Organic & Biomolecular Chemistry
Page 4 of 5
DOI: 10.1039/C5OB00776C
2-(4-Methoxyphenyl)imidazo[1,2-a]pyridine-3-carbaldehyde
(3g):8 White solid; m.p. 171-172 °C; 1H NMR (CDCl3, 400
MHz): 10.06 (s, 1H), 9.67 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 8.0
Hz, 3H), 7.55 (t, J = 8.0 Hz, 1H), 7.11 (t, J = 8.0 Hz, 1H), 7.07
(d, J = 8.0 Hz, 2H), 3.89 (s, 3H); 13C NMR (CDCl3,100 MHz): δ
179.6, 161.1, 158.4, 147.8, 131.2, 130.5, 128.9, 124.8, 120.5,
117.2, 115.1, 114.4, 55.5; IR (CHCl3): max 2918, 2850, 1733,
1634, 1409, 1253, 1215 cm-1; ESI-MS: m/z 253.10 [M+H]+; HR-
ESIMS: m/z 253.1000 calcd for C15H12N2O2 +H+ (253.0972).
1641, 1534, 1215 cm-1; ESI-MS: m/z 282.09 [M+H]+; HR-
ESIMS: m/z 282.0900 calcd for C15H11N3O3+H+ (282.0873).
6-Methyl-2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde (3m):
1
Yellow sticky solid; H NMR (CDCl3, 400 MHz): 10.70 (s,
5
60 1H), 9.48 (s, 1H), 7.82 (d, J = 8.0 Hz, 2H), 7.75 (d, J = 8.0 Hz,
1H), 7.51 (s, 3H), 7.45 (d, J = 8.0 Hz, 1H), 2.44 (s, 3H) ; 13C
NMR (CDCl3, 100 MHz): δ 179.6, 158.1, 146.6, 133.4, 132.3,
129.9, 129.8, 128.9, 126.8, 125.7, 120.5, 116.6, 18.4; IR (CHCl3):
max 3436, 2924, 1724, 1594, 1442, 1275, 1018 cm-1; ESI-MS:
10 2-(4-Methoxyphenyl)-8-methylimidazo[1,2-a]pyridine-3-
65 m/z 237.20 [M+H]+; HR-ESIMS: m/z 237.1020 calcd for
1
carbaldehyde (3h):14 Brown solid; m.p. 165-166 °C; H NMR
(CDCl3, 400 MHz): 10.02 (s, 1H), 9.48 (s, 1H), 7.78 (d, J = 8.0
Hz, 2H), 7.69 (d, J = 8.0 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.05
(d, J = 12.0 Hz, 2H), 3.88 (s, 3H), 2.44 (s, 3H); 13C NMR
15 (CDCl3,100 MHz): δ 179.4, 161.0, 158.1, 146.8, 133.2, 131.1,
126.9, 125.2, 125.0, 120.3, 116.5, 114.4, 55.4, 18.3; IR (CHCl3):
max 3436, 1636, 1415, 1219, 1020 cm-1; ESI-MS: m/z 266.90
[M+H]+; HR-ESIMS: m/z 267.1125 calcd for C16H14N2O2+H+
(267.1128).
C15H12N2O+H+ (237.1022).
DFT studies. Density functional (DFT) analysis was carried out
to explore the reaction mechanism for CuBr catalyzed synthesis
of
3-formyl-2-phenyl-imidazo[1,2-a]pyridines
from
2-
70 aminopyridine and cinnamaldehyde. The GAUSSIAN09 suite of
programs was used to carry out the geometry optimization of all
the structures on the possible reaction mechanism pathways and
to estimate the Gibbs free energy values at each step. Complete
optimizations without any symmetry constraints were carried out
75 using Becke−Lee−Yang−Parr (B3LYP) method with the 6-
311+G(d,p) basis set. Same basis set was used to analytically
compute frequencies to characterize the stationary points to
minima and the transition states. Each transition state is a first-
order saddle point with only one imaginary vibrational mode on
20 2-(4-Methoxyphenyl)-6-methylimidazo[1,2-a]pyridine-3-
1
carbaldehyde (3i):7 Yellow solid; m.p. 119-120 °C; H NMR
(CDCl3, 400 MHz): 10.01 (s, 1H), 9.47 (s, 1H), 7.78 (d, J = 8.0
Hz, 2H), 7.69 (d, J = 12.0 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.05
(d, J = 8.0 Hz, 2H), 3.88 (s, 3H), 2.44 (s, 3H); 13C NMR
25 (CDCl3,100 MHz): δ 180.7, 162.3, 159.4, 148.0, 134.5, 132.4, 80 the potential energy surface.
128.2, 126.5, 126.3, 117.7, 115.7, 56.7, 19.6; IR (CHCl3): max
2916, 1733, 1633, 1383, 1019 cm-1; ESI-MS: m/z; 267.00
Acknowledgements
[M+H]+; HR-ESIMS: m/z 267.1100 calcd for C16H14N2O2 + H+
Authors thanks analytical department IIIM for analytical support.
(267.1128).
The financial support for this work was received from CSIR 12th
FYP project (BSC-0205). JBB thanks CSIR Innovation center
85 project ITR-001 for project fellowship. SA thanks UGC for SRF.
