzaldehyde derivative was reacted first in the presence of a catalystic quantity of Lewis acid with acid chloride of the general formule (III), end from the^-chloro-ester obtained the pC-cyano-ester was formed in a substitution reactin with sodium-cyanide reagent (French Pat. No. 407 200). Applying this process e.g. the cypermetrine can be obtained with a yield of about 70%, however because of the weak quality of the product it could not be applied in en industrial scale.

Applying a similar reaction chain the acid chlorides of the general formula (III) were reacted below 10°C with the melt of phenoxy-benzaldehyde and the ^-chloro-ester was added to alkali-cyanide and the aqueous solution of a special phase-transfer catalyst (Hungarian Pat.

Specification No. 191 333). The quality of the product is even in this case not satisfying, among others because of the catalyst-traces remaining present.

Disadvantage of the applied phase-transfer-catalysts * 25 is. that thRy accelerate the reaction, but they are 4 accelerating the side reactions in a similar extent, end this way they further the hydrolysis of the ecid chloride of the general formula (III) end in a smell extent that -5of the cypermetrine too. But without these catalysts the reaction can be realised only with a yield of 64% and the quality of the product obtained is very poor too and requires chromatographic purification (US. Pat.-Spec, No. 835 176 1). As phase-transfer-catalysts onium” e.g. quaternary ammonium compounds (Hungarian Pat. Spec. No. 1Θ1 362, Japanese document laid open to public inspection No. 77 142046), tertiary amines (2 110 727 Brit. Pat. Spec.), tertiary amine salts (Hungarian Pat. Spec. No. 189 096), amino-alkyl-sulphonic acids (USP No. 4 322 535 1) wars applied.

Reproducing the processes mentioned above we stated, that in the reaction mixture generally three liquid phases are present, namely one aqueous and two organic phases. Accordingly the transport of the substances, the transport of the reagents respectively is slowing down the reaction and it is raising a possibility to the start of side-reactions.

According to the solvation of the present invention only two solvent phases are formed and the coincidence of the reactants is assured too in a way, that in a quick reaction a very pure product can ba obtained.

Our recognition is putting the judgement of the reaction in a new light. The role of the medium was examined in details and a statement was achieved according to which (Hungarian Pet. Spec. No, 181 632) the apolar solvents are favourable to the running down of the reaction, while increasing the polarity the yield ie -6decreasing. According to the data published e.g. in the case of dichloro-methane the yield is only 46%, while in the case of dimethyl-sulptvo'xide it is 0% (during 8-18 hours).

Realizing the present invention because of the aqueous medium the reaction is taking place unanimously under polar circumstances - however - in a dramatic contrast - with an uncommon yield compared to that awaited.

A subBtancial recognition of the present invention is to avoid problems of getting rid of different auxiliaries and that how to remove the byproducts.

In the course of our examinations we examined circumstantially the individual parameters of the reaction.

Ws examined the scales of the use of organic solvents in the case carrying out the reaction in an aqueous medium. We verified that the oroanlc solvent can bB applied only maximum to β 0.1 molar equivalent content.. Using moru Hie deteotabln nn called thrRR phase state, the yield and parallel the quality are becoming worse. It is interesting that this rule relates also to solvents considered as bad ones in the previous literature (dichloro-ethane, carbon tetrachloride, dichloromethane) and to those recommended, as aliphatic praffines (hexane, heptane, etc.).

According to the invention secondary or tertiary amines - advantageously - trietyl-amine or imidazole ere -7applied in a quantity of 0.15-0.25 inol-equivalents calculated on the aldehyde of the general formula (IV). The alkali-cyanide is applied expediently in a 7-9 mol’s aqueous solution.

It is advantageous to carry out tho acylation reaction at a temperature of 5-15°C in the course of 2-3 hours. Using a suitable equipment, reacting the components in a shorter time even a higher temperature is not damaging the reaction.

According to the present invention not only the oisor trans-isomers or mixtures of thorn of an optional ratio from the possible acid chlorides can be applied, but also the optical ismores too^ in the course of thB reaction no isomerization occurs.

