CS269604B1 - Process for preparing 1,2,4,5-tetrazine derivatives - Google Patents

Abstract

a method for preparing 1,2,4,5-tetrazine derivatives of general formula I, where R. and R- denote hydrogen, methyl, ethyl, phenyl, o-chlorothenyl, by oxidizing 1,2-dihydro-1,2,4,5-tetrazine derivatives of general formula II by using ferric chloride in an aqueous medium in the presence of a wetting agent at temperatures of 50 to 100 °C for the oxidation

Description

The examples below illustrate embodiments of the invention.

Example 1

30.5 g of 3,6-bis (2-chlorophenyl) 1,2-dihydro-1,2,4,5-tetrazine, 200 g of water, 56.8 g are charged to a reactor equipped with a stirrer, reflux condenser, thermometer and heat exchange system. g of FeClp 6H ₂ O and 0.1 g of Slovasol 0. The reaction system is heated to 100 ° C and kept at this temperature with stirring for 2.5 hours. Then the reaction system is cooled to room temperature, the solid product is filtered off and the filter cake washed distilled water until loss of reaction to the presence of chloride ions. The obtained paste was dried in an oven and 30.1 g of a red-violet color product was obtained with mp 178-182 ° C. Yield 99.3%.

Example 2

In the same way 1,2,4,5-tetrazine was prepared by oxidation of 1,2-dihydro-1,2,4,5-tetrazine in a yield of 97.8%.

Example 3

As described in Example 1, 3,6-dimethyl-1,2,4,5-tetrazine was prepared from 3,6-dimethyl-1,2-dihydro-1,2,4,5-tetrazine in 98.9% yield. .

Example 4

Following the procedure described in Example 1, 3-methyl-1,2,4,5-tetrazine was prepared from 3-methyl-1,2-dihydro-1,2,4,5-tetrazine using PLURONIC® 75 as a wetting agent in a yield of 97, 5%. Example 5

According to the procedure described in Example 1, 3,6-bis-phenyl-1,2-dihydro-1,2,4,5-tetrazine was prepared using PLURONIC 75 as a wetting agent in a yield of 97.2%.

Example 6

In the same manner, 3-ethyl-1,2,4,5-tetrazine was prepared from 3-ethyl-1,2-dihydro-1,2,4,5-tetrazine in a yield of 98.9%.

Claims (3)

I will invent the subject. Method for preparing derivatives 1, 2,4,5-tetrazine of general formula I where Rp R ₂ are H, methyl, ethyl, phenyl, o-chlorophenyl oxidation of 1,2-dihydro-1,2,4,5-tetrazine derivatives of general formula II ^C - R ₂ (II)/ NH - NH-------------where Rp R ₂ have the above-mentioned meaning, characterized in that the oxidation is carried out by the action of ferric chloride in an aqueous medium in the presence of a wetting agent based on a copolymer of ethylene and propylene oxides at temperatures of 50 to 100 °C, preferably 35 to 100 °C. CS 269 604 Bl i: The invention relates to an improved process for the preparation of s-tetrazine derivatives by an oxidative process from the corresponding 1,2-dihydro-1,2,4,5-tetrazine derivatives. The aim of the invention is to provide an advantageous and technologically simple practical process for the preparation of the said compounds. The interest in the production of tetrazine derivatives is closely related to the discovery of their acaricidal, ovicidal, anti-inflammatory and bactericidal effects. In US Patent 3863010, phenyl and phenyl-substituted tetrazine derivatives exhibiting anti-inflammatory effects are disclosed. In The Journal of Agriculture and Food. Chemistry Vol 25 NO 4 1977 pp. 888-892 tetrazine derivatives exhibiting herbicidal properties are listed. Europatent 0005912 provides an overview of tetrazine derivatives exhibiting excellent activity against spider mites and mealybugs, their eggs and larvae. A typical representative of these agents is 3,6-disubstituted-1,2,4,5-tetrazine introduced to the market by the English company FBC Ltd and distributed as a 50 t solution of the active substance under the trade name APOLLO. Derivatives of 1,2-dihydro-1,2,4,5-tetrazines are relatively easy to oxidize and spontaneously, even in the presence of a weak oxidant, e.g. atmospheric oxygen, they convert to a 1,2,4,5-tetrazine derivative. The first laboratory procedure for the oxidation of 1,2-dihydro-1,2,4,5-tetrazine is described in the work of Curtis T. and Hess A.: J. Prakt. Chem. 125, 40, 1930. The authors perform the oxidation with sodium nitrite in acetic acid. The same oxidation procedure is recommended by the authors of EP 0029657 and in addition they mention other oxidizing agents such as CrO ₃ , dichromates, periodate, chlorine, bromine, etc. The authors of Japanese patent 49-4532 use antimony in acetic acid, alkaline bromide and FeClj for the oxidation of 3,6-diphenyl-1,2-dihydro-1,2,4,5-tetrazine. 6H ₂ O in ethanol. Oxidation yields range from 80 to 91%. It is obvious that the disadvantage of all the above procedures is the relatively low yield, even for easily oxidizable substances such as 3,6-diphenyl-1,2,4,5-tetrazine and in the case of industrial use, additionally the necessity of regeneration of the solvents used - acetic acid, ethanol, etc. The method of preparing 1,2,4,5-tetrazine derivatives of the general formula I where Rj, R ₂ are H, methyl, ethyl, phenyl, o-chlorophenyl by oxidation of 1,2-dihydro-1,2,4,5-tetrazine derivatives of the general formula II .N - N _R1 - <> - ₂ ^ÍU1 ' where Rp Rj have the above-mentioned meaning consists, according to the invention, in that the oxidation is carried out by the action of ferric chloride in an aqueous medium in the presence of a wetting agent based on a copolymer of ethylene and propylene oxides at temperatures of 50 to 100 °C, preferably 85 to 100 °C. The invention is based on the discovery that the oxidation of 1,2-dihydro-1,2,4,5-tetrazine derivatives with ferric chloride in an aqueous medium in the presence of a wetting agent proceeds practically quantitatively with a yield exceeding 97%. The almost quantitative yield is achieved mainly because the use of a wetting agent removes diffusion barriers to the oxidation process taking place in a suspensoid reaction system. Given the high yield and suitable environment, this production process represents progress both in terms of economy and ease of industrial use.