Development of an Optimized Process for 2,4-Dichloro-5-fluoroacetophenone: A Key Intermediate of Ciprofloxacin

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-07-24 DOI:10.1021/acs.oprd.4c0020810.1021/acs.oprd.4c00208

Kai Yin*, Youlan He, Hao Wu, Xubin He and Yiwei Zhang*,

{"title":"Development of an Optimized Process for 2,4-Dichloro-5-fluoroacetophenone: A Key Intermediate of Ciprofloxacin","authors":"Kai Yin*, Youlan He, Hao Wu, Xubin He and Yiwei Zhang*, ","doi":"10.1021/acs.oprd.4c0020810.1021/acs.oprd.4c00208","DOIUrl":null,"url":null,"abstract":"Herein, we report an optimized process for 2,4-dichloro-5-fluoroacetophenone, a key intermediate of ciprofloxacin. In the nitration step, the traditional mixed acid process was replaced by a microchannel continuous reaction technology. For the fluorination reactions, the traditional quaternary ammonium salt catalyst was replaced by a novel CNC+ catalyst, which led to improved catalytic efficiency, lowered reaction temperatures, and increased product yields. Furthermore, a cost-effective method for utilizing waste gases with high concentrations of nitrogen oxides was developed for the nitrochlorination reaction. In the acetylation step, magnetic materials featuring both Bronsted and Lewis acid sites were utilized to immobilize the bisacid site catalyst [HPhIm][FeCl4]/MPNs, replacing the traditional AlCl3 approach. The overall yield of this new sustainable process across all four steps reached 86.4%, marking a significant improvement of over 10% compared to the traditional method. Moreover, the new process has resulted in an 87% reduction in waste acid emissions and a remarkable 96% reduction in exhaust emissions.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"28 8","pages":"3284–3294 3284–3294"},"PeriodicalIF":3.5000,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.oprd.4c00208","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}

引用次数: 0

Abstract

Herein, we report an optimized process for 2,4-dichloro-5-fluoroacetophenone, a key intermediate of ciprofloxacin. In the nitration step, the traditional mixed acid process was replaced by a microchannel continuous reaction technology. For the fluorination reactions, the traditional quaternary ammonium salt catalyst was replaced by a novel CNC⁺ catalyst, which led to improved catalytic efficiency, lowered reaction temperatures, and increased product yields. Furthermore, a cost-effective method for utilizing waste gases with high concentrations of nitrogen oxides was developed for the nitrochlorination reaction. In the acetylation step, magnetic materials featuring both Bronsted and Lewis acid sites were utilized to immobilize the bisacid site catalyst [HPhIm][FeCl₄]/MPNs, replacing the traditional AlCl₃ approach. The overall yield of this new sustainable process across all four steps reached 86.4%, marking a significant improvement of over 10% compared to the traditional method. Moreover, the new process has resulted in an 87% reduction in waste acid emissions and a remarkable 96% reduction in exhaust emissions.

Abstract Image

查看原文本刊更多论文

开发 2,4-二氯-5-氟苯乙酮的优化工艺：环丙沙星的关键中间体

在此，我们报告了环丙沙星的关键中间体 2,4-二氯-5-氟苯乙酮的优化工艺。在硝化步骤中，传统的混合酸工艺被微通道连续反应技术所取代。在氟化反应中，传统的季铵盐催化剂被新型 CNC+ 催化剂取代，从而提高了催化效率，降低了反应温度，增加了产品收率。此外，在硝基氯化反应中，还开发了一种利用高浓度氮氧化物废气的经济有效的方法。在乙酰化步骤中，利用同时具有布郎斯特德和路易斯酸位点的磁性材料固定双酸位点催化剂 [HPhIm][FeCl4]/MPNs，取代了传统的 AlCl3 方法。这一新的可持续工艺在所有四个步骤中的总产率达到了 86.4%，与传统方法相比显著提高了 10%以上。此外，新工艺还使废酸排放量减少了 87%，废气排放量显著减少了 96%。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.