NL7907332A - Phenoxy:benzyl di:methyl chloro:propenyl cyclopropane carboxylate cpd. - useful as an insecticide, prepd. from methyl 2,2-di:methyl oxo:propyl cyclopropane carboxylate deriv. - Google Patents

Abstract

3-Phenyoxybenzyl-1R, cis-2,2-dimethyl-3-(2-chloropropenyl)cyclopropane carboxylate (I) and its C=C geometrical isomers are new. (I) is an insecticide and is closely related structurally to PErmethrin. (I) is effective against e.. flies, mosquitoes, cockroaches. The LD50 (topical applicn.) against flies is 0.005-0.01 mu g/fly. For mosquitoes and cockroaches the LD50 is similar to that of the fly and falling to 0.1 mg/kg.

Description

* £ - VO 8413

Method of preparing insecticides from the pyretroid group.

A number of synthetic insecticides, which are structurally related to the natural pyretrins and cinerines, have been prepared in recent years and have been used successfully in the United Kingdom, the United States, Japan and other countries.

Compared to other insecticides, these insecticides have the advantage of combining a high insecticidal activity with a low toxicity to mammals. In addition to the natural pyretrins, they have the advantage that they are more resistant to light and therefore more suitable. 10 for agricultural applications.

An important commercial compound from this group is permethrin (MDC 143) of formula 1.

In structure, most synthetic pyretroids are esters of 2,2-dimethyl-3-benzyl-cyclopropanecarboxylic acid with 15 alcohols, such as 3-phenoxybenzyl alcohol (as in Figure 1) or 5-benzyl-3-furylmethyl alcohol (as in resemethrin) ). Varying the vinyl substituent in the 3-position of the cyclopropane ring is possible without loss of insectidide activity. For example, several 3-vinyl-substituted derivatives have been prepared and have been shown to have insecticidal activity (for review, see Ji. "Elliot" Synthetic Pyrethroids ", ACS Symposium Series No. 1).

42, 1977 »PP-1 and the literature cited there. The synthesis of the various 3-vinyl-substituted analogs was performed by reacting suitable Wittich reagents with a caronaldehyde ester (Nature, 244, 456 (1973); Journal of Chemical Society, Perkin Transactions I, 2470 (1974). Permetrine has been prepared both by a Wittig reaction of the type mentioned and starting from non-cyclic intermediates cyclizing the cyclopropane ring (N. Itaya et al. "Synthetic Pyrethroids", ACS Symposium 30 Series Ho. 42, 1977, pp. 45).

The relationship between the stereochemistry of the pyretroid insecticides at positions 1 and 3 of the cyclopropane ring and their insecticidal activity is known to show that the cis isomers are about twice as potent as the trans isomers and that the absolute configuration 1R is insecticidal, while 1S has very little activity (Iï. Itaya et al.

5 Loc.cit).

The invention relates to the synthesis of a new insecticide closely related in structure to permetrine, namely the IR, cis-3- (2-chloroprop-1-enyl) -2,2-dimethyl -cyolopropanecarboxylic acid ester of 3-phenoxy-benzyl alcohol, which is a mixture of the isomers of formulas 2a and 2b.

This mixture is also referred to as the mixture of formula II.

The mixture of formula 2 is. Starting from 1R, cis-3- (2-oxopropyl) -2,2-dimethylcyclopropanecarboxylic acid ~ 15 ester of methanol of the formula 3, prepared in the following 3 steps: Step 1

The 1R, cis-3- (2-oxopropyl) -2,2-dimethylcyclopropane carboxylic acid methyl ester is treated with. phosphorus pentachloride to form a mixture of isomers of IR, cis-3- (2-chloro-20-prop-1-enyl) -2,2-dimethylcyclopropanecarboxylic acid methyl esters of formula 1+, which isomers differ in structure at the double bond .

Stage 2

The mixture of the isomers 1 and 2 is saponified with KOH in methanol, so that a mixture of the acids of formula 6 is obtained with the same configurations as in Fig. U. These acids are thereby obtained in the form of their. potassium salts. Stage 3

The mixture of the potassium salts obtained in step 2 is esterified with 3-phenoxybenzyl bromide or its triethyl ammonium salt.

The reaction of phosphorus pentachloride (PCl ^) with carbonyl compounds to form a mixture of a mineral dichloride and vinyl chloride derivatives had already been investigated and has been described in literature "790 7 3 32 4r ^ 3" JACS 59, 2te5 (1937); ibidem 73 5382 (1951)) Treating the ester of formula III with an excess of PCl2 yields as a main product a mixture of the geometric isomer and of the formulas and Vb in a yield of 68.3%. also small amounts of the isomer of formula 5 are formed, with the double bond shifted.

