Microwave assisted synthesis, characterization and evaluation for their antimicrobial activities of some novel pyrazole substituted 9-anilino acridine derivatives
Rajagopal Kalirajan, V Muralidharan, Selvaraj Jubie, S Sankar
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Ootacamund, Tamil Nadu, India
Rajagopal Kalirajan
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Ootacamund - 643 001, Tamil Nadu
Objective: The paper focuses on the microwave synthesis of a new series of 9-anilinoacridine derivatives 4a-g, 5a-g, and 6a-g. Materials and methods: The compounds were confirmed by physical and analytical data. The synthesized compounds when screened for in vitro anti-microbial activity showed promising activity for many compounds. The in vitro anti-microbial activities of the synthesized compounds were evaluated against some bacteria and fungi strains. Results and Discussions: The results suggested that, the products 4a-g, 5a-g, and 6a-g exhibited good inhibitory effect against most of the tested organisms. Especially, 4b, 5a, 5d, 6b, and 6e were shown to be most effective against Bacillus subtilis, Escherichia coli at the concentration of 25 μg/ml and Candida albicans at the concentration of 50 μg/ml.
Keywords: Acridine, anti-microbial, chalcone, microwave synthesis, pyrazole
Kalirajan R, Muralidharan V, Jubie S, Sankar S. Microwave assisted synthesis, characterization and evaluation for their antimicrobial activities of some novel pyrazole substituted 9-anilino acridine derivatives. Int J Health Allied Sci 2013;2:81-7
Kalirajan R, Muralidharan V, Jubie S, Sankar S. Microwave assisted synthesis, characterization and evaluation for their antimicrobial activities of some novel pyrazole substituted 9-anilino acridine derivatives. Int J Health Allied Sci [serial online] 2013 [cited 2020 Jan 23];2:81-7. Available from: http://www.ijhas.in/text.asp?2013/2/2/81/115682
Acridine derivatives are principally used in medicine and have enormous potential as pharmaceutical agents due to their biological activities, [1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14] such as anti-microbial, anti-oxidant, anti-cancer, anti-malarial, anti-inflammatory, analgesic, anti-leishmanial, anti-nociceptive, acetyl cholinesterase inhibitors, and anti-herpes. The chemical modification of 9-anilinoacridines such as the introduction of different substitutions or hetero atoms has allowed expansion of research on the structure activity relationship to afford new insight into molecular interactions at the receptor level. In fact, it is well-established that slight structural modification on the 9-anilinoacridine ring may bring various pharmacological effects. Pyrazole derivatives also have various biological activities. [15],[16],[17] In order to look for some new compounds with an interesting biological properties we would like to synthesize some novel chalcone and pyrazole derivatives of 9-anilinoacridine.
Melting points were determined on a veego (model- VMP-1) melting point apparatus and are uncorrected. InfraRed (IR) spectra were recorded on a shimadzu 8400S Fourier Transform InfraRed spectrometer. 1 H Nuclear Magnetic Resonance (NMR) spectra and 13 C NMR on Bruker AV III 500 MHz spectrometer (500 MHz for 1 H NMR spectra and 125 MHz for 13 C NMR) using Trimethyl silane (TMS) as internal standard and CDCl 3 as solvent. The chemical shifts are expressed in Parts per million (ppm) (δ). Mass spectra were obtained on JOEL GC mate Mass spectrometer. Reactions were carried and monitored by a thin layer chromatography plates (5 cm × 20 cm) with 0.2 mm silica gel GF and the spots were viewed in UV or iodine chamber. Microwave irradiation was carried out in cata scientific microwave synthesis system 2400 MHZ, catalyst systems, India.
Synthesis of N-phenylanthranilic acid (1)
In a 250 ml flask, a mixture of 38.595 g (0.415 mol) of aniline, 10.177 g (0.065 mol) of o-chloro benzoic acid, 10.366 g (0.075 mol) of technical anhydrous potassium carbonate and 0.5 g of copper oxide were taken and subjected to microwave irradiation for 10 min at 80% intensity (560 W). After completion of the reaction, the excess of unreacted aniline was removed by steam distillation and 5 g of decolorizing carbon was added to the brown residual solution. The mixture was boiled for 15 min and filtered by suction. The filtrate was added, with stirring, to a mixture of 25 ml of concentrated hydrochloric acid and 100 ml of water. The precipitated acid was filtered with suction when cold and dried crystallized from alcohol-water.
