CA1121831A - Preparation of cyclopropane derivatives - Google Patents
Preparation of cyclopropane derivativesInfo
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- CA1121831A CA1121831A CA000294304A CA294304A CA1121831A CA 1121831 A CA1121831 A CA 1121831A CA 000294304 A CA000294304 A CA 000294304A CA 294304 A CA294304 A CA 294304A CA 1121831 A CA1121831 A CA 1121831A
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Abstract
ABSTRACT
Compounds, and a process for their preparation, having the following general formula:- (I) wherein X is a halogen atom; R1 is an alkyl group of from 1 to 6 carbon atoms; R2 is an alkyl group of from 1 to 6 carbon atoms;
or R1 and R2 together represent an alkylene chain of up to 5 carbon atoms; or a salt, anhydride, carboxamide or alkyl (1-6 carbon) ester thereof, which comprises particularly dehalogenating a cyclopropane-carboxylic acid of the following general formula:- (II) o- a salt, anhydride, carboxamide or alkyl ester thereof, in the presence of zinc and an alkanoic acid, the symbols R1, R2 and X
in formula II having the same meaning as in formula I and Y
representing a halogen atom having an atomic number which is the same as or more than that of the halogen atom represented by X.
These compounds find use in synthesizing compounds of the pyre-throid type, which are known insecticides.
Compounds, and a process for their preparation, having the following general formula:- (I) wherein X is a halogen atom; R1 is an alkyl group of from 1 to 6 carbon atoms; R2 is an alkyl group of from 1 to 6 carbon atoms;
or R1 and R2 together represent an alkylene chain of up to 5 carbon atoms; or a salt, anhydride, carboxamide or alkyl (1-6 carbon) ester thereof, which comprises particularly dehalogenating a cyclopropane-carboxylic acid of the following general formula:- (II) o- a salt, anhydride, carboxamide or alkyl ester thereof, in the presence of zinc and an alkanoic acid, the symbols R1, R2 and X
in formula II having the same meaning as in formula I and Y
representing a halogen atom having an atomic number which is the same as or more than that of the halogen atom represented by X.
These compounds find use in synthesizing compounds of the pyre-throid type, which are known insecticides.
Description
L83~L
This invention relates to a process for the preparation of cyclopropane derivatives which are of particular interest as starting materials in the manufacture of agricultural chemicals related to the so-called "synthetic pyrethroids". Typical pro-cedures are to be found in Canadian Patent 1,093,563. The cyclo-propane derivatives produced by the process according to the invention are novel compounds and are claimed as such.
Accordingly the present invention provides both compounds, and a process for their preparation, h~ving the follo~ing general formula:-H
R1 2 \ COOH (I) R H
wherein X is a halogen atom; Rl is an alkyl group of from 1 to 6carbon atoms; R2 is an alkyl group of from 1 to 6 carbon atoms;
or Rl and R2 together represent an alkylene chain of up to 5 carbon atoms; or a salt, anhydride, carboxamide or alkyl (1-6 carbon) ester thereof, which comprises partially dehalogenating a cyclopropane-carboxylic acid of the following general formula:-Y\/
R1 2 \ -COOH (II) R H
or a salt, anhydride, carboxamide or alkyl ester thereof, in the
This invention relates to a process for the preparation of cyclopropane derivatives which are of particular interest as starting materials in the manufacture of agricultural chemicals related to the so-called "synthetic pyrethroids". Typical pro-cedures are to be found in Canadian Patent 1,093,563. The cyclo-propane derivatives produced by the process according to the invention are novel compounds and are claimed as such.
Accordingly the present invention provides both compounds, and a process for their preparation, h~ving the follo~ing general formula:-H
R1 2 \ COOH (I) R H
wherein X is a halogen atom; Rl is an alkyl group of from 1 to 6carbon atoms; R2 is an alkyl group of from 1 to 6 carbon atoms;
or Rl and R2 together represent an alkylene chain of up to 5 carbon atoms; or a salt, anhydride, carboxamide or alkyl (1-6 carbon) ester thereof, which comprises partially dehalogenating a cyclopropane-carboxylic acid of the following general formula:-Y\/
R1 2 \ -COOH (II) R H
or a salt, anhydride, carboxamide or alkyl ester thereof, in the
- 2 - ~
3~
presence of zinc and an alkanoic acid, the symbols R1, ~2 and X
in formula II having the same meaning as in formula I and Y repre-senting a halogen atom having an atomic number which is the same as or more than that of the halogen atom represented by X.
In general Eormula II, when X represents a fluorine atom Y represents a fluorine, chlorine, bromine or iodine atom. When X
represents a chlorine atom, Y represents a chlorine, bromine or iodine atom. When X represents a bromine atom, Y represents a bromine or an iodine atom and when X represents an iodine atom, Y
also represents an iodine atom. X and Y are preferably equal and preferably represent chlorine atoms.
The substituents Rl and R2 are preferably both methyl groups or one of them is a methyl group and the other a hydrogen atom.
Examples of preferred compounds of formula I are 3-chloro-2,2-dimethylcyclopropanecarboxylic acid, methyl 3-chloro-2,2-dimethylcyclopropanecarboxylate, and tert-butyl 3-chloro-2,2-dimethylcyclopropanecarboxylate.
The dehalogenating agent may be any agent capable of selectively removing one of the halogen atoms from the starting material of formula II and is preferably zinc and an alkanoic acid or a tri(hydrocarbyl) tin hydride, e.g. tributyltin hydride.
