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CN-121974819-A - Method for continuously synthesizing high-steric-hindrance tertiary amide

CN121974819ACN 121974819 ACN121974819 ACN 121974819ACN-121974819-A

Abstract

The invention discloses a method for continuously synthesizing high-steric-hindrance tertiary amide. The method takes N, N-di-long chain alkylamine and acid as raw materials, and carries out amidation reaction in a micro-channel reactor, wherein the micro-channel reactor comprises a premixing section and a reaction section which are sequentially connected, the two raw materials are salified in the premixing section, and then in the reaction section, a high steric hindrance tertiary amide target product is generated through reaction under the catalysis of a Lewis acid catalyst zinc salt. The temperature of the premixing section is 40-90 ℃, and the molar ratio of N, N-dialkylamine to the catalyst is 1:0.04-0.2. The method can be used for continuous synthesis of the tertiary amide with high steric hindrance, can obviously improve the reaction selectivity and yield of the target product, and simultaneously ensures high purity and lower cost.

Inventors

  • HONG XIN
  • LI TAO
  • YAN ZHIMING
  • CAI LIN
  • WANG YONG
  • LIU LEI
  • YING SIBIN
  • WANG WEIMING
  • HONG XU
  • Tan Bangjie
  • LI YUXIN
  • CHEN JIEYA

Assignees

  • 浙江新化化工股份有限公司
  • 浙江大学

Dates

Publication Date
20260505
Application Date
20260407

Claims (15)

  1. 1. A method for continuously synthesizing N, N-dialkyl acetamide is characterized by being carried out in a micro-channel reactor, wherein the micro-channel reactor comprises a premixing section and a reaction section which are sequentially connected, the method comprises the following steps of adding N, N-dialkyl amine and acid into the premixing section, adding a catalyst into the reaction section for amidation reaction to obtain the N, N-dialkyl acetamide, the temperature of the premixing section is 40-90 ℃, the catalyst is a Lewis acid catalyst and is zinc salt, the acid is acetic acid and/or acetic anhydride, and the molar ratio of the N, N-dialkyl amine to the catalyst is 1:0.04-0.3.
  2. 2. The method for continuously synthesizing N, N-dialkylacetamides according to claim 1, wherein the alkyl group is an alkyl group having 4 to 12 carbon atoms, and/or the catalyst is selected from one or more of zinc chloride, zinc acetate and zinc nitrate, and/or the catalyst is added at the beginning of the reaction section.
  3. 3. A process for the continuous synthesis of N, N-dialkylacetamides according to claim 1 or 2, characterized in that the catalyst is added in the form of an aqueous solution.
  4. 4. A process for the continuous synthesis of N, N-dialkylacetamides according to claim 3, characterized in that the catalyst is added in the form of a saturated aqueous solution.
  5. 5. The method for continuously synthesizing N, N-dialkylacetamide according to claim 1, wherein the molar ratio of the N, N-dialkylamine to the catalyst is 1:0.05 to 0.15.
  6. 6. The method for continuously synthesizing N, N-dialkylacetamides according to claim 1, wherein the alkyl group is an alkyl group having 4 to 8 carbon atoms.
  7. 7. The method for continuously synthesizing N, N-dialkylacetamide according to claim 6, wherein the N, N-dialkylamine is selected from the group consisting of di-N-butylamine, di-N-pentylamine, di-N-hexylamine, di-N-octylamine, di-iso-octylamine and di-Zhong Xinan.
  8. 8. The method for continuously synthesizing N, N-dialkylacetamide according to claim 1, wherein the method comprises the steps of 1) mixing and reacting the N, N-dialkylamine and acid in the premixing section to obtain corresponding ammonium salt, and 2) adding the catalyst in the reaction section, wherein the ammonium salt is subjected to amidation reaction in the presence of the catalyst to obtain the N, N-dialkylacetamide.
  9. 9. The method for continuously synthesizing N, N-dialkylacetamide according to claim 1, wherein the molar ratio of the N, N-dialkylamine, the acid and the catalyst is 1:0.55 to 1.2:0.04 to 0.2.
  10. 10. The method for continuously synthesizing N, N-dialkylacetamide of claim 9, wherein the molar ratio of N, N-dialkylamine to acetic acid is 1:1.1 to 1.2 when the acid is acetic acid, or 1:0.55 to 0.6 when the acid is acetic anhydride.
  11. 11. The method for continuously synthesizing N, N-dialkylacetamides according to claim 1, wherein the temperature of the reaction section is 60-160 ℃ and/or the inner diameter of the premixing section is larger than the inner diameter of the reaction section.
  12. 12. The method for continuously synthesizing N, N-dialkylacetamides according to claim 1, wherein the residence time of the reaction solution in the premixing section is 1 to 5min, and/or the inner diameter of the premixing section is 1.5 to 2mm, and/or the liquid holding capacity of the premixing section is 15 to 25mL.
  13. 13. The method for continuously synthesizing N, N-dialkylacetamides according to claim 1, wherein the residence time of the reaction solution in the reaction section is 2 to 10min, and/or the inner diameter of the reaction section is 0.5 to 1mm, and/or the liquid holding amount of the reaction section is 30 to 50mL.
  14. 14. The method for continuously synthesizing N, N-dialkylacetamides according to claim 1, wherein the pressure in the microchannel reactor is 0.3 to 1.5MPa.
  15. 15. The method for continuously synthesizing N, N-dialkylacetamide according to claim 1, further comprising the steps of separating water from oil in the reaction system after the completion of the reaction to obtain an aqueous phase containing the catalyst and an oil phase containing the N, N-dialkylacetamide, and distilling the oil phase to obtain the N, N-dialkylacetamide.

