PAPER
Alternative Synthesis of 2-Alkylidene-3,4-dihydro-2H-1,4-benzoxazines
131
13C NMR (150.81 MHz, CDCl3): d = 48.4 (t), 54.7 (t), 88.8 (t),
113.8 (d), 115.8 (d), 119.6 (d), 122.0 (d), 127.3 (d), 127.6 (d), 127.6
(d), 128.6 (d), 128.6 (d), 135.7 (s), 137.2 (s), 143.7 (s), 152.0 (s).
1H NMR (599 MHz, CDCl3): d = 5.79 (s, 1 H), 7.05 (dd, J = 8.0, 1.1
Hz, 1 H), 7.03–7.15 (m, 1 H), 7.22 (td, J = 7.7, 1.3 Hz, 1 H), 7.26–
7.33 (m, 1 H), 7.38 (dd, J = 7.6, 1.3 Hz, 1 H), 7.41 (t, J = 7.7 Hz, 2
H), 7.77 (d, J = 7.6 Hz, 2 H), 7.81 (s, 1 H).
13C NMR (150.81 MHz, CDCl3): d = 112.5 (d), 115.3 (d), 123.9 (d),
127.8 (d), 128.1 (d), 128.5 (d), 128.5 (d), 129.0 (d), 129.0 (d), 129.5
(d), 132.5 (s), 134.0 (s), 143.4 (s), 145.5 (s), 154.5 (s).
HPLC-MS (ESI): m/z = 238.29 [MH+].
Anal. Calcd for C16H15NO: C, 80.98; H, 6.37; N, 5.90. Found: C,
81.15; H, 6.16; N, 5.73.
These data are consistent with the partially reported literature
values.3a
HPLC-MS (ESI): m/z = 222.25 [MH+].
HRMS (EI): m/z calcd for C15H11NO: C, 81.43; H, 5.01; N, 6.33.
[(2Z)-2-Ethylidene-2,3-dihydro-4H-1,4-benzoxazin-4-yl](phe-
nyl)methanone [(Z)-2f]
Found: C, 81.67; H, 4.84; N, 6.27.
Yield: 51%; white solid; mp 129–131 °C (i-Pr2O).
IR (Nujol): 1705 cm–1.
Acknowledgment
The authors thank the Ministero dell’Università e della Ricerca for
financial support (PRIN 2008KRBX3B) and for the award of a
Ph.D. fellowship to M.R. (Progetto Giovani 2006), and Stefano
Provera for spectroscopic characterization of the compounds and
valuable discussion.
1H NMR (599 MHz, CDCl3): d = 1.78 (d, J = 6.9 Hz, 3 H), 4.38 (br
s, 2 H), 4.63–4.79 (m, 1 H), 6.70 (br s, 1 H), 6.70 (br s, 1 H), 7.01–
7.14 (m, 1 H), 7.03–7.18 (m, 1 H), 7.29–7.40 (m, 2 H), 7.42–7.47
(m, 1 H), 7.48–7.55 (d, J = 6.9 Hz, 2 H).
13C NMR (150.81 MHz, CDCl3): d = 9.3 (q), 44.7 (t), 101.7 (d),
116.9 (d), 120.8 (d), 124.3 (d), 125.8 (d), 127.2 (s), 128.2 (d), 128.2
(d), 128.6 (d), 128.6 (d), 130.7 (d), 134.7 (s), 144.5 (s), 145.5 (s),
168.3 (s).
References
(1) (a) Hietala, P. K.; Virtanen, A. I. Acta Chem. Scand. 1960,
14, 502. (b) Nagao, T.; Otsuka, H.; Kohda, H.; Sato, T.;
Yamasaki, K. Phytochemistry 1985, 24, 2959. (c) Otsuka,
H.; Hirai, Y.; Nagao, T.; Yamasaki, K. J. Nat. Prod. 1988,
51, 74. (d) Neimeyer, H. M. Phytochemistry 1988, 27,
3349. (e) Lyans, P. C.; Hipskind, H. D.; Wood, K. V.;
Nicholson, R. L. J. Agric. Food Chem. 1988, 36, 57.
(f) Hartenstein, H.; Sicker, D. Phytochemistry 1994, 827.
(g) Fukuyama, Y.; Hasegawa, T.; Toda, M.; Kodama, M.;
Okazaki, H. Chem. Pharm. Bull. 1992, 40, 252. (h) Achari,
B.; Mandal, S. B.; Dutta, P. K.; Chowdhury, C. Synlett 2004,
2449.
(2) (a) Fukuda, T.; Setoguchi, M.; Inaba, K.; Shoji, H.; Tahara,
T. Eur. J. Pharmacol. 1991, 196, 299. (b) Hosoe, K.;
Hidaka, T. Antimicrob. Agents Chemother. 1995, 39, 2295.
(3) (a) Yamamoto, M. J. Chem. Soc., Perkin Trans. 1 1979,
3161. (b) Kundu, N. G.; Chaudhuri, G.; Upadhyay, A.
J. Org. Chem. 2001, 66, 20. (c) Gabriele, B.; Salerno, G.;
Veltri, L.; Mancuso, R.; Li, Z.; Crispini, A.; Bellusci, A.
J. Org. Chem. 2006, 71, 7895.
HPLC-MS (ESI): m/z = 266.30 [MH+].
Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C,
76.91; H, 5.91; N, 5.05.
[(2E)-2-Ethylidene-2,3-dihydro-4H-1,4-benzoxazin-4-yl](phe-
nyl)methanone [(E)-2f]
Yield: 32%; white solid; mp 116–117 °C (i-Pr2O).
IR (Nujol): 1730 cm–1.
1H NMR (599 MHz, CDCl3): d = 2.02 (br s, 3 H), 4.44–4.56 (m, 2
H), 4.78 (br s, 1 H), 6.68 (br s, 1 H), 6.80 (br s, 1 H), 7.04–7.12 (m,
2 H), 7.16–7.22 (m, 2 H), 7.24–7.29 (m, 1 H), 7.33 (d, J = 7.2 Hz, 2
H).
13C NMR (150.81 MHz, CDCl3): d = 22.2 (q), 44.4 (t), 100.4 (d),
121.2 (d), 124.4 (d), 127.7 (d), 127.7 (d), 128.1 (d), 128.1 (d), 128.2
(d), 129.1 (d), 129.8 (d), 135.4 (s), 135.5 (s), 151.0 (s), 152.9 (s),
169.7 (s).
HPLC-MS (ESI): m/z = 266.30 [MH+].
(4) For some recent examples of heterocyclic synthesis by
different transition metal-catalyzed reactions of alkynes,
see: (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Perboni, A.;
Sferrazza, A.; Stabile, P. Org. Lett. 2010, 12, 3279.
(b) Laroche, C.; Kerwin, S. M. J. Org. Chem. 2009, 74,
9229. (c) Füger, B.; Bolm, C. Synlett 2009, 1601.
(d) Arcadi, A.; Alfonsi, M.; Chiarini, M.; Marinelli, F.
J. Organomet. Chem. 2009, 694, 576. (e) Facoetti, D.;
Abbiati, G.; D’Avolio, L.; Ackermann, L.; Rossi, E. Synlett
2009, 2273. (f) Beccalli, E. M.; Borsini, E.; Broggini, G.;
Palmisano, G.; Sottocornola, S. J. Org. Chem. 2008, 73,
4746. (g) Conreaux, D.; Belot, S.; Desbordes, P.; Monteiro,
N.; Balme, G. J. Org. Chem. 2008, 73, 8619. (h) Bhunia,
S.; Wang, K.-C.; Liu, R.-S. Angew. Chem. Int. Ed. 2008, 47,
4851. (i) Tsukamoto, H.; Kondo, Y. Angew. Chem. Int. Ed.
2008, 47, 4851. (j) Gabriele, B.; Mancuso, R.; Salerno, G.;
Plastina, P. J. Org. Chem. 2008, 73, 756. (k) Jung, H. H.;
Floreancig, P. E. J. Org. Chem. 2007, 72, 7359. (l) Kimura,
M.; Ezoe, A.; Mori, M.; Tamaru, Y. J. Am. Chem. Soc. 2005,
127, 201.
Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C,
77.14; H, 5.51; N, 5.39.
(2Z)-2-Benzylidene-4-[(4-methylphenyl)sulfonyl]-3,4-dihydro-
2H-1,4-benzoxazine [(Z)-2g]
Yield: 36%; white solid; mp 144–145 °C (i-Pr2O).
1H NMR (599 MHz, CDCl3): d = 2.02 (s, 3 H), 4.33 (s, 2 H), 5.18
(s, 1 H), 6.89 (d, J = 7.9 Hz, 2 H), 7.02 (d, J = 7.9 Hz, 1 H), 7.11 (t,
J = 7.7 Hz, 1 H), 7.12–7.21 (m, 1 H), 7.24–7.34 (s, 7 H), 7.76 (dd,
J = 7.9, 0.9 Hz, 1 H).
13C NMR (150.81 MHz, CDCl3): d = 21.1 (q), 47.7 (t), 107.8 (d),
116.8 (d), 122.4 (d), 124.9 (s), 126.5 (d), 127.4 (d), 127.4 (d), 127.5
(d), 127.9 (d), 128.0 (d), 128.2 (d), 128.5 (d), 128.5 (d), 129.2 (d),
129.2 (d), 133.7 (s), 133.9 (s), 141.0 (s), 144.3 (s), 147.2 (s).
HPLC-MS (ESI): m/z = 378.45 [MH+].
Anal. Calcd for C22H19NO3S: C, 70.01; H, 5.07; N, 3.71. Found: C,
70.11; H, 5.11; N, 3.63.
(2Z)-2-Benzylidene-2H-1,4-benzoxazine [(Z)-4]
Yield: 7%; white solid; mp 112–113 °C (i-Pr2O).
Synthesis 2011, No. 1, 127–132 © Thieme Stuttgart · New York