The dehalogenation with zinc and an alkanoic acid is suitably carried out in the presence of an ammonium salt or water, because this enhances the conversion of the starting cyclopropane derivative; preferably, both an ammonium salt and water are ~;Z1831.
present. Examples of ammonium salts are ammonium chloride and ammonium sulphate. Very good results have been obtained with ammonium chloride. The molar ratios of ammonium salt to zinc and of water to alkanoic acid are not critical and may vary within wide limits, but the best results are usually obtained at molar ratios ranging from -- 3a -3~
0.01:1 to 1 1.
The selectivity to the cyclopropanecarboxylic acid of the general formula I or to a salt, an anhyclride, a carboxamide or an al}yl ester thereof is usually very high and often 100~b, when use la made of a dehalogenating agent obtained by mixing zinc and an alkalloic acid for example acetic acid or propionic acidO ~he use of acetic acid has given very good resulta. ~he expression"selectivity to a certain compound", given in a percentage, i3 defined as:-b x 100 wherein a is the molar amount of the compound of formula II, or of a salt, an anhydride, a carboxamide or an alkyl ester thereof, converted into that certain compound, and b is the molar amount of the converted compound of formula II, or of a salt~ an anhydride, a carboxamide or an alkyl ester thereof.
The reaction temperature for the procesa according to the invention may lie within the range 50 to 150 C, although lower temperatures may be necessary in the first stages of the reaction when a hydrocarbyl tin hydride dehalogenating agent is employed.
~he conversion of the starting cyclopropane derivative i3 enhanced by carrying out the process under an atmosphere of an inert gas, such as nitrogen or a noble gas.
The molar ratio of zinc to the compound of formula II
may vary within a wide range but is usually between 0.5:1 and 20:1, and preferably between 1:1 and 10:1. The zinc may be used in the form of dust, powder or granulea. Zinc duat and powder are preferred, because small particlea enhance the conversion of the compound of formula II and the proportion of the zinc used for the partial dehalogenation.
Simple derivatives of the carboxylic acid of formula I, e.g. the acyl halides, can be prepared from this acid in a manner known in the art.
As has been ~tated hereinbefore the products of the procesa according -to the invention, i.e. the compounds of the general formula I are novel compounds and these are claimed as such.
The invention i3 further illustrated in the following Examples. ~he ~ spectra quoted were measured at 60 ~z using solutions of the compounds in deuterochloroform.
E~e~ Pr~aration of methyl_3-chloro-2,2-dimethylcyclo-propanecarboxylate __________________ A 500 ml, round-bottomed, three-necked flask, equipped with a mechanical stirrer, thermometer and reflux condenser, was charged with acetic acid, ammonium chloride and 0.1 mol of methyl 3,3-dichloro-2,2-dimethylcyclopropanecarboxylate. After the contents of the flask had been heated with stirring to reflux temperature - about 110 C - 0.46 mol of zinc powder was gradually added over a period of 3 hours under an atmosphere of nitrogen. When the addition was complete the mixture was ~irred under reflux for a period of 17 hours. At the end of this period the conversion of the starting methyl e~ter ~as 71% anc the selectivity to the title ester 100%.
~hen 0.23 mol o zinc powder was added in one portion and stirring was continued for 7 hours. At the end of this period the con~ersion of the starting ester wa& 80~6 and the ~electi~ity to the title ester 100%. ~hen 0.23 mol of zinc powder was added in one portion and stirring was continued for 16 hours, the molar ratio of ammonium chloride to the total amount of æinc added being 0.09. At the end of the latter period the selectivity to the title ester was 95%
at 91% conversion o~ the starting ester.
~he molar ratio~ used were ae follows:
acetic acid to methyl 3,3-dichloro-2,2-dimethylcyclopropane-carboxylate 35 : 1 water to acetic acid 0.31: 1 zinc to methyl 3,3-dichloro-2,2-dimethylcyclopropane-carboxylate 9.2 : 1 ammonium chloride to zinc 0.09: 1 The mixture obtained was allowed to adopt a temperature ilZi~3~
of 22C and the unreacted zinc powder ~.ra3 recovered by decantation. The amount of zinc thus recovered corresponded to 7h5S of the starting amount. A~ 10% of the starting amount of the zino had dechlorinated the starting methyl ester, 16%
o~ the starting amount of the zinc had reacted with acetic acid, but had not been used for the dechlorination.
The dec~nted liquid obtained after the reco~ery of the unreacted zinc was poured out into 650 ml of water and the mixture of the organic and aqueous pha~es thus formed was extrac-ted with three 50-ml portions of dichloromethane. The three extract pha~es ~ere combined ana the liquid thus obtained t~ra~ washed with 100 ml of a 3aturated aqueous solution of sodium bicarbonate. The washed liquid was dried over anhydrous magnesium sulphate and the dichloromethane was removed from the dried liquid under reduced pressure.
~ractional distillation of the residue at 18 mm Hg y~elded the following three fractions:
~raction ~oilOng range, Content of, ~m, Cstarting methyl title ester ester trans cis ________ ____________________________________ _____ III 87-90 16 >80 ~4 ___________________________________________________________ The total yield of the title ester ~as 70~, calculated on starting methyl ester.