30 2-(2-Nitrophenyl)imidazo[1,2-a]pyridine-3-carbaldehyde (3j):17
Pale yellow solid; m.p. 197-198 °C; 1H NMR (CDCl3, 400 MHz):
9.80 (s, 1H), 9.62 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H),
7.80 (dd, J = 8.0, 20 Hz, 2H), 7.71-7.60 (m, 3H), 7.19 (t, J = 8.0
Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 177.9, 154.3, 149.7,
35 148.2, 133.1, 132.7, 130.7, 130.6, 128.7, 127.3, 125.0, 121.4,
117.8, 115.9; IR (CHCl3): max 3436, 1643, 1533, 1494, 1323,
1117 cm-1; ESI-MS: m/z 267.90 [M+H]+; HR-ESIMS: m/z
268.0710 calcd for C14H9N3O3 + H+ (268.0717).
Notes and Reference
1. M. S. Butler, J. Nat. Prod., 2004, 67, 2141-2153.
2. For a review on the biological activities of imidazo[1,2-a]pyridines,
90
95
see: C. Enguehard-Gueiffier and A. Gueiffier, Mini-Rev. Med.
Chem., 2007, 7, 888-899.
3. (a) S. Z. Langer, S. Arbilla, J. Benavides and B. Scatton, Adv.
Biochem. Psychopharmacol, 1990, 46, 61-72; (b) T. Swainston
Harrison and G. M. Keating, CNS Drugs, 2005, 19, 65-89; (c) M.
Lancel and A. Steiger, Angew. Chem. Int. Ed., 1999, 38, 2852-
2864.
8-Methyl-2-(2-nitrophenyl)H-imidazo[1,2-a]pyridine-3-
40 carbaldehyde (3k): Brown solid; m.p. 142-143 °C; 1H NMR
(CDCl3, 400 MHz): 9.77 (s, 1H), 9.47 (d, J = 8.0 Hz, 1H), 8.11
(d, J = 8.0 Hz, 1H), 7.75 (t, J = 8.0 Hz, 1H), 7.67 (t, J = 8.0 Hz,
2H), 7.41 (d, J = 4.0 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 2.66 (s,
3H); 13C NMR (CDCl3,100 MHz): δ 177.0, 153.8, 150.1, 148.0,
45 133.2, 132.7, 132.6, 130.5, 129.7, 128.0, 126.3, 124.9, 115.8,
16.9; IR (CHCl3): max 3436, 2917, 1733, 1639, 1465, 1377,
1019 cm-1; ESI-MS: m/z 282.09 [M+H]+; HR-ESIMS: m/z
282.0900 calcd for C15H11N3O3+H+ (282.0873).
4. S. Boggs, V. I. Elitzin, K. Gudmundsson, M. T. Martin and M. J.
Sharp, Org. Process Res. Dev., 2009, 13, 781-785; K.
Gudmundsson and S. D. Boggs, Chemical compounds,
WO2006026703 A2 (2006), Smithkline Beecham Corp., USA.
5. (a) C. J. Chen, K. Bando, H. Ashino, K. Taguchi, H. Shiraishi, K.
Shima, O. Fujimoto, C. Kitamura, Y. Morimoto, H. Kasahara, T.
Minamizawa, C. Jiang, M. R. Zhang, T. Suhara, M. Higuchi, K.
Yamada and B. Ji, Neurosci. Lett., 2014, 581, 103-108; (b) C. J.
Chen, K. Bando, H. Ashino, K. Taguchi, H. Shiraishi, K. Shima, O.
Fujimoto, C. Kitamura, S. Matsushima, K. Uchida, Y. Nakahara, H.
Kasahara, T. Minamizawa, C. Jiang, M. R. Zhang, M. Ono, M.
Tokunaga, T. Suhara, M. Higuchi, K. Yamada and B. Ji, J. Nucl.
Med., 2015, 56, 120-126.
100
105
6-Methyl-2-(2-nitrophenyl)imidazo[1,2-a]pyridine-3-
50 carbaldehyde (3l): Yellow solid; m.p. 135-136 °C; 1H NMR
(CDCl3, 400 MHz) 9.76 (s, 1H), 9.43 (s, 1H), 8.10 (d, J = 8.0
Hz, 1H), 7.74 (t, J = 8.0 Hz, 1H), 7.69-7.64 (m, 3H), 7.48 (d, J =
8.0 Hz, 1H), 2.47 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 177.8,
154.2, 150.1, 146.7, 133.6, 133.1, 132.6, 130.5, 126,7, 126.2,
55 124.9, 121.1, 117.0, 18.4; IR (CHCl3): max 3435, 2918, 1731,
110 6. For reviews on the synthesis of imidazo[1,2-a]pyridines, see: (a) A.
K. Bagdi, S. Santra, K. Monira and A. Hajra, Chem. Commun.,
2015, 51, 1555-1575; (b) K. Pericherla, P. Kaswan, K. Pandey and
A. Kumar, Synthesis, 2015, 47, 887-912.
7. H. Wang, Y. Wang, D. Liang, L. Liu, J. Zhang and Q. Zhu, Angew.
115
Chem. Int. Ed., 2011, 50, 5678-5681.
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