In this study,a continuous-flow procedure containing four steps has been developed to synthesize Pigment Red 53 and modify its crystal structure.This process avoided the problems of conveying highly insoluble reaction...In this study,a continuous-flow procedure containing four steps has been developed to synthesize Pigment Red 53 and modify its crystal structure.This process avoided the problems of conveying highly insoluble reaction intermediates by removing intermediate operating steps.After optimization,the overall yield of Pigment Red 53:1 reached 97.1%in the total residence time of 80 s by this diazotizationcoupling-laking-crystal transition process.From batch to continuous flow,the purity of products increased from 97.1%to 98.2%and the median diameter of pigment particles decreased from 14μm to 1.9μm.This process achieved a similar crystal transition effect in 18 s as in batch,producingα,δandνcrystals of Pigment Red 53:2 as expected.In conclusion,this continuous-flow procedure displays advantages in both synthesis and crystal transition,indicating another potential use for industrial application.展开更多
Erlotinib is an orally administered, highly effective, specific epidermal growth factor receptor tyrosine kinase inhibitor, used to treat non-small cell lung cancer and pancreatic cancer. The traditional synthetic met...Erlotinib is an orally administered, highly effective, specific epidermal growth factor receptor tyrosine kinase inhibitor, used to treat non-small cell lung cancer and pancreatic cancer. The traditional synthetic methods for Erlotinib exhibit long reaction time and safety concern. Herein, we describe a novel five-step route for the synthesis of Erlotinib in flow. These five steps comprise etherification, nitration, reduction,addition and cyclization reactions. All steps were optimized and converted to continuous flow process,which drastically reduces the reaction time and considerably improves the process safety as well as the total yield. Enabled by five continuous flow units, Erlotinib is efficiently afforded with an E-factor of 38,an overall yield of 83%, and a total residence time of 25.1 min. Majority steps in this process have been optimized for quantitative conversion, which offers the possibility of telescoping the entire process.展开更多
Tonalid,an important fragrance ingredient with widespread applicatio n,was synthesized via two FriedelCrafts reactions,which were catalyzed by AlCl_(3).The traditional tonalid production was conducted in batch stirrin...Tonalid,an important fragrance ingredient with widespread applicatio n,was synthesized via two FriedelCrafts reactions,which were catalyzed by AlCl_(3).The traditional tonalid production was conducted in batch stirring tank reactors,suffering from low production capacity and the safety hazard of temperature runaway.To solve these problems,the continuous-flow technologies were developed for the highefficiency and intrinsically safe synthesis of tonalid in microreactors.Catalyst AlCl_(3)was neatly homogenized in proper solvents by forming complex with reactant,which was a necessary step for the continuous synthesis in microreactors.Several reaction conditions,including reactant molar ratio,catalyst concentration,temperature,and microchannel hydrodynamic diameter,were investigated for the two Friedel-Crafts reactions in micro reactors.At optimized conditions,the yields of the two Friedel-Crafts reactions were 44.15%and 97.55%,respectively.In comparison with the batch reactors,the reaction times of these two reactions could both be reduced by nearly two thirds in microreactors at the similar yield.展开更多
基金financial support from Shanghai Municipal Science and Technology Commission (No.21520761100)the Open Project of State Key Laboratory of Chemical Engineering (No. SKL-Ch E-21C07)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Program of Leading Talents (2013)
文摘In this study,a continuous-flow procedure containing four steps has been developed to synthesize Pigment Red 53 and modify its crystal structure.This process avoided the problems of conveying highly insoluble reaction intermediates by removing intermediate operating steps.After optimization,the overall yield of Pigment Red 53:1 reached 97.1%in the total residence time of 80 s by this diazotizationcoupling-laking-crystal transition process.From batch to continuous flow,the purity of products increased from 97.1%to 98.2%and the median diameter of pigment particles decreased from 14μm to 1.9μm.This process achieved a similar crystal transition effect in 18 s as in batch,producingα,δandνcrystals of Pigment Red 53:2 as expected.In conclusion,this continuous-flow procedure displays advantages in both synthesis and crystal transition,indicating another potential use for industrial application.
基金the National Natural Science Foundation of China(Nos.21878088, 21476077)Key Projects of Shanghai Science and Technology Commission (No.18DZ1112703) for financial support。
文摘Erlotinib is an orally administered, highly effective, specific epidermal growth factor receptor tyrosine kinase inhibitor, used to treat non-small cell lung cancer and pancreatic cancer. The traditional synthetic methods for Erlotinib exhibit long reaction time and safety concern. Herein, we describe a novel five-step route for the synthesis of Erlotinib in flow. These five steps comprise etherification, nitration, reduction,addition and cyclization reactions. All steps were optimized and converted to continuous flow process,which drastically reduces the reaction time and considerably improves the process safety as well as the total yield. Enabled by five continuous flow units, Erlotinib is efficiently afforded with an E-factor of 38,an overall yield of 83%, and a total residence time of 25.1 min. Majority steps in this process have been optimized for quantitative conversion, which offers the possibility of telescoping the entire process.
基金financial support for this work from the National Natural Science Foundation of China(No.21706034)the Natural Science Foundation of Fujian Province(No.2021J01645)the Key Program of Qingyuan Innovation Laboratory(No.00221004)。
文摘Tonalid,an important fragrance ingredient with widespread applicatio n,was synthesized via two FriedelCrafts reactions,which were catalyzed by AlCl_(3).The traditional tonalid production was conducted in batch stirring tank reactors,suffering from low production capacity and the safety hazard of temperature runaway.To solve these problems,the continuous-flow technologies were developed for the highefficiency and intrinsically safe synthesis of tonalid in microreactors.Catalyst AlCl_(3)was neatly homogenized in proper solvents by forming complex with reactant,which was a necessary step for the continuous synthesis in microreactors.Several reaction conditions,including reactant molar ratio,catalyst concentration,temperature,and microchannel hydrodynamic diameter,were investigated for the two Friedel-Crafts reactions in micro reactors.At optimized conditions,the yields of the two Friedel-Crafts reactions were 44.15%and 97.55%,respectively.In comparison with the batch reactors,the reaction times of these two reactions could both be reduced by nearly two thirds in microreactors at the similar yield.
