Standard Lab Report Template

Standard Lab Report Template - ORGANIC LETTERS Facile...

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Facile Preparation of 3-Substituted Benzisothiazoles from o -Mercaptoacylphenones Nelmi O. Devarie-Baez and Ming Xian* Department of Chemistry, Washington State Uni V ersity, Pullman, Washington 99164 mxian@wsu.edu Received December 9, 2009 ABSTRACT A synthesis of 3-substituted benzisothiazoles starting from readily available o -mercaptoacylphenones is presented. The key cyclization step features a mild S -nitrosation and its succeeding intramolecular aza-Wittig reaction leading to the construction of the title compounds. Benzisothiazole is a unique heterocyclic structure that has been visualized as an important pharmacophore of some bioactive molecules. These molecules have been reported to possess many interesting biological activities such as antibacterial, 1 anti-HIV, 2 antiproliferative activities of B- lymphoblastic leukemia cells, 2 and others. 3 As an example, Ziprasidone, which contains a key benzisothiazole subunit, is an FDA-approved antipsychotic drug for the treatment of schizophrenia. 4 Due to the importance of this scaffold in drug discovery, the synthesis of benzisothiazoles has received considerable attention from organic chemists. Currently, most of the methods to access benzisothiazoles rely on multistep chemical manipulations. 5 Only a few single ±ask strategies have been developed and the range of the substrates is limited. 6 In our recent efforts to develop chemical probes for the detection of protein S -nitrosation, 7 it was noticed that organophosphines reacted with S -nitrosothiols to form azay- lide intermediates under very mild conditions. These reactive intermediates could undergo intramolecular reactions with different electrophiles attached on the phosphine substrates, leading to the formation of different ²nal products. With this information in mind, we proposed a new synthesis of 3-substituted benzisothiazoles from readily available o - mercaptoacylphenones. As shown in Scheme 1, nitrosation of the o -mercaptoacylphenone starting material should provide the corresponding S -nitroso derivative 1 . It is well- known that S -nitroso compounds are unstable species and their puri²cation/isolation is always problematic. 8 Therefore, (1) Zani, F.; Vicini, P. Arch. Pharm. Pharm. Med. Chem. 1998 , 331 , 219. (2) Vicini, P.; Geronikaki, M. I.; Bernadetta, B.; Poni, G.; Cabras, C. A.;
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This note was uploaded on 03/03/2010 for the course CHEM 240 taught by Professor Mandal during the Spring '10 term at Illinois Tech.

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Standard Lab Report Template - ORGANIC LETTERS Facile...

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