MXPA98000440A - Procedure for the preparation of carboxilic and intermediary cyclopropan acids of the mis - Google Patents

Abstract

The compounds of 3- (2,2-dichloro-3,3,3-trifluoro-1-hydroxypropyl) -2, 2-dimethyl- (1R-3R) -cyclopropane carboxylic acid, cis-3- (2,2-dichloro) -3,3,3-trifluoro-1-hydroxypropyl) -2,2-dimethyl-cyclopropane carboxylic acid, and (1R, 5S) -4- (1,1-dichloro-2,2,2-trifluoroethyl) -6, 6-Dimethyl-3-oxabicyclo (3.1.0.) Hexane-2-one, they occur as intermediates in a process for the preparation of insecticidally active cyclopropane carboxylate esters, said 6,6-dimethyl-4-hydroxylation procedure 3-oxabicyclo [3.1.0] hexan-2-one (Biocartol) which is reacted with the compound CF3-CCIX2 (X = halogen) in the presence of zi

Description

PROCEDURE FOR THE PREPARATION OF CYCLOPROPAN CARBOXYLIC ACIDS AND INTERMEDIARIES OF THEM The present invention relates to compounds that can be used as intermediates in the preparation of cyclopropane carboxylic esters, and also, the invention relates to processes for preparing these compounds. The cyclopropane carboxylate esters are insecticidally active compounds that are known as "pyrethroids", and since they combine exceptionally good insecticidal properties with very low toxicity to mammals, they are of considerable interest. Therefore, a great effort has been devoted to finding economically favorable ways to prepare them and to prepare their most important intermediaries. la: IR, cis, Z Ib: 1RS, cis, Z A class of these pyrethroid compounds showing markedly elevated activity has the general formula I in which the carbon atoms are labeled 1 and 3 are asymmetric carbon atoms and R 'is selected from a group of radicals known to impart insecticidal activity to the molecule, for example RS-α-cyano-3-phenoxybenzyl or Sa-cyano-3-phenoxybenzyl or -methylbiphenyl-3-ylmethyl or 2,3,5,6, -tetrafluoro-4-methylbenzyl. Superscripts \ 2 etc. in the following descriptions e refers to the list of references at the end of the present description.

It is known1 that the stereoisomeric configuration of the acidic portion of the ester should have the geometry 1f ?, cis, Z, to obtain a maximum insecticidal activity, that is, the absolute configuration at the carbon atom 1 is R, the two atoms of Hydrogen at the carbon atoms 1 and 3 are in the cis position, and the chlorine atom and the cyclopropane group are on the same side of the carbon-carbon double bond. Therefore, it is of great importance to have the ability to prepare the active isomer I in a technical manner as well as economically attractive to minimize in this way the amount of active substance (insecticide) applied in the treatment of agricultural crops, rooms and the like . From this it follows that if such formula compounds are to be prepared, it is necessary either to provide a stereospecific chemical synthesis pathway or to isolate the desired estereoisomer from the racemic mixture by physical separation techniques. The latter method is normally expensive and is rarely used on an industrial scale. It is known2 that the following Biocartol of formula II can be reacted with a halogenated carbon compound such as CHBr3, CHCI3 or CHCIF2 in the presence of a strong base to obtain cyclopropane carboxylic acid derivatives. It is also known3 that the following racemic compound of formula IVb can be prepared by cyclization of 4-diazoacetoxy-5-5-dichloro-6,6,6, -trifluoro-2-methyl-2-hexene in a suspension of copper acetyl acetonate (II) in boiling dioxane, in which the cyclopropoan ring is formed as the final step of the reaction sequence. Furthermore, it has been suggested3 that the following racemic compound of formula IVb can be formed by the reaction between the esters of cis-3-formyl-2,2-dimethyl-cyclopropane carboxylic acid and 1,1,1-trichloro-2,2, 2, trifluoro-ethane in the presence of zinc. A route has now been found for commercially important compounds of type I which use as the starting material the substance Biocartol (formula II) which can be used as a starting material. prepare easily in optically pure form Ha starting from the natural substance (+) - 3-carene45,6 or in a racemic form llb through ozonolysis of chrysanthemic acid or derivatives thereof3. The methyl ester of Trans-3- (dimethoxymethyl) -2,2-dimethyl-cyclopropane carboxylic acid which is commercially obtainable in for example Aldrich-Chemie, also constitutes, through epimerization-lactonization, a source of llb. The synthesis route is quite specific with respect to the steroisomerism of products such as the geometry of Ha that can be found again in the product. In this way, expensive racemate resolutions are avoided, and yield losses in useless isomers are also avoided.

Biocartol A variety of new syntheses (see Reaction Scheme) of the acid portion (1 R, cis, Z) -in the pyrethroid esters of the formula (R -H) of Biocartol lia, through the novel intermediaries Illa and / or IVa of the invention. These synthetic methods can be used in the same way to prepare the racemic acid portion (1RS, cis, Z) in the pyrethroid esters of the formula Ib (R '= H) of racemic Biocartol llb through the novel intermediate lllb. Synthetic routes for I (R '= H) (single-step synthesis) are also described here from II where intermediates III and / or IV are not isolated, but are recognized and characterized by GC. These synthetic methods are used for the synthesis of the from Ha and Ib from llb.

Reaction Scheme CFjCCIXII NaO-t-Bu DMF, THF H) í = H) CF3CCIX2 MY2 The present invention relates to compounds of the general formula III or to the compounds of the general formula IV, wherein X represents a halogen atom, particularly chlorine. Preferred compounds of the general formula III are cis -3- (2,2-dichloro-S.S.S.-trifluoro-1-hydroxypropyl) .S-dimethyl-1R.SRJ-cyclopropoane carboxylic acid (Illa, X = CI). The compound lllb (X = CI) and the compound Illa (X = CI) are characterized as ideal and novel starting materials for the synthesis of IVb (X = CI) and IVA (X = CI), respectively, and finally of Ib (R -H) and (R -H), respectively. This has also been illustrated by the aforementioned one-step synthesis of I from II by the successive addition of reagents in which III and IV are produced as intermediates. The preferred compound of the general formula IV is (1R, 5S) -4- (1,1-dichloro-2,2,2-trifluoroethyl) -6,6-dimethyl-3-oxabicyclo (3.1.0) - hexane-2-one of the following formula IVa (X = CI).

The compound IVa (X = CI) is characterized as a novel and ideal starting material for the synthesis of (RH), as well as by the fact that it has been found, surprisingly, that the subsequent reaction results almost exclusively the Z isomer of I. Taking into account the asymmetric carbon atom adjacent to the CXCI group and the asymmetry in the same group CXCI (for X? Cl), the compounds Illa and IVa (and similarly lllb and IVb) may exist in a variety of isomeric forms and not necessarily in equal amounts. The proportions are observed in the GC and NMR analyzes. All these isomers result in obtaining the same final product (Ib) The NMR and CG analyzes performed on the final products la and Ib show that the Z isomer is preferably isolated, usually more than 90% of the Z isomer , and the crude products are easily purified so that there is more than 90% of the Z-isomer. The present invention relates to the preparation of the compounds of the general formula I, wherein R \ represents H, and the two hydrogen atoms in the cyclopropane ring are in cis position with respect to each other, by reaction of the compounds of the general formula II and the compound CF3-CCIX2 where X represents a halogen atom, particularly chlorine or bromine, in an inert medium such as for example DMF in the presence of an excess of metallic zinc, and conveniently at temperatures between 0 and 150 ° C, preferably between 20 and 100 ° C. After a period of time in which the GC analysis of the reaction mixture shows that the starting compound II has been consumed, that the intermediates III and IV have been formed and that the final product I has been formed in an amount smaller, a dehydrating agent, preferably acetic anhydride, is added, which immediately converts intermediate III into intermediate IV, as verified by GC. After an additional period of time the intermediate IV is completely converted to the final product I, predominantly as the Z-isomer, both in optically pure form and in racemic form, provided that the unreacted metallic zinc is permanently present. When metal reagents are used in the aforementioned case, said reagents can be replaced, conceivably, by catalytic amounts of the same metal that is regenerated electrochemically during the reaction.