The ~ spectrum of the title ester showed the following absorptions relative to a tetramethylsilane standard;
the cis structure: the trans structure:
o = 1.22 ppm (singlet, trans )CH3) ~ o 1.26 ppm (singlet,trans1)CH3) ~ = 1.39 ppm (singlet, cis1)CH3) ~ = 1.35 ppm (singlet,cis1)CH3) o = 1.79 p~m (doùblet, HCCOOC~3); 6 = 1.77 ppm (doublet,HCCOOCH3);
I=7.8 Hz H-H I=4.2 Hz H-H
b = 3.26 ppm (doublet, HCCl); o - 3.50 ppm (doublet,HCCl);
I=7.8 Hz H-H I=4.2 Hz H-~
b = 3.71 ppm (singlet, COOCH3) ~ = 3.71 ppm (singlet,COOCH3) 1) with respect to the COOCH3 group.
~lZ1831 ~xample II - Preparation of 3-chloro-2,2-dimethylcyclopropane-________________ _____________________________________________ carboxylic acid ________________ The flask used in E~ample I was flushed with nitrogen and charged witll acetic acid, water, ammonium chloride and 0.165 mol of 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid. After the contents of the flask had been heated to reflux temperature with stlrring, zinc powder - originating from a bottle that h~d been opened for the first time - was gradually added over a period of 45 minutes. ~hen the flask was kept at this temperature for a period of 20 hours. The molar ratios used were as follows:
acetic acia to ~,3-dichloro-2,2-dimethyl-cyclopropanecarboxylic acid 32 : 1 water to acetic acid 0.31: 1 zinc to 3,3-dichloro-2,2-dimethylcyclo-propanecarboxylic acid 4.2 : 1 ammonium chloride to zinc 0.12: 1 At the end of the latter period the selectivity to the title aGid was 100yo at 80,~ conversion of 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid.
The mixture obtained was allowed to adopt a temperature of 22C and the unreacted zinc powder was recovered by decantation.
The amount of zinc thus recovered corresponded to 49% of the starting amount. As 19~ of the starting amount of the zinc had dechlorinated the starting acid, 32% of the starting amount of the zinc had reacted with acetic acid, but had not been used for the dechlorination.
~he acetic acid wa~ flashed off from the decanted liquid obtained after recovery of the zinc powder at a pressure of 12 mm ~g and the residue obtained was mixed with 200 ml of water. ~he mixt-u e formed was extracted with five 50-mol portions of dichloromethane, the five extract phases were combined, the liquid thus obtained was dried over anhydrous magnesium sulphate and the dichloromethane was removed from the dried liquid under reduced pressure. ~ractional distillation of the residue yielded the following four fractions:
~33i ~raction 130iling point~ Pressure~ Content of, !/dll~
C n~nHg ace-tic acid starting titl& acid acid trans cis _~______ _____.__ ._____ _______.__ _____~ ___ _. ______ _____ ___ 50-55 0.2 98 0 5II 78 0 1)5 1 12 31 45 III 85 0.15 17 27 56 __________________________________________________________________ ~ he total yield of the title acid was 62%, calculated on starting 3,3-dichloro-2,2-di-methJl-cyclo-propane-carboxylic acid.
The ~ R spectrum of the title acid showed the following absorptions relative to a tetramethylsilane standard:
the Ci3 struc ture the trans structure ~ = 1.24 ppm (singlet, trans1)CH3) o = 1.32 ppm (singïet,trans1)CH3) o = 1~40 ppm (sin~let, cis1)CH3) b = 1.39 ppm (sin~let, cis1 )C~3) o = 1.78 ppm (doublet, HCCOOCH3); o = 1.77 ppm (doublet, HCCOOCH3);
I-7.9 Hz ~-H I=4.1 ~z H-X
o = 3.28 ppm (doublet, ECCl); o = 3.51 ppm (doublet, ICCl);
I=7.9 Hæ H-H I=4.1 Hz H~H
'o = 11.1 ppm (singlet, COOH) ~o = 11.1 ppm (singlet, COOH).
1 )with re3pect to the COOH group.
~aml~les III-VII - Prel~aration of 3-chloro-2,2-dimethylcyclopropane-______________________.___~__________________________________________ carbox;rlic acid ~ 100-ml, ~ound-bottomed, three-necked flask, equipped with a magnetic stirrerp thermometer and reflux condenser was charged with 3~3-dichloro-2,2-dimethylcyclopropanecarboxylic acid, water, ammonium chloride, if any, and zinc. l'he flask had not been flushed with nitrogen, ~he contents of the flask were heated with stirring to reflux temperature and kept at this temperature for a certain period. ~t the end of this period the conversion of 3,3-dichloro-2,2-dimethylcyclopropane-carboxylic acid and the selectivity to the title acid were determined. ~wo of the molar ratios used were as follows:
acetic acid to 3,3-dichloro-2,2-dimethylcyclopropane-carbo~cylic acid 32: 1 sinc to 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid 4.2:1 11;~ 3~
~ive experiments were carried out in the manner described above. llhe ~able shows the starting amount of 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid, the molar ratio of water to acetic acid and of ammonium chloride to zinc, the type of ~inc used, the reaction time and t,he convereion of 3,3-dichloro-2~2-dimethylcyclopropanecarboxylic acid at the end of -this time, The selec-tivity to the title acid wa~ 100~/o in the five experiment~.
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a~ +~ 1 ~ 1I G~
presence of zinc and an alkanoic acid, the symbols R1, ~2 and X
in formula II having the same meaning as in formula I and Y repre-senting a halogen atom having an atomic number which is the same as or more than that of the halogen atom represented by X.
In general Eormula II, when X represents a fluorine atom Y represents a fluorine, chlorine, bromine or iodine atom. When X
represents a chlorine atom, Y represents a chlorine, bromine or iodine atom. When X represents a bromine atom, Y represents a bromine or an iodine atom and when X represents an iodine atom, Y
also represents an iodine atom. X and Y are preferably equal and preferably represent chlorine atoms.
