CS212300B2 - Method of preparation of esters of the dihalogenvinylcyclopropancarboxyl acid - Google Patents

Description

The invention relates to a novel process for the preparation of cyclopropane ring-containing organic compounds, in particular to substituted cyclopropanes which are useful as pyrethroid insecticides or as intermediates for the preparation of pyrethroid insecticides and to new useful compositions containing these compounds.

The class of pyrethroid insecticides includes both natural and synthetic compounds. Active natural products are extracted from the flowers of the pyrethre flowers (Chrysanthemum oinerariae folios), growing predominantly in East Africa. The extracts contain at least six closely related vinyl cyclopropanecarboxylates: pyrethrin I, pyrethrin II, cinerin I, cinerin II, jasmoline I and jasmoline II. The most important natural pyrethroid insecticide is pyrethrin I, which has the structure shown below. The structures of the other five components differ from the pyrrolidine I in the portion of the molecule indicated by the arrows. In oinerin II and jasmoline II, the dimethylamino group is in the 2-position (methyl) (carbomethoxy) vinyl, while for cinerins the pentadienyl side chain is in the alcohol moiety 2-butenyl and for jasmolines 2-pentenyl.

To date, 1,1,1-trichloro-2,2- (bis-p-chlorophenyl) ethane (DDT) and 1,2,3,4,5,6-hexaehlorocyclohexene (BHC) have been extensively used as insecticides. However, due to their resistance to biodegradation and their environmental stability, new insecticidal compounds are sought which are less harmful to the environment. Pyrethroid compounds have long been of interest since they are effective against a wide range of insect species, exhibit relatively low mammalian toxicity and do not leave harmful residues. For example, pyrethrin I is more than 100 times more potent against Phaedon cochleariae than DDT and only one-quarter to one-half toxic to rats.

212230

Pyrethrin I

O

Structure II

structure III

Although these compounds exhibit a number of desirable characteristics, natural pyrethroids undergo rapid biodegradation, have low photooxidation stability, are uncertain and expensive to extract and prepare. Recognizing the structure of natural pyrethroids, it was possible to prepare synthetic pyrethroids, and for many years attempts have been made throughout the world to produce synthetic pyrethroid insecticides that would reduce the disadvantages of natural products. In particular, recent progress has been the finding of dihalvinyl cyclopropanecarboxylate (structure II), which is toxic more than 10,000 times that of DDT and whose oral toxicity to mammals is similar to that of pyrethrin I [Elliot et al Nature 244, 456 (1973)] · Although structure II in which the alcohol moiety is 5-benzyl-3-furylmethyl, does not exhibit unusual photooxidic stability, Elliot et al. have found that 3-phenoxybenzyl analogs (structure III, where X is a halogen atom) are significantly more resistant to photooxidative degradation [Nature 246, 169 (1973). Belgian patents 800, 006 and 818.81 lj.

The invention relates to methods for the synthesis of pyrethroids wherein the cyclopropanecarboxy moiety contains a dihalo-vinyl group at the 2-position and describes novel compositions which are useful in practice. The processes of the invention lead to esters of these acids which are pyrethroid insecticides or can be easily converted to them. The main advantage of the invention is a suitable synthetic route for pyrethroid compounds of the type represented by structures II and III.

Methods known prior to the invention for varying the substituents at the 2-position of the cyclopropane ring included the following:

1. Chrysanthemic acid or naturally occurring chrysanthemates were subjected to ozonolysis to produce caronaldehyde [FarkaS et al. Coli. Czech. Chem. Com. 24, 2230 (1959) J. The aldehyde was then reacted with phosphonium or sulfonium ylide in the presence of a strong base, followed by hydrolysis [Crombie et al. J. Chem. Soc. (c) 1076 (1970); British Patent 1,285,350]. The reaction sequence is shown below:

The reaction can be used when X is alkyl as well as when X is a halogen atom Ejiho African Patent 733,528, J. Am. Chem. Soc. 84, 854, 1312, 1745 (1962)]. The reaction was used to prepare ethyl 2- (P, p-dichlorvinyl) -3,3-dimethylcyclopropane-1-carboxylate, a precursor of structures II and III. While the ylide reaction proceeds in about 80% yield, the aldehyde yield from the oxidation is typically only 20%. The oxidative degradation originally used to prove the structure has never been considered for large scale preparative use. The oxidation itself requires many hours after completion, since only mild conditions must be used to prevent further oxidation of the organic compound. A total yield of 16% is acceptable in the research procedure, but is too low for practical use. In addition, the starting material is expensive because it is derived from an expensive natural product.

2. The original Staudinger synthesis of chrysanthemic acid involves the reaction of ethyldiazoacetate with 2,5-dimethylhexa-2,4-diene, followed by saponification of the β-Helv ester. Chim. Acta 2,390 (1924)]. The addition of carbene to the carbon-carbon unsaturation has become a general reaction for the preparation of the cyclopropane ring of CMills et al., J. Chem. Soc. 133 (1973); patents 2,727,900 and 3,808 26θ]. This reaction, shown below, was used in the preparation of pyrethroids as well as ethyl 2- (p, β-dichlorvinyl) -3,3-dimethylcyclopropane-1-carboxylate, precursor II and III [Farkas et al. Czech. Chem. Comm. 24, 2230 (1959)]. In the preparation of the latter, the starting material may be a mixture of pentenols obtained by condensation of chloral and isobutylene.

mixture of acetates

OH

CCI 3 +

OH //

AC, 0 mixture

-and-. of acetates of Zn, HOAc

CCI.

CCI, //

CCI,

CCI, p-toluene sulfonic acid // T CCI,

Cl.

// V

CCI,

N ₂ CHCOOEt

Cl

COOEt

The conversion of the pentenol mixture to 1,1-dichloro-4-methyl-1,3-pentadiene is reported to be only about 50%. This, coupled with the fact that the last step requires the preparation of a diazoester, with which all large-scale work is extremely dangerous, greatly limits the applicability of the process. Furthermore, it can be assumed that, if the pyrethroids of structure III find greater agricultural application, the industrial production of a sufficient amount of dihalvinyl vinyl cyclopropanecarboxylate could deplete the world's zinc reserves.

3. Julia described the third general method for substituting the substituents at the 2-position of the cyclopropane ring C of U.S. Patents 3,077,496, 3,354,196 and 3,652,652; Bull. Soc. Chim. Fr. 1476, 1487 (1964)]. According to this method, shown below, the appropriately substituted lactone is first reacted with a halogenating agent, the ring is opened, followed by base-induced dehydrohalogenation and cyclopropane is formed.

Even in a relatively uncomplicated case, where the end groups on the vinyl group are methyl and the product is ethylchrysanthemeth, the yield is only 40%. In addition, the lactones that are desired, such as 3- (β, β-dichlorvinyl) -4-methyl-γ-valerolactone, are not readily available.

The 3-isobutenyl-4-methyl-γ-valerolactone from which ethylchrysanthemeth is prepared requires a three-step synthesis from 2-methyl-hex-2-en-5-one, including the Grignard reaction. Grignard reactions are difficult to carry out on a large scale and in any case would probably not be applicable without decomposing any dihalogen vinyl group present.

In summary, the prior art processes for changing the natural substituents at the 2-position of the cyclopropane ring, especially those for introducing the 2-halvinyl group, have a number of disadvantages, the most important of which are:

1. yields of cyclopropanecarboxylates are too low for practical applications;

2. starting materials are not readily available, requiring additional synthetic steps, increasing the cost and price of products on the merchant market;

3. all procedures involve at least one reaction that is difficult or dangerous to carry out on a large scale and therefore presents a risk of fire or explosion.

The present invention relates to a process for the preparation of dihalogenvinylcyclopropanecarboxylic acid derivatives of the general formula I,

^ ^CX 2

COOR where

R is ethyl, benzyl or 3-phenoxybenzyl, (I)

3

R and S are both hydrogen, methyl or phenyl

R is hydrogen, methyl or ethyl; and

X is a chlorine or bromine atom, characterized in that the compound of formula II is dehydrohalogenated,

where

D is X,

E is a hydrogen atom,

F is hydrogen and

G is X, or

D + E together form a bond,

F is hydrogen and

G is X, or

D is X,

E + G together form a bond and

F is hydrogen, or

D + F together form a bond,

E is hydrogen and

G is X and? 3 7

R, R, ^RJ and R are as defined above, preferably in an anhydrous solvent, by reaction with 1 to 5 molar equivalents of preferably an anhydrous base, such as sodium hydride or an alkali metal alkoxide, at a temperature of 50 to 200 ° C until remove at least one, but not more than two, moles of the hydrohalic acid of formula HX from the starting compound.

In the following examples and elsewhere in this specification, temperatures are given in degrees Celsius and percentages are by weight. For each boiling point carried out under reduced pressure, pressures are given in Pascals, for example a boiling point of 116/24 Pa means that the boiling point is 116 ° C at 24 Pa. Where infrared spectra are reported, only the frequencies of the most significant absorption maxima are given. For NMR spectra, tetramethylsilane is used as an internal standard and the NMH data in abbreviations have the following meanings: s-singlet, d-doublet, t-triplet, q-quartet, m-multiplet. Any of these abbreviations may be preceded by abbreviation b, denoting Wide, and abbreviation d denoting double, for example dd. means double doublet and m.p. means a broad triplet.

Example 1

Synthesis of 3-phenoxybenzyl 2- (p, p-dichlorovinyl) -3,3-dimethylcyclopropanecarboxylate

A. Preparation of ethyl 3,3-dimethyl-4-pentenoethe

A mixture of 0.65 g of 3-methyl-2-buten-1-ol and 2.43 g of ethyl orthoacetate and 50 g of phenol is heated to 120 ° with stirring. After two hours, the temperature was raised to 40 ° C and maintained at that temperature for 20 hours. After completion of the ethanol evolution, the mixture was dissolved in benzene to a total volume of 5 ml. Gas chromatographic analysis of the benzene solution showed that ethyl 3,3-dimethyl-4-penteonate was prepared in 92% yield (physical properties see Example 5).

212300 6

B. Transesterification between 3-phenoxybenzyl alcohol and ethyl 3,3-dimethyl-4-pentenoethane

A mixture of 374 mg of ethyl 3,3-dimethyl-4-pentenoate, 400 mg of 3-phenoxybenzyl alcohol and 16 mg of sodium ethoxide in 10 ml of toluene was heated to boiling in a Dean-Stark apparatus for 24 hours containing molecular sieves to absorb the liberated ethanol. The mixture was neutralized by addition of anhydrous ethereal hydrogen chloride solution. The neutral solution was poured into water. The ether phase is separated, dried over magnesium sulphate and distilled to give 520 mg (70% yield) of 3-phenoxybenzyl 3,3-dimethyl-4-pentenoate, m.p. 155-158 DEG C./40 mbar.

Analysis for ^C 20 ^H 22 ° ^3: Calc: C, 77.39; H, 7.14;

Found: C 77.14, H 7.11.

NMRδppm (CC1 _4): 7.32 to 7.08 (m, 4H), 7.05 to 6.70 (m, 5H), 5.76 (dd, 1H), 4.92 (s, 2H); 4.96-4.70 (m, 2H), 2.22 (s, 2H), 1.08 (s, 6H).

C. Addition of carbon tetrachloride to 3-phenoxybenzyl-3,3-dimethyl-4-pentenoate

A mixture of 245 mg of 3-phenoxybenzyl 3,3-dimethyl-4-pentenoate in 5 ml of carbon tetrachloride was placed in a pressure vessel and 2 mg of benzoyl peroxide was added. The vessel was purged with argon and sealed. The sealed pressure vessel was heated at 140 ° C for five hours, cooled and 2 mg of benzoyl peroxide was added. The vessel was again purged with argon, sealed and heated to 140 ° C for five hours. The procedure is repeated two more times, after which the vessel is cooled and the contents are washed successively with water, saturated aqueous sodium bicarbonate solution and water. The washed mixture was dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue is purified by chromatography on silica gel using benzene as eluent. 300 mg (82%) are obtained.

3-phenoxybenzyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate.

Analysis for ^C 2 ^C1 4 ^ 2 ° ^3: Calculated: C 54.33, H 4.78, Cl 30.55;

Found: C 54.76, H 4.88, Cl 30.24.

NMR δppm (CCl ₄ ): 7.35-7.05 (m, 4H), 7.05-6.75 (m, 5H), 4.96 (s, 2H), 4.30 (dd, 1H)

3.30-2.80 (m, 2H), 2.57 (d, 1H), 2.26 (d, 1H), 1.15 (s, 3H), 1.07 (s,

3H).

