PDF《Pure & Appl. Chem., Vol. 69, No. 3》

Pure &

Appl.

Chem.,Vol. 69, No. 3, pp. 559-564, 1997. Printed in Great Britain. (B

1997 IUPAC Synthesis of heterocyclic compounds via vicarious nucleophilic substitution of hydrogen MieczyslawMqkosza Institute of Organic Chemistry, PolishAcademy of Sciences ul. Kasprzaka44, 01-224 Warsaw, Poland Abstract: Possibilities of synthesisof a variety of nitrogen heterocycles via intramolecularVNS reaction in nitroarenesand via transformationsof pro- ducts of the VNS reaction are presented. Vicarious Nucleophilic Substitution of Hydrogen, VNS is presently a well established methodology for direct introduction of functionalized alkyl substituents into electrophilic arenes, mainly nitroarenes(1) The reaction is a general process applicable also to nitro-derivatives of aromatic heterocycles, heterocycles which are electrophilic due to the electronic configuration (2) and even electrophilic alkenes (3). The VNS can serve also as an efficient methodof introduction of hydroxy and amino groups into electrophilicarenes via the reactionwith alkylhydroperoxides(4) and aminotriazoles and sulfenamides(5). The VNS reactioncan serve therefore as a versatile tool for functionalization and transformationof heterocycliccompounds(2). This methodof direct introductionof functionalizedalkyl substituents into nitroaromaticrings, particularlyortho to the nitro group, provides broad possibilitiesin synthesis of heterocyclicrings via interactionof the introduced substituentswith the nitro group as such or upon its reduction. Potentialfor controllingthe orientationof VNS (6) enhances attractivenessof this approach. Inthis paper, the rich possibilities of synthesis of a variety of heterocyclic ring systems via the VNS reaction will be presented, without discussing introduction of substituents into electrophilic heterocycles. lndoles belong to the most important heterocyclesbecausethe indole ring is present in numerous alkaloids and pharmaceuticals. There are many general and specific methods of indole ring synthesis. VNS offers some new possibilities and can provide readily available key starting materialsfor known methods. The intramolecular VNS reaction of m-nitrochloroacetanilides yields directly substituted nitrooxindoles(7).

559 560 M. MAKOSZA It should be stressedthat such nitrooxindolesare not readily available by other methods because nitrationof oxindoles gives different isomerswhereas the intramolecular Friedel-Craftsapproach is not applicable. Direct synthesis of substituted nitroindoles via the VNS reaction in rn-isocyanonitro ben- zenes preparedfrom readily available rn-nitroanilinesrepresents great practical value (8). Y The products of VNS are formed as nitrobenzylic carbanions, which cyclize rapidly via intramolecular nucleophilic addition to the isocyano group. Thus, the conversion of the isocyanonitrobenzenesto nitroindoles is practicallya one pot reaction. Productsof the VNS reaction:o-nitrobenzylaryl sulfones, o-nitroarylacetonitriles etc. can be converted into indoles ina variety of ways. Alkylation of the methylenegroups in the nitrileswith allylichalides producesthe corresponding ally1derivatives,which, when treatedwith triethylamine and trimethylchlorosilane, cyclize to give substituted 1-hydroxy-2-vinyl indoles (9). 2-(o-Nitroaryl)crotonitriles,available via the Knoevenagelcondensationof o-nitroarylacetonitriles with aliphatic aldehydes, cyclizeto give indolesand quinolines under various basic conditions. In the presence of potassium carbonate in methanol 1-hydroxy-2-hydroxymethylindoles can be obtainedas the main products(10). + CH,-C,