PAPER
Suzuki and Negishi Approaches to Pyridines and Pyrimidines
3505
13C NMR (50 MHz, CDCl3): d = 21.2, 37.4 (d, 3J = 3.2 Hz), 115.5
(d, 2J = 22.0 Hz), 121.6 (d, J = 1.6 Hz), 124.2 (d, 4J = 2.8 Hz), 126.8
1H NMR (200 MHz, CDCl3): d = 2.17 (s, 3 H, CH3) 2.47 (s, 6 H, 2
× SCH3), 4.06 (s, 4 H, 2 × CH2), 6.67 (s, 2 H, H-3py and H-5py), 7.19
2
3
3
(d, J = 15.8 Hz), 128.3 (d, J = 7.9 Hz), 131.6 (d, J = 4.7 Hz),
(br s, 8 H, Haryl).
148.4, 159.2, 161.2 (d, 1J = 243.8 Hz).
13C NMR (50 MHz, CDCl3): d = 16.3, 21.1, 44.1, 121.7, 127.2,
129.9, 136.1, 136.9, 148.3, 160.3.
MS (EI, 70 eV): m/z (%) = 289 (100), 308 (22), 309 (15), 212 (12),
294 (10), 198 (10), 109 (6), 185 (6).
HRMS: m/z [M + Na]+ calcd for C20H17F2N + Na: 332.1227; found:
MS (EI, 70 eV): m/z (%) = 365 (100), 364 (65), 350 (23), 137 (10),
240 (8), 194 (8), 121 (6), 302 (5).
332.1227.
HRMS: m/z [M + Na]+ calcd for C22H23NS2 + Na: 388.1170; found:
388.1177.
2,6-Bis(4-fluorobenzyl)-4-methylpyridine (4c)
Yield: 152 mg (79%); pale yellow solid; mp 71–73 °C.
2,6-Bis(2,5-dimethoxybenzyl)-4-methylpyridine (4h)
Yield: 110 mg (45%); pale brown oil.
1H NMR (200 MHz, CDCl3): d = 2.14 (s, 3 H, CH3), 3.71 and 3.76
(2 s, each 6 H, OCH3), 4.11 (s, 4 H, 2 × CH2), 6.66 (s, 2 H, H-3py
and H-5py), 6.76–6.90 (m, 6 H, Haryl).
13C NMR (50 MHz, CDCl3): d = 21.2, 38.5, 55.8, 56.3, 111.8, 112.0,
117.0, 121.4, 129.7, 130.3, 148.0, 151.7, 153.7, 160.0.
1H NMR (200 MHz, CDCl3): d = 2.19 (s, 3 H, CH3), 4.07 (s, 4 H, 2
× CH2), 6.70 (s, 2 H, H-3py and H-5py), 6.92–7.24 (m, 8 H, Haryl).
13C NMR (50 MHz, CDCl3): d = 21.1, 43.8, 115.4, (d, 2J = 21.7 Hz),
4
121.7, 130.7 (d, 3J = 7.6 Hz), 135.5 (d, J = 3.3 Hz), 148.4, 160.3,
161.7 (d, 1J = 243.8 Hz).
MS (EI, 70 eV): m/z (%) = 308 (100), 309 (38), 212 (22), 294 (20),
109 (17), 198 (11), 185 (7), 133 (5).
HRMS: m/z [M + Na]+ calcd for C20H17F2N + Na: 332.1227; found:
MS (EI, 70 eV): m/z (%) = 362 (100), 332 (11), 393 (7), 257 (5), 181
(7), 121 (5), 211 (4), 304 (4).
332.1222.
HRMS: m/z [M + Na]+ calcd for C24H27NO4 + Na: 416.1838; found:
416.1840.
2,6-Bis(2-methoxybenzyl)-4-methylpyridine(4d)
Yield: 150 mg (72%); pale yellow solid; mp 57–59 °C.
2,6-Bis(3,4,5-trimethoxybenzyl)-4-methylpyridine (4i)
Yield: 82 mg (29%); pale yellow solid; mp 122–124 °C.
1H NMR (200 MHz, CDCl3): d = 2.23 (s, 3 H, CH3), 3.81 (s, 12 H,
4 × OCH3 at C-3 and C-5), 3.82 (s, 6 H, 2 × OCH3 at C-4), 4.05 (s,
4 H, 2 × CH2), 6.50 (s, 4 H, Haryl), 6.77 (s, 2 H, H-3py and H-5py).
13C NMR (50 MHz, CDCl3): d = 21.3, 45.0, 56.3, 61.0, 106.3, 121.8,
135.5, 136.6, 148.4, 153.4, 160.3.
1H NMR (200 MHz, CDCl3): d = 2.13 (s, 3 H, CH3), 3.80 (s, 6 H, 2
× OCH3), 4.14 (s, 4 H, 2 × CH2), 6.63 (s, 2 H, H-3py and H-5py),
6.85–6.92 (m, 4 H, Haryl), 7.13–7.22 (m, 4 H, Haryl).