D. Simultaneous cylclization and dehydrochlorination

A solution of 200 mg of 3-phenoxybenzyl 4,6,6,6-tetreohloro-3,3-dimethylhexanoate in 1 ml of anhydrous tetrahydrofuran was added dropwise to a suspension of 124 mg of sodium tert-butoxide in 5 ml of anhydrous tetrahydrofuran, during which time the reaction mixture was cooled with ice. . After one hour, the mixture was allowed to warm to room temperature and then heated to boiling for one hour. The mixture was neutralized by addition of anhydrous hydrogen chloride solution. The neutralized mixture was poured into ice water and extracted with diethyl ether. The ether extract was dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography using benzene as eluent. 126 mg (75% yield) of 3-phenoxybenzyl 2- (β, β-dichlorovinyl) -3,3-diraethylcyclopropanecarboxylate are obtained.

Analysis:

NMR δ ppm (CCl ₄ ): 6.80-6.50 (m, 9H), 6.25 (bd, 0.5H), 5.60 (d, 0.5H), 5.05 (s, 2H) ,

2.40-1.40 (m, 2H); 1.40-1.05 (m, 6H).

Example 2

Synthesis of ethyl 2- (β, β-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate

A. Addition of carbon tetrachloride to ethyl 3,3-dimethyl-4-pentenoate

To a solution of 135.2 mg (0.5 mmol) of ferric chloride hexahydrate and 146.3 mg (2.0 mmol) of n-butylamine in 2.19 g of dimethylformamide in a pressure vessel was added 1.56 g (10 mmol) of ethyl 3,3-dimethyl-4-pentenoate and 4.26 g (30 mmol) of carbon tetrachloride. The pressure vessel was sealed and heated to 100 ° C for 15 hours. The vessel was then cooled and the contents dissolved in diethyl ether. The ether solution was washed successively with 1N hydrochloric acid solution, saturated aqueous sodium bicarbonate solution and saturated sodium chloride solution. The washed solution was dried over anhydrous magnesium sulfate and distilled to give 2.79 g (90% yield) of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate, b.p. 116 DEG C./0.4 mbar.

Analysis for C, _o ^H 16 ° ^{C 1} 2 ^4: Calculated: C 38.74, H 5.20, Cl 45.74;

Found: C 38.91, H 5.07, Cl 45.85.

NMR δppm (CCl ₄ ): 4.37 (dd, 1H), 4.07 (q, 2H), 3.40 - 2.85 (m, 2H), 2.40 (q, 2H), 1.27 (t, 3H), 1.20 (d, 6H).

B. Simultaneous cyclization and dehydrochlorination

To a solution of 3.1 g (10 mmol) of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 40 ml of absolute ethanol was added dropwise 20 ml of an ethanol solution containing 1.5 g (22 mmol) of ethoxide. sodium. The mixture was stirred at room temperature for one hour after the addition was complete and then stirred at reflux for one hour. The mixture is concentrated to about one tenth of the original volume by distillation and cooled with ice, and the residue is neutralized by addition of 1N hydrochloric acid. The neutral solution was extracted with diethyl ether and the ethereal extract was washed successively with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, 2.12 g (89% yield) of ethyl 2- (β, β-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate, m.p. 77 ° C / 40 Pa (physical properties see Example 3) are obtained by distillation of the solution.

The starting compounds described above used in the process of the invention can be prepared by the processes illustrated by the following chemical equations.

Stage 1

212300 Stage 1

A + R ⁸ OH

Stage 2

A or A < + >

(B)

Stage 3

B 4-base->

CX ₃

COOR

R '

C

CX, of ²

COOR

3 7

The substituents R, R, ^RJ and R are as defined above and X is a halogen atom. The radicals -COOr 'and -COOR ⁸ are carboxyl functions, OR ¹ and OR ⁸ are the radicals of alcohols where R ¹ is alkyl

O and 1 to 6 carbon atoms and R is a radical of formula

R ⁹

-CH

R ¹⁰

R ¹¹

where R ⁹ Yippee R ¹⁰ de R ¹¹ d® R « ² d ^e R d®

hydrogen or cyano, hydrogen, alkyl of 1 to 6 carbon atoms, phenoxyl, benzyl or phenylthio, hydrogen or alkyl of 1 to 6 carbon atoms, divalent oxygen or sulfur, or vinylene -CH = CH-, either R ¹ or R ⁸ .

In the process of Step 1, the alkenol is reacted with an orthoester to form a gamma-unsaturated carboxylate of structure A. It has been found that the mixed orthoester of structure W is an intermediate and can be isolated. Other reactants capable of forming this intermediate useful in the process can be used to prepare Compound A; for example, an alkenol can be reacted with the appropriate ketene acetal to form this mixed ortho-ester, from which gamma-unsaturated carboxylate A can be prepared. The product of step 1 is an alkyl ester which may optionally be reacted in step 1 to exchange esters with an alcohol R OH, which is selected from the group of alcohols commonly found in pyrethroids, such as #

3-Phenoxybenzyl alcohol. The ester thus formed, structure A *, can be reacted in steps a 3 to produce the product of step 3, dihalvinyl cyclopropanecarboxylate, which is a pyrethroid insecticide.

In the process of Step 2, the gamma-unsaturated carboxylate A or A * is then reacted with carbon tetrachloride to form a gamma-halocarboxylate of structure B. This gamma-halocarboxylate can then be dehydrohalogenated in turn to form one of four different products depending selecting the reaction conditions. The starting compounds represented by the structures X, Y and Z or formula II resulting from the elimination of 1 mole of HX from gamma-halocarboxylate B are isolated. Each of products X, X and Z is useful and can be converted to the dihalo-vinyl cyclopropanecarboxylate of structure C by eliminating the additional mole of HX. If the ester exchange of step 1 * is not carried out with gamma-unsaturated carboxylate A, the R ¹ group of the dihalvinylcyclopropane Q carboxylate G can be converted to R in a known manner to form the active insecticide.

Other halogen introduction methods can also be used to prepare the starting compounds capable of dehydrohalogenation and cyclization in step 3. The gamma-unsaturated alkenoates can be halogenated at the epsilon position with a halogenating agent, such as N-bromosuccinimide (NBS), to give compounds analogous to intermediates X described above. These compounds also undergo dehydrohalogenation and cyclization to form cyclopropanecarboxylates.

Stage 1

The process for preparing the starting compounds is represented by Step 1, wherein the alkenol is reacted with an orthoester to form a gamma-unsaturated carboxylate, A, via a mixed orthoester, W, an intermediate, which may or may not be isolated. Examples of alkenols that may be used in Step 1 are allyl alcohol, crotyl alcohol, 4-methyl-1-phenyl-3-penten-2-ol, 4-methyl-3-penten-2-ol, cinnamyl alcohol, 3-methyl 2-Buten-1-ol, 2,4-dimethyl-3-penten-2-ol, 3-methyl-4-hexen-3-ol, 2-methyl-2-hepten-4-ol, 1-cyclopentyl -3-methyl-2-buten-1-ol and the like. The exact type of alkenols to be used in step 1 depends on the type of substituents R ² , R ¹ , R 2 and R 4 required. These alkenols are readily available or can be readily prepared from commercial raw materials. Preferably, 3-methyl-2-buten-1-ol is used to prepare 2-dihalinyl vinyl cyclopropanecarboxylates of structural formula II or III having a dimethyl substitution at the 3-position of the cyclopropane ring; 3-Methyl-2-buten-1-ol is available as a by-product in the manufacture of isoprene.

Examples of orthoesters which are useful in the process of Step 1 include, in the alkanoic acid moiety such as acetic, propionic, butyric, isobutyric and valeric, and in the alcohol moiety, lower alkanols such as methanol and ethanol such as ethyl orthopropionate, methyl orthoacetate , ethyl orthoacetate and the like. The acid moiety and the alcohol moiety in the orthoesters are selected to provide the desired groups r ', R ^b and / or gamma-unsaturated carboxylate. Orthoesters can be prepared easily by alcoholysis of the corresponding nitriles. Orthoacetate is preferably used in the preparation of the gamma-unsaturated carboxylate which is to be converted to the dihalo-vinyl cyclopropanecarboxylate with the remaining processes according to the invention.

Although the reaction between alkenol and orthoester does not require this, an acid catalyst can be used to increase the rate of reaction. Examples of useful acid catalysts are phenols such as phenol, ortho, meta- or para-nitrophenol, ortho, meta- or para-cresol, ortho, meta- or para-xylenol, 2,6-dimethylphenol, 2,6 -di-i-butylphenol, 2,4,6-tri-sec-butylphenol,

2,4,6-tri-t-butylphenol, 4-methyl-2,6-di-i-butylphenol, 4-methyl-3,5-di-i-butylphenol, hydroquinone, 2,5-di-t- butyl hydroquinone, alpha or beta-naphthol and the like, lower aliphatic acids such as acetic, propionic, butyric, isobutyric, cyclohexanecarboxylic, valeric and the like, aromatic carboxylic acids such as benzoic acid, methachlorobenzoic acid and the like, sulfonic acids such as benzenesulfonic, para-toluenesulfonic acid and the like, inorganic acids such as hydrochloric, sulfuric, phosphoric, boric and the like, and Lexis acids such as zinc chloride, ferric chloride, mercuric acetate, etc. To avoid side reactions such as dehydration of alkenols , phenols, C 2 -C 6 aliphatic acids and aromatic acids are generally used as catalysts. Phenols are suitable and effective

The process of Step 1 does not require a solvent but does not adversely affect the reaction or product when used. Useful solvents include decalin, n-octane, toluene, ortho, meta- or para-xylene, di-n-butyl ether, N, N-dimethylformamide and the like.

Although the stoichiometrically contemplates that alkenol and the orthoester are to be used in equimolar amounts, it is preferable to use an excess of the orthoester, for example a 20 to 100% excess or more. The acid catalyst may be used in an amount of about 0.001 to 20% by weight, preferably 1 to 15% by weight, based on the amount of alkenol used.

The process of step 1 can be carried out at a temperature of from 20 ° to 250 ° C and the efficient process is carried out in two steps, the first step at a temperature between 20 ° and 120 ° C, the second step at a temperature between 100 ° and 250 ° C. When ethyl orthoacetate is used as the reactant, the reaction is carried out at atmospheric pressure, the first step is usually carried out at 100 ° and 120 ° C, the ethanol formed is distilled off and the second step is usually carried out at a temperature between 140 ° and 170 ° C.

Stage 1 ’

Optionally, the gamma-unsaturated carboxylate, A, can be reacted according to step # A1 in which the alcohol residue, OR, is replaced with a lower alkanol residue, OR, to prepare a gamma-unsaturated carboxylate A *, wherein the OR® group is selected from alcoholic residues commonly found in pyrethroids. The gamma-unsaturated carboxylate, A, can be converted directly to steps 2 and 3 of the present invention into dihalo-vinylcyclopropanecarboxylate C, which is a pyrethroid insecticide, for example of structure XXI.

In the process of Step 1, and R 6 are as defined above.

R 6, R 6, R 6 and R 6 are hydrogen, alkyl, alkenyl, C 1 -C 6 alkynyl, cycloalkyl, phenyl or arylalkyl, such as benzyl, and each pair of R 6 with R 6 and R 6 with R 6 and R 6 with R 6 and R 6 is R 6; it may form a lower alkylene chain with at least two carbon atoms.

The gamma-unsaturated carboxylate and alcohol can be used in equimolar amounts, but generally one reactant is used in excess. The ethyl ester is preferably used, especially when sodium ethoxide is used as a catalyst. During the reaction, ethanol is removed from the reaction mixture. Toluene may be used as the solvent.

O

Instead of introducing the R group as described above, the exchange can be carried out in another stage 1A of the process, and other synthetic methods such as hydrolysis followed by esterification can be used to convert the R ester to the R ester, for example reaction of dihalogeninyl vinyl cyclopropanecarboxylic acid base.

Stage 2

The process represented by step 2 is a reaction between a gem-unsaturated carboxylate A or a 'and a carbon tetrachloride halide in the presence of a catalyst to form a gem-halocarboxylate

B. Gamma-unsaturated carboxylates A or A * can be prepared as described above.

o * 3 ft 7

For the purposes of Step 2, R, R and ^J are as defined above; R and R 'are hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, phenyl, arylalkyl such as benzyl, alkoxycarbonyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms,

Aroyl, such as benzoyl, dialkylamide, nitrile or haloalkyl, and each of the pairs of R 5 and R 6 with R 6; it may form a lower alkylene chain containing at least 2 carbon atoms; R ^A and R 6 are hydrogen atoms.

Carbon tetrachloride, carbon tetrachloride, carbon tetrabromide, bromotrichloromethane, bromochlorodifluoromethane and iodotrichloromethane may be used as the carbon tetrachloride in the process of the invention.

Generally, carbon tetrachloride contains no more than two fluorine atoms and no more than one iodine atom. If dichlorvinyl cyclopropanecarboxylate is to be prepared according to the procedure of

No. 212300 of the invention, carbon tetrachloride, bromotrichloromethane or dibromodichloromethane may be used; although bromotrichloromethane reacts more smoothly, carbon tetrachloride is more readily available and less expensive.

