Synlett, Table of Contents Synlett DOI: 10.1055/a-2704-6387 Letter Facile Synthesis of 11H-Indolo[3,2-c]quinolines Through Pictet–Spengler Cyclization and Aromatization by Oxygen Authors Author Affiliations Kranthi Chatragadda 1 School of Chemistry, University of Hyderabad, Hyderabad, Telangana, India (Ringgold ID: RIN429079) Rajagopal Nagarajan 1 School of Chemistry, University of Hyderabad, Hyderabad, Telangana, India (Ringgold ID: RIN429079) Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract An operationally simple and facile synthesis of 11H-indolo[3,2-c] quinolines through p-TSA-mediated Pictet–Spengler reaction followed by aerobic oxidation using oxygen is reported. The reaction is robust, efficient, metal-free, and versatile with broad functional group tolerance. Keywords KeywordsAlkaloids - Indoloquinolines - Cyclization - Aerobic oxidation - Pictet–Spengler reaction - p-TSA - O2 atmosphere Full Text References References 1 Thongsornkleeb C, Tummatorn J, Ruchirawat S. Chem Asian J 2022; 17: e202200040 2 Agarwal PK, Sawant D, Sharma S, Kundu B. Eur J Org Chem 2009; 292-303 3 Gellert E, Schlittler RHE. Helv Chim Acta 1951; 34: 642-651 4 Thobokholt EN, Larghi EL, Bracca ABJ, Kaufman TS. RSC Adv 2020; 10: 18978-19002 5 Mendez MV, Heredia DA, Larghi EL, Bracca ABJ, Kaufman TS. RSC Adv 2017; 7: 28298-28307 6a Lavrado J, Moreira R, Paulo A. Curr Med Chem 2010; 17: 2348-2370 6b Haheim KS, Lindback E, Tan KN. et al. Molecules 2021; 26: 3268 6c Akitake N, Noda S, Miyoshi K, Sonoda M, Tanimori S. J Org Chem 2021; 86: 17727-17737 7 Bonjean K, Pauw-Gillet DMC, Defresne MP. et al. Biochemistry 1998; 37: 5136-5146 8 Guo S, Tao L, Zhang W, Zhang X, Fan X. J Org Chem 2015; 80: 10955-10964 9 Aksenov AV, Aksenov DA, Griaznov GD, Aksenov NA, Voskressensky LG, Rubin M. Org Biomol Chem 2018; 16: 4325-4332 10 Teng F, Hu W, Hu H, Luo S, Zhu Q. Adv Synth Catal 2019; 361: 1414-1418 11 Baghernejad B. Curr Org Chem 2011; 15: 3091-3097 12 Aksenov AV, Aksenov DA, Orazova NA, Aksenov NA, Griaznov GD, De Carvalho A, Kiss R, Mathieu V, Kornienko A, Rubin M. J Org Chem 2017; 82: 3011-3018 13 Typical experimental procedure: 11H-indolo[3,2-c]quinoline: An oven dried Schlenk tube, equipped with a magnetic stir bar, charged with 2-(1H-indol-2-yl)aniline (100 mg) in 2 mL of xylene, formaldehyde (1.5 equiv) and p-TSA (1.2 equiv) were added and continued stirring at room temperature. This Schlenk tube was shifted to pre-heated oil bath maintained at 120°C with stirring. Reaction continued in the same temperature for 3 days in open air. Upon completion, reaction mixture was cooled to room temperature and poured into ice-cold water and neutralized using saturated Na2CO3 solution until pH reaches 7. Then extracted with DCM (15 mL × 3), washed with brine and dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by using column chromatography with hexane and EtOAc mixture. White solid; yield: 30%; m p: - >200 °C; Rf = 0.42 (EtOAc: Hexane, 3:7); IR (neat): 3394, 2923, 2853, 1650, 1275, 824, 761, 569 cm−1. 1H NMR (500 MHz, DMSO-d 6 ): δ 12.74 (br s, 1H), 9.60 (s, 1H), 8.53 (d, J = 7.8 Hz, 1H), 8.33 (d, J = 7.7 Hz, 1H), 8.14 (d, J = 8.1 Hz, 1H), 7.76–7.768 (m, 3H), 7.51 (t, J = 7.2 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H). 13C (100 MHz, DMSO-d 6 ): δ 145.9, 145.3, 140.2, 139.2, 130.0, 128.5, 126.2, 126.0, 122.6, 122.3, 121.0, 120.6, 117.6, 114.8, 112.4; HRMS (ESI); m/z [M+H]+ calcd for C15H10N2: 219.0922; found: 219.0941. Synthesis of Isocryptolepine (1): From 11H-indolo[3,2-c]quinoline (3), natural product Isocryptolepine (1) can be synthesized using the reported procedure.12 Supplementary Material Supplementary Material Supplementary Material (PDF) (opens in new window)
