CS205109B2 - Method of making the sters of 3-substituted 2,2-dimethyl cyclopropancarboxyl acids - Google Patents

Description

The invention relates to a process for the preparation of novel esters of 3-substituted 2,2-dimethylcyclopropanecarboxylic acids. These compounds are useful as starting materials for the preparation of the insecticidally active cyclopropane derivatives described in Czechoslovak Patent Specification No. 205,108.

The compounds produced by the process according to the invention correspond to the general formula I

O

R ¹ R ^Z C = CH-CH-CH-CH 2

AND

H »C

OL (I) wherein one of R ¹ and R ² is a radical of formula

W— (CF2) anywhere

W represents a hydrogen, fluorine or chlorine atom and m has a value of 1 or 2, and the other of those symbols refers to a fluorine, chlorine or bromine atom or a radical of formula

Y

AND

X-C-,

From where

X, Y and Z are each independently hydrogen, fluorine or chlorine, and

Q represents an alkoxy group having 1 to 6 carbon atoms.

The compounds of formula (I) above are prepared in accordance with the invention by reaction of a diene of formula (II)

Rl CHs

R ²

C = CH - CH = C \

CH3, (II) with the corresponding alkyl ester of diazoacetic acid. In this way the desired compound of formula (I) is obtained directly. The reaction is expediently carried out using an excess of diene as the solvent for the diazoacetic acid alkyl205109 ester and in the presence of a metal catalyst, for example copper powder or copper bronze.

In one variation of the above process, a compound of formula III can be prepared first

OH

O

II

R ¹ R ^Z C-CH.-CH-CH-C- O.

** \ /

CH,

CH, (III) by reacting an unsaturated alcohol of formula IV

OH CH3

I Z

R 1 R 2 C-CH 2 —CH = C

CH3, (IV) with the appropriate alkyl ester of diazoacetic acid, and then converting this compound to a compound of formula I wherein Q is an alkoxy group as defined above by dehydration with a chemical dehydrating agent such as phosphorus pentoxide.

This variant of the palzoacetate process is not applicable to the preparation of those compounds in which one of R ¹ and R ² is a halogen atom, but is very useful for the preparation of compounds in which both R ¹ and R ² are trifluoromethyl or where one of R ¹ and R ² are trifluoromethyl and the other of these is difluoromethyl.

The starting materials of formula IV can be prepared by reacting a ketone of formula V

O

R1-C-R2, (V) with 3-methyl-1-butene, preferably under pressure. The corresponding compounds of formula II can be obtained by dehydrating compounds of formula IV, for example with phosphorus pentoxide.

Compounds of formula (II) in which both R ¹ and R ² are haloalkyl, or wherein one of R 1 and R ² is haloalkyl and the other of them is methyl, may also be obtained by reacting the corresponding ketone of formula V with an ylide prepared by treating a 3,3-dimethylallyl-triphenylphosphonium halide with a suitable dehydrohalogenating agent, for example an alkyl lithium derivative such as n-butyllithium, preferably -chloride or -bromide. The phosphonium halide can be obtained by reacting triphenylphosphine with 3,3-dimethylallyl halide. The dienes which can be prepared by this process include compounds of formula II wherein R 1 and R ² have the meanings as follows:

Rl R ² CF3 CF3 CHF2 CHF2 GF3 GH3 CF3 chf ₂ CF2CI CF2CI CHF2 CF2CI

Examples of compounds of formula IV include 5-hydroxy-2-methyl-6,6,6-trifluoro-5-trifluoromethylhex-2-ene and 5-hydroxy-2-methyl-6,6-difluoro-5-trifluoromethylhex- 2-ene, which compounds can be dehydrated to 2-methyl-6,6,6-trifluoro-5-trifluoromethylhexa-2,4-diene and 2-methyl-6,6-difluoro-5-trifluoromethylhexa-2,4- dienes, which are examples of compounds of formula II.

