On-line phenylethanol beta-amino-alcohol derivative synthesis method on basis of enzymatic aminolysis by flow chemistry

A phenethyl alcohol and amino alcohol technology, which is applied in biochemical equipment and methods, enzymology/microbiology devices, enzyme production/bioreactors, etc., can solve the problems of long reaction time, unsatisfactory conversion rate, etc. Reaction cost, high conversion and selectivity, effect of shortened reaction time

Active Publication Date: 2019-05-03
ZHEJIANG UNIV OF TECH
View PDF9 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Candida rugosalipase from Candida rugosa lipase CRL (Candida rugosalipase from Candida rugosa) can effectively catalyze the reaction, but this method requires a long reaction time (8h ~ 12h), and the conversion rate for specific substrate reactions is not particularly ideal

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • On-line phenylethanol beta-amino-alcohol derivative synthesis method on basis of enzymatic aminolysis by flow chemistry
  • On-line phenylethanol beta-amino-alcohol derivative synthesis method on basis of enzymatic aminolysis by flow chemistry
  • On-line phenylethanol beta-amino-alcohol derivative synthesis method on basis of enzymatic aminolysis by flow chemistry

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Synthesis of 2-(2-methylanilino)phenethyl alcohol

[0032]

[0033] Device reference figure 1 : Dissolve o-toluidine (2.0 mmol) in 10 mL of MeOH, and dissolve styrene oxide (2.0 mmol) in 10 mL of MeOH, and then put them into 10 mL syringes for use. 0.87g of lipase LipozymeRM IM was evenly filled in the reaction channel. Driven by the PHD2000 syringe pump, the two reaction solutions were injected at 15.6μL·min respectively. -1 The flow rate of 200 μL enters the reaction channel through the “Y” joint to carry out the reaction. The temperature of the reactor is controlled at 35°C by a water bath thermostat, and the reaction solution flows continuously in the reaction channel for 20min. The reaction results are tracked and detected by thin-layer chromatography (TLC).

[0034] The reaction solution was collected online through a product collector, the solvent was distilled off under reduced pressure, and the column was wet-packed with 200-300 mesh silica gel. ...

Embodiment 2-5

[0038] The solvent in the microfluidic microchannel reactor was changed, and the temperature was controlled to 35°C. Others were the same as those in Example 1. The results are shown in Table 1:

[0039] Table 1: Effect of solvent on reaction

[0040]

[0041]

[0042] The results in Table 1 show that when the ratio of the amount of o-toluidine and styrene oxide substrate substances is 1:1, the flow rate is 15.6 μL·min -1 , the reaction time is 20min, and the reaction temperature is 35°C. The conversion rate and selectivity of the reaction are the best when the reactor uses MeOH as the organic solvent. Therefore, the optimal solvent in the microfluidic microchannel reactor in the present invention is methanol.

Embodiment 6-9

[0044] Taking the consumption of o-toluidine as a benchmark, change the ratio of the amount of the substrate material of o-toluidine and styrene oxide in the microfluidic microchannel reactor, and control the temperature to 35 ° C. Others are the same as in Example 1, and the results are shown in Table 2. Show:

[0045] Table 2: Effect of the ratio of the amount of o-toluidine and styrene oxide substrate species on the reaction

[0046] Example

[0047] The results in Table 2 show that when the flow rate is 15.6 μL·min -1 , the reaction time is 20min, the reaction temperature is 35℃, the reactor uses MeOH as the organic solvent, with the increase of the reactant styrene oxide, the conversion rate of the reaction also increases, when the substrate is o-toluidine and benzene oxide When ethylene is 1:1, the conversion rate and selectivity of the reaction are optimal, so the ratio of the optimal amount of substrate substances in the microfluidic microchannel reactor in ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses an on-line phenylethanol beta-amino-alcohol derivative synthesis method on basis of enzymatic aminolysis by flow chemistry. The on-line phenylethanol beta-amino-alcohol derivative synthesis method on basis of enzymatic aminolysis by flow chemistry comprises the following steps: taking methanol as a reaction solvent, aniline compounds and styrene oxide as raw materials, wherein the molar ratio of the aniline compounds to the styrene oxide is 1 to (0.6-1.4), and lipase Lipozyme RM IM as a catalyst; putting the raw materials and the reaction solvent into a syringe; uniformly filling a reaction channel of a microfluidic channel reactor with the lipase Lipozyme RM IM and continuously introducing the raw materials and the reaction solvent into the reaction channel under push force of an injection pump so as to be subjected to ring-opening reaction, wherein the inner diameter of the reaction channel of the microfluidic channel reactor is 0.8-2.4 millimeters and the length of the reaction channel is 0.5-1.0m; carrying out ring-opening reaction at 30-50 DEG C for 10-30 minutes, and collecting reacted solution on line by using a product collector; and then, performingconventional post-processing on the reacted solution so as to obtain phenylethanol beta-amino-alcohol derivatives. The on-line nitroimidazole derivative synthesis method disclosed by the invention has the advantages of being short in reaction time, excellent in selectivity and high in yield.

Description

(1) Technical field [0001] The invention relates to a method for online synthesis of phenethyl alcohol β-amino alcohol derivatives based on flow chemical enzymatic aminolysis reaction. (2) Background technology [0002] β-Amino alcohol is a widely used organic synthesis intermediate, which is widely used in the synthesis of biologically active natural substances, unnatural amino acids, medicinal chemistry, chiral auxiliaries and ligands, etc., in medicinal chemistry and biology Occupying a very important position, many clinically widely used drugs, such as antihypertensive drugs, antidiabetic drugs, antiasthma drugs and antimalarial drugs, contain β-amino alcohol structural units. More than 75% of drugs or drug intermediates in organic molecules contain amino functional groups. Chiral aminoalcohols with both amino and hydroxyl functional groups have shown good chiral induction in the field of asymmetric catalysis. N atoms and O atoms with good coordination ability in chira...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C12P13/00C12M1/40C12M1/00
Inventor 杜理华陈平锋龙瑞杰罗锡平周娜妮薛苗陶佳丽郑泽灿陈昱晗
Owner ZHEJIANG UNIV OF TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap