Syntheses of Formylpyrido[2,1-b]benzoxazoles
SCHEME 1. Meth-Cohn Quinoline Synthesis
of more modifiable, elaborate, and usefully functionalized
pyrido[2,1-b]benzoxazoles are strongly in demand.
On the other hand, the Vilsmeier reaction, one of the most
useful synthetic methods for the introduction of one or more
formyl groups into electron-rich aromatic and heteroaromatic
compounds since its discovery by Vilsmeier and Haack,4,5 has
also shown great usefulness in the construction of a large number
of heterocyclic systems,6 such as pyridines,7pyridones,7h,8
pyrroles,9 pyrans,10 pyrones,7c,11 pyrimidines,12 pyrazoles,13
oxazoles,13a,14 quinolines,15 and so on.16 Among them, the Meth-
Cohn quinoline synthesis, which involves the conversation of
acylanilides into 2-chloro-3-substituted quinolines by the action
of Vilsmeier reagent in hot POCl3 solution, is of particular
interest because of its ease of operation, wide general applicabil-
ity, and the great importance of the products.17 Notably, a large
range of acetanilides, both activated and unactivated, have been
explored under the original or modified reaction conditions,
giving cyclization products in moderate to good yields (Scheme
1).18
(4) For reviews, see: (a) Jones, G.; Stanforth, S. P. The Vilsmeier Reaction
of Fully Conjugated Carbocycles and Heterocycles. In Organic Reactions;
Paquette, L. A., Eds.; John Wiley: New York, 1997; Vol. 49, pp 1-330. (b)
Marson, C. M.; Giles, P. R. Synthesis using Vilsmeier Reagents; CRC Press:
Boca Raton, 1994; pp 1-247. (c) Marson, C. M. Tetrahedron 1992, 48, 3659–
3726. (d) Jutz, C. Iminium Salts in Organic Chemistry. In AdVances in Organic
Chemistry; Taylor, E. C., Ed.; John Wiley & Sons: New York, 1976; Vol. 9,
Part I, pp 225-342.
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When the substituted group R on acetanilide is o-hydroxy,
namely, the substrate is o-acetaminophenol (2a), the product
might be 2-chloro-8-hydroxyquinoline-3-carbaldehyde according
to Meth-Cohn’s procedure, but no one has put it into practice
up to now. A previous report by Chandramohan in 1972 revealed
that o-acetaminophenol reacted with Vilsmeier reagent in DMF
at 60 °C to give 2-(benzoxazol-2′-yl)-3-dimethylaminoacrolein
(4a).19 In connection with our interest in porphyrin-based red-
light emission materials,20 we attempted to prepare this fascinat-
ing 8-hydroxyquinolinecarbaldehyde via the Meth-Cohn method.
To our surprise, no desired 8-hydroxyquinolinecarbaldehyde was
detected, but an unexpected product 2-formylpyrido[2,1-b]ben-
zoxazole (5a) was obtained in addition to the known compound
4a (Scheme 2). During the course of elucidating the structure
of 5a, its isomer, 4-formylpyrido[2,1-b]benzoxazole (6a), was
also synthesized. Herein we present the results.
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