untitled European Journal of Chemistry 8 (2) (2017) 125‐129 European Journal of Chemistry ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2017 Atlanta Publishing House LLC ‐ All rights reserved ‐ Printed in the USA http://dx.doi.org/10.5155/eurjchem.8.2.125-129.1553 European Journal of Chemistry Journal webpage: www.eurjchem.com A new facile and efficient synthesis of 2‐((5‐aryl‐1,3,4‐oxadiazol‐2‐yl) methoxy)‐3‐methyl quinoxaline and 3‐methylquinoxalin‐2‐yl‐2‐(5‐aryl‐2H‐ tetrazol‐2‐yl)acetate derivatives Shashikala Kethireddy 1, Hemalatha Kotakommula 2, Laxminarayana Eppakayala 3 and Thirumala Chary Mariganti 2,* 1 Geethanjali College of Engineering and Technology, Keesara, Rangareddy, 501301, Telangana, India 2 Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad, 500085, Telangana, India 3 Sreenidhi Institute of Science and Technology, Ghatkesar, Hyderabad, 501301, Telangana, India * Corresponding author at: Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad, 500085, Telangana, India. Tel.: +91.984.8511562. Fax: +91.984.8511562. E‐mail address: mtcharya@yahoo.com (T.C. Mariganti). ARTICLE INFORMATION ABSTRACT DOI: 10.5155/eurjchem.8.2.125-129.1553 Received: 11 February 2017 Received in revised form: 19 March 2017 Accepted: 19 March 2017 Published online: 30 June 2017 Printed: 30 June 2017   Newly synthesized compounds containing quinoxaline ring fused with tetrazoles and oxadiazoles show array of pharmacological activities, especially, anti‐inflammatory, analgesic and anticonvulsant activities. The ability to serve as surrogates or bioisosteres for carboxylic acids, esters and carboxamides made them important moieties in drug designing. Considering the importance of quinoxalines, tetrazoles and 1,3,4‐oxadiazoles to both medicinal and heterocyclic chemistry, the following 2‐((5‐aryl‐1,3,4‐oxadiazol‐2‐ yl)methoxy)‐3‐methyl quinoxaline and 3‐methylquinoxalin‐2‐yl‐2‐(5‐aryl‐2H‐tetrazol‐2‐ yl)acetate derivatives are synthesized. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR and Mass spectral data. All the synthesized derivatives were tested in vitro for their antibacterial activity. KEYWORDS Tetrazole Quinoxalines Antiviral activity 1,3,4‐Oxadiazole Antibacterial activity Anticonvulsant activity Cite this: Eur. J. Chem. 2017, 8(2), 125‐129 1. Introduction Tetrazoles are heterocyclic, five‐membered rings containing four nitrogens and one carbon atom (CN4H2) [1]. Presence of four nitrogen atoms makes them acidic. They undergo electrophilic as well as nucleophilic substitution [2]. They can act as pharmacophore for the carboxylate group, which increases their utility. Tetrazoles are Angiotensin II blockers as in Losartan and Candesartan [1,3,4]. Tetrazoles and its derivatives show most promising biological activities like antibacterial, antiviral, antifungal, anticonvulsant, anti‐ cancer, hypoglycemic, antinociceptive and ulcerogenicity index [5‐16]. They are cyclooxygenase inhibitors and therefore exhibit analgesic, anti‐inflammatory