Benzisoxazole Explained

Benzisoxazole should not be confused with 2,1-Benzisoxazole.

1,2-Benzisoxazole is an aromatic organic compound with a molecular formula C₇H₅NO containing a benzene-fused isoxazole ring structure.^[1] The compound itself has no common applications; however, functionalized benzisoxazoles and benzisoxazoyls have a variety of uses, including pharmaceutical drugs such as some antipsychotics (including risperidone, paliperidone, ocaperidone, and iloperidone) and the anticonvulsant zonisamide.

Its aromaticity makes it relatively stable;^[2] however, it is only weakly basic.

Synthesis

Benzisoxazole may be prepared from inexpensive salicylaldehyde, via a base catalyzed room temperature reaction with hydroxylamine-O-sulfonic acid.^[3]

Reactions

Kemp elimination

First reported by Daniel S. Kemp,^{[4] [5] [6]} the relatively weak N-O bond can be cleaved by a strong base to yield a 2-hydroxybenzonitrile species.

See also

Structural isomers

• Benzoxazole
• Anthranil

Notes and References

1. Book: Clayden, J. . Greeves . N. . Warren . S. . Wothers . P. . Organic Chemistry . Oxford University Press . Oxford, Oxfordshire . 2001 . 0-19-850346-6 . registration .
2. Domene. Carmen. Jenneskens. Leonardus W.. Fowler. Patrick W.. Aromaticity of anthranil and its isomers, 1,2-benzisoxazole and benzoxazole. Tetrahedron Letters. 46. 23. 2005. 4077–4080. 0040-4039. 10.1016/j.tetlet.2005.04.014. 1874/14837. free.
3. Kemp. D.S.. Woodward. R.B.. The N-ethylbenzisoxazolium cation—I. Tetrahedron. 21. 11. 1965. 3019–3035. 0040-4020. 10.1016/S0040-4020(01)96921-2.
4. Casey . Martha L. . Kemp . D. S. . Paul . Kenneth G. . Cox . Daniel D. . Physical organic chemistry of benzisoxazoles. I. Mechanism of the base-catalyzed decomposition of benzisoxazoles . The Journal of Organic Chemistry . June 1973 . 38 . 13 . 2294–2301 . 10.1021/jo00953a006.
5. Kemp . D. S. . Cox . Daniel D. . Paul . Kenneth G. . Physical organic chemistry of benzisoxazoles. IV. Origins and catalytic nature of the solvent rate acceleration for the decarboxylation of 3-carboxybenzisoxazoles . Journal of the American Chemical Society . December 1975 . 97 . 25 . 7312–7318 . 10.1021/ja00858a018.
6. Kemp . Daniel S. . Decarboxylation of benzisoxazole-3-carboxylic acids. Catalysis by extraction of possible relevance to the problem of enzymic mechanism . Journal of the American Chemical Society . April 1970 . 92 . 8 . 2553–2554 . 10.1021/ja00711a061.