The substituents Rl and R2 are preferably both methyl groups or one of them is a methyl group and the other a hydrogen atom.
Examples of preferred compounds of formula I are 3-chloro-2,2-dimethylcyclopropanecarboxylic acid, methyl 3-chloro-2,2-dimethylcyclopropanecarboxylate, and tert-butyl 3-chloro-2,2-dimethylcyclopropanecarboxylate.
The dehalogenating agent may be any agent capable of selectively removing one of the halogen atoms from the starting material of formula II and is preferably zinc and an alkanoic acid or a tri(hydrocarbyl) tin hydride, e.g. tributyltin hydride.
The dehalogenation with zinc and an alkanoic acid is suitably carried out in the presence of an ammonium salt or water, because this enhances the conversion of the starting cyclopropane derivative; preferably, both an ammonium salt and water are ~;Z1831.
present. Examples of ammonium salts are ammonium chloride and ammonium sulphate. Very good results have been obtained with ammonium chloride. The molar ratios of ammonium salt to zinc and of water to alkanoic acid are not critical and may vary within wide limits, but the best results are usually obtained at molar ratios ranging from -- 3a -3~
0.01:1 to 1 1.
The selectivity to the cyclopropanecarboxylic acid of the general formula I or to a salt, an anhyclride, a carboxamide or an al}yl ester thereof is usually very high and often 100~b, when use la made of a dehalogenating agent obtained by mixing zinc and an alkalloic acid for example acetic acid or propionic acidO ~he use of acetic acid has given very good resulta. ~he expression"selectivity to a certain compound", given in a percentage, i3 defined as:-b x 100 wherein a is the molar amount of the compound of formula II, or of a salt, an anhydride, a carboxamide or an alkyl ester thereof, converted into that certain compound, and b is the molar amount of the converted compound of formula II, or of a salt~ an anhydride, a carboxamide or an alkyl ester thereof.
The reaction temperature for the procesa according to the invention may lie within the range 50 to 150 C, although lower temperatures may be necessary in the first stages of the reaction when a hydrocarbyl tin hydride dehalogenating agent is employed.
~he conversion of the starting cyclopropane derivative i3 enhanced by carrying out the process under an atmosphere of an inert gas, such as nitrogen or a noble gas.
The molar ratio of zinc to the compound of formula II
may vary within a wide range but is usually between 0.5:1 and 20:1, and preferably between 1:1 and 10:1. The zinc may be used in the form of dust, powder or granulea. Zinc duat and powder are preferred, because small particlea enhance the conversion of the compound of formula II and the proportion of the zinc used for the partial dehalogenation.
Simple derivatives of the carboxylic acid of formula I, e.g. the acyl halides, can be prepared from this acid in a manner known in the art.
As has been ~tated hereinbefore the products of the procesa according -to the invention, i.e. the compounds of the general formula I are novel compounds and these are claimed as such.
The invention i3 further illustrated in the following Examples. ~he ~ spectra quoted were measured at 60 ~z using solutions of the compounds in deuterochloroform.
E~e~ Pr~aration of methyl_3-chloro-2,2-dimethylcyclo-propanecarboxylate __________________ A 500 ml, round-bottomed, three-necked flask, equipped with a mechanical stirrer, thermometer and reflux condenser, was charged with acetic acid, ammonium chloride and 0.1 mol of methyl 3,3-dichloro-2,2-dimethylcyclopropanecarboxylate. After the contents of the flask had been heated with stirring to reflux temperature - about 110 C - 0.46 mol of zinc powder was gradually added over a period of 3 hours under an atmosphere of nitrogen. When the addition was complete the mixture was ~irred under reflux for a period of 17 hours. At the end of this period the conversion of the starting methyl e~ter ~as 71% anc the selectivity to the title ester 100%.
~hen 0.23 mol o zinc powder was added in one portion and stirring was continued for 7 hours. At the end of this period the con~ersion of the starting ester wa& 80~6 and the ~electi~ity to the title ester 100%. ~hen 0.23 mol of zinc powder was added in one portion and stirring was continued for 16 hours, the molar ratio of ammonium chloride to the total amount of æinc added being 0.09. At the end of the latter period the selectivity to the title ester was 95%
at 91% conversion o~ the starting ester.
~he molar ratio~ used were ae follows:
acetic acid to methyl 3,3-dichloro-2,2-dimethylcyclopropane-carboxylate 35 : 1 water to acetic acid 0.31: 1 zinc to methyl 3,3-dichloro-2,2-dimethylcyclopropane-carboxylate 9.2 : 1 ammonium chloride to zinc 0.09: 1 The mixture obtained was allowed to adopt a temperature ilZi~3~
of 22C and the unreacted zinc powder ~.ra3 recovered by decantation. The amount of zinc thus recovered corresponded to 7h5S of the starting amount. A~ 10% of the starting amount of the zino had dechlorinated the starting methyl ester, 16%
o~ the starting amount of the zinc had reacted with acetic acid, but had not been used for the dechlorination.
The dec~nted liquid obtained after the reco~ery of the unreacted zinc was poured out into 650 ml of water and the mixture of the organic and aqueous pha~es thus formed was extrac-ted with three 50-ml portions of dichloromethane. The three extract pha~es ~ere combined ana the liquid thus obtained t~ra~ washed with 100 ml of a 3aturated aqueous solution of sodium bicarbonate. The washed liquid was dried over anhydrous magnesium sulphate and the dichloromethane was removed from the dried liquid under reduced pressure.