In the process according to the invention, the products of formula (I) usually result as mixtures of different geometric isomers. This can result in a mixture of cis- and trans-isomers, in which one form often predominates, and in cases where R 1 is not the same meaning as R ² , E- and Z-isomers of both the cis- and trans-forms may arise, where again one form prevails.

The above isomeric forms can be separated by physical methods, for example, by fractional crystallization of the corresponding carboxylic acids.

All of the aforementioned isomeric forms are within the scope of the invention.

The invention is illustrated by the following non-limiting examples.

For NMR spectra, the abbreviations have the following meanings:

s = singlet d = doublet t = triplet q = quartet m = multiplet.

Example 1

This example illustrates the preparation of 1-chloro-1,1-difluoro-2-chlorodifluoromethyl-5-methylhexa-2,4-diene of the formula

CH 3 CF 2 Cl 2

C = CH = CH = C

OF \

CH3 CF2Cl (a) Preparation of 3,3-dimethylallyl-triphenylphosphonium bromide

50.0 g of 3,3-dimethylallyl bromide,

88.0 g of triphenylphosphine and 500 ml of dry toluene were heated under reflux for 1 hour and then allowed to stand at room temperature for 18 hours. The precipitated white 3,3-dimethylallyl-triphenylphosphonium bromide melting at 242 DEG C. is filtered off and dried after washing with diethyl ether.

(bj Preparation of 1-chloro-1,1-difluoro-2-chlorodifluoromethyl-5-methylhexa-2,4-diene

To a vigorously stirred suspension of 65.0 g of 3,3-dimethylallyl-trifenylfosfomumbromidu in 500 ml of dry petroleum ether (b.p. 30-40 ° C) at 0 ° C under nitrogen was slowly added 65.0 ml of 15 ° / _o solution (weight n-butyllithium in hexane, the mixture was allowed to react at room temperature for 18 hours, then cooled to 0 ° C and 31.44 g of 1,3-dichlorotetrafluoroacetone was added. The reaction mixture was allowed to warm to room temperature over 2 hours and the precipitate formed was filtered off. The filtrate is concentrated by evaporation to a volume of about 70 ml, poured through a short column of alumina, and the remaining solvent is evaporated at atmospheric pressure at 69 ° C. The liquid residue is subjected to fractional distillation, collecting the fraction boiling at 80 ° C / 2666 Pa, which, according to identification by IR and NMR spectroscopy, consists of 1-chloro-1,1-difluoro-2-chlorodifluoromethyl-5-methylhexa-2 , 4-diene.

NMR (carbon tetrachloride, ppm):

1.88-1.94 (m, 6H)

6.3 (d, 1 H),

7.08 (d, IH).

Example 2

The following dienes are also prepared from the corresponding ketones in an analogous manner to Example 1:

(and)

From 1,1,1-trifluoroacetone 2-methyl-5-trifluoromethylhexa-2,4-diene;

NMR (carbon tetrachloride, ppm):

1.76-1.82 (m, 9H),

5.85 - 6.00 (m, 1H,

6.62 - 6.78 (m, 1H).

(hj

From 1-chloro-1,1,2,2-tetrafluoroacetone 1,1-difluoro-2-chlorodifluoromethyl-5-methylhexa-2,4-diene;

IR (liquid film):

3000, 1650, 1264 ^cm-first

(iii)

From 1,1,3,3-tetrafluoroacetone 1,1-difluoro-2-difluoromethyl-5-methylhexa-2,4-diene;

NMR (carbon tetrachloride, ppm):

1.90 - 2.02 (m, 6H),

5.05-7.10 (in, 4H). ..

Example 1 a d 3

This example illustrates the preparation of 5-hydroxy-2-methyl-6,6,6-trifluoro-5-trifluoromethylhex-2-ene.

