3
diaminopropane (1.3 mmol) and p-toluene sulphonic acid (1.0
acetate. Further di-imines undergo hydrolysis, condensation,
elimination and oxidation to afford the final compound.
mmol) was stirred under oxygen atmosphere in THF. In this Pd
(OAc)2 (0.1 mmol) was added and reaction mixture was heated to
reflux temperature for 8-12 hours. After completion of the reaction
(TLC), reaction mixture was cooled to room temperature and
concentrated under reduce pressure. The resulting concentrated
solution was further diluted with water and then extracted with ethyl
acetate. The ethyl acetate layer was washed with Na2S2O3 solution,
dried over anhydrous Na2SO4 and concentrated under reduced
pressure to get the crude product. The product was then purified by
using silica gel column chromatography (Hexane-EtOAc).
2-Phenyl pyridine (3a)14a : Yellow oil; Yield 89%; b. p. 142-143 oC
(lit. 144-146oC); 1H NMR (400 MHz, CDCl3 δ 8 8 (dt, J = 4.8, 1.4
Hz, 1H), 7.99 –7.96 (m, 2H), 7.69–7.68 (m, 2H), 7.47 –7.46 (m, 2H),
7.44 –7.39 (m, 1H), 7.37–7.16 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 157 4 14 2 13 3 , 136.73, 128.94, 128.73, 126.90, 122.08,
120.54. HRMS m/z (ESI): calcd. For [C11H9N+H]+ 156.08 Found:
157.05.
2-(4-methylphenyl) pyridine (3b)14b : Yellow oil; Yield 91%; b. p.
o
124 oC (lit. 122-124 C); 1H NMR (400 MHz, CDCl3 δ 8 dt J =
Scheme 2. Plausible reaction mechanism
4.8, 1.2 Hz, 1H), 7.88 (d, J = 8.2 Hz, 2H), 7.70 –7.67 (m, 2H), 7.27
(d, J = 8.0 Hz, 2H), 7.25 – 7.16 (m, 1H), 2.39 (s, 3H); 13C NMR (100
MHz, CDCl3 δ 157 43, 149.54, 138.90, 136.64, 136.54, 129.44,
126.73, 121.76, 120.23, 21.24; HRMS m/z (ESI): calcd. For
[C12H11N+H] +: 170.09 Found: 170.07
In conclusion, a novel, facile and highly efficient methodology
has been developed to synthesize 2-aryl pyridine derivatives from
easily available aryl/heteroaryl ketones and 1, 3-diaminopropane
in the presence of palladium acetate as a catalyst and oxygen as
the oxidant. This methodology bears a broad range of functional-
group tolerance.
2-(4-chlorophenyl) pyridine (3e) 11: Yellow solid, Yield 84% m. p.
47-51 oC (lit. 49-52 oC); 1H NMR (400 MHz, CDCl3 δ 8 71– 8.66
(m, 1H), 7.97 –7.87 (m, 2H), 7.78 –7.69 (m, 1H), 7.67 (dt, J = 8.0,
1.0 Hz, 1H), 7.45 –7.38 (m, 2H), 7.24 (ddd, J = 7.3, 4.8, 1.2 Hz, 1H);
13C NMR (100 MHz, CDCl3 δ 15 21 14 8 137 78 136.66,
135.15, 128.90, 128.19, 122.30, 120.33; HRMS m/z (ESI): calcd. for
[C11H8ClN+H]+: 190.04 Found: 190.05.
Acknowledgment
SMG thank University Grants Commission India (UGC-SAP) for
financial support. VNT thanks the Science and Engineering
Research Board (SERB), New Delhi, India, for providing
financial support.
2, 2’- bipyridine (3j) 9 : White solid; Yield 84%; m. p. 67-69 oC (lit
1
68-70 oC) H NMR (400 MHz, CDCl3 δ 8 5 dd J = 4 7 7 Hz
2H), 8.37 (d, J = 8.0 Hz, 2H), 7.80 (td, J =S147.8, 1.8 Hz, 2H), 7.28
(ddd, J = 7.5, 4.8, 1.1 Hz, 2H); 13C NMR (100 MHz, CDCl3 δ
156.09, 149.14, 136.88, 123.67, 121.04; HRMS m/z (ESI) : calcd. for
[C10H8N2+H]+: 157.07 Found: 156.05
(a) Andrea, M.; Lodovico, L.; Susan, L.; Renzo, R.; Manfred,
S. Eur. J. of Org. Chem., 2011, 33, 6725; (b) Michael, A. G.;
George R. N.; Joel, S. J. Organomet. Chem., 1980, 3, 341
Supplementary data
Experimental procedure and spectral data associated with this
1016/j.tetlet.2016
14.
References
1.
(a) Zheng, S.; Zhong, Q.; Mottamal, M.; Zhang, Q.; Zhang, C.;
LeMelle, E.; McFerrin, H.; Wang, G. J. Med. Chem. 2014, 57, 3369.
(b) Thomas, S. W.; Venkatesan, K.; Muller, P.; Swager, T. M. J. Am.
Chem. Soc. 2006, 128, 16641 (c) Bringmann, G.; Reichert, Y.; Kane,
V. V. Tetrahedron 2004, 60, 3539.
2.
3.
Curtis, S. P.; Bockow, B.; Fisher, C.; Olaleye, J.; Compton, A.; Ko,
A. T.; Reicin, A.S. BMC Musculoskeletal Disorders, 2005, 6, 58.
Nagarajan, N.; Vanitha, G.; Ananth, D.; Rameshkumar, A.;
Sivasudha, T.; Renganathan, R. J. of Photochemistry and
Photobiology B: Biology, 2013, 127, 212
4.
5.
Sapra, S.; Sharma, K.; Bhalla Y.; Dhar, K. L. Chem. Sci. J. 2016, 7, 2
Tomkinson, H.; Kemp, J.; Oliver, S.; Swaisland, H.; Taboada, M.;
Morris, T. BMC Clinical Pharmacology, 2011, 11, 3.
Hantzsch, A. Ber. Dtsch. Chem. Ges. 1881, 14, 1637.
Tschitschibabin, A. E. J. Prakt. Chem. 1924, 107, 122.
(a) Zecher, W.; Krohnke, F. Chem. Ber. 1961, 94
, F. Chem. Ber. 1961, 94, 698.
6.
7.
8.
9.
Xi, L-Y.; Zhang, R-Y.; Liang, S.; Chen, S-Y.;Yu, X-Q.; Org. Lett.,
2014, 16, 5269.
10.
11.
12.
13.
Wu, K.; Huang, Z.; Liu, C.; Zhang, H.; Lei, A.; Chem. Commun.
2015, 51, 2286.
Sharma, R.; Patel, N.; Vishwakarma, R. A.; Bharatam, P. V.;
Bharate, S. B. Chem. Commun., 2016, 52, 1009.
Hu, B.; Li, Y.; Dong, W.; Xie, X.; Wan, J.; Zhang, Z. New J. Chem.
2016, 6, 48315.
General Procedure for preparation of 2- phenyl pyridines
derivatives (entry 1 -10) A mixture of aryl ketones (1.0 mmol), 1, 3