Step 2 requires a catalyst and it has been found that two different types of catalytic systems are applicable:

1. free radical initiator,

2. Transit metal salts or coordination complexes between transition metal salts and various electron donors such as organic amines, carbon monoxide, acetylacetone and the like.

The reaction may also be catalysed by radiation, for example ultraviolet light, and various reactions in which free radicals are used as catalysts. In order to effectively catalyze the reaction with visible light, the carbon tetrachloride should contain at least one bromine or iodine atom.

Examples of free radicals useful in the invention are azobisisobutyronitrile (A1BN), benzoyl peroxide (BPO), acetyl peroxide, di-i-butylperoxide, t-butylperacetate, t-butylperbenzoate, i-butylperphthalate, i-butyl hydroperoxide and the like. however, an amount of about 20%, based on the number of moles of gamma-unsaturated carboxylate, can be used, especially when the catalyst is added sequentially.

Examples of useful transition metal salts that are useful are: cuprous chloride, copper chloride, ferrous chloride, ferric chloride, cobalt, nickel, zinc, palladium, rhodium or ruthenium chlorides, copper cyanide, copper thiocyanide, copper oxide, copper sulfide, azetates copper or iron, iron citrate, iron sulfate, iron oxide, copper or iron acetylacetonate and the like, including hydrates of said salts.

Examples of organic amines that may be used in conjunction with transition metal salts are aliphatic amines such as n-butylamine, diisopropylamine, triethylamine, cyclohexylamine, benzylamine, ethylenediamine, ethanolamine and the like, aromatic amines such as aniline, toluidine and the like, heterocyclic amines such as pyridine, as well as amine salts such as diethylamine hydrochloride and the like. In view of the availability of materials and optimum yield, a combination of a transition metal halide and an aliphatic amine, especially ferric chloride hexahydrate and n-butylamine, is preferred. For maximum yield of the desired product, it has been found convenient to use more than about 1.5 moles, preferably between 2 and 10 moles of organic amine per mole of the transition metal salt. Generally, the transition metal catalyst can be used in a catalytic amount of about 0.01%, based on the number of moles of gamma-unsaturated carboxylate, but a higher concentration increases the reaction rate, and preferably 10% or more is used.

If a free radical is used, approximately equimolar amounts of starting materials are used. Generally, the reaction is carried out in the absence of a solvent, but solvents which do not adversely affect the reaction, such as, for example, carbon disulfide or hydrocarbon solvents, such as benzene or toluene, may also be used. The reaction can also be carried out in the presence of an excess amount of carbon tetrachloride as solvent, the excess being isolated and recycled. The reaction is generally carried out at a molar ratio of carbon tetrachloride to gamma-unsaturated carboxylate between 1: 1 and 4: 1.

When the catalysis is carried out by light, the reaction is carried out at a temperature between 25 ° and 100 ° C. When free radicals are used as catalysts, the reaction is generally carried out at a temperature between about 50 ° C and 150 ° C.

When transition metal salts or a coordination complex thereof are used as catalyst, the reactants may be used in approximately equimolar amounts, but carbon tetrachloride may also be used in excess. Solvents which do not adversely affect the reaction or product may optionally be used for the reaction. Suitable solvents include, for example, acetonitrile, dimethylformamide, alcohols, aliphatic hydrocarbons, aromatic hydrocarbons and the like. Alternatively, carbon tetrachloride may be used as the solvent. as a reactant, when the tetrahalogenated carbon is a liquid. If a solvent other than an excess of carbon tetrachloride is used, a polar solvent is preferred, as this generally increases the yield. The electron donor metal salt coordination complex is usually more preferred than the salt itself, butylamine is preferred as the donor, and ferric chloride hexyhydrate is the preferred salt. When the metal salt or coordination complex is used as a catalyst, the reaction is carried out at a temperature of 50 to 200 ° C, preferably a temperature of 70 to 150 ° C.

Coordination complex catalysts are preferable to free radicals, since their activity remains the same for a long time and can also be used again.

Stage 3

Step 3 involves the base-induced dehydrohalogenation of gamma-halocarboxylate B, to form dihalinyl vinyl cyclopropanecarboxylate C, via intermediates i, χ or δ, included in formula I, i.e., compounds which are used as starting compounds in the process of the invention. When converting B to C, two moles of HX acid are eliminated, and the elimination can be performed by eliminating one mole each.

The structure of gamma-halocarboxylate B is predetermined by the structures of the materials used in steps 1, 1 'and 2.

For the purposes of the procedure under Step 3

3

R @ 1 and R @ 2 are as defined above, R @ ⁶ is hydrogen,

R is hydrogen, methyl or ethyl.

If dihalogen vinyl cyclopropanecarboxylate is to be prepared which can readily be converted to pyrethroid insecticides of the type represented by structures II and III. gamma-haloA K7 oo carboxylate. is selected so that R ¹ ', R, R and R' are hydrogen, BT and R ^j are methyl and X is chlorine. Among these compounds was the new compound, ethyl 3,3-dimethyl-4,6,

6,6-tetrachlorohexanoate, found to be particularly suitable.

The type and quality of the base to be used, the solvent and the temperature depend on whether the reaction product is one of the intermediates X, Ϊ or Z.

In step 3 to form the starting product X, the reaction is carried out at a temperature of up to 25 ° C to avoid formation of the product X formed over X, and the gamma-halogen atom in B usually has a higher atomic number, such as bromine or iodine. Usually, the use of aprotic solvents favors the formation of X, and as such diethyl ether, tetrahydrofuran, dimethylformamide, dimethylsulfoxide and the like can be used. Any of the bases mentioned above for the preparation of dihalvinylcyclopropaharboxylate C can be used. Generally, between 1 and 2 moles of base per mole of gamma-halocarboxylate may be used, for example about 1.2 moles of base per mole of gamma-halocarboxylate is used.

In order to carry out the process of step 3 so as to form the starting product from gamma-halocarboxylate B, generally polar aprotic solvents and higher temperatures are used, a combination of sodium ethoxide in dimethylformamide and a temperature between 25 and 150 ° C, preferably 50 and 150 Deň: 32 ° C. The starting product X can also be prepared from the starting product X by heating the starting product or using a catalytic amount of acid. Below 50 ° C, the reaction proceeds slowly, while above 200 ° C unwanted by-products are formed. The effective temperature is between 00 and 170 ° C. Examples of acid catalysts that can be used for isomerization are aliphatic acids such as acetic acid, propionic butyric, isobutyric and the like, phenols such as phenol, hydroquinone and the like, Lewis acids such as aluminum chloride, zinc chloride and the like. acids are generally more preferred than Lewis acids since they give higher yields. The acid catalyst is generally used in an amount of from 0.05 to 10 mol. It is believed that the combination of an acid catalyst with thermal treatment increases the isomerization rate. It is not necessary for the isomerization to be carried out in the presence of a solvent, but optionally solvents that do not adversely affect the reaction or product may be used, for example, benzene, toluene, xylene, tetralin, petroleum ether, dimethoxyethane, di (methoxyethyl) ether and the like.

The process of step 3 is also used to prepare the starting product Z from gamma-halocarboxylate B using sodium or potassium tert-butoxide as the base, preferably using an excess to gamma-halocarboxylate. As solvents, benzene, dioxane, dimethylformamide or tetrahydrofuran can be used. Tert-butyl alcohol can also be used, especially in combination with benzene. The reaction is successfully carried out at a temperature of from 25 to 50 ° C.

To prepare dihalinyl vinyl cyclopropanecarboxylate C from any of the starting products X, Y or Z, compound B is reacted with an anhydrous base, including, for example, sodium hydroxide and potassium hydroxide, the solvent being anhydrous, alkali metal alkoxides such as sodium ethoxide, sodium methoxide, tert-butoxide. sodium hydride, potassium tert-butoxide, and the like, either preformed or directly prepared, sodium hydride, sodium naphthalenate, and the like. Sodium hydride or an alkali metal alkoxide are particularly useful. The reaction uses at least 1.5 molar equivalents of base, for example 2 to 5 molar equivalents per mole of gamma-halocarboxylate. The process is preferably carried out in a solvent such as methanol, ethanol, t-butanol and the like, as well as ethers such as diethyl ether, tetrahydrofuran, dimethoxyethane and the like.

It has been found that the ratio of cis to trans isomers in the final product varies within an unexpected range simply according to the temperature used. For example, if the combination of base and solvent is sodium tert-butoxide in tetrahydrofuran and the reaction is carried out at a temperature of about 0 ° C, the cis: trans ratio is about 50:50, while if the reaction is carried out at near room temperature from intermediate Y, cis: trans about 10:90.

The process of the invention is illustrated in more detail in the following examples.

Example 3

Synthesis of ethyl 2- (p, p-dichlorvinyl) -3,3-dimethyleyclopropanecarboxylate

A. Preparation of ethyl 3,3-dimethyl-4-pentenoate

A mixture of 12.9 g (0.15 mol) of 3-methyl-2-buten-1-ol, 48.6 g (0.3 mol) of ethyl orthoacetate and 0.5 g of hydroquinone is heated to 140 ° C with stirring for 20 hours. Ethanol is running Heating distilled off. At the end of 20 hours, the mixture was distilled under reduced pressure, and after removal of unreacted ethyl orthoacetate, 17.6 g (75% yield) of ethyl 3,3-dimethyl-4-pentenoate were obtained, m.p. 74-78 ° C / 50 mm Hg.

B. Addition of bromotrichloromethane to ethyl 3,3-dimethyl-4-pentenoate mg azobisisobutyronitrile was added to a solution of 1.56 g (0.01 mol) of ethyl 3,3-dimethyl-4-pentenoate in 5 mL of bromotrichloromethane. The mixture was then heated at 130 ° C for 10 hours. Unreacted bromotrichloromethane was evaporated and the residue was distilled under reduced pressure to give 3.2 g (89% yield) of ethyl 4-bromo-6,6,6-trichloro-3,3-dimethylhexanoate, mp 102-105 ° C. 13,3 Pa.

Analysis for C ₁ q ^ ^ Og gBrCl Calculated: C 33.88, H 4.55 »Found: C 33.83, H 4.35.

NMR δppm (CCl ₄ ): 4.49 (q, 1H), 4.08 (q, 2H), 3.29 (s, 1H), 3.32; d, 1Ή), 2.42 (q, 1H); 2H),. 1.35-1.13 (m, 9H).

C. Simultaneous cyclization and dehydroohlorination

A solution of 709 mg (2 mmol) of ethyl 4-bromo-6,6,6-trichloro-3,3-diaethylhexanoate in 5 ml of anhydrous tetrahydrofuran was added dropwise to a suspension of 448 mg (4 mmol) of potassium tert-butoxide in 15 ml of tetrahydrofuran and the mixture was heated to boiling point for two hours. The mixture was then allowed to cool and an additional 220 mg of potassium tert-butoxide was added. The mixture was heated to boiling for one hour and then an additional 110 mg of potassium tert-butoxide was added and the mixture was heated to boiling again for one hour. The mixture was poured into ice water and extracted with diethyl ether. The ether extract is dried over anhydrous magnesium sulfate, the ether is distilled off and the residue is distilled under reduced pressure to give 330 mg ¢ 70% yield of ethyl 2- (β, β-dihlorovinyl) -3,3-dimethylcyclopropanecarboxylate, bp 86 ° C / 66, 6 Pa.

Analysis:

NMR δppm (CCl ₄ ): 6.22 (d, 0.5H), 5.56 (d, 0.5H), 4.05 (bq, 2H), 2.35-1.05 (m, 11H);

Ιδ (cm ^-1 ): 3,060, 1,730, 1,615, 1,230, 1,182, 1,145, 1,120, 1,087, 925, 860, 817,

790, 765, 702, 650.

Example 4

Synthesis of ethyl 2- (p, P-dibromvinyl) -3,3-dimethyloyclopropanecarboxylate

A. Addition of carbon tetrabromide to ethyl 3,3-dimethyl-4-pentenoate mg azobisisobutyronitrile is added to a mixture of 1.56 g (0.01 mol) of ethyl 3,3-dimethyl-4-pentenoate and 3.32 g ( 0.01 mol) of carbon tetrabromide. The mixture was heated at 120 ° C for five hours under argon. The mixture was then allowed to cool and purified by silica gel column chromatography using a 1: 1 mixture of benzene and hexane as eluent. Concentration of the eluate gave 3 g (60% yield) of ethyl 4,6,6,6-tetrabromo-3,3-dimethylhexanoate.

Analysis for C ^ HH ^B ^Og!

calculated: C 24.62, H 3.31, Br 65.51;

Found: C 24.87, H 3.25, Br 65.60.

NMR δppm (CCl ₄ ): 4.35 (q, 1H), 4.07 (q, 2H), 3.55 (m, 2H), 2.43 (q, 2H), 1.40-1.15 (m, 9H).

