Microwave-assisted Synthesis of Some N-alkylisatin-B-thiocarbohydrazones
Abstract
The effectiveness of microwave-assisted preparation of N-alkylisatin--thiocarbohydrazones, where alkyl group is methyl and ethyl, was evaluated. The corresponding N-alkylisatin--thiocarbohydrazones were predominantly obtained by TCH and N-alkyl substituted isatin in molar ratio 3:1. Reactions of carbonyl-amine condensation were performed in water acidified to pH 1.5 as a solvent system. Reaction mixtures were exposed to microwave irradiation under 300W and pressure 200 psi, for a specified incubation period of 5-15 min. The yield of products obtained by microwave assisted reaction was similar to that had been obtained using conventional reflux method (about 70% to 80%), with reduction of time. The structures of synthesized N-alkylisatins and corresponding N-alkylisatin--thiocarbohydrazones were established on the basis of recorded spectral data from IR, GC-MS, 1H NMR and 13C NMR.
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Introduction
Discovery of small molecules (MW < 1500 Da) play an essential role in medicinal chemistry. Some of these organic compounds derived from natural products and are endogenous, such as isatin (indoline-2,3-dione) identified in human, mammalians and plants [1, 2]. Isatin was discovered by Erdmann and Laurent in 1840 as an oxidation product of indigo, and numerous of its derivatives have been synthetically obtained and characterized so far [3, 4].
Isatins are a group of organic compounds containing the heterocyclic indole nucleus, where the aryl ring (A) is mono, di-, or tri-substituted, as can be seen on Fig.1. Some of isatin analogues have been obtained by derivatization of the indole nitrogen and/or carbonyl moieties: lactam and keto group on C2 and C3, respectively
Conclusion
N-alkylisatins (1) and N-alkylisatin-β-thiocarbohydrazones (2), where alkyl group is methyl or ethyl, have been prepared by two-step reaction pathway including (i) nucleophilic substitution of alkyl halide with isatin anion and (ii) subsequent carbonyl-amine condensation of N-alkylisatin with TCH. Reactions were performed using conventional heating technique and microwave-assisted synthesis. N-alkylisatins (1) and title compounds (2) were obtained by microwave irradiation for 10 to 15 minutes, so one of the advantages over conventional heating is reducing the reaction time. Investigation of the effect of the mole ratio of reactants and elected solvent indicated that the monothiocarbohydrazone derivatives of isatin were predominantly obtained in acidic media in water as solvent and triple molar excess of TCH. In ethanol and acetonitrile solutions, spyro compounds were detected. Synthesized compounds were characterized using GC-MS, 1H-NMR and 13CNMR. N-ethylisatin-β-thiocarbohydrazone has cytostatic activity towards malignant melanoma cells.