Synlett 2021; 32(04): 395-400
DOI: 10.1055/a-1344-6175
cluster
Radicals – by Young Chinese Organic Chemists

Synthesis of Amidine Derivatives by Intermolecular Radical ­Addition to Nitrile Groups of AIBN Derivatives

Min Su
a   Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, State Key Laboratory of Structural Chemistry, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of ­Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, Fujian 350002, P. R. of China
b   University of Chinese Academy of Sciences, No.19(A) Yuquan Road, ­Shijingshan District, Beijing 100049, P. R. of China
,
Nengbo Zhu
a   Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, State Key Laboratory of Structural Chemistry, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of ­Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, Fujian 350002, P. R. of China
,
Mong-Feng Chiou
a   Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, State Key Laboratory of Structural Chemistry, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of ­Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, Fujian 350002, P. R. of China
,
Hongli Bao
a   Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, State Key Laboratory of Structural Chemistry, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of ­Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, Fujian 350002, P. R. of China
b   University of Chinese Academy of Sciences, No.19(A) Yuquan Road, ­Shijingshan District, Beijing 100049, P. R. of China
› Author Affiliations
We thank the National Key R&D Program of China (Grant No. 2017YFA0700103), the NSFC (Grant Nos. 21602028, 21672213, 21871258), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB20000000), and the Haixi Institute of CAS (Grant No. CXZX-2017-P01) for financial support.


Dedicated to Professor Xue-Long Hou on the occasion of his 65th birthday.

Abstract

A synthesis of amidine derivatives through intermolecular addition of nitrogen-centered radicals to nitriles is reported. Experimental studies and density functional theory calculations were conducted to probe the mechanism of this reaction. The results suggest that the alkyl nitriles are activated by attracting chlorine atoms and are subsequently attacked by nitrogen-centered radicals, resulting in the intermolecular radical addition of nitriles to amidines.

Supporting Information



Publication History

Received: 21 October 2020

Accepted after revision: 02 January 2021

Publication Date:
02 January 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
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  • 19 2-{[2-Chloro-1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-methylpropylidene]amino}-2-methylpropanenitrile (3aa); Typical ProcedureA Schlenk tube containing a stirrer bar was charged with N-chlorophthalimide (1a; 0.5 mmol, 1 equiv), AIBN (2a; 1.25 mmol, 2.5 equiv), and o-xylene (2 mL) under N2, and the mixture was stirred at 90 °C in an oil bath for 6 h. The mixture was then cooled to rt and purified by flash column chromatography [silica gel, PE–EtOAc (20:1)] to give a white solid; yield: 144.5 mg (92%); mp 181.4–182.4 °C.IR (KBr): 2998, 2940, 2228, 1785, 1738, 1665 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.97–7.90 (m, 2 H), 7.82–7.75 (m, 2 H), 1.88 (s, 6 H), 1.68 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 166.77, 150.02, 134.94, 131.68, 124.63, 120.96, 71.28, 53.61, 32.00, 29.88. HRMS (ESI): m/z [M + Na]+ calcd for C16H16ClN3NaO2: 340.0823; found: 340.0827.The structure of 3aa was confirmed by single-crystal x-ray analysis. CCDC 2022501 contains the supplementary crystallographic data for this compound. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures