Benzisoxazole

Benzisoxazole
Names
	Preferred IUPAC name 1,2-Benzoxazole
	Other names Benzo[d]isoxazole; Indoxazine
Identifiers
CAS Number	271-95-4 ;
3D model (JSmol)	Interactive image;
Beilstein Reference	2154
ChEBI	CHEBI:51554 ;
ChEMBL	ChEMBL314871 ;
ChemSpider	64227 ;
ECHA InfoCard	100.005.440
EC Number	205-983-1;
PubChem CID	71073;
UNII	D879RKM5NQ ;
CompTox Dashboard (EPA)	DTXSID20181567 ;
	InChI InChI=1S/C7H5NO/c1-2-4-7-6(3-1)5-8-9-7/h1-5H Key: KTZQTRPPVKQPFO-UHFFFAOYSA-N ; InChI=1/C7H5NO/c1-2-4-7-6(3-1)5-8-9-7/h1-5H Key: KTZQTRPPVKQPFO-UHFFFAOYAI;
	SMILES n2oc1ccccc1c2;
Properties
Chemical formula	C7H5NO
Molar mass	119.123 g·mol−1
Appearance	Colorless liquid
Density	1.18 g/cm3
Boiling point	35 to 38 °C (95 to 100 °F; 308 to 311 K) (at 2.67 hPa); 101-102 °C (at 2 kPa)
Hazards
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H315, H319, H335
Precautionary statements	P261, P264, P271, P280, P302 P352, P304 P340, P305 P351 P338, P312, P321, P332 P313, P337 P313, P362, P403 P233, P405, P501
Flash point	58 °C (136 °F; 331 K)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

1,2-Benzisoxazole is an aromatic organic compound with a molecular formula C₇H₅NO containing a benzene-fused isoxazole ring structure.^[1]^[2] 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;^[3] 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.^[4]

Synthesis of 1,2-Benzisoxazol aus Salicylaldehyd und HOSA

Reactions

Kemp elimination

First reported by Daniel S. Kemp,^[5]^[6]^[7] the relatively weak N-O bond can be cleaved by a strong base to yield a 2-hydroxybenzonitrile species.

References

^ Katritzky, A. R.; Pozharskii, A. F. (2000). Handbook of Heterocyclic Chemistry (2nd ed.). Academic Press. ISBN 0080429882.
^ Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. (2001). Organic Chemistry. Oxford, Oxfordshire: Oxford University Press. ISBN 0-19-850346-6.
^ Domene, Carmen; Jenneskens, Leonardus W.; Fowler, Patrick W. (2005). "Aromaticity of anthranil and its isomers, 1,2-benzisoxazole and benzoxazole". Tetrahedron Letters. 46 (23): 4077–4080. doi:10.1016/j.tetlet.2005.04.014. hdl:1874/14837. ISSN 0040-4039.4077-4080&rft.date=2005&rft_id=info:hdl/1874/14837&rft.issn=0040-4039&rft_id=info:doi/10.1016/j.tetlet.2005.04.014&rft.aulast=Domene&rft.aufirst=Carmen&rft.au=Jenneskens, Leonardus W.&rft.au=Fowler, Patrick W.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">
^ Kemp, D.S.; Woodward, R.B. (1965). "The N-ethylbenzisoxazolium cation—I". Tetrahedron. 21 (11): 3019–3035. doi:10.1016/S0040-4020(01)96921-2. ISSN 0040-4020.3019-3035&rft.date=1965&rft_id=info:doi/10.1016/S0040-4020(01)96921-2&rft.issn=0040-4020&rft.aulast=Kemp&rft.aufirst=D.S.&rft.au=Woodward, R.B.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">
^ Casey, Martha L.; Kemp, D. S.; Paul, Kenneth G.; Cox, Daniel D. (June 1973). "Physical organic chemistry of benzisoxazoles. I. Mechanism of the base-catalyzed decomposition of benzisoxazoles". The Journal of Organic Chemistry. 38 (13): 2294–2301. doi:10.1021/jo00953a006.2294-2301&rft.date=1973-06&rft_id=info:doi/10.1021/jo00953a006&rft.aulast=Casey&rft.aufirst=Martha L.&rft.au=Kemp, D. S.&rft.au=Paul, Kenneth G.&rft.au=Cox, Daniel D.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">
^ Kemp, D. S.; Cox, Daniel D.; Paul, Kenneth G. (December 1975). "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. 97 (25): 7312–7318. doi:10.1021/ja00858a018.7312-7318&rft.date=1975-12&rft_id=info:doi/10.1021/ja00858a018&rft.aulast=Kemp&rft.aufirst=D. S.&rft.au=Cox, Daniel D.&rft.au=Paul, Kenneth G.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">
^ Kemp, Daniel S. (April 1970). "Decarboxylation of benzisoxazole-3-carboxylic acids. Catalysis by extraction of possible relevance to the problem of enzymic mechanism". Journal of the American Chemical Society. 92 (8): 2553–2554. doi:10.1021/ja00711a061.2553-2554&rft.date=1970-04&rft_id=info:doi/10.1021/ja00711a061&rft.aulast=Kemp&rft.aufirst=Daniel S.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">

