GB1594224A - Preparation of cyclopropane derivatives - Google Patents
Preparation of cyclopropane derivatives Download PDFInfo
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- GB1594224A GB1594224A GB3164/77A GB316477A GB1594224A GB 1594224 A GB1594224 A GB 1594224A GB 3164/77 A GB3164/77 A GB 3164/77A GB 316477 A GB316477 A GB 316477A GB 1594224 A GB1594224 A GB 1594224A
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- dichloro
- alkyl group
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- 238000002360 preparation method Methods 0.000 title claims description 12
- 125000001559 cyclopropyl group Chemical class [H]C1([H])C([H])([H])C1([H])* 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 25
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 125000005907 alkyl ester group Chemical group 0.000 claims abstract description 13
- 125000005843 halogen group Chemical group 0.000 claims abstract description 12
- 150000008064 anhydrides Chemical class 0.000 claims abstract description 11
- 150000003857 carboxamides Chemical class 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 57
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 48
- 239000011701 zinc Substances 0.000 claims description 37
- 229910052725 zinc Inorganic materials 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 20
- YUBCVMNXGPVXID-UHFFFAOYSA-N 2,2-dichloro-3,3-dimethylcyclopropane-1-carboxylic acid Chemical compound CC1(C)C(C(O)=O)C1(Cl)Cl YUBCVMNXGPVXID-UHFFFAOYSA-N 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 150000003863 ammonium salts Chemical class 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- GHXJAGHRKSJMPQ-UHFFFAOYSA-N 3-chloro-2,2-dimethylcyclopropane-1-carboxylic acid Chemical compound CC1(C)C(Cl)C1C(O)=O GHXJAGHRKSJMPQ-UHFFFAOYSA-N 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 238000006298 dechlorination reaction Methods 0.000 claims description 6
- LNEFGAYKTMMXDW-UHFFFAOYSA-N tert-butyl 2,2-dichloro-3,3-dimethylcyclopropane-1-carboxylate Chemical compound CC(C)(C)OC(=O)C1C(C)(C)C1(Cl)Cl LNEFGAYKTMMXDW-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 4
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 4
- 238000010908 decantation Methods 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
- 238000005695 dehalogenation reaction Methods 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 150000001721 carbon Chemical class 0.000 claims description 2
- 230000002349 favourable effect Effects 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 150000002894 organic compounds Chemical class 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- VEMKTZHHVJILDY-UXHICEINSA-N bioresmethrin Chemical compound CC1(C)[C@H](C=C(C)C)[C@H]1C(=O)OCC1=COC(CC=2C=CC=CC=2)=C1 VEMKTZHHVJILDY-UXHICEINSA-N 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract description 2
- 150000007513 acids Chemical class 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 150000001942 cyclopropanes Chemical class 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 3
- ZJAJKMDQAODLNY-UHFFFAOYSA-N methyl 2,2-dichloro-3,3-dimethylcyclopropane-1-carboxylate Chemical compound COC(=O)C1C(C)(C)C1(Cl)Cl ZJAJKMDQAODLNY-UHFFFAOYSA-N 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical class C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000004508 fractional distillation Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- VPQWGHHXCIHSCW-UHFFFAOYSA-N methyl 3-chloro-2,2-dimethylcyclopropane-1-carboxylate Chemical compound COC(=O)C1C(Cl)C1(C)C VPQWGHHXCIHSCW-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000000061 acid fraction Substances 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 210000000540 fraction c Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- -1 if any Chemical compound 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- QCRGTFXKYABKHU-UHFFFAOYSA-N tert-butyl 3-chloro-2,2-dimethylcyclopropane-1-carboxylate Chemical compound ClC1C(C1C(=O)OC(C)(C)C)(C)C QCRGTFXKYABKHU-UHFFFAOYSA-N 0.000 description 1
Abstract
Compounds of the general formula: <IMAGE> in which X represents a halogen atom, while R<1> represents a hydrogen atom or an alkyl group, and R<2> represents an alkyl group, or R<1> and R<2>, together, represent an alkylene chain, or the salts, anhydrides, carboxamides or alkyl esters of these acids. Use as starting material for synthetic pyrethroids.
Description
(54) PREPARATION OF CYCLOPROPANE
DERIVATIVES
(71) We, SHELL INTERNATIONALE RESEARCH MAATSCHAPPIJ B.V., a Company organised under the laws of The Netherlands, of 30 Carel van Bylandtlaan, The Hague, The Netherlands, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- 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". The cyclopropane derivatives produced by the process according to the invention are novel compounds and are claimed as such.
