Pub Date : 2026-02-09DOI: 10.1021/acs.oprd.5c00411
Woosun Lee,Namyong Kim,Sangsun Joung,Beomjoo Maeng,Eunchae Song,Sangsun Park
A robust and scalable continuous-flow hydrogenation process was developed for the synthesis of 1,2,3,4-tetrahydroisoquinoline (THIQ) scaffold using a commercially available heterogeneous Pt/Al2O3 catalyst in a trickle-bed reactor. This study outlines the systematic selection of catalysts and solvents as well as process optimization using the Design of Experiments (DoE). A scale-up run was successfully demonstrated at a 13 kg scale of THIQ with a 99% isolated yield in pilot equipment. This work demonstrates a practical strategy for the continuous-flow synthesis of THIQ, highlighting its potential for industrial.
{"title":"Scalable Continuous Flow Hydrogenation of Isoquinoline in Trickle-Bed Reactors","authors":"Woosun Lee,Namyong Kim,Sangsun Joung,Beomjoo Maeng,Eunchae Song,Sangsun Park","doi":"10.1021/acs.oprd.5c00411","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00411","url":null,"abstract":"A robust and scalable continuous-flow hydrogenation process was developed for the synthesis of 1,2,3,4-tetrahydroisoquinoline (THIQ) scaffold using a commercially available heterogeneous Pt/Al2O3 catalyst in a trickle-bed reactor. This study outlines the systematic selection of catalysts and solvents as well as process optimization using the Design of Experiments (DoE). A scale-up run was successfully demonstrated at a 13 kg scale of THIQ with a 99% isolated yield in pilot equipment. This work demonstrates a practical strategy for the continuous-flow synthesis of THIQ, highlighting its potential for industrial.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"45 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146139058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An efficient, scalable, and chromatography-free six-step synthesis of the laxative drug bisacodyl (1) has been developed, starting from inexpensive 2-picolinic acid. This practical route achieves an overall yield of 46% and delivers the active pharmaceutical ingredient (API) in 99.88% HPLC purity. Key innovations include a crystallization-based workup for the key acid chloride intermediate, a highly selective Friedel–Crafts acylation/alkylation sequence, and a final acetylation employing a solvent-free system to suppress impurity formation. The process is distinguished by its operational simplicity, featuring direct filtration for the isolation of intermediates in five of the six steps and has been successfully demonstrated on a 500 g scale. This approach offers a robust, cost-effective, and environmentally friendly alternative to existing literature methods for the industrial manufacturing of bisacodyl.
{"title":"Development of a Robust, Efficient, and Scalable Process for the Synthesis of Bisacodyl","authors":"Wentao Bian, Jiamin Chen, Kongling Duan, Qilei Shen, Jianhong Zhao","doi":"10.1021/acs.oprd.5c00465","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00465","url":null,"abstract":"An efficient, scalable, and chromatography-free six-step synthesis of the laxative drug bisacodyl (<b>1</b>) has been developed, starting from inexpensive 2-picolinic acid. This practical route achieves an overall yield of 46% and delivers the active pharmaceutical ingredient (API) in 99.88% HPLC purity. Key innovations include a crystallization-based workup for the key acid chloride intermediate, a highly selective Friedel–Crafts acylation/alkylation sequence, and a final acetylation employing a solvent-free system to suppress impurity formation. The process is distinguished by its operational simplicity, featuring direct filtration for the isolation of intermediates in five of the six steps and has been successfully demonstrated on a 500 g scale. This approach offers a robust, cost-effective, and environmentally friendly alternative to existing literature methods for the industrial manufacturing of bisacodyl.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"6 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-02DOI: 10.1021/acs.oprd.5c00348
Zoe A. Arnaut,Alexandre P. Felgueiras,Fábio M. S. Rodrigues,Rafael T. Aroso,Sandra C. C. Nunes,Alberto A. C. C. Pais,Mariette M. Pereira
In this work, design of experiments (DoE) methodologies were applied to optimize the continuous-flow synthesis of various meso-aryl-substituted porphyrins. Starting from the synthesis of meso-tetraphenylporphyrin (TPP), a response surface model was established correlating yield with temperature and residence time. The study was then extended to structurally and electronically diverse aldehydes, leading to the classification of substrates into four electronic families (groups A–D), based on Mulliken charge calculations at the carbonyl carbon. For each group, optimized quadratic models were developed, enabling the prediction of specific experimental conditions for maximum yield. These predictions were validated through the synthesis of over 10 porphyrin derivatives under continuous-flow conditions. Notably, yields as high as 50% were achieved, and significant productivities were recorded. This modular approach demonstrates the power of combining DoE modeling with electronic structure calculations for scalable, efficient, and generalizable synthesis of functional porphyrins, paving the way for their broader application in catalysis, photomedicine, and materials science.
