CA2028650C

CA2028650C - Preparation of cis-2-(1h-1,2,4-triazol-1-ylmethyl)-2-(halophenyl)-3-(halophenyl)oxirane

Info

Publication number: CA2028650C
Application number: CA002028650A
Authority: CA
Inventors: Eckhard Hickmann; Rainer Seele; Reiner Kober; Heinz Isak
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 1989-11-04
Filing date: 1990-10-26
Publication date: 2003-09-30
Anticipated expiration: 2010-10-26
Also published as: EP0427061A2; JPH03153682A; MD332C2; EP0427061B1; CA2028650A1; ES2066089T3; KR910009695A; DE59008135D1; KR0157314B1; DK0427061T3; DE3936821A1; EP0427061A3; MD332B1; RU2071473C1; JP2983054B2; ATE116315T1

Abstract

Abstract of the Disclosure: A process is described for the preparation of cis-2-(1H-1,2,4-triazol-1-ylmethyl)-2-(halophenyl)-3-(halophenyl)oxirane I

by epoxidizing Z-3-(1H-1,2,4-triazol-1-yl)-2-(halo-phenyl)-1-(halophenyl)propene II,

Description

~o2ss~o O.Z. 0050/41223 Preparation of cis-2-~~1H-1 2 4-triazol 1 ylmethyl) 2 (halophenvl)-3-(haloohen3rltoxirane The present invention relates to a process for the preparation of cis-2-(1H-1,2,4-triazol-1-ylmethyl)-2-(halophenyl)-3-(halophenyl)oxirane I
Hal t~~ ~hN~ r C~H
r ~
Hal by epoxidizing Z-3-(1H-1,2,4-triazol-1-yl)-2-(halo-phenyl)-1-(halophenyl)propene II, Hal r H
r Hal where halogen is in each case fluorine, chlorine or bromine.
The preparation of epoxides of structure I is described, for example, in German Laid-Open Applications DE-OS 32 18 129 and 32 18 130 and in EP-A-196 038.
After an epoxidation of an olefin using peroxide compounds, such as hydrogen peroxide, alkyl hydro peroxides, dialkyl peroxides, peroxycarboxylic acids or diacyl peroxides, any residues of the latter present in the crude reaction mixture are usually destroyed, for example on a noble-metal catalyst (usually Pt or Pd) or by adding a chemical reducing agent. This aftertreatment of the crude products of epoxidation reactions is carried out for purely safety reasons, ie. to ensure that the peroxide compounds, which are without exception high in energy, cannot decompose in an uncbntrolled, disastrous manner during further work-up. For the purposes of the invention, peroxide compounds are, for example, inorganic and organic peroxides, hydroperoxides and peracids.