[Katritzky2nd-1] Katritzky, A. R.; Pozharskii, A. F. (2000). Handbook of Heterocyclic Chemistry (2nd ed.). Academic Press. ISBN 0080429882.

[Clayden1st-2] Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. (2001). Organic Chemistry. Oxford, Oxfordshire: Oxford University Press. ISBN 0-19-850346-6.

[DomeneJenneskens2005-3] Domene, Carmen; Jenneskens, Leonardus W.; Fowler, Patrick W. (2005). "Aromaticity of anthranil and its isomers, 1,2-benzisoxazole and benzoxazole". Tetrahedron Letters. 46 (23): 4077–4080. doi:10.1016/j.tetlet.2005.04.014. hdl:1874/14837. ISSN 0040-4039.4077-4080&rft.date=2005&rft_id=info:hdl/1874/14837&rft.issn=0040-4039&rft_id=info:doi/10.1016/j.tetlet.2005.04.014&rft.aulast=Domene&rft.aufirst=Carmen&rft.au=Jenneskens, Leonardus W.&rft.au=Fowler, Patrick W.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">

[KempWoodward1965-4] Kemp, D.S.; Woodward, R.B. (1965). "The N-ethylbenzisoxazolium cation—I". Tetrahedron. 21 (11): 3019–3035. doi:10.1016/S0040-4020(01)96921-2. ISSN 0040-4020.3019-3035&rft.date=1965&rft_id=info:doi/10.1016/S0040-4020(01)96921-2&rft.issn=0040-4020&rft.aulast=Kemp&rft.aufirst=D.S.&rft.au=Woodward, R.B.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">

[5] Casey, Martha L.; Kemp, D. S.; Paul, Kenneth G.; Cox, Daniel D. (June 1973). "Physical organic chemistry of benzisoxazoles. I. Mechanism of the base-catalyzed decomposition of benzisoxazoles". The Journal of Organic Chemistry. 38 (13): 2294–2301. doi:10.1021/jo00953a006.2294-2301&rft.date=1973-06&rft_id=info:doi/10.1021/jo00953a006&rft.aulast=Casey&rft.aufirst=Martha L.&rft.au=Kemp, D. S.&rft.au=Paul, Kenneth G.&rft.au=Cox, Daniel D.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">

[6] Kemp, D. S.; Cox, Daniel D.; Paul, Kenneth G. (December 1975). "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. 97 (25): 7312–7318. doi:10.1021/ja00858a018.7312-7318&rft.date=1975-12&rft_id=info:doi/10.1021/ja00858a018&rft.aulast=Kemp&rft.aufirst=D. S.&rft.au=Cox, Daniel D.&rft.au=Paul, Kenneth G.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">

[7] Kemp, Daniel S. (April 1970). "Decarboxylation of benzisoxazole-3-carboxylic acids. Catalysis by extraction of possible relevance to the problem of enzymic mechanism". Journal of the American Chemical Society. 92 (8): 2553–2554. doi:10.1021/ja00711a061.2553-2554&rft.date=1970-04&rft_id=info:doi/10.1021/ja00711a061&rft.aulast=Kemp&rft.aufirst=Daniel S.&rfr_id=info:sid/en.wikipedia.org:Benzisoxazole" class="Z3988">

[1]

[2]

[3]

[4]

[5]

[6]

[7]

Benzisoxazole

Contents

Synthesis

Reactions

Kemp elimination

See also

References