NO763934L - - Google Patents

Description

"Procedure for the manufacture of

a vinyl cyclopropane carboxylate"

important information

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This invention relates to a new method for developing position of |orga-ni-ske—f-orb-i nde-l-ser-t-which -contain r \ <cycl op r opa n Wi. rhoctyl<ft 'rings-y-s-feemeti', especially jsubs-t-i-tue-r-te' cyclopropanes which are useful as pyrethroid insecticides or as intermediates in the manufacture of pyrethroid insecticides,, and-it—concerns— new—s-fcof -f-~-bia-nd-tnge-r- which-are-r-- new-t-tige-by-the-development-of- this- procedure \

The group of pyrethroid insecticides includes both natural and synthetic substances. The active natural products

is extracted from the fruiting flowers of pyrethrum flowers (Chrysanthemum cinerariaefolium) which are mainly grown in East Africa. The extracts

comprises at least six closely related vinylcyclopropane carboxylates: pyrethrin I, pyrethrin II, cinerin I, cinerin II, jasmolin I and jasmolin II. The most important natural pyrethroid, pyrethrin I, has the structure illustrated below. The structures of the other five components differ from pyrethrin I in the parts of the molecule shown by the arrows. In cinerin II and jasmoline II, the dimethyl-vinyl group in the 2-position becomes (methyl)(carbomethoxy)vinyl, while the pentadienyl side chain in the alcohol part in the cinerines is 2-butenyl and in the jasmolines 2-pentenyl.

Until recently, 1,1,1-trichloro-2,2-(bis-p-chlorophenyl)ethane (DDT) and 1,2,3,4,5,6-hexachlorocyclohexane (BHC) have been widely used as insecticides. But with a view to the resistance that these materials show to biological degradation and to their persistent presence in the environment, new insecticides have been searched for that cause less damage to nature. Pyrethroids have long been of interest because they are active against a large number of insect species, they show relatively low toxicity to mammals and they do not leave any harmful residues. Pyrethrin I, for example, is more than 100 times as powerful against mustard beetles (Phaedon cochleariae) as DDT. but only from a quarter to half as toxic to rats.

Although they have a number of desirable properties, the natural pyrethroids are quickly degraded biologically, they have a bad

photooxidative stability, their availability is uncertain and it is expensive to extract and prepare them. The discovery of the structure of the natural pyrethroids has made it possible to produce synthetic pyrethroids, and for a number of years attempts have been made around the world to produce synthetic pyrethroid insecticides which can overcome the disadvantages of the natural products.

13 n be t-yde-l-i g -nye re- -u tv i kling — was—the-discover-lsen-a v -e t -d i ha logen— t»

vinyl cyclopropane carboxylate (structure II) which has a toxicity/</>against insects more than 10,000 times greater than that of DDT,,and with an oral toxicity to mammals similar to that of pyrethrin I t^Elliott et al., Nature , 244, 456 (1973)3] Although structure II, where the alcohol moiety is 5-benzyl-3-furylmethyl, has no/exceptional photooxidative stability, Elliott et al. discovered that

3-phenoxybenzyl analogues (structure III where X is halogen) were remarkably resistant to photooxidative degradation (Jrature, 246, 169 (1973), Belgian Patents No./800,006 and No.

818 81l] /

;This method includes several methods of synthesis

of pyrethroids in which the cyclopropane carboxylic acid moiety contains a dihalovinyl group in 2-still none, and describes new compounds useful in carrying out these processes. Accordingly, methods according to this invention lead to esters of such acids which either are or/can easily be converted into pyrethroid insecticides. The main advantage of this invention is that it provides a convenient method of synthesis for pyrethroids of the type indicated by structures Ij/and III.

Prior to the present invention, the known methods for varying the nature of the substituents in the 2-position of cyclopropane Ingeryi included the following: 1) Chrysan-£emic acid or a naturally occurring chrysanthemum can be subjected to ozonolysis to form caronaldehyde [Farkas et al., Coll.. Czec)/ Chem. Com. , 24_, 2230 (1959)]]. The aldehyde can then be treated with a phosphonium or sulfonium ylide in the presence of a strong base, followed by hydrolysis [crombie et al., J. Chem. Soc. (c), 1076

(19?0) and British Patent No. 1 285 35(TJ . Such a reaction series is shown below.

sUi-sse- f or bind else r-can--and so—used—fe-i-1 å---f-rems td-ld-e—p-s'U"b5Tti"tuérté vinylcyclopropa nka rboksy la te r where a p-substitue.n-t-"ér is different from halogen. For example, ethyl-4,_6--dl*k"1,or-3,3-dimethyl-5-hexenoate is reacted with natrLum-t-butoxide in benzene to form ethyl 2-2 (p-chloroviny-1-)-~3~ , 3-dimethylcyclopropanecarboxylate. ;^^,.-Deh can also be used other means to introduce halogen;- to - to— prepare- f o r b i n d e l s e r - so o m- e r - i ~-s t a n d—t i-l— to~~b li- d e h y dTtr= halogenated for rings! out tet- i—tri nn -3 ■. | Y-unsaturated alkenoates can be halogenated in the <5-position with a halogenating agent, for example N-bromosuccinimide (NBS) to pass through ndeises which are analogous —me-d-■ X-me-l-l-omp-r-od-ukte-ne—besk-r-evet—ovenf or . Such compounds will also be dehydrohalogenated and cyclized to form cyclopropane carboxylates. The reaction series is illustrated below: ; where a) R is lower alkyl, b) R 2 and R 3 are each hydrogen, lower alkyl, lower cycloalkyl, phenyl or aralkyl such as benzyl, R 2 and R 3 can together form a lower alkylene chain with at least 2 carbon atoms, and when one of R 2 and R 3 is different from hydrogen, the other may be lower alkoxycarbonyl, lower alkanoyl, aroyl such as benzoyl, di(lower alkyl)amide or nitrile, c) R 3 is hydrogen, lower alkyl, lower cycloalkyl , phenyl, aralkyl such as benzyl, lower alkoxycarbonyl, lower alkanoyl, aroyl such as benzoyl, di(lower alkyl)amide or nitrile,d) R 13 and R 14 are each hydrogen, lower alkyl or phenyl, and ;e) X is halogen.;— T- r- i- n- n— 1-The f first-progress must te—in—respect— ti-1—up f••i-nnei se n—e r-frera-st- i-1 t—at—step- -1— -whereby - en- alke noi-—becomes— omsa -t-t~-with - en—or toe ster—f or to —f-r e mb ring e -fe—Y— urne fatet- - ka r book-s-yia-t—A—ved —h j ei p —a v-d e n—bia-ndede- ;i9-. -methyl— 1 -butyr-yi-2-(p:7-(3-di-chlorvin-ny-1)-3-cyanocyclopropaji*'