~ractional distillation of the residue at 18 mm Hg y~elded the following three fractions:
~raction ~oilOng range, Content of, ~m, Cstarting methyl title ester ester trans cis ________ ____________________________________ _____ III 87-90 16 >80 ~4 ___________________________________________________________ The total yield of the title ester ~as 70~, calculated on starting methyl ester.
The ~ spectrum of the title ester showed the following absorptions relative to a tetramethylsilane standard;
the cis structure: the trans structure:
o = 1.22 ppm (singlet, trans )CH3) ~ o 1.26 ppm (singlet,trans1)CH3) ~ = 1.39 ppm (singlet, cis1)CH3) ~ = 1.35 ppm (singlet,cis1)CH3) o = 1.79 p~m (doùblet, HCCOOC~3); 6 = 1.77 ppm (doublet,HCCOOCH3);
I=7.8 Hz H-H I=4.2 Hz H-H
b = 3.26 ppm (doublet, HCCl); o - 3.50 ppm (doublet,HCCl);
I=7.8 Hz H-H I=4.2 Hz H-~
b = 3.71 ppm (singlet, COOCH3) ~ = 3.71 ppm (singlet,COOCH3) 1) with respect to the COOCH3 group.
~lZ1831 ~xample II - Preparation of 3-chloro-2,2-dimethylcyclopropane-________________ _____________________________________________ carboxylic acid ________________ The flask used in E~ample I was flushed with nitrogen and charged witll acetic acid, water, ammonium chloride and 0.165 mol of 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid. After the contents of the flask had been heated to reflux temperature with stlrring, zinc powder - originating from a bottle that h~d been opened for the first time - was gradually added over a period of 45 minutes. ~hen the flask was kept at this temperature for a period of 20 hours. The molar ratios used were as follows:
acetic acia to ~,3-dichloro-2,2-dimethyl-cyclopropanecarboxylic acid 32 : 1 water to acetic acid 0.31: 1 zinc to 3,3-dichloro-2,2-dimethylcyclo-propanecarboxylic acid 4.2 : 1 ammonium chloride to zinc 0.12: 1 At the end of the latter period the selectivity to the title aGid was 100yo at 80,~ conversion of 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid.
The mixture obtained was allowed to adopt a temperature of 22C and the unreacted zinc powder was recovered by decantation.
The amount of zinc thus recovered corresponded to 49% of the starting amount. As 19~ of the starting amount of the zinc had dechlorinated the starting acid, 32% of the starting amount of the zinc had reacted with acetic acid, but had not been used for the dechlorination.
~he acetic acid wa~ flashed off from the decanted liquid obtained after recovery of the zinc powder at a pressure of 12 mm ~g and the residue obtained was mixed with 200 ml of water. ~he mixt-u e formed was extracted with five 50-mol portions of dichloromethane, the five extract phases were combined, the liquid thus obtained was dried over anhydrous magnesium sulphate and the dichloromethane was removed from the dried liquid under reduced pressure. ~ractional distillation of the residue yielded the following four fractions:
~33i ~raction 130iling point~ Pressure~ Content of, !/dll~
C n~nHg ace-tic acid starting titl& acid acid trans cis _~______ _____.__ ._____ _______.__ _____~ ___ _. ______ _____ ___ 50-55 0.2 98 0 5II 78 0 1)5 1 12 31 45 III 85 0.15 17 27 56 __________________________________________________________________ ~ he total yield of the title acid was 62%, calculated on starting 3,3-dichloro-2,2-di-methJl-cyclo-propane-carboxylic acid.
The ~ R spectrum of the title acid showed the following absorptions relative to a tetramethylsilane standard:
the Ci3 struc ture the trans structure ~ = 1.24 ppm (singlet, trans1)CH3) o = 1.32 ppm (singïet,trans1)CH3) o = 1~40 ppm (sin~let, cis1)CH3) b = 1.39 ppm (sin~let, cis1 )C~3) o = 1.78 ppm (doublet, HCCOOCH3); o = 1.77 ppm (doublet, HCCOOCH3);
I-7.9 Hz ~-H I=4.1 ~z H-X
o = 3.28 ppm (doublet, ECCl); o = 3.51 ppm (doublet, ICCl);
I=7.9 Hæ H-H I=4.1 Hz H~H
'o = 11.1 ppm (singlet, COOH) ~o = 11.1 ppm (singlet, COOH).
1 )with re3pect to the COOH group.
~aml~les III-VII - Prel~aration of 3-chloro-2,2-dimethylcyclopropane-______________________.___~__________________________________________ carbox;rlic acid ~ 100-ml, ~ound-bottomed, three-necked flask, equipped with a magnetic stirrerp thermometer and reflux condenser was charged with 3~3-dichloro-2,2-dimethylcyclopropanecarboxylic acid, water, ammonium chloride, if any, and zinc. l'he flask had not been flushed with nitrogen, ~he contents of the flask were heated with stirring to reflux temperature and kept at this temperature for a certain period. ~t the end of this period the conversion of 3,3-dichloro-2,2-dimethylcyclopropane-carboxylic acid and the selectivity to the title acid were determined. ~wo of the molar ratios used were as follows:
acetic acid to 3,3-dichloro-2,2-dimethylcyclopropane-carbo~cylic acid 32: 1 sinc to 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid 4.2:1 11;~ 3~
~ive experiments were carried out in the manner described above. llhe ~able shows the starting amount of 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid, the molar ratio of water to acetic acid and of ammonium chloride to zinc, the type of ~inc used, the reaction time and t,he convereion of 3,3-dichloro-2~2-dimethylcyclopropanecarboxylic acid at the end of -this time, The selec-tivity to the title acid wa~ 100~/o in the five experiment~.
