阅读说明：本技术 一种2,3二氰基丙酸乙酯的生产工艺 (Production process of ethyl 2, 3-dicyanopropionate ) 是由 刘长庆 于 2020-07-21 设计创作，主要内容包括：本发明提供一种2,3二氰基丙酸乙酯的生产工艺,包括以下步骤：步骤S1：原料预混合：先将氰乙酸乙酯、二甲基亚砜和丙二酸二乙酯加入反应釜中,混合搅拌形成预混合物；步骤S2：合成反应：向反应釜中投入氰化钠、多聚甲醛,搅拌混合条件下,恒温反应15-20h,形成反应混合液；步骤S3：加酸；步骤S4：萃取；步骤S5：减压蒸馏回收；步骤S6：精馏：除去少量前馏分杂质后得到红色油状目标产物2,3二氰基丙酸乙酯。按重量份数计,原料中的个组分的配比如下：氰乙酸乙酯100份、二甲基亚砜100-150份、氰化钠60-100份、多聚甲醛50-80份、丙二酸二乙酯20-30份。本发明提供一种安全性高、产物收率高、副产物少的2,3二氰基丙酸乙酯的生产工艺。(The invention provides a production process of 2, 3-dicyanopropionic acid ethyl ester, which comprises the following steps: step S1: premixing raw materials: adding ethyl cyanoacetate, dimethyl sulfoxide and diethyl malonate into a reaction kettle, and mixing and stirring to form a premix; step S2: and (3) synthesis reaction: adding sodium cyanide and paraformaldehyde into a reaction kettle, and reacting for 15-20h at constant temperature under the condition of stirring and mixing to form reaction mixed liquid; step S3: adding acid; step S4: extracting; step S5: recovering by reduced pressure distillation; step S6: and (3) rectification: removing a small amount of front cut impurities to obtain the target product 2, 3-dicyano ethyl propionate of red oil. The raw materials comprise the following components in parts by weight: 100 parts of ethyl cyanoacetate, 100 parts of dimethyl sulfoxide, 150 parts of sodium cyanide, 50-80 parts of paraformaldehyde and 20-30 parts of diethyl malonate. The invention provides a production process of ethyl 2, 3-dicyanopropionate, which has high safety, high product yield and few byproducts.)

1. A production process of ethyl 2, 3-dicyanopropionate is characterized by comprising the following steps:

step S1: premixing raw materials: adding ethyl cyanoacetate, dimethyl sulfoxide and diethyl malonate into a reaction kettle, and mixing and stirring to form a premix;

step S2: and (3) synthesis reaction: adding sodium cyanide and paraformaldehyde into a reaction kettle, and reacting for 15-20h at constant temperature under the condition of stirring and mixing to form reaction mixed liquid;

step S3: adding acid: dropwise adding hydrochloric acid into the reaction mixed solution until the pH value is 5.4-6.7;

step S4: and (3) extraction: adding dichloroethane for extraction for four times;

step S5: and (3) reduced pressure distillation recovery: the extracted water layer is used for recovering dimethyl sulfoxide, the extract liquor is combined and washed for four times by water, the washed extract liquor is subjected to reduced distillation to remove dichloroethane, and a crude product of the dehydrated and dried dichloroethane is formed;

step S6: and (3) rectification: immediately transferring the crude product of the dried dichloroethane into stainless steel rectification for high vacuum rectification, and removing a small amount of front fraction impurities to obtain a red oily target product, namely ethyl 2, 3-dicyanopropionate;

the raw materials comprise the following components in parts by weight: 100 parts of ethyl cyanoacetate, 100 parts of dimethyl sulfoxide, 150 parts of sodium cyanide, 50-80 parts of paraformaldehyde and 20-30 parts of diethyl malonate.

2. A process for the production of ethyl 2, 3-dicyanopropionate according to claim 1, characterized in that: the raw materials also comprise 5-10 parts of 2-amino-3-hydroxypyridine according to parts by weight.

3. A process for the production of ethyl 2, 3-dicyanopropionate according to claim 1, characterized in that: the raw materials also comprise 1-5 parts of 2-amino-2-methyl-1, 3-propanediol according to parts by weight.

4. A process for the production of ethyl 2, 3-dicyanopropionate according to claim 1, characterized in that: the temperature in the reaction kettle of the step S1 is 5-10 ℃.

5. A process for the production of ethyl 2, 3-dicyanopropionate according to claim 1, characterized in that: the constant temperature in the step S2 is 15-20 ℃.

6. A process for the production of ethyl 2, 3-dicyanopropionate according to claim 1, characterized in that: at the end of the reaction of step S2, the degree of reaction of ethyl cyanoacetate, as determined by gas chromatography, is greater than 99.5%.

Technical Field

The invention relates to the technical field of production of pharmaceutical intermediates, in particular to a production process of 2, 3-dicyanopropionic acid ethyl ester.

Background

The ethyl 2, 3-dicyanopropionate is colorless to red oily liquid, is dissolved in ethyl ether and ethyl acetate, is insoluble in water, is hydrolyzed with alkali into corresponding acid, is deeply hydrolyzed into the 1, 2-dicyanoethane, is frozen, sealed and is preserved in the dark.