It is an object of the present invention to prevent unsatisfactory yields in the epoxidation of olefins II and the associated high purification costs.
We have found that this object is achieved by a process for the preparation of cis-2-(1H-1,2,4-triuzol-1.-ylmethyl)-2-(halophenyl)-3-(halophenyl)oxirane I
r---IN H a 1 N~ ~~N~
~..c~0.c ~"H
i Hal by epoxidizing Z-3-(1H-1,2,4-triazol-1-yl)-2-(halo-phenyl)-1-(halophenyl)propene II, Hal ~N~~N~~
Hal where halogen is indepeurdeni~:l.y fluor:i_ne, chlorine or bromine, with a peroxide compound, and .~ubj ect ing the crude product of the epoxidation to a reductive aftertreatment with one or more reducing agents, which are added to the reaction mixture in ~ ~~c~ansiderable ~~x~~F~ss over the amount necessary to destroy a:ny peroxide c~ompounds present, wherein, after destruction of the peroxide compounds, the amount; of reduc.i.ng agents is of from 10 mol- o to 2000 rnol- ~ based on tree numbF:n: of moles of Z-3-(1H-1,2,4,-triazol-1-yll-2--(halophen~.~l)-1-°halo-phenyl) propene II used as starting material, where.~_n the pE~roa~ic~e c~ornp~::urua is selected from the group consists.nc~ of. inorganic peroxides, organic peroxides, hydroperoxides and pera~..~.i.ds, and G <
wherein said at 7..ea~t one reducing agent is selected from the group consisting c:~f catalytic hydro-genating agents on catalyst=s, transfer hydrogenating agents, hydrogen in state rascendi, com~~lex metal hydrides, element hydrides, salts of mE~t,a~.s i_~~ lc:w oxidation states, compounds of elements from main groups 5 and 6 of the periodic table in low oxidation states and organic compounds.
The surprising yield- and purity-improving action of reducing agents in the present process according to the invention is only observed if they are employed in excess, ie. more is added than necessary for the rapid reduction of surviving peroxide compounds, the amount of which can be determined in a conventional manner, for example by iodometric titration. If, by contrast, the reaction batches, after catalytic or reductive des-truction of the residual peroxide compounds, are worked up without reductive aftertreatment of the peroxide-free crude product, maximum yields of 65 ~ of theory are obtained in the crude product ( see comparative examples ~ .
Target-product losses in the purification operations which are necessary, for example during crystallization, reduce the isolated yield of target product to a maximum of 50 ~ of theory.
A wide range of reducing agents and reduction processes are suitable for the reductive aftertreatment according to the invention, for example catalytic hydro-genation on catalysts, eg. Co, Pt, Pd or Raney nickel, transfer hydrogenation using, for example, ammonium formate on palladium reductions using hydrogen in statu nascendi, eg. zinc/
glacial acetic acid, iron/hydrochloric acid or aluminum/
sodium hydroxide solution, reductions using complex metal hydrides, eg. sodium borohydride, sodium dimethoxyborohydride or sodium triacetoxyborohydride, reduction using element hydrides, eg. diborane, reduction using salts of metals in low oxidation states, eg. tin(II) chloride, iron(II) sulfate or titanium(III) chloride, - 3a -reductions using compounds of elements from main groups and 6 of the periodic table in low oxidation states, eg. hydrazine, hydroxylamine, trimethyl phosphite, triphenylphosphine, phosphorus trichloride, hydrophos-phites, thionyl chloride, sulfur dioxide, hydrogen sulfites, disulfites, dithionites, thiosulfates, sulfin-ates; hydrogen sulfides and sulfides, reduction using reducing organic compounds, eg. formal dehyde, glyoxal, glyoxylic acid, formic acid, a-hydroxy sulfinic acids, a-hydroxysulfonic acids and salts thereof, eg. alkali metal or alkaline earth metal a-hydroxyalkylsulfonate or -sulfinate.
Particular preference is given to reductive aftertreatment by catalytic hydrogenation using sulfites, hydrogen sulfite, disulfite or dithionite.
The reducing agent additionally used in excess to reduce the amounts of residual peroxide is employed in ~02~36~0 - 4 - O.Z. 005D/41223 amounts of from about 10 mol-% to about 2000 mol-%, preferably from about 50 mol-% to about 1500 mol-%, based on Z-3-(1H-1,2,4-triazol-1-yl)-2-(halophenyl)-1-(halo-phenyl)propene II.
The reductive aftertreatment can be carried out in one or more steps. For example, the residual peroxide compounds can first be reduced or decomposed on a noble-metal catalyst, and then treated with a reducing agent, if desired a different one, in the abovementioned excess amounts, or the two operations can be combined in one.
The treatment with excess reducing agent is expediently carried out in the presence of the solvent used for the epoxidation, and the reaction mixture may comprise one or more phases. However, it is also possible to change the solvent, preferably after destruction of the residual peroxide compounds, if the reducing agent is incompatible with the solvent for the epoxidation.
Examples of suitable solvents for the reductive aftertreatment are aromatic hydrocarbons, eg. benzene, toluene and xylenes; ether, eg. tert-butyl methyl ether and diethylene glycol di.methyl ether; chlorinated hydro-carbons, e.g methylene chloride, 1,2-dichloroethane, 1,1,1-trichloroethane and chlorobenzene; alcohols, eg.
methanol, isopropanol, sec- and tart-butanol and ethylene glycol; carboxylic acids, eg. acetic acid and propionic acid; esters, eg. ethyl acetate, i-amyl acetate, methyl butyrate and dimethyl succinate; amides, eg. dimethyl-formamide and N-methylpyrrolidone; nitriles, eg. aceto-nitrile, ureas, eg. N,N,N',N'-tetramethylurea, N,N'-dimethylethyleneurea and N,N'-dimethylpropyleneurea;
water, and single- and multiphase mixtures of these. In general, the reducing agents are selected so that they do not themselves react With the solvent. However, they can also be intentionally combined so that the active reduc-ing agent is only formed in situ, eg. diborane from sodium borohydride and methylene chloride, and sodium dimethoxyborate from sodium borohydride and methanol.

