N. G. Kundu, G. Chaudhuri / Tetrahedron Letters 42 (2001) 2883–2886
2885
The mechanism of the reaction can be envisaged to
involve the following steps: (a) The conversion of 5
(through its copper-salt) to 6–13 through Sonogashira–
Hagihara coupling is well established;13 (b) a rearrange-
ment of 6–13 to allene intermediates (A) took place
involving alkyne–allene rearrangement in the propargyl
group attached to the nitrogen atom;14 (c) subsequent
nucleophilic attack by the amide nitrogen on the termi-
nal carbon (next to the N-atom) of the allenes would
result in the quinazolinones 14–21.
5. (a) Chowdhury, C.; Kundu, N. G. J. Chem. Soc., Chem.
Commun. 1996, 1067–1068; (b) Chowdhury, C.; Chaud-
huri, G.; Guha, S.; Mukherjee, A. K.; Kundu, N. G. J.
Org. Chem. 1998, 63, 1863–1871.
6. (a) Khan, M. W.; Kundu, N. G. Synlett 1997, 1435–1437;
(b) Kundu, N. G.; Khan, M. W. Tetrahedron Lett. 1997,
38, 6937–6940; (c) Kundu, N. G.; Khan, M. W.; Mukho-
padhyay, R. Tetrahedron 1999, 55, 12361–12376; (d)
Kundu, N. G.; Khan, M. W. Tetrahedron 2000, 56,
4777–4792.
7. Chaudhuri, G.; Chowdhury, C.; Kundu, N. G. Synlett
1998, 1273–1275.
8. De, M.; Majumder, D. P.; Kundu, N. G. J. Indian Chem.
Soc. 1999, 76, 665–674.
9. Chaudhuri, G.; Kundu, N. G. J. Chem. Soc., Perkin
Trans. 1 2000, 775–779.
10. Both bis(triphenylphosphine)palladium(II) chloride and
CuI were found to be essential for the C-arylation
reaction.
11. 20 mol% of CuI was found to be the optimum needed for
the cyclisation reaction.
Thus, we have described a very interesting and useful
procedure for the conversion of a substituted terminal
alkyne through palladium-catalysed reactions and sub-
sequent copper-catalysed cyclisation to quinazoline
derivatives. The method is very mild, requires inexpen-
sive starting materials and reagents and is very easy to
operate. We believe this is the first reported synthesis of
quinazolines through copper-catalysed cyclisation.
Since quinazolines are of wide natural occurrence15 and
of great biological importance,16 our method will con-
stitute a general and important method for the synthe-
sis of substituted quinazoline derivatives.
12. Typical 1H NMR data for compound 15 (300 MHz,
CDCl3, TMS): 2.35 (3H, s, ArCH3), 2.94 (3H, s, -NCH3),
5.13 (1H, d, J=7.8 Hz, N2CH), 6.18 (1H, dd, J1=7.8 Hz,
J2=15.6 Hz, -CHꢀCAr), 6.57 (1H, d, J=15.6 Hz,
ꢀCHAr), 6.67 (1H, d, J=8.1 Hz, ArH), 6.89–6.93 (3H, m,
ArH), 7.15–7.28 (5H, m, ArH), 7.40–7.43 (1H, m, ArH),
8.05 (1H, dd, J1=1.8 Hz, J2=7.8 Hz, ArH). 13C NMR
(75 MHz CDCl3, TMS): l 21.52, 36.06, 81.52, 112.91,
117.62, 119.19, 122.56, 125.78, 127.22, 127.56, 127.63,
127.90, 129.77, 130.26, 134.43, 137.42, 138.52, 140.71,
147.23, 162.63. DEPT (75 MHz, CDCl3, TMS): l 21.23,
35.77, 81.23, 112.62, 118.90, 122.27, 125.49, 126.93,
127.27, 127.35, 127.62, 129.48, 129.97, 134.14. IR (KBr):
wmax 1647, 1632, 1605 cm−1. Calcd for C22H20N2OS: C,
73.30; H, 5.59; N, 7.77%. Found: C, 73.16; H, 5.68; N,
7.97%.
References
13. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 4467–4469.
1. Some selected references: Hegedus, L. S. Angew. Chem.,
Int. Ed. Engl. 1988, 27, 1113–1126; Andersson, P. G.;
Backvall, J. E. J. Am. Chem. Soc. 1992, 114, 8696–8698;
Larock, R. C., Berrios-Pena, N. G.; Fried, C. A.; Yum,
E. K.; Tu, C.; Leong, W. J. Org. Chem. 1993, 58,
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S.-Y.; Liu, F. Chem. Rev. 1996, 96, 365–393; Bouyssi, D.;
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Chem. Soc., Perkin Trans. 1 1999, 529–534; Larock, R. C.
J. Organomet. Chem. 1999, 576, 111–124.
2. (a) Kundu, N. G.; Pal, M.; Mahanty, J. S.; Dasgupta, S.
K. J. Chem. Soc., Chem. Commun. 1992, 41–42; (b)
Kundu, N. G.; Pal, M.; Mahanty, J. S.; De, M. J. Chem.
Soc., Perkin Trans. 1 1997, 2815–2820.
3. (a) Kundu, N. G.; Pal, M. J. Chem. Soc., Chem. Com-
mun. 1993, 86–88; (b) Kundu, N. G.; Pal, M.; Nandi, B.
J. Chem. Soc., Perkin Trans. 1 1998, 561–568.
14. (a) Theron, F.; Verry, M.; Vessiere, R, Rearrangements
Involving Acetylenes in the Chemistry of the Carbon–Car-
bon Triple Bond; Patai, S., Ed., J. Wiley and Sons:
Chichester, 1978; Part I, Chapter 10, pp. 381–445; (b)
Recently we observed that 3-(2-aminophenylthio)prop-1-
yne was converted to 2-substituted benzothiazolines
through palladium–copper catalysis involving similar
copper-catalysed alkyne–allene rearrangement in
a
propargyl group attached to the sulphur atom, Nandi, B.;
Kundu, N. G. Org. Lett. 2000, 2, 235–238.
15. Quinazolines of natural occurrence: for general reference,
see: Brown, D. J. In Pyrimidines and their Benzoderiva-
tives; The Quinazoline Alkaloids in Comprehensive Hete-
rocyclic Chemistry; Katritzky, A. R.; Rees, C. W., Eds.,
Pergamon Press: Oxford, 1984; Vol. 3, pp. 148–150;
Brown, D. J. The Chemistry of Heterocyclic Compounds,
Quinazolines, Supplement I, Wiley: New York, 1996.
16. (a) Quinazolines as tyrosine kinase inhibitors: Rewcastle,
G. W.; Denny, W. A.; Bridges, A. J.; Zhou, H.; Cody, D.
R.; McMichael, A.; Fry, D. W. J. Med. Chem. 1995, 38,
3482–3487; Bridges, A. J.; Zhou, H.; Cody, D. R.; Rew-
castle, G. W.; McMichael, A.; Showalter, H. D. H.; Fry,
D. W.; Kraker, A. J.; Denny, W. A. J. Med. Chem. 1996,
4. (a) Kundu, N. G.; Mahanty, J. S.; Das, P.; Das, B.
Tetrahedron Lett. 1993, 34, 1625–1628; (b) Mahanty, J.
S.; De, M.; Das, P.; Kundu, N. G. Tetrahedron 1997, 53,
13397–13418.