The ethyl 2, 3-dicyanopropionate is an important intermediate for synthesizing phenyl pyrazole insecticides. The phenylpyrazole pesticide prepared from the ethyl 2, 3-dicyanopropionate has a wide insecticidal spectrum, has strong control capability on chloride metabolism controlled by insect gamma-aminobutyric acid, can kill pests from three aspects of stomach toxicity, contact poisoning and systemic absorption, is mainly used for preventing and controlling pests such as aphids, leafhoppers, lice, lepidoptera larvae, flies, coleoptera and the like, has no crop phytotoxicity, is operated by adopting a soil and leaf surface spraying mode, has long-lasting pesticide effect, and has great requirements on sanitation and dry farmland seed coating agents such as corn and the like.

Disclosure of Invention

The invention aims to provide a production process of ethyl 2, 3-dicyanopropionate, which has high safety, high product yield and few byproducts.

The technical purpose of the invention is realized by the following technical scheme:

a production process of ethyl 2, 3-dicyanopropionate comprises the following steps:

step S1: premixing raw materials: adding ethyl cyanoacetate, dimethyl sulfoxide and diethyl malonate into a reaction kettle, and mixing and stirring to form a premix;

step S2: and (3) synthesis reaction: adding sodium cyanide and paraformaldehyde into a reaction kettle, and reacting for 15-20h at constant temperature under the condition of stirring and mixing to form reaction mixed liquid;

step S3: adding acid: dropwise adding hydrochloric acid into the reaction mixed solution until the pH value is 5.4-6.7;

step S4: and (3) extraction: adding dichloroethane for extraction for four times;

step S5: and (3) reduced pressure distillation recovery: the extracted water layer is used for recovering dimethyl sulfoxide, the extract liquor is combined and washed for four times by water, the washed extract liquor is subjected to reduced distillation to remove dichloroethane, and a crude product of the dehydrated and dried dichloroethane is formed;

step S6: and (3) rectification: immediately transferring the crude product of the dried dichloroethane into stainless steel rectification for high vacuum rectification, and removing a small amount of front fraction impurities to obtain a red oily target product, namely ethyl 2, 3-dicyanopropionate;

the raw materials comprise the following components in parts by weight: 100 parts of ethyl cyanoacetate, 100 parts of dimethyl sulfoxide, 150 parts of sodium cyanide, 50-80 parts of paraformaldehyde and 20-30 parts of diethyl malonate.

According to the further setting of the invention, the raw materials also comprise 5-10 parts of 2-amino-3-hydroxypyridine in parts by weight.

As a further setting of the invention, the raw materials also comprise 1-5 parts of 2-amino-2-methyl-1, 3-propanediol by weight.

As a further arrangement of the invention, the temperature in the reaction kettle of the step S1 is 5-10 ℃.

As a further arrangement of the present invention, the constant temperature in step S2 is 15-20 ℃.

As a further configuration of the present invention, at the end of the reaction of step S2, the degree of reaction of ethyl cyanoacetate, as determined by gas chromatography, is greater than 99.5%.

The invention has the beneficial effects that:

1. according to the production process of the ethyl 2, 3-dicyanopropionate, ethyl cyanoacetate and dimethyl sulfoxide are added into a reaction kettle, sodium cyanide and paraformaldehyde are added for reaction, and then the reaction product is dissolved in water, acidified by hydrochloric acid, extracted by dichloromethane and desolventized to finally obtain a red oily product, so that the conventional raw material of hydroxyacetonitrile is not needed, the dimerization side reaction of nitrile is avoided, and the content of byproducts in the product is effectively reduced; compared with the traditional production process, the method changes the adding sequence of the raw materials, the ethyl cyanoacetate is added firstly, then the sodium cyanide and the paraformaldehyde are added for reaction, compared with the material adding sequence of firstly adding the paraformaldehyde and then adding the ethyl cyanoacetate, the intensity of the reaction is effectively reduced, the reaction temperature is controllable, the safety phenomena of material flushing and the like caused by the excessively intense heat release of the reaction are prevented, and therefore the prepared product has high yield and purity, the production operation process is simplified, the transfer and leakage chances of highly toxic articles are reduced, and the safety is high.

2. According to the production process of the ethyl 2, 3-dicyanopropionate, diethyl malonate is added into raw materials, alpha carbon of the diethyl malonate is positioned between two carbonyl groups, hydrogen on the alpha carbon position has strong chemical activity and can interact with the cyano groups to improve the reaction activity of the cyano groups, the cyano groups are mutually connected to form an active connecting body together to generate larger polarity, so that sodium cyanide and paraformaldehyde of the raw materials can quickly enter the active connecting body under the action of polarity force to react, the reaction speed and the reaction degree of the reaction are improved, and the yield of the reaction and the purity of the product are improved.

3. The production process of the ethyl 2, 3-dicyanopropionate further comprises the step of adding 2-amino-3-hydroxypyridine (pyridine) into the raw materials, wherein the 2-amino-3-hydroxypyridine can inhibit the acidolysis reaction of the raw material ethyl cyanoacetate in the reaction to form acid, so that the utilization rate of the raw materials is effectively improved, and the yield and the product purity of the reaction are improved.

4. The production process of the ethyl 2, 3-dicyanopropionate also adds 2-amino-2-methyl-1, 3-propanediol into the raw material, and the 2-amino-2-methyl-1, 3-propanediol introduces an amide group, thereby effectively improving the polarity of the active coupling system of the ethyl cyanoacetate, further improving the reaction efficiency of the sodium cyanide of the ethyl cyanoacetate and paraformaldehyde, and improving the reaction yield and the product purity.

Detailed Description

The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. It is to be understood that the described embodiments are merely a few embodiments of the invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments of the present invention without any inventive step, are within the scope of the present invention.