The way to obtain cis-2-(1h-1,2,4-triazole-1-yl-methyl)-2- (halogenfree)-3-(halogenfree)-oxirane

 

(57) Abstract:

Use: in organic chemistry. The inventive product - CIS-2-(1H-1,2,4-triazole-1-yl-methyl)-2_ (halogenfree)-3-(halogenfree)- -oxiran. Reagent 1:Z-3-(1H-1,2,4-triazole-1-yl)-2-(halogenfree)-1-(halogenfree)-prop - called Reagent 2: parmaliana acid. Reaction conditions: the restorer - hydrosulfite sodium, dithionite sodium or thiosulfonate sodium or hydrogen in the presence of Raney Nickel, use the reducing agent in excess of the amount required to fracture possibly available permalinki acid, not less than 10%. mol. the excess of reducing agent relative to the compound of the above propene. Containing permaline acid the reaction product of epoxidation clear of permalinki acid, and then subjected to subsequent restorative treatment.

The present invention relates to a method of producing CIS-2-(1H-1,2,4-triazole-1-yl-methyl)-2-(halogenfree)-3-(halogenfree)-oxirane formula I:

(1)

A method of obtaining the compounds of formula I epoxydecane of olefin permalinki acid.

Usually after the reaction of epoxidation of olefin using peroxide compounds containing percarbonate acid or diarilpirimido, deteriorating. It is possible to implement, for example, by catalytic decomposition on the catalyst of a noble metal (usually from Pt or Pd) or by adding a chemical reductant. This additional processing of the crude reaction products of the epoxidation due to reasons relating solely to safety, thus want to be sure that peroxide, always with great energy, will not be able to decompose upon further processing in the form of a controlled destructive reactions. Under peroxy compounds mean, for example, inorganic and organic peroxides, gidroperekisi and percolate.

The purpose of the invention increase the yield of the target product.

This goal is achieved by a method of obtaining CIS-2-(1H-1,2,4-triazole-1-yl-methyl)-2-(halogenfree)-3-(halogenfree)- -3-(halogenfree)-oxirane formula I.

< / BR>
by epoxidation of Z-3-(1H-1,2,4-triazole-1-yl)-2-(halogenfree)-1-(halogenfree)-propene of the formula II:

(II)

moreover, under the halogen in each case understood to mean fluorine, chlorine or bromine, permalinki acid with subsequent restoration, the distinguishing feature of which are the two who I or hydrogen in the presence of Raney Nickel, moreover, the reducing agent is added to the reaction mixture in excess of the amount required for the destruction of possible permalinki acid, not less than 10 mol% excess of reducing agent relative to the compound of formula II.

And containing permaline acid the reaction product of epoxidation clear of permalinki acid, and then subjected to subsequent restorative treatment.

Processing the excess amount of reducing agent should be carried out in the presence of a solvent used in epoxysilane, the reaction mixture may be single or multiphase. But it is possible also that it is better to do after decomposition of residual peroxide compounds, to change the solvent is taken if the reducing agent and is incompatible with the solvent used epoxydecane.

As solvents for the recovery and subsequent processing are taken into account, for example, aromatic hydrocarbons such as benzene, toluene, xylenes, ethers, for example, tert.-butyl methyl ether, methyldiethanolamine ether, chlorinated hydrocarbons such as methylene chloride, 1.2-dichloroethane, 1 the new acid, for example, acetic acid and propionic acid, esters, e.g. ethyl ester acetic acid, i-amyl ester acetic acid, methyl ester butyric acid, dimethyl succinic acid, amides, such as dimethylformamide, N-organic, NITRILES, such as acetonitrile, urea, for example, N,N,N',N'-tetramethylrhodamine, N,N'-dimethyl-ethylene - N,N'-dimethyl-propylene-urea, water, and single - and multi-phase mixtures of these compounds. In General, the reducing agent should be selected so that they do not react with the solvent. But they can also consciously be combined so that the active reducing agent formed only in a desired location, for example, DIBORANE from sodium borohydride and methylene chloride, dimethoxysilane sodium from sodium borohydride and methanol.

The reaction temperature during the reduction post-processing typically were in the range from 0 to 150oC, preferably from 20 to 80oC.

Duration of response in General is from 0.5 to 10 hours, preferably from 1 to 3 hours.

The preferred pH value of rehabilitation subsequent processing is determined by the known optimum value is x, and hydrosulfite sodium in acidic media.

CIS-2-(1H-1,2,4-triazole-1-yl-methyl)-2-(halogenfree)-3-(halogenfree)-oxiran formula I is allocated by known methods: filtration or centrifugation, or, in certain cases, separation of the phases, by precipitation of bicrystalline or evaporation. For further purification it is usually enough to wash or multiple mixing with water. To obtain products of high purity instead, or additionally, you can conduct multiple mixing with an organic solvent (a mixture) or recrystallization from it.

The epoxidation reaction preferably carried out in the presence of a large excess of percolate, for example, permalinki acid, which is preferable to obtain in situ in quantities of from 5 to 30, in particular from 5 to 10 molar equivalents of maleic anhydride, in terms of the olefin of the formula II, in quantities less than stoichiometric amount of hydrogen peroxide solution, in terms of the anhydride of maleic acid. In General, the ratio of the molar concentration of the anhydride to N2O2ranges from 1.5 to 10, in particular from 2 to 4. It is preferable to use 30-50% in the 0 to 100oC, in particular from 20 to 80oC.

The following examples illustrate how proposed in accordance with the present invention the method, which can be moved to other azolylmethyl-stilbene.

Example 1.