activities [4,17]. It was observed that several highly mutagenic and carcinogenic quinoxalines have been found in heated meat and fried fish. Some of the quinoxaline derivatives have been identified as mild hypo glycaemic agents and used for treating pain, epilepsy and other neurodegenerative disorders. Due to DNA binding properties of quinoxalines, they show highest activity against the herpes virus. They are part of well‐known antibiotics such as levomycin, echinomycin, and actinoleutin that are known to inhibit growth of gram positive bacteria. Quinoxalines show various biological activities such as anti‐viral, anti‐depressant and as kinase inhibitors. They are active against transplantable tumors. Fusion of tetrazole with quinoxalinesis considered as planar acidic heterocyclic analogue of carboxylic function, which has the ability to increase potency and enhance bioavailability [18,19]. 1,3,4‐Oxadiazole is a neutral aromatic molecule which is thermally stable [20]. Quinoxalines containing 1,3,4‐oxadi‐ azole have been shown to possess a broad biological activity spectrum including antibacterial, antifungal, antiviral, anti‐ cancer, antihypertensive, anticonvulsant and anti‐diabetic properties [20,21]. 126 Kethireddy et al. / European Journal of Chemistry 8 (2) (2017) 125‐129 Ar: 5a 5Ph; 5b 3F‐Ph; 5c 4F‐Ph; 5d 2OH‐Ph; 5e 3OH‐Ph; 5f 4‐OCH3‐Ph; 5g 2OCH3‐Ph; 5h 3‐OCH3‐Ph Ar: 6a 5Ph; 6b 3F‐Ph; 6c 4F‐Ph; 6d 2OH‐Ph; 6e 3OH‐Ph; 6f 4‐OCH3‐Ph; 6g 2OCH3‐Ph; 6h 3‐OCH3‐Ph Reagents and conditions: a) C2H5OH, ethyl chloroacetate, dry K2CO3, reflux, 80 °C, overnight; b) Ethanol, NH2NH2, reflux, 80‐90 °C, 5 hrs; c) RCHO, DMF, glacial acetic acid, reflux, 3 hr; d) Chloramine‐T, ethanol, reflux, 80‐90 °C, 5 hrs.; e) Aryl tetrazole, acetone, anhydrous K2CO3. Scheme 1 Quinoxalines when fused with oxadiazole moiety was also identified as a Selective inhibitor of Guanylyl Cyclase (SGC) and important heme‐site inhibitors for nitric oxide donor bioactivation. Moreover, the combined presence of quino‐ xaline and 1,3 4‐oxadiazole in one frame are expected to show promising anti‐inflammatory, analgesic and anticonvulsant activities. Taking into account the importance of quinoxalines, tetrazoles and 1,3,4‐oxadiazoles to both medicinal and heterocyclic chemistry, the following 2‐((5‐aryl‐1,3,4‐oxadi‐ azol‐2‐yl)methoxy)‐3‐methyl quinoxaline and 3‐methyl quinoxalin‐2‐yl‐2‐(5‐aryl‐2H‐tetrazol‐2‐yl)acetate are synthe‐ sized. The structures of the synthesized compounds were confirmed by IR, 1H NMR, 13C NMR and Mass spectral data. All the synthesized derivatives were tested in vitro for their antibacterial activity. 2. Experimental 2.1. Instrumentations and reagents All chemicals and reagents were of analytical grade and purchased from Merck. Solvents were used in purified form. For thin‐layer chromatography (TLC) E. Merck AL silica gel 60F254 plates were used and spots were visualized under UV light. Melting points were determined by using Mel‐temp apparatus and are uncorrected. IR spectra were recorded on Perkin Elmer (FT‐IR) spectrometer. Only intense peaks are diagnosed and reported. 