Acylating ths 2,2-dimethyl-3-(2',2*-dichloro-vinyl)cyclopropane-carboxylic-acid chloride isomers with a mixture containing acid chlorides in a mass ratio of cia 2 - trans 3, the cipermetrine emulsion obtained is extracted with an apolar solvent and after distilling the apolar solvent the remaining oily product - is crystallized - advantageously from any alcohol C^_^a crystalline cipermetrine of 98% purity, melting at 3840°C containing the possible isomers in a ration of about cis 2:trans· 3 can ba isolated. According to our knowledge up to the present cipermetrine was not prepared in such a pure, crystalline form.

As a product of such a purity is crystallizing spontaneously by recrystallization a particularly pure -8(ebovB 98%) product can be prepared.

Substantial advantage of the process is that because of using an aqueous medium a much more diluted cyanide solution can be applied, which makes the controlsbility of the pH value much easier.

In the case of industrial manufacture e further advantage ie, that the reaction can be carried out very quickly and after the addition the reaction mixture can be worked up Immediately.

Our method ie surpassing tho known ones in respect of reliability, simplicity and rentability and can be applied even in industrial scales.

Amongst the recognitions forming the baee of the present invention the preparation and the mood of reacting on the cyanhydride takes a very important place. The suitable aldehyde ie reacted in a diluted aqueous solution with cyanide, to avoid the Canizzaro-reaction in the presence of at most 0.3 moles aminu (calculated on aldehyde).

The cyanhydride formed in the equilibrium reaction is reacted in statu nascens, in the aqueous medium, quickly - and accordingly at a suitable temperature with the added acid chloride parallel to its formation. This way the equilibrium is shifted and thB formation of cyanhydride is made complete - on thB other hand by the immediate a cylation it is prevented that cyanhydrine should be subject in a basic-cyanic medium to sidereactions. This way the process is becoming so selective -9that the side-products - among them products of the general formulas (V) and (VI) - , their formation respectively - are practically completely eupressed.

Summarized it can be stated, that according to the invention the amine catalyst is selective, that is it catalyses only the main reaction, while the ionic phase-transfer catalysts are not selective: but decreasing the surface tension they are catalysing in the same degree the undesirable e.g. hydrolytic side processes, as the main reaction. Ihe process according to the invention thus differs from the simple phase-transfer-catalysis.

The symptoms are: a) A very quick reaction, b) A vury pure product (a 97% purity, usual in the laboratory) and this way: c) Cipermetrine is crystallized with a nearly quantitative yield (91%) even in caae of 8 isomers - while a crystalline product was not known up to the present. d) The reaction can ba carried out practically without a solvent, with polar solvents respectively which was considered as impossible previously. This accentuates the surprising character of the invention. ihe process accurding to the invuuliun ie detailed in the fallowing examples. The products were determined by gaschromatographic and fluidchromstographic methods of high pressure. (Analytical Methods for Pesticides and -10Plent Growth Regulators XIII. Ed. by: Gunter Zwelg and Joseph Sherma, Academic Press 1964). As analytical data the results are published always In mess%.

Exapmle 1 (R.S) g^-cyano-3-phenoxybenzyl-(lR.5)-cls-trana“3(2 1.2 '-dichloro-vinyl)2t2-dlmethyl-cyclopropanBcarboxylate To 210.10 1 of water and 51.1 kg of sodium-cyanide weighed in a 3000 1 duplicator 27.4 1 of triethylamine are let to flow. To the mixture 190.2 kg of m-phenoxybenzaldehyde are added and while stirring and cooling in 2 hours continuously 238,9 kg of 2,2-dimethyl-3-(2',2'dichlDro-vinyl)-cyclopropane-carboxylic-acid chloride (cis-trans isomer ration 42:58) are added. After the reaction the mixture is post reacted at room temperature for 1 hour, whereafter the mixture is extracted with a mixture of 200 1 water and of BOO 1 1,2-dictiloro-ethane. The solution is evaporated and thus 414.2 kg of a pale yellow viscous oil are obtained. Yield related to the mphenoxy-benzaldehyde active ingredient content 99,5%. According to gaschromatographic determination the active ingredient content of the product is 97%. 400 kg of the oil thiin nhtained is dissolved in 720 1 of methyl alcohol and after filtration and inoculation the solution is cooled and crystallized. The product is filtered and dried at room temperature. 372 kg of snow white crytals are obtained. Yield related to the weighed oil is 93%.

