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

Min Su; Nengbo Zhu; Mong-Feng Chiou; Hongli Bao

doi:10.1055/a-1344-6175

Synlett, Table of Contents

Synlett 2021; 32(04): 395-400
DOI: 10.1055/a-1344-6175

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Radicals – by Young Chinese Organic Chemists

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

Authors

Min Su

^aKey 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

^bUniversity of Chinese Academy of Sciences, No.19(A) Yuquan Road, Shijingshan District, Beijing 100049, P. R. of China
Nengbo Zhu

^aKey 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

^aKey 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 ∗

^aKey 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

^bUniversity of Chinese Academy of Sciences, No.19(A) Yuquan Road, Shijingshan District, Beijing 100049, P. R. of China

Abstract

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

Key words

amidines - nitriles - catalyst-free reaction - nitrogen-centered radicals - intermolecular radical addition

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References

References and Notes

1a Aly AA, Bräse S, Gomaa MA. M. ARKIVOC 2018; (vi): 85
1b Greenhill JV, Lue P. Prog. Med. Chem. 1993; 30: 203
1c Kaneda M. J. Antibiot. 2002; 55: 924
1d Prevorsek D. J. Phys. Chem. 1962; 66: 769
1e Soeiro MN. C, Werbovetz K, Boykin DW, Wilson WD, Wang MZ, Hemphill A. Parasitology 2013; 140: 929

2a Crone WJ. K, Vior NM, Santos-Aberturas J, Schmitz LG, Leeper FJ, Truman AW. Angew. Chem. Int. Ed. 2016; 55: 9639
2b Shimamura H, Gouda H, Nagai K, Hirose T, Ichioka M, Furuya Y, Kobayashi Y, Hirono S, Sunazuka T, Ōmura S. Angew. Chem. Int. Ed. 2009; 48: 914

3 Roholt K, Nielsen B, Kristensen E. Chemotherapy 1975; 21: 146
4 Ledet MM, Anderson R, Harman R, Muth A, Thompson PR, Coonrod SA, Van de Walle GR. BMC Cancer 2018; 18: 412

5a Buckman BO, Chou Y.-L, McCarrick M, Liang A, Lentz D, Mohan R, Morrissey MM, Shaw KJ, Trinh L, Light DR. Bioorg. Med. Chem. Lett. 2005; 15: 2249
5b Yin Z, Zhang Z, Zhu J, Wong H, Kadow JF, Meanwell NA, Wang T. Tetrahedron Lett. 2005; 46: 4919

6a Charette AB, Grenon M. Tetrahedron Lett. 2000; 41: 1677
6b Das VK, Thakur AJ. Tetrahedron Lett. 2013; 54: 4164

7 Chavan NL, Naik NH, Nayak SK, Kusurkar RS. ARKIVOC 2010; (ii): 248

8a Hagadorn JR, McNevin MJ. Organometallics 2003; 22: 609
8b Obenauf J, Kretschmer WP, Bauer T, Kempe R. Eur. J. Inorg. Chem. 2013; 537

9a Meilahn MK, Augenstein LL, McManaman JL. J. Org. Chem. 1971; 36: 3627
9b Wu Y, Chen X, Zhang M.-M. Synthesis 2020; 52: 1773
9c Youn SW, Lee EM. Org. Lett. 2016; 18: 5728
9d Shriner RL, Neumann FW. Chem. Rev. 1944; 35: 351

10a Duchamp E, Hanessian S. Org. Lett. 2020; 22: 8487
10b Garigipati RS. Tetrahedron Lett. 1990; 31: 1969

11 Luo Y.-R. Comprehensive Handbook of Chemical Bond Energies. CRC Press; Boca Raton: 2007: 403
12 Androvič L, Bartáček J, Sedlák M. Res. Chem. Intermed. 2016; 42: 5133
13 De Vleeschouwer F, Van Speybroeck V, Waroquier M, Geerlings P, De Proft F. Org. Lett. 2007; 9: 2721
14 Xie Y, Guo S, Wu L, Xia C, Huang H. Angew. Chem. Int. Ed. 2015; 54: 5900

15a Barolli JP, Maia PI. S, Colina-Vegas L, Moreira J, Plutin AM, Mocelo R, Deflon VM, Cominetti MR, Camargo-Mathias MI, Batista AA. Polyhedron 2017; 126: 33
15b Kang Q.-Q, Liu Y, Huang X.-J, Li Q, Wei W.-T. Eur. J. Org. Chem. 2019; 7673
15c Yu J, Sheng H.-X, Wang S.-W, Xu Z.-H, Tang S, Chen S.-L. Chem. Commun. 2019; 55: 4578
15d Liu Y, Meng Y.-N, Huang X.-J, Qin F.-H, Wu D, Shao Q, Guo Z, Li Q, Wei W.-T. Green Chem. 2020; 22: 4593

16a Zhang C, Pi J, Chen S, Liu P, Sun P. Org. Chem. Front. 2018; 5: 793
16b Yang T, Xia W.-J, Shang J.-Q, Li Y, Wang X.-X, Sun M, Li Y.-M. Org. Lett. 2019; 21: 444
16c Li Y.-M, Wang S.-S, Yu F, Shen Y, Chang K.-J. Org. Biomol. Chem. 2015; 13: 5376
16d Wang S.-S, Fu H, Shen Y, Sun M, Li Y.-M. J. Org. Chem. 2016; 81: 2920
16e Ji L, Gu W, Liu P, Sun P. Org. Biomol. Chem. 2020; 18: 6126

17a Grivas JC, Taurins A. Can J. Chem. 1961; 39: 761
17b Rousselet G, Capdevielle P, Maumy M. Tetrahedron Lett. 1993; 34: 6395

18 Zhu N, Li Y, Bao H. Org. Chem. Front. 2018; 5: 1303
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

Supplementary Material

Supporting Information (PDF)

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

Authors

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