1H NMR spectra were recorded using Varian NMR‐400 MHz instrument. All the chemical shifts were reported in δ (ppm) using TMS as an internal standard. Signals are indicated as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad); and coupling constants in Hz. Mass spectra were recorded with a PESciex model API 3000 mass spectrometer. All the reactions were carried out under the atmosphere of an inert gas, argon. 2.2. Synthesis 2.2.1. Synthesis of ethyl‐2‐(2‐methylquinoxalin‐3‐yloxy) acetate (2) 3‐Methyl quinoxalin‐2‐ol (0.01 mmol) was dissolved in ethanol (15 mL). To this solution ethylchloro acetate (0.01 mmol) and dry potassium carbonate (3 g) were added and refluxed at 80 °C for overnight. After the completion of reaction (monitored by TLC), the mixture was poured into ice cold water and filtered to separate the solid. The product was recrystallized from methanol (Scheme 1). Color: Yellow. Yield: 76%. M.p.: 196‐198 °C. FT‐IR (KBr, , cm‐1): 2943 (C‐H), 1712 (C=O). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.80 (m, 2H, Ar‐H), 7.68 (m, 2H, Ar‐H), 5.21 (s, 2H, O‐CH2‐C=O), 4.23 (q, 2H, O‐CH2‐ CH3), 2.30 (s, 3H, N=CH‐CH3), 1.23 (t, 3H, O‐CH2‐CH3). MS (EI, m/z (%)): 246.1 (M+H). 2.2.2. Synthesis of 2‐(2‐methylquinoxalin‐3‐yloxy)aceto hydrazide (3) To a solution of ethyl 2‐(2‐methylquinoxalin‐3‐yloxy) acetate (2) (0.01 mmol) in ethanol, was added hydrazine hydrate (99%, 20 mL) and refluxed for 5 h on a water bath at 80‐90 °C. The reaction mixture was cooled and poured into crushed ice with stirring and kept aside for 30min for the precipitate to settle. The resultant precipitate was filtered, washed with water, dried and recrystallized from ethanol (Scheme 1). Color: Brown. Yield: 81%. M.p.: 204‐206 °C. FT‐IR (KBr, , cm‐1): 3532 (NH) 3011 (C‐H) 1722 (C=O). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.31 (d, 2H, Ar‐H), 8.18 (d, 2H, Ar‐H), 7.40 (brs, 1H, NH), 5.20 (s, 2H, O‐CH2), 4.70 (brs, 2H, NH2), 2.31 (s, 3H, CH3). MS (EI, m/z (%)): 232.1 (M+H) Kethireddy et al. / European Journal of Chemistry 8 (2) (2017) 125‐129 127 2.2.3. Synthesis of N'‐Arylidene‐2‐((3‐methylquinoxalin‐2‐ yl)oxy)acetohydrazides (4a‐h) A mixture of 2‐(2‐methylquinoxalin‐3‐yloxy)acetohydra‐ zide (3) (0.01 mmol) and aldehyde (0.01 mmol) were dissolved in 25 mL of DMF and 2 mL of glacial acetic acid was added. This mixture was refluxed for 3h. After the completion of the reaction (monitored by TLC), reaction mixture was poured into crushed ice. Solid product thus obtained was filtered, washed with water and recrystallized from ethanol (Scheme 1). N'‐Benzylidene‐2‐((3‐methylquinoxalin‐2‐yl)oxy)acetohydra zide (4a): Color: Brown. Yield: 76%. M.p.: 202‐204 °C. FT‐IR (KBr, , cm‐1): 3432 (NH) 3035 (C‐H) 1718 (C=O). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.21(brs, 1H, NH), 8.11(s, 1H, N=CH), 7.91 (m, 2H, Ar‐H), 7.79 (m, 2H, Ar‐H), 7.30 (m, 3H, Ar‐ H), 7.27 (m, 2H, Ar‐H), 5.21 (s, 2H, O‐CH2), 2.30 (s, 3H, CH3). MS (EI, m/z (%)): 320.13 (M+H). N'‐(3‐Fluorobenzylidene)‐2‐((3‐methyl quinoxalin‐2‐yl)oxy) acetohydrazide (4b): Color: White. Yield: 82%. M.p.: 204‐206 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.25(brs, 1H, NH), 8.10(s, 1H, N=CH), 7.90 (m, 2H, Ar‐H), 7.80 (m, 2H, Ar‐H), 7.31 (m, 2H, Ar‐H), 7.26 (m, 2H, Ar‐H), 5.22 (s, 2H, O‐CH2), 2.35 (s, 3H, CH3). MS (EI, m/z (%)): 339 (M+H). N'‐(4‐Fluorobenzylidene)‐2‐((3‐methyl quinoxalin‐2‐yl)oxy) acetohydrazide (4c): Color: light brown. Yield: 80%. M.p.: 202‐ 204 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.26(brs, 1H, NH), 8.09(s, 1H, N=CH), 7.92 (m, 2H, Ar‐H), 7.81 (m, 2H, Ar‐H), 7.32 (m, 2H, Ar‐H), 7.26 (m, 2H, Ar‐H), 5.21 (s, 2H, O‐CH2), 2.33 (s, 3H, CH3). MS (EI, m/z (%)): 339 (M+H). N'‐(2‐Hydroxybenzylidene)‐2‐((3‐methyl quinoxalin‐2‐yl) oxy)acetohydrazide (4d): Color: Light yellow. Yield: 78%. M.p.: 206‐208 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 10.30 (brs, 1H, OH), 8.22 (brs, 1H, NH), 8.11 (s, 1H, N=CH), 7.91 (d, 2H, Ar‐ H), 7.80 (d, 2H, Ar‐H), 7.33 (m, 2H, Ar‐H), 7.28 (m, 2H, Ar‐H), 5.23 (s, 2H, O‐CH2), 2.35 (s, 3H, CH3). MS (EI, m/z (%)): 337 (M+H). N'‐(3‐Hydroxybenzylidene)‐2‐((3‐methyl quinoxalin‐2‐yl) oxy)acetohydrazide (4e): Color: Light yellow. Yield: 76%. M.p.: 204‐206 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 10.28 (brs, 1H, OH), 8.23 (brs, 1H, NH), 8.12 (s, 1H, N=CH), 7.93 (d, 2H, Ar‐ H), 7.82 (d, 2H, Ar‐H), 7.32 (m, 1H, Ar‐H), 7.27 (m, 3H, Ar‐H), 5.25 (s, 2H, O‐CH2), 2.32 (s, 3H, CH3). MS (EI, m/z (%)): 337 (M+H). N'‐(4‐Methoxybenzylidene)‐2‐((3‐methyl quinoxalin‐2‐yl) oxy)acetohydrazide (4f): Color: White. Yield: 84%. M.p.: 200‐ 202 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.24 (brs, 1H, NH), 8.11 (s, 1H, N=CH), 7.95 (d, 2H, Ar‐H), 7.81 (d, 2H, Ar‐H), 7.33 (m, 2H, Ar‐H), 7.28 (m, 2H, Ar‐H), 5.22 (s, 2H, O‐CH2), 3.78 (s, 3H, OCH3), 2.33 (s, 3H, CH3). MS (EI, m/z (%)): 351 (M+H). N'‐(2‐Methoxybenzylidene)‐2‐((3‐methyl quinoxalin‐2‐yl) oxy)acetohydrazide (4g): Color: yellow. Yield: 80%. M.p.: 204‐ 206 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.21 (brs, 1H, NH), 8.10 (s, 1H, N=CH), 7.98 (d, 2H, Ar‐H), 7.83 (d, 2H, Ar‐H), 7.35 (m, 2H, Ar‐H), 7.29 (m, 2H, Ar‐H), 5.23 (s, 2H, O‐CH2), 3.80 (s, 3H, OCH3), 2.35 (s, 3H, CH3). MS (EI, m/z (%)): 351 (M+H). N'‐(3‐Methoxybenzylidene)‐2‐((3‐methyl quinoxalin‐2‐yl) oxy)acetohydrazide (4h): Color: Brown. Yield: 75%. M.p.: 204‐ 206 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.22 (brs, 1H, NH), 8.10 (s, 1H, N=CH), 7.99 (d, 2H, Ar‐H), 7.83 (d, 2H, Ar‐H), 7.36 (m, 2H, Ar‐H), 7.30 (m, 2H, Ar‐H), 5.23 (s, 2H, O‐CH2), 3.79 (s, 3H, OCH3), 2.35 (s, 3H, CH3). MS (EI, m/z (%)): 351 (M+H). 