Assessment of substituent effects and antimicrobial activities of some 2ʹ,5ʹ-dimethyl phenyl chalcones

Available online at www.ilcpa.pl International Letters of Chemistry, Physics and Astronomy 5 (2014) 99-123 ISSN 2299-3843 Assessment of substituent effects and antimicrobial activities of some 2ʹ,5ʹ-dimethyl phenyl chalcones S. John Joseph1, D. Kamalakkannan1, R. Arulkumaran1, S. P. Sakthinathan1, R. Suresh1, R. Sundararajan1, S. Vijayakumar1, K. Ranganathan1, G. Vanangamudi1,*, G. Thirunarayanan2 1 PG & Research Department of Chemistry, Government Arts College, C-Mutlur, Chidambaram - 608102, India 2 Department of Chemistry, Annamalai University, Annamalainagar - 608002, India *E-mail address: ABSTRACT Some 2ʹ,5ʹ-dimethyl phenyl chalcones have been synthesized by Crossed-Aldol condensation between 2,5-dimethyl acetophenone and various substituted benzaldehydes using catalytic amount of sodium hydroxide and ethanol. The yields of the chalcones are more than 93 %. The purities of these chalcones have been checked by their physical constants, UV, IR, NMR and MASS spectral data. The spectral data of these chalcones have been correlated with Hammett sigma constants, F and R parameters using single and multi-linear regression analysis. From the results of statistical analysis, the effects of substituents on the spectral group frequencies have been discussed. The anti-microbial activities of these chalcones have been evaluated using Bauer-Kirby method. Keywords: Substituted styryl 2ʹ,5ʹ-dimethyl phenyl chalcones; UV spectra; IR spectra; NMR spectra; Substituent effects; Antimicrobial activities 1. INTRODUCTION Chalcones are, α, β unsaturated ketones, possess methylene structural moieties and they belongs to biomolecules. Many alkyl-alkyl, alkyl-aryl and aryl-aryl categories of chalcones have been synthesized [1] and extracted from natural plants [2] by organic chemists. Various methods available for synthesizing chalcones such as Aldol, Crossed-Aldol, Claisen-Schmidt, Knovenagal reactions, Greener methods-Grinding of reactants, solvent free and oxides of nanoparticles with microwave heating. Also microwave assisted solvent free Aldol and Crossed-Aldol condensation [3-5] was useful for synthesis of carbonyl compounds. Due to CC single bond rotation [6] of carbonyl and alkene carbons, they exist as E s-cis and s-trans and Z s-cis and Z s-trans conformers. These structural conformers of chalcones have been confirmed by NMR and IR spectroscopy. International Letters of Chemistry, Physics and Astronomy 5 (2014) 99-123 Compounds with the backbone of chalcone possesses various biological activities such as anti-microbial [7], anti-inflammatory [8], analgesic [9], anti-ulcerative [10], immunemodulatory [11], anti-malarial [12], anti-cancer [13], anti-viral [14], anti-leishmanial [15], anti-oxidant [16], anti-tubercular [17], anti-hyperglycemic [18] etc. A compound having antioxidant activity prevents and counteracts the damage of the human tissue by the normal effects of physiological oxidation [19]. Presence of the reactive keto group and the vinylenic group in the chalcone and their analogues possesses the antioxidant activity [20]. Compounds that associated with the antioxidant properties are hydroxyl and phenyl group. Oxidative stress which is caused by the free radical damage is help to deal with the antioxidants [21]. Spectroscopic data is useful for study of effects of substituents on the specified spectral group frequencies using Hammett substituent constants, F and R parameters by single and multi-regression analysis. From the results the ground state molecular equilibration can be predicted. Recently Subramanian et. al. [22,23] has studied the synthesis and spectral correlations of some heterocyclic chalcones and they observed satisfactory correlations. In their studies, they observed satisfactory and good correlations for each spectral data with Hammett substituent constants, F and R parameters. Chalcones possess various multipronged activities such as antimicrobial [7], antidepressants [26], antiplosmodial [27], anti-aids [28] and insect antifeedant activities [24,25]. In the present investigation, the authors have synthesized a series of some substituted styryl 2,5-dimethyl pheny chalcones, studied the spectral correlations and to evaluate the antimicrobial activities using Bauer-Kirby [29] method. 2. EXPERIMENTAL 2. 1. General All chemicals used were purchased from Sigma-Aldrich and E-Merck chemical companies. Melting points of all chalcones were determined in open glass capillaries on Mettler FP51 melting point apparatus and are uncorrected. The ultraviolet spectrophotometer was utilized for recording the absorption maxima (λmax, nm), of all chalcones in spectral grade solvent. Infrared spectra (KBr, 4000-400 cm-1) were recorded AVATAR-300 Fourier transform spectrophotometer. BRUKER AVANCE III-500 MHz NMR spectrometer was used for recording NMR spectra operating at 500 MHz for 1H spectra and 125.46 MHz for 13C spectra in CDCl3 solvent using TMS as internal standard. Mass spectra of all chalcones were recorded on SHIMADZU spectrometer using chemical ionization technique. 2. 2. Synthesis of Chalcones A solution of benzaldehyde (0.01 mol) and 2,5-dimethyl acetophenone (0.01 mol), sodium hydroxide (0.5 g) and 10 ml of ethanol was shaken occasionally for 1 hour [30]. After the completion of the reaction, as monitored by TLC, the mixture was cooled at room temperature. The resulting precipitate was filtered and washed with cold water. The product appeared as light green solid. Then this was recrystallised using ethanol to obtain light green glittering solid melting at 116-117 °C. The physical constants, analytical and mass fragments were presented in Table 1. 100 International Letters of Chemistry, Physics and Astronomy 5 (2014) 99-123 CH3 CH3 O O H NaOH C C CH3 C Ethanol O C H C H X X H3C H3C Where X = H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-OCH3, 4-CH3, 3-NO2, 4-NO2 Scheme 1. Synthesis of substituted styryl 2ʹ,5ʹ-dimethyl phenyl ketones. Table 1. Physical constants and mass spectral data of substituted styryl 2ʹ,5ʹ-dimethyl phenyl ketones. Entry X M. F. M. W. Yield (%) m.p. (C) Mass (m/z) 1 H C17H16O 236 93 116-117 236[M+] 2 4-Br C17H15BrO 315 91 131-133 315[M+], 317[M2+] 3 2-Cl C17H15ClO 270 88 108-109 270[M+], 272[M2+] 4 4-Cl C17H15ClO 270 89 101-103 270[M+], 272[M2+] 5 4-F C17H15FO 254 88 94-96 254[M+], 256[M2+] 6 4-OCH3 C18H18O2 267 87 96-98 267[M+] 7 4-CH3 C18H18O 250 90 111-113 250[M+] 8 3-NO2 C17H15NO3 281 89 145-147 281[M+] 9 4-NO2 C17H15NO3 281 84 139-141 281[M+] 3. RESULTS AND DISCUSSION In the present study the authors have studied the effects of substituents on the spectral data such as ultraviolet absorption maxima (λmax, nm), infrared spectral carbonyl and deformation modes (ν, cm-1), the chemical shifts (δ, ppm) of α, β protons, and carbonyl carbons of synthesized 2,5-dimethyl phenyl chalcones with Hammett substituent constants, F and R parameters using single and (...truncated)