阅读说明：本技术 一种合成丙炔醇的制备方法 (Preparation method for synthesizing propiolic alcohol ) 是由 邓秋林 黄晓枫 于 2020-06-02 设计创作，主要内容包括：本发明提供了一种合成丙炔醇的制备方法。该方法的合成路线如下：首先,在无水无氧条件下,将金属镁、碘单质和溶剂加入反应器中搅拌均匀,然后滴加卤代烃并持续搅拌,经格氏反应得到烃基卤化镁格氏试剂；再将乙炔通入反应器中发生格氏交换反应得到乙炔基卤化镁；最后将甲醛通入反应器中与乙炔基卤化镁反应后产物经水解得到丙炔醇。本发明提供的制备方法具有简单安全,操作条件温和的优点。(The invention provides a preparation method for synthesizing propiolic alcohol. The synthetic route of the method is as follows: firstly, adding metal magnesium, iodine simple substance and solvent into a reactor under anhydrous and anaerobic conditions, uniformly stirring, then dropwise adding halohydrocarbon and continuously stirring, and obtaining a hydrocarbyl magnesium halide Grignard reagent through Grignard reaction; then introducing acetylene into the reactor to carry out a Grignard exchange reaction to obtain ethynyl magnesium halide; and finally, introducing formaldehyde into the reactor to react with the ethynyl magnesium halide, and hydrolyzing the product to obtain the propiolic alcohol. The preparation method provided by the invention has the advantages of simplicity, safety and mild operation conditions.)

1. A preparation method for synthesizing propiolic alcohol mainly comprises the following steps:

(1) and (3) performing a Grignard reaction: adding metal magnesium, iodine simple substance and solvent into a reactor under anhydrous and anaerobic conditions, uniformly stirring, then dropwise adding halohydrocarbon, and continuously performing reflux reaction for 1-3 h at a certain temperature after dropwise adding is finished to obtain a product, namely a hydrocarbyl magnesium halide Grignard reagent;

(2) grignard exchange reaction: introducing acetylene into a reactor to react for 2-4 h at a certain temperature, and carrying out a Grignard exchange reaction with alkyl magnesium halide to obtain ethynyl magnesium halide;

(3) nucleophilic addition reaction: introducing formaldehyde into a reactor, reacting for 1-3 h at a certain temperature, carrying out nucleophilic addition reaction with ethynyl magnesium halide, and hydrolyzing the product to obtain the propiolic alcohol.

2. A process for the preparation of a synthetic propargyl alcohol as claimed in claim 1, wherein: a compound of the formula:

R-X

wherein R is one of alkyl, alkenyl and phenyl; x is one of chlorine, bromine and iodine.

3. A process for the preparation of a synthetic propargyl alcohol as claimed in claim 1, wherein: the solvent is at least one of anhydrous diethyl ether and tetrahydrofuran.

4. A process for the preparation of a synthetic propargyl alcohol as claimed in claim 1, wherein: the reflux temperature in the step (1) is 60-100 DEG C^oC; the reaction temperature in the step (2) is-20 to 40 DEG C^oC; the reaction temperature in the step (3) is 20-40 DEG^oC。

5. A process for the preparation of a synthetic propargyl alcohol as claimed in claim 1, wherein: the molar ratio of the halogenated hydrocarbon to the acetylene in the step (2) is 1 (0.8-1.5); in the step (3), the molar ratio of the ethynyl magnesium halide to the formaldehyde is 1 (0.8-1.5).

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of propiolic alcohol.

Background

The propiolic alcohol is a key intermediate widely applied to the industries of medicines, pesticides, electroplating and resins, and is mainly used for preparing medicines such as sulfadiazine, fosfomycin, pesticide propargite, electroplated nickel plating brightener and the like (CN 109369328A). Meanwhile, two flexible and variable functional groups, namely alkynyl and hydroxyl, can be converted through the functional groups, so that the functional groups have great potential application values in the aspect of molecular diversity. Propiolic alcohol can be prepared by the addition reaction of terminal group alkyne to aldehyde or ketone, and the reaction process is generally that an active metal reagent such as alkyl zinc, butyl lithium and the like firstly reacts with terminal alkyne to generate alkynyl zinc or alkynyl lithium reagent, and then the propargyl alcohol compound is obtained by the addition reaction to carbonyl compound (CN 105017016A; CN 105017016A). However, metal reagents such as zinc alkyl and butyl lithium are extremely sensitive to water, the water content of a reaction system needs to be strictly controlled, and reagents, solvents and vessels required by the reaction need to be strictly dried without water, so that the reaction conditions are severe and the operation is inconvenient. The industrial production of propiolic alcohol basically adopts a Reppe process, and because a large amount of acetylene gas and flammable and explosive acetylene copper catalyst are used in the process, the acetylene pressure reaches 2 MPa, and the safety problem always troubles the process. In the 70's of the 20 th century, a modified Reppe process was developed, which employs a slurry bed or suspension bed technique, and the reaction was carried out under normal or low pressure. However, the improved Reppe process has higher requirements for catalyst and process operating conditions (CN 109772353 a). Therefore, the development of a simple, efficient and safe green reaction process is still of great significance.

Disclosure of Invention

Aiming at the defect of safety of the existing propiolic alcohol preparation technology, the invention provides a simple and safe preparation method for synthesizing propiolic alcohol.

A preparation method for synthesizing propiolic alcohol mainly comprises the following steps:

(1) and (3) performing a Grignard reaction: adding metal magnesium, iodine simple substance and solvent into a reactor under anhydrous and anaerobic conditions, uniformly stirring, then dropwise adding halohydrocarbon, and continuously performing reflux reaction for 1-3 h at a certain temperature after dropwise adding is finished to obtain a product, namely a hydrocarbyl magnesium halide Grignard reagent;

(2) grignard exchange reaction: introducing acetylene into a reactor to react for 2-4 h at a certain temperature, and carrying out a Grignard exchange reaction with alkyl magnesium halide to obtain ethynyl magnesium halide;

(3) nucleophilic addition reaction: introducing formaldehyde into a reactor, reacting for 1-3 h at a certain temperature, carrying out nucleophilic addition reaction with ethynyl magnesium halide, and hydrolyzing the product to obtain the propiolic alcohol.

The reaction process of the invention is as follows:

the method prepares alkynyl magnesium halide by taking metal magnesium and halogenated hydrocarbon as raw materials, and further prepares propiolic alcohol by addition reaction with formaldehyde, and has the advantages of mild reaction conditions and simple operation.

Further, compounds of the formula:

R-X

wherein R is one of alkyl, alkenyl and phenyl; x is one of chlorine, bromine and iodine.

Further, the solvent is at least one of anhydrous diethyl ether and tetrahydrofuran.

Further, the reflux temperature in the step (1) is 60-100 DEG^oC; the reaction temperature in the step (2) is-20 to 40 DEG C^oC; the reaction temperature in the step (3) is 20-40 DEG^oC。

Further, the molar ratio of the halogenated hydrocarbon to the acetylene in the step (2) is 1 (0.8-1.5); in the step (3), the molar ratio of the ethynyl magnesium halide to the formaldehyde is 1 (0.8-1.5).

Detailed Description

The following examples are helpful in understanding the present invention, but are not limited to the summary of the invention. The simple replacement or improvement of the present invention by those skilled in the art is within the technical scheme of the present invention.