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.

 
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  • 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.