Pergamon Tetrahedron Letters 41 (2000) 1845–1847 TETRAHEDRON LETTERS A novel one-pot synthesis of isomeric naphtho[1,2-d]isoxazole 2-oxide and naphtho[1,8-de][1,2]oxazine ring systems. A case of simultaneous o- and peri-cyclisation in naphthalene Paraskevi Supsana, a Petros G. Tsoungas b and George Varvounis a,* a Department of Chemistry, University of Ioannina, 451 10, Ioannina, Greece b Department of Research and Technology, Ministry of Development, Messogeion Ave. 14-18, 115 10 Athens, Greece Received 25 October 1999; revised 7 December 1999; accepted 23 December 1999 Abstract 2-Hydroxy-1-naphthaldehyde oxime 1 undergoes a one-pot o- and peri-oxidative cyclisation with lead(IV) acetate to give the isomeric naphtho[1,2-d]isoxazole 2-oxide 2 and naphtho[1,8-de][1,2]oxazine 3. A common o- nitroso quinonemethide intermediate is invoked for both isomers. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: naphthalenes; oximes; lead and compounds; oxidation; N-oxides; hydroxylation. Isoxazoles and their benzo derivatives have numerous applications in medicine and agriculture. 1 1,2-Oxazine derivatives on the other hand are mainly used as intermediates in organic synthesis. 2 Oxidative cyclisation of suitably o-disubstituted aromatics with lead(IV) acetate (LTA) is a particularly effective route to a variety of nitrogen heterocycles. 3 This approach has been applied to the synthesis of 1,2-benzisoxazole 2-oxides. 4 To date, no oxidative reaction has been used in the preparation of 1,2- oxazines. In particular, peri-annelated naphtho-1,2-oxazines are synthesised by peri-cyclisation of 8- acyl-1-naphthols. 5 A recent review covers the synthesis of peri-naphthalene heterocycles. 6 During our studies on heterocyclic mesomeric betaines we have observed that reaction of 1 with LTA affords a mixture of the isomers 2 and 3 (Scheme 1). 7a After separation by column chromatography the products were obtained in 35 and 42% yield, respectively. Evidently this reaction provides easy access to two diverse isomeric ring systems. Confirmation of the structure of 3 was provided by ring opening to 2,8-dihydroxy-1-naphthonitrile 4 7b followed by methylation to 2,8-dimethoxy-1-naphthonitrile 5. The latter has been prepared independently from 2,8-dihydroxy-1-naphthaldehyde. 8 Compounds 2–4 9 were characterised by satisfactory elemental analyses, and from their mass, 13 C and 1 H NMR spectra. In Criegee’s 10 work on the oxidation of hydroxy compounds by LTA, it was proposed that an organolead intermediate is formed via either a cyclic or an acyclic transition state. It is, therefore, * Corresponding author. Tel: +30 651 98 382; fax: +30 651 45 840; e-mail: gvarvoun@cc.uoi.gr (G. Varvounis) 0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(00)00029-0 tetl 16309