Accordingly the present invention provides a process for the preparation of compounds having the following general formula:
wherein
X is a halogen atom;
R1 is an alkyl group;
R2 is an alkyl group; or R' and R2 together represent an alkylene chain; or a salt, anhydride, carboxamide or alkyl ester thereof, which comprises partially dehalogenating a cyclopropane-carboxylic acid of the following general formula:
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.
Preferred compounds prepared by the process according to the invention are those having general formula I wherein
X is a halogen atom;
R' is an alkyl group of 1 to 6 carbon atoms;
R2 is an alkyl group of 1 to 6 carbon atoms; or
R1 and R2 together represent an alkylene chain of up to 5 carbon atoms; or the alkyl (1--6 carbon) esters, the alkali metal, alkaline earth metal and ammonium salts thereof.
In the general formula 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 R' and R2 are preferably both methyl groups.
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 dehalogenation with zinc and an alkanoic acid is suitably carried out in the presence of an ammonium salt and/or water, because this enhances the conversion of the starting cyclopropane derivative; preferably, both an ammonium salt and water are 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 0.01:1 to 1:1.
The selectivity to the cyclopropanecarboxylic acid of the general formula I or to a salt, an anhydride, a carboxamide or an alkyl ester thereof is usually very high and often 100%, when use is made of a dehalogenating agent obtained by mixing zinc and an alkanoic acid for example acetic acid or propionic acid. The use of acetic acid has given very good results. The expression "selectivity to a certain compound", given in a percentage, is defined as:
a -x100 b 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 compound of formula II, or of a salt, an anhydride, a carboxamide or an alkyl ester thereof consumed in the course of the reaction.
The reaction temperature for the process according to the invention may lie within the range 500 to 1500C.
The conversion of the starting cyclopropane derivative is 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 granules. Zinc dust and powder are preferred, because small particles 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 stated hereinbefore the products of the process according to the invention, i.e. the compounds of the general formula I are novel compounds and these are claimed as such.
The invention is further illustrated in the following Examples. The NMR spectra quoted were measured at 60 MHz using solutions of the compounds in deuterochloroform.
Example I
Preparation of Methyl 3-Chloro-2,2-dimethylcyclopropanecarboxylate
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 1 100C - 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 stirred under reflux for a period of 17 hours. At the end of this period the conversion of the starting methyl ester was 71 Ó and the selectivity to the title ester 100%.Then 0.23 mol of zinc powder was added in one portion and stirring was continued for 7 hours. At the end of this period the conversion of the starting ester was 80% and the selectivity to the title ester 100%.
Then 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 zinc added being 0.09. At the end of the latter period the selectivity to the title ester was 95% at 91% conversion of the starting ester. The molar ratios used were as follows:
acetic acid to methyl 3,3 - dichloro - 2,2
dimethylcyclopropanecarboxylate 35:1
water to acetic acid 0.31:1 zinc to methyl 3,3 - dichloro - 2,2
dimethylcyclopropanecarboxylate 9.2:1
ammonium chloride to zinc 0.09:1
The mixture obtained was allowed to adopt a temperature of 22"C and the unreacted zinc powder was recovered by decantation. The amount of zinc thus recovered corresponded to 74% of the starting amount.As 10% of the starting amount of the zinc had dechlorinated the starting methyl ester, 16% of the starting amount of the zinc had reacted with acetic acid, but had not been used for the dechlorination.
The decanted liquid obtained after the recovery of the unreacted zinc was poured out into 650 ml of water and the mixture of the organic and aqueous phases thus formed was extracted with three 50 ml portions of dichloromethane. The three extract phases were combined and the liquid thus obtained was washed with 100 ml of a saturated 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.Fractional distillation of the residue at 18 mm Hg yielded the following three fractions:
Content of, %m,
Boiling range, starting methyl title ester
Fraction "C ester trans cis I 83-85 < 5 71 24
II 85-87 8 82 8
III 87-90 16 > 80 < 4
The total yield of the title ester was 70%, calculated on starting methyl ester.
The NMR spectrum of the title ester showed the following absorptions relative to a tetramethylsilane standard:
the cis structure the trans structure 8=1.22 ppm (singlet, trans1 CH3) b=1.26 ppm (singlet, trans1 CH3) =1.39 ppm (singlet, cis" CH3) 8=1.35 ppm (singlet, cis" CH3) s=1.79 ppm (doublet, HCCOOCH3); 8=1.77 ppm (doublet, HCCOOCH3);
I=7.8 Hz H-H I=4.2 Hz H-H 8=3.26 ppm (doublet, HCCI); 8=3.50 ppm (doublet, HCCI); ; I=7.8 Hz H-H I=4.2 Hz H-H 8=3.71 ppm (singlet, COOCH3) 8=3.71 ppm (singlet, COOCH3) "with respect to the COOCH3 group.
