Synthesis and fragmentation behavior study of n-alkyl/benzyl isatin derivatives present in small/complex molecules: Precursor for the preparation of biological active heterocycles

Abstract

N-Alkyl/benzyl substituted isatin derivatives are intermediates and synthetic precursors for the preparation of biological active heterocycles. N-alkyl/benzyl isatins have showed various biological activities, such as cytotoxicity, antiviral, caspase inhibition, cannabinoid receptor 2 agonists for the treatment of neuropathic pain, etc. In this study, N-alkyl/benzyl isatin derivatives were synthesized from isatin and alkyl/benzyl halides in presence of K2CO3 in DMF and excellent to quantitative yields (~95%) were obtained. Isatins and benzyl-isatins were condensed with fluorescein hydrazide to form fluorescein hydrazone. All the compounds were subjected to their fragmentation behavior study using LC/MSn. N-Alkyl substituted isatin derivatives fragmented at nitrogen-carbon (N-C) bond, hence gave daughter ion as [RN+H]+. Whereas, N-benzyl substituted isatin derivatives fragmented at carbon-carbon (C-C) bond of alkyl chain which linked with nitrogen molecules, therefore gave N-methyl fragments [RNCH2]+. This study demonstrated that, isatin moiety present in a small/large molecule or in a matrix of reaction mixture with/without N-alkyl/benzyl substituents can be identified by mass spectroscopic fragmentation behavior study.