American Journal of Organic Chemistry 2012, 2(2): 32-40 DOI: 10.5923/j.ajoc.20120202.06 Utility of Activated Nitriles in the Synthesis of Some New Heterocyclic Compounds A. A. Fadda 1 , M. M. Mukhtar 1 , Hala M. Refat 2,* 1 Department of Chemistry, Faculty of Science, Mansoura University, ET-35516, Mansoura, Egypt 2 Department of Chemistry, Faculty of Education, Suez Canal University, Al-Arish, Egypt Abstract New 4-(2-cyanoacetamido)benzoic acid (1) was utilized as key intermediate for the synthesis of some new thiazole, pyrazole, oxazole, pyrimidine, 1,3-dithiolane, thiophene, coumarin, oxazine and pyridazine derivatives. Newly synthesized compounds were characterized by elemental analyses and spectral data (IR, 1 H NMR and mass spectra). Keywords Cyanoacetamide, Cyanoketen N,S-acetal derivative, Enaminonitrile, 1,3-Dithiolane derivative 1. Introduction Cyanoacetamides are highly reactive compounds. They are extensively utilized as reactants or reaction intermediates since the carbonyl and the cyano functions of these com- pounds are suitably situated to enable reactions with com- mon bidentate reagents to form a variety of heterocyclic compounds. Moreover function, the active hydrogen on C-2 of these compounds can take part in a variety of condensa- tion and substitution reactions. The synthesis of cyanoacetamides may be carried out in several ways. The most economical method involves the treatment of substituted aryl or heteryl amines with alkyl cyanoacetates using different reaction conditions to yield cyanoacetamide derivatives. There are some methods used to prepare N- aryl or N-heterylcyanoacetamides [1, 2]. Cyano- acetyl pyrazole is a very handly and cheap cyanoacetylation reagent, which was the first time synthesized and introduced in common practice in late 1950 by Ried et al [3]. It was successfully applied for the synthesis of various N-alkyl and N-aryl cyanoacetamides. Cyanoacetamides are polyfunctional compounds pos- sessing both electrophilic and nucleophilic properties. Typical nucleophilic positions are NH and C-2 with reactiv- ity order C-2 > NH. These chemical properties have been used to design different heterocyclic moiety with different ring size such as azirine, pyrrole, thiophene, pyrazole, imi- dazole, thiazole, thiadiazole, pyridine, pyrane, pyridazine, pyrimidine, and triazine. On the other hand, cyanoacetamide posses electrophilic positions especially at C-3, C-1 with reactivity order C-3 > C-1. So, cyanoacetamide can be useful for synthesis of three membered rings[4], five membred * Corresponding author: hala7223530@hotmail.com (Hala M. Refat) Published online at http://journal.sapub.org/ajoc Copyright © 2012 Scientific & Academic Publishing. All Rights Reserved rings such as pyrrole derivative [5], pyrazole and their fused derivatives[6-8], imidazole[9], thiazole[10, 11], 1,3-dithio- lane[12], thiadiazole and their derivatives[13, 14], thiophene [15, 16], also, six membered rings such as pyridine[17, 18], pyrane[19], pyradazine[20], thiazine[21] and triazine de- rivatives[22]. Ar N H O CN 1 2 3 Figure 1. 2. Results and Discussion The new starting compound, 4-(2-cyanoacetamido) ben- zoic acid (1) was prepared via treatment of p-aminobenzoic acid with 1-cyanoacetyl-3,5-dimethyl pyrazole as cyanoacetylation reagent in dry toluene. The structure 1 was established on the basis of spectral data. The IR spectrum revealed absorption band at 3322 cm -1 for NH group, broad peak around 3000 cm -1 for OH function of the carboxylic group, sharp band at 2260 cm -1 for cyano function and a strong broad band at 1695 cm -1 and 1650 cm -1 for two car- bonyl groups, respectively. It's 1 H NMR spectrum (DMSO-d 6 ) revealed the presence of three singlet signals at δ 3.96 ppm, δ 10.59 ppm and at δ 12.77 ppm assignable to the methylene protons, NH proton and carboxylic proton, re- spectively. Its mass spectrum showed a molecular ion peak at m/z = 204 corresponding to a molecular formula (C 10 H 8 N 2 O 3 ). Scheme 1 Moreover, Gewald reaction of 4-(2-cyanoacetamido) benzoic acid (1) with elemental sulfur and phenyl isothio- cyanate in warming ethanol containing triethylamine as a basic catalyst afforded 4-(4-amino-3-phenyl-2-thioxo-2,3- dihydrothiazole-5-carboxamido) benzoic acid (2) (Scheme