The invention is further illustrated in the following examples. The yields and purities were determined by gas and / or liquid chromatography, as well as by NMR spectroscopy.

Example 1 Preparation of 3- (2,2-dichloro-3,3,3-trifluoro-1-hydroxypropyl) -2,2-dimethyl- (1R, 3R) -cyclopropanecarboxylic acid (Illa, X = CI) from of Biocartol Ha.

To a stirred solution 0.02 mol of Ha (2.84 g) and 0.022 mol of 1,1-dichloro-2,2,2-trifluoroethane (3.36 g) in a mixture of 5 g of dry DMF, and 25 ml of dry THF , cooled by external cooling to -70 ° C, 27 ml of a 1M solution of potassium t-butoxide were slowly added to maintain the temperature in the reaction mixture below -55 ° C. The subsequent reaction is carried out at the same temperature for 30 minutes, and then the reaction mixture is cooled with the calculated amount of conc. HCl. (aqueous). After spontaneous heating to room temperature, the resulting solution is poured into a water-methyl t-butyl ether mixture. The aqueous phase and the organic phase are separated and the aqueous phase is extracted with an additional 2 x 25 thousand methyl t-butyl ether (MTBE). The combined organic phase is dried over Na 2 SO 4 and evaporated under reduced pressure. 1.1 g of crude product having a purity of 60% as measured by gas chromatography is obtained. The crude product is purified by crystallization from hexane and 0.4 Ha (28% theoretical) is isolated, which has a melting point of 125-9 ° C (decomp.) And a purity according to an NMR of > 95% Specific rotation (a) D25 = -11o (1, 28 g / 100 m I, THF). 1 H-NMR (250 MHz, CDCl 3 + CD 3 OD): 1.2.1 ppm (s, 3H); 1.31 ppm (s, 3H); 1.7 ppm (m, 2H); 4.51 ppm (d, J - 8.8 Hz, 1 H); 4.8 ppm (broad signal, 2H) of the major isomer. 1.27 ppm (s 3H); 1. 39 ppm (s, 3H) of the minor isomer. 13 C-NMR (63 MHz, CDCl 3 + CD 3 OD): 16.1 ppm (q); 28.4 ppm (s); 28.6 ppm (q); 29.5 ppm (d); 35.8 ppm (d); 71.4 ppm (d); 88.9 ppm (qs, 32 Hz); 122.9 ppm (qs, 282 Hz); 174.8 ppm (s).

In the same manner, cis-3- (2,2-dichloro-3,3,3-trifluoro-1-hydroxypropyl) -2,2-dimethyl-cyclopropane carboxylic acid (lllb, X = CI) = is prepared from Melting point 127-30 ° C 1 H-NMR (250 Mhzm CDCl 3): 1.24 ppm (s, 3H); 1.31 ppm (s, 3H); 1.8 ppm (m, 2H); 4.50 ppm (d, 8.6 Hz, 1H). 13 C-NMR (63 MHz, CDCI): 15.4 ppm (q); 28.1 ppm (q); 29.0 ppm (d); 29.2 ppm (s); 35.7 ppm (d); 71.0 ppm (d); 87.5 ppm (qs, 39 Hz); 121.9 ppm (qs, 277 Hz); 177.4 ppm (s).