Saponify the mixture of. the esters with the for-. mules ha en te with KOE and methanol provides a mixture of the corresponding acids of formula 6. The potassium salt of. the acid of formula 6 when reacted with 3-phenoxybenzyl bromide or its triethylammonium salt in a polar solvent, such as methyl isobutyl ketone, yields in good yield (56-65%) the mixture of the compounds of formula 2, ie the insecticide according to the invention.

This new insecticide was tested against the common housefly (Musea domestica) and was found to be highly effective and to have an LD1 for flies in topical application, which ranged from 0.005-0.01 mierogram / fly. Also, the substance is highly toxic to mosquitoes and cockroaches, while the LD ^ q is about the same as that for the housefly and falls in the range of 0.6-1.0 mg / kg body weight.

Since the ester of formula 3 can be obtained from (+} - carene-3, which is an inexpensive, readily available and domestically produced by-product of pine oil, the new synthetic method described above allows the new insecticide to be produced in good yield. to be prepared from a cheap and readily available starting material.

The invention is explained. by "the following examples.

Example I

a) Reaction of PCl4 with the ester of formula III

The IR-cis-3- (2-oxopropyl) -2,2-dimethylcyclopropanecarboxylic acid methyl ester of formula 3 (8 g, Q, o mol) was dropped over 16 g at 16 g ice-cooled phosphorus over half an hour. 35 forpentachloride (0.077 mol) with shaking in a round bottom flask of 790 73 32 100 ml. After everything was added, it was left. the reaction mixture was allowed to warm to room temperature (25 ° C.) and at that temperature the mixture was left for 15 hours. The reaction mixture was then diluted with 50 ml of henzene and. poured, on crushed ice 5 with stirring. The henzene layer was then separated and the water layer was extracted twice with 5-0 ml of henzen each time.

, The united hen strata were first washed with. water and then with. an aqueous solution of sodium bicarbonate to remove any acid. Then, the henzene solution was washed twice with water and then dried with sodium sulfate. After distilling the phenylene, a residue of 8.5 g was left and this was purified by distillation to obtain a mixture of the ethyl esters (geometric isomers Ua. And tb) together with a. small amount of. the isomer of formula 5, 15 which is also formed. The yield. " On. distilled material was 6 g (68.3%]; boiling point 75 DEG-8 DEG C. at 1.5 mm Kvik pressure (with GlC analysis, 3 peaks were observed in a carbowax column at approximately 1 HO - 150 ° C and these peaks had a mutual ratio of :2: 36: 22) '.

H) Saponification of the mixture of the ethyl esters of the formulas Ha and Hh.

A cooled solution of 3 g of KOE in 25 ml of methanol and 2.5 ml of water was added in small portions with shaking, he added the 6.0 g of the mixture, of the ester of formulas Ha and 25 Hh and the resulting homogeneous solution 25 ° G left for 16 hours. Then, the solution was diluted with 30 ml of water and most of the methanol was distilled off under reduced pressure, keeping the temperature below 50 ° C. The residue was then extracted twice with 25 ml of ether each time to remove the unsaponified ester. The water layer was acidified with hydrochloric acid at 25 ° C until the solution was acidic on Congo red paper. The solution was then extracted three times with 30 ml of ether each time, the combined ether layers were washed with water and dried with sodium sulfate. Evaporation of 790 7 3 32 5 from the ether gave a mixture of the acids of formulas 6a and 6b. Yield k9k g (80 $).

c) Esterification of the mixture of the acids of formulas 6a and 6b with 3-phenoxybenzylbramidetriethyl ammonium salt.

The mixture of the acids of formulas 6a and 6b. treated with 1.65 g of potassium carbonate in 5 ml of water and stirred at room temperature for 2 hours. Then, 50 ml of methyl isobutyl ketone was added to this solution and the mixture was refluxed in a 150 ml round bottom flask while a water trap was present to collect the azeotropically distilled water and this boiling was continued until no more water was drained. Then, 90 g of 3-phenozybenzyltriethylammonium bromide was placed in the flask and the boiling was continued for 3 hours at 1 ° C. Then the methyl isobutyl ketone was distilled off under reduced pressure and the residue was taken up in an ether solution, washed with water and. then dried with sodium sulfate. Evaporation of the ether yielded a mixture containing the esters of formulas 2a and 2b. Yield 7.7 g (85 $). The resulting mixture with the esters of formulas 2a and 2b was tested as such for insecticidal activity.