Example II
Preparation of 3-Chloro-2,2-dimethylcyclopropanecarboxylic Acid
The flask used in Example I was flushed with nitrogen and charged with 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 stirring, zinc powder -- originating from a bottle that had been opened for the first time - was gradually added over a period of 45 minutes. Then the flask was kept at this temperature for a period of 20 hours.The molar ratios used were as follows:
acetic acid to 3,3 - dichloro - 2,2
dimethylcyclopropanecarboxylic acid 32:1
water to acetic acid 0.31:1
zinc to 3,3 - dichloro - 2,2
dimethylcyclopropanecarboxylic acid 4.2:1
ammonium chloride to zinc 0.12:1
At the end of the latter period the selectivity to the title acid was 100% at 80%
conversion of 3,3 - dichloro - 2,2 - dimethylcycopropanecarboxylic acid.
The mixture obtained was allowed to adopt a temperature of 22 C 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.
The acetic acid was flashed off from the decanted liquid obtained after
recovery of the zinc powder at a pressure of 12 mm Hg and the residue obtained
was mixed with 200 ml of water. The mixture 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.
Fractional distillation of the residue yielded the following four fractions:
Content of, %m,
Boiling point, Pressure, acetic starting title acid
Fraction C mm Hg acid acid trans cis
1 50-55 0.2 98 0 1 1
II 78 0.05 1 12 31 45
III 85 0.15 0 17 27 56
IV 85 0.15 0 24 17 59
The total yield of the title acid was 62%, calculated on starting 3,3 - dichloro
2,2 - dimethylcyclopropanecarboxylic acid.
The NMR spectrum of the title acid showed the following absorptions relative
to a tetramethylsilane standard:
the cis structure the trans structure #=1.24 ppm (singlet, trans"CH3) #=1.32 ppm(singlet, trans" CH3) #=1.40 ppm (singlet, cis" CH3) #=1.39 ppm(singlet, cis" CH3) #=1.78 ppm (doublet, HCCOOCH3) #=1.77 ppm(doublet, HCCOOCH3);
I=7.9 Hz H-H I=4.1 Hz H-H #=3.28 ppm (doublet, HCCl); #=3.51 ppm (doublet, HCCl);
I=7.9 Hz H-H I=4.1 Hz H-H #=11.1 ppm (singlet, COOH) #=11.1 ppm (singlet, COOH) "with respect to the COOH group.
Examples IlI-VIl Preparation of 3-Chloro-2,2-dimethylcyclopropanecarboxylic Acid
A 100 ml, round-bottomed, three-necked flask, equipped with a magnetic
stirrer, thermometer and reflux condenser was charged with 3,3 - dichloro - 2,2
dimethylcyclopropanecarboxylic acid, water, ammonium chloride, if any, and zinc.
The flask had not been flushed with nitrogen. The contents of the flask were heated
with stirring to reflux temperature and kept at this temperature for a certain period.
At the end of this period the conversion of 3,3 - dichloro - 2,2
dimethylcyclopropanecarboxylic acid and the selectivity to the title acid were
determined. Two of the molar ratios used were as follows:
acetic acid to 3,3 - dichloro - 2,2 - dimethylcyclo
propanecarboxylic acid 32:1 zinc to 3,3 - dichloro - 2,2 - dimethylcyclopropane
carboxylic acid 4.2:1
Five experiments were carried out in the manner described above. The Table
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 zinc used, the reaction time and the
conversion of 3,3 - dichloro - 2,2 - dimethylcyclopropanecarboxylic acid at the
end of this type.The selectivity to the title acid was 100% in the five experiments. TABLE
Conversion of
Starting amount 3,3-dichloroof 3,3-dichloro- Molar ratio 2,2-dimethyl- Zinc,% of starting amount reacted 2,2-dimethylcyclo- water to NH4Cl Type of Reaction cyclopropane- for depropanecarboxylic acetic to zinc time, carboxylic chlori- not for de
Example acid,mol acid zinc used h acid,% recovered nation chlorination
III 0.022 0.31:1 0:1 powder 6 32 78 8 14
IV 0.011 0.94:1 0:1 ditto 22 39 75 10 15
V 0.011 0.31:1 0.12:1 ditto 21 61 82 15 3
VI 0.011 0.31:1 0.61:1 ditto 20 42 58 10 32
VII 0.011 0.31:1 0.12:1 20 mesh" 1.5 9 19 2 79 "U.S. Sieve Series A.S.T.M. -E-11-61, largest dimension of particles being 0.841 mm.