Synthesis of 9-chloroacridine (2)
In a 250 ml flask, a mixture of 1.278 g (0.006 mol) of N-phenylanthranilic acid, 19.781 g (0.131 mol) of phosphorous oxy chloride were taken and subjected to microwave irradiation for 3 min at 65% intensity (455 W). After completion of the reaction excess of phosphorus oxy chloride was removed by distillation from an oil bath at 140°C to 150°C under vacuum. After cooling to room temperature, the reaction mixture was poured into a well-stirred mixture of 5.21 ml concentrated ammonia, 13 g of crushed ice and allowed to stand for 30 min to precipitate the solid. The precipitate formed was filtered with suction washed 3 times with saturated sodium carbonate solution and finally with water and dried and crystallized from ethanol.
Synthesis of 1-(4-[Acridin-9-ylamino] phenyl) ethanone (3)
In a 250 ml flask, a mixture of 4.06 g (0.03 mol) of 4-aminoacetophenone, 5.4528 g (0.0256 mol) of 9-chloroacridine and 80 ml of 2-butanol were taken and subjected to microwave irradiation for 3 min at 65% intensity (455 W). After completion of the reaction, the reaction mixture was allowed to cool to room temperature then it was poured into 150 ml of ice water. A precipitate formed was filtered by suction, washed with water and dried crystallized from ethanol. The yield was 80%.
General procedure for synthesis of chalcones under microwave irradiation (4a-g)
In a 25 ml flask, 0.0032 mol of corresponding aldehyde, 5 ml of ethylene glycol, 0.5 ml of piperidine and 0.9984 g (0.0032 mol) of 9-anilinoacridine were taken and subjected to microwave irradiation for 4 min at 100% intensity (700 W). Irradiation was carried out in successive 30 s periods to avoid over heating of the solvent and the reaction mixture, another 30 s at room temperature as a time gap between every successive irradiation period. After completion of the reaction, the reaction mixture was cooled and poured into 10 ml of water. The precipitated solid was filtered off washed with water and dried and crystallized from ethanol.
(E)-1-(4-[acridin-9-ylamino] phenyl)-3-(4-methoxyphenyl) prop-2-en-1-one (4a)
Yellow crystals, yield 71%, mp 179-181°C. IR (KBr, υ, cm–1 ): 3273 (N-H), 3100-3000 (Ar C-H), 1626 (α,β-unsaturated C = O), 1607 and 1510 (Ar C = C), 1260 (C-N), 1168 (C-O), 748 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.01 ( s, 1H, NH), 7.56 (d, 1H CH), 7.90 (d, 1H CH), 8.06-6.62 (m, 14H, Ar-H), 3.73 (s, 3H, OCH 3 ). MS (m/z): 431 (M + 1).
(E)-1-(4-[acridin-9-ylamino] phenyl)-3-phenylprop-2-en-1-one (4b)
Yellow crystals, yield 70%, mp 180-182°C. IR (KBr, υ, cm –1 ): 3269 (N-H), 3057-3000 (Ar C-H), 1647 (α,β-unsaturated C = O), 1604 and 1516 (Ar C = C), 1226 (C-N), 759 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.02 ( s, 1H, NH), 8.06-6.62 (m, 16H, Ar-H), 7.56 (d, 1H, CH), 7.90 (d, 1H, CH), MS (m/z): 401.1 (M + 1).
(E)-1-(4-[acridin-9-ylamino] phenyl)-3-(2-hydroxyphenyl) prop-2-en-1-one (4c)
Yellow crystals, yield 61%, mp 209-211°C. IR (KBr, υ, cm–1 ): 3560 (N-H), 3302 (O-H), 3100-3000 (Ar C-H), 1654 (α,β-unsaturated C = O), 1627 and 1516 (Ar C = C), 1280 (C-N), 1151 (C-O), 748 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.12 ( s, 1H, NH), 5.08 ( s, 1H, OH), 7.56 (d, 1H, CH), 7.90 (d, 1H, CH) 8.03-6.65 (m, 14H, Ar-H). MS (m/z):416.2 (M+).
