Synthetic Organic Chemistry Research Papers (original) (raw)

Benzoheterocycles such as benzothiazoles, benzimid azoles and benzoxazoles can serve as unique and versatile scaffolds for experimental drug design. Among the all benzohaterocycles, benzothiazole has considerable place in research area especially in synthetic as well as in pharmaceutical chemistry because of its potent and significant pharmacological activities. Since, a wide range of methods are available for synthesizing benzothiazole nucleus and its derivatives but a real need exists for new procedures that support many kinds of structural diversity and various substitution. The present review deals with the common methods adopted and reported to focus the synthesis as well as cyclisation of benzothiazole nucleus. INTRODUCTION Benzothiazole is a privileged bicyclic ring system. Due to its potent and significant biological activities it has great pharmaceutical importance; hence, synthesis of this compound is of considerable interest. The small and simple benzothiazole nucleus if present in compounds involved in research aimed at evaluating new products that possess interesting biological activities. 2-substitued benzothiazole has emerged in its usage as a core structure in the diversified therapeutically applications. The studies of structure–activity relationship interestingly reveal that change of the structure of substituent group at C-2 position commonly results the change of its bioactivity. Among those 2-substituted benzothiazole derivatives with fluorine substituted molecules have already received considerable attention due to their potential bioactivities (Jian Haoa et al.; 2007). Since most of the benzothiazole derivatives were reported for their diversified activity viz., antitumor, antitubercular, antimalarial, anticonvulsant, anthelmintic, analgesic, antiinflammatory, antifungal, a topical carbonic anhydrase inhibitor and an antihypoxic (Hutchison et al., 2003; Latrofa et al., 2005; Yoshida et al., 2005; Latrofa et al., 2005; Caryolle et al., 1990) In 1887, 2 substituted benzothiazole was first synthesized by A. W. Hofmann then because of diversified activity as well as simple cyclization mechanism number of synthetic routes have been adopted and reported. 2-substitutedbenzothiazoles are most commonly synthesized via one of two major routes: the most common direct method involves the condensation of an ortho-amino thiophenol with a substituted aromatic aldehyde, carboxylic acid, acyl chloride or nitrile. This method, however, is often not appropriate for manysubstituted 2-arylbenzothiazoles due to the difficulties encountered in the synthesis of the readily oxidisable 2-amino thiophenols bearing substituent groups. The other methods used extensively in the laboratories which are based on the potassium ferricyanide (Jacobsen cyclization) radical cyclization of thiobenzanilides which involve cyclization onto either carbon atom ortho to the anilido nitrogen produces only one product, hence, the Jacobsen cyclization is a highly effective strategy for benzothiazole synthesis e.g. for the synthesis of 6- substituted benzothiazoles, radical cyclization of the 3-fluoro- or 3,4-difluoro-substituted thiobenzanilides (Ben-Alloum et al., 1997). A similar mixture of regioisomeric products from the Jacobsen cyclization has also been observed by Roe and Tucker for the synthesis of 5- and 7-fluoro-2-phenylbenzothiazoles (Roe et al., 1965). A regiospecific synthesis of 2-arylbenzothiazoles unsubstituted in the phenyl ring was developed through the use of a bromo substituent ortho to the anilido nitrogen and formation of a benzyne intermediate followed by intramolecular cyclization. A similar strategy has been developed for the synthesis of wide range of 7-substituted benzothiazoles via directed ortho metallation followed by benzyne formation and subsequent cyclization (Stanetty et al 1996). These strategies, however, were found to be incompatible with the nitro functionality on the aryl ring and do not represent a general route to functionalised 2- arylbenzothiazoles (Hutchinson et al., 2000; Shi et al., 1996). CONCLUSION Benzothiazole belongs to an important class of heterocyclic compounds and exhibits a wide range of biological properties and due to its potent activities, thus the synthesis of benzothiazole is an area of current interest. Several methods for the synthesis and cyclization of benzothiazole have been reported such as Hofmann Method Jacobson synthesis and oxidation by bromine, sulphuric acid, benzyltrimethylammoniumtribromide, copper and palladium, chloroformamidium salt, Appel's salt to facilitate formation of the thiyl radical from the thiobenzamide, which cyclizes with loss of a hydrogen atom and Baker's yeast cyclization to produce the benzothiazole. Since, individual method has their own advantages and disadvantages, but the most common classical methods for the synthesis of benzothiazole are based on cyclization of thiobenzamides (Jacobson synthesis) which involves the use of potassium ferricyanide with sodium hydroxide and cyclization of substituted aniline in the presence of potassium thiocyanate achied through oxidation by bromine. The cyclization as well as structural elaboration in lead optimization, the points of attachment on the benzoheterocycle can be through a number of atoms on either the benzene or heterocyclic rings. In general, the formation of heteroatom linkages between any points on the benzoheterocyclic nucleus for example, any aromatic, lipid-like, peptide, heterocyclic or even carbohydrate appendage may take advantage of S, and N nucleophilicity. However, the formation of carbon–carbon bonds to the benzoheterocyclic nucleus from these appendages may be more involved, particularly in the presence of sensitive heteroatom functionality on the heterocyclic portion of the nucleus