At the end of the reaction time the mixtures were allowed to adopt a temperature of 22"C and the unreacted zinc was recovered by decantation. The amounts of zinc recovered, used for dechlorination and reacted but not used for dechlorination, are also presented in the table.
Example VIII
Preparation of 3-Chloro-2,2-dimethylcyclopropanecarboxylic Acid
The flask used in Example III was charged with 0.018 mol of tert-butyl 3,3 dichloro - 2,2 - dimethylcyclopropanecarboxylate, acetic acid and zinc powder.
The molar ratios used were as follows:
acetic acid to tert-butyl 3,3 - dichloro - 2,2
dimethylcyclopropanecarboxylate 39:1
zinc to tert-butyl 3,3 - dichloro - 2,2
dimethylcyclopropanecarboxylate 5:1
The contents of the flask were heated with stirring to reflux temperature and kept at this temperature for 18 hours. After 30 minutes' heating the tert-butyl ester had been quantitatively converted into 3,3 - dichloro - 2,2 dimethylcyclopropanecarboxylic acid.At the end of the period of 18 hours the selectivities were as follows:
to 3,3 - dichloro - 2,2 - dimethylcyclopropane
carboxylic acid 80% to 3 - chloro - 2,2 - dimethylcyclopropanecarboxylic 10% acid to organic compounds with an open chain of carbon
atoms 10%
Comparison of the conversion of 3,3 - dichloro - 2,2 dimethylcyclopropanecarboxylic acid - which was only 20% -- and the selectivity to 3 - chloro - 2,2 - dimethylcyclopropanecarboxylic acid of this example with those of Example III shows the favourable effect of water.
WHAT WE CLAIM IS:
1. A process for the preparation of compounds having the following general formula:
wherein
X is a halogen atom; R' is an alkyl group;
R2 is an alkyl group; or R' and R2 together represent an alkylene chain: or a salt, anhydride, carboxamide or alkyl ester thereof, which comprises partially dehalogenating a cyclopropane-carboxylic acid of the following general formula:
or a salt, anhydride, carboxamide or alkyl ester thereof, in the presence of zinc and an alkanoic acid, the symbols R', R2 and X in formula 11 having the same meaning
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (15)
1. A process for the preparation of compounds having the following general formula:
wherein
X is a halogen atom; R' is an alkyl group;
R2 is an alkyl group; or R' and R2 together represent an alkylene chain: or a salt, anhydride, carboxamide or alkyl ester thereof, which comprises partially dehalogenating a cyclopropane-carboxylic acid of the following general formula:
or a salt, anhydride, carboxamide or alkyl ester thereof, in the presence of zinc and an alkanoic acid, the symbols R', R2 and X in formula 11 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 in formula I:- X is a halogen atom;
R' is an alkyl group of I to 6 carbon atoms;
R2 is an alkyl group of I to 6 carbon atoms; or
R' and R2 together represent an alkylene chain of up to 5 carbon atoms; or the alkyl (1--6 carbon) esters, the alkali metal, alkaline earth metal and ammonium salts thereof.
3. A process according to Claim 1 or 2, wherein X and Y are chlorine and R' and R2 are both methyl groups.
4. A process according to any one of the preceding claims, 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 Claims 4, 5 or 6, wherein the alkanoic acid is acetic or propionic acid.
8. A process according to any one of the preceding claims, wherein the molar ratio of zinc to the compound of formula II is in the range 0.5:1 to 20:1.
9. A process according to Claim 1, wherein 2,2 - dihalo - 3,3 dimethylcyclopropanecarboxylic 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 - dimethylcyclopropanecarboxylic acid or its lower alkyl ester.
10. A process for the preparation of compounds having the general formula I substantially as hereinbefore described and with reference to any one of Examples.
11. A compound of formula I prepared by a method claimed in any one of the preceding claims.
12. A compound of the following general formula:
wherein
X is a halogen atom;
R' is an alkyl group;
R2 is an alkyl group; or R' and R2 together represent an alkylene chain; or a salt, anhydride, carboxamide or alkyl ester thereof.
13. A compound according to Claim 12, wherein
X is a halogen atom;
R' is an alkyl group of I to 6 carbon atoms;
R2 is an alkyl group of 1 to 6 carbon atoms; or
R' and R2 together represent an alkylene claim of up to 5 carbon atoms; or an alkyl (1--6 carbon) ester, or alkali metal, alkaline earth metal or ammonium salt thereof.
