Method for improving conversion rate of diethyl 2-cyanoethyl malonate

Abstract

The invention discloses a method for improving the conversion rate of diethyl 2-cyanoethyl malonate, which is characterized in that a byproduct dicyanoethyl malonate generated by reaction is subjected to secondary conversion to obtain the diethyl 2-cyanoethyl malonate, so that the yield of the diethyl 2-cyanoethyl malonate is improved, the utilization rate of raw materials is effectively improved, and the cost of the raw materials is reduced; meanwhile, the three-waste treatment capacity is reduced, the environmental protection pressure is remarkably reduced, and the method can be better suitable for industrial large-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of chemical intermediate synthesis, and in particular to a method for improving the conversion rate of diethyl 2-cyanoethylmalonate. Background Art

[0002] Diethyl 2-cyanoethylmalonate is one of the important intermediates for synthesizing melatonin, a raw material for health products. Currently, conventional synthetic routes mostly use diethyl malonate to react with acrylonitrile under alkaline conditions for cyanoethylation to generate diethyl 2-cyanoethylmalonate, but this reaction produces a byproduct, diethyl bis-cyanoethylmalonate (accounting for about 20%).

[0003]

[0004] For this reason, the prior art has developed a method using diethyl malonate with potassium carbonate as an alkaline catalyst and ethyl acetate as a solvent. Under the catalytic action of potassium carbonate, diethyl malonate and acrylonitrile are subjected to cyanoethylation reaction in an ethyl acetate solvent to obtain 2-cyanoethyl diethyl malonate with a yield of 83%. However, the disadvantage of this method is that ethyl acetate is easily hydrolyzed under alkaline conditions, and potassium carbonate is not easily soluble in ethyl acetate, so that the reaction time is long, and operations such as extraction and dehydration are required, and the process is relatively complicated.

[0005] In addition, the prior art also uses a solvent-free method, that is, diethyl malonate is directly cyanoethylated with acrylonitrile under the action of metallic sodium as an alkaline catalyst, and then distilled and purified, but the final yield is 63.7%. The disadvantage of this method is that metallic sodium is used as an alkaline catalyst, and the alkalinity of metallic sodium is too strong. During the insulation process, more diethyl malonate is over-cyanoethylated, and more diethyl bis-cyanoethyl malonate impurities are generated, resulting in a reduced yield. In addition, metallic sodium is not easy to operate during the production process, which is accompanied by greater safety risks.

[0006] In addition, there is also a method in which excess diethyl malonate is used as a solvent and a reaction raw material to carry out a cyanoethylation reaction with acrylonitrile under the action of an alkaline catalyst. In this method, excess diethyl malonate is subsequently separated and reused, with a final yield of 80.9% (based on acrylonitrile). The disadvantage is that the reaction process takes a long time and a large amount of diethyl malonate needs to be evaporated, which increases production energy consumption.

[0007] At present, the existing technology generally has the problem that a large amount of diethyl malonate is over-cyanoethylated in the preparation method of diethyl 2-cyanoethyl malonate, resulting in a reduced yield, and there are disadvantages of low utilization rate of diethyl malonate raw materials and high cost. Therefore, how to improve the synthesis yield of diethyl 2-cyanoethyl malonate, reduce the cost of raw materials, and reduce the pressure of three wastes treatment is extremely critical for the production of melatonin. Summary of the invention

[0008] The object of the present invention is to overcome the deficiencies of the prior art and provide a method for improving the conversion rate of diethyl 2-cyanoethyl malonate, wherein the by-products produced by the reaction are converted twice, thereby improving the yield of diethyl cyanoethyl malonate and reducing the amount of three wastes to be treated, so as to be better suitable for industrial-scale production.

