Development of a Safer Continuous Flow Process for B2(OH)4-Mediated Chemoselective Reduction of Nitroarenes to Anilines

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-09-12 DOI:10.1021/acs.oprd.4c00267

Omkar Revu, Maksim Vasilev, Praveen Gajula, Nageswara Rao Kalikinidi, Madhusudhan Reddy Gadi, Huiping Zhao, Shanika M. P. Gamage, Graham Hibbert, Ongolu Ravikumar, Lalitha Gummidi, Venkatarathnam Nasipireddy, Arun Vinodini, Jonathan Bietsch, Zhirui Wang, Jack D. Brown, Gopal Sirasani, Joseph D. Armstrong, III, Aravind S. Gangu, Bo Qu, Chris H. Senanayake

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Abstract

Tetrahydroxydiboron [B₂(OH)₄] is a chemoselective reducing reagent for nitro reductions in the presence of other labile functional groups. However, there are significant process safety challenges associated with the application of this reducing reagent, including rapid heat release and thermal instability of B₂(OH)₄ in aprotic polar solvents. Herein, we report the development of a safer continuous flow process applying B₂(OH)₄-mediated chemoselective nitro reduction conditions. The safety challenges were addressed by employing continuous flow technology along with identifying a suitable protic cosolvent EtOH. Functional group tolerance toward cyano groups, halides, carboxylic acids, olefins, imines, and benzylic alcohols was demonstrated in flow with higher reaction yield compared to that in batch synthesis. The modified reaction conditions provide a potentially scalable approach to widespread applications of this key transformation for the generation of highly functionalized diversified aniline derivatives.

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开发更安全的 B2(OH)4 介导的硝基烯烃化学选择性还原苯胺的连续流工艺

四羟基二硼[B2(OH)4]是一种化学选择性还原试剂，可在存在其他易变官能团的情况下进行硝基还原。然而，这种还原试剂的应用面临着巨大的工艺安全挑战，包括 B2(OH)4 在钝极性溶剂中的快速热释放和热不稳定性。在此，我们报告了一种应用 B2(OH)4 介导的化学选择性硝基还原条件的更安全的连续流工艺的开发情况。通过采用连续流技术和确定合适的原生共溶剂 EtOH，我们解决了安全方面的难题。与间歇合成相比，在流动条件下，反应产率更高，对氰基、卤化物、羧酸、烯烃、亚胺和苄醇的官能团耐受性也得到了证实。改进后的反应条件为广泛应用这一关键转化技术生成高官能度的多样化苯胺衍生物提供了一种潜在的可扩展方法。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.