阅读说明：本技术 微波辅助法合成n,n’-二环己基碳二亚胺的方法 (Method for synthesizing N, N' -dicyclohexylcarbodiimide by microwave-assisted method ) 是由 王辉 王静 孙铎 于 2020-12-25 设计创作，主要内容包括：本发明涉及有机合成技术领域,具体涉及一种微波辅助法合成N,N’-二环己基碳二亚胺的方法。在微波辐射下,将N,N’-二环己基脲溶于溶剂中,加入氧化剂和负载在分子筛上的催化剂,保温回流；再加入相转移催化剂,调节pH值,发生碱解反应；过滤,分液,蒸出溶剂,减压蒸馏,得到N,N’-二环己基碳二亚胺。本发明负载在分子筛上的催化剂比表面积大,催化效率高；采用微波辅助法,并加入相转移催化剂,克服了传统工艺两相反应难、反应不彻底的问题,大大提高了反应转化率,缩短了反应时间,产品具有纯度和收率高的特点。(The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing N, N' -dicyclohexylcarbodiimide by a microwave-assisted method. Under microwave radiation, dissolving N, N' -dicyclohexylurea in a solvent, adding an oxidant and a catalyst loaded on a molecular sieve, and carrying out heat preservation and reflux; adding a phase transfer catalyst, adjusting the pH value, and carrying out alkaline hydrolysis reaction; filtering, separating liquid, evaporating the solvent, and distilling under reduced pressure to obtain the N, N' -dicyclohexylcarbodiimide. The catalyst loaded on the molecular sieve has large specific surface area and high catalytic efficiency; by adopting a microwave-assisted method and adding a phase transfer catalyst, the problems of difficult two-phase reaction and incomplete reaction in the traditional process are solved, the reaction conversion rate is greatly improved, the reaction time is shortened, and the product has the characteristics of high purity and high yield.)

1. A method for synthesizing N, N' -dicyclohexylcarbodiimide by a microwave-assisted method is characterized by comprising the following steps: under microwave radiation, dissolving N, N' -dicyclohexylurea in a solvent, adding an oxidant and a catalyst loaded on a molecular sieve, and carrying out heat preservation and reflux; adding a phase transfer catalyst, adjusting the pH value, and carrying out alkaline hydrolysis reaction; the solvent was distilled off, and the N, N' -dicyclohexylcarbodiimide was obtained by distillation under reduced pressure.

2. The microwave-assisted method for synthesizing N, N' -dicyclohexylcarbodiimide according to claim 1, wherein: the solvent is one or more of ethylene glycol monobutyl ether, amyl acetate, toluene cyclohexanone, ethylene glycol monomethyl ether, ethyl acetoacetate or N, N-dimethylformamide; the mass ratio of the N, N' -dicyclohexylurea to the solvent is 1: 3-6.

3. The microwave-assisted method for synthesizing N, N' -dicyclohexylcarbodiimide according to claim 1, wherein: the oxidant is thionyl chloride, trichloroacetyl chloride or benzoyl chloride; the mass ratio of the N, N' -dicyclohexylurea to the oxidant is 1: 1.1-2.4.

4. The microwave-assisted method for synthesizing N, N' -dicyclohexylcarbodiimide according to claim 1, wherein: the catalyst is anhydrous ferric trichloride, anhydrous aluminum trichloride or anhydrous stannic chloride; the dosage of the catalyst is 1-3% of the mass of the N, N' -dicyclohexylurea.

5. The microwave-assisted method for synthesizing N, N' -dicyclohexylcarbodiimide according to claim 1, wherein: the microwave radiation power is 100-300W; the heat preservation reflux temperature is 30-50 ℃, and the heat preservation reflux time is 1-4 h.

6. The microwave-assisted method for synthesizing N, N' -dicyclohexylcarbodiimide according to claim 1, wherein: the alkaline hydrolysis reaction time is 20-60 min; the temperature of alkaline hydrolysis reaction is 0-20 ℃; the stirring speed in the alkaline hydrolysis reaction is 100-300 r/min.

7. The microwave-assisted method for synthesizing N, N' -dicyclohexylcarbodiimide according to claim 1, wherein: the phase transfer catalyst is trioctylmethylammonium chloride, dodecyltrimethylammonium chloride or tetradecyltrimethylammonium chloride; the mass ratio of the phase transfer catalyst to the N, N' -dicyclohexylurea is 1: 100-120.

8. The microwave-assisted method for synthesizing N, N' -dicyclohexylcarbodiimide according to claim 1, wherein: adjusting pH to 8-10 with N, N-dimethylethanolamine, tri-N-butylamine or triethylamine.

9. The microwave-assisted method for synthesizing N, N' -dicyclohexylcarbodiimide according to any one of claims 1 to 8, wherein: under the microwave radiation, dissolving N, N' -dicyclohexylurea in a solvent, cooling, adding an oxidant and a catalyst loaded on a molecular sieve, heating, preserving heat, refluxing, and cooling; adding phase transfer catalyst, regulating pH value, making alkaline hydrolysis reaction, filtering and separating liquid; the solvent is distilled off, and then the N, N' -dicyclohexylcarbodiimide is obtained by reduced pressure distillation.

10. The microwave-assisted method for synthesizing N, N' -dicyclohexylcarbodiimide according to claim 9, wherein: dissolving N, N' -dicyclohexylurea in a solvent, and cooling to 10-12 ℃; after heat preservation and reflux, cooling to 5-6 ℃; the pressure of the reduced pressure distillation is 0.6-1.2 KPa.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing N, N' -dicyclohexylcarbodiimide by a microwave-assisted method.

Background

N, N' -Dicyclohexylcarbodiimide (DCC) is a colorless transparent solid at normal temperature, is liquid at the temperature of more than 35 ℃, and is commonly used as a low-temperature dehydrating agent for synthesizing compounds such as aldehyde, anhydride, ketone, amino acid, ester and the like in laboratories. And the method is also one of the most important reagents for acylation reaction of amine (or alcohol) and carboxylic acid in industry, plays a unique role in the reaction of synthesizing important and scarce-source macrocyclic lactam and macrolide, and is mainly used for producing products such as glutathione, amikacin and the like in China.

In the prior art, the chemical synthesis method of N, N' -dicyclohexylcarbodiimide mainly relates to the following methods: the thiourea method, the isocyanate method, and the phosgene method.

The thiourea method has two synthetic methods, the first method is to use sodium hypochlorite as a reaction reagent, Chinese patent CN101096349A discloses a production process of N, N '-dicyclohexyl carbodiimide, dicyclohexyl thiourea and sodium sulfide are generated by the reaction of cyclohexylamine and carbon disulfide, dicyclohexyl thiourea is subjected to secondary oxidation by sodium hypochlorite to remove hydrogen sulfide to generate N, N' -dicyclohexyl carbodiimide, the method is characterized in that when dicyclohexyl thiourea is oxidized by sodium hypochlorite, a catalyst is added to react, triethyl benzyl ammonium chloride (TEBA) or polyethylene glycol is used as the catalyst, and sodium sulfide generated by the first step of reaction is added into an organic phase separated after the secondary oxidation to react with sulfur in the organic phase to remove sulfur in the organic phase. The second method adopts mercury oxide as a reaction reagent, but the method adopts mercury oxide as a highly toxic substance, so that environmental pollution is easily caused, and industrial production is not facilitated.

Isocyanate method: chinese patent CN101524650A discloses a preparation method and application of an organophosphorus solid-phase catalyst for synthesizing dicyclohexylcarbodiimide. The patent adopts an organophosphorus solid polymer catalyst for catalytic condensation of cyclohexyl isocyanate to obtain a dicyclohexylcarbodiimide product, and has the advantages of higher reaction temperature, difficult preparation of the catalyst, easy generation of waste gas and environmental pollution.

A phosgene method: U.S. Pat. No. 4, 5648537A discloses a process for preparing dicyclohexylcarbodiimide by reacting dicyclohexylurea with gaseous phosgene in methyl tert-butyl ether. Although the yield of the process is high, the process adopts the highly toxic phosgene as the raw material, which seriously influences the production safety and the health of operators, and the use of gaseous materials has high requirements on equipment, large production investment and difficult storage, which is not favorable for industrial production.

Chinese patent CN104262200A discloses a production method for preparing N, N ' -dicyclohexylcarbodiimide by recycling waste water, wherein N, N ' -dicyclohexylurea generated after N, N ' -dicyclohexylcarbodiimide is used is firstly washed by water to remove impurities, then reacts with an oxidant in an organic solvent, the reaction liquid is dripped into an alkaline water solution for neutralization reaction, a neutralization reaction product is filtered and then stands for layering, and the DCC product is obtained by distilling and separating an organic layer. The patent has low reaction yield and more byproducts, and is not suitable for large-scale production.

Disclosure of Invention

The invention aims to provide a method for synthesizing N, N' -dicyclohexylcarbodiimide by a microwave-assisted method, wherein a catalyst loaded on a molecular sieve has large specific surface area and high catalytic efficiency; by adopting a microwave-assisted method and adding a phase transfer catalyst, the problems of difficult two-phase reaction and incomplete reaction in the traditional process are solved, the reaction conversion rate is greatly improved, and the product has the characteristics of high purity and high yield.