{"title":"A New Rule(r) for Nitrobenzene-Based Synthesis of meso-Tetraarylporphyrins under Continuous-Flow: Design of Experiments-Guided Optimization","authors":"Zoe A. Arnaut,Alexandre P. Felgueiras,Fábio M. S. Rodrigues,Rafael T. Aroso,Sandra C. C. Nunes,Alberto A. C. C. Pais,Mariette M. Pereira","doi":"10.1021/acs.oprd.5c00348","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00348","url":null,"abstract":"In this work, design of experiments (DoE) methodologies were applied to optimize the continuous-flow synthesis of various meso-aryl-substituted porphyrins. Starting from the synthesis of meso-tetraphenylporphyrin (TPP), a response surface model was established correlating yield with temperature and residence time. The study was then extended to structurally and electronically diverse aldehydes, leading to the classification of substrates into four electronic families (groups A–D), based on Mulliken charge calculations at the carbonyl carbon. For each group, optimized quadratic models were developed, enabling the prediction of specific experimental conditions for maximum yield. These predictions were validated through the synthesis of over 10 porphyrin derivatives under continuous-flow conditions. Notably, yields as high as 50% were achieved, and significant productivities were recorded. This modular approach demonstrates the power of combining DoE modeling with electronic structure calculations for scalable, efficient, and generalizable synthesis of functional porphyrins, paving the way for their broader application in catalysis, photomedicine, and materials science.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"64 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-02DOI: 10.1021/acs.oprd.5c00373
Stefanie Swiecki,Alonso J. Argüelles
The generation and application of kinetic models are of significant interest to process chemists, as they can enable rationale-driven process development, model-based optimization, and bolster and codify process understanding. However, there is a current critical gap in laboratory automation technologies in the gathering of representative, data-rich kinetic data at reasonable throughput to support the early and broad deployment of kinetic models. The novel ReactAll workstation seeks to close this gap. Herein, an evaluation of this workstation was carried out to investigate its suitability within the context of kinetic modeling activities. As a result, a kinetic model for an acid-catalyzed diethyl acetal deprotection process was developed that unexpectedly supported quinolinium species to be catalytically active.
{"title":"Expedited Kinetic Modeling Workflow Leveraging Medium-Throughput Automation","authors":"Stefanie Swiecki,Alonso J. Argüelles","doi":"10.1021/acs.oprd.5c00373","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00373","url":null,"abstract":"The generation and application of kinetic models are of significant interest to process chemists, as they can enable rationale-driven process development, model-based optimization, and bolster and codify process understanding. However, there is a current critical gap in laboratory automation technologies in the gathering of representative, data-rich kinetic data at reasonable throughput to support the early and broad deployment of kinetic models. The novel ReactAll workstation seeks to close this gap. Herein, an evaluation of this workstation was carried out to investigate its suitability within the context of kinetic modeling activities. As a result, a kinetic model for an acid-catalyzed diethyl acetal deprotection process was developed that unexpectedly supported quinolinium species to be catalytically active.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"31 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-02DOI: 10.1021/acs.oprd.5c00459
Peng Zhang,Yuqin Chu,Yang Zhu,Peng Ma,Congming Ma
4,4′-Biphenyl bis(benzyl azide) (BPDBA) is a high-energy compound containing dual benzyl azide groups, whose thermal stability and risk of uncontrolled reaction urgently need assessment. This Article presents a systematic study of BPDBA. Using techniques such as differential scanning calorimetry, thermogravimetric analysis, and accelerating rate calorimetry, the thermal decomposition characteristics of BPDBA under different conditions were investigated. The main thermodynamic parameters, safety parameters, and reaction patterns of its thermal decomposition process were obtained. Experimental results indicate that under high-temperature or cooling failure conditions, BPDBA exhibits significant thermal hazards. Density functional theory was used to study the thermal decomposition characteristics and mechanism of BPDBA. This study provides a theoretical basis for improving the intrinsic safety of BPDBA applications and formulating corresponding safety prevention measures.
