Facile One Pot Microwave Induced Solvent-Free Synthesis and Antifungal, Antitubercular Screening of Spiro [1,5]-Benzothiazepin-2,3'[3'H]indol-2[1'H]-ones

Abstract

Studies on chemistry and pharmacology of 1,5-benzothiazepines have provided the famous cardiovascular drugs Diltiazem, Clentiazem, etc. to the mankind and those in which the fused benzene ring is substituted at various positions have been found to be more potent.1) The research on the chemistry of indoles has continued unabated due to their wide spread occurrence in nature and biological activities [2][3][4] and the compounds in which the bio-active indole nucleus is spiro fused with another heterocycle at the C-3 position shows immense pharmaceutical applications.5-7) Further, spiro-3-indole derivatives, incorporating five and six membered heterocycles have been extensively reviewed [8][9][10][11][12] but few reports are available regarding those incorporating a seven membered thiazepine moiety. Also, 3-aroyl-2H-indol-2-ones (4a, b) have been found as the essential synthetic building block [13][14][15] for the synthesis of a wide variety of 3-spiro indolines and condensed indole derivatives. The investigation of their reaction with substituted aminobenzenethiols to form the title products was found interesting in view of the fact that different reaction sites are available in the key intermediates which may lead to a mixture of products as observed earlier in reactions with several other nitrogen containing nucleophiles. [16][17][18][19][20] The use of microwave (MW) for assisting different organic reactions has become very popular in the last few years and recently the use of supported reagents coupled with MW irradiation has gained special attention [21][22][23] due to its ecofriendliness and safety. Many review articles [24][25][26][27][28][29][30] have been published in this field. Due to timeliness, ease of workability, dramatic rate enhancement and increased selectivity, microwave technology provides a promising alternative to environmentally unacceptable conventional procedures that may be time consuming or using toxic, expensive, problematic versus pollution and often flammable solvents in large amounts.Hence, we were encouraged by the vast potential of rapid and efficient solvent-less MW induced method that have manipulative advantages over heterogeneous reactions and in continuation to our earlier interest on the synthesis of various biodynamic spiro-3-indole derivatives [31][32][33][34][35][36][37][38] under MW irradiation. So, we report here in a facile and enviro-economic synthesis of the title compounds 7a-e incorporating two biologically important heterocycles (1,5-benzothiazepine and indole) with the assumption that the combination of these moieties may enhance the biological profile of the compound many fold versus its parent nuclei. Results and DiscussionThe usual thermal procedure for the synthesis of 4a, b requires a two steps procedure 39) which involves reaction of isatin (1) However, when the same reaction was studied under MW irradiation using basic alumina as the inorganic solid support, the compounds 4a, b were obtained in quantitative yields with reasonable purity in 5-6 min without...

Nonthermal Effects of Microwaves in Organic Synthesis

“…1,2-Asymmetric induction of up to 76% diastereoisomeric excess was observed in reactions of several amines with β-substituted acrylic acid esters from d-(+)-mannitol, in the absence of solvent, after exposure to MWs for 12 min [150]. MW activation coupled with a dry media technique as a Green Chemistry procedure has been applied to the synthesis of a series of 1,5-benzothiazepines [151][152][153]. These compounds are well-known cardiovascular drugs acting as calcium channel blockers.…”

5′′-(2,4-Dichlorobenzylidene)-1′-(2,4-dichlorophenyl)-1′′-methyl-1′,2′,3′,5′,6′,7′,8′,8a'-octahydrodispiro[acenaphthylene-1,3′-indolizine-2′,3′′-piperidine]-2,4′′(1H)-dione

“…For the importance of spiro compounds, see: Biava et al (2006); Chande et al (2005); Dandia et al (2003); Shaharyar et al (2006); Sriram et al (2006). For related acenaphthylene structures, see: Hazell & Hazell (1977); Hazell & Weigelt (1976); Jones et al (1992); Sundar et al (2002).…”

Reactions of α‐diazoketones with indolinone imines: Synthesis of new 1,3,3‐triaryl‐1′‐methylspiro[azetidine‐2,3′‐indoline]‐2′,4‐diones

“…The literature reveals diverse types of biological activities associated with indoline-2,3-dione isatin [7][8][9]. We, therefore, initiated studies on the reactions of diarylketenes with isatin derivatives.…”