An improved procedure for the regiospecific synthesis of electron deficient 4- and 6-substituted isatins

Tetrahedron Letters

Volumn 39, Issue 42, 1998, Pages 7679-7682

  Kraynack, Erica A ^a,b   Dalgard, Jackline E ^a,b   Gaeta, Federico C A ^a  

^a GERON CORPORATION   (United States)

^b Axys Pharmaceuticals Inc   (United States)

Author keywords

Annulation; Nitro compounds; Nitrogen heterocycles; Regiospecificity

Indexed keywords

HETEROCYCLIC NITRO COMPOUND; ISATIN DERIVATIVE; NITROBENZENE DERIVATIVE;

ARTICLE; CHEMICAL REACTION; HALOGENATION; STEREOISOMERISM; STEREOSPECIFICITY; SYNTHESIS;

EID: 0032532225     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01719-5     Document Type: Article

References (16)

1. [1] As intermediates, use of Sandmeyer procedure: Carling, R. W.; Leeson, P. D.; Moore, K. W.; Moyes, C. R.; Duncton, M.; Hudson, M. L.; Baker, R.; Foster, A. C.; Grimwood, S.; Kemp, J. A.; Marshall, G. R.; Tricklebank, M. D.; Saywell, K. L. J. Med. Chem. 1997, 40, 754-765.
2. [2] As drug candidates: Webber, S. E.; Tikhe, J.; Worland, S. T.; Fuhrman, S. A.; Hendrickson, T. F.; Matthews, D. A.; Love, R. A.; Patick, A. K.; Meador, J. W. J. Med. Chem. 1996, 39, 5072-5082.
3. [3] More examples of Sandmeyer procedure: Popp, F. D. in Advances in Heterocyclic Chemistry A. R. Katritzky and A. J. Boulton (eds.), Academic Press: New York, 1975; Vol. 18, pp. 2-58 and references cited therein.
4. [4] Example of Friedel-Crafts acylation: Welstead, W. J., Jr.; Moran, H. W.; Stauffer, H. F.; Turnbull, L. B.; Sancilio, L. F. J. Med. Chem. 1979, 22, 1074-1078.
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6. [6] Non-electrophilic annulation: Meth-Cohn, O.; Goon, S. Tetrahedron Lett. 1996, 37, 9381-9384.
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12. [12] Halonitrobenzenes 1a-b and 1d were purchased from Aldrich Chemical Co. white compound 1 c was purchased from Lancaster Synthesis. The 4-chloro-3-nitrobenzophenone starting materials (compounds 1e-g) required for the synthesis of the substituted 6-benzoylisatins (compounds 5e-g) were made through the Friedel-Crafts acylation of toluene, chlorobenzene and anisole, respectively, by 4-chloro-3-nitrobenzoyl chloride. See Raeymaekers, A. H. M.; Van Gelder, J. L. H.; Roevens, L. F. C.; Janssen, P. A. J. Arzneim. Forsch. 1978, 28, 586-594.
13. 1H NMR spectroscopy and HPLC-MS only.
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16. 1H NMR spectra of these compounds with those of other 5,6-disubstituted oxindoles revealed that the aromatic ring had been substituted at the 5-position. Mass spectral analysis demonstrated that bromination had ensued.