Intramolecular Nitrilimine
Cycloadditions leading to the Pyrazolo[1,5-a][6,1]benzoxazonine
and
Pyrazolo[1,5-a][7,1]benzoxazecine Skeletons
Dipartimento di Chimica
Organica e Industriale dell'Università, via Golgi 19, 20133 Milano,
Italy
Fax ++39-2-2364369
Intramolecular 1,3-dipolar cycloadditions represent a valuable
tool in the synthesis of a large variety of heterocyclic systems containing
a five- membered heterocycle fused or bridged to another hetero- or carbo-cyclic
ring.1 However, despite to the usefulness
of this methodology, the examples in which is implied the formation of
a medium-sized ring are still rare.2,3
A fruitful approach to the hitherto unreported pyrazolo[1,5-a][6,1]benzoxazonine
and pyrazolo[1,5-a] [7,1]benzoxazecine skeletons is here reported,
based on the intramolecular cycloaddition of properly chosen nitrilimines.
The hydrazonyl chlorides 2, which we have devised as the precursors
for the in situ generation of the nitrilimines 3, were obtained
starting from isatoic anhydride and the appropriate alkynols (see Scheme).
The treatment of 2 with an excess of silver carbonate in refluxing
acetonitrile gave the desired cycloadducts in good yields (see Table).
It is to be added that, under the experimental conditions described above,
the nitrilimines 3 underwent, as a side reaction, the 1,3-dipolar
cycloaddition onto the solvent to give the triazole derivatives 5.
In wiew of the well-known factors working against
the formation of large-ring system,4 the
observed yields of cyclization can be considered worthy of noting.
Table. Treatment of Hydrazonyl Chlorides 2 with silver carbonate in refluxing acetonitrile.
| Entry | Time (h) |
Products | Yield* (%) |
Mp (°C) |
IR (nujol) (cm-1) |
1H-NMR J (Hz) |
| a | 7 | 4a
5a |
41
15 |
148
171 |
1730, 1720
1730, 1710 |
2.30-2.55 (4H, m), 3.94 (3H, s), 4.95 (2H, br t), 6.69 (1H, s), 7.38-7.86
(4H, m) 1.70-1.85 (2H, m), 1.92 (1H, t, J 2.4), 2.18 (2H, dt, J 6.5, 2.4), 2.32 (3H, s), 3.94 (3H, s), 4.18 (2H, t, J 6.5), 7.32-8.21 (4H, m) |
| b | 3 | 4b
5b |
60
15 |
110
146 |
1740, 1720
1730, 1710 |
1.70-3.00 (6H, m), 3.92 (3H, s), 4.74-4.98 (2H, m), 6.74 (1H, s), 7.40-8.30
(4H, m) 1.55-1.90 (4H, m), 1.95 (1H, t, J 2.5), 2.15 (2H, dt, J 6.2, 2.5), 2.31 (3 H, s), 3.92 (3H, s), 4.11 (2H, t, J 6.0), 7.20-8.20 (4H, m) |
* Afetr chromatographic separation with dichloromethane-ethyl acetate (3:1) as eluent.
References
1. A. Padwa, "1,3-Dipolar Cycloaddition Chemistry",
Vol. II, p. 277-406, A. Padwa Ed.; Wiley-Interscience, New York, 1984.
2. G. Broggini, L. Garanti, G. Molteni, G. Zecchi, J. Chem. Res.
1995, 385 (S), 2389 (M).
3. G. Broggini, L. Garanti, G. Molteni, G. Zecchi, Org. Prep. and Proc.
Int. 1996, 28, 699.
4. M. A. Winnick, Chem. Rev. 1981, 81, 491.
Comments
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