[0009] The purpose of the present invention is achieved through the following technical solutions:

[0010] The present invention provides a method for improving the conversion rate of diethyl 2-cyanoethylmalonate, comprising the following steps:

[0011] (1) dissolving diethyl biscyanoethyl malonate in an organic solvent, then adding an alkaline catalyst, adding diethyl malonate at a temperature of 30 to 60° C., reacting for 2 to 5 hours, and obtaining a 2-cyanoethyl diethyl malonate reaction liquid; the mass ratio of diethyl biscyanoethyl malonate: organic solvent is 1:1 to 5, the mass ratio of diethyl biscyanoethyl malonate: alkaline catalyst is 1:0.01 to 0.03, and the mass ratio of diethyl biscyanoethyl malonate: diethyl malonate is 1 to 2:1;

[0012] (2) subjecting the reaction solution of diethyl 2-cyanoethylmalonate to negative pressure distillation, and collecting a positive fraction with a gas phase temperature of 110-115° C. at a vacuum degree below 50 Pa, which is diethyl 2-cyanoethylmalonate.

[0013] Furthermore, the organic solvent of the present invention is ethyl acetate, methanol, or petroleum ether. The alkaline catalyst is one of tetramethylammonium hydroxide, sodium tert-butoxide, and an organic metal lithium compound, or a combination thereof.

[0014] In the above scheme, the GC detection content of diethyl 2-cyanoethylmalonate of the present invention is greater than 95%, and the molar conversion rate is greater than 50%.

[0015] The present invention has the following beneficial effects:

[0016] (1) In the synthesis process of diethyl 2-cyanoethyl malonate, the highest molar yield of the reaction reported in the literature is 80-83%, and diethyl bis-cyanoethyl malonate accounts for about 17-20%. The present invention converts the by-product diethyl bis-cyanoethyl malonate into diethyl 2-cyanoethyl malonate for a second time, and the molar conversion rate reaches more than 50%. The GC detection content of the obtained diethyl 2-cyanoethyl malonate reaches more than 95%, which effectively improves the utilization rate of raw materials and reduces the cost of raw materials;

[0017] (2) The present invention converts the distillation residue by-product diethyl bis-cyanoethyl malonate, which originally needs to be incinerated, into a product through a reversible reaction, thereby reducing the amount of three wastes to be treated and significantly reducing environmental pressure. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The present invention will be further described in detail below with reference to the embodiments and accompanying drawings:

[0019] Figure 1 This is the GC content graph of diethyl biscyanoethyl malonate in Example 1 of the present invention;

[0020] Figure 2 This is the GC content graph of diethyl 2-cyanoethylmalonate prepared in Example 1 of the present invention;

[0021] Figure 3 This is the GC content graph of diethyl 2-cyanoethylmalonate obtained in Example 2 of the present invention;

[0022] Figure 4 This is the GC content graph of diethyl 2-cyanoethylmalonate prepared in Example 3 of the present invention. DETAILED DESCRIPTION

[0023] Embodiment 1:

[0024] The present embodiment provides a method for improving the conversion rate of diethyl 2-cyanoethylmalonate, and the steps are as follows:

[0025] (1) Take a 1000 ml dry four-necked flask equipped with a thermometer, a magnetic stirrer, a constant pressure burette, and a spherical condenser. Add 112.19 g of diethyl dicyanoethyl malonate (such as Figure 1 As shown, GC content 58.19%, peak time 15.940min) was dissolved in 282g of organic solvent ethyl acetate, and then 1.41g of alkaline catalyst sodium tert-butoxide was added and dissolved until no solid particles remained, and the temperature was raised to 60°C for reaction for 1h, 70.5g of diethyl malonate was put into a constant pressure burette, and diethyl malonate was added dropwise under stirring, the reaction was exothermic, and the temperature was controlled at 60°C in a water bath. After the dripping was completed for 1h, the reaction was kept at 60°C for 3h, and acid was added to neutralize to neutrality after the reaction was completed to obtain a 2-cyanoethyl diethyl malonate reaction solution;

[0026] (2) The above-mentioned diethyl 2-cyanoethylmalonate reaction solution was transferred into a 1000 ml vacuum distillation device for negative pressure distillation, and the positive fraction with a gas phase temperature of 110 to 115° C. was collected at a vacuum degree below 50 Pa to obtain 27.7 g of diethyl 2-cyanoethylmalonate (such as Figure 2 As shown, GC content 97.6%, peak time 13.237min), molar yield is 51.7%.

