CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Heyong Wang,Meiluan Wang,Guixiang Huang,Mingye Zhao,Yongzhen Peng,Ning Zhu,Zheng Fang,Yujing Hu,Kai Guo
Optically active ethyl ( R )-2-hydroxy-4-phenylbutanoate (( R )-HPBE), is a key component in the production of angiotensin-converting enzyme (ACE) inhibitors, which are essential for treating hypertension. However, the high cost of starting materials has been a barrier to the industrial synthesis of ( R )-HPBE. Herein, we have established for the first time a four-step enzymatic reaction in continuous flow for the efficient synthesis of ( R )-HPBE from inexpensive benzaldehyde and pyruvic acid. This route also overcomes the issues of chemical disequilibrium and incompatibility of reaction conditions that are common in multi-enzyme cascades. The immobilization methods for aldolase/ene-reductase/keto-reductase were developed, and the immobilized enzymes were initially used in three individual flow modules to produce ( R )-2-hydroxy-4-phenylbutanoic acid (( R )-HPB), achieving high space–time yields of 3103 g (OPBEA) L −1 d −1 , 1685 g (OPBE) L −1 d −1 and 1709 g ( R )-HPB L −1 d −1 respectively. Moreover, integrating three modules in continuous flow achieved a space–time yield of about 350 g ( R )-HPB L −1 d −1 after 108 h, and maintained high operational stability with a conversion of >99 % and a product ee of >99.9 % after 192 h. Subsequently, the ethyl esterification of ( R )-HPB as the fourth module for producing ( R )-HPBE obtained a high space–time yield of 2117 g ( R )-HPBE L −1 d −1 , marking a substantial 74.5-fold increase over the batch system.
研究领域:
生物化学
·
制药工程
·
酶工程
✓ 已验证
DOI
高影响因子
Journal of Flow Chemistry
·
2018
·Vol. 8
·期 3
·129-138
·
IF 1.658
Li Xin,Liu Zhuang,Qi Hao,Fang Zheng,Huang Siyu,Miao Shanshan,Guo Kai
To reduce the cost and improve the efficiency for rifampicin preparation, a continuous flow synthesis of rifampicin starting from rifamycin S and tert -butylamine was studied in a microreactor. Two reaction steps and one purification step were coupled in a microreactor, and rifampicin was obtained with 67% overall yield. This method used 25% less 1-amino-4-methyl piperazine and got 16% higher overall yield without changing solvent and purification process between steps. This method has a good potential for further industrial application.
研究领域:
制药工程
·
有机化学
✓ 已验证
DOI
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2016
·
IF 2.567
Wei He,Zheng Fang,Qitao Tian,Weidong Shen,Kai Guo
In this study, a novel protocol consisting of peroxidatic reaction and epoxidation process was developed. Besides, a specific continuous extraction apparatus was also employed in the continuous flow synthesis process. Without additional purification, m-chloroperbenzoic acid (m-CPBA) generated in situ could react with cyclohexene, leading to high quality cyclohexene oxide. In the first stage, m-CPBA was obtained within a few seconds at room temperature by reacting m-chlorobenzoyl chloride with hydrogen peroxide, while cyclohexene oxide was prepared at 30 °C for 10 min in the following stage.
研究领域:
有机化学
·
化学工程
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Qilin Xu,Jun Chen,Zihao Wang,Yongjun Zang,Guosi Li,Fucheng Zhu,Dong Liu,Chaoyue Sun
Olaparib is a top-selling pharmaceutical approved for the treatment of ovarian cancer. Herein, a two-step cascaded flow process was developed to synthesize Olaparib in microreactor. Since two different acyl groups are in the piperazine ring of Olaparib, a highly selective monoacylation route of piperazine is crucial for the efficient synthesis of Olaparib. For the first step (i.e., the monoacylation of piperazine), N , N' -carbonyldiimidazole was screened as coupling reagent due to its excellent selectivity , safety and greenness, a high monoacylation yield of 83 % was obtained in the microreactor. To understand the selective monoacylation reaction more deeply, the intrinsic kinetics was investigated based on mechanism cognition and experimental data. The established kinetic model was in good agreement with the experimental results in validation experiments. To further realize continuous manufacturing, the following step (i.e., amidation) was cascaded with the monoacylation in a microreactor system, Olaparib was continuously synthesized in the two-step cascaded microreactor with an overall yield of 78 % within 25 min. Relative to existing processes, the reaction steps were reduced, the economy and efficiency were remarkably improved, indicating efficient process intensification.