B. Simultaneous cyclization and dehydrobromation

To 1.46 g of ethyl 4,6,6,6-tetrabromo-3,3, -dimethylhexanoate in 16 ml of absolute ethanol is added dropwise a solution of 5 ml of ethanol containing 0.62 g of sodium ethoxide. The mixture was cooled with ice during the addition, then allowed to warm to room temperature and stirred for six hours. An additional 2.5 mL of ethanolic sodium ethoxide solution (about 0.3 g) was added and the mixture was stirred for an additional 12 hours. The mixture was poured into ice water and extracted with diethyl ether. The ether solution was dried over anhydrous magnesium sulfate and distilled to give 0.77 g (79% yield) of ethyl 2- (β, β-dibromvinyl) -3,3-dimethylcyclopropanecarboxylate, b.p. 98-101 ° C / 1 mm Hg.

For ^C 10 ^H 14 ^Br 2 O 2 ^: calculated: C 36.84, H 4.33, Br 49.02;

Found: C 37.07, H 4.40, Br 49.27.

NMR 6ppm (CC1 _4): 6.12 (d, 1H), 4.08 (q, 2H), 2.20 to 1.40 (m, 2H), 1.37 - 1.10 (m, 9H) .

ID (cm "): 1,725, 1,223, 1,175, 855, 800, 762.

Example 5

Synthesis of ethyl 3,3-dimethyl-4-pentenoate

A. With phenol as a catalyst

A mixture of 43 g (0.5 mol) of 3-methyl-2-buten-1-ol, 97 g (0.6 mol) of ethyl orthoacetate and 7.0 g (0.075 mol) of phenol is heated to 135-140 with stirring. ° C for 9 to 10 hours. During the course of the reaction, ethanol is distilled off from the reaction mixture. After the ethanol evolution had ceased, the heating was stopped and the mixture was allowed to cool to room temperature. The mixture was then dissolved in diethyl ether and the ethereal solution was treated with 1 N hydrochloric acid to decompose unreacted ethyl orthoacetate. The ether solution was washed successively with a saturated aqueous solution of sodium bicarbonate and water, and then dried over magnesium sulfate. The dried solution was concentrated and distilled under reduced pressure to give 60.8 g (78% yield) of ethyl 3,3-dimethyl-4-pentenoate, b.p. 57-60 ° C / 1.5 kPa.

Analysis:

NUR 8ppm (CC1 _4): 6.15 to 5.60 (dd, 1H), 5.15 to 4.68 (m, 2H), 4.02 (q, 2H), 2.19 (s, 2H) 1.45-1.05 (m, 9H).

ID (cm "): 3,090, 1,740, 1,640, 1,370, 1,240, 1,120, 1,030, 995, 910.

B. Using other catalysts

In the methods described in Examples IA and 5A, the following catalysts can be successfully used in the preparation of ethyl 3,3-dimethyl-4-pentenoate: boric acid, phosphonic acid, isobutyric acid, mercuric acetate and hydroquinone.

C. Without catalyst

O

A mixture of 4.3 g of 3-methyl-2-buten-1-ol and 8.1 g of ethyl orthoacetate is heated with stirring. The temperature was allowed to rise slowly from room temperature to 165 ° C over two hours, during which time 2.21 g of ethanol was collected. The temperature was maintained at 165 ° C for 26 hours, during which time 1.52 g of ethanol were collected. The reaction mixture was allowed to cool and diluted with diethyl ether. The ether solution was washed successively with dilute hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution. The washed solution was dried over magnesium sulphate and distilled to give 4.03 g (52% yield) of ethyl 3,3-dimethyl-4-pentenoate, b.p. 80-85 ° C / 6.9 kPa.

D. Via 1,1-diethoxy-1- (3-methyl-2-buten-1-yloxy) ethane (intermediate W)

1. Preparation of 1,1-diethoxy-1- (3-methyl-2-buten-1-yloxy) ethane

A mixture of 4.3 g of 3-methyl-2-buten-1-ol and 16.2 g of ethyl orthoacetate is heated with stirring. The pdmal temperature rises to 120 ° C over two hours, during which time 1.8 g of ethanol are released and removed. Heating at 120 ° C was continued for 30 minutes, followed by distillation

212300 16 removes 8.5 g of unreacted ethyl orthoacetate (at 50-65 ° C / 7.6 kPa) to give 4.25 g of 1,1-diethoxy-1- (3-methyl-2-buten-1-yloxy) of ethane, b at 75 to 76 ° C / 0.8 kPa.

Analysis for ^c 22 ^H 22 ® 3 ^! calculated :. C 65.31, H 10.96} found: C 65.52, H 10.74.

2. Preparation of ethyl 3,3-dimethyl-4-pentenoate

A mixture of 2.02 g of 1,1-diethoxy-1- (3-methyl-2-buten-1-yloxy) ethane and 20 mg of phenol is heated at 150-160 ° C for 12 hours, during which time ethanol is released. Distillation of the residue gave 1.12 g (72% yield) of ethyl-3,3-dimethyl-4-pentenoate, b.p. 80-83 ° C / 7.6 kPa.

Similarly, in the absence of phenol, 2.02 g of 1,1-diethoxy-1- (3-methyl-2-buten-1-yloxy) ethane was heated at 150-160 ° C for 20 hours. Distillation yielded 1.06 g (68% yield) of ethyl 3,3-dimethyl-4-pentenoate, b.p. 87-89 ° C / 8.2 kPa.

Example 6

Synthesis of other gamma-unsaturated carboxylates

The following gamma-unsaturated carboxylates can be prepared by the procedures described in Examples 1A and SA:

A. Ethyl 2,3,3-trimethyl-4-pentenoate

b. 90 to 92 ° C / 6.0 kPa

Analysis:

NMRδppm <CC1 _4): 6.10 to 5.55 (dd, 1H), 5.10 to 4.70 (m, 2H), 4.05 (q, 2H), 2.25 (q,

1H), 1.22 (t, 3H), 1.20 - 0.96 (m, 9H).

B. Ethyl 2-methyl-3-phenyl-4-pentenoet

b. 104 ° C / 0.2 kPa

Analysis:

APPM NMR (CC1 _4): 7.12 (b, s, 5H), 6.30 - 4.80 (m, 3H), 4.26 - 3.20 (m, 3H), 3.00 - 2 50 (m, 1H); 1.40-0.78 (m, 6H).

C. Ethyl 2,3-dimethyl-4-pentenoate

b. 90 to 92 ° C / 8.6 kPa

Analysis:

NMRSppm (CC1 _4): 5.85 to 5.37 (m, 1H), 5.04 to 4.78 (m, 2H), 4.02 (q, 2H), 2.56 - 1.98 (m 1 H, 1.22 (t, 3H), 1.20-0.88 (m, 6H).

D. Methyl 2-ethyl-3,3-dimethyl-4-pentenoate

b., 91-94 ° C / 6.0 kPa

Analysis:

NMR δppm (CCl ₄ ): 5.78 (dd, 1H), 5.13-4.70 (m, 2H), 3.61 (s, 3H), 2.32-1.98 (m, 1H), 1.90-1.20 (m, 2H), 1.02 (s, 6H), 0.80 (bt, 3H).

E. Ethyl 3-phenyl-4-pentenoate

b. 76-77 ° C / 26.6 kPa.

F. Ethyl 3-methyl-4-pentenoeth

b. 85 to 89 ° C / 8.4 kPa.

G. Ethyl 2,3,3-trimethyl-4-hexenoate

b. 97-99 ° C / 4.9 kPa.

H. Ethyl 2,3,3,5-tetramethyl-4-hexenoate

b., 115-117 ° C / 5.3 kPa.

I. Ethyl 2,3,3-trimethyl-4-heptenoate

b. 120 to 122 ° G / 6.0 kPa.

J. Ethyl 2,3,3-trimethyl-4-octenoate

b., 128-131 ° C / 5.3 kPa.

K. Methyl 2-ethyl-3,3-di-methyl-4-hexenoate

b. 97 to 100 ° C / 4.0 kPa.

L. Ethyl 3,3-l-dimethyl-4-hexenoate

b. 103-105 ° C / 7.6 kPa.

M. Ethyl-3,3, dimathyl-4-heptenoate

b. 103-107 ° C / 5.0 kPa.

N. Ethyl 3,3-dimethyl-4-octenoate

b. 114-116 ° C / 4.4 kPa.

O. Ethyl 3,3,5-trimethyl-4-hexenoate

b. 100 to 104 ° C / 6.0 kPa.

P. Bthyl-5-cyclopentyl-3,3-dimethyl-4-pentenoate

b. 119-123 ° C / 2.0 kPa.

Q. Ethyl 3,3,6-trimethyl-4-heptenoate

b. 90 to 93 ° C / 4.0 kPa.

R. Ethyl 3,3,5-trimetbyl-4-heptenoate

b. 100 to 104 ° C / 2.6 kPa.

S. Benzyl 3,3-dimethyl-4-pentenoate

Following the procedure of Example 1B, 810 mg of benzyl alcohol was reacted with 1122 mg of ethyl 3,3-dimethyl-4-pentenoate in the presence of 48 mg of sodium ethoxide in 30 ml of toluene and obtained

1.0 g (65% yield) of benzyl 3,3-dimethyl-4-pentenoate, m.p. 92 DEG-98 DEG C./0.3 mbar.

For C 8 HH GOOO: C, 76.49; H, 8.51;

Found: G 76.79, H 8.25.

NMR 8 ppm (CCl +): 7.29 (bs, 5H), 5.84 (dd, 1H), 5.05 (s, 2H), 5.05-4.70 (m, 2H),

2.22 (s, 2H); 1.06 (s, 6H).

T. The following gamma-unsaturated carboxylates can be prepared as described above:

1. Isopropyl 2-benzyl-3,3-dimethyl-4-pentenoate;

2. E-butyl-3,3-dimethyl-4-pentenoate

3. Ethyl 2-cyclopentyl-4-pentenoate;

4-ethyl-3-ethyl-3-methyl-4-pentenoate

5. Ethyl 3-ethyl-3-isopropyl-4-pentenoate

6. ethyl-3-n-butyl-3-propyl-4-pentenoate,

7. Ethyl 3-methyl-3-vinyl-4-pentenoate

8. ethyl 3- (2-butenyl) -3-ethyl-4-pentenoate;

9. ethyl 2- (1-vinylcyclohexyl) acetate,

10. Ethyl 3- (2-butynyl) -3-methyl-4-pentenoate;

II. ethyl 3-cyclohexyl-3-methyl-4-pentenoate,

12. Ethyl 3-benzyl-3-methyl-4-pentenoate

13 · ethyl 2-benzoyl-3-carbethoxy-4-pentenoate,

14. Ethyl 3-acetyl-4-pentenoate

15. Ethyl 3-benzoyl-4-pentenoate

16. Ethyl 3- (N, N-dimethylcarboxamido) -4-pentenoate

17. ethyl 3- (N-ethyl-N-isopropylcarboxamido) -4-pentenoate;

18. Ethyl 3-cyano-2-ethynyl-4-pentenoate;

19. ethyl 3-chloromethyl-4-pentenoate,

20. Ethyl 3- (2-bromoethyl) -4-pentenoate

21. ethyl 3- (1-fluoro-1-methylethyl) -4-pentenoate,

22. ethyl 3,3-diphenyl-4-pentenoate,

23. ethyl 5-allyl-3,3-dimethyl-4-hexenoate;

24. ethyl-3,3-dimethyl-5-phenyl-4-pentenoate;

25. methyl 5-cyclohexyl-4-pentenoate,

26. ethyl 4-cyclohexylidene-3,3-dimethylbutanoate,

27. ethyl 5-carbomethoxy-3,3-di-methyl-4-pentenoate;

28. ethyl 5- (2-butynyl) -3,3-dimethyl-5-isopropoxy-4-pentenoate;

29. Ethyl 5-acetyl-3,3-dimethyl-4- pentenoate;

30. ethyl 5-benzyl-3,3-dimethyl-4-pentenoate;

31. ethyl-3,3-dimethyl-5- (N, N-dimethylcarboxamido) -4-pentenoate;

32. ethyl 5-cyano-3,3-dimethyl-4-pentenoate,

33. ethyl 5-benzoyl-3,3-dimethyl-4-pentenoate,

34. ethyl 5- (2-bromoethyl) -3,3-dimethyl-4-pentenoate;

35. ethyl 2,2,3,3-tetramethyl-4-pentenoate;

36. ethyl 2,3,3-trimethyl-2-isopropyl-4-pentenoate;

37. ethyl 2-chloromethyl-2-phenyl-4-pentenoate;

38. ethyl 3,3-dimethyl-2,2-diphenyl-4-pentenoate,

39. ethyl-2-carbomethoxy-3,3-dimethyl-4-pentenoeth;

40. Ethyl 2-acetyl-3,3-dimethyl-4-pentenoate

41. ethyl-2-butyryl-3,3-dimethyl-4-pentenoeth;

42. Ethyl 3,3-dimethyl-2- (N, N-dimethylcarboxamido) -4-pentenoate

43. Ethyl 2-cyano-3,3-dimethyl-4-pentenoate

44. Ethyl 1-allyl-1-cyclohexanecarboxylate

45. methyl 2-cyano-3-ethyl-4-heptenoate,

46. Isopropyl 5-chloromethyl-2-vinyl-4-pentenoate

47. methyl 3-cyano-2- (N, N-dimethylcarboxamido) -5- (2-fluoroethyl) -4-hexenoate.

