Synthesis, Reactions and Antimicrobial Activity of Some New 3-Substituted Indole Derivatives

Asmaa S. Salman, Naema A. Mahmoud, Anhar Abdel-Aziem, Mona A. Mohamed, Doaa M. Elsisi
2015 International Journal of Organic Chemistry  
Reaction of indole-3-carboxaldehydes 4 with hydrazine derivatives and different substituted acid hydrazides afforded the corresponding hydrazine derivatives 5a-c and acid hydrazide derivatives 7-11 respectively. Condensation of indole-3-carboxaldehydes 4 with phenacyl bromide and thiourea gives 1,3-thiazol-2-amine derivative 18. On the other hand, reaction 4 with 3-acetylchromene-2one afforded chalcone derivative 19. Compound 4 undergoing Knoevenagel condensation with cyanoacetamide, ethyl
more » ... acetate, benzimidazol-2-ylacetonitrile, rhodanine-3-acetic acid, 2,3dihydropyrimidin-4-one derivative and 2,4-dihydropyrazol-3-one afforded the compounds 20a,b, 22, 23, 27 and 28 respectively. The structure of the newly synthesized compounds has been confirmed by elemental analysis and spectra data. The antimicrobial activities of the some newly synthesized compounds were measured and showed that most of them have high activities. Keywords Indole-3-Carboxaldehyde, Acid Hydrazide, 1,3-Thiazole, Pyrimidine, Antimicrobial A. S. Salman et al. 82 Heterocyclic compounds containing nitrogen have been described for their biological activity against various micro-organisms. The indole unit is the key building block for a variety of compounds which have crucial roles in the functions of biologically important molecules. Many indole alkaloids are recognized as one of the rapidly growing groups of marine invertebrate metabolites for their broad spectrum of biological properties [2] [3] . For example, five new indole alkaloids, meridianins A-E have been isolated from the tunicate Aplidium meridianum, which showed cytotoxicity toward murine tumor cell lines [4] . Introduction of different groups to the modified indole structure can produce a series of compounds with multiple activities. Various 3-substituted indoles had been used as starting materials for the synthesis of a number of alkaloids, agrochemicals, pharmaceuticals and perfumes. Also 3-substituted indole derivatives possess various types of broad spectrum's biological activities such as antimicrobial, antitumor, hypoglycemic, anti-inflammatory, analgesic and antipyretic activities [5] [6]. Moreover the substitution at the 3-position of the indole ring can take place by connecting an additional heterocyclic ring, such as imidazole (topsentins, nortopsentins) [7] [8], dihydroimidazole (discodermindole) [9], oxazole (pimprinols A-C, almazole C) [10] [11], thiazole (bacillamide A) [12], quinazoline (tremorgens) [13], and pyrimidine [14]. Therefore, 3-substituted indoles still represent a significant synthetic challenge. In view of the important biological properties of the indole ring, we planned to synthesize a new series of 3-substituted indole derivatives bearing side chains with different structures; as such derivatives could possess interesting and useful antimicrobial activity. Materials and Methods Experimental Melting points were measured on a Gallenkamp apparatus and are uncorrected. IR spectra were recorded on Shimadzu FT-IR 8101 PC infrared spectrophotometer (υ max in cm −1 ). The 1H NMR and 13 C NMR spectra were determined in DMSO-d6 at 300 MHz on a Varian Mercury VX 300 NMR spectrometer using TMS as an internal standard. Mass spectra were measured on a GCMS-QP1000 EX spectrometer at 70 Ev. Elemental analyses were carried out at the Microanalytical Center of Cairo University. Spectral data of the synthesized compounds were given in Table 1 . General Procedure for the Synthesis of 2-Substituted-Indole (3a-d) Synthesis of 2-substituted-1H-indole 3a-d was carried out by the procedure of Fischer indole synthesis. Phenylhydrazone derivatives 2a-d were prepared by warming a mixture of compounds 1a-d (0.04 mol) and phenyl hydrazine (0.072 ml, 0.04 mol) with 60 ml of ethanol and few drops of glacial acetic acid. The resulting reaction mixture was allowed to stirring for about 2 h. The reaction mixture was then poured into ice water (50 ml) where upon the crude compound was precipitated. The residue obtained after filtration was washed with water and used in second step. A mixture of 2a-d (0.01 mol) and polyphosphoric acid (20 ml) was refluxed for 6 h. After the completion of the reaction, it was filtered and filtrate was poured into ice cooled water. The solid obtained was filtered and recrystallized from the ethanol to give 3a-d. 2-(4-Methylphenyl)-1H
doi:10.4236/ijoc.2015.52010 fatcat:jkvmrro6wrenhnekjus2fajsa4