2.2.4. Synthesis of 2‐(((3‐methylquinoxalin‐2‐yl)oxy) methyl)‐5‐aryl‐1,3,4‐oxadiazole (5a‐h) A solution of N'‐arylidene‐2‐((3‐methylquinoxalin‐2‐yl) oxy)acetohydrazide (4) (0.01 mmol) and chloramine‐T (0.05 mmol) in ethanol (25 mL) was refluxed for 5 h on a water bath at 80‐90 °C. The reaction mixture was cooled and poured into crushed ice with stirring and kept aside for 30min for the precipitate to settle down. The resultant precipitate was filtered, washed with water, dried and recrystallized from ethanol (Scheme 1). 2‐((5‐Phenyl‐1, 3, 4‐oxadiazol‐2‐yl)methoxy)‐3‐methyl quino xaline (5a): Color: White. Yield: 79%. M.p.: 198‐200 °C. FT‐IR (KBr, , cm‐1): 2934 (C‐H) 1422 (C=N). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 7.90 (m, 1H, Ar‐H), 7.8 (d, 1H, Ar‐H), 7.74 (d, 2H, Ar‐H), 7.62 (m, 2H, Ar‐H), 7.40 (m, 1H, Ar‐H), 7.24 (m, 2H, Ar‐H), 5.40 (s, 2H, O‐CH2), 2.30 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 168.02, 40.2, 135.1, 135.6, 132.4, 132.0, 130.3, 128.1, 126.6, 126.0, 125.9, 124.8, 123.2, 121.5, 118.4, 118.2, 71.1, 23.2. MS (EI, m/z (%)): 318.11 (M+H). 2‐((5‐(3‐Fluoro phenyl)‐1, 3, 4‐oxadiazol‐2‐yl)methoxy)‐3‐ methyl quinoxaline (5b): Color: Yellow. Yield: 78%. M.p.: 202‐ 204 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 7.91 (m, 1H, Ar‐ H), 7.81 (m, 3H, Ar‐H), 7.62 (m, 1H, Ar‐H), 7.42 (m, 2H, Ar‐H), 7.30 (m, 1H, Ar‐H), 5.38 (s, 2H, O‐CH2), 2.31 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 168.2, 140.8, 138.9, 135.4, 135.2, 132.1, 1320.8, 130.1, 128.3, 128.1, 126.4, 126.3, 124.5, 123.6, 118.1, 70.6, 22.3. MS (EI, m/z (%)): 337 (M+H). 2‐((5‐(4‐Fluoro phenyl)‐1,3,4‐oxadiazol‐2‐yl)methoxy)‐3‐ methyl quinoxaline (5c): Color: White. Yield: 68%. M.p.: 200‐ 202 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 7.90 (m, 2H, Ar‐ H), 7.81 (m, 2H, Ar‐H), 7.62 (m, 2H, Ar‐H), 7.41 (m, 1H, Ar‐H), 7.32 (m, 1H, Ar‐H), 5.40 (s, 2H, O‐CH2), 2.30 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 168.1, 140.9, 138.9, 135.5, 135.3, 132.2, 130.9, 130.2, 128.4, 128.2, 126.5, 126.4, 124.6, 123.6, 118.1, 70.5, 23.0. MS (EI, m/z (%)): 337 (M+H). 2‐((5‐(2‐Hydroxy phenyl)‐1,3,4‐oxadiazol‐2‐yl)methoxy)‐3‐ methyl quinoxaline (5d): Color: White. Yield: 69%. M.p.: 202‐ 203 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 10.80 (brs, 1H, OH), 8.01 (m, 2H, Ar‐H), 7.88 (m, 2H, Ar‐H), 7.64 (m, 2H, Ar‐H), 7.42 (m, 1H, Ar‐H), 7.30 (m, 1H, Ar‐H), 5.41 (s, 2H, O‐CH2), 2.31 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 168.2, 140.8, 139.0, 135.6, 135.4, 132.2, 140.0, 130.2, 128.5, 128.3, 126.5, 126.3, 124.5, 123.7, 118.2, 70.6, 22.9. MS (EI, m/z (%)): 335 (M+H). 2‐((5‐(3‐Hydroxy phenyl)‐1, 3, 4‐oxadiazol‐2‐yl)methoxy)‐3‐ methyl quinoxaline (5e): Color: Brown. Yield: 67%. M.p.: 206‐ 208 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 10.78 (brs, 1H, OH), 7.99 (m, 2H, Ar‐H), 7.89 (m, 2H, Ar‐H), 7.64 (m, 2H, Ar‐H), 7.42 (m, 1H, Ar‐H), 7.32 (m, 1H, Ar‐H), 5.42 (s, 2H, O‐CH2), 2.32 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 168.5, 140.9, 139.1, 135.8, 135.5, 132.4, 130.2, 130.0, 128.5, 128.3, 126.5, 126.2, 124.6, 123.7, 118.3, 71.0, 23.1. MS (EI, m/z (%)): 335 (M+H). 