Example 7

Synthesa ethyl 4,6,6,6-tetrahalogen-3,3-dimethylhexanoates by addition of tetrahalogenides carbonated to ethyl 3,3-dimethyl-4-pentenoates

A. Addition of carbon tetrachloride in the presence of ferric chloride, bytlamine and acetonitrile

Example 2A is repeated

1. with acetonitrile as the solvent instead of dimethylformamide; and

2. without solvent, and ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate was obtained in yields of 82% and 72%, respectively.

B. Addition of carbon tetrabromide in the presence of ferric chloride, butylamine and dimethylformamide

Following the procedure described in Example 2A, 3.32 g (10 mmol) of carbon bromide was added to 1.56 g (10 mmol) of ethyl 3,3-dimethyl-4-pentenoate to give 2.9 g (60% yield) of ethyl. -4,6,6,6-tetrabromo-3,3-dimethylhexanoate, bp 144 ° C / 26.6 Pa.

C. Addition of bromotrichloromethane in the presence of iron (III) chloride, butylamine and di-methylformamide

Example 7B was repeated using 2.0 g (10 mmol) of bromotrichloromethane instead of carbon tetrabromide to give 3.1 g (70% yield) of ethyl 4-bromo-6,6,6-tri-chloro-3,3-dimethylhexanoate mp 128 ° C / 33.3 Pa.

D. Addition of carbon tetrachloride in the presence of ferric chloride, butylamine and dimethylformamide

A mixture of 94.5 mg (0.35 mmol) of ferric chloride hexahydrate, 102 mg (1.4 mmol) of butylamine, 1.2 ml of dimethylformamide, 780 mg (5 mmol) of ethyl 3,3-dimethyl-4-pentenoate and 1 54 g (10 mmol) of carbon tetrachloride were heated in a sealed tube at 120 ° C for 15 hours. The contents of the tube were cooled to room temperature and then diluted with carbon tetrachloride to a final volume of 5 ml. Gas chromatographic analysis of the solution revealed that ethyl 4,6,6,6-tetrachloro-3,3-dimethyl-hexanoate was formed in 95% yield.

E. Other additions of carbon tetrachloride in the presence of other salts and butylamine

Example 7D is repeated and ferrous chloride, cuprous chloride and cuprous cyanide are used in place of ferric chloride. Ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate is obtained in 82%,

76% and 72% yield (as analyzed by gas chromatography).

Repeat Example 7D using 690 mg of absolute ethanol instead of dimethylformamide to give ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 80% yield.

F. Addition of carbon tetrachloride in the presence of benzoyl peroxide

A mixture of 3.12 g (0.02 mol) of ethyl 3,3-dimethyl-4-pentenoate, 30 ml of carbon tetrachloride and 50 mg of benzoyl peroxide was heated to 140 DEG C. in a pressure vessel for 4 hours. The pressure vessel was cooled, an additional 50 mg of benzoyl peroxide was added and reheated to 140 ° for 4 hours. After cooling to room temperature, the mixture was washed successively with a saturated aqueous solution of sodium bicarbonate and water. The mixture was dried over magnesium sulphate and distilled to give 4.56 g (74% yield) of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate (b.p. 107-108 °).

G. Photocatalysed addition of carbon bromide

A mixture of ethyl 3,3-dimethyl-4-pentenoate (0.78 g) and carbon tetrabromide (3.32 g) was irradiated with a 200 Watt visible light source for 10 hours at room temperature under continuous argon purge. The resulting dark brown oil was purified by column chromatography to give 1.46 g (59.8% yield) of ethyl 4,6,6,6-tetrabromo-3,3-dimethylhexanoate.

Example 8

Addition of carbon halide to other gamma-unsaturated carboxylates

A. Ethyl 4,6,6,6-tetrachloro-2,3,3-trimethylhexanoate

A mixture of 1.36 g (8 mmol) of ethyl 2,3,3-trimethyl-4-pentenoate, 20 ml of carbon tetrachloride and 50 ml of benzoyl peroxide is placed in a pressure vessel. The vessel was purged with argon, sealed, and heated at 130-140 ° C for five hours. The pressure vessel is then cooled at five-hour intervals, an additional 50 mg of benzyl peroxide is added, the reactor is purged, resealed and heating is continued until a total of 200 mg of benzoyl peroxide is added. After 20 hours of reaction, the mixture was allowed to cool and was washed successively with a saturated aqueous solution of sodium bicarbonate, a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Distillation yielded 1.81 g (70% yield) of ethyl 4,6,6,6-tetrachloro-2,3,3-trimethylhexanoate, b.p.

Analysis:

NMR δ ppm (CCl ₄ ): 4.43-3.85 (m, 3H), 3.45-3.00 (m, 2H), 2.97-2.63 (m, 1H), 1.35 0.95 (m, 12H);

The same product was prepared (49% yield) by reaction with ferric chloride hexahydrate, n-butylamine and dimethylformamide instead of benzoyl peroxide.

B. Ethyl 4,6,6,6-tetrachloro-3-methylhexanoate

Following the procedure of Example 8A, 3-methyl-4-pentenoate, carbon tetrachloride and benzoyl peroxide were reacted to give ethyl 4,6,6,6-tetrachloro-3-methylhexanoate (63% yield), bp 103-105 ° / 53, 3 Pa.

Analysis:

NMR δ ppm (CCl ₄ ): 4.60-4.30 (m, 1H), 4.11 (q, 2H), 3.25-3.00 (m, 2H), 2.75-2.10 (m, 3H), 1.26 (t, 3H), 1.22-0.95 (m, 3H).

This product was also prepared in 40% yield using ferric chloride as the catalyst of Example 7D.

C. Ethyl 4-bromo-6,6,6-trichloro-2,3,3-trimethylhexanoate

A mixture of 1.70 g (0.01 mol) of ethyl 2,3,3-trimethyl-4-pentenoate, 5 ml of bromotrichloromethane and 50 mg of benzoyl peroxide was heated to reflux for 10 hours under argon. Distillation of the mixture then afforded 3.0 g (81% yield) of ethyl 4-bromo-6,6,6-trichloro-2,3,3-trimethylhexanoate, b.p. 1.5-120 ° / 1 mm Hg.

Analysis: '

NMR δ ppm (CCl ₄ ): 4.60-3.80 (m, 3H), 3.70-3.10 (m, 2H), 3.10-2.70 (m, 1H),

1.60-0.95 (m, 12H).

D. Ethyl 4-bromo-6,6,6-trichloro-3-methylhexanoate

Following the procedure of Example 8C, ethyl 3-methyl-4-pentenoate, bromotrichloromethane and benzoyl peroxide were reacted to give ethyl 4-bromo-6,6,6-triohloro-3-methylhexanoate (55% yield), bv 110-113 ° / 66.6 Pa.

Analysis:

NMR δ ppm (CCl ₄ ): 4.65-4.35 (m, 1H), 4.14 (q, 2H), 3.45-3.10 (m, 2H), 2.65-2.10 (m, 3H), 1.24 (t, 3H), 1.25-0.95 (m, 3H).

The following compounds can also be prepared by the procedure of Example 8A using benzoyl peroxide as a catalyst.

E. Ethyl 4,6,6,6-tetrachloro-2,3-dimethylhexanoate

b. 95-98 ° / 40 Pa

Analysis:

NMR δ ppm (CCl ₄ ): 4.52-4.20 (m, 1H), 4.06 (bq, 2H), 3.20-3.00 (m, 2H), 2.75-1.82 (m, 2H), 1.40-0.91 (m, 9H).

F. Ethyl-4,6,6,6-trachlor-3-phenylhexanoate m.p.

b. v. 143 to 45 ° / 40 Pa

Analysis:

NMR δ ppm (CCl ₄ ): 7.50 - 7.15 (m, 5H), 4.85 - 4.34 (m, - 3.42 (m, 1H), 3.40 - 2.60 (m , 4H),

1HJ, 4.33-3.80 (m, 2H), 3.78 1.37-0.95 (m, 3H).

G. Ethyl 4,6,6,6-tetrachloro-2-methyl-3-phenylhexanoate

b. 160-165 ° / 0.13 kPa

Analysis:

NMR δ ppm (CCl ₄ ): 7.45-7.00 (m, 5H), 4.75-4.30 (m, 1H), 4.22-2.20 (m, 6H), 1.42 0.64 (m, 6H).

H. Methyl 4,6,6,6-tetrachloro-2-ethyl-3,3-dimethylhexanoeth

b. 93-97 ° / 26.6 Pa

Analysis:

NMR δ ppm (CCl ₄ ): 4.10 (dd, 1H), 3.67 (s, 3H), 3.45-2.30 (m, 3H), 1.95-1.20 (m, 2H) 1, 20 - 0.70 (m, 9H).

Following the procedure of Example 8A, using the ferric chloride hexahydrate catalyst, the following compounds were prepared:

I. Benzyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate

Analysis for ^C 15 ^H 18 ° ^{C 1} 2 ^4: Calculated: C 48.42, H 4.88, Cl 38.11;

Found C 48.69, H 5.13, Cl 38.42.

NMR δ ppm (CCl ₄ ): 7.22 (bs, 5H), 4.98 (s, 2H), 4.31 (dd, 1H), 3.32-2.80 (m, 2H),

2.58 (d, 1H); 2.28 (d, 1H), 1.17 (s, 3H), 1.08 (s, 3H).

<J. The following tetrahalocarboxylates can be prepared according to the above methods:

1. ethyl 4,6,6,6-tetrachlorgexanoate;

2. ethyl 4,6,6,6-tetrachloro-3-ethyl-3-methylhexanoate;

Third ^and ethyl _4,6), 6,6-tetrachloro-3 "-ethyl-3-isopropylhexanoát,

4. Ethyl 3-t-butyl-4,6,6,6-tetrachloro-3-propylhexanoate;

5. ethyl 4,6,6,6-tetrachloro-3,3-diphenylhexanoate;

6. Ethyl 2-f- (1,3,3,3-tetrachloropropyl) cyclohexyl acetate;

7. ethyl 4,6,6,6-tetrachloro-3-cyclobutylhexanoate;

8. methyl 3-benzyl-4,6,6,6-tetrachlorohexanoate;

9. Isopropyl-3-benzoyl-4,6,6,6-tetrabromohexanoate;

10. Ethyl 3-carbethoxy-4,6,6,6-tetrachlorohexanoate

II. Ethyl 3-acetyl-4,6,6,6-tetrachlorohexanoate

12. Ethyl 3-butyryl-4,6,6,6-tetrachlorohexanoate

13. Ethyl 4,6,6,6-tetrachloro-3- (N, N-dimethylcarboxamido) hexanoate

14. Ethyl 4,6,6,6-tetrachloro-3- (N-ethyl-N-isopropylcarboxamido) hexanoate

15. Ethyl 3-cyano-4,6,6,6-tetraohlorohexanoate

16. ethyl 4,6,6,6-tetra-chloro-3-chloromethylhexanoate;

17. ethyl 2-benzyl-3- (2-bromoethyl) -4,6,6,6-tetrachlorohexanoate;

18. ethyl 4,6,6,6-tetrechloro-3- (1-fluoro-1-methylethyl) hexanoate,

19. ethyl 2-benzoyl-4-bromo-6,6,6-trichlorohexanoate,

20. Methyl-6,6,6-trichloro-2-cyclohexyl-4-iodohexanoate

21. Ethyl 4,6-dichloro-6,6-difluorohexanoate

22. methyl 4-bromo-6,6,6-trichloro-2,2,3,3-tetramethylhexanoate;

23. methyl 4-bromo-6,6,6-trichloro-2-isopropyl-2,3,3-trimethylhexanoate;

24. Isopropyl 6,6,6-trichloro-4-iodo-2-phenylhexanoate

25. Isopropyl 6,6-dichloro-6-fluoro-4-iodo-3-methyl-2,2-diphenylhexanoate

26. ethyl-2-carbomethoxy-4,6,6,6-tetrachlorohexanoet;

27. ethyl 2-acetyl-4,6,6,6-tetrachloro-3,3-dimethylhexanoate;

28. Ethyl 2-butyryl-4,6,6,6-tetrachloro-3,3-dimethylhexanoate;

29. ethyl-4,6,6,6-tetrachloro-2- (N, N-dimethylcarboxamido) hexanoet;

30. Ethyl 4,6-dibromo-2-cyano-6,6-difluoro-3,3-dimethylhexanoate

31. ethyl 1- (2-bromo-4,4,4-trichloro-1,1-dimethylbutyl) -1-cyclohexanecarboxylate;

32. t-butyl 4-bromo-6,6,6-trichloro-2-cyano-3-ethylhexanoate.

