[288-42-6]  · C3H3NO  · Oxazole  · (MW 69.07)

(2-aza Diels-Alder diene,2 precursor to N-formylformamide3)

Physical Data: mp -87 to -84 °C; bp 69-70 °C; d 1.050 g cm-3; lmax 205 nm (ε 3900).

Form Supplied in: colorless oil.

Preparative Methods: two methods have been reported for the preparation of oxazole.4,5 The more recent approach entails three steps (eqs 1 and 2) and an overall yield of 39%.

General Discussion.

Oxazole functions as an azadiene in the Diels-Alder reaction.2 The resulting [4 + 2] product is normally not isolated, instead rearranging to pyridines (eq 3). High regioselectivity has been reported6 for this reaction (see also 4-Phenyloxazole). Oxazole can also perform as a dienophile, as in the reaction with tetrazines (eq 4).7

Treatment of oxazole with one equivalent of Ozone cleaves the C-C bond and yields N-formylformamide (4) (eq 5).3 Subsequent addition of primary or secondary amines gives high yields of formamides (eq 6). Formylation of alcohols is substantially slower.

Metalation at C-2 of oxazole is rapid with n-Butyllithium, and the metalated product is in equilibrium with the ring-opened isocyanide (eq 7). Highly reactive electrophiles yield products from the enolate form of (5) (eqs 8 and 9), while less reactive electrophiles react with the carbanion form (eqs 10 and 11).8

Palladium-catalyzed coupling of chloropyrazines with oxazole occurs at C-2, yielding the diaryl in good yield (eq 12).9

1. Turchi, I. J. In Oxazoles; Turchi, I. J., Ed. (The Chemistry of Heterocyclic Compounds; Weissberger, A.; Taylor, E. C., Eds.; Vol. 45); Wiley: New York, 1986; p 1.
2. Lakhan, R.; Ternai, B. Adv. Heterocycl. Chem. 1974, 17, 99.
3. Kashima, C.; Arao, H.; Hibi, S.; Omote, Y. TL 1989, 30, 1561.
4. Cornforth, J. W.; Cornforth, R. H. JCS 1947, 96.
5. Bredereck, H.; Bangert, R. CB 1964, 97, 1414.
6. Fr. Patent 1 550 352 (CA 1970, 72, 31 629c).
7. Seitz, G.; Mohr, R.; Hoferichter, R. CZ 1989, 113, 17.
8. Hodges, J. C.; Patt, W. C.; Connolly, C. J. JOC 1991, 56, 449.
9. Aoyagi, Y.; Inoue, A.; Koizumi, I.; Hashimoto, R.; Tokunaga, K.; Gohma, K.; Komatsu, J.; Sekine, K.; Miyafuji, A.; Kunoh, J.; Honma, R.; Akita, Y.; Ohta, A. H 1992, 33, 257.

Scott McN. Sieburth

State University of New York at Stony Brook, NY, USA

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