Since the crude product thus obtained was contaminated with other more polar impurities (as shown by TLC with petroleum ether and benzene in a ratio of 1: k), it was purified by column chromatography on silica (1:10) and eluting with petroleum ether and benzene ( 1: 1 ·) to obtain a fraction of 6.3 g (56 $) consisting essentially of the compounds of formulas 2a and 2b. The purified product showed greater insecticidal activity.

Example II

Step A was performed in the same manner as in Example I.

Stage B and C.

A cooled solution of 0.620 g Κ0Η in 10 ml methanol and 1 ml water was dropped with shaking at 2 g 7907332

V

6 of a mixture of the esters of formulas 4a and 4b (see example I, step A), after which the homogeneous solution was stored for an additional 16 hours at room temperature (-25 ° C.) * Then the reaction mixture was ml of water were added and the methanol was distilled off under reduced pressure. The "residue" was extracted with ether to recover the unsaponified ester (.1 g) and the water was removed from the aqueous layer by azeotropic distillation with benzene. After distillation of the benzene, the residue containing the potassium salt was refluxed at 140 ° C for 3 hours with 3-phenoxybenzyltriethylethylnefum bromide (1.8 g) in 20 ml of methyl isobutyl ketone. The reaction mixture was then worked up as in Example 1. stage C, where, a. mixture, the esters of formulas 2a and 2b were obtained. (- 1.45 gm, 79.2%).

Example III

15 The stairs. A. and B were performed in the same manner as in Example I.

Step C

1.2 g of the mixture of the acids of formulas 6a and 6b were treated with 0.73 g of potassium carbonate and 2 ml of water and the mixture was allowed to stand for 2 hours at 25 ° C with occasional shaking. This mixture was then treated with. 20 ml of methyl isobutyl ketone and 2.63 g of 3-phenoxyhenzyl bromide and it was boiled for 3 hours at 140 ° C using a water separator for azeotropic distillation. The methyl isobutyl ketone was distilled off under reduced pressure and the residue was extracted with ether after dilution with water. The ether layer was washed twice with water, dried over sodium sulfate and then evaporated to dryness. mixture was obtained from the esters of formula 2a and 2b (3.5 g, 94.6%). The crude mixture contained a small amount of unreacted 3-phenoxyhenzyl bromide in addition to more polar contaminants, as shown by TLC.

790 7 3 32

Claims (3)

1. IR, cis-3- (2-chloroprop-1-enyl) -2,2-dimethyl-cyclopropanecarboxylic acid ester Tan 3-phenoxybenzyl alcohol (mixture of the isomers of formulas 2a and 2b). 2. Process for preparing the IR, cis-3- (2-chloro-prop-1-enyl) - 2,2-dimethylcyclopropanecarboxylic acid ester of 3-phenoxybenzyl alcohol (mixture Tan isomers of formulas 2a and 2b) characterized in * that the IR ,. eis-3- (2-oxopropyl) -2,2-dimethyl-eyelopropanecarboxylic acid methyl ester treated with phosphorus pentachloride under Torming Tan a mixture Tan de 1R, cis-3- (2-chloroprop-1-enyl) -2 , 2-dimethylchloropropanecarboxylic acid methyl ester, the latter Soaps with KOH in methanol under Torming Tan a mixture of the corresponding acids, converts these acids into the corresponding potassium salts and converts the resulting potassium salts with 3-phenoxybenzyl bromide or with 3-phenoxybenzyltriethyl ammonium bromide. 15 3. Process according to claim 1, characterized in that the reaction with PCl 2 is carried out at 0-25 ° C. Process for preparing insecticidal preparations containing synthetic pyrethroids, characterized in that the active substance used is a mixture according to claim 1. 790 73 32 ν · χ · '2α PVs%' 5Λ jf 0 Λ, ί ^ ι 10 Λ Ct ^ Cl HjC- ^ CI LJL / J 0 v 0 "^" ^ IR Q 2t V> l \ T 1 ^ ^ V00 * α c% öuQ * A: 4? £> i? OCH, .¾ V '1 z 6> "ct ^ X °" JL !, ftj l? 2. 790 7 3 32 ^ μηιλι’Ί Λ / »4 ·« +. ·? # 4 ί »& ΤηΛιιβ + .τ'ΐ al Pea« * 3 * eh