Example 2 Preparation of 3- (2,2-dichloro-3,3,3, trifluoro-1-hydroxypropyl) -2,2-dimethyl- (1R, 3R) -cyclopropanecarboxylic acid (Illa, X = CI) from of Biocartol Ha. 13 ml of a 1M solution of potassium t-butoxide (13 mmol) in THF was cooled to about -70 ° C under a dry nitrogen atmosphere. To this was added dropwise a mixture of 5 mmol of Ha (0.7 g), 8 mmol of 1,1-dichloro-2,2,2-trifluoroethane (1.22 g), 1.0 g of dry DMF and 5 ml of dry THF while cooling and stirring so that the temperature did not exceed -55 ° C. After 90 minutes, an additional 2 ml of potassium tert-butoxide (2 mmol) was added and immediately 2 mmol of 1,1-dichloro-2,2,2-trifluoroethane (0.31 g) was added, this was repeated twice more. at the same time interval. In this way a total of 19 ml of potassium tert-butoxide and 14 mmol of 1,1-dichloro- 2,2,2-trifluoroethane. After a reaction period of 6 hours, 4 ml of concentrated HCl was added under continuous cooling to < 55 ° C, after which the reaction mixture was allowed to stand to warm up spontaneously at room temperature. The reaction mixture was worked up as in Example 1. The yield is 0.9 g of an Illa powder (61% theoretical) which was analyzed by NMR demonstrating a purity of > 95% In an identical manner, cis-3- (2,2-dichloro-3,3,3-trifluoro-1-hydroxypropyl) -2,2-dimethyl-cyclopropanecarboxylic acid (Ibl, X = CI) was prepared from llb.

Example 3 Preparation of (1 R, 5S) -4- (1,1-dichloro-2,2,2-trifluoroethyl) -6,6-dimethyl-3-oxabicyclo (3.1.0) hexane-2-one (IVa , X = CI) of Illa.

Illa (0.005 mol, 1.52 g) dissolved in 10 ml of acetic anhydride was stirred at 85 ° C for 21/4 hours, cooled to room temperature, treated with aqueous NaHPO and extracted twice with MTBE which was dried over Na2SO4y. It vanished. 1.35 g were isolated and purified by chromatography on silica (CH2Cl2). 1.23 g of IVa was isolated (purity 93.4%, GC, yield 83%). Recrystallization of 0.51 g of this product from 10 ml of n-hexane gives 0.31 g of colorless needles of a purity greater than 95% (NMR analysis) and a melting point of 91-93 ° C. Specific rotation (a) D25 = 5 ° (1.27 g / 100 ml, CHCl3). ? -NMR (250 MHz, CDCl 3): 1.25 ppm (s, 3H); 1.26 ppm (s, 3H); 2.13 ppm (d, J = 5.9 Hz, 1H); 2. 38 ppm (d, J = 5.9 Hz, 1H); 4.63 ppm (s, 1H). 13 C-NMR (63 MHz, CDCl 3): 15.1 ppm (q); 23.4 ppm (s); 25.3 ppm (q); 30.0 ppm (d); 31.6 ppm (d); 77.6 ppm (d); 85.1 ppm (qs, 34 Hz); 121.5 (qs, 284 Hz); 171.9 ppm (s). Crystallographic X-ray examinations of the recrystallized product IVa showed the following crystalline structure: Crystal form: monoclinic: Space group: P2 / 1 a = 9.3871 (17) A; b: 10.6301 (51) A; c = 6.2997 (12) A a: 90 °, ß = 110.505 (12) °, W y = 90 ° volume of the cell unit = 588.79 (33) A3 Number of molecules per cell unit, Z = 2 Calculated Density = 1.5627 Mg / m3 F (000) = 280.0000 Mo Ka radiation = 0.71073 A; μ = 5.717 crn "1; 298 K The coordinates of the individual atoms in the cell unit are shown in the following table.