A mixture of 235 g of hexafluoroacetone and 100 g of 3-methylbut-1-ene was heated at 125 DEG C. for 20 hours under a pressure of 1.7 MPa. Distillation of the reaction mixture under reduced pressure gave 5-hydroxy-2-methyl-6,6,6-trifluoro-5-trifluoromethylhex-2-ene as a mobile colorless liquid, bp 43 ° C / 2000 Pa.

NMR (carbon tetrachloride, ppm):

1.77 (d, 6H).

2.58 - 3.00 (m, 3H),

5.0-5.4 (m, 1H).

Example 4

Using a procedure analogous to that of Example 3, 5-hydroxy-2-methyl-6,6-difluoro-5-trifluoromethylhex-2-ene was prepared from pentafluoroacetone.

NMR (carbon tetrachloride, ppm):

1.78 (d, 6H).

2.5-2.75 (m, 3H),

5.18 (m, IH);

5.80 (t, IH).

Example 1 a d 5

This example illustrates the preparation of ethyl (±) - cis / trans -3- (2-hydroxy-3,3,3-trifluoro-2-trifluoromethyl-1-yl) -2,2-dimethylcyclopropanecarboxylate.

To 18.9 g of 5-hydroxy-2-methyl-6,6,6-trifluoromethylhex-2-ene in the presence of a catalytic amount of anhydrous copper sulphate at 110 to 120 ° C is added dropwise a solution of 9.12 g of diazoacetate ethyl ester over 48 hours. of acid in 400 ml of dichloromethane.

The resulting mixture was washed with water, dried over anhydrous magnesium sulfate and distilled. Several fractions are obtained in the range of 68 to 90 ° C / 20 Pa. According to NMR, IR and mass spectroscopy, these fractions consist essentially of the (± β-cis- and (±) -trans-isomers of ethyl-3- (2-hydroxy-3,3,3-trifluoro-2-trifluoromethylprop-). 1-yl) -2,2-dimethylcyclopropanecarboxylate in various ratios.

NMR (CDCl3, ppm):

1.04 - 1.40 (m, 9H);

1.55 - 2.43 (m, 4H),

4.00-4.37 (m, 2H).

Example 6

In an analogous manner to Example 5, 5-hydroxy-2-methyl-6,6-difluoro-5-trifluoromethylhex-2-ene was converted to ethyl- (±) - cis / trans-3- (2-hydroxy-3), 3-Difluoro-2-trifluoromethylprop-1-yl) -2,2-dimethylcyclopropanecarboxylate.

NMR (carbon tetrachloride, ppm):

1.3-2.4 (m, 13H),

4.0 - 4.35 (m, 2H);

4.6-4.8 (m, 1H);

5.2-6.4 (m, IH).

Example 7

This example illustrates the preparation of ethyl (±) - cis / trans -3- (3,3,3-trifluoro-2-trifluoromethylprop-1-en-1-yl) -2,2-dimethylcyclopropanecarboxylate.

Mixture of 4,62 g of ethyl (±) - cis / trans-3- (2-hydroxy-3,3,3-trifluoro-2-trifluoromethylprop-1-yl) -2,2-dimethylcyclopropanecarboxylate,

2.2 g of phosphorus oxychloride and 5.3 ml of dry pyridine are heated at 110 DEG C. for 65 hours, then poured into ice water and stirred for 5 hours. The resulting mixture was extracted with diethyl ether, the extracts were washed with water, dried over anhydrous sodium sulfate and the ether was evaporated under reduced pressure. The oily residue was distilled under reduced pressure to give ethyl (±) - cis / trans-3- (3,3,3-trifluoro-2-trifluoromethylprop-1-en-1-yl) -2,2-dimethylcyclopropanecarboxylate as a colorless oil. boiling at 60 to 65 ° C / 67 Pa.

NMR (CDCl3, ppm):

1.15-1.39 (m, 9H),

1.75-2.60 (m, 2H);

4.02 - 4.34 (m, 2H);

6.36 and 7.36 (double d, 1H).

