In this work, a liquid-gas heterogeneous microreactor was developed for investigating continuous crystallization of dolutegravir sodium(DTG), as well as revealing reaction kinetics and mixing mechanism with 3-min data...In this work, a liquid-gas heterogeneous microreactor was developed for investigating continuous crystallization of dolutegravir sodium(DTG), as well as revealing reaction kinetics and mixing mechanism with 3-min data acquisition. The reaction kinetics models were established by visually recording the concentration variation of reactants over time in the microchannel via adding pH-sensitive fluorescent dye. The mixing intensification mechanism of liquid-gas flow was quantified through the fluorescent signal to indicate mixing process, demonstrating an outstanding mixing performance with a mixing time less than 0.1 s. Compared with batch crystallization, continuous synthesis of dolutegravir sodium using liquid-gas heterogenous microreactor optimizes crystal distribution size, and successfully modifies the crystal morphology in needle-like habit instead of rod-like habit. The microreactor continuous crystallization can run for 5 h without crystal blockage and achieve D90 of DTG less than 30 μm. This work provides a feasible approach for continuously synthesizing dolutegravir sodium, and can optimize the existing pharmaceutical crystallization.展开更多
The methanolysis of amides,which is widely employed in the synthetic organic chemistry,hardly occurs under mild conditions.To safely and controllably intensify the methanolysis reaction with hightemperature and high-p...The methanolysis of amides,which is widely employed in the synthetic organic chemistry,hardly occurs under mild conditions.To safely and controllably intensify the methanolysis reaction with hightemperature and high-pressure environment,a continuous tubular reaction technology is developed,whose space-time yield is over twice of that of the conventional batch reaction.The methanolysis of acetanilide is selected as the representative reaction,and the influences of temperature,pressure,reactant and catalyst concentration,and residence time on the reaction performances are systematically investigated.Taking the advantages of precise temperature and reaction time control by the tubular reactor,the kinetics of acetanilide methanolysis are determined and compared to the kinetics of acetanilide hydrolysis reaction.The tubular reaction method is also employed to test a variety of other amides to show the effects of substituents,steric hindrance,and alkalinity on the reaction rate of methanolysis.展开更多
For the characteristics of the continuous stirred-tank reactor(CSTR) with coil and jacket cooling system,a CSTR temperature dual control solution based on the analysis of the CSTR exothermic reaction control character...For the characteristics of the continuous stirred-tank reactor(CSTR) with coil and jacket cooling system,a CSTR temperature dual control solution based on the analysis of the CSTR exothermic reaction control characteristic was proposed for an organic material polymerization production.The control solution has passive fault-tolerant ability for the jacket cooling water cutting off fault and active fault-tolerant potential for the coil cooling water cutting off fault,and it has good control ability,high saving energy and reducing consumption performance.Fault detection and diagnosis and fault-tolerant control strategy are designed for the coil cooling fault to achieve the active fault-tolerant control function.The CSTR temperature dual control,process fault detection and diagnosis and active fault-tolerant control were full integrated into the CSTR temperature fault-tolerant control system,which achieve fault tolerance control of CSTR temperature for any severe malfunction of jacket cooling or coil cooling cutting off,and the security for CSTR exothermic reaction is improved.Finally,the effectiveness of this system was validated by semi-physical simulation experiment.展开更多
室温下接种成熟的好氧颗粒污泥于由独立的缺氧池和好氧池组成的缺氧/好氧交替连续流系统中,以实际生活污水为进水基质,探究曝气强度和水力停留时间对连续流系统的影响.研究表明在回流比为2,较小的曝气强度(0.6 m L·min^(-1))和适...室温下接种成熟的好氧颗粒污泥于由独立的缺氧池和好氧池组成的缺氧/好氧交替连续流系统中,以实际生活污水为进水基质,探究曝气强度和水力停留时间对连续流系统的影响.研究表明在回流比为2,较小的曝气强度(0.6 m L·min^(-1))和适当的水力停留时间(9 h)条件下更有利于污染物的去除,此时TP平均去除率为80.43%,TN平均去除率为83.6%,COD平均去除率为90.39%,污泥浓度为2 100 mg·L^(-1)左右,污泥体积指数保持在50 mL·g^(-1)以下,颗粒粒径在700~800 nm之间.用EEM-PARAFAC模型对不同阶段的EPS表征结果表明,EPS组成成分随着运行参数的改变而改变,水力停留时间对连续流系统有更大的影响.此外通过高通量测序的方法评估连续流系统中的微生物多样性,建立污染物去除模型,并在系统中发现了与脱氮除磷相关的11种主要功能菌.展开更多
基金supported by the Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality(No.19ZR1472200)National Natural Science Foundation of China(No.22178072)。
文摘In this work, a liquid-gas heterogeneous microreactor was developed for investigating continuous crystallization of dolutegravir sodium(DTG), as well as revealing reaction kinetics and mixing mechanism with 3-min data acquisition. The reaction kinetics models were established by visually recording the concentration variation of reactants over time in the microchannel via adding pH-sensitive fluorescent dye. The mixing intensification mechanism of liquid-gas flow was quantified through the fluorescent signal to indicate mixing process, demonstrating an outstanding mixing performance with a mixing time less than 0.1 s. Compared with batch crystallization, continuous synthesis of dolutegravir sodium using liquid-gas heterogenous microreactor optimizes crystal distribution size, and successfully modifies the crystal morphology in needle-like habit instead of rod-like habit. The microreactor continuous crystallization can run for 5 h without crystal blockage and achieve D90 of DTG less than 30 μm. This work provides a feasible approach for continuously synthesizing dolutegravir sodium, and can optimize the existing pharmaceutical crystallization.
基金the financial support from the National Natural Science Foundation of China(21991104)the Shandong Province Major Science and Technology Innovation Project(2019JZZY020401)。
文摘The methanolysis of amides,which is widely employed in the synthetic organic chemistry,hardly occurs under mild conditions.To safely and controllably intensify the methanolysis reaction with hightemperature and high-pressure environment,a continuous tubular reaction technology is developed,whose space-time yield is over twice of that of the conventional batch reaction.The methanolysis of acetanilide is selected as the representative reaction,and the influences of temperature,pressure,reactant and catalyst concentration,and residence time on the reaction performances are systematically investigated.Taking the advantages of precise temperature and reaction time control by the tubular reactor,the kinetics of acetanilide methanolysis are determined and compared to the kinetics of acetanilide hydrolysis reaction.The tubular reaction method is also employed to test a variety of other amides to show the effects of substituents,steric hindrance,and alkalinity on the reaction rate of methanolysis.
基金Project(2013JM8024)Supported by Natural Science Basic Research Plan in Shaanxi Province of China
文摘For the characteristics of the continuous stirred-tank reactor(CSTR) with coil and jacket cooling system,a CSTR temperature dual control solution based on the analysis of the CSTR exothermic reaction control characteristic was proposed for an organic material polymerization production.The control solution has passive fault-tolerant ability for the jacket cooling water cutting off fault and active fault-tolerant potential for the coil cooling water cutting off fault,and it has good control ability,high saving energy and reducing consumption performance.Fault detection and diagnosis and fault-tolerant control strategy are designed for the coil cooling fault to achieve the active fault-tolerant control function.The CSTR temperature dual control,process fault detection and diagnosis and active fault-tolerant control were full integrated into the CSTR temperature fault-tolerant control system,which achieve fault tolerance control of CSTR temperature for any severe malfunction of jacket cooling or coil cooling cutting off,and the security for CSTR exothermic reaction is improved.Finally,the effectiveness of this system was validated by semi-physical simulation experiment.
