Synthesis of Multibromo-Substituted Quinolines by NBS-Mediated Cascade Electrophilic Bromination/Cyclization of N-(3-Phenylprop-2-ynyl)anilines

Abstract

A new and convenient protocol is presented here for the synthesis of 3,6,8-tribromoquinolines via cascade cyclization of N-(3-phenylprop-2-ynyl)anilines employing N-bromosuccinimide as an electrophile. The metal-free process is carried out under mild conditions and is compatible with a variety of substituents. The Sonogashira coupling reaction regioselectively occurs at position C-6 of the obtained products.

Key words

tribromoquinolines - electrophilic cyclization - N-bromosuccinimide - propargylanilines

• References


For selected reviews on pharmaceutical applications of quinolines, see:
• 1a Singh S, Kaur G, Mangla V, Gupta MK. J. Enzyme Inhib. Med. Chem. 2015; 30: 492
• 1b Hussaini SM. A. Expert Opin. Ther. Pat. 2016; 26: 1201
• 1c Marella A, Tanwar OP, Saha R, Ali MR, Srivastava S, Akhter M, Alam MM. Saudi Pharm. J. 2013; 21: 1
• 1d Keri RS, Patil SA. Biomed. Pharmacother. 2014; 68: 1161
• 2a Michael JP. Nat. Prod. Rep. 2008; 25: 166
• 2b Michael JP. Nat. Prod. Rep. 2007; 24: 223
• 2c Michael JP. Nat. Prod. Rep. 2003; 20: 476
• 3a Nainwal LM, Tasneem S, Akhtar W, Verma G, Khan MF, Parvez S, Shaquiquzzaman M, Akhter M, Alam MM. Eur. J. Med. Chem. 2019; 164: 121
• 3b Afzal O, Kumar S, Haider MR, Ali MR, Kumar R, Jaggi M, Bawa S. Eur. J. Med. Chem. 2015; 97: 871
• 3c Chung PY, Bian ZX, Pun HY, Chan D, Chan AS. C, Chui CH, Tang JC. O, Lam KH. Future Med. Chem. 2015; 7: 947

For selected reviews on quinoline synthetic progress, see:
• 4a Ramann GA, Cowen BJ. Molecules 2016; 21: 986
• 4b Prajapati SM, Patel KD, Vekariya RH, Panchal SN, Patel HD. RSC Adv. 2014; 4: 24463
• 5a Rehan M, Hazra G, Ghorai P. Org. Lett. 2015; 17: 1668
• 5b Ryabukhin SV, Naumchik VS, Plaskon AS, Grygorenko OO, Tolmachev AA. J. Org. Chem. 2011; 76: 5774
• 6 Ökten S, Çakmak O, Erenler R, Yüce Ö, Tekin Ş. Turk. J. Chem. 2013; 37: 896
• 7 Sahin A, Çakmak O, Demirtas I, Ökten S, Tutar A. Tetrahedron 2008; 64: 1006
• 8a Theoclitou M.-E, Robinson LA. Tetrahedron Lett. 2002; 43: 3907
• 8b Badger G, Crocker H, Ennis B, Gayler J. Aust. J. Chem. 1963; 16: 814
• 8c Long R, Schofield K. J. Chem. Soc. 1953; 3161
• 8d Leonova T, Nadeyskaya E, Yashunskii V. Pharm. Chem. J. 1987; 21: 430
• 8e Calaway PK, Henze HR. J. Am. Chem. Soc. 1939; 61: 1355
• 8f Camps R. Ber. Dtsch. Chem. Ges. 1899; 32: 3228
• 8g Friedlaender P. Ber. Dtsch. Chem. Ges. 1882; 15: 2572
• 9a Song X.-R, Li R, Ding H, Chen X, Yang T, Bai J, Xiao Q, Liang YM. Org. Chem. Front. 2018; 5: 1537
• 9b Jin F, Yang T, Song X.-R, Bai J, Yang R, Ding H, Xiao Q. Molecules 2019; 24: 3999
• 9c Song X.-R, Yang R, Xiao Q. Adv. Synth. Catal. 2021; 363: 852

Selected references on the construction of N-heterocycles:
• 10a Peshkov VA, Pereshivko OP, Nechaev AA, Peshkov AA, Van der Eycken EV. Chem. Soc. Rev. 2018; 47: 3861
• 10b Costello JP, Ferreira EM. Org. Lett. 2019; 21: 9934
• 10c Xie J, Guo Z, Huang Y, Qu Y, Song H, Liu Y, Wang Q. Adv. Synth. Catal. 2019; 361: 490
• 10d Huo Z, Gridnev ID, Yamamoto Y. J. Org. Chem. 2010; 75: 1266
• 10e Likhar PR, Subhas MS, Roy S, Kantam ML, Sridhar B, Seth RK, Biswas S. Org. Biomol. Chem. 2009; 7: 85
• 10f Zhang Y, Liu X.-K, Wu Z.-G, Wang Y, Pan Y. Org. Biomol. Chem. 2017; 15: 6901

Selected references on Larock’s work:
• 11a Zhang X, Yao T, Campo MA, Larock RC. Tetrahedron 2010; 66: 1177
• 11b Zhang X, Campo MA, Yao T, Larock RC. Org. Lett. 2005; 7: 763
• 11c Yue D, Della Cà N, Larock RC. Org. Lett. 2004; 6: 1581

Selected references on the construction of O-heterocycles:
• 12a Feng S, Li J, Liu Z, Sun H, Shi H, Wang X, Xie X, She X. Org. Biomol. Chem. 2017; 15: 8820
• 12b Zheng D, Yu J, Wu J. Angew. Chem. Int. Ed. 2016; 55: 11925
• 12c Barluenga J, Vázquez-Villa H, Ballesteros A, González JM. J. Am. Chem. Soc. 2003; 125: 9028
• 12d Arcadi A, Cacchi S, Di Giuseppe S, Fabrizi G, Marinelli F. Org. Lett. 2002; 4: 2409
• 13a Navakouski M, Zhylitskaya H, Chmielewski PJ, Żyła-Karwowska M, Stępień M. J. Org. Chem. 2020; 85: 187
• 13b Natho P, Allen LA. T, White AJ. P, Parsons PJ. J. Org. Chem. 2019; 84: 9611
• 13c Yang T, Wang W, Wei D, Zhang T, Han B, Yu W. Org. Chem. Front. 2017; 4: 421
• 13d Wang AF, Zhu YL, Wang SL, Hao WJ, Li G, Tu SJ, Jiang B. J. Org. Chem. 2016; 81: 1099
• 13e Zhang N, Yang R, Zhang-Negrerie D, Du Y, Zhao K. J. Org. Chem. 2013; 78: 8705
• 13f Zhao Y, Wong YC, Yeung YY. J. Org. Chem. 2015; 80: 453
• 14 CCDC 2048602 (2a), CCDC 2048406 (2u) and CCDC 2048600 (4) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.