Example 8

Analogously to Example 7, ethyl (±) - cis / trans-3- (3,3-difluoro-2-trifluoromethylprop-1-en-1-yl) -2,2- was obtained from the product prepared in Example 6. dimethylcyclopropanecarboxylate.

NMR (carbon tetrachloride, ppm):

1.2-1.4 (m, 9H)

1.6-2.6 (m, 2H);

4.0-4.4 (m, 2H);

5.4-7.2 (m, 2H).

Example 9

Using an analogous procedure to that of Example 5, the following ethyl esters of formula I are obtained from the dienes below by reaction with ethyl diazoacetic acid ester:

(and)

From 1,1-difluoro-2-difluoromethyl-5-methylhexa-2,4-diene ethyl- (±) - cis / trans-3- (3,3-difluoro-2-difluoromethylprop-1-en-1-one) yl) -2,2-dimethylcyclopropanecarboxylate;

NMR (carbon tetrachloride, ppm):

1.25-1.44 (m, 9H),

1.60-2.40 (m, 2H);

4.0-4.30 (m, 2H);

5.58 - 7.34 (complex signal, 3H).

(ii)

From 2-trifluoromethyl-5-methylhexa-2,4-diene ethyl (±) -, cis / trans-3- (E / Z-2-trifluoromethylprop-1-en-1-yl) -2,2-dimethylcyclopropanecarboxylate ;

NMR (carbon tetrachloride, ppm):

1.10 - 1.40 (m, 9H);

1.50-2.10 (m, 5H),

4.0 - 4.38 (m, 2H);

5.24-6.46 (m, IH).

(iii)

From 1-chloro-1,1-difluoro-2-chlorodifluoromethyl-5-methylhexa-2,4-diene ethyl- (±) - cis / trans -3- (3-chloro-3,3-difluoro-2) - chlorodifluoromethylprop-1-en-1-yl) -2,2-dimethylcyclopropanecarboxylate;

NMR (carbon tetrachloride, ppm):

1.28-1.42 (m, 9H),

1.78 - 2.60 (m, 2H),

08 - 4.26 (m, 2H);

6.20 and 7.16 (double d, 1H).

(iv)

From 1,1-difluoro-2-chlorodifluoromethyl-5-methylhexa-2,4-diene ethyl- (±) - cis / trans-3- (E / Z-3,3-difluoro-2-chlorodifluoromethylprop- 1-en-1-yl) -2,2-dimethylcyclopropanecarboxylate;

NMR (carbon tetrachloride, ppm):

1.24-1.52 (m, 9H)

1.64 - 2.50 (m, 2H);

3.90-4.30 (m, 2H);

5.50-7.04 (m, 2H).

Claims (4)

SUBJECT OF THE INVENTION A process for the preparation of 3-substituted 2,2-dimethylcyclopropanecarboxylic acid esters of general formula I O R ¹ R ^Z C = CH- CH- CH-C- & H ^ C \ / A ca (II) wherein one of R ¹ and R ² is a radical of formula W - (CF ₂ ) _m -, where W represents a hydrogen, fluorine or chlorine atom, and m has a value of 1 or 2, and the other of these represents an atoim of fluorine, chlorine or bromine or a radical of formula Y X — C—, From where X, Y and Z are each independently hydrogen, fluorine or chlorine, and Q represents an alkoxy group having 1 to 6 carbon atoms, characterized in that the diene (II) is present R ¹ CH3 \ / C = CH = CH = C X \ R2 CH3 dL) in which R ¹ and R ² have the above meanings, is reacted with an alkyl diazoacetate, alkyl containing 1 to 6 carbon atoms. 2. The process of claim 1, wherein the diazoacetic acid alkyl ester is ethyl diazoacetic acid. 3. Process according to claim 1 or 2, characterized in that the diene (II) is used in excess. 4. The process according to any one of claims 1 to 3, wherein the reaction is carried out in the presence of a metal catalyst.