研究领域:
药物化学
·
合成化学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2023
·
IF 4.7
Shunkai Xia,Tian Yang,Jianhong Xu,Zhuo Chen
Di-(3,5,5-trimethylhexanoyl) peroxide (TMHP) is a low-temperature diacyl peroxide in liquid form, which is widely used as an initiator for the polymerization of vinyl monomers , especially for the production of polyvinyl chloride by suspension polymerization . However, the high reaction heat and the extreme instability of the product of the peroxidation reaction to synthesize TMHP often lead to safety concerns, therefore, the batch reaction processes often sacrifice efficiency in return for better safety. In this work, continuous-flow microreaction technology is utilized to realize an efficient and safe synthesis of TMHP. Under the conditions of T 2 = 30°C, NaOH eq. = 1.05, and H 2 O 2 eq. = 1.20, 94% yield could be obtained within 2.80 min, while batch reactors require hours to perform the same yield. It proves that, compared with batch processes, the efficiency is significantly improved by microreaction technology. Besides, a post-processing method for microreactor effluent is also proposed. After four post-processing steps of aging, washing, drying, and formulation, commercial TMHP product could finally be obtained. This work first reports the efficient and safe synthesis of TMHP based on microreaction technology and a post-processing method for microreactor effluent, which not only develops an efficient route from raw material to TMHP commercial products but also provides a basis for the process development of synthesizing other similar organic peroxides in a more efficient and safer manner.
研究领域:
化学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
ORGANIC PROCESS RESEARCH & DEVELOPMENT
·
2024
·
IF 3.1
Yu Zhang,Minghui Xiao,Ranran Feng,Hong-Yu Zhang,Yuecheng Zhang,Jiquan Zhao
5-Methyltetrahydrofolate (5-MTHF) is an active form of folic acid (FA) and an essential micronutrient preventing anemia and numerous other adverse health conditions such as cardiovascular disease and cancer. Herein, a continuous flow sequence synthesis of 5-MTHF from FA was developed, involving three elementary steps: catalytic hydrogenation of FA to tetrahydrofolic acid (THFA), methylenation of THFA with formaldehyde, and hydrogenation of the methylenation intermediates to 5-MTHF. This process features an expeditious synthesis of 5-MTHF in an integrated flow platform with water as the sole solvent and without any intermediate purification. The overall yield of this three-step flow process was up to 53.54% in a total residence time of 71.4 min. The separated yield of 5-MTHF reached 49.3%.
研究领域:
生物化学
·
制药工程
·
营养学
✓ 已验证
产品关联
DOI
高影响因子
Chemical Engineering and Processing-Process Intensification
·
2017
·
IF 2.234
Jianguo Xu,Jiangang Yu,Yi Jin,Jie Li,Zhiqun Yu,Yanwen Lv
A new procedure of microwave-assisted organic synthesis in flow was designed and introduced for Fischer indole synthesis of 7-ethyltryptophol (7-ET). By using back-pressure regulator (BPR), a reaction temperature of 180 °C could be easily and readily achieved even in a low-boiling solvent [water/ethylene glycol(EG)]. At this temperature, the synthesis of 7-ET from 2-ethylphenylhydrazine and 4-hydroxybutanal in flow was successful (78% net yield) and practical (short residence time: 30 s) with a simple purification process of extraction.
研究领域:
有机化学
·
合成化学
✓ 已验证
DOI
高影响因子
Journal of Flow Chemistry
·
2018
·Vol. 8
·期 1
·29-34
·
IF 1.658
Yu Jiangang,Xu Jianguo,Li Jie,Jin Yi,Xu Wanghui,Yu Zhiqun,Lv Yanwen
A two-step flow reactor has been set up for an expeditious synthesis of 4-benzylidene-pyrazol-5-one derivatives. This procedure involved cyclization of aromatic hydrazine/ β -keto ester and subsequent Knoevenagel condensation reaction with aromatic aldehydes in tandem without isolation of intermediates. Residence time was reduced to less than 2 min in total through conducting this reaction at a relatively high temperature. Accordingly, 15 samples were achieved and isolated in moderate to excellent yields.