(E)-1-(4-[acridin-9-ylamino] phenyl)-3-(furan-2-yl) prop-2-en-1-one (4d)
Yellow crystals, yield 68%, mp 179-181°C. IR (KBr, υ, cm –1 ): 3300 (N-H), 3057-3034 (Ar C-H), 1651 (α,β-unsaturated C = O), 1606 and 1512 (Ar C = C), 1230 (C-N), 1176 (C-O), 759 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.04 ( s, 1H, NH), 7.58 (d, 1H, CH), 7.91 (d, 1H, CH), 8.04-6.64 (m, 14H, Ar-H). MS (m/z): 391.14 (M + 1).
(E)-1-(4-[acridin-9-ylamino] phenyl)-3-(4-hydroxyphenyl) prop-2-en-1-one (4e)
Yellow crystals, yield 60%, mp 208-210°C. IR (KBr, υ, cm–1 ): 3302 (N-H), 3238 (O-H), 3059-3034 (Ar C-H), 1626 (α,β-unsaturated C = O), 1626 and 1527 (Ar C = C), 1280 (C-N), 1151 (C-O), 748 (Ar-C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.02 ( s, 1H, NH), 5.06 ( s, 1H, OH), 7.57 (d, 1H, CH), 8.02-6.62 (m, 14H, Ar-H). MS (m/z): 416.1 (M+).
(E)-1-(4-[acridin-9-ylamino] phenyl)-3-(4-[dimethylamino] phenyl) prop-2-en-1-one (4f)
Orange crystals yield 69%, mp 165-167°C. IR (KBr, υ, cm –1 ): 3313 (N-H), 3099-2999 (Ar C-H), 1654 (α,β-unsaturated C = O), 1604 and 1500 (Ar C = C), 1261 (C-N), 750 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.03 ( s, 1H, NH), 2.83 ( s, 6H, CH 3 ), 7.54 (d, 1H, CH), 8.02-6.62 (m, 15H, Ar-H). MS (m/z):444.20 (M + 1).
(E)-1-(4-[acridin-9-ylamino] phenyl)-3-(2, 4-dichlorophenyl) prop-2-en-1-one (4 g)
Orange crystals yield 71%, mp 228-230°C. IR (KBr, υ, cm –1 ): 3294 (N-H), 3100-3000 (Ar C-H), 1649 (α,β-unsaturated C = O), 1606 and 1518 (Ar C = C), 1257 (C-N), 756 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.1 ( s, 1H, NH), 7.34 (d, 1H, CH), 8.17 (d, 1H, CH), 8.02-6.62 (m, 14H, Ar-H). MS (m/z):470.08 (M + 1).
Synthesis of pyrazole substituted 9-anilinoacridines under microwave irradiation (5a-g)
In a 50 ml flask, a solution of 0.0025 mol of the corresponding chalcones 4a-g in 20 ml of absolute ethanol and 0.2503 g (0.005 mol) of hydrazine hydrate (99%) were taken and subjected to microwave irradiation for 15-20 min at 20% intensity (140 W). After completion of the reaction, solvent was removed by vacuum distillation, residue obtained was washed well with water, dried and recrystallized from ethanol.
N-(4-[5-[4-methoxyphenyl]-1H-pyrazol-3-yl] phenyl) acridin-9-amine (5a)
Orange crystals yield 57%, mp 97-99°C. IR (KBr, υ, cm –1 ): 3306 (N-H), 3100-2999 (Ar C-H), 1593 and 1514 (Ar C = C), 1263 and 1151 (C-O), 1246 (C-N), 750 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 13.01 ( s, 1H, Pyrazole, NH), 4.18 (s, 1H, NH), 7.80-6.65 (m, 17H, Ar-H), 3.80 (s, 3H, OCH 3 ); 13 C NMR: 126.7, 127.45, 130.89, 126.02, 127.03, 125.75, 151.74, 117.42, 134.93, 133.42, 120.35, 132.75, 123.64, 128.27, 125.16, 121.34, 123.17, 140.21, 113.71, 135.11, 129.13, 127.51, 129.13, 159.16, 121.42, 127.51, 55.32. MS EI (m/z): 441.67 (M+, 20%), 426.84 (24%), 397.14 (48%), 306.88 (100%), 289.93 (60%), 263.11 (64%). 217.32 (40%), 190.44 (38%), 175.51 (50%).