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`~
11 E~
O O r-l I 11 ~: h p, ~ I 11 ~ o o o ,~ ,( o I 11 ~ ~ ~ 1 11 0 .~ o.~ h I C~l ~ ~ ~ ~ 11 r~
bD ~i O C) O I O O O O O 1l 0 ~1 r~ rt ~ I O O O O 0 ll r~ I P,~ I il P
o3 c\J o ,l I 11 C~
- h I ¦¦ u~
a~ I 11 ! ~ ~ H H ,, P
~;~ I H H rS P r~ 11 ~~
~3 i 'I ~
i!331 At the end of the reaction time the mixtures we~e allowed to adopt a temperature of 22 ~ and the unreacted zinc was recovered by decantation. The amounts of zinc recovered, used for dechlorination and reacted but not used for dechlorination, are al50 prese~ted in the table.
Exam~le rx - Pre~aration of 3-chloro-2,2-dimethylcyclopro~ane-_ _ _ _ _ _ ___ __ _ __ _ .~ _ _ . ._ _ .___ __ _ _ . _ _ _ _ _ __ _ __ _ _ _ ___ _ ____ __ _ ___ __ _ _ carboxylic acid The flaQk u~ed in Example III wa~ charged with 0.018 mol of tert-butyl 3,3-dichloro-2,2-dimethylcyclopropanecarboxylate, acetic acid and zinc powder. ~he molar ratios used were a3 follo~s:
acetic acid ~o tert-butyl 3,3-dichloro-2,2-dimethylcyclopropanecarboxylate39 : 1 zinc to tert butyl 3,3-dichloro-2,2-di-methylcyclopropanecarbo~ylate 5 : 1 l'he contents of the flask were heated with stirring to reflux temperature and kept at thi3 temperature for 18 hours.
After 30 minutes' heating the tert-butyl ester had been quantitatively converted into 3,3-dichloro-2,2-dimethylcyclo-propanecarboxylic acid. At the end of the period of 18 hours the selectivities were as follow3:
to 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid 80%
to 3-chloro-2,2-dimethylcyclopropanecarboxylic acid 10%
to organic compounds with an open chain of carbon atoms 10%.
Comparison of the conversion of 3,3-dichloro-2,2-dimethyl-cyclopropanecarboxylic acid - which was only 20% - and the selecti~ity to 3-chloro-2,2-dimethylcyclopropanecarboxylic acid of this example with those of Example III shows the favourable effect of water.
Example X - Preparat~on of tert-butyl 3-chloro-2,2-dimethyl-__________~____~_.__________________________________________ cyclopropanecarboxylate A lO0-ml, round-bottomed, three-necked flask, equipped with a magnetic stirrer, thermometer, reflux condenser, calcium chloride tube, inlet for nitrogen and dropping funnel was charged with 0.0344mol of tert-butyl 3,3-dichloro-2,2-dimethylcyclopropane-~l~tB3i carboxylate. After cooling of the fla~k to O C, 0.0344 mol of tributyltinhydride was ~radually added with stirring over a period of 15 minutes. ~hen the reaction mixture was ~lowly warmed to a temperature between 35 and 40C and kept at this temperature for 18 hours. At the end of this period the conversion of tert-butyl 3,3-dichloro-2~2-dimethylcyclopropane-carboxylate was 10~6. The temperature was raised to 85C and after the reaction time indicated below the following conversions were found:
10Reaction time, Conversion, h %
______________ ___________ 7 bO
______________ ___________ ~he reaction times 3tated were measured from the moment the temperature had reached 85 C.
~he selectivity to tert-butyl 3-chloro-2,2-dimethylcyclo-propanecarboxylate was 100~. The reaction mixture thus obtained was distilled at 42-52C and 0.25-0.30 mm Hg, to give the title ester in a yield of 47%, calculated on starting tert-butyl ester. The cis/trans ratio was 1.1.
~he NMR spectrum of the title ester showed the following absorptions relative to a tetramethylsilane standard:
the cis structure the trans structure 6 = 1.19 ppm (singlet, trans1)CH3) o = 1.24 ppm (singlet,trans1)CH3) = 1.38 ppm (~inglet, cis1)CH3) ~ = 1.34 ppm (singlet,cis1)CH3) = 1.48 ppm (sin~let, C4~9) ~ = 1.47 ppm (singlet, C4H9) b = 1.67 ppm (doublet, HCCOOC4~ ); o = 1.66 ppm (doublet,HCCOOC4~9);
I=8.1 Hz H-H 9 I=4.1 Hz H-H
~ = 3.13 ppm (doublet, HCCl); ~ = 3.41 ppm (doublet, HCCl);
I=8.1 Hz H-H I=4.1 Hz H-H
)with respect to the COOC4H9 group.
o o ~ I h ~11 h 0 1 a~ o o o 0 11 ~ ~ l o r~ o ll f4 E~ t P~ ~ ~ ~ C~l 11 E~ ~
c~ o r~ ~ I O O O O 0 , ~ ~; ~ I 'I ~
hh I 11 O a~oo tooooo11 I 11 f.