Description

Method for continuously synthesizing high-steric-hindrance tertiary amide Technical Field The invention relates to the technical field of organic synthesis, in particular to a method for continuously synthesizing high-steric-hindrance tertiary amide. Background The amide N atom of the tertiary amide with high steric hindrance has a longer chain segment with two substituents (for example, the carbon number is 4-12), and the reaction selectivity and the reaction yield are lower due to the higher steric hindrance of the long chain segment during synthesis. The high-steric-hindrance tertiary amide compound is an important organic synthesis intermediate and an industrial extractant, wherein di-n-butyl acetamide is widely applied to the fields of organic synthesis and extraction separation, di-sec-octyl acetamide has excellent extraction performance on phenol and the like, is indispensable in phenol-containing wastewater treatment, and exhibits unique application value in fine chemical engineering and salt lake resource extraction. Conventional tertiary amide preparation methods are generally used to prepare tertiary amides having a shorter substituent on the N atom, for example, the prior art relating to N, N-dimethylacetamide preparation methods is relatively high. In the preparation method, batch synthesis is carried out by adopting a kettle-type reactor, secondary amine and an acylating reagent (such as acyl chloride, anhydride, carboxylic acid and the like) are taken as raw materials, and an acylating reaction is carried out under an alkaline condition to obtain the corresponding short-chain substituted tertiary amide. However, during batch synthesis, the mass and heat transfer efficiency of the reactor is low, the temperature and concentration distribution of each region in the reaction system are uneven, side reactions are easy to occur, the reaction selectivity and the yield of target products are low, industrial continuous production cannot be realized, and the economic efficiency is low. In addition, in the above reaction, dimethylamine, which is one of the reaction raw materials, has a higher reactivity than a di-substituted amine having a longer chain, such as di-n-butylamine, di-n-octylamine, etc., and therefore, when a highly sterically hindered amine having a significantly reduced reactivity and a longer substituted chain is used as the reaction raw material to synthesize tertiary amide, the reactivity is lower and the yield of the target product is lower. Liu Jianwu et al disclose in the paper "catalytic reaction distillation method for continuously preparing N, N-dimethylacetamide" that N, N-dimethylacetamide is synthesized by a distillation method, self-made Lewis acid (with undefined composition) is used as a catalyst, acetic acid and dimethylamine are used as raw materials, and N, N-dimethylacetamide is continuously prepared by a distillation method, wherein the method can improve the separation efficiency, but requires special distillation equipment, has complex flow and high energy consumption, and in addition, the method has the advantages of high target product yield to be improved and long reaction residence time. And, the process produces N-short chain substituted amides, not highly sterically hindered amides. Patent CN110156621a discloses a method for liquid-liquid homogeneous synthesis of N, N-dimethylacetamide in a microchannel reactor, which uses sodium methoxide as a catalyst and anhydrous dimethylamine and methyl acetate as reaction raw materials, and synthesizes the target product N, N-dimethylacetamide through nucleophilic substitution type amidation reaction. Although the method can realize continuous production, the yield of the target product needs to be improved, one of the raw materials of the reaction is methyl acetate, the reaction product is amide and organic methanol, and the use and separation of two phases of an aqueous phase and an organic phase are not involved, but when the traditional acid or anhydride and amine are adopted for reaction to synthesize the amide, the reaction product contains water, sodium methoxide cannot be used as a catalyst in the reaction system, and the sodium methoxide and the water react to decompose to generate methanol and sodium hydroxide, so that the catalyst is deactivated. And, the process produces N-short chain substituted amides, not highly sterically hindered amides. Disclosure of Invention In view of the shortcomings and drawbacks of the prior art, the present invention provides an improved method for synthesizing tertiary amides. The synthesis method can be used for continuous synthesis of the tertiary amide with high steric hindrance, can obviously improve the reaction selectivity and yield of the target product, and simultaneously ensures high purity and lower cost. In order to achieve the above purpose, the invention adopts the following technical scheme: A method for continuously synthesizing N, N-dialkyl acetamide is carried o