ATOM C11 0.3223 (2) 0.7909 0.2218 (3) C12 0.3155 (2) 0.7445 (4) 0.6668 (3) F1 0.5513 (4) 0.6180 (7) 0.5499 (10) F2 0.4148 (6) 0.5328 (7) 0.2415 (12) F3 0.3865 (7) 0.4839 (9) 0.5457 (18) 01 -0.0170 (6) 0.5798 (7) -0.2696 (7) 02 0.1060 (5) 0.5573 (5) 0.0998 (6) C1 -0.0700 (6) 0.7212 (8) -0.0046 (9) ÁTOMO X Y Z C2 0.0025 (7) 0.6177 (8) -0.0841 (9) C3 0.1273 (6) 0.6236 (7) 0.3045 (9) C4 0.0086 (6) 0.7265 (8) 0.2502 (9) C5 -0.1548 (6) 0.6869 (7) 0.1514 (9) C6 -0.2043 (7) 0.5552 (10) 0.1695 (10) C7 -0.2674 (8) 0.7845 (12) 0.1647 (15) C8 0.2905 (6) 0.6752 (7) 0.3986 (8) C9 0.4102 (8) 0.5711 (13) 0.4301 (19) H1 -0.1052 (76) 0.8094 (88) -0.108 (11) H3 0.1286 (54) 0.5547 (63) 0.4182 (78) H4 0.0299 (61) 0.8053 (72) 0.3330 (83) H6a -0.2554 0.5325 0.2692 H6b -0.1131 0.5042 0.2146 H6c -0.2669 0.5305 0.0223 H7a -0.3201 0.7626 0.2682 H7b -0.3404 0.7966 0.0219 H7c -0.2142 0.8607 0.2216 Identically, 4-1 (1,1-dichloro-2,2,2-trifluoroethyl) -6,6-dimethyl-3-oxabicyclo (3.1.0) hexane-2-one was prepared (IVb, X = CI ) was prepared from Hilo. 1 H-NMR (250 MHz, CDCl 3): 1.25 ppm (s, 3H); 1.26 ppm (s, 3H); 2.13 ppm (dd, J = 0.8 and 5.9 Hz, 1H); 2.38 ppm (d, J = 5.9 Hz, 1H); 4.63 ppm (d, J = 0.8 Hz, 1 H). 13 C-NMR (63 MHz, CDCl 3): 15.1 ppm (q); 23.4 ppm (s); 25.3 pp m (q); 30.1 ppm (d); 31.7 ppm (d); 77.6 ppm (d); 85.1 ppm (qs, 34z); 121.5 ppm (qs, 284 Hz); 171.9 ppm (s).

Example 4 Preparation of 3- (2-bromo-2-chloro-3,3,3-trifluoro-1-hydroxypropyl) -2,2-dimethyl- (1R, 3R) -cyclopropanecarboxylic acid (lllb, X = Br ) of Biocartol llb.

Same as Example 2, but with 1-bromo-1-chloro-2,2,2, -trifluoroethane, instead of 1,1-dichloro-2,2,2-trifluoroethane. Recrystallization from toluene gave a white powder (IIIb) having a melting point of 170-2 ° C and a purity greater than 95% (NMR, sum of several isomers). 1 H-NMR (250 MHz, DMSO-d 6): 1.14 ppm (s, 3H); 1.24 ppm (s, 3H); 1.53 ppm (dd, 9.1 Hz and 9.6 Hz, 1H); 1.65 ppm (d, 9.1 Hz, 1H); 4.17 ppm (d, 9.6 Hz, 1H); 6.2 ppm (1H widths); 11.9 ppm (width s, 1H); 13 C-NMR (63 MHz, DMSO-d 6): 15.7 (q); 27.2 ppm (s); 27.8 ppm (q); 28.3 ppm (d); 35.8 ppm (d); 69.8 ppm (d); 79.5 ppm (qs, 30 Hz); 122.3 (qs, 282 Hz); 172.0 ppm (s).

The spectrography data are of the major isomer.

Example 5 Preparation of Z-cis-3- (2-chloro-3,3,3, trifluoro-1-propenyl) -2,2-dimethyl-cyclopropane carboxylic acid (Ib) from Ib.

A suspension of Zn powder (0.03 mol, 1.96 g) in a solution of llb (0.005 mol, 0.71 g) and 1,1,1-trichloro-trifluoroethane (0.015 mol); 2.81 g) in 10 ml of dry DMF were stirred under reflux for about 4 hours at 65 ° C, until GC analysis showed that all of the llb had been converted to a mixture of lllb and IVb as well as smaller amounts of Ib. . Acetic anhydride (0.01 mol, 1.02 g) was added and stirring was continued at 60 ° C for about 5 hours, ensuring permanently that the unreacted powder Zn was present in the reaction mixture. The product was isolated from the reaction mixture, to which aqueous HCl had been added by extraction with MTBE. The MTBE phase was dried over Na2SO4 and evaporated. The yield of lb: 0.57 g (> 95% pure, 47% theoretical). Recrystallization from n-heptane gives a product of a melting point of 106-8 ° C. (The literature reports 108-10 ° C for Ib).