N-(4-[5-phenyl-1H-pyrazol-3-yl] phenyl) acridin-9-amine (5b)
Orange crystals yield 78%, mp 110-112°C. IR (KBr, υ, cm –1 ): 3269 (N-H), 3100-3000 (Ar C-H), 1591 and 1489 (Ar C = C), 1263 (C-N), 754 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 13.05 ( s, 1H, Pyrazole, NH), 3.96 (s, 1H, NH), 7.80-6.65 (m, 18H, Ar-H); 13 C NMR: 127.59, 127.73, 130.54, 127.52, 127.46, 130.51, 127.66, 151.48, 117.36, 130.88, 130.74, 120.35, 130.65, 126.14, 128.80, 126.36, 128.84, 125.79, 142.89, 114.81, 133.45, 128.83, 128.51, 128.73, 125.16, 123.85, 128.51. MS EI (m/z): 411.59 (M+, 100%), 391.17 (24%), 382.40 (16%), 308.90 (30%), 291.94 (22%), 266.08 (32%), 204.06 (16%), 177.54 (12%).
2-(3-[4-[acridin-9-ylamino] phenyl]-1H-pyrazol-5-yl) phenol (5c)
Yellow crystals yield 57%, mp 203-205°C. IR (KBr, υ, cm –1 ): 3313 (N-H), 3100-2995 (Ar C-H), 1604 and 1498 (Ar C = C), 1261 (C-N), 1147 (C-O), 750 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 13.11 ( s, 1H, Pyrazole, NH), 5.04 (s, 1H, OH), 4.09 (s, 1H, NH), 7.77-6.83 (m, 17H, Ar-H); 13 C NMR: 125.71, 127.07, 130.02, 125.71, 125.73, 130.08, 126.76, 124.62, 151.74, 116.65, 130.90, 130.60, 120.35, 130.62, 121.46, 128.24, 124.62, 128.22, 121.34, 147.35, 115.49, 135.11, 129.13, 159.16, 129.13, 120.36, 121.35, 128.21. MS EI (m/z): 427.52 (M+, 20%), 356.16 (10%), 318.84 (56%), 309.87 (100%), 294.86 (68%), 266.10 (74%), 177.50 (70%).
N-(4-[5-[furan-2-yl]-1H-pyrazol-3-yl] phenyl) acridin-9-amine (5d)
Brownish orange crystals yield 78%, mp 108-110°C. IR (KBr, υ, cm –1 ): 3100-3000 (Ar C-H), 1591 and 1485 (Ar C = C), 1263 (C-N), 1151 (C-O), 752 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 13.02 ( s, 1H, Pyrazole, NH), 4.09 (s, 1H, NH), 7.85-6.22 (m, 16H, Ar-H); 13 C NMR: 125b. 64, 127.50, 130.41, 125.10, 125.13, 130.41, 126.99, 123.65, 152.15, 105.93, 130.68, 130.41, 110.27, 130.68, 120.35, 130.68, 121.35, 128.21, 117.25, 147.42, 105.93, 142.24, 116.60, 154.89, 129.12, 127.56, 114.71. MS EI (m/z): 399.14 (M + -3, 100%), 387.30 (20%), 308.84 (24%), 291.91 (32%), 266.04 (28%), 177.51 (24%).
4-(3-[4-[acridin-9-ylamino] phenyl]-1H-pyrazol-5-yl) phenol (5e)
Brownish orange crystals yield 56%, mp 152-154°C. IR (KBr, υ, cm –1 ): 3313 (N-H), 3194 (C-O), 3100-2995 (Ar C-H), 1604 and 1523 (Ar C = C), 1276 (C-N), 1261 and 1147 (C-O), 750 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 13.23 ( s, 1H, Pyrazole, NH), 3.97 (s, 1H, NH), 5.62 (s, 1H, OH) 7.86-6.79 (m, 17H, Ar-H); 13 C NMR: 125.71, 127.07, 130.02, 124.62, 124.63, 130.02, 126.74, 121.45, 152.27, 116.67, 133.45, 130.85, 120.37, 130.60, 120.35, 128.22, 121.34, 128.22, 127.07, 147.75, 115.49, 135.11, 129.10, 127.07, 129.10, 159.11, 121.47, 127.07. MS EI (m/z): 427.12 (M+, 8%), 400.15 (10%), 377.41 (12%), 309.67 (20%), 232.83 (16%), 192.44 (24%), 177.46 (44%).