`~
11 E~
O O r-l I 11 ~: h p, ~ I 11 ~ o o o ,~ ,( o I 11 ~ ~ ~ 1 11 0 .~ o.~ h I C~l ~ ~ ~ ~ 11 r~
bD ~i O C) O I O O O O O 1l 0 ~1 r~ rt ~ I O O O O 0 ll r~ I P,~ I il P
o3 c\J o ,l I 11 C~
- h I ¦¦ u~
a~ I 11 ! ~ ~ H H ,, P
~;~ I H H rS P r~ 11 ~~
~3 i 'I ~
i!331 At the end of the reaction time the mixtures we~e allowed to adopt a temperature of 22 ~ and the unreacted zinc was recovered by decantation. The amounts of zinc recovered, used for dechlorination and reacted but not used for dechlorination, are al50 prese~ted in the table.
Exam~le rx - Pre~aration of 3-chloro-2,2-dimethylcyclopro~ane-_ _ _ _ _ _ ___ __ _ __ _ .~ _ _ . ._ _ .___ __ _ _ . _ _ _ _ _ __ _ __ _ _ _ ___ _ ____ __ _ ___ __ _ _ carboxylic acid The flaQk u~ed in Example III wa~ charged with 0.018 mol of tert-butyl 3,3-dichloro-2,2-dimethylcyclopropanecarboxylate, acetic acid and zinc powder. ~he molar ratios used were a3 follo~s:
acetic acid ~o tert-butyl 3,3-dichloro-2,2-dimethylcyclopropanecarboxylate39 : 1 zinc to tert butyl 3,3-dichloro-2,2-di-methylcyclopropanecarbo~ylate 5 : 1 l'he contents of the flask were heated with stirring to reflux temperature and kept at thi3 temperature for 18 hours.
After 30 minutes' heating the tert-butyl ester had been quantitatively converted into 3,3-dichloro-2,2-dimethylcyclo-propanecarboxylic acid. At the end of the period of 18 hours the selectivities were as follow3:
to 3,3-dichloro-2,2-dimethylcyclopropanecarboxylic acid 80%
to 3-chloro-2,2-dimethylcyclopropanecarboxylic acid 10%
to organic compounds with an open chain of carbon atoms 10%.
Comparison of the conversion of 3,3-dichloro-2,2-dimethyl-cyclopropanecarboxylic acid - which was only 20% - and the selecti~ity to 3-chloro-2,2-dimethylcyclopropanecarboxylic acid of this example with those of Example III shows the favourable effect of water.
Example X - Preparat~on of tert-butyl 3-chloro-2,2-dimethyl-__________~____~_.__________________________________________ cyclopropanecarboxylate A lO0-ml, round-bottomed, three-necked flask, equipped with a magnetic stirrer, thermometer, reflux condenser, calcium chloride tube, inlet for nitrogen and dropping funnel was charged with 0.0344mol of tert-butyl 3,3-dichloro-2,2-dimethylcyclopropane-~l~tB3i carboxylate. After cooling of the fla~k to O C, 0.0344 mol of tributyltinhydride was ~radually added with stirring over a period of 15 minutes. ~hen the reaction mixture was ~lowly warmed to a temperature between 35 and 40C and kept at this temperature for 18 hours. At the end of this period the conversion of tert-butyl 3,3-dichloro-2~2-dimethylcyclopropane-carboxylate was 10~6. The temperature was raised to 85C and after the reaction time indicated below the following conversions were found:
10Reaction time, Conversion, h %
______________ ___________ 7 bO
______________ ___________ ~he reaction times 3tated were measured from the moment the temperature had reached 85 C.
~he selectivity to tert-butyl 3-chloro-2,2-dimethylcyclo-propanecarboxylate was 100~. The reaction mixture thus obtained was distilled at 42-52C and 0.25-0.30 mm Hg, to give the title ester in a yield of 47%, calculated on starting tert-butyl ester. The cis/trans ratio was 1.1.
~he NMR spectrum of the title ester showed the following absorptions relative to a tetramethylsilane standard:
the cis structure the trans structure 6 = 1.19 ppm (singlet, trans1)CH3) o = 1.24 ppm (singlet,trans1)CH3) = 1.38 ppm (~inglet, cis1)CH3) ~ = 1.34 ppm (singlet,cis1)CH3) = 1.48 ppm (sin~let, C4~9) ~ = 1.47 ppm (singlet, C4H9) b = 1.67 ppm (doublet, HCCOOC4~ ); o = 1.66 ppm (doublet,HCCOOC4~9);
I=8.1 Hz H-H 9 I=4.1 Hz H-H
~ = 3.13 ppm (doublet, HCCl); ~ = 3.41 ppm (doublet, HCCl);
I=8.1 Hz H-H I=4.1 Hz H-H
)with respect to the COOC4H9 group.
Claims (13)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the preparation of compounds having the following general formula:- (I) wherein X is a halogen atom; R1 is an alkyl group of from 1 to 6 carbon atoms; R2 is an alkyl group of from 1 to 6 carbon atoms;
or R1 and R2 together represent an alkylene chain of up to 5 carbon atoms; or a salt, anhydride, carboxamide or alkyl (1-6 carbon) ester thereof, which comprises partially dehalogenating a cyclopropane-carboxylic acid of the following general formula:- (II) or a salt, anhydride, carboxamide or alkyl ester thereof, in the presence of zinc and an alkanoic acid, the symbols R1, R2 and X
in formula II having the same meaning as in formula I and Y
representing a halogen atom having an atomic number which is the same as or more than that of the halogen atom represented by X.
or R1 and R2 together represent an alkylene chain of up to 5 carbon atoms; or a salt, anhydride, carboxamide or alkyl (1-6 carbon) ester thereof, which comprises partially dehalogenating a cyclopropane-carboxylic acid of the following general formula:- (II) or a salt, anhydride, carboxamide or alkyl ester thereof, in the presence of zinc and an alkanoic acid, the symbols R1, R2 and X
in formula II having the same meaning as in formula I and Y
representing a halogen atom having an atomic number which is the same as or more than that of the halogen atom represented by X.