~Q28650 - 5 - O.Z. 0050/41223 The reaction temperature during the reductive aftertreatment is generally from 0 to 150°C, preferably from 20 to 80°C.
The reaction generally takes from 0.5 to 10 hours, preferably from 1 to 3 hours.
In the reductive aftertreatment, the preferred pH
depends on the known optimum of the particular reducing agent. Thus, sodium dithionite or sodium hydroxymethyl sulfinate are used in the alkaline pH range, and sodium hydrogen sulfite in the acidic range.
The cis-2-(iH-1,2,4-triazol-1-ylmethyl)-2-(halo-phenyl)-3-(halophenyl)oxirane I is isolated by con-ventional methods, eg, by filtration, centrifugation or, if necessary after phase separation, by precipitation, crystallization or evaporation. For purification, washing or digestion with water is generally sufficient. To prepare high purity products, digestion or recrystalli-zation using an organic solvent (mixture) can be carried out instead of or in addition to the above.
The epoxidation reaction itself is carried out in a conventional manner, for example as described in the prior art cited at the outset. Under the conditions indicated therein or appropriately modified conditions, the olefins II are oxidized using peroxycarboxylic acids, such as perbenzoic acid, 3-chloroperbenzoic acid, 4-nitroperbenzoic acid, monoperphthalic acid, peracetic acid; perpropionic acid, permaleic acid, monopersuccinic acid, perpelargonic acid or trifluoroperacetic acid, in inert solvents, preferably chlorinated hydrocarbons, eg.
methylene chloride, chloroform, carbon tetrachloride or dichloroethane, or, if desired, in acetic acid, ethyl acetate or dimethylformamide, if desired in the presence of a buffer, such as sodium acetate, sodium carbonate, sodium hydrogen carbonate or disodium hydrogen phosphate.
The reaction is carried out at from 10 to 100°C and catalyzed, if desired, by iodine, sodium tungstate or light.

~~28650 - 6 - O.Z. 0050/41223 The epoxidation is preferably carried out in the presence of a large excess of peracid, eg. permaleic acid, which is advantageously pregared in situ from 5 to 30 mol equivalents, in particular from 5 to 10 mol equivalents of malefic anhydride, based on the olefin II, and less than stoichiometric amounts of hydrogen peroxide solution, based on the malefic anhydride. In general, anhydride : H202 molar ratios of from 1.5 to 10, in particular from 2 to 4, are employed. A 30 to 50 %
strength aqueous solution of hydrogen peroxide can advantageously be used.
The reaction temperature for the epoxidation can be from 0 to 100°C, in particular from 20 to 80°C.
The examples below illustrate the process accord ing to the invention, which can also be applied to other azolylmethyl stilbenes.