2‐((5‐(4‐Methoxy phenyl)‐1,3,4‐oxadiazol‐2‐yl)methoxy)‐ 3‐methyl quinoxaline (5f): Color: Yellow. Yield: 76%. M.p.: 208‐ 210 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 7.98 (m, 2H, Ar‐ H), 7.88 (m, 2H, Ar‐H), 7.65 (m, 2H, Ar‐H), 7.43 (2H, Ar‐H), 5.40 (s, 2H, Ar‐H), 3.86 (s, 3H, O‐CH2), 2.31 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 167.2, 141.2, 139.5, 135.8, 136.5, 136.2, 134.5, 131.2, 130.8, 128.5, 128.2, 126.5, 126.1, 124.5, 123.8, 118.5, 70.8, 67.5, 23.2. MS (EI, m/z (%)): 349 (M+H). 2‐((5‐(2‐Methoxy phenyl)‐1,3,4‐oxadiazol‐2‐yl)methoxy)‐3‐ methyl quinoxaline (5g): Color: Yellow. Yield: 80%. M.p.: 206‐ 208 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 7.99 (m, 2H, Ar‐ H), 7.89 (m, 2H, Ar‐H), 7.63 (m, 2H, Ar‐H), 7.42 (m, 2H, Ar‐H), 5.40 (s, 2H, O‐CH2), 3.85 (s, 3H, OCH3), 2.30 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm):167.1, 141.2, 139.5, 136.5, 136.3, 134.6, 131.3, 130.8, 128.6, 128.3, 126.4, 126.1, 124.4, 123.8, 118.6, 70.8, 67.6, 23.1. MS (EI, m/z (%)): 349 (M+H). 2‐((5‐(3‐Methoxy phenyl)‐1,3,4‐oxadiazol‐2‐yl)methoxy)‐3‐ methyl quinoxaline (5h): Color: Yellow. Yield: 82%. M.p.: 206‐ 208 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.00 (m, 2H, Ar‐ H), 7.88 (m, 2H, Ar‐H), 7.62 (m, 2H, Ar‐H), 7.42 (m, 2H, Ar‐H), 5.39 (s, 2H, O‐CH2), 3.86 (s, 3H, OCH3), 2.32 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 167.2, 141.3, 139.4, 136.5, ss136.2, 134.5, 131.4, 130.8, 128.5, 128.2, 126.5, 126.0, 124.5, 123.8, 118.5, 70.7, 67.5, 23.0. MS (EI, m/z (%)): 349 (M+H). 128 Kethireddy et al. / European Journal of Chemistry 8 (2) (2017) 125‐129 Table 1. Anti‐bacterial activity of 1,3,4‐oxadiazole and tetrazole derivatives. Compound Ar Gram negative Gram positive E. coli (ATCC 25922) P. aeruginosa (ATCC 27853) S. aureus (ATCC 12598) B. subtilis (ATCC 6633) Zones of inhibition of compounds in mm 5a 5Ph 15 18 17 15 5b 3F‐Ph 17 19 17 16 5c 4F‐Ph 22 21 20 17 5d 2OH‐Ph 17 17 16 15 5e 3OH‐Ph 16 16 15 14 5f 4OCH3‐Ph 15 26 19 21 5g 2OCH3‐Ph 18 13 16 17 5h 3OCH3‐Ph 11 15 18 18 6a 5Ph 9 8 11 14 6b 3F‐Ph 13 12 13 14 6c 4F‐Ph 12 14 12 13 6d 2OH‐Ph 15 26 24 19 6e 3OH‐Ph 11 16 18 28 6f 4OCH3‐Ph 23 15 17 16 6g 2OCH3‐Ph 13 27 21 19 6h 3OCH3‐Ph 19 22 11 23 Gentamycin ‐ 35 36 30 35 2.2.5. Synthesis of 3‐methylquinoxalin‐2‐yl‐2‐(5‐aryl‐2H‐ tetrazol‐2‐yl)acetate (6a‐h) A round‐bottom flask equipped with a magnetic stirrer was charged with aryltetrazole (0.14 mmol) and acetone (25 mL). The suspension was cooled to 0 °C before adding anhydrous potassium carbonate. After stirring for 30 minutes at 0 °C, 3‐methylquinoxalin‐2‐yl 2‐bromoacetate (0.16 mmol) was added to the opaque mixture. The reaction was stirred for 16 h while slowly warming to room temperature. The mixture was filtered and thoroughly washed with additional acetone. The clear filtrate was concentrated under reduced pressure to give solid (Scheme 1). 3‐Methylquinoxalin‐2‐yl‐2‐(5‐phenyl‐2H‐tetrazol‐2‐yl) acetate (6a): Color: White. Yield: 80%. M.p.: 200‐202 °C. FT‐IR (KBr, , cm‐1): 3011 (C‐H) 1248 (C=N). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.16 (d, 1H, Ar‐H), 7.95 (m, 1H, Ar‐H), 7.81 (m, 3H, Ar‐H), 7.58 (d, 2H, Ar‐H), 7.32 (d, 1H, Ar‐H), 7.28 (m, 1H, Ar‐H), 5.40 (s, 2H, CO‐CH2), 2.30 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 174.1, 159.5, 136.2, 134.4, 132.8, 130.1, 129.5, 128.0, 126.8, 126.5, 126.1, 125.9, 124.5, 122.1, 122, 119.8, 118.2, 66.5, 20.1. MS (EI, m/z (%)): 346.12 (M+H). 3‐Methylquinoxalin‐2‐yl‐2‐(5‐(3‐fluorophenyl)‐2H‐tetrazol‐ 2‐yl)acetate (6b): Color: Yellow. Yield: 82%. M.p.: 202‐204 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.28 (d, 1H, Ar‐H), 7.72 (d, 1H, Ar‐H), 7.60 (d, 1H, Ar‐H), 7.54 (m, 2H, Ar‐H), 7.32 (m, 1H, Ar‐H), 7.22 (m, 2H, Ar‐H), 5.42 (s, 2H, CO‐CH2), 2.28 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 174.2, 159.5, 159.0, 138.0, 136.1, 134.2, 130.1, 129.2, 128.8, 128.2, 127.8, 126.7, 126.2, 124.2, 119.4, 65.8, 19.8. MS (EI, m/z (%)): 365 (M+H). 3‐Methylquinoxalin‐2‐yl‐2‐(5‐(4‐fluorophenyl)‐2H‐tetrazol‐ 2‐yl)acetate (6c): Color: Yellow. Yield: 78%. M.p.: 202‐204 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.26 (d, 1H, Ar‐H), 7.74 (d, 1H, Ar‐H), 7.65 (d, 1H, Ar‐H), 7.55 (m, 2H, Ar‐H), 7.31 (m, 1H, Ar‐H), 7.24 (m, 2H, Ar‐H), 5.43 (s, 2H, CO‐CH2), 2.30 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 174.1, 159.6, 159.2, 138.2, 136.2, 134.1, 130.2, 129.1, 128.8, 128.2, 127.8, 126.7, 126.6, 126.2, 124.1, 119.5, 66.0, 19.9. MS (EI, m/z (%)): 365 (M+H). 3‐Methylquinoxalin‐2‐yl‐2‐(5‐(2‐hydroxyphenyl)‐2H‐tetra zol‐2‐yl)acetate (6d): Color: Brown. Yield: 82%. M.p.: 204‐206 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 10.81 (brs, 1H, OH), 8.18 (d, 2H, Ar‐H), 7.66 (d, 1H, Ar‐H), 7.56 (d, 2H, Ar‐H), 7.26 (m, 1H, Ar‐H), 7.31 (m, 1H, Ar‐H), 7.24 (m, 1H, Ar‐H), 5.43 (s, 2H, CO‐CH2), 2.30 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 174.2, 160.1, 159.2, 139.5, 136.5, 134.0, 130.5, 130.2, 129.0, 128.5, 127.6, 126.5, 126.1, 124.0, 118.5, 66.5, 21.5. MS (EI, m/z (%)): 363 (M+H). 3‐Methylquinoxalin‐2‐yl‐2‐(5‐(3‐hydroxyphenyl)‐2H‐tetra zol‐2‐yl)acetate (6e): Color: Yellow. Yield: 84%. M.p.: 204‐206 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 10.84 (brs, 1H, OH), 8.16 (d, 2H, Ar‐H), 7.67 (d, 2H, Ar‐H), 7.55 (m, 2H, Ar‐H), 7.35 (m, 1H, Ar‐H), 7.25 (m, 1H, Ar‐H), 5.41 (s, 2H, CO‐CH2), 2.30 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 174.3, 160.2, 159.6, 139.6, 136.6, 134.2, 130.6, 130.1, 129.3, 128.6, 127.6, 126.6, 126.1, 124.2, 119.6, 66.8, 21.5. MS (EI, m/z (%)): 363 (M+H). 3‐Methylquinoxalin‐2‐yl‐2‐(5‐(4‐methoxyphenyl)‐2H‐tetra zol‐2‐yl)acetate (6f): Color: Yellow. Yield: 80%. M.p.: 210‐212 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.16 (d, 2H, Ar‐H), 7.68 (d, 2H, Ar‐H), 7.56 (m, 2H, Ar‐H), 7.36 (m, 2H, Ar‐H), 5.40 (s, 2H, CO‐CH2), 3.84 (s, 3H, OCH3), 2.31 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 175.1, 161.3, 159.5, 140.3, 136.5, 134.5, 130.7, 130.2, 129.8, 128.6, 127.9, 126.5, 126.1, 124.8, 120.3, 68.9, 22.6. MS (EI, m/z (%)): 377 (M+H). 