CN-118754823-B - Green synthesis method of cyanohydrin ester compound

Abstract

The invention discloses a green synthesis method of cyanohydrin ester compounds, which comprises the steps of mixing acyl nitrile, carboxylic acid, an activating agent and corresponding solvents, and then realizing deoxidization esterification of acyl nitrile carbonyl under mild conditions to obtain a series of cyanohydrin ester compounds. The invention can efficiently realize the efficient synthesis of the cyanohydrin ester compound, has mild conditions, and avoids the conditions of releasing or converting CN — anions which have biotoxicity and are unfavorable for the environment in the traditional reaction process. In addition, the method has the advantages of high reaction yield, simple operation, capability of realizing amplification of the reaction, and wide application prospect and practical value.

Inventors

• ZI YOU
• HUANG YUANYUAN
• WANG NAN
• HUANG WEICHUN
• WANG MENGKE

Assignees

• 南通大学

Dates

Publication Date

20260505

Application Date

20240607

Claims (7)

1. 1. The green synthesis process of cyanohydrin ester compound includes the steps of adding acyl nitrile, carboxylic acid and solvent into reaction container, stirring to react at room temperature, adding activator, eliminating solvent after the reaction, and simple separation to obtain target product lipid compound; The synthetic method has the following reaction route: ; Wherein R 1 is aryl or substituted aryl, R 2 is aryl, substituted aryl or alkyl; The activator is hexamethyltriamine phosphine; The solvent is one or a mixture of more of tetrahydrofuran, acetonitrile, 1, 2-dichloroethane, dichloromethane, N-dimethylformamide or toluene.
2. 2. The method for synthesizing a cyanohydrin ester compound according to claim 1, wherein the acyl nitrile is an aryl acyl nitrile.
3. 3. The method for synthesizing a cyanohydrin ester compound according to claim 1, wherein the carboxylic acid is an aryl carboxylic acid.
4. 4. The method for synthesizing a cyanohydrin ester compound according to claim 1, wherein the molar ratio of the acyl nitrile to the carboxylic acid to the activator is 1.0-1.2:1.0:1.0-1.3.
5. 5. The method for synthesizing a cyanohydrin ester compound according to claim 1, wherein the concentration of the carboxylic acid is 0.25-1.0M.
6. 6. The method for synthesizing a cyanohydrin ester compound according to claim 1, wherein the reaction temperature is 25-50 ℃.
7. 7. The method for synthesizing a cyanohydrin ester compound according to claim 1, wherein the reaction time is 2 to 12 hours.

Description

Green synthesis method of cyanohydrin ester compound Technical Field The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for synthesizing cyanohydrin ester compounds by using acyl nitrile and carboxylic acid in the presence of trivalent phosphine. Background Cyanohydrin esters are an important component of natural products, pharmaceuticals and agrochemicals, including pesticides of great commercial interest, such as deltamethrin and mavric, which are considered one of the safest, most effective pesticides due to their fast efficacy against insects and low toxicity against mammals. In addition, cyanohydrin esters play a key role in organic synthesis, providing an important means in the construction of a variety of valuable multifunctional molecules. They have a variety of conversion potentials, such as synthetic oxazoles, isocoumarins, ortho-carbonyl esters, and the like. For the synthesis of cyanohydrin esters, the most common method is to cyanide the aldehyde using cyanating reagents (e.g., metal cyanide and TMSCN) followed by carbonylation with an acyl halide or anhydride (Tetrahedron Lett.2015,56,7172-7175;Tetrahedron Lett.2005,46,7487-7490). However, the use of toxic cyanating reagents and the relatively cumbersome two-step reaction present serious drawbacks to these processes. In order to avoid the use of toxic cyanide and simplify the process, people aim at the cyanide compound. In the presence of additives (e.g., carbonates, amines, phosphines, bu3SnCN, etc.), the cyanide compounds can be synthesized into cyanohydrin esters (Synthesis 1996,1996,1188–1190;Chem.Eur.J.2015,22,3821–3829;Tetrahedron 2006,62,8715–8719;J.Org.Chem.1995,60,6229–6231). by in situ cyanation and esterification processes, however, in situ formation of CN — anion remains a key history of initiating the cyanation-acylation reaction process. Even if K 3Fe(CN)6 and K 4Fe(CN)6 etc. were developed as environmentally friendly alternatives (chem. Commun.2023,59,11544-11547;Synlett 2010,2010,2164-2168), release of CN — anions still presents an unavoidable risk. Among the numerous synthetic strategies for cyanohydrin esters, there are few examples in which cyanating agents are not used. In addition, most reported methods of synthesizing cyanohydrin esters are limited to active and expensive aldehyde starting materials and acetate or benzoate products. Therefore, development of alternative methods for synthesizing cyanohydrin ester compounds is of great importance, and particularly, the method for synthesizing various cyanohydrin ester compounds from cheap and easily available carboxylic acids more effectively without generating or converting toxic CN — anions is applicable to construction of more diversified compound frameworks. Disclosure of Invention The invention aims to provide a green synthesis method of a cyanohydrin ester compound. According to the green synthesis method of the cyanohydrin ester compound, provided by the invention, after the acyl nitrile, the carboxylic acid, the activating agent and the corresponding solvent are mixed, the deoxidization and esterification reaction of the acyl nitrile carbonyl can be realized under mild conditions, so that a series of cyanohydrin ester compounds are obtained; Adding acyl nitrile, carboxylic acid and solvent into a reaction container, stirring at room temperature for reaction, adding an activating agent, removing the solvent after the reaction is finished, and obtaining a lipid compound of a target product through simple separation by column chromatography; the synthetic method has the following reaction route: Wherein R 1 is alkyl or (hetero) aryl and R 2 is alkyl or (hetero) aryl; the activating reagent is a phosphinous compound, and has the structure as follows: Wherein R 3、R4、R5 is one of alkyl, aryl, alkoxy, aryloxy, alkylamino or arylamino, and is preferably hexamethyltriamine phosphine. The solvent is one or a mixture of tetrahydrofuran, acetonitrile, 1, 2-dichloroethane, dichloromethane, N-dimethylformamide and toluene, and preferably tetrahydrofuran. Further, the acyl nitrile is alkyl substituted acyl nitrile or (hetero) aryl substituted acyl nitrile. Further, the carboxylic acid is an alkyl-substituted primary, secondary or tertiary carboxylic acid or a (hetero) aryl carboxylic acid. Further, the activating reagent is a trivalent phosphorus compound, preferably hexamethyltriamine phosphine. Further, the molar ratio of the acyl nitrile, the carboxylic acid and the activating reagent is 1.0-1.2:1.0:1.0-1.3, preferably 1.1:1.0:1.1. Further, the reaction temperature of the carboxylic acid esterification is 25-50 ℃, preferably 25 ℃. Further, the reaction time of the carboxylic acid esterification is 2 to 12 hours, preferably 2 hours. The beneficial effects of the invention are as follows: 1. The invention can efficiently realize the efficient and green synthesis of the cyanohydrin ester compound, and has mild conditions.