13C NMR (50 MHz, CDCl3): d = 21.2, 38.5, 55.6, 110.6, 120.7,
121.2, 127.7, 128.5, 131.0, 147.7, 157.6, 160.1.
MS (EI, 70 eV): m/z (%) = 302 (100), 303 (19), 270 (12), 91 (10),
332 (8), 286 (7), 121 (7), 181 (6).
HRMS: m/z [M + Na]+ calcd for C22H23NO2 + Na: 356.1627; found:
MS (EI, 70 eV): m/z (%) = 453 (100), 439 (71), 454 (31), 422 (8),
392 (6), 407 (6), 181 (5), 219 (5).
356.1628.
HRMS: m/z [M + Na]+ calcd for C26H31NO6 + Na: 476.2049; found:
476.2051.
2,6-Bis(3-methoxybenzyl)-4-methylpyridine (4e)
Yield: 162 mg (78%); yellow solid; mp 45–47 °C.
1H NMR (200 MHz, CDCl3): d = 2.17 (s, 3 H, CH3), 3.76 (s, 6 H, 2
× OCH3), 4.09 (s, 4 H, 2 × CH2), 6.72 (s, 2 H, H-3py and H-5py),
6.74–6.87 (m, 6 H, Haryl), 7.17–7.21 (m, 2 H, Haryl).
13C NMR (50 MHz, CDCl3): d = 21.0, 44.5, 55.1, 111.7, 114.8,
121.5, 121.6, 129.4, 141.3, 148.0, 159.7, 160.0.
Acknowledgment
We acknowledge the financial support from the Polish Ministry of
Science and Higher Education in the form of grant N N204 241834.
We also thank Mrs. Krystyna Wojtasiewicz for her valuable help in
the purification of several compounds.
MS (EI, 70 eV): m/z (%) = 332 (100), 333 (51), 302 (9), 318 (8), 274
(6), 168 (5), 121 (5), 183 (4).
HRMS: m/z [M + Na]+ calcd for C22H23NO2 + Na: 356.1627; found:
References
(1) (a) Joule, J. A.; Mills, K.; Smith, G. F. In Heterocyclic
Chemistry; Chapman & Hall: London, 1995. (b) Itami, K.;
Yamazaki, D.; Yoshida, J.-i. J. Am. Chem. Soc. 2004, 126,
15396. (c) Baldwin, B. C.; Corran, A. J.; Robson, M.
J. Pestic. Sci. 1995, 44, 81. (d) Wong, K.-T.; Hung, T. S.;
Wu, Ch. Ch.; Lee, G.-H.; Peng, S.-M.; Chou, Ch.-S.; Su, Y.
O. Org. Lett. 2002, 4, 513.
(2) (a) van der Ark, A. M.; Sinnema, A.; Theeuwen, A. B. E.;
van der Torn, J. M.; Verweij, A. M. A. Pharm. Weekbl.
1978, 113, 41. (b) van der Ark, A. M.; Sinnema, A.;
van der Torn, J. M.; Verweij, A. M. A. Pharm. Weekbl.
1978, 113, 341. (c) van der Ark, A. M.; Verweij, A. M. A.;
Sinnema, A. J. Forensic Sci. 1978, 23, 693.
(3) (a) Cloonan, S. M.; Keating, J. J.; Corrigan, D.; O’Brien, J.
E.; Kavanagh, P. V.; Wiliams, D. C.; Meegan, M. J. Bioorg.
Med. Chem. 2010, 18, 4009. (b) Bohn, M.; Bohn, G.;
Blaschke, G. Int. J. Leg. Med. 1993, 106, 19. (c) Błachut,
D.; Wojtasiewicz, K.; Czarnocki, Z. Forensic Sci. Int. 2005,
152, 157.
356.1630.
2,6-Bis(4-methoxybenzyl)-4-methylpyridine (4f)
Yield: 165 mg (80%); pale beige solid; mp 96–98 °C.
1H NMR (200 MHz, CDCl3): d = 2.15 (s, 3 H, CH3), 3.78 (s, 6 H, 2
× OCH3), 4.06 (s, 4 H, 2 × CH2), 6.67 (s, 2 H, H-3py and H-5py), 6.82,
6.86, 7.16, 7.21 (AA¢XX¢, 8 H).
13C NMR (50 MHz, CDCl3): d = 21.2, 43.8, 55.4, 114.1, 121.5,
130.3, 132.1, 148.1, 158.3, 160.8.
MS (EI, 70 eV): m/z (%) = 332 (100), 333 (88), 318 (79), 224 (19),
121 (18), 210 (8), 181 (7), 274 (7).
HRMS: m/z [M + Na]+ calcd for C22H23NO2 + Na: 356.1627; found:
356.1625.
2,6-Bis(4-methylthiobenzyl)-4-methylpyridine (4g)
Yield: 68 mg (30%); beige solid; mp 97–99 °C.
Synthesis 2011, No. 21, 3496–3506 © Thieme Stuttgart · New York