{"title":"Thermal Hazard Assessment of 4,4′-Biphenyl Bis(benzyl azide): Combining Experimental and Theoretical Approaches","authors":"Peng Zhang,Yuqin Chu,Yang Zhu,Peng Ma,Congming Ma","doi":"10.1021/acs.oprd.5c00459","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00459","url":null,"abstract":"4,4′-Biphenyl bis(benzyl azide) (BPDBA) is a high-energy compound containing dual benzyl azide groups, whose thermal stability and risk of uncontrolled reaction urgently need assessment. This Article presents a systematic study of BPDBA. Using techniques such as differential scanning calorimetry, thermogravimetric analysis, and accelerating rate calorimetry, the thermal decomposition characteristics of BPDBA under different conditions were investigated. The main thermodynamic parameters, safety parameters, and reaction patterns of its thermal decomposition process were obtained. Experimental results indicate that under high-temperature or cooling failure conditions, BPDBA exhibits significant thermal hazards. Density functional theory was used to study the thermal decomposition characteristics and mechanism of BPDBA. This study provides a theoretical basis for improving the intrinsic safety of BPDBA applications and formulating corresponding safety prevention measures.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"82 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We report a telescoped continuous-flow process for vanillin synthesis utilizing a newly developed CoOx/HT catalyst. This robust and highly selective catalyst achieves the continuous synthesis of vanillin with 90% yield and excellent selectivity through aerobic oxidative decarboxylation from vanillylmandelic acid. The use of a catalyst that shows high performance even under high-concentration conditions enables improvements in productivity and significant reductions in solvent consumption throughout the entire flow process. Therefore, a continuous-flow process consisting of two reaction steps, including a catalytic reaction and three in-line extraction steps, demonstrates continuous vanillin synthesis with a total yield, productivity, and STY of 67%, 12 g h–1, and 30 g h–1 L–1, respectively.
我们报道了一种利用新开发的CoOx/HT催化剂合成香兰素的伸缩连续流工艺。该催化剂稳定性好，选择性高，以香兰香扁桃酸为原料，通过有氧氧化脱羧，以90%的收率连续合成香兰素。使用即使在高浓度条件下也表现出高性能的催化剂，可以提高生产率，并在整个流程中显著减少溶剂消耗。因此，由两个反应步骤组成的连续流程，包括催化反应和三个在线提取步骤，证明了香草醛的连续合成，总收率，生产率和STY分别为67%，12 g h-1和30 g h-1 L-1。
{"title":"Enhanced Telescoped Continuous-Flow Synthesis of Vanillin via Process Intensification Using Robust Cobalt Catalysts and Online UHPLC Analysis","authors":"Tomohiro Ichitsuka, Masahide Sato, Takayuki Ishizaka","doi":"10.1021/acs.oprd.5c00277","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00277","url":null,"abstract":"We report a telescoped continuous-flow process for vanillin synthesis utilizing a newly developed CoO<sub><i>x</i></sub>/HT catalyst. This robust and highly selective catalyst achieves the continuous synthesis of vanillin with 90% yield and excellent selectivity through aerobic oxidative decarboxylation from vanillylmandelic acid. The use of a catalyst that shows high performance even under high-concentration conditions enables improvements in productivity and significant reductions in solvent consumption throughout the entire flow process. Therefore, a continuous-flow process consisting of two reaction steps, including a catalytic reaction and three in-line extraction steps, demonstrates continuous vanillin synthesis with a total yield, productivity, and STY of 67%, 12 g h<sup>–1</sup>, and 30 g h<sup>–1</sup> L<sup>–1</sup>, respectively.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"35 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1021/acs.oprd.5c00370
Zijin You, Shengzhen Liu, Qihao Li, Shengtao Sun, Ti Wu, Yuguang Feng, Jin Cao, Lanlan Hou, Zhaohui Yu
As essential building blocks of next-generation optoelectronic devices, polymer semiconductors hold great promise for applications in displays, biology, the Internet of Things, wearable electronics, and related emerging technologies. Nowadays, most solution-processable polymer semiconductors still rely on chlorinated solvents, which pose serious risks to both human health and the environment. With the optoelectronics industry moving toward sustainable practices, increasing attention has been devoted to the development of polymer semiconductors that are compatible with green solvents, and notable progress has already been made in this area. In this review, we summarize recent advances in the design and processing of eco-friendly green-solvent-processable polymer semiconductors. We further discuss various strategies to eliminate hazardous solvents, particularly focusing on molecular design approaches, including backbone engineering, side-chain engineering, and asymmetric synthesis. Finally, we outline the remaining challenges and future opportunities for advancing sustainably processed conjugated polymer semiconductors. By bridging materials innovation with sustainable processing, these efforts pave the way toward safer, greener, and more scalable optoelectronic technologies.
