Synlett 2016; 27(06): 912-918
DOI: 10.1055/s-0035-1560385
letter
© Georg Thieme Verlag Stuttgart · New York

Alkaline-Earth-Catalyzed sp3 C–H Functionalization of Methyl Azaarenes and Its Use in a One-Pot Four-Component Synthesis of Azaarenyl Benzylpyrazolones

Srinivasarao Yaragorla*
Department of Chemistry, Central University of Rajasthan, Bandarsindri, NH-8, Ajmer District, Rajasthan, 305817, India   Email: srinivasarao@curaj.ac.in   Email: ysriict@gmail.com
,
Ravikrishna Dada
Department of Chemistry, Central University of Rajasthan, Bandarsindri, NH-8, Ajmer District, Rajasthan, 305817, India   Email: srinivasarao@curaj.ac.in   Email: ysriict@gmail.com
,
Garima Singh
Department of Chemistry, Central University of Rajasthan, Bandarsindri, NH-8, Ajmer District, Rajasthan, 305817, India   Email: srinivasarao@curaj.ac.in   Email: ysriict@gmail.com
› Author Affiliations
Further Information

Publication History

Received: 03 October 2015

Accepted: 23 October 2015

Publication Date:
23 December 2015 (online)


Abstract

The sp3 C–H functionalization of methyl azaarenes by using calcium triflate as the catalyst is described, together with its use in the first synthesis of azaarenyl benzylpyrazolones by a one-pot four-component reaction.

