Simple and Efficient Microwave Assisted N-Alkylation of Isatin 英文参考文献.docVIP

Molecules 2008, 13, 831-840 molecules ISSN 1420-3049 ? 2008 by MDPI /molecules Full Paper Simple and Efficient Microwave Assisted N-Alkylation of Isatin María Sol Shmidt, Ana María Reverdito, Lautaro Kremenchuzky, Isabel Amalia Perillo* and María Mercedes Blanco Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 (1113) Buenos Aires, República Argentina * Author to whom correspondence should be addressed; e-mail: iperillo@ffyb.uba.ar Received: 11 March 2008; in revised form: 9 April 2008 / Accepted: 9 April 2008 / Published: 10 April 2008 Abstract: We present herein the results of microwave promoted N-alkylations of isatin (1) with different alkyl, benzyl and functionalized alkyl halides. Reactions were carried out under different conditions, always employing methodologies compatible with MW assisted chemistry. Generation of isatin anion employing diverse bases and solvents or using the preformed isatin sodium salt was tested. The best results were achieved using K2CO3 or Cs2CO3 and a few drops of N,N-dimethylformamide or N-methyl-2-pyrrolidinone. These reactions present noteworthy advantages over those carried out employing conventional heating. Keywords: Isatin, N-alkylation, microwave irradiation, conventional heating, isatin sodium salt. Introduction N-alkylation of isatin (1, Scheme 1) reduces the lability of the isatin nucleus towards bases, while maintaining its typical reactivity. Thus, N-substituted isatins 2 have been frequently used as intermediates and synthetic precursors for the preparation of a wide variety of heterocyclic compounds [1, 2]. In addition, properly functionalized N-alkyl isatins present different biological activities [1], and in recent years compounds showing potent cytotoxicity in vitro [3], antiviral activity [4] and potent and selective caspase inhibition [5] have been reported, among others.  Mole