Example 6 Preparation of Z-3- (2-chloro-3,3,3-trifluoro-1-propenyl) -2,2-dimethyl- (1R, 3R) -cyclopropanecarboxylic acid (a) from IVa.

A suspension of powdered Zn (0.004 mol, 0.26 g) in a solution of IVa (0.0026 mol, 0.72 g) in 3 ml of DMF was stirred at 60 ° C for 71/2 hours, and after cooling to room temperature they added 10 ml of water and 5 ml of concentrated HCl. The mixture was extracted three times with MTBE which was dried over Na2SO4 and evaporated. The result was 0.65 g of crystals that according to the GC analysis are almost 100% pure. Performance approximately 100%. Recrystallization from 10 ml of n-heptane gives 0.21 g of white crystals of melting point of 105-8 ° C. Specific rotation: (at D25 = + 47 ° (1.14 g / 1000 ml, CHCl 3).? -NMR (250 MHz, CDCP): 1.32 ppm (s, 2 x 3H), 1.99 ppm (d, J = 8.3 Hz, 1H), 2.23 ppm (dd, J = 9.3 and 8.3 Hz, 1H); 6.87 ppm (d, J = 9.3 Hz, IH); 10.8 ppm (wide signal, 1H). At 6.58 ppm (d, J = 9.6 Hz) a signal is suspected which corresponds to a content of approximately 5% of the E-isomer which completely disappears by recrystallization of the substance. 13 C-NMR (63 MHz, CDC13): 14.9 ppm (q); 28.6 ppm (q); 29.5 ppm (s); 31.6 ppm (d); 32.7 ppm (d); 120.5 ppm (qs, 38 Hz); 122.1 ppm (qs, 271 Hz); 129.7 ppm (qd, 5 Hz); 176.6 ppm (s). The reaction of a minor amount of the one with an excess of thionyl chloride and subsequently with an excess of methanol yields the methyl ester of the. Analysis of this ester on a chiral GC column shows that it has an optical purity of 95% enantiomeric excess.

Example 7 Preparation of Z-3- (2-chloro-3,3,3-trifluoro-1-propenyl) -2,2-dimethyl- (1R-3R) -cyclopropane carboxylic acid (a) from IVa.

Electro Micro Flow Cell (from Electrocell AB, Sweden) was used, with a lead cathode and a graphite anode, each electrode having an area of 10 cm 2. Seleion® CMV, a selective cation membrane of the Japanese firm Asahi Glass Co. was prepared with ion-selective membrane. 10 ml of concentrated sulfuric acid was carefully dissolved in 300 ml of methanol. 150 ml were poured as catholyte and 150 ml as anolyte. Circulating pumps were started, and when the temperature was stabilized at 50 ° C, a solution of IVa (0.0072 mol, 2.00 g) in 10 ml of methanol was added to the catholyte. The electrode wires were fixed, the power supply was turned on and the constant voltage was adjusted to 4.0 volts. At time = 0 the current is 0.30 amperes.

The samples were taken approximately every 30 minutes, and after 270 minutes, the current was interrupted the wires were removed. The current at the end of the experiment was 0. 20 amps. The catholyte was discharged and worked by distilling the methanol on a rotary evaporator at 50 ° C and 100 mm Hg after the addition of 50 ml of water. The aqueous phase was then extracted with methyl t-butyl ether which was dried and evaporated. 1.68 g of an oil was obtained which was mixed with 10 μl of 2N aqueous NaOH and allowed to stand with stirring for 2 hours. The aqueous phase was acidified with concentrated HCl (aqueous) and extracted with methyl t-butyl ether which was dried and evaporated. 1.33 g of crystals were obtained which according to the GC analyzes are of a purity of > 95% Performance: approximately 75%.