 
  • References


    • For syntheses of methyl azaarenyl derivatives, see:
    • 1a Komai H, Yoshino T, Matsunaga S, Kanai M. Org. Lett. 2011; 13: 1706
    • 1b Rueping M, Tolstoluzhsky N. Org. Lett. 2011; 13: 1095
    • 1c Qian B, Guo S, Shao J, Zhu Q, Yang L, Xia C, Huang H. J. Am. Chem. Soc. 2010; 132: 3650
    • 1d Qian B, Xie P, Xie Y, Huang H. Org. Lett. 2011; 13: 2580
    • 1e Yan Y, Xu K, Fang Y, Wang Z. J. Org. Chem. 2011; 76: 6849
    • 1f Niu R, Yang S, Xiao J, Liang T, Li X. Cuihua Xuebao 2012; 33: 1636
    • 1g Niu R, Xiao J, Liang T, Li X. Org. Lett. 2012; 14: 676
    • 1h Lou S.-J, Xu D.-Q, Shen D.-F, Wang Y.-F, Liu Y.-K, Xu Z.-Y. Chem. Commun. 2012; 48: 11993
    • 1i Jin J.-J, Niu H.-Y, Qu G.-R, Guo H.-M, Fossey JS. RSC Adv. 2012; 2: 5968
    • 1j Meshram HM, Rao NN, Rao LC, Kumar SN. Tetrahedron Lett. 2012; 53: 3963
    • 1k Mulla SA. R, Pathan MY, Chavan SS. RSC Adv. 2013; 3: 20281
    • 1l Graves VB, Shaikh A. Tetrahedron Lett. 2013; 54: 695
    • 1m Jin J, Wang D.-C, Niu H.-Y, Wu S, Qu G.-R, Zhang Z, Guo H. Tetrahedron 2013; 69: 6579
    • 1n Rao NN, Meshram HM. Tetrahedron Lett. 2013; 54: 5087
    • 1o Pi D, Jiang K, Zhou H, Sui Y, Uozumi Y, Zou K. RSC Adv. 2014; 4: 57875
    • 1p Shao Z, Wang L, Xu L, Zhao H, Xiao J. RSC Adv. 2014; 4: 53188
    • 1q Chatterjee S, Bhattacharjee P, Temburu J, Nandi D, Jaisankar P. Tetrahedron Lett. 2014; 55: 6680
    • 1r Jiang K, Pi D, Zhou H, Liu S, Zou K. Tetrahedron 2014; 70: 3056
    • 1s Blocker M, Immaneni S, Shaikh A. Tetrahedron Lett. 2014; 55: 5572
    • 1t Kumar NS, Rao LC, JagadeeshBabu N, Kumar VD, Murthy US. N, Meshram HM. Synlett 2015; 26: 1808
    • 1u Jamal Z, Teo Y.-C. RSC Adv. 2015; 5: 26949
    • 1v Hao S.-H, Zhang X.-Y, Dong D.-Q, Wang Z.-L. Chin. Chem. Lett. 2015; 26: 599
    • 1w Kumar A, Shukla RD. Green Chem. 2015; 17: 848
    • 1x Obora Y, Ogawa S, Yamamoto N. J. Org. Chem. 2012; 77: 9429
    • 1y Xu L, Shao Z, Wang L, Zhao H, Xiao J. Tetrahedron Lett. 2012; 55: 6856
    • 1z Jamal Z, Teo Y.-C. Synlett 2014; 25: 2049
    • 1aa Li VM, Gavrishova TN, Budyka MF. Russ. J. Org. Chem. 2012; 48: 823
    • 2a Mekouar K, Mouscadet JF, Desmaële D, Subra F, Leh H, Savouré D, Auclair C, Angelo J. J. Med. Chem. 1998; 41: 2846
    • 2b Fournet A, Mahieux R, Fakhfakh MA, Franck X, Hocquemiller R, Figadère B. Bioorg. Med. Chem. Lett. 2003; 13: 891
    • 2c Fakhfakh MA, Fournet A, Prina E, Mouscadet J.-F, Franck X, Hocquemiller R, Figadère B. Bioorg. Med. Chem. 2003; 11: 5013
    • 3a Bayle MN, Bénard C, Zouhiri F, Mouscadet J.-F, Leh H, Thomas C.-M, Mbemba G, Desmaële D, d’Angelo J. Bioorg. Med. Chem. Lett. 2005; 15: 4019
    • 3b Bénard C, Zouhiri F, Normand-Bayle M, Danet M, Desmaële D, Leh H, Mouscadet J.-F, Mbemba G, Thomas C.-M, Bonnenfant S, Le Bret M, d’Angelo J. Bioorg. Med. Chem. 2004; 14: 2473
  • 5 Michael JP. Nat. Prod. Rep. 2005; 22: 627
  • 6 Zwaagstra ME, Schoenmakers SH. H. F, Nederkoorn PH. J, Gelens E, Timmerman H, Zhang M.-Q. J. Med. Chem. 1998; 41: 1439
    • 7a Zamboni R, Belley M, Champion E, Charette L, DeHaven R, Frenette R, Gauthier JY, Jones TR, Leger S, Masson P, McFarlane CS, Metters K, Pong SS, Piechuta H, Rokach J, Thérien M, Williams HW. R, Young RN. J. Med. Chem. 1992; 35: 3832
    • 7b King A, Corley EG, Anderson RK, Larsen RD, Verhoeven TR, Reider PJ, Xiang YB, Belley M, Leblanc Y. J. Org. Chem. 1993; 58: 3731
    • 7c McNamara JM, Leazer JL, Bhupathy M, Amato JS, Reamer RA, Reider PJ, Grabowski EJ. J. J. Org. Chem. 1989; 54: 3718
  • 8 Merschaert A, Boquel P, Van Hoeck J.-P, Gorissen H, Borghese A, Bonnier B, Mockel A, Napora F. Org. Process Res. Dev. 2006; 10: 776
    • 9a Felpin F.-X, Lebreton J. Eur. J. Org. Chem. 2003; 3693
    • 9b Carey JS, Laffan L, Thompson C, Williams MT. Org. Biomol. Chem. 2006; 4: 2337
    • 10a Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F, Ebner H, Ebner C. J. Allergy Clin. Immunol. 2003; 111: 882
    • 10b Watanabe T, Yuki S, Egawa M, Nishi H. J. Pharmacol. Exp. Ther. 1994; 268: 1597
    • 10c Kawai H, Nakai H, Suga M, Yuki S, Watanabe T, Saito KI. J. Pharmacol. Exp. Ther. 1997; 281: 921