Example 9

Direct synthesis of ethyl 2- (beta, -dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate from ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate

A. Use of potassium t-butoxide in tetrahydrofuran

A solution of 1.8 g (5.8 mmol) of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 2 ml of anhydrous tetrahydrofuran was added dropwise to a suspension of 1.3 g (11.6 mmol) of tert-butoxide. of potassium in 20 ml of anhydrous tetrahydrofuran. The mixture was then stirred at room temperature for one hour. An additional 0.65 g (5.8 mmol) of potassium tert-butoxide was then added and the mixture was heated under reflux for two hours. The mixture was allowed to cool, poured into ice water and extracted with diethyl ether. After drying over magnesium sulphate, the ether solution is distilled to give 0.93 g (68% yield) of ethyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate, b.

B. Using sodium tert-butoxide in tetrahydrofuran

A suspension of 2.11 g (0.011 mol) of sodium tert-butoxide in 40 ml of anhydrous tetrahydrofuran is cooled to 0 ° and a solution of 1.55 g (0.005 mol) of ethyl 4,6,6,6-tetrachloro-3 is added dropwise to the cold suspension. 3-dimethylhexanoate in 10 ml of anhydrous tetrahydrofuran. After the addition was complete, the mixture was stirred at 0 ° for two hours. The cold mixture was neutralized by addition of a solution of hydrogen chloride in diethyl ether. The solution was filtered and the filtrate was diluted with ether. The ethereal solution was washed with water, dried over magnesium sulfate and distilled to give 1.08 g (91% yield) of a mixture of cis and trans ethyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate, bp 63-66 ° / 26.6 Pa. The cis to trans ratio is 1: 1 by NMR spectrum.

C. Using sodium in ethanol

To a cold solution of 1.01 g (44 mmol) of sodium metal in 80 ml of absolute ethanol, 20 ml of an ethanol solution containing 6.2 g (20 mmol) of ethyl-4,6,6,6-tetrachloro-3 is added dropwise under ice-cooling, 3-dimethylhexanoate. After the addition was complete, the mixture was stirred at room temperature for one hour and then heated at reflux for 0.5 hours. The mixture was then cooled to 0 ° and neutralized by dropwise addition of hydrogen chloride in ethanol. The neutral mixture is filtered and the filtrate is concentrated to one tenth of the original volume. The thickened mixture was diluted with diethyl ether and the ethereal solution was washed successively with a saturated aqueous solution of sodium bicarbonate and brine. The washed solution was dried over anhydrous magnesium sulfate and distilled to give 4.47 g (94% yield) of ethyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate, m.p. 72-74 ° / 53.3. Pa · According to gas chromatography, the distribution of cis and trans isomers is 34% cis and 66% trans.

D. Using potassium in ethanol, ml of a solution containing 3.10 g (10 mmol) of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate in absolute ethanol is added dropwise to a cold solution of 860 mg (22 mmol) while cooling. of potassium in 80 ml of absolute ethanol. After the addition was complete, the mixture was stirred at room temperature for one hour and then heated to reflux for 0.5 hours. The mixture was worked up as in Example 9C to give 2.30 g (96% yield) of ethyl 2- (beta, beta-dichlorvinyl) -3,3-dimethyl-cyclopropanecarboxylate, which was a gas chromatographic mixture 26% cis and 74% trans isomers.

E. Using sodium in methanol

Example 9D was repeated using a solution of 575 mg (25 mmol) of sodium in 80 mL of absolute methanol to which was added 20 mL of a solution of 3.1 g (10 mmol) of ethyl-4,6,6,6-tetrachloro-3,3 -dimethylhexanoate in absolute methanol. 2.09 g (93% yield) of methyl 2- (beta, beta-diethylvinyl) -3,3-dimethylcyclopropanecarboxylate, bv 68-70 ° / 26.6 Pa, which contained 23% cis by gas chromatography, was isolated as product. 77% trans isomers.

K. Using potassium in methanol

Examples 9D are repeated using a solution of 860 mg (22 mmol) of potassium in 80 ml of absolute methanol and to this solution is added 20 ml of a solution of 3.1 g (10 mmol) of ethyl-4,6,6,6-tetrachloro-3, 3-dimethylhexanoate in absolute methanol. 2.13 g (95% yield) of methyl 2- (beta, beta-diohlorvinyl) -3,3-dimethyloyclopropanecarboxylate, which contains 25% cis and 75% trans isomers according to gas chromatography, is isolated as product.

Example 10

Synthesa ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate (Intermediate X) ml of anhydrous tetrahydrofuran solution containing 709 mg (2 mmol) of ethyl 4-bromo-6,6,6-trichloro-3, 3-Dimethylhexanoate was added dropwise to a suspension of 163 mg (2.4 mmol) of sodium ethoxide in 20 ml of anhydrous tetrahydrofuran. The mixture was stirred at room temperature for about 16 hours, poured into ice water, and the cold aqueous mixture was extracted with diethyl ether. The extract was dried over magnesium sulphate and then distilled to give 448 mg (82% yield) of ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate, m.p.

Analysis for C ^ HH ^ClgOg:

calculated: C 43.90, H 5.53, Cl 38.87;

Found: C 44.12, H 5.35, Cl 38.11.

NURáppm (CC1 _4): 6.13 (q, 2H), 4.07 (q, 2H), 2.29 (s, 2H), 1. 50-1. 00 (m, 9H).

Example 11

Synthesa ethyl 4,6,6-trichloro-3,3-dimethyl-5-hexanoate (intermediate Y)

A. From ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate

1. Using sodium ethoxide

A solution of 2.04 g of sodium ethoxide in 60 ml of dimethylformamide was added to a hot solution (140 DEG) of 3.1 g of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 20 ml of dimethylformamide. The mixture was held at 140 ° for two hours, then cooled to 0 ° neutralized with anhydrous hydrogen chloride and poured into ice water. The aqueous mixture was extracted with ether and the extract was washed successively with a saturated aqueous solution of sodium bicarbonate and sodium chloride. The washed extract was dried over magnesium sulfate and distilled to give 1.81 g (77% yield) of ethyl 4,6,6-trichloro-3,3-dimethyl-5-hexenoate, b.p.

2. Using 1,5-diazabicyclo (3,4,0) non-5-ene

A solution of 1.42 g of ethyl 4,6,6,6-tetrBchloro-3,3-dimethylhexanoate in 10 ml of anhydrous dimethylhexanoate in 10 ml of anhydrous dimethylformamide was added dropwise over 30 minutes to a stirred solution of 1.58 g of 1,5-diazabicyclo ( 3,4,0) non-5-ene in 10 ml of anhydrous dimethylformamide and the temperature is maintained at 0 °. The mixture was stirred for an additional two hours with cooling, poured into ice water and extracted with diethyl ether. The ethereal extract was washed with water, dried over anhydrous magnesium sulphate and distilled to give a liquid b at 87-90 ° / 16 Pa which, according to NMR spectral analysis, consisted of 800 mg of ethyl 4,6,6-trichloro-3,3-dimethyl-5. hexenoate and 160 mg of ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate. Combined yield 88%.

B. Rearrangement of ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate (Intermediate X)

1. Warming up

A solution of 547 mg (2 mmol) of ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate in 2 mL of tetralin was heated to 150 ° under argon for 24 h and then distilled to give 356 mg (65%). yield) ethyl 4,6,6-trichloro-3,3-dimethyl-5-hexenoate, mp 88-90 ° / 26.6 Pa.

Analysis for ^C 10 ^H 15 ° ^{C 1} 2 3 ^Calculated: C 43.90, H 5.53, Cl 38.87;

Found: C 44.18, H 5.39, Cl 38.65.

NMR δ ppm (CCl ₄ ): 5.96 (d, 1H), 4.85 (d, 1H), 4.06 (q, 2H), 2.41 (d, 1H), 2.23 (d, 1H),

1.23 (t, 3H); 1.11 (s, 6H).

IR (KBr, cm -1): 1735, 1613.

The same product was also prepared in a similar manner by heating in an inert atmosphere using bis (2-methoxyethyl) ether cells as solvent or without solvent.

2. Using acid catalysis

Switching of the same intermediate X to the same intermediate Y is also carried out by 1) heating 547 mg of intermediate X with 30 mg of isobutyric acid in xylene at boiling point under argon for 6 hours, 2) stirring 247 mg of intermediate X with 30 mg of aluminum chloride at temperature room for 24 hours.

Example 12

Synthesis of ethyl 2- (beta, beta, beta-trichloroethyl) -3,3-dimethylcyclopropanecarboxylate (intermediate Z)

A solution of sodium tert-butoxide is prepared by dissolving 280 mg of sodium in a mixture of 60 ml of tert-butanol and 30 ml of benzene while protecting the reaction mixture from atmospheric humidity. To this solution was added at room temperature 3.1 g (0.01 mol) of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate and the mixture was stirred for two hours. An excess of anhydrous hydrogen chloride was then added and the mixture was diluted with water and extracted with diethyl ether. The ether extract was washed successively with a saturated aqueous solution of sodium bicarbonate and sodium chloride. The washed extract was dried over magnesium sulfate and distilled to give 2.03 (74%) of ethyl 2- (beta, beta, beta-trichloroethyl) -3,3-diaethylcyclopropanecarboxylate, b.

212300 26

Analysis for C ^ HH ^Cl ^Og:

H, 5.53; Cl, 38.87. Found: C, 43.80; H, 5.41; Cl, 38.87.

NMR δ ppm (CCl ₄ ): 4.03 (dq, 2H), 3.1-2.7 (m, 2H), 2.1-1.5 (m, 2H), 2.1-1.5 (m, 2H), 1.35 (s, 6H), 1.34 (dt, 3H).

In a similar manner, the same intermediate Z was also prepared from ethyl 4-bromo-6,6,6-trichloro-3,3-dimethylhexanoate.

Example 13

Synthesis of ethyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate from intermediate X, Y and Z

A. From ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate (Intermediate X)

A solution of 410 mg of ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate in 1.5 ml of anhydrous tetrahydrofuran was added dropwise with stirring to a suspension of 202 mg of potassium tert-butoxide in 20 ml of anhydrous tetrahydrofuran. The mixture was heated to boiling with stirring for three hours and then poured into ice water. The aqueous mixture was extracted with diethyl ether, the ether extract was dried over magnesium sulfate and distilled to give 281 mg (79% yield) of ethyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate, bv 72-74 ° / 26.6 Bye.

B. From ethyl 4,6,6-triohloro-3,3-dimethyl-5-hexenoate (intermediate Y)

1. Using sodium in ethanol

A solution of 547 mg (2 mmol) of ethyl 4,6,6-triohloro-3,3-dimethyl-5-hexenoate in 2 ml of ethanol was added dropwise to a solution of 57 mg (2.5 mmol) of sodium in 10 ml of absolute ethanol with stirring. . The mixture was stirred at room temperature for five hours, cooled with ice and then neutralized with a solution of hydrogen chloride in anhydrous ethanol. The mixture is concentrated to one tenth of the original volume by distilling off the ethanol and then 50 ml of diethyl ether are added. The mixture is poured into an ice bath, the phases are separated and the ether phases are washed successively with a saturated aqueous solution of sodium bicarbonate and sodium chloride. The washed ether solution was dried over magnesium sulfate and distilled to give 436 mg (92% yield) of ethyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropenecarboxylate, b. According to gas chromatography analysis, the ratio of cis: trans isomers is 2: 8.

NMR spectrum of the trans isomer is distinct bands (6ppm, CC1 ₄₎ 5.56 (d, H), 4.05 (bq, 2H), 2.12 (dd, 1H), 1.47 (d, 1H) 1.50-1.10 (m, 9H);

whereas specific bands of the cis isomer are observed at 6.22 (d) and 2.35-2.10 (m).

2. Using sodium t-butoxide in tetrahydrofuran

A solution of 547 mg (2 mmol) of ethyl 4,6,6-tri-chloro-3,3-dimethyl-5-hexenoate in 2 ml of anhydrous tetrahydrofuran was added dropwise to a suspension of 288 mg (3 mmol) of sodium t-butoxide in 10 ml of anhydrous tetrahydrofuran. . The mixture was stirred at room temperature for two hours and then poured into an ice water bath. The aqueous mixture was extracted with diethyl ether, and the ether extract was dried over magnesium sulfate. The dried extract by distillation gave 427 mg (90% yield) of ethyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate, b. According to gas chromatography, the cis: trans ratio is about 1: 9.