Example 8 Preparation of Z-3- (2-Chloro-3,3,3-trifluoro-1-propenyl) -2,2-dimethyl- (1R-3R) -cyclopropanecarboxylic acid (la) from Ha.

A suspension of Zn powder (0.045 mol, 2.94 g) in a solution of Ha (0.015 mol, 2.13 g) and 1, 1,1-trichloro-trifluoroethane (0.038 mol, 7.12 g) in 25 ml of dry DMF was stirred in a 50 ml Teflon-lined autoclave for about 2 hours at 50 ° C. The autoclave was opened and the CG analysis showed that the whole Ha had been converted into a mixture of Illa and IVa as well as smaller amounts of the. Acetic anhydride (0.018 mol, 1.84 g) was added, the autoclave was closed, heated for 15 minutes at 50 ° C and opened again. The GC analysis shows that the entire Illa had been converted to IVa. Zn powder (0.018 mol) was added; 1.18g), the autoclave was closed again and allowed to stand with stirring at 70 ° C for about 2 hours. The autoclave was opened and the product was isolated by MTBE extraction of the reaction mixture to which aqueous HCl had been added. The MTBE phase was dried over Na2SO4 and evaporated. Yield of 2.48 g (> 95% purity, 68% theory). Recrystallization of n-heptane gave a product with a melting point of 105-7 ° C.

List of references: 1 British Patent 2.000.764 (March 23, 1977), ICI. 2 Danish patent application 2849/78 (June 26, 1978) Roussel-Uclaf, 3 3 M. Fujita, K. Kondo and T. Hiyama, Tetrahedron Letters, 27, 2139-2142 (1986) resp. Bol. Quím. Soc. Jap. 60,4385-4394 (1987) 4 Arun K Mandal, et al., Tetrahedron, 42,5715 (1986) 5 D Bakshi, VK, Mahindroo, R. So an, S. Dev. Tetrahedron, 45, 767-774 (1989 ) Danish patent application DK 5633/78 (December 14, 1978), Shell Internationale Research Maatschappji B .V. U.S. Patent No.4333950 (June 8, 1982), FMC Corporation

Claims (7)

REIV '"INDICAC"' ION "'EN /

1. - A process for the preparation of compounds having the general formula I where R1 represents H, and the two hydrogen atoms, in the cyclopropane ring are located cis with respect to each other, which comprises the reaction between a compound of general formula II and the compound CF3-CC1X2, wherein X represents a halogen atom, particularly chlorine or boron, in an inert medium in the presence of Zn and conveniently at temperatures between 0 and 150 ° C, preferably between 20 and 100 ° C, during which reaction compounds III and IV III IV are produced as intermediaries that are not isolated, and when after a period of time the analyzes show that the starting compound II has been substantially consumed, that the preceding intermediaries III and IV have been formed, and that the The final product is a minor amount, the addition of a dehydrating agent is made which immediately converts the intermediate III into the intermediate IV and after an additional period of time converts the intermediate IV substantially completely into the final product I predominantly as the Z isomer, in optically pure form and in racemic form, taking great care that it permanently presents unreacted metallic zinc.

2 - A method according to claim 1, wherein the inert medium is DMF.

3. A process according to claim 1 or 2, wherein the dehydrating agent is acetic anhydride.

4. A process according to any of claims 1 to 3, wherein part or all of the metal reagent is replaced by electrochemically generated metallic material.

5.- The compound of 3- (2-2-dichloro-3,3,3-trifluoro-1-hydroxypropyl) -2,2-dimethyl- (1 R, 3R) -cyclopropane carboxylic acid (Illa, X = CI ).

6. - The cis-3- (2-2-dichloro-3,3,3-trifluoro-1-hydroxypropyl) -2,2-dimethyl-cyclopropane carboxylic acid compound (lllb, X = CI).

7. The compound of (1R, 5S) -4- (1,1-dichloro-2,2,2-trifluoroethyl) -6,6-dimethyl-3-oxabicyclo (3.1.0) hexane-2-one ( IVa, X = CI).