{"title":"Toward Ecofriendly Solvent-Processable Conjugated Polymers: Recent Advances in Molecular Engineering","authors":"Zijin You, Shengzhen Liu, Qihao Li, Shengtao Sun, Ti Wu, Yuguang Feng, Jin Cao, Lanlan Hou, Zhaohui Yu","doi":"10.1021/acs.oprd.5c00370","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00370","url":null,"abstract":"As essential building blocks of next-generation optoelectronic devices, polymer semiconductors hold great promise for applications in displays, biology, the Internet of Things, wearable electronics, and related emerging technologies. Nowadays, most solution-processable polymer semiconductors still rely on chlorinated solvents, which pose serious risks to both human health and the environment. With the optoelectronics industry moving toward sustainable practices, increasing attention has been devoted to the development of polymer semiconductors that are compatible with green solvents, and notable progress has already been made in this area. In this review, we summarize recent advances in the design and processing of eco-friendly green-solvent-processable polymer semiconductors. We further discuss various strategies to eliminate hazardous solvents, particularly focusing on molecular design approaches, including backbone engineering, side-chain engineering, and asymmetric synthesis. Finally, we outline the remaining challenges and future opportunities for advancing sustainably processed conjugated polymer semiconductors. By bridging materials innovation with sustainable processing, these efforts pave the way toward safer, greener, and more scalable optoelectronic technologies.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"260 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1021/acs.oprd.5c00460
Michał Wrzecionek, Antoni Jaroń, Dominik Kłudkiewicz, Justyna Pijarowska-Kruszyna
Ethylenediamine-N,N′-diacetic acid (EDDA) is an important chelating agent used in radiopharmaceutical formulations. In addition, 99mTc-EDDA/HYNIC-TOC (Tektrotyd) is an approved radiopharmaceutical used in the diagnosis of neuroendocrine tumors. Despite its importance, most of the literature relies on commercially sourced EDDA, and no comprehensive studies of its synthesis have been conducted. This study presents the development and optimization of a GMP-compliant process for the production of pharmaceutical-grade EDDA. Three synthetic routes were evaluated, revealing that the autocatalytic pathway is the most efficient in terms of yield, purity, and process mass intensity. In situ FTIR monitoring allowed the hydrolysis time to be reduced from 10 to 3 h. The optimization of maceration resulted in a simplified and highly effective purification procedure. The overall process time was reduced, and the reaction mixture volume decreased by almost 50%, thereby improving the process economy and aligning with the principles of green chemistry. Organic impurities were identified and controlled in accordance with the ICH and GMP requirements. The optimized process enabled the production of 115 g of EDDA, achieving a total yield of 22% and a chemical purity exceeding 99.9%. As EDDA is not currently described in any pharmacopoeia, the data presented here lay the groundwork for a future monograph and support its reliable use in radiopharmaceutical manufacturing.
乙二胺-N，N ' -二乙酸（EDDA）是放射性药物制剂中重要的螯合剂。此外，99mTc-EDDA/ hynicc - toc （Tektrotyd）是一种被批准用于诊断神经内分泌肿瘤的放射性药物。尽管它很重要，但大多数文献依赖于商业来源的EDDA，并没有对其合成进行全面的研究。本研究提出了一种符合gmp的制药级EDDA生产工艺的开发和优化。对三种合成途径进行了评价，表明自催化途径在产率、纯度和工艺质量强度方面是最有效的。原位FTIR监测使水解时间从10小时减少到3小时。浸渍的优化导致了简化和高效的纯化过程。整个过程时间缩短，反应混合物体积减少近50%，从而提高了过程经济性，符合绿色化学的原则。有机杂质按照ICH和GMP要求进行鉴定和控制。优化后的工艺可生产115 g EDDA，总收率为22%，化学纯度超过99.9%。由于目前没有任何药典描述EDDA，本文提供的数据为未来的专著奠定了基础，并支持其在放射性药物制造中的可靠使用。
{"title":"Process Development and Optimization of EDDA Synthesis for Radiopharmaceuticals According to GMP Standards","authors":"Michał Wrzecionek, Antoni Jaroń, Dominik Kłudkiewicz, Justyna Pijarowska-Kruszyna","doi":"10.1021/acs.oprd.5c00460","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00460","url":null,"abstract":"Ethylenediamine-<i>N</i>,<i>N</i>′-diacetic acid (EDDA) is an important chelating agent used in radiopharmaceutical formulations. In addition, <sup>99m</sup>Tc-EDDA/HYNIC-TOC (Tektrotyd) is an approved radiopharmaceutical used in the diagnosis of neuroendocrine tumors. Despite its importance, most of the literature relies on commercially sourced EDDA, and no comprehensive studies of its synthesis have been conducted. This study presents the development and optimization of a GMP-compliant process for the production of pharmaceutical-grade EDDA. Three synthetic routes were evaluated, revealing that the autocatalytic pathway is the most efficient in terms of yield, purity, and process mass intensity. In situ FTIR monitoring allowed the hydrolysis time to be reduced from 10 to 3 h. The optimization of maceration resulted in a simplified and highly effective purification procedure. The overall process time was reduced, and the reaction mixture volume decreased by almost 50%, thereby improving the process economy and aligning with the principles of green chemistry. Organic impurities were identified and controlled in accordance with the ICH and GMP requirements. The optimized process enabled the production of 115 g of EDDA, achieving a total yield of 22% and a chemical purity exceeding 99.9%. As EDDA is not currently described in any pharmacopoeia, the data presented here lay the groundwork for a future monograph and support its reliable use in radiopharmaceutical manufacturing.