Synlett 2015; 26(07): 970-974
DOI: 10.1055/s-0034-1379895
letter
© Georg Thieme Verlag Stuttgart · New York

Direct N-Alkylation of Aromatic Amines Using a Microflow Reactor: Enhancement of Selectivity and Reactivity

Yong-Sung Choi
a   College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Yeonsu-gu, Incheon 406-840, Republic of Korea   Email: organicjeong@yonsei.ac.kr
b   College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea
,
Yoon-Jung Kim
a   College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Yeonsu-gu, Incheon 406-840, Republic of Korea   Email: organicjeong@yonsei.ac.kr
,
Liu-Lan Shen
a   College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Yeonsu-gu, Incheon 406-840, Republic of Korea   Email: organicjeong@yonsei.ac.kr
c   Vismer Co., Ltd. Hanyang University Business Incubator, Suite 505, Sangnok-gu, Ansan, Kyunggi-do 426-791, Republic of Korea
,
Yong Sup Lee
b   College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea
,
Jin-Hyun Jeong*
a   College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Yeonsu-gu, Incheon 406-840, Republic of Korea   Email: organicjeong@yonsei.ac.kr
› Author Affiliations
Further Information

Publication History

Received: 09 December 2014

Accepted after revision: 15 January 2015

Publication Date:
18 February 2015 (online)


Abstract

A simple and highly atom-economical method for the direct N-alkylation of aromatic amines by using a microflow reactor was developed to overcome the problem of over-alkylation. In the developed method, high-yield conversion (up to 100%) was achieved in a relatively short reaction time. The ratio of mono- to di-benzylated products (3.57:1) was higher than that achieved with batch reactions conducted in a 1 L scale flask (0.87:1). The structural features of the microflow reactor meant that short-chain alkyl halides could be converted into products with high reactivity and selectivity under superheating conditions, although their boiling point was much lower than the reaction temperature. This method was successfully applied to the synthesis of a range of secondary amines including an intermediate of indobufen synthesis.

Supporting Information

 
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