The technical scheme adopted by the invention for solving the technical problems is as follows:

the microwave-assisted method for synthesizing the N, N' -dicyclohexylcarbodiimide comprises the following steps: under microwave radiation, dissolving N, N' -dicyclohexylurea in a solvent, adding an oxidant and a catalyst loaded on a molecular sieve, and carrying out heat preservation and reflux; adding a phase transfer catalyst, adjusting the pH value, and carrying out alkaline hydrolysis reaction; filtering, separating liquid, evaporating the solvent, and distilling under reduced pressure to obtain the N, N' -dicyclohexylcarbodiimide.

Wherein:

the solvent is one or more of ethylene glycol monobutyl ether, amyl acetate, toluene cyclohexanone, ethylene glycol monomethyl ether, ethyl acetoacetate or N, N-dimethylformamide, and preferably the N, N-dimethylformamide; the mass ratio of the N, N' -dicyclohexylurea to the solvent is 1: 3-6.

The oxidant is thionyl chloride, trichloroacetyl chloride or benzoyl chloride, preferably trichloroacetyl chloride; the mass ratio of the N, N' -dicyclohexylurea to the oxidant is 1:1.1-2.4, preferably 1: 1.8.

The catalyst is anhydrous ferric trichloride, anhydrous aluminum trichloride or anhydrous stannic chloride, and anhydrous aluminum trichloride is preferred; the amount of catalyst used is 1 to 3%, preferably 1.8% by mass of N, N' -dicyclohexylurea.

The temperature of the heat preservation reflux is 30-50 ℃, and preferably 40 ℃; the heat preservation reflux time is 1-4h, preferably 2.5 h.

The microwave radiation power is 100-300W.

The alkaline hydrolysis reaction time is 20-60 min; the temperature of alkaline hydrolysis reaction is 0-20 ℃; the stirring speed in the alkaline hydrolysis reaction is 100-300 r/min.

The phase transfer catalyst is trioctylmethylammonium chloride, dodecyltrimethylammonium chloride or tetradecyltrimethylammonium chloride, preferably dodecyltrimethylammonium chloride; the mass ratio of the phase transfer catalyst to the N, N' -dicyclohexylurea is 1: 100-120.

Adjusting pH to 8-10 with N, N-dimethylethanolamine, tri-N-butylamine or triethylamine, preferably adjusting pH with triethylamine.

Preferably, the microwave-assisted method for synthesizing the N, N' -dicyclohexylcarbodiimide comprises the following steps: under the microwave radiation, dissolving N, N' -dicyclohexylurea in a solvent, cooling, adding an oxidant and a catalyst loaded on a molecular sieve, heating, preserving heat, refluxing, and cooling; adding phase transfer catalyst, regulating pH value, making alkaline hydrolysis reaction, filtering and separating liquid; the solvent is distilled off, and then the N, N' -dicyclohexylcarbodiimide is obtained by reduced pressure distillation.

Wherein:

dissolving N, N' -dicyclohexylurea in a solvent, and cooling to 10-12 ℃; after heat preservation and reflux, the temperature is reduced to 5 to 6 ℃.

The pressure of the reduced pressure distillation is 0.6-1.2 KPa.

The reaction process of the invention is as follows:

the invention has the following beneficial effects:

the catalyst loaded on the molecular sieve has large specific surface area and high catalytic efficiency, can be partially recycled, saves the cost, and fundamentally eliminates the problems of large smell, strong toxicity and heavy pollution in the traditional process; the invention has the characteristics of simple operation process and high safety factor.

Because the reaction of the invention is heterogeneous reaction, the reaction has the characteristics of low yield, slow reaction and more impurities, but the invention adds a phase transfer catalyst into the reaction system, and after adding alkali to adjust the pH value to 8-10, the phase transfer catalyst can be combined with hydroxide ions in a water phase, and the hydroxide ions are quickly transferred into an organic phase to participate in alkaline hydrolysis reaction, so that the reaction is quickly carried out; the invention has low alkaline hydrolysis reaction temperature, thorough reaction and less by-products, and greatly improves the purity and the yield.