Analysis: IRcis R and IScis 5 23.5% (HPLC) lRcis 5 and IScis R 18.1% IRtrans R and IS trans S 34.3% total 99.0% impurities 1.0% Melting point: 42-46% C22H19C12N03 Calculated: Found: Example 2 (K,S) o(-cyano-3 C: 63.47% C: 64.20% li: 4.60% H: 4.80% Ν» 3.36% N: 3.21% uhenoxybenzyl-Cl R.S-trans-3-) (21,21-dichloro-vinyl 2t2-diroethyl-cyclopropanecerboxylate Jn a fournecked spherical flask provided with a thermometer and dropping funnel 210 ml of water are weighed and 51.5 g of sodium-cyanide, after total solution 27.4 ml of triethylamine and 198.2 g of mphenoxy-bBnzaldehyde are added. While stirring and cooling in the course of 2 hours 238.9 g (—)-tranc-3(2',2’-diehloro-vinyl)-2,2-dimethyl-cyclopropanscarboxylic-acid chloride are added.

Ihe mixture is stirred for further 30 minutes at room temperature whereafter it is heated with 560 ml of n-heptane to 60°C and extracted. After distillation of the solvent 411.3 g of e yellow oil are obtained. Yield 98.8%. Active ingredient content 97.2%.

Example 3 (R,S) p4-cyano-3-phenoxybenzyl-(lR ,S cls)-3-12(21,2 *-dichloro-vinyl)2,2-dlmethyl-cyclopropanBcarboxylate One proceed according to example 2 with the difference, that instead of triethylemlne 6.8 g of imidazole and instead of trans acid chloride (-) cis acid chloride are applied. The process of working up, as the product is a crystalline one, differs from that described. The precipitated crystals are filtered, wsshed with water and lsopropanol and dried. 413.4 g cf a white crystalline product are obtained. Yleldt 97.8%. Active ingredient content: 98.8%. Melting point: 54°C.

Example 4 (R,S) c(.-cvBno-3-phnnoxybenzyl~(lR,S cls)-3(2 1,2'-dibromo-vinyl)2,2-dimethyl-cyclopropanecarboxylate One proceeds according to example 2 with the difference, that instead of 238.9 kg of trans acid chloride 332.1 kg of (—) cls-3-(2',2’-dibromo-vinyl (2,2-dimethyl-cyclopropane-carboxylic-acid chloride are added to the reaction mixture. As a result 469.9 g of a yellow oil are obtained. Yield: 97.0%. Active ingredient content: 97.2%.

C22H19Br2N03 Mw* 505·22 Calculated: C: 52.53% Ht 3.79% Nt 2.77% Found: C: 51.8% lb 3.90% N: 2.75% Example 5 (R,5) t<-cyano-3-phenoxybenzyl-(lR.S trans)-3-(2methyl-l-propenyl)-2,2-dlmethyl-cyclopropane-13carbQxylate One proceeds according to example 2 with the difference that instead of 238.9 g of trans-permetrinicacid chloride 195.8 g of (-)-trans-3-(2-methyl-l5 propenyl)-2,2-dimethyl-cyclopropanc-carboxylic-Bcid chloride are added drop by drop to the reaction mixture. As a reasult 360.3 g of a yellow oil is obtained. Yield related to 3-phenoxy-benzaldehyde 96.0%. Active ingredient of the oil obtained: 96.8%.