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"17 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1021/acs.oprd.5c00450
Christophe Allais, Ian Hotham, Aran K. Hubbell, Dylan Pedro, Sergei Tcyrulnikov, Anna Chiara Vicini, David J. Bernhardson
The field of nonprecious metal catalysis (NPMC) continues to provide alternatives to transformations that are traditionally mediated by precious metals, as well as reactivity unique to the first-row transition metals. These advances are of interest due to their lower cost, better sustainability, and expanding range of applications. This review is part of a triannual series published by chemists from AbbVie, Boehringer-Ingelheim, and Pfizer focused on NPMC articles selected for their utility to the chemical and pharmaceutical industries from November 2024 to February 2025.
{"title":"Recent Advances in Nonprecious Metal Catalysis","authors":"Christophe Allais, Ian Hotham, Aran K. Hubbell, Dylan Pedro, Sergei Tcyrulnikov, Anna Chiara Vicini, David J. Bernhardson","doi":"10.1021/acs.oprd.5c00450","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00450","url":null,"abstract":"The field of nonprecious metal catalysis (NPMC) continues to provide alternatives to transformations that are traditionally mediated by precious metals, as well as reactivity unique to the first-row transition metals. These advances are of interest due to their lower cost, better sustainability, and expanding range of applications. This review is part of a triannual series published by chemists from AbbVie, Boehringer-Ingelheim, and Pfizer focused on NPMC articles selected for their utility to the chemical and pharmaceutical industries from November 2024 to February 2025.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"388 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-26DOI: 10.1021/acs.oprd.5c00437
Marta Redaelli,Jana Rohacova,Jakub Táborský,Tomáš Holas,Martin Štefko
A unique set of water- and air-tolerant conditions has been developed for the Diels–Alder cycloaddition, leading to a key intermediate in the preparation of synthetic cantharidin (CNR). Lithium iodide acts as an exceptional catalyst, enabling excellent conversion efficiency of the reaction along with the highest stereoselectivity (exo-selectivity) reported to date. The optimized reaction parameters were supported through a Design of Experiments (DoE) study. Moreover, we report here for the first time a crystallization-based isolation protocol, allowing us to obtain a pure exo-isomer key intermediate, free from byproducts and residual salt. Furthermore, the developed isolation conditions give the possibility of a dedicated recovery procedure for lithium iodide to further enhance the cost efficiency of the overall process. The entire synthesis was successfully scaled to the hundred-gram level using straightforward reactions and isolation procedures.
{"title":"Scalable Synthesis of Cantharidin: Lithium Iodide as a Stereoselective and Efficient Catalyst in the Diels–Alder Reaction toward a Key Intermediate","authors":"Marta Redaelli,Jana Rohacova,Jakub Táborský,Tomáš Holas,Martin Štefko","doi":"10.1021/acs.oprd.5c00437","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00437","url":null,"abstract":"A unique set of water- and air-tolerant conditions has been developed for the Diels–Alder cycloaddition, leading to a key intermediate in the preparation of synthetic cantharidin (CNR). Lithium iodide acts as an exceptional catalyst, enabling excellent conversion efficiency of the reaction along with the highest stereoselectivity (exo-selectivity) reported to date. The optimized reaction parameters were supported through a Design of Experiments (DoE) study. Moreover, we report here for the first time a crystallization-based isolation protocol, allowing us to obtain a pure exo-isomer key intermediate, free from byproducts and residual salt. Furthermore, the developed isolation conditions give the possibility of a dedicated recovery procedure for lithium iodide to further enhance the cost efficiency of the overall process. The entire synthesis was successfully scaled to the hundred-gram level using straightforward reactions and isolation procedures.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"288 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：