carboxyla t

20. ethyl-2-(p,p-dibromovinyl)-1-(N,N-dimethylcarboxamido)-3-methylcyclopropanecarboxylate_ 21. methyl -1-cyano-2 - (p,,-P ^d in fluorovinyl) -3 - fe ny lcyclopropa nkar-boxy lat 22 . ^e-thy-l-ethynyl-2 - (p , p-dichlorovinyl)-3 , 3-dimethyl cyclopropane--k-a-rbok-sy-la t-.—: Application of the method^ according to this invention to prepare vinyl cyclopropane carboxylates from the dihalogen v-in-nyl, examples are given in the following examples:

■ E- k- s e- mpe- l-^- V- I-

A. Preparation of ethyl-L,3,3-trimethyl-2-vinylcyclopropanecarboxylate. 1. A mixture of 920 mg (5 mmol) ethyl 1-2,3,3-trimethyl-4-hexenoate, 10 ml carbon tetrachloride, 107 g (6 mmol) N-bromosuccinimide and 50 mg benzoyl peroxide was heated under reflux for approx. 2 hours.

The insoluble succinimide was removed by filtration. The filtrate was washed successively with saturated aqueous sodium bicarbonate solution and water and then dried over magnesium sulfate. The dried solution was distilled to give 1.14 g (86% yield) of ethyl 6-bromo-2,3,3-trimethyl-4-hexenoate, m.p. 80-81°/0.8mm.

Analysis:

nmr 8 ppm (CCl4): 5.84-5.37 (m, 2H), 4.01 (q, 2H), 3.85 (d, 2H), 2.24 (q, 1H), 1.22 (t, 3H) , 1.13-0.97 (m, 9H) . 2. A solution of 526 mg (2 mmol) ethyl 1-6-bromo-2,3,3-trimethyl-4-hexenoate in 2 ml anhydrous tetrahydrofuran was added dropwise to a suspension of 224 mg (2 mmol.) potassium-t -butoxide in 10 ml of tetrahydrofuran. The mixture was heated under reflux for 2 hours and then allowed to cool to room temperature. A further 116 mg (1 mmol) of potassium t-butoxide was added and the mixture was again heated under reflux for 2 hours. The reaction mixture was poured into ice water and the aqueous mixture was extracted with diethyl ether. The ether extract was dried over magnesium sulfate and distilled to give 200 mg (55% yield) of ethyl 1,3,3-trimethyl-2-vinylcyclopropanecarboxylate, m.p. 92-95°/l.5 mm.

Ana light:

nmrSppm (CC14): 6.40-4.80 (m, 3H) , 4.03 (b.q, 2H) , 2.08

(b.d, 1H),

1.40-1.00 (m, 12H):

B. Preparation of ethyl-3,3-dimethyl-2-vinylcyclopropanecarboxylate. 1. By the method in example XVI^Al, ethyl 1-6-bromo-3,3-dimethyl-4-hexenoate was prepared, b.p. 85°/0.5 mm. ir (cm"<1>): 1730, 1365, 1215, 1033, 970, 710, 590. 2. By the method in Example XVI-A2, ethyl 6-bromo-3,3-dimethyl-4-hexenoate was converted to ethyl 3,3-dimethyl-2-vinylcyclopropanecarboxylate, b.p. 68-75°/25 mm.

ir (cm-1):. 1728, 1630, 1187, 1148, 1097, 1030, 990, 902.

Claims (1)

Process for the production of a vinylcyclopropane carboxylate with the formula 1 2 3 where R is a lower alkyl group; R and R are each a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower cycloalkyl group, a phenyl group or 2 3 an aralkyl group; or R + R is a lower alkylene chain of at least 2 carbon atoms; and when one of R 2 and R 3 is different from hydrogen, the other is a lower alkoxycarbonyl group, a lower alkanoyl group, an aroyl group, a di(lower alkyl)amide group or a nitrile group; R 7 is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower cycloalkyl group, a phenyl group, an aralkyl group, a lower alkoxycarbonyl group, a lower alkanoyl group, an aroyl group, a di(lower alkyl)amide group or a nitrile group; 13 14 R and R are each a hydrogen atom, a lower alkyl group or a phenyl group; and X is a halogen atom, characterized in that a y-unsaturated-e-halogen carboxylate with the formula is dehydrohalogenated with a base to produce ring closure to form the cyclopropane carboxylate.