C. From ethyl 2- (beta, beta-trichloroethyl) -3,3-dimethylcycloporopanecarboxylate (intermediate Z)

A solution of 2.72 g (0.01 mol) of ethyl (2-beta, beta, beta-trichloroethyl) _-3-f 3-dimethylcyclopropanecarboxylate in 20 mL of absolute ethanol was added dropwise to a solution of 250 mg (0.011 mol) of sodium in 80 ml of absolute ethanol . The mixture was refluxed for five hours, then cooled with ice, and the cold mixture was neutralized with hydrogen chloride gas. The mixture is concentrated to one tenth of the original volume and then diluted with diethyl ether. The ether solution was washed successively with saturated aqueous sodium bicarbonate solution and water. The solution was dried over magnesium sulfate and distillation gave 1.94 g (82% yield) of ethyl 2- (beta, beta-dichlorovinyl) -3,3-dimethylcyclopropanecarboxylate, bp 75-76 ° / p _and 33.3.

Example 14

Synthesis of ethyl 2- (beta, beta-dibromvinyl) -3,3-dimethylcyclopropanecarboxylate

A. Dehydrobromination of ethyl 4,6,6,6-tetrabromo-3,3-dimethylhexanoate ml of ethanolic solution containing 92 mg (4 mmol) of sodium is added dropwise to a cold solution of 1.95 g (4 mmol) of ethyl-4,6 6,6-tetrabromo-3,3-dimethylhexanoate in 10 ml of absolute ethanol. The cold mixture was stirred for two hours and then poured into cooled 1N hydrochloric acid. The acidic mixture was extracted with diethyl ether and the extract was washed successively with a saturated aqueous solution of sodium bicarbonate and sodium chloride. The washed extract was dried over magnesium sulphate and distilled to give 846 mg (52% yield) of ethyl 4,6,6-tribromo-3,3-dimethyl-9-hexenoate, m.p.

Analysis:

NMR δ ppm (CCl ₄ ): 6.64 (d, 1H), 4.95 (d, 1H), 4.12 (q, 2H), 2.38 (bd, 2H), 1.4-1, 1 (m, 8H)

B. Cyclization of ethyl 4,6,6-tribromo-3,3-dimethyl-5-hexenoate (intermediate Ϊ)

A solution of 407 mg (1 mmol) of ethyl 4,6,6-tribromo-3,3-dimethyl-5-hexenoate in 1.5 ml of absolute ethanol is added dropwise to a solution of 30 mg (1.3 mmol) of sodium in 5 ml of absolute ethanol. The mixture was stirred at room temperature for three hours and 270 mg (83% yield) of ethyl 2- (beta, beta-dibromvinyl) -3,3-dimethylcyclopropanecarboxylate, b. V. 95-9 ° C / 40Pa were prepared as described in Example 13A.

Analysis:

NMR δ ppm (CCl ₄ ): 6.70-6.07 (d, 1H), 4.05 (q, 2H), 2.45-1.40 (m, 2H), 1.35-1.10 (m, 8H)

IR (cm ^-1 ): 1725, 1223, 1175, 855, 800, 762 «

Example 15

Synthesis of other 2-dihalvinylcyclopropanecarboxylates

The following compounds, which are characterized in more detail, are prepared by the methods described above:

A. Ethyl 2- (beta, beta-dichlorvinyl) -1,3,3-trimethylcyclopropanecarboxylate

This compound is prepared from ethyl 4,6,6,6-tetrachloro-2,3,3-trimethylhexanoate and has the following characteristics: b. V. 71-76 ° / 10.6 Pa

Analysis:

NUK δ ppm (CCl ₄ ): 6.26-5.57 (d, 1H), 4.10 (bq, 2H), 2.28-1.52 (d, 1H), 1.40-0.90 (m, 11H)

This spectrum shows that the product consists of 30% cis and 70% trans isomers. The trans isomer is distinguishable by bands at 5.57, 4.10, 2.28 and 1.40-0.90, while the cis isomer is distinguishable by bands at 6.26 and 1.52.

The same cyclopropanecarboxylate is thus prepared (1) from ethyl 4-bromo-6,6,6-trichloro-2,3,3-trimethyl-4-hexenoate mentioned above, (2) from ethyl-6,6 ₎ 6- Intermediate X trichloro-2,3,3-trimethyl-4-hexenoate ₁ having the following characteristics: bv 92 to 95 ° / 26.6 Pa

Analysis:

NMR δ ppm (CCl ₄ ): 6.19 (q, 2H), 4.07 (q, 2H), 2.70-2.10 (m, 1H), 1.30-0.90 (m, 12H) ).

(3) from ethyl 4,6,6-trichloro-2,3,3-trimethyl-5-hexenoate, Intermediate Y with the following characteristics: b. 91-93 ° / 16 Pa.

Analysis:

NMR δ ppm (CCl ₄ ): 5.95-5.94 (d, 1H), 4.77-4.62 (d, 1H), 4.03-4.02 (q, 2H), 2.80 -2.35 (m, 1 H), 1.35-0.90 (m, 12 H).

B. Ethyl 2- (beta, beta-dichlorvinyl) -3-methylcyclopropanecarboxylate

This compound is prepared from ethyl 4,6,6,6-tetrachloro-3-methylhexanoate and has the following characteristics: b.

Analysis:

IR (KBr, cm -1): 3,040, 1,725, 1,615, 190, 1,045, 922, 883, 861, 824, 645.

The same compound was also prepared from ethyl 4-bromo-6,6,6-trichloro-3-methylhexanoate and ethyl 6,6,6-trichloro-3-methyl-4-hexenoate (intermediate X).

C. Ethyl 2- (beta, beta-dichlorvinyl) -3-phenylcyclopropanecarboxylate

This compound was prepared from ethyl 4,6,6,6-tetrachloro-3-phenylhexanoate and distilled at 105-115 ° / 13.3 Pa. The NMR spectrum of the product indicated that it consisted of a mixture of isomers.

Major NMR bands are (δ ppm, CCl ₄ ): 7.20 (m, 5H), 6.10 (bd, 0.5H), 5.13 (d, 0.5H), 4.17 (bq, 2H) ), 3.10-2.00 (m, 3H), 1.32 (bt, 3H).

D. Benzyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate

This compound was prepared from benzyl-4,6,6,6-tetrachloro-3,3-diaethylhexanoátu and has the following characteristics: bp 114 to I18 ° / 17.3 Pa i5 Analysis for ^{C H} | g ^{Cl2 O2:} Calc H, 5.39; Cl, 23.70. Found: C, 60.12; H, 5.39;

NMR δ ppm (CCl ₄ ): 7.22 (bq, 5H), 6.18 (d, 0.5H), 5.50 (d, 0.5H), 5.01 (s, 2H), 2, 4-1.5 (m, 2H); 1.42-1.05 (m, 6H).

E. The above methods are also prepared. following! cyclopropanecarboxylates:

1.

2.

3.

4.

5.

6.

7.

8. 9.

, 0.

11.

12.

13.

14.

15 Dec

16.

17.

18.

19 Dec

20 May

21.

22nd

ethyl 2- (beta, beta-dichlorvinyl) -cyclopropanecarboxylate, ethyl 3-benzyl-2- (beta, beta-dichlorvinyl) cyclopropanecarboxylate, ethyl 2- (beta, beta-dichlorvinyl) -3-isopropyl-3-methylcyclopropanecarboxylate , ethyl 1-benzoyl-3- (2-butenyl) -2- (beta, beta-dichlorvinyl) -3-ethylcyclopropanecarboxylate, methyl 2- (beta, beta-dichloroxinyl) -3-ethyl-3-phenylcyclopropanecarboxylate, ethyl -2- (beta, beta-dichlorvinyl) -spiro [2,5] -octane-1-carboxylate, methyl 3-allyl-3-carbomethoxy-2- (beta, beta-dichlorvinyl) cyclopropanecarboxylate, methyl 3-carbomethoxy -2- (beta, beta-dichlorvinyl) -3-cyanocyclopropanecarboxylate, ethyl 3-acetyl-1-benzyl-2- (beta, beta-dichlorvinyl) -, - cyclohexyl-3-ethylcyclopropanecarboxylate, methyl-3-benzoyl- 2- (beta, beta-dibromvinyl) -3-phenylcyclopropanecarboxylate, ethyl 3-acetyl-2- (beta, beta-dibromvinyl) -3- (N, N-dimethylcarboxamido) cyclopropanecarboxylate, ethyl-3-cyano-2 - (beta.beta-difluorvinyl) -3-ethylcyclopropanecarboxylate, ethyl 2- (beta, beta-dichlorvinyl) -1-ethyl-3,3-dimethylcyclopropanecarbo xylate, isopropyl 2- (beta-bromo-beta-chlorvinyl) -1,3-dimethylcyclopropanecarboxylate, methyl 2- (beta, beta-difluorvinyl) -3,3-dimethyl-1-phenylcyclopropanecarboxylate, ethyl-1-vinyl 2- (beta, beta-dichlorvinyl) -3-cyclohexyl-3-ethylcyclopropanecarboxylate, methyl 1-carboisopropoxy-2- (beta, beta-dibromvinyl) -3,3-dimethylcyclopropanecarboxylate, ethyl-1-acetyl-2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate, methyl 1-butyryl-2- (beta, beta-dichlorvinyl) -3-cyanocyclopropanecarboxylate, ethyl 2- (beta, beta-dibromvinyl) -1 - (N , N-dimethylcarboxamido) -3-methylcyclopropanecarboxylate, methyl, -, cyano-2- (beta-beta-difluorvinyl) -3-phenylcyclopropanecarboxylate, ethyl 1-ethynyl-2- (beta, beta-dichlorvinyl) -3,3 -dimethylcyclopropanecarboxylate.

The use of the processes of the invention for the preparation of vinyl cyclopropanecarboxylates other than dihalvinyl is shown in the following examples.

Example, 6

Preparation of ethyl _1,3) ^{3-trimethyl-2-vinylcyklopx,} opankarboxylátů

1. A mixture of 920 mg (5 mmol) of ethyl 2,3,3-trimethyl-4-hexenoate, 1.0 ml of carbon tetrachloride, 107 g (6 mmol) of N-bromosuccinimide and 50 mg of benzoyl peroxide was heated to boiling for 2 hours. The insoluble succinimide is filtered off. The filtrate was washed successively with a saturated aqueous solution of sodium bicarbonate and water, and then dried over magnesium sulfate. Distillation of the dried solution gave 1.14 g (86% yield) of ethyl 6-bromo-2,3,3-trimethyl-4-hexenoate, m.p. 80-81 ° / 0.1 kPa.

Analysis:

NMH δ ppm (CCl ₄ ): 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) of ethyl 6-bromo-2,3,3-trimethyl-4-hexenoate in 2 ml of anhydrous tetrahydrofuran was added dropwise to a suspension of 224 mg (2 mmol) of potassium tert-butoxide in 1.0 ml of tetrahydrofuran . The mixture was heated to boiling for two hours and then allowed to cool to room temperature. An additional 116 mg (1 mmol) of potassium tert-butoxide was then added and the mixture was again heated to reflux for two 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 sulphate and distilled to give 200 mg (55% yield) of ethyl 1,3,3-trimethyl-2-vinylcyclopropanecarboxylate, m.p. 92-95 ° / 0.2 kPa.

Analysis:

NMR δ ppm (CCl ₄ ): 6.40-4.80 (m, 3H), 4.03 (bq, 2H), 2.08 (bd, 1H), 1.40-1.00 (m, 12H) ).

Příprava »Preparation of ethyl 3,3-dimethyl-2-vinylcyclopropanecarboxylate

1. By the method of Example 16 (A), ethyl 6-bromo-3,3-dimethyl-4-hexenoate was prepared, b. V. 85 ° / 66.6 Pa.

IR (cm ^-1 ):

730, 1,365, 1,215, 1,033, 970, 710, 590.

2. By the method of Example 16 A2), ethyl 6-bromo-3,3-dimethyl-4-hexenoate was converted to ethyl 3,3-dimethyl-2-vinylcyclopropanecarboxylate, b. V. 68-75 ° / 3.3 kPa.

IR (cm -1): 1,728, 1,630, 1,187, 1,148, 1,097, 1,030, 990, 902.

Example 17

Synthesis of alpha-cyano-3-phenoxybenzyl-2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate by dehydrohalogenation followed by transesterification of alcohol residue A. Preparation of 2- (beta, beta-dichlorvinyl) -3,3-dimethyleyclopropane-1-carboxylic acid

A solution containing 97 g (0.434 mol) of methyl 2- (beta, beta-dichlorvinyl) -3,3-dimethyloyclopropanecarboxylate, 6.8 ml of concentrated sulfuric acid and 17 ml of water in 170 ml of acetic acid is heated at reflux for 5 hours. During this time, 26.8 g of low-boiling material, predominantly methyl acetate, was distilled off. Acetic acid is then distilled off from the reaction mixture and the residue is treated with 125 ml of an aqueous solution containing 25% by weight of sodium hydroxide, while maintaining the temperature below 50 ° C by external cooling. The resulting aqueous solution (pH 11) was then extracted twice with 100 ml portions of n-hexane. The aqueous phase is then adjusted to pH 1.6 with 20 ml of concentrated sulfuric acid and the temperature is again maintained below 50 ° C by external cooling. The acidic solution was extracted twice with 100 ml portions of n-heptane. The combined extracts were evaporated at 50 ° C under vacuum to give n-heptane to give 83 g (96%) of 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropane-1-carboxylic acid.

