1,2,4-triazole and preparation method therefor

Patent metadata

Field	Value
Publication number	US-11072589-B2
Application number	US-202017067721-A
Country	US
Kind code	B2
Filing date	Oct 11, 2020
Priority date	Apr 15, 2018
Publication date	Jul 27, 2021
Grant date	Jul 27, 2021

Abstract

A method for preparing 1,2,4-triazole includes using a fluoroborate aryl diazonium salt, a diazoester derivative and an organic nitrile as reaction substrates, a transition metal salt as a catalyst, and an inorganic base as an additive in a cyclization reaction. The method has the following characteristics: the reaction is economical; the substrate is universal; the post-functionalization is easy; the reaction conditions are mild; the reaction can be performed in air; the catalyst amount used is less; and the post-treatment is simple. Meanwhile, the raw materials, such as the reactants and the catalyst used, are inexpensive and easily available; the reaction composition is reasonable; no ligand is needed; there are less reaction steps; and only one step of reaction is required to obtain a high yield, meeting the requirements and directions of contemporary green chemistry and medicinal chemistry, being suitable for screening highly active 1,2,4-triazole drugs.

First claim

The invention claimed is:

1. A method of preparing a 1,2,4-triazole, comprising:
conducting a cyclization reaction of a fluoroborate aryl diazonium salt, a diazonium ester derivative and an organic nitrile, in the presence of a copper salt as a catalyst and an inorganic base as an additive, to obtain the 1,2,4-triazole,
wherein the fluoroborate aryl diazonium salt has the following chemical structural formula:

 and Ar is selected from the group consisting of an aryl group, a monosubstituted aryl group, a disubstituted aryl group, and naphthyl;
wherein the diazonium ester derivative has the following chemical formula:

 and R 1 is selected from the group consisting of ethyl, isopropyl, tert-butyl, cyclohexyl, phenyl, benzyl,

 —CH 2 CH 2 CH 2 OCH 3 , —CH 2 CF 3 , —CH 2 CH 2 Br,

 and —CH 2 CH 2 CH═CH 2 ;
wherein the organic nitrile has the following chemical structural formula: R 2 —C≡N, and R 2 is selected form the group consisting of methyl, isopropyl, tert-butyl, benzyl, —CH 2 CH 2 CH 2 Cl, —CH 2 CH 2 OCH 3 , —CH 2 CH═CH 2 , —CH═CHCH 3 , and

wherein the 1,2,4-triazole has the following chemical structural formula:

2. The method according to claim 1 , wherein the cyclization reaction is conducted at 40° C. for 1 hour in the air.

3. The method according to claim 1 , wherein the copper salt was a halogen copper salt, and the additive is selected from the group consisting of lithium carbonate, potassium carbonate, cesium carbonate, sodium acetate, and lithium tert-butoxide.

4. The method according to claim 3 , wherein the copper salt is cuprous bromide, and the additive is lithium carbonate.

5. The method according to claim 1 , wherein the aryl group is phenyl; the monosubstituted aryl group has the following chemical structural formula:

and R is selected from the group consisting of hydrogen, methyl, isopropyl, tert-butyl, isopropyl, methoxy, fluoride, chlorine, bromine, trifluoromethyl, and trifluoromethoxy; and the disubstituted aryl group is selected from the group consisting of

6. The method according to claim 1 , wherein a molar ratio of the catalyst to the fluoroborate aryl diazonium salt is 20%; and a molar ratio of the additive to the fluoroborate aryl diazonium salt is 1.

7. The method according to claim 1 , wherein a molar ratio of the organic nitrile to the fluoroborate aryl diazonium salt is 20-50; and a molar ratio of the diazonium ester derivative to the fluoroborate aryl diazonium salt is 3.

Assignees

• Univ Soochow

Inventors

• Li Haiyan
• Li Huihuang
• Wang Yaxiong
• Wan Xiaobing

Classifications

• C07D249/10 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• B01J23/78 Primary

  with alkali- or alkaline earth metals · CPC title

• B01J27/122

  of copper · CPC title

• B01J23/72

  Copper · CPC title