14. A compound according to Claim 12 or 13, wherein X and Y are chlorine and R' and R2 are both methyl groups.
15. A compound according to Claim 12 specifically named herein.
Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB3164/77A GB1594224A (en) | 1977-01-26 | 1977-01-26 | Preparation of cyclopropane derivatives |
| CA000294304A CA1121831A (en) | 1977-01-26 | 1978-01-04 | Preparation of cyclopropane derivatives |
| MX678678U MX4672E (en) | 1977-01-26 | 1978-01-24 | PROCEDURE FOR PREPARING CYCLOPROPAN DERIVATIVES |
| BE184604A BE863272A (en) | 1977-01-26 | 1978-01-24 | PREPARATION OF CYCLOPROPANE DERIVATIVES |
| JP588578A JPS5392743A (en) | 1977-01-26 | 1978-01-24 | Cyclopropane derivative and its preparation |
| IT7819574A IT7819574A0 (en) | 1977-01-26 | 1978-01-24 | PROCESS FOR THE PREPARATION OF CYCLOPROPANE DERIVATIVES. |
| BR7800411A BR7800411A (en) | 1977-01-26 | 1978-01-24 | PROCESS FOR THE PREPARATION OF CYCLE-PROPANE DERIVATIVES AND PRODUCTS OBTAINED |
| DE19782802967 DE2802967A1 (en) | 1977-01-26 | 1978-01-24 | PROCESS FOR MANUFACTURING CYCLOPROPAN DERIVATIVES |
| FR7801895A FR2378740A1 (en) | 1977-01-26 | 1978-01-24 | PREPARATION OF CYCLOPROPANE DERIVATIVES |
| NL7800811A NL7800811A (en) | 1977-01-26 | 1978-01-24 | PROCESS FOR THE PREPARATION OF CYCLOPROPANE DERIVATIVES. |
| CH75178A CH634035A5 (en) | 1977-01-26 | 1978-01-24 | Derivatives of cyclopropane and processes for preparing them |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB3164/77A GB1594224A (en) | 1977-01-26 | 1977-01-26 | Preparation of cyclopropane derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1594224A true GB1594224A (en) | 1981-07-30 |
Family
ID=9753142
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB3164/77A Expired GB1594224A (en) | 1977-01-26 | 1977-01-26 | 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) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004060851A1 (en) * | 2003-01-07 | 2004-07-22 | Daiichi Pharmaceutical Co., Ltd. | Process for reductive dehalogenation |
Families Citing this family (1)
| 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 |
-
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 BR BR7800411A patent/BR7800411A/en unknown
- 1978-01-24 IT IT7819574A patent/IT7819574A0/en unknown
- 1978-01-24 BE BE184604A patent/BE863272A/en not_active IP Right Cessation
- 1978-01-24 JP JP588578A patent/JPS5392743A/en active Pending
- 1978-01-24 FR FR7801895A patent/FR2378740A1/en active Granted
- 1978-01-24 MX MX678678U patent/MX4672E/en unknown
- 1978-01-24 DE DE19782802967 patent/DE2802967A1/en not_active Withdrawn
- 1978-01-24 CH CH75178A patent/CH634035A5/en not_active IP Right Cessation
- 1978-01-24 NL NL7800811A patent/NL7800811A/en not_active Application Discontinuation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004060851A1 (en) * | 2003-01-07 | 2004-07-22 | Daiichi Pharmaceutical Co., Ltd. | Process for reductive dehalogenation |
| CN1304356C (en) * | 2003-01-07 | 2007-03-14 | 第一制药株式会社 | Process for reductive dehalogenation |
| US7199260B2 (en) | 2003-01-07 | 2007-04-03 | Daiichi Pharmaceutical Co., Ltd. | Process for reductive dehalogenation |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2378740B1 (en) | 1981-08-21 |
| CA1121831A (en) | 1982-04-13 |
| FR2378740A1 (en) | 1978-08-25 |
| MX4672E (en) | 1982-07-23 |
| DE2802967A1 (en) | 1978-07-27 |
| IT7819574A0 (en) | 1978-01-24 |
| CH634035A5 (en) | 1983-01-14 |
| BE863272A (en) | 1978-07-24 |
| BR7800411A (en) | 1978-08-22 |
| JPS5392743A (en) | 1978-08-15 |
| NL7800811A (en) | 1978-07-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| PCNP | Patent ceased through non-payment of renewal fee |