The invention adopts a microwave-assisted method, under the microwave radiation, N' -dicyclohexylurea is dissolved in a solvent, an oxidant and a catalyst loaded on a molecular sieve are added, and the heat preservation and reflux are carried out; adding a phase transfer catalyst, adding alkali to adjust the pH value, and carrying out alkaline hydrolysis reaction; filtering and separating liquid; finally, evaporating the solvent, and carrying out reduced pressure distillation to obtain the N, N' -dicyclohexylcarbodiimide. The microwave radiation can uniformly heat a reaction system, promotes the reaction, overcomes the problems of difficult two-phase reaction and incomplete reaction in the traditional process, greatly improves the reaction conversion rate, shortens the reaction time, and has the characteristics of high purity and yield of the product, the purity of the product reaches over 99.75 percent, the yield of the product reaches over 90 percent, and the capacity of the product is greatly increased, thereby being very suitable for industrial production.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of N, N' -dicyclohexylcarbodiimide in example 1 of the present invention.

Detailed Description

The present invention is further described below with reference to examples.

Example 1

Adding 100g N, N' -Dicyclohexylurea (DCU) into 400g of ethylene glycol monobutyl ether at room temperature by using a microwave reactor under the condition that the microwave radiation power is 100W, cooling to 10-12 ℃, adding 180g of trichloroacetyl chloride, and 1.5g of anhydrous aluminum trichloride loaded on a molecular sieve, heating to 30 ℃, preserving heat, refluxing for 2h, and cooling to 5 ℃; adding 1.0g of phase transfer catalyst dodecyl trimethyl ammonium chloride, then dropwise adding N, N-dimethylethanolamine to adjust the pH value to 8-9, carrying out alkaline hydrolysis reaction, controlling the temperature of the alkaline hydrolysis reaction to be 5 ℃, the time of the alkaline hydrolysis reaction to be 20min, and the stirring speed of the alkaline hydrolysis reaction to be 100 r/min; filtering and separating the reaction liquid, distilling off the solvent, carrying out reduced pressure distillation at 0.7-0.9KPa, and collecting the fraction at the temperature of 135-145 ℃ to obtain 83.01g of N, N' -dicyclohexylcarbodiimide, wherein the yield is 90.15% and the purity is 99.88%.

The nuclear magnetic hydrogen spectrum of the N, N' -dicyclohexylcarbodiimide is shown in figure 1. The hydrogen on the N, N' -dicyclohexylcarbodiimide was numbered as follows. As can be seen from the data in FIG. 1, the chemical shifts of the two hydrogens in the 1 and 1 'positions are 3.323-3.385ppm, the chemical shifts of the eight hydrogens in the 2 and 2' positions are 1.515-1.838ppm, the chemical shifts of the eight hydrogens in the 3 and 3 'positions are 1.284-1.461ppm, and the chemical shifts of the four hydrogens in the 4 and 4' positions are 1.188-1.292 ppm.

Example 2

Adding 100g N, N' -Dicyclohexylurea (DCU) into 400g of toluene cyclohexanone at room temperature by using a microwave reactor under the microwave radiation power of 150W, cooling to 10-12 ℃, adding 180g of thionyl chloride, and 1.8g of anhydrous ferric trichloride loaded on a molecular sieve, heating to 40 ℃, preserving heat, refluxing for 2h, and cooling to 5 ℃; adding 0.84g of phase transfer catalyst, namely trioctylmethylammonium chloride, dropwise adding tri-n-butylamine to adjust the pH value to 9-10, carrying out alkaline hydrolysis reaction, controlling the temperature of the alkaline hydrolysis reaction to be 10 ℃, the time of the alkaline hydrolysis reaction to be 30min, and stirring the alkaline hydrolysis reaction at 200 r/min; filtering and separating the reaction liquid, distilling off the solvent, carrying out reduced pressure distillation at 0.9-1.1KPa, and collecting the fraction at 145 ℃ of 135-materials to obtain 83.04g of N, N' -dicyclohexylcarbodiimide, wherein the yield is 90.08% and the purity is 99.77%.

Example 3

Adding 100g N, N' -Dicyclohexylurea (DCU) into 400g of ethyl acetoacetate at room temperature by using a microwave reactor under the microwave radiation power of 180W, cooling to 10-12 ℃, adding 180g of benzoyl chloride, and 2.1g of anhydrous stannic chloride loaded on a molecular sieve, heating to 50 ℃, preserving heat, refluxing for 2h, and cooling to 5 ℃; adding 0.9g of phase transfer catalyst tetradecyltrimethyl ammonium chloride, then dropwise adding triethylamine to adjust the pH value to 9-10, carrying out alkaline hydrolysis reaction, controlling the temperature of the alkaline hydrolysis reaction to be 20 ℃, the time of the alkaline hydrolysis reaction to be 40min, and the stirring speed of the alkaline hydrolysis reaction to be 300 r/min; filtering and separating the reaction liquid, distilling off the solvent, carrying out reduced pressure distillation at 0.9-1.0KPa, and collecting the fraction at 145 ℃ of 135-materials to obtain 83.22g of N, N' -dicyclohexylcarbodiimide, wherein the yield is 90.31% and the purity is 99.81%.

