%0 Journal Article
%T Utility of Activated Nitriles in the Synthesis of Novel Heterocyclic Compounds with Antitumor Activity
%A Asmaa S. Salman
%J Organic Chemistry International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/259348
%X Reaction of cyanoacetic acid hydrazide (1) with 4-methoxyacetophenone and 4-chlorobenzaldehyde (2a,b) afforded the corresponding 2-cyanoacetohydrazide derivatives (3a,b) respectively. The latter compounds were utilized as a key intermediate for the synthesis of new heterocyclic compounds. Newly synthesized compounds were characterized by elemental analyses and spectral data. The antitumor evaluation of some newly synthesized compounds was screened in vitro against human breast cancer cell line (MCF-7). 1. Introduction In many reports, hydrazide-hydrazones are considered to be good candidates for different pharmaceutical applications, where such compounds were considered to exert anticonvulsant [1], analgesic [2], anti-inflammatory [3], antiplatelet [4], antimalarial [5], antimicrobial [6], antitumoral [7, 8], vasodil-ator [9], and antiviral activity [10]. With the aim of obtaining new hydrazide-hydrazones with such wide spectrum of pharmaceutical applications, in this research, synthesis of a series of hydrazide-hydrazones and some of their heterocyclic transformations, followed by antitumor evaluations of newly synthesized products was done. 2. Experimental All melting points were determined in open glass capillaries on a Gallenkamp apparatus and are uncorrected. IR spectra (cm£¿1) were recorded on a Pye-Unicam spectrophotometer type 1200 using KBr discs. 1H-NMR spectra were recorded on a Varian EM-390 (90£¿MHz) spectrometer using TMS as an internal standard and DMSO-d6 as a solvent. Chemical shifts were expressed in ¦Ä (ppm) values and mass spectra were determined on Finnigan Incos 500 (70£¿ev). Elemental analyses were determined using a Parkin-Elmer 240C Microanalyzer. The microanalyses were performed at the Microanalytical Unit, Faculty of Science, Cairo University. 2.1. General Procedure for Synthesis of 3a,b To a solution of 2-cyanoacetohydrazide (0. 99£¿g, 0.01£¿mol) in ethanol (20£¿mL), 4-methoxyacetophenone and/or p-chlorobenzaldehyde (0.01£¿mol) was added. The reaction mixture was heated under reflux for 2£¿h, then left to cool, and poured into ice/water. The obtained product was filtered, washed with water, and recrystallized from the appropriate solvent to give 3a,b. 2.1.1. Cyano-N¡ä-[1-(4-methoxyphenyl)ethylidene]acetohydrazide (3a) Yield, 75%; m.p. 186¨C188¡ãC (ethanol); IR (KBr, cm£¿1): 3204 (NH), 1675 (CO), 2256 (CN); 1H NMR (DMSO: ¦Ä£¿ppm): 2.23 (s, 3H, CH3), 3.81 (s, 3H, OCH3), 4.18 (s, 2H, CH2), 10.90 (s, 1H, NH), 6.93¨C7.76 (m, 4H Ar¨CH); MS m/z (%): 231 (M+, 98.11), 216 (27.99), 191 (40.26), 163 (48.64), 148 (80.06), 134 (87.96), 121 (39.49), 119
%U http://www.hindawi.com/journals/oci/2013/259348/