[0027] Embodiment 2:

[0028] The present embodiment provides a method for improving the conversion rate of diethyl 2-cyanoethylmalonate, and the steps are as follows:

[0029] (1) Take a 1000ml dry four-necked flask equipped with a thermometer, a magnetic stirrer, a constant pressure burette, and a spherical condenser. Dissolve 130.51g of diethyl bis-cyanoethyl malonate (GC content 58.19%) in 244.2g of organic solvent methanol, then add 2.44g of alkaline catalyst tetramethylammonium hydroxide pentahydrate and dissolve until no solid particles remain, heat to 50°C and react for 1h, take 81.4g of diethyl malonate and put it into a constant pressure burette, add diethyl malonate dropwise under stirring, the reaction is exothermic, the temperature is controlled at 50°C in a water bath, after the dripping is completed for 1h, keep the temperature at 50°C for 3h, add acid to neutralize to obtain a 2-cyanoethyl diethyl malonate reaction solution;

[0030] (2) The above-mentioned diethyl 2-cyanoethylmalonate reaction solution was transferred into a 1000 ml vacuum distillation device for negative pressure distillation, and the positive fraction with a gas phase temperature of 110 to 115° C. was collected at a vacuum degree below 50 Pa to obtain 32.3 g of diethyl 2-cyanoethylmalonate (such as Figure 3 As shown, GC content 96.3%, peak time 13.223min), molar yield is 51.5%.

[0031] Embodiment three:

[0032] The present embodiment provides a method for improving the conversion rate of diethyl 2-cyanoethylmalonate, and the steps are as follows:

[0033] (1) Take a 1000ml dry four-necked flask equipped with a thermometer, a magnetic stirrer, a constant pressure burette, and a spherical condenser. Dissolve 159.82g of diethyl bis-cyanoethyl malonate (GC content 58.19%) in 500g of organic solvent butyl acetate, then add 2.5g of alkaline catalyst trimethylethylammonium hydroxide and dissolve until no solid particles remain, heat to 55°C and react for 1h, take 81.4g of diethyl malonate and put it into a constant pressure burette, add diethyl malonate dropwise while stirring, the reaction is exothermic, control the temperature in a water bath at 55°C, after the dripping is completed for 1h, keep the temperature at 55°C for 3h, add acid to neutralize to neutrality after the reaction is completed, and obtain a 2-cyanoethyl diethyl malonate reaction solution;

[0034] (2) The above-mentioned diethyl 2-cyanoethylmalonate reaction solution was transferred into a 1000 ml vacuum distillation device for negative pressure distillation, and the positive fraction with a gas phase temperature of 110 to 115° C. was collected at a vacuum degree below 50 Pa to obtain 38.9 g of diethyl 2-cyanoethylmalonate (such as Figure 4 As shown, GC content 95.9%, peak time 13.229min), molar yield is 51.2%.

Claims

1. A method for improving the conversion rate of diethyl 2-cyanoethylmalonate, characterized in that The following steps are involved: (1) dissolving diethyl biscyanoethyl malonate in an organic solvent, then adding an alkaline catalyst, adding diethyl malonate at a temperature of 30 to 60° C., reacting for 2 to 5 hours, and obtaining a 2-cyanoethyl diethyl malonate reaction liquid; the mass ratio of diethyl biscyanoethyl malonate: organic solvent is 1:1 to 5, the mass ratio of diethyl biscyanoethyl malonate: alkaline catalyst is 1:0.01 to 0.03, and the mass ratio of diethyl biscyanoethyl malonate: diethyl malonate is 1 to 2:1; (2) subjecting the reaction solution of diethyl 2-cyanoethylmalonate to negative pressure distillation, and collecting a positive fraction with a gas phase temperature of 110-115° C. at a vacuum degree below 50 Pa, which is diethyl 2-cyanoethylmalonate.

2. The method according to claim 1, wherein the conversion of diethyl 2-cyanoethylmalonate is: The organic solvent is ethyl acetate, methanol and petroleum ether.

3. The method according to claim 1, wherein the conversion of diethyl 2-cyanoethylmalonate is: The alkaline catalyst is one of tetramethylammonium hydroxide, sodium tert-butoxide, and an organic metal lithium compound, or a combination thereof.

4. The method according to claim 1, wherein the conversion of diethyl 2-cyanoethylmalonate is: The GC detected content of the diethyl 2-cyanoethylmalonate is greater than 95%, and the molar conversion rate is greater than 50%.

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