Example 4

Adding 100g N, N' -Dicyclohexylurea (DCU) into 400g of amyl acetate at room temperature by using a microwave reactor under the microwave radiation power of 100W, cooling to 10-12 ℃, adding 240g of trichloroacetyl chloride, and 1.8g of anhydrous ferric trichloride loaded on a molecular sieve, heating to 30 ℃, preserving heat, refluxing for 2 hours, and cooling to 5 ℃; adding 0.95g of phase transfer catalyst tetradecyltrimethyl ammonium chloride, then dropwise adding N, N-dimethylethanolamine to adjust the pH value to 8.5-10, carrying out alkaline hydrolysis reaction, controlling the temperature of the alkaline hydrolysis reaction to be 5 ℃, the time of the alkaline hydrolysis reaction to be 40min, and the stirring speed of the alkaline hydrolysis reaction to be 100 r/min; filtering and separating the reaction liquid, distilling off the solvent under reduced pressure at 1.0-1.2KPa, collecting the fraction at 145 ℃ of 135 materials to obtain 83.13g of N, N' -dicyclohexylcarbodiimide, wherein the yield is 90.16%, and the purity is 99.75%.

Example 5

Adding 100g N, N' -Dicyclohexylurea (DCU) into 400g of ethylene glycol monomethyl ether at room temperature by using a microwave reactor under the microwave radiation power of 150W, cooling to 10-12 ℃, adding 240g of thionyl chloride, and 1.5g of anhydrous aluminum trichloride loaded on a molecular sieve, heating to 40 ℃, preserving heat, refluxing for 2h, and cooling to 5 ℃; adding 1.0g of phase transfer catalyst, namely trioctylmethylammonium chloride, dropwise adding tri-n-butylamine to adjust the pH value to 9-10, carrying out alkaline hydrolysis reaction, controlling the temperature of the alkaline hydrolysis reaction to be 10 ℃, the time of the alkaline hydrolysis reaction to be 30min, and stirring the alkaline hydrolysis reaction at 200 r/min; filtering and separating the reaction liquid, distilling off the solvent, carrying out reduced pressure distillation at 0.9-1.1KPa, and collecting the fraction at the temperature of 135-145 ℃ to obtain 83.24g of N, N' -dicyclohexylcarbodiimide, wherein the yield is 90.32%, and the purity is 99.79%.

Example 6

Adding 100g N, N' -Dicyclohexylurea (DCU) into 400g of N, N-dimethylformamide at room temperature by using a microwave reactor under the microwave radiation power of 180W, cooling to 10-12 ℃, adding 240g of benzoyl chloride and 2.1g of anhydrous stannic chloride loaded on a molecular sieve, heating to 50 ℃, preserving heat, refluxing for 2.5h, and cooling to 5 ℃; adding 0.9g of phase transfer catalyst dodecyl trimethyl ammonium chloride, then dropwise adding triethylamine to adjust the pH value to 8-10, carrying out alkaline hydrolysis reaction, controlling the temperature of the alkaline hydrolysis reaction to be 20 ℃, the time of the alkaline hydrolysis reaction to be 20min, and the stirring speed of the alkaline hydrolysis reaction to be 300 r/min; filtering and separating the reaction liquid, distilling off the solvent, carrying out reduced pressure distillation at 0.9-1.1KPa, and collecting the fraction at the temperature of 135-145 ℃ to obtain 84.17g of N, N' -dicyclohexylcarbodiimide, wherein the yield is 91.39% and the purity is 99.86%.

Comparative example 1

The same procedure as in example 1 was repeated except that anhydrous aluminum trichloride supported on a molecular sieve was not added; 79.49g of N, N' -dicyclohexylcarbodiimide was obtained in 85.89% yield and 99.38% purity.

Comparative example 2

The same procedure as in example 1 was repeated except that dodecyltrimethylammonium chloride was not added as a phase transfer catalyst; 78.80g of N, N' -dicyclohexylcarbodiimide were obtained in 84.98% yield and 99.19% purity.

Comparative example 3

The reaction is carried out without adopting microwave radiation, and the rest steps are the same as the example 1; 79.01g of N, N' -dicyclohexylcarbodiimide were obtained in 85.12% yield and 99.08% purity.