3‐Methylquinoxalin‐2‐yl‐2‐(5‐(2‐methoxyphenyl)‐2H‐tetra zol‐2‐yl)acetate (6g): Color: Yellow. Yield: 76%. M.p.: 210‐212 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.15 (d, 2H, Ar‐H), 7.68 (d, 2H, Ar‐H), 7.60 (m, 2H, Ar‐H), 7.40 (m, 2H, Ar‐H), 5.41 (s, 2H, CO‐CH2), 3.82 (s, 3H, OCH3), 2.30 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 174.3, 161.2, 159.5, 140.4, 136.5, 134.5, 130.8, 130.2, 129.8, 128.5, 127.9, 126.6, 126.2, 124.8, 120.2, 68.9, 22.5. MS (EI, m/z (%)): 377 (M+H). 3‐Methylquinoxalin‐2‐yl‐2‐(5‐(3‐methoxyphenyl)‐2H‐tetra zol‐2‐yl)acetate (6h): Color: Yellow. Yield: 78%. M.p.: 210‐212 °C. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 8.14(d, 2H, Ar‐H), 7.68 (d, 2H, Ar‐H), 7.58 (m, 2H, Ar‐H), 7.40 (m, 2H, Ar‐H), 5.40 (s, 2H, CO‐CH2), 3.83 (s, 3H, OCH3), 2.31 (s, 3H, CH3). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 174.5, 161.3, 159.5, 140.5, 136.6, 134.6, 131.2, 130.8, 130.2, 129.8, 128.8, 127.9, 127.1, 126.3, 125.2, 120.5, 69.0, 65.4, 22.3. MS (EI, m/z (%)): 377 (M+H). 2.2.6. Anti‐bacterial activity Agar well diffusion method was used to determine the anti‐microbial activity of synthesized compounds, 2‐((5‐aryl‐ 1,3,4‐oxadiazol‐2‐yl)methoxy)‐3‐methyl quinoxalines and 3‐ methylquinoxalin‐2‐yl‐2‐(5‐aryl‐2H‐tetrazol‐2‐yl)acetates. All the compounds were tested against Gram positive strains (Staphylococcus aureus (ATCC 12598) and Bacillus subtilis (ATCC 6633) and Gram negative strains (Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853) and standard anti‐bacterial drug Gentamycin is used as reference drug (Table 1). Kethireddy et al. / European Journal of Chemistry 8 (2) (2017) 125‐129 129 3. Results and discussions Taking into account the importance of quinoxalines, tetrazoles and 1,3,4‐oxadiazoles to both medicinal and heterocyclic chemistry, 2‐((5‐aryl‐1,3,4‐oxadiazol‐2‐yl) met‐ hoxy)‐3‐methyl quinoxaline and 3‐methylquinoxalin‐2‐yl‐2‐ (5‐aryl‐2H‐tetrazol‐2‐yl)acetate derivatives are synthesized from N'‐Arylidene‐2‐((3‐methylquinoxalin‐2‐yl)oxy)aceto hydrazide. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR and Mass spectral data. They have been screened for their antibacterial activity against four pathogenic strains. The screening results of antibacterial activity of 1,3,4‐ oxadiazole and tetrazole derivatives 5a‐f and 6a‐f are summa‐ rized in Table 1. Compounds 5c, 6d and 6g show moderate activity in the range of 20‐24 mm against S. aureus. Compounds 5f and 6h exhibit moderate activity against B. subtilis. Compounds 5c and 6f against E. coli and compounds 5c and 6h against P. aeruginosa. Compounds 5f, 6d and 6g exhibit excellent activity in the range of 25‐28 mm against P. aeruginosa. Compound 6e shows appreciable activity against B. subtilis. 4. Conclusion Herein we reported the synthesis of some new, 2‐((5‐aryl‐ 1,3,4‐oxadiazol‐2‐yl)methoxy)‐3‐methyl quinoxaline and 3‐ methylquinoxalin‐2‐yl‐2‐(5‐aryl‐2H‐tetrazol‐2‐yl)acetate derivatives and recorded their antibacterial activity. 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