N-(3-氨基-4-甲基苯基)苯酰胺的连续合成及其微流系统动力学研究

IF 2 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Qilin Xu, Guosi Li, Fucheng Zhu, Naidong Chen, Cuiwu Chen, Zhiqun Yu
{"title":"N-(3-氨基-4-甲基苯基)苯酰胺的连续合成及其微流系统动力学研究","authors":"Qilin Xu,&nbsp;Guosi Li,&nbsp;Fucheng Zhu,&nbsp;Naidong Chen,&nbsp;Cuiwu Chen,&nbsp;Zhiqun Yu","doi":"10.1007/s41981-022-00241-1","DOIUrl":null,"url":null,"abstract":"<div><p><i>N</i>-(3-Amino-4-methylphenyl)benzamide (<b>1</b>) is a crucial building blocks of many drug candidates. In this paper, a continuous flow microreactor system was developed to synthesize <b>1</b> and determine intrinsic reaction kinetics parameters. By screening the acylating reagents and reaction conditions, <b>1</b> was obtained by the selective acylation of 4-methylbenzene-1,3-diamine (<b>2</b>) with benzoic anhydride (<b>3</b>). Since the two amine groups in <b>2</b> are in different chemical environments, parallel by-products and serial by-products coexist, which makes the selective monoacylation process relatively complicated. To reveal the reaction process clearly, reaction rate constants and their 95% confidence intervals, activation energies, pre-exponential factors were acquired by kinetics study in microflow system. The established kinetic model can calculate the selectivity and conversion of the acylation reaction, which are in good agreement with the experimental results. Subsequently, the kinetic model was used to optimize reaction conditions, as a result, <b>1</b> was synthesized in the microreactor with a yield of 85.7% within 10 min.</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-022-00241-1.pdf","citationCount":"0","resultStr":"{\"title\":\"Continuous synthesis of N-(3-Amino-4-methylphenyl)benzamide and its kinetics study in microflow system\",\"authors\":\"Qilin Xu,&nbsp;Guosi Li,&nbsp;Fucheng Zhu,&nbsp;Naidong Chen,&nbsp;Cuiwu Chen,&nbsp;Zhiqun Yu\",\"doi\":\"10.1007/s41981-022-00241-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><i>N</i>-(3-Amino-4-methylphenyl)benzamide (<b>1</b>) is a crucial building blocks of many drug candidates. In this paper, a continuous flow microreactor system was developed to synthesize <b>1</b> and determine intrinsic reaction kinetics parameters. By screening the acylating reagents and reaction conditions, <b>1</b> was obtained by the selective acylation of 4-methylbenzene-1,3-diamine (<b>2</b>) with benzoic anhydride (<b>3</b>). Since the two amine groups in <b>2</b> are in different chemical environments, parallel by-products and serial by-products coexist, which makes the selective monoacylation process relatively complicated. To reveal the reaction process clearly, reaction rate constants and their 95% confidence intervals, activation energies, pre-exponential factors were acquired by kinetics study in microflow system. The established kinetic model can calculate the selectivity and conversion of the acylation reaction, which are in good agreement with the experimental results. Subsequently, the kinetic model was used to optimize reaction conditions, as a result, <b>1</b> was synthesized in the microreactor with a yield of 85.7% within 10 min.</p></div>\",\"PeriodicalId\":630,\"journal\":{\"name\":\"Journal of Flow Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2022-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s41981-022-00241-1.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Flow Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s41981-022-00241-1\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Flow Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s41981-022-00241-1","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

摘要

N-(3-氨基-4-甲基苯基)苯酰胺(1)是许多候选药物的重要组成部分。本文研制了一种连续流微反应器系统,用于合成1并测定本征反应动力学参数。通过对酰化试剂和反应条件的筛选,4-甲基苯-1,3-二胺(2)与苯甲酸酐(3)选择性酰化得到1。由于2中的两个胺基处于不同的化学环境中,平行副产物和串联副产物并存,使得选择性单酰化过程相对复杂。为了更清晰地揭示反应过程,通过微流系统动力学研究获得了反应速率常数及其95%置信区间、活化能、指前因子。建立的动力学模型可以计算出酰化反应的选择性和转化率,与实验结果吻合较好。随后,利用动力学模型对反应条件进行优化,在10 min内,在微反应器中合成了1,产率为85.7%。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Continuous synthesis of N-(3-Amino-4-methylphenyl)benzamide and its kinetics study in microflow system

Continuous synthesis of N-(3-Amino-4-methylphenyl)benzamide and its kinetics study in microflow system

N-(3-Amino-4-methylphenyl)benzamide (1) is a crucial building blocks of many drug candidates. In this paper, a continuous flow microreactor system was developed to synthesize 1 and determine intrinsic reaction kinetics parameters. By screening the acylating reagents and reaction conditions, 1 was obtained by the selective acylation of 4-methylbenzene-1,3-diamine (2) with benzoic anhydride (3). Since the two amine groups in 2 are in different chemical environments, parallel by-products and serial by-products coexist, which makes the selective monoacylation process relatively complicated. To reveal the reaction process clearly, reaction rate constants and their 95% confidence intervals, activation energies, pre-exponential factors were acquired by kinetics study in microflow system. The established kinetic model can calculate the selectivity and conversion of the acylation reaction, which are in good agreement with the experimental results. Subsequently, the kinetic model was used to optimize reaction conditions, as a result, 1 was synthesized in the microreactor with a yield of 85.7% within 10 min.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Flow Chemistry
Journal of Flow Chemistry CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
6.40
自引率
3.70%
发文量
29
审稿时长
>12 weeks
期刊介绍: The main focus of the journal is flow chemistry in inorganic, organic, analytical and process chemistry in the academic research as well as in applied research and development in the pharmaceutical, agrochemical, fine-chemical, petro- chemical, fragrance industry.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信