58.9 g (0.601 mol) of malefic anhydride and 18.6 g of 97.2 % (0.0576 mol) Z_-3-(1H-1,2,4-triazol-1-ylmethyl) 2-(fluorophenyl)-1-(2-chlorophenyl)propene are dissolved at 40°C in 150 ml of 1,2-dichloroethane, 20.6 g (0.303 mol) of 50 % strength aqueous hydrogen peroxide solution are added dropwise at a uniform rate over the course of 1 hour, and the reaction mixture is stirred at 40°C for 7 hours. A sample taken while stirring contains 0.4 % of peroxide compounds, calculated as hydrogen peroxide, on iodometric titration; this requires 6.9 ml of 38 % strength sodium hydrogen sulfite solution to reduce the peroxide compounds. 100 m1 of water are added, the aqueous phase is buffered at pH 3 using 50 % strength sodium hydroxide solution, and 170 ml of 38 % strength sodium hydrogen sulfite solution axe added, corresponding to an excess of 1385 mol-%, based on the olefin employed, and the two-phase reaction mixture is stirred vigorously at 50°C for 3 hours. The aqueous phase is neutralized using 50 % strength sodium hydroxide solution, and about 94 % of the 1,2-dichloroethane employed are recovered by - 7 - O.Z. 0050/41223 azeotropic distillation at atmospheric pressure (azeo-trope boiling point : 72°C). The cis-2-(1H-1,2,4-triazol-1-ylmethyl)-2-(4-fluorophenyl)-3-(2-chlorophenyl)oxirane which crystallizes out completely on cooling the aqueous phase which remains is separated off, washed thoroughly with water and dried at 90°C under reduced pressure, giving 17.7 g of product with a purity of 93.4 %, deter-mined by quantitative high-pressure liquid chromatography (HPLC). This corresponds to a yield of 87 % of theory.

The epoxidation is carried out as described in Example 1, the malefic acid, most of which precipitates out after cooling, is filtered off, the filter cake is washed with a little 1,2-dichloroethane, and the filtrate and washings are combined. This crude product solution weighs 242 g and contains, according to iodometric titration, 0.08 % of peroxide compounds, calculated as hydrogen peroxide. This requires 0.99 g of sodium di-thionite to reduce the per-compounds. 12.0 g of sodium dithionite in 40 ml of water, corresponding to an excess of 110 mol-%, based on the olefin employed, are added, the two-phase reaction mixture is stirred at from 70 to 75°C for 3 hours, and the organic phase is worked up, to give 18.0 g of c s-2-(1H-1,2,4-triazol-1-ylmethyl)-2-(4-fluorophenyl)-3-(2-chlorophenyl)oxirane in a purity of 95.2 % (quantitative HPLC), corresponding to a yield of 90.2-% of theory.

By a method similar to that of Example l, a mixture of 9.3 g of 97.2 % (0.0288 mol) Z_-3-(1H-1,2,4 triazol-1-ylmethyl)-2-(4-fluorophenyl)-1-(2-chloro phenyl)propene, 55 ml of 1,2-dichloroethane, 28 g of malefic anhydride, 0.3 g of 2,6-di-tert-butylphenol and 7.3 g of 50 % strength hydrogen peroxide is stirred at 50°C for 6 hours and at 70°C for a further 2 hours. The small amount of peroxide compounds remaining is destroyed by adding a 10 % strength aqueous sodium thiosulfate - 8 - O.Z. 0050/41223 solution, the reaction mixture is neutralized using 50 %
strength sodium hydroxide solution, the organic phase is separated off and evaporated, the residue is dissolved in 70 ml of methanol, 0.5 g of Raney nickel is added, and the mixture is stirred at 50°C for 2 hours under 2 1 of hydrogen (corresponding to 310 mol-%, based on the olefin employed) . The catalyst is filtered off, and the solution is evaporated to give 8.9 g of cis-2-(1H-1,2,4-triazol-1-ylmethyl)-2-(4-fluorophenyl)-3-(2-chlorophenyl)oxirane in a purity of 94.1 % (quantitative HPLC), corresponding to a yield of 88.2 % of theory.
COMPARATIVE EXAMPLES

The epoxidation is carried out as described in Example 1, the residual peroxide compounds are reduced using the stoichiometric amount of 38 % strength sodium hydrogen sulfite solution (8.2 ml), and the mixture is worked up without reductive aftertreatment with excess bisulfite solution, giving 17.2 g of crude product containing 70.4 % of cis-2-(1H-1,2,4-triazol-1-ylmethyl) 2-(4-fluorophenyl)-3-(2-chlorophenyl)oxirane (quantita tive HPLC), corresponding to a yield of 63.7 % of theory.

