CN-121991001-A - Method for synthesizing oxazole-2-methyl formate from triazole and oxalyl chloride monomethyl ester mediated by mixed alkali

CN121991001ACN 121991001 ACN121991001 ACN 121991001ACN-121991001-A

Abstract

The oxazole ring is taken as a classical nitrogen-containing heteroaromatic ring skeleton, and has irreplaceable application value in the leading-edge fields of pharmaceutical chemistry, functional material creation, bioactive molecule research and development and the like. Among them, methyl oxazole-2-carboxylate has become a core synthesis precursor of various drug molecules and high value-added fine chemicals by virtue of unique structural characteristics and reactivity. Aiming at the bottleneck problems of low yield, insufficient product purity, severe reaction conditions and the like commonly existing in the existing synthesis process, the patent aims at efficient green synthesis of the oxazole-2-methyl formate, and the system explores the regulation and control effects of key parameters such as reaction solvent, reaction time, reaction temperature, alkali types and dosage and the like on the synthesis process. The result shows that 1.0 equivalent of 1H-1,2, 3-triazole and 1.2 equivalent of oxalyl chloride monomethyl ester are used as starting materials, a mixed base catalytic system is constructed by adopting 1.0 equivalent of sodium hydride and 1.0 equivalent of potassium carbonate, sulfolane is used as a solvent, and the reaction is carried out for 2 hours at 80 ℃, so that the oxazole-2-methyl formate can be efficiently prepared by a one-pot method, the product yield is up to 92%, and the purity is up to 98%. The purity of the product obtained by the process meets the application requirements of subsequent separation and purification, structural modification and large-scale preparation of medical intermediates, provides a feasible technical path for industrial production of the oxazole derivatives, and has remarkable application potential and popularization value.

Inventors

LIN TINGZHI
WANG ZILONG
LI YONGXIN
GU SHENGQI
LI XIANGYI

Assignees

南京工业大学

Dates

Publication Date: 20260508
Application Date: 20251231

Claims (6)

1. A method for synthesizing oxazole-2-methyl formate by using mixed alkali mediated 1H-1,2, 3-triazole and oxalyl chloride monomethyl ester is characterized in that: 1H-1,2, 3-triazole shown in formula 1 and oxalyl chloride monomethyl ester shown in formula 2 are adopted to synthesize oxazole-2-methyl formate shown in formula 3 in the presence of mixed alkali and an organic solvent.
2. The method of claim 1, wherein the mixed base is NaH and K 2 CO 3 .
3. The method according to claim 2, wherein the ratio of the mixed alkali NaH to K 2 CO 3 is 1:1.
4. The method of claim 1, wherein the organic solvent is sulfolane.
5. The synthesis method according to claim 1, wherein the molar ratio of 1H-1,2, 3-triazole (1) shown in the formula 1 to oxalyl chloride monomethyl ester (2) shown in the formula 2 to the mixed base is 1:1.2:2.
6. The synthetic method of claim 1 wherein the reaction temperature of the synthetic method is 80 ℃.

Description

Method for synthesizing oxazole-2-methyl formate from triazole and oxalyl chloride monomethyl ester mediated by mixed alkali Technical Field The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of oxazole-2-methyl formate. Background The heterocyclic compounds are cyclic organic compounds containing at least one heteroatom in a molecular framework, are used as core structural units of medicines, functional materials and bioactive molecules, and have key effects on promoting medicine research and development, new material creation and life science exploration. Oxazole is an important class of five-membered heterocyclic compounds, which contain one nitrogen atom and one oxygen atom in their molecular structure. The structure is widely applied to various natural compounds, is a core skeleton forming a plurality of bioactive molecules and drug lead structures, and has important research value in pharmaceutical chemistry and organic synthesis. Oxazole derivatives exhibit a rich biological activity and their potential for use is of great interest in drug discovery. For example, compound Texaline (formula a) isolated from ami-tree has been shown to have good antitubercular activity, 2-methoxybenzoxazole (formula B) is a class of benzoxazole derivatives with significant biological activity. Research shows that the compound has excellent inhibitory activity on various pathogenic fungi, has good application potential in the field of antifungal drug development, and has obvious activity on various tumor cell lines. In addition, oxazole derivatives also exhibit important application value in fields other than pharmaceutical chemistry. Taking 5-chlorobenzoxazole-2-amine (formula D) as an example, the compound is taken as a ligand with stable structure and excellent coordination capability, has been widely used in the design and development of various metal catalysts, plays a key role in organic synthesis and catalytic reaction, and 2, 5-diphenyl oxazole (formula E) is an important fluorescent material precursor, is often used as a key structural unit in the design and synthesis of organic scintillators, has important significance in developing high-performance radiation detection materials, and oxazole pesticides such as fenoxaprop-p-ethyl (formula F) play an important role in plant protection. Therefore, how to realize the efficient and convenient synthesis of the oxazole compounds is always a research focus and hot spot problem in the chemical synthesis field. Disclosure of Invention According to the invention, 1.0 equivalent of 1H-1,2, 3-triazole and 1.2 equivalent of oxalyl chloride monomethyl ester are used as starting materials, 1.0 equivalent of sodium hydride and 1.0 equivalent of potassium carbonate form a mixed alkali system, sulfolane is used as a solvent, and the mixed alkali system is reacted for 2 hours at 80 ℃, so that the oxazole-2-methyl formate is prepared with a yield of 92% and a purity of 98% by a one-pot method. Effectively solves the problems of low yield, insufficient purity, harsh reaction conditions and the like existing in the existing process for synthesizing the oxazole-2-methyl formate. The specific scheme is as follows: the synthesis method of the oxazole-2-methyl formate adopts 1H-1,2, 3-triazole and oxalyl chloride monomethyl ester as starting materials, sodium hydride and potassium carbonate form a mixed alkali system, sulfolane is used as a solvent, and the mixed alkali system and the organic solvent are mixed to react at 80 ℃ to synthesize the oxazole-2-methyl formate shown in the formula 3. The method can realize the one-pot method for generating the oxazole-2-methyl formate, reduces reaction steps, thereby improving the product yield, and has multiple raw material acquisition paths and higher economic benefit. Preferably, the mixed alkali is NaH and K 2CO3. Preferably, the ratio of the mixed alkali NaH to K 2CO3 is 1:1. Preferably, the organic solvent is sulfolane. Preferably, the molar ratio of 1H-1,2, 3-triazole (1) shown in the reaction formula 1 to oxalyl chloride monomethyl ester (2) shown in the reaction formula 2 to the mixed alkali is 1:1.2:2. Preferably, the reaction temperature of the synthesis process is 80 ℃. Preferably, compounds of the following structure can be produced using the methods of the present invention: The technical scheme of the invention can at least achieve one of the following beneficial effects: the synthetic method of the invention adopts cheap raw materials, has diversified acquisition paths and has higher economic benefit; The invention adopts a one-pot synthesis method, reduces the loss of raw materials, saves the reaction time and improves the product yield and the reaction efficiency due to fewer reaction steps; The invention has the advantages of simple operation steps, no need of extreme temperature rise or temperature reduction, reaction under normal pressure, safety, convenience and low energ