Dissolved at a temperature of 40oC of 58.9 g (0,601 mole) maleic anhydride and 18.6 g 97,2% (0,0576 mol)-Z-3-(1H-1,2,4-triazole-1-yl-methyl)-2-(forfinal)-1-(2-chlorophenyl)-propene in 150 ml of 1,2-dichloroethane, uniformly added dropwise within 1 h of 20.6 g (0,303 mole) of 50% aqueous hydrogen peroxide and stirred the reaction mixture for 7 hours at a temperature of 40oC. Iodometric titration taken during the mixing of the sample shows the result of the content of peroxide compounds in an amount of 0.4% in terms of hydrogen peroxide, this requires 6.9 ml 38% Hydrosulphite solution of sodium to restore peroxide compounds. After adding 100 ml of water and setting the pH of the aqueous phase equal to 3, with 50% sodium hydroxide solution add 170 ml of 38% Hydrosulphite solution of sodium, which corresponds to the excess equal 1385 molar in terms of olefin used, and produce intensive mixing of the two-phase reaction mixture for 3 hours at a temperature of 50oC). Upon cooling, the remaining aqueous phase is completely bicrystalline CIS-2-(1H-1,2,4-triazole-1-yl-methyl)-2-(4-forfinal)-3-(2-chlorophenyl)-oxiran separated, thoroughly washed with water and dried in a vacuum at a temperature of 90oC. Gain of 17.7 g of the product with the content of 93.4% determination was carried out using quantitative liquid chromatography under high pressure (ghvd). This corresponds to a yield equal to 87% of theoretical.

Example 2.

Epoxidation is conducted as described in example 1 is filtered maleic acid, rapidly drop after cooling, washed the filter residue with a small amount of 1,2-dichloroethane and combine the filtrate and the wash liquid. This solution of crude product weighs 242 grams and contains the results of iodometric titration of 0.08% peroxide compounds in terms of hydrogen peroxide. This requires 0,99 g dithionite sodium to restore peroxide compounds. After adding 12.0 g of dithionite of sodium in 40 ml of water, which corresponds to the excess equal to 110 molar in terms of olefin used, mix two is. Obtain 18.0 g of CIS-2-(1H-1,2,4-triazole-1-yl-methyl)-2-(4-forfinal)-3-(2-chlorophenyl)-oxirane with the content of 95.2 per cent (quantitative ghvd), which corresponds to a yield equal to 90.2 per cent of theoretical.

Example 3.

By analogy with example 1 is stirred mixture consisting of 9.3 g 97,2% (0,0288 mole) of Z-3-(1H-1,2,4-triazole-1-yl-methyl)-2-(4-forfinal)-1-(2-chlorophenyl)-propene, 55 ml of 1,2-dichloroethane, 28 g of maleic anhydride, 0.3 g of 2,6-di-tert-butylphenol and 7.3 g of 50% hydrogen peroxide for 6 hours at a temperature of 50oC and subsequent 2 hours at a temperature of 70oC. After decomposition minor residual amounts of peroxide compounds by adding 10% aqueous sodium thiosulfate solution, neutralizing the reaction mixture with 50% sodium hydroxide solution, separation and evaporation of the organic phase dissolve the residue in 70 ml of methanol, add 0.5 g of Raney Nickel and stirred for 2 h at temperatures 50oC under 2 liters of hydrogen (310 corresponds to the moles, in terms of olefin used). After filtering off the catalyst and evaporation of the solution gain of 8.9 g of CIS-2-(1H-1,2,4-triazole-1-yl-methyl)-2-(4-forfinal)-3-(2-chlorophenyl)-oxirane content 94,1% (quantitative ghvd), which corresponds to the output about the W ill result epoxidation as well as described in example 1, to restore the residual peroxide as time sufficient quantities of 38% Hydrosulphite solution of sodium (8.2 ml) and operate without performing recovery processing by an excess of a solution of bisulphite. Get to 17.2 g of the crude product with a content of 70.4% CIS-2-(1H-1,2,4-triazole-1-yl-methyl)-2-(4-forfinal)-3-(2-chlorophenyl)-oxirane (quantitative ghvd), which corresponds to a yield equal to, or 63.7% of theoretical.

Comparative example 2.

At the same carrying out the epoxidation reaction as in example 2, decompose residual peroxide as time sufficient quantities of dithionite sodium (1.4 g), but recovery without further processing by the excess solution detonite get 17,5 g of the crude product with a content of 66.7% CIS-2-(1H-1,2,4-triazole-1-yl-methyl)-2-(4-forfinal)-3-(2-chlorophenyl)-oxirane, which corresponds to a yield equal to 61.4% of theoretical.

Comparative example 3.

Work in the same way as described in example 3, however, lower recovery subsequent processing does not contain peroxide compounds of the crude product with hydrogen and Raney Nickel. Obtain 8.6 g of crude product is of tucta, equal to 59.4% of theoretical.

Thus the proposed method can improve the yield of the target product to the 87-90,2%

1. The way to obtain CIS-2-(1H-1,2,4-triazole-1-yl-methyl)- -2-(halogen-phenyl)-3-(halogenfree)-oxirane General formula I

< / BR>
where Hal is fluorine, chlorine or bromine,

by epoxidation of Z-3-(1H-1,2,4-triazole-1-yl)-2-(halogenfree)-1-(halogenfree)-propene of General formula II

< / BR>
permalinki acid with subsequent restoration, characterized in that, to increase the yield of the target product, in use as a reducing agent hydrosulfite sodium, dithionite sodium or sodium thiosulfate or hydrogen in the presence of Raney Nickel, and the reducing agent is added to the reaction mixture in excess of the amount required to fracture possibly available permalinki acid, not less than 10 mol. the excess of reducing agent relative to the compound of formula II.

2. The method according to p. 1, characterized in that the containing permaline acid the reaction product of epoxidation clear of permalinki acid, and then subjected to subsequent restorative treatment.

 

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