The epoxidation is carried out in the same manner as i~n Example 2, the residual peroxide compounds are destroyed using the stoichiometric amount of sodium dithionite (1.4 g), but without reductive aftertreatment with excess dithionite solution, to give 17.5 g of crude product containing 66.7 % of cis-2-(1H-1,2,4-triazol-1 ylmethyl)-2-(4-fluorophenyl)-3-(2-chlorophenyl)oxirane, corresponding to a yield of 61.4 % of theory.

The procedure is as described in Example 3, but the reductive aftertreatment of the peroxide-free crude product with hydrogen and Raney nickel is omitted. 8.6 g - 9 - O.Z. 0050/41223 of crude product containing 65.6 % of cis-2-(1H-1,2,4-triazol-1-ylmethyl)-2-(4-fluorophenyl)-3-(2-chloro-phenyl)oxirane, corresponding to a yield of 59.4 % of theory, are obtained.

Claims

1. A process for the preparation of cis-2- (1H-1,2,4-triazol-1-ylmethyl)-2-(halophenyl)-3-halophenyl) oxyrane I:

wherein Hal is independently fluorine, chlorine or bromine, which comprises the steps of:
epoxidizing Z-3-(1H-1,2,4-triazol-1-yl)-2-(halo-phenyl)-1-(halopenyl) propene II,~

with a peroxide compound, and subjecting the crude reaction product of the epoxidation to a reductive aftertreatment with at least one reducing agent added to the reaction mixture in a considerable excess over the amount necessary to destroy any peroxide compounds present;
wherein, after destruction of the peroxide compounds, the amount of reducing agents is of from 10 mol-% to 2000 mol-% based on the number of moles of Z-3-(1H-1,2,4, -triazol-1-yl) -2- (halophenyl) -1- (halo-phenyl) propene II used as starting material.

wherein the peroxide compound is selected from the group consisting of inorganic peroxides, organic peroxides, hydroperoxides and peracids, and wherein said at least one reducing agent is selected from the group consisting of catalytic hydro-genating agents on catalysts, transfer hydrogenating agents, hydrogen in statu nascendi, complex metal hydrides, element hydrides, salts of metals in low oxidation states, compounds of elements from main groups 5 and 6 of the periodic table in low oxidation states and reducing organic compounds.

2. The process as claimed in claim l, wherein the peroxide-containing crude product is freed from peroxide compounds prior to being subjected to the reductive aftertreatment.

3. The process as claimed in claim 1 or 2, wherein the amount of reducing agent(s) that is present after destruction of the peroxide compounds, is of from 50 to 1500 mol-%, based on the number moles of Z-3- (1H-1,2,4-triazol-1-yl) -2 (halophenyl) -1- (halophenyl)propene used as starting material.

4. The process as claimed in any one of claims 1 to 3, wherein the reductive aftertreatment is carried out using hydrogen or a hydrogen donor and a metallic catalyst selected from the group consisting of nickel, cobalt, platinum and palladium.

5. The process as claimed in any one of claims 1 to 3, wherein the reductive aftertreatment is carried out using a hydrogen sulfite, sulfite, disulfite or dithionite of an alkali metal or alkaline earth metal.

6. The process as claimed in any one of claims 1 to 5, wherein the reductive aftertreatment is carried out at from 20 to 80°C.

7. The process as claimed in any one of claims 1 to 6, wherein cis-2-(1H-1,2,4-triazol-1-ylmethyl)-2-(4-fluorophenyl)-3-(2-chlorophenyl) oxirane is prepared.