2. A process according to claim 1 wherein the compound of formula I is in the form of the acid or the alkyl (1-6 carbon) ester, the alkali metal, alkaline earth metal or ammonium salt thereof.
3. A process according to claim 1 wherein the molar ratio of zinc to the compound of formula II is in the range 0.5:1 to 20:1.
4. A process according to claim 3 wherein dehalogenation is achieved with zinc and an alkanoic acid in the presence of an ammonium salt.
5. A process according to claim 4 carried out in the additional presence of water.
6. A process according to claim 5 wherein the molar ratios of ammonium salt to zinc and of water to alkanoic acid are in the range 0.01:1 to 1:1.
7. A process according to claim 6 wherein the alkanoic acid is acetic or propionic acid.
8. A process according to claim 1, 2 or 6 wherein X and Y are chlorine and R1 and R2 are both methyl groups.
9. A process according to claim 1 wherein 2,2-dihalo-3,3-dimethylcyclopropane-carboxylic acid or its lower alkyl ester is partially dehalogenated in the presence of zinc, acetic acid, an ammonium salt and water to give 2-halo-3,3-dimethylcyclopropane-carboxylic acid or its lower alkyl ester.
10. Compounds of the following general formula:- (I) wherein X is a halogen atom, R1 is an alkyl group of from 1 to 6 carbon atoms; R2 is an alkyl group of from 1 to 6 carbon atoms;
or R1 and R2 together represent an alkylene chain of up to 5 carbon atoms or a salt, anhydride, carboxamide or alkyl (1-6 carbon) ester thereof.
or R1 and R2 together represent an alkylene chain of up to 5 carbon atoms or a salt, anhydride, carboxamide or alkyl (1-6 carbon) ester thereof.
11. Compounds according to claim 10 in the form of the acid or the alkyl (1-6 carbon) ester, the alkali metal, alkaline earth metal or ammonium salt thereof.
12. Compounds according to claim 10 wherein X is chlorine and R1 and R are both methyl groups.
13. Compounds according to claim 12 in the form of the acid or the methyl or t-butyl ester.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB3164/77 | 1977-01-26 | ||
| GB3164/77A GB1594224A (en) | 1977-01-26 | 1977-01-26 | Preparation of cyclopropane derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1121831A true CA1121831A (en) | 1982-04-13 |
Family
ID=9753142
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000294304A Expired CA1121831A (en) | 1977-01-26 | 1978-01-04 | Preparation of cyclopropane derivatives |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS5392743A (en) |
| BE (1) | BE863272A (en) |
| BR (1) | BR7800411A (en) |
| CA (1) | CA1121831A (en) |
| CH (1) | CH634035A5 (en) |
| DE (1) | DE2802967A1 (en) |
| FR (1) | FR2378740A1 (en) |
| GB (1) | GB1594224A (en) |
| IT (1) | IT7819574A0 (en) |
| MX (1) | MX4672E (en) |
| NL (1) | NL7800811A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3026093C2 (en) * | 1980-07-10 | 1983-02-10 | Degussa Ag, 6000 Frankfurt | 1-methyl-2-chlorocyclopropanecarboxylic acid and its branched and unbranched C? 1? to C 6 alkyl esters, and processes for their preparation |
| DE602004030091D1 (en) * | 2003-01-07 | 2010-12-30 | Daiichi Sankyo Co Ltd | PROCESS FOR REDUCING DESHALOGENIZATION |
-
1977
- 1977-01-26 GB GB3164/77A patent/GB1594224A/en not_active Expired
-
1978
- 1978-01-04 CA CA000294304A patent/CA1121831A/en not_active Expired
- 1978-01-24 NL NL7800811A patent/NL7800811A/en not_active Application Discontinuation
- 1978-01-24 FR FR7801895A patent/FR2378740A1/en active Granted
- 1978-01-24 JP JP588578A patent/JPS5392743A/en active Pending
- 1978-01-24 BE BE184604A patent/BE863272A/en not_active IP Right Cessation
- 1978-01-24 CH CH75178A patent/CH634035A5/en not_active IP Right Cessation
- 1978-01-24 DE DE19782802967 patent/DE2802967A1/en not_active Withdrawn
- 1978-01-24 IT IT7819574A patent/IT7819574A0/en unknown
- 1978-01-24 MX MX678678U patent/MX4672E/en unknown
- 1978-01-24 BR BR7800411A patent/BR7800411A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX4672E (en) | 1982-07-23 |
| FR2378740B1 (en) | 1981-08-21 |
| JPS5392743A (en) | 1978-08-15 |
| BE863272A (en) | 1978-07-24 |
| IT7819574A0 (en) | 1978-01-24 |
| BR7800411A (en) | 1978-08-22 |
| CH634035A5 (en) | 1983-01-14 |
| NL7800811A (en) | 1978-07-28 |
| FR2378740A1 (en) | 1978-08-25 |
| GB1594224A (en) | 1981-07-30 |
| DE2802967A1 (en) | 1978-07-27 |
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