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研究领域:
有机化学
·
药物化学
✓ 已验证
DOI
高影响因子
Nanomaterials
·
2022
·Vol. 12
·期 6
·1018
·
IF 5.719
Jianming Yu,Lijie Yang,Jing Jiang,Xunyi Dong,Zhiyang Cui,Chao Wang,Zhenda Lu
Silver nanowires (Ag NWs) have shown great potential in next-generation flexible displays, due to their superior electronic, optical, and mechanical properties. However, as with most nanomaterials, a limited production capacity and poor reproduction quality, based on the batch reaction, largely hinder their application. Here, we applied continuous-flow synthesis for the scalable and high-quality production of Ag NWs, and built a pilot-scale line for kilogram-level per day production. In addition, we found that trace quantities of water could generate sufficient vapor as a spacer under high temperature to efficiently prevent the back-flow or mixed-flow of the reaction solution. With an optimized synthetic formula, a mass production of pure Ag NWs of 36.5 g/h was achieved by a multiple-channel, continuous-flow reactor.Keywords:continuous-flow synthesis;silver nanowires;flow chemistry;pilot-scale synthesis
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2015
·
IF 8.354
Mingxia Jiao,Jianfeng Zeng,Lihong Jing,Chunyan Liu,Mingyuan Gao
PEGylated Fe3O4 nanoparticles were prepared through flow synthesis upon the pyrolysis of ferric acetylacetonate (Fe(acac)3) in anisole at 250 °C under pressure of 33 bar, in the presence of α,ω-dicarboxyl-terminated polyethylene glycol (HOOC–PEG–COOH) and oleylamine. In combination with theoretical analysis, the effects of linear velocity, residence time, and reactor dimension on particle size distribution were systematically investigated. In addition, the impact of Ostwald ripening on particle size distribution was also revealed. In particular, the impacts of monomer concentration distributions along both axial and radial directions of the tube reactor on the particle size distribution were carefully investigated. Under optimized conditions, PEGylated Fe3O4 nanoparticles with the relative standard deviation of particle size down to 10.6% were thus obtained. The resulting 4.6 nm particles exhibited excellent colloidal stability and high longitudinal relaxivity (r1) up to 11.1 mM–1·s–1, which manifested the reliability of flow synthesis in preparing PEGylated Fe3O4 nanoparticles as contrast agents for magnetic resonance imaging applications.
研究领域:
材料科学
·
医学影像
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Journal of Flow Chemistry
·
2023
·Vol. 13
·期 4
·375-383
·
IF 2.7
Lai Liangchuan,Gao Liang,Liu Minjie,Guo Yongxing,Cheng Dang,Jiang Meifen,Chen Fener
Continuous flow technology has been widely adopted in manufacturing active pharmaceutical ingredients (APIs). Herein, we report an expeditious multi-step continuous-flow strategy for an efficient and highly productive flow synthesis of 7-methoxy-1-tetralone, which is an essential intermediate for the opioid analgesic drug (-)-dezocine. Compared with the traditional batch operation, this work presents significant advantages of continuous-flow chemistry with dramatically reduced reaction time, highly improved reaction efficiency, good controls over reaction optimizing conditions, etc. The flow protocol in this work provided the desired product in an overall yield of up to 76.6% with 99% purity, much higher than those from batch process (i.e., 50% yield, 92% purity). Moreover, reaction efficiency is highly improved with a throughput of 0.49 g/h, the total reaction time is markedly reduced from hours in batch to minutes in flow process. Graphical abstract
研究领域:
有机化学
·
制药工程
·
药物合成
✓ 已验证
DOI
高影响因子
Chemical Engineering and Processing-Process Intensification
·
2018
·
IF 2.826
Fajun Wang,Jinpei Huang,Jianhong Xu
Azo dye is a kind of synthetic dye containing azo group (Ar-N=N-Ar). In this paper, an efficient process intensification for the continuous synthesis of azo dye is developed by using a microreactor system. Firstly, the reaction conditions of azo-coupling reaction were optimized and a microreactor was utilized as the mixing and reacting unit. 1- (4- sulfonicphenyl) -3- methyl -5- pyrazolone was the coupling component and aniline was the diazo component. The results show that the yield of azo-coupling reaction was higher than 96% under optimized condition. Then, the reaction conditions of diazotization were optimized by orthogonal experiments in a microreactor system. Combined with the optimization of azo-coupling reaction conditions, the optimal conditions of continuous-flow synthesis of azo dyes in microreactoras were determined. Then, four model azo dyes were synthesized by the continuous method in microreactors. The yields of No. 1, No. 2 and No. 4 azo dyes were above 96% and the yield of No. 3 azo dye was above 90%. Finally, the commercial azo dyes were synthesized continuously in microreactors and the yields were above 94%. The continuous-flow synthesis of azo dyes in a microreactor system has great potential in industrial applications.
研究领域:
化学工程
·
染料化学
·
过程强化
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）