B. Preparation of 2v (bete, beta-dichlorvinyl) -3,3-dimethylcyclopropane-1-kerbonyl chloride

A mixture of 83 g (0.40 mol) of 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropane-1-carboxylic acid and 48 ml of n-heptane is heated to 35 ° C and 61.3 g is added to the stirred mixture. thionyl chloride (0.516 mol). The solution was then stirred at 45-50 ° C for two hours. The excess thionyl chloride and n-heptane were removed under reduced pressure and the residue was distilled under vacuum.

72.3 g of 2- (beta, beta-dichloro-3-ynyl) -3,3-dimethylcyclopropane-1-carbonyl chloride are obtained, m.p.

C. Preparation of alpha-cyano-3-phenoxybenzyl-2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate.

To a mixture of 4.87 moles of alpha-cyano-3-phenoxybenzyl alcohol and 5.35 moles of pyridine in toluene at 40 ° C under nitrogen atmosphere was added dropwise over one hour 4.87 moles of 2- (beta, beta-dichlorvinyl) -3,3. -dimethylcyclopropane-1-carbonyl chloride dissolved in toluene. After stirring at 40 ° C for two hours, the reaction mixture was washed successively with water, aqueous 2N hydrochloric acid solution, aqueous 2N sodium hydroxide solution and water. The organic and aqueous phases are separated, the organic phase is dried over magnesium sulphate, filtered and heated to 50 ° C under vacuum to remove toluene. The residue contains alpha-cyano-3-phenoxybenzyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate in a yield of 94%.

Example 18

Synthesis of 3-phenoxybenzyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanksrboxylate by dehydrohalogenation and subsequent transesterification of the alcoholic residue

A. From methyl 2- (beta, beta-dichloropynyl) -3,3-dimethylcyclopropanecarboxylate

A mixture of methyl 2- (beta, beta-diethylvinyl) -3,3-dibethylcyclopropanecarboxylate (0.1 mol), 3-phenoxybenzyl alcohol (0.1 mol) and toluene (175 ml) was dried by distilling off 10 ml of the azeotropic toluene / water. Sodium (0.01 mol) was then added and the mixture was heated for 1.5 hours and the ethanol was distilled continuously. Analysis of the residue by gas chromatography showed 3-phenoxybenzyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate in 86% yield.

B. From ethyl 2- (beta, beta-dichlorovinyl) -3,3-diaethylcyclopropanecarboxylate

A mixture of ethyl 2- (beta, beta-dichlorvinyl) -3,3-dimethylcyclopropanecarboxylate (0.5 mol), 3-phenoxybenzyl alcohol (0.5 mol) and xylene (300 ml) is dried by distilling off 30 ml of azeotropic xylene / water mixture. Niobium ethoxide (0.005 mol) is then added and the mixture is heated for 24 hours while ethanol is continuously distilled off. Analysis of the residue by gas chromatography showed that 3-phenoxybenzyl 2- (beta, beta-dichlorvinyl) -3,3-diraethylcyclopropanecarboxylate was obtained in 62% yield.

Claims (16)

1. A process for the preparation of dihalogenvinylcyclopropanecarboxylic acid derivatives of the general formula I, R ² R ³ where R is ethyl, benzyl or 3-phenoxybenzyl, R ^3a are both hydrogen, methyl or phenyl, γ R is hydrogen, methyl or ethyl; and X is a chlorine or bromine atom, characterized in that the compound of formula (Ii) is dehydrohalogenated, IX * F X COOR (I) (li) where D j® X, E Yippee hydrogen atom, F Yippee hydrogen atom and G Yippee X, or D + E together form a bond, 1 'is hydrogen and G is X, or D is X E + G together form a bond and F is hydrogen, or D + F together form a bond, E is hydrogen and G is X and 2 3 7 R, R, R and R are as hereinbefore defined, preferably in an anhydrous solvent, by reaction with 1 to 5 molar equivalents, preferably an anhydrous base, such as sodium hydride or an alkali metal alkoxide, at a temperature of 50 to 200 ° C to remove at least one, but not more than two, moles of the hydrohalic acid of formula HX from the starting compound. 2. A process according to claim 1, wherein the compound is of the formula (II): Where R is ethyl, benzyl or phenoxybenzyl R and R are both methyl, R ¹ is hydrogen, X is chlorine or bromine, D is chlorine or bromine, E is hydrogen, F is hydrogen and G is chlorine or bromine, or D + E together form a bond, F is hydrogen and G is chlorine or bromine or D is chlorine or bromine, E + G forms a bond and F is hydrogen, or D + F forms a bond, E is hydrogen and G is chlorine or bromine. 3. A process according to claim 1, wherein the process is based on a compound of the general formula Wherein R is ethyl, R and R are both hydrogen, methyl or phenyl, R is hydrogen, methyl or ethyl, X is chlorine or bromine, D is chlorine or bromine, E is hydrogen , F is hydrogen and G is chlorine or bromine, or D + E forms a bond together, F is hydrogen, and G is chlorine or bromine, or D is chlorine or bromine, E + G forms a bond, and F is hydrogen, or I) + F forms a bond, E is hydrogen and G is the chlorine or bromine atom and the 3-phenoxybenzyl are then exchanged for R. 4. A process according to claim 1, wherein the process is based on a compound of the general formula Wherein R is ethyl, R and R are both hydrogen, methyl or phenyl, R is hydrogen, methyl or ethyl, X is chlorine or bromine, D is chlorine or bromine, E is atom hydrogen, P is hydrogen and G is chlorine or bromine, or D + E forms a bond together, F is hydrogen and G is chlorine or bromine, or D is chlorine or bromine, E + G forms a bond and F is hydrogen or D + F forms a bond, E is hydrogen and G is chlorine or bromine . 5. A process as claimed in claim 1 or 2, wherein the compound is a starting material Wherein R is benzyl or 3-phenoxybenzyl, R and K are both hydrogen, methyl or phenyl; is hydrogen, methyl or ethyl, X is chlorine or bromine, D is chlorine or bromine, E is hydrogen, F is hydrogen and G is chlorine or bromine, or D + E forms a bond, F is a hydrogen atom and G is a chlorine or bromine atom, or D is a chlorine or bromine atom, E + G together form a bond and F is a hydrogen atom, or B + F together form a bond, E is a hydrogen atom and G is chlorine or bromine atom. 6. A process according to claim 5, wherein the compound is of the formula (II): Wherein R is 3-phenoxybenzyl, R and R are both hydrogen, methyl or phenyl, R is hydrogen, methyl or ethyl, X is chlorine or bromine, D is chlorine or bromine, E is hydrogen, F is hydrogen and G is chlorine or bromine or D + E is a bond, F is hydrogen and G is chlorine or bromine, or D is chlorine or bromine, E + G is bond and F is hydrogen or D + F together form a bond, E is hydrogen and G is chlorine or bromine. 7. A process according to any one of claims 1 to 6, wherein 2 moles of the hydrohalic acid are removed from the starting compound. 8. A process as claimed in claim 7, wherein 1 mol of hydrohalic acid is first removed from the starting compound of formula (II) wherein R is ethyl, benzyl or 3-phenoxy-27 benzyl, R and R are both hydrogen, methyl, or methyl. phenyl, R is hydrogen, methyl or ethyl, X is chlorine or bromine, D is chlorine or bromine, E is hydrogen, F is hydrogen and G is chlorine or bromine to form a compound of formula II wherein: 2 3 R is ethyl, benzyl, or 3-phenoxybenzyl; R and R are both hydrogen, methyl, or phenyl; is hydrogen, methyl or ethyl, X is chlorine or bromine, D + E forms a bond together, F is hydrogen and G is chlorine or bromine by dehydrohalogenating the starting compound 1 and 2 equivalents of a base, preferably a lower sodium or potassium alkoxide, in an aprotic solvent at a temperature below 25 ° C, and then removing the second mole of hydrohalic acid of formula II wherein R is ethyl, benzyl or 3-phenoxybenzyl, 2 3 7 R and R are both hydrogen, methyl or phenyl, R 'is hydrogen, methyl or ethyl and X is chlorine or bromine, D + E forms a bond, F is hydrogen and G is chlorine or bromine, at temperature Mp 50-200 ° C. 9. The process of claim 7, wherein 1 mol of hydrohalic acid is first removed from the starting compound of formula II wherein R is ethyl, benzyl or 3-phenoxybenzyl, R and R are both hydrogen, methyl, or phenyl. , R is hydrogen, methyl or ethyl, X is chlorine or bromine, D is chlorine or bromine, E is hydrogen, F is hydrogen and G is chlorine or bromine to give a compound of formula (II) wherein: 3 R is ethyl, benzyl or 3-phenoxybenzyl, R and R are both hydrogen, methyl or phenyl, σ R is hydrogen, methyl or ethyl, X is chlorine or bromine, D is chlorine or bromine, E + G forms a bond and F is hydrogen, by dehydrohalogenation of the parent compound in a polar aprotic solvent at 25 to 150 ° C , and then removing the second mole of the hydrohalic acid by dehydrohalogenating the compound of formula II wherein R is 2 3 7 ethyl, benzyl or 3-phenoxybenzyl, R and R are both hydrogen, methyl or phenyl, R is hydrogen, methyl or ethyl, X is chlorine or bromine, D is chlorine or bromine, E + G is together is a bond and F is hydrogen, at a temperature of 50 to 200 ° C. 10. The process of claim 9, wherein the first mole of the hydrohalic acid is removed by dehydrohalogenation of the starting compound with sodium ethoxide as the base and in dimethylformamide as the solvent. 11. The process of claim 7, wherein 1 mol of the hydrohalic acid is first removed from the starting compound of formula (II) wherein R is ethyl, benzyl or 3-phenoxybenzyl; 3 7 R and 3 are both hydrogen, methyl or phenyl, R is hydrogen, methyl or ethyl, X is chlorine or bromine, D is chlorine or bromine, E is hydrogen, F is hydrogen and G is chlorine or bromine to give a compound of formula II wherein R is ethyl, benzyl or 3-phenoxybenzyl, R and R ^J are both hydrogen, methyl or phenyl, R is hydrogen, methyl or ethyl, X is chlorine or bromine, D + F forms a bond, E is hydrogen and G is chlorine or bromine, by dehydrohalogenation of the parent compound in an aprotic solvent with an alkali metal tert-butoxide base at 25 to 50 ° C, and then removing the second mole of the hydrohalic acid by dehydrogenating the compound wherein R is ethyl, 2 3 7 benzyl or 3-phenoxybenzyl R and R ^J are both hydrogen, methyl or phenyl, H is hydrogen, methyl or ethyl, X is chlorine or bromine, D + F form together a bond, E is hydrogen and G is a chlorine or bromine atom, at a temperature of 50 to 200 ° C. 12. A process according to any one of Claims 6 to 11, wherein the starting compound is selected from the group consisting of 3-phenoxybenzyl-4,6,6,6-tetrachloro-3,3-dimetbylhexanoate, 3-phenoxybenzyl-4-bromo-6. , 6,6-trichloro-3,3-dimethylhexanoate, ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate and ethyl 4-bromo-6,6,6-trichloro-3,3-dimethylhexanoate . 13. A process as claimed in any one of claims 1 to 6, wherein the starting material is a compound of general formula Wherein R is ethyl, benzyl or 3-phenoxybenzyl; R and R are both hydrogen, methyl, or phenyl; is hydrogen, methyl or ethyl, X is chlorine or bromine D + E together form a bond, F is hydrogen and G is chlorine or bromine atom, or D is chlorine or bromine atom, E + G together form a bond, F is hydrogen or D + F together form a bond, E is hydrogen and G is chlorine or bromine, and 1 mole of hydrohalic acid is removed from the starting compound. 14. A process according to claim 13, wherein the starting compound is selected from the group consisting of ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate and ethyl 6,6,6-trichloro2; 3,3-trimethyl-4-hexenoate. 15. The method of claim 13, wherein the starting compound is selected from the group consisting of ethyl 4,6,6-trichloro-3,3-dimethyl-5-hexenoate, ethyl 4,6,6-tribromo-3. , 3-dimethyl-5-hexenoate and ethyl-4,6,6-trifluoro-2,3,3-triraethyl-5-hexenoate, 16. The process of claim 13, wherein the starting compound is ethyl 2- (beta, beta, beta-trichloroethyl-3,3-dimethylcyclopropanecarboxylate).