One Pot Catalyst‐free Synthesis of Substituted Di‐amino N‐tosyl Benzoyl Thiazoles byRegioselective C−N Bond Cleavage and Its Anticancer Activity

Abstract

The synthesis of hitherto unknown thiazole derivatives have been disclosed via purely green approach. This proposed work is novel in terms of C−C bond formation at guanidino carbon in 2‐amino benzimidazole moiety. The unstable benzimidazol‐hemiaminals have been used as a source of reactive intermediates.The catalyst‐free synthesis of diamino benzoyl N‐tosyl thiazole governed bythe sequential chemical conversions, which was steered by simple N‐tosylation of benzimidazol‐hemiaminal. The reaction was internally edge forward by thiazolidine ring opening, N‐tosylation, C−C bond formation and regioselective cleavage of C−N bondat guanidino carbon in a single step. Oxidation of tertiary alcohol to ketone with ring opening by C−N bond cleavage and N‐tosylation are the valuable conversions to accomplish the regioselectivity in the development of new desired thiazole ring. Moreover benzimidazol‐hemiaminal used as a storage of 2‐oxo‐2‐phenylethyl N′‐(1H‐benzo[d]imidazol‐2‐yl)‐N‐phenylcarbamimidothioate which is again highly unstable intermediate. The reverse back step mechanism was developed for the synthesis of thiazoles unlike other hemiaminals. The protocol is free of catalyst and toxic solvents.Use of ionic liquid, shorter reaction time, high yielding and easy isolation of products makes this strategy more environmental‐friendly. The importance of products attributed to the presence of active benzoyl and amino groups. Product thiazoles (T3) (IC50=7.906 μM), (T4) (IC50=5.250 μM) and (T7) (IC50=4.709 μM) were found potent anticancer agents against lung cancer with reference to doxorubicin as standard.

Stable hemiaminals from axially chiral pyridine compounds

“…Hemiaminal structure could be encountered in the structure of many biologically active natural products such as psymberin, zampanolide, and lucilactaene showing important cytotoxic activities 17 . In recent years, the hemiaminal scaffold 2‐iminothiazolidin‐4‐ol bearing compounds have received remarkable attention because such compounds were shown to suppress lung cancer growth 18–21 …”

“…17 In recent years, the hemiaminal scaffold 2-iminothiazolidin-4-ol bearing compounds have received remarkable attention because such compounds were shown to suppress lung cancer growth. [18][19][20][21] The common pathway for the formation of hemiaminals is the condensation of amines with carbonyl compounds in which hemiaminals come about as intermediate products and easily dehydrate to the related compounds. 22 In the earlier investigations, we reported the synthesis of hemiaminals from the reduction of thiohydantoins 23 and thiazolidinones 4,5 with LiAlH 4 as relatively stable hemiaminals, which yielded thiazol-2-imines via spontaneous water elimination with time.…”