Green Synthesis of Novel Class of Benzazocine Derivatives, their Crystal Structures and Anticancer Activity

Abstract

Background: Heterocyclic molecules have been synthesized by a green and facile strategy. These mole-cules contain a 8-membered azocine ring. The structures have been determined by spectral analysis and single crystal X-ray analysis. These compounds have anticancer activity. Method: A mixture of ninhydrin and acetone/ethylmethylketone in acetic acid in molar ratio 1: 1 were heated on water bath for 15 minutes. The reaction mixtures were dried on rotary evaporator and crystallized with chloro-form- n-hexane (1: 1 v/v) to give the colorless crystals of 1 And 2 respectively. Compounds 3 and 4 were synthe-sized by adding o-phenylenediamine to the completed reaction mixtures of 1 and 2 and each was further heated on water bath for 5 minutes. The dried reaction mixtures were chromatographed over a silica gel column and crystalized as 3 and 4. Results: This strategy resulted novel class of anticancer benzazocines (3 and 4). Conclusion: This method features mild reaction conditions and simple operation. The synthesis completes in two steps; from ninhydrin to 1 and 2 and from 1 and 2 to 3 and 4. The same basic skeleton of 3 and 4 and the same synthesis procedure clearly shows the general applicability of this reaction that is also proved enough by single crystal X-ray analysis and the strategy can be applicable for a wide range of other substrates. The obtained compounds are potential anticancer agents.