Synthesis 2016; 48(09): 1331-1343
DOI: 10.1055/s-0035-1561386
paper
© Georg Thieme Verlag Stuttgart · New York

Facile Synthesis of Substituted 4-Alkoxy-2-oxazolines and Exploration of the Reaction Mechanism

Jianming Zhu
a  CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P. R. of China   Email: boli@simm.ac.cn   Email: wlzhu@simm.ac.cn
,
Xiaolong Li
b  Nano Science and Technology Institute, University of Science and Technology of China, Suzhou, 215123, P. R. of China
,
Guimin Wang
a  CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P. R. of China   Email: boli@simm.ac.cn   Email: wlzhu@simm.ac.cn
,
Bo Li*
a  CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P. R. of China   Email: boli@simm.ac.cn   Email: wlzhu@simm.ac.cn
,
Zhijian Xu
a  CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P. R. of China   Email: boli@simm.ac.cn   Email: wlzhu@simm.ac.cn
,
Shikai Tian
b  Nano Science and Technology Institute, University of Science and Technology of China, Suzhou, 215123, P. R. of China
,
Adrian Hall
c  UCB Biopharma SPRL, Chemin du Foriest, Braine-l’Alleud, 1420, Belgium   Email: jiye.Shi@ucb.com
,
Jingshan Shen
a  CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P. R. of China   Email: boli@simm.ac.cn   Email: wlzhu@simm.ac.cn
,
Jiye Shi*
c  UCB Biopharma SPRL, Chemin du Foriest, Braine-l’Alleud, 1420, Belgium   Email: jiye.Shi@ucb.com
d  Kellogg College, University of Oxford, 60–62 Banbury Road, Oxford, OX2 6PN, UK
,
Weiliang Zhu*
a  CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P. R. of China   Email: boli@simm.ac.cn   Email: wlzhu@simm.ac.cn
› Author Affiliations
Further Information

Publication History

Received: 10 December 2015

Accepted after revision: 22 January 2016

Publication Date:
25 February 2016 (online)


Abstract

Substituted 4-alkoxy-2-oxazolines have been synthesized via the reaction of nitriles with beta-hydroxyacetals promoted by trifluoromethanesulfonic acid. The reaction is proposed to be initiated by the protonation of the acetals to produce carbocations that are then attacked by nitrogen atom of the nitriles, followed by an intramolecular cyclization reaction to form the 4-alkoxy-2-oxazolines. The proposed reaction mechanism has been validated by quantum chemistry calculations, key intermediate synthesis, and NMR spectra.

Supporting Information

 
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