C24H25NO3 Mw' 375»471 Calculated: C: 76.77% H: 6.71% N: 3.73% Found: C: 77.0% Hi 6.20% N: 3.70% Example 6 CR ,5) »<-cyano-3-phenoxybenzyl-(lR,S cis)-3-(2*,2 1 15 dichloro-vinyl)-2,2-ditnethyl-cyclopropanecarboxylate One proceeds according to example 2 with the difference, that instead of trans-permetrinic-acid chloride (+)-cis-3-(2’,2’-dichloro-vlnyl)-2,2-dimethyl20 cyclopropane-carboxylic-acid chloride is added dropwise to the reaction mixture. As g result 410 g of a yellow oil are·obtained. Yield related to 3-phenoxy-benzaldehyde 98.7%. Active ingredient of the oil obtained: 98.0%.C22H19C12N03 Mw‘ 416·307 25 Calculated: C: 63.47% H: 4.60% N: 3.36% Found: C: 63.90%, H: 4.65% N: 3.30%

Claims (8)

CLAIMS:

1. Process to ths preparation of pyrethroide derivatives suitable to controlled crystallization in a 5 great purity of the general formula (I) wherein - A is a chlorine atom or bromine atom or a methyl group - Y is a hydrogen, a fluor or a chlorine etom - the wave line means an R respectively S configuration in the course of which cyanhydride of the general formula (II) ic acylated with acid chloride of the general formula (III) (II) Ο (HI) wherein - the meaning of A and Y is the same es mentioned above 10 and the cyanhydrine of the general formula (II) is prepared from benzaldehyde uf Uio general formula (IV) 0-CH (IV) wherein - the meaning of A and Y is the same as mentioned 20 above by reacting the same with alkali cyanide and water using an amine cstalyst, characterized by , that in the anuenue alkali-cyanide solution of 7-9 mol% benzaldehyde of the general formula (IV) 25 - Y has the same meaning es mentions above is added in the presence of 0.15-0.25 mol equivalent of amine calculated on the aldehyde end the cyanhydrine of the general formula (II) formed in the reaction mixture -16is acylated in statu nascens parallel to the formation of cyanhydrine with an acid chloride of the general formula (III) or with an acid chloride mixture of optional configuration - A has the same meaning ae mentioned above added continuously, controlling the temperature balence of the reaction in a way, that the acylation should take placB between 0.2-4 hours at a temperature of 80-100°C and the cypermetrine emulsion obtained is extracted advantageously with an apolar solvent and after distilling off the solvent the remaining oily product is advantageously isolated from a C^_-j alcohol.

2. Process according to Claim lcharacteri z e d by, that a secondary or tertiary amine, advantageously triethylamine or imidazole are applied. J. Prooooo according to any of Rlflimn 1-2, characterized by, that the acylation reaction is carried out at a temperature of 5-15°C within 2-

3. Hours.

4. Process according to ny of Claims 1-3, characterized by, that amongst the poeaible acid chlorids only the cis- or only the trans isomers are applied and the acylation iu carried out with chlorides of the following acids: 2,2-dimethy1-3-(2 1 ,2'-dichloro-vinyl)-cyclopropanecarboxylic-acid , or 2,2-dimethyl-3-(2',2’-dibromo-vinyl)eyelopropene-carboxylic-acid.

5. Process according to Claim 1 to the preparation -17of cipcrmetrine of 98% purity, melting at 3B-40°C, orystelline form end containing the possible 8 iRomers in a ratio of about cis 2 : trans 3,characterized by, that th£ acylation is carried out with a mixture 5 containing the four isomers of the 2,2-dimethyl-3-(2',2dichloro-vinyl)-cyclopropane-carboxylic-acid chloride in a ratio of about cis 2: trans 3.

6. Process for the preparation of pyrethroide derivatives of the general formula (I) herein substantially as described /£> in the Examples.

7. Pyrethroide derivatives of the general formula (I) herein whenever prepared by a process as claimed in any one of the preceding claims.

8. The features of the foregoing specification, or any obvious equivalent thereof, in any novel selection.