    • 10d Wu TW, Zeng LH, Wu J, Fung KP. Life Sci. 2002; 71: 2249
    • 10e Al-Haiza MA, El-Assiery SA, Sayed GH. Acta Pharm. (Zagreb, Croatia) 2001; 51: 251
    • 10f Castagnolo D, Manetti F, Radi M, Bechi B, Pagano M, De Logu A, Meleddu R, Saddi M, Botta M. Bioorg. Med. Chem. 2009; 17: 5716
    • 10g Radi M, Bernardo V, Bechi B, Castagnolo D, Pagano M, Botta M. Tetrahedron Lett. 2009; 50: 6572
    • 10h Moreau F, Desroy N, Genevard JM, Vongsouthi V, Gerusz V, Le Fralliec G, Oliveira C, Floquet S, Denis A, Escaich S, Wolf K, Busemann M, Aschenbsenner A. Bioorg. Med. Chem. Lett. 2008; 18: 4022
    • 10i Badawey EA. M, El-Ashmawey IM. Eur. J. Med. Chem. 1998; 33: 349
    • 10j Pasha FA, Muddassar M, Neaz MM, Cho SJ. J. Mol. Graphics Modell. 2009; 28: 54
    • 10k Rosiere CE, Grossman MI. Science 1951; 113: 651
    • 10l Bailey DM, Hansen PE, Hlavac AG, Baizman ER, Pearl J, Defelice AF, Feigenson ME. J. Med. Chem. 1985; 28: 256
    • 10m Chauhan PM. S, Singh S, Chatterjee RK. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1993; 32: 858
    • 10n Gunasekaran P, Perumal S, Yogeeswari P, Sriram D. Eur. J. Med. Chem. 2011; 46: 4530
    • 11a Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
    • 11b Rotstein BH, Zaretsky S, Rai V, Yudin AK. Chem. Rev. 2014; 114: 8323
    • 12a Simon M.-O, Li C.-J. Chem. Soc. Rev. 2012; 41: 1415
    • 12b Jessop PG. Green Chem. 2011; 13: 1391
    • 13a Forkel NV, Henderson DA, Fuchter MJ. Green Chem. 2012; 14: 2129
    • 13b Arrowsmith M, Shepherd WM. S, Hill MS, Kociok-Köhn G. Chem. Commun. 2014; 50: 12676
    • 13c Crimmin MR, Casely IJ, Hill MS. J. Am. Chem. Soc. 2005; 127: 2042
    • 13d Begouin J, Niggemann M. Chem. Eur. J. 2013; 19: 8030
    • 13e Niggemann M, Meel MJ. Angew. Chem. Int. Ed. 2010; 49: 3684
    • 14a Yaragorla S, Pareek A, Dada R. Tetrahedron Lett. 2015; 56: 4770
    • 14b Yaragorla S, Saini PL, Singh G. Tetrahedron Lett. 2015; 56: 1649
    • 14c Yaragorla S, Singh G, Saini P, Reddy MK. Tetrahedron Lett. 2014; 55: 4657
    • 14d Yaragorla S, Sudhakar A, Kiranmai N. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2014; 53: 1471
    • 14e Yaragorla S, Kumar GS. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2015; 54: 240
  • 15 2-Aryl-4-(1-Aryl-2-hetarylethyl)-5-methyl-1,2-dihydro-3H-pyrazol-3-ones 5au; General Procedure Ca(OTf)2 (10 mol%) was added to a stirred solution of MeCOCO2Et (1.13 mmol), arylhydrazine 3 (0.942 mmol), aryl aldehyde 2 (0.934 mmol), and 2-methylazarene 1 (0.942 mmol) in H2O (3 mL), and the mixture was heated to 100 °C. When the reaction was complete (TLC; ~5 h), the mixture was extracted with EtOAc (3 × 5 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated to give a crude solid that was purified by column chromatography. 5-Methyl-2-phenyl-4-(1-phenyl-2-quinolin-2-ylethyl)-1,2-dihydro-3H-pyrazol-3-one (5a) Pink solid; yield: 227.9 mg (80%); mp 67–68 °C. 1H NMR (500 MHz, CDCl3): δ = 7.97 (t, J = 9 Hz, 2 H), 7.83 (d, J = 7.5 Hz, 2 H), 7.69–7.62 (m, 2 H), 7.63 (t, J = 7 Hz, 1 H), 7.44 (t, J = 7 Hz, 2 H), 7.17–7.02 (m, 7 H), 4.32 (d, J = 9 Hz, 1 H), 3.77 (dd, J = 2, 13.5 Hz, 1 H), 3.76 (t, J = 13.5 Hz, 1 H), 1.72 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 160.3, 148.5, 144.8, 144.3, 139.6, 138.3, 132.7, 130.6, 129.1 (2C), 128.6 (2C), 128.4, 127.8, 127.7 (2C), 126.8, 126.4, 126.2, 125.1, 122.9, 121.8 (2C), 100.8, 42.7, 42.1, 13.4. 4-[2-(7-Chloroquinolin-2-yl)-1-(4-nitrophenyl)ethyl]-5-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (5m) Brown solid; yield: 222.7 mg (78%); mp 105–106 °C. 1H NMR (500 MHz, CDCl3): δ = 8.01–7.95 (m, 4 H), 7.8 (d, J = 7.5 Hz, 2 H), 7.66 (d, J = 8.5 Hz, 1 H), 7.45–7.38 (m, 3 H), 7.26 (d, J = 7.5 Hz, 2 H), 7.21–7.18 (m, 1 H), 7.06 (d, J = 8.5 Hz, 1 H), 4.48 (d, J = 9.5 Hz, 1 H), 3.77 (t, J = 13.5 Hz, 1 H), 3.66 (dd, J = 2.5, 14.0 Hz, 1 H), 1.74 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 160.3, 151.5, 150.7, 147.9, 146.5, 145.3, 139.2, 138.5, 137.2, 129.0, 128.8, 128.6, 128.4, 125.6, 125.5, 125.2, 123.7, 122.9, 122.0, 99.4, 42.0, 41.4, 13.3.