N-(4-[5-[4-[dimethylamino] phenyl]-1H-pyrazol-3-yl] phenyl) acridin-9-amine (5f)
Brown crystals yield 56%, mp 138-140°C. IR (KBr, υ, cm –1 ): 3313 (N-H), 3100-3000 (Ar C-H), 1599 and 1473 (Ar C = C), 1261 (C-N), 750 (Ar C-H).). 1 H NMR (CDCl 3 ) δ ppm: 13.12 ( s, 1H, Pyrazole, NH), 4.13 (s, 1H, NH), 3.04 (s, 6H, 2CH 3 ) 7.85-6.67 (m, 17H, Ar-H); 13 C NMR: 122.10, 127.49, 130.89, 117.35, 117.34, 130.64, 126.78, 117.28, 152.13, 112.08, 130.85, 130.64, 113.71, 130.85, 111.24, 129.55, 114.76, 147.51, 111.96, 133.42, 129.89, 128.26, 129.73, 160.81, 114.50, 128.26, 40.22, 40.31. MS EI (m/z): 454.44 (25%), 387.87 (12%), 355.46 (20%), 322.12 (56%), 308.76 (36%), 284.70 (32%), 217.80 (26%), 198.95 (32%), 176.32 (22%).
N-(4-[5- [2, 4-dichlorophenyl]-1H-pyrazol-3-yl] phenyl) acridin-9-amine (5 g)
Orange crystals yield 58%, mp 110-112°C. IR (KBr, υ, cm –1 ): 3282 (C-N), 3100-3000 (Ar C-H), 1606 and 1515 (Ar C = C), 1263 (C-N), 752 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 13.03 ( s, 1H, Pyrazole, NH), 4.07 (s, 1H, NH), 7.68-6.66 (m, 16H, Ar-H); 13 C NMR: 128.43, 129.30, 130.40, 125.15, 128.33, 131.75, 129.01, 127.58, 151.53, 117.42, 138.73, 133.67, 120.27, 133.36, 127.46, 130.60, 127.53, 130.61, 125.79, 147.44, 114.78, 138.90, 130.80, 138.90, 130.80, 138.73, 123.78, 130.40. MS EI (m/z): 480.26 (M+, 8%), 464.18 (32%), 455.64 (36%), 414.84 (28%), 333.68 (28%), 307.89 (100%), 290.93 (56%), 265.07 (62%), 168.47 (32%).
Synthesis of N-Phenyl pyrazole substituted 9-anilinoacridines under mw irradiation (6a-g)
In a 50 ml flask, a solution of 0.0125 mol of the corresponding chalcones 4a-g in 20 ml of absolute ethanol and 0.24 g (0.0016 mol) of phenyl hydrazine hydrochloride were taken and subjected to microwave irradiation for 15-20 min at 20% intensity (140 W). After completion of the reaction, solvent was removed by vacuum distillation residue obtained was washed well with water and dried.
N-(4-[5-[4-methoxyphenyl]-1-phenyl-1H-pyrazol-3 -yl] phenyl) acridin-9-amine (6a)
Brick red crystals yield 68%, mp 280-282°C. IR (KBr, υ, cm –1 ): 3250 (N-H), 3091-2953 (Ar C-H), 1589 and 1496 (Ar C = C), 1273 (C-N), 1251 and 1165 (C-O), 750 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.05 (s, 1H, NH), 8.06-6.35 (m, 21H, Ar-H), 3.78 (s, 3H, OCH 3 ); 13 C NMR: 129.13, 129.75, 126.28, 128.89, 126.22, 127.03, 129.65, 125.75, 153.68, 114.72, 129.93, 130.12, 117.15, 128.25, 123.14, 128.32, 120.16, and 129. 4, 120.17, 114.75, 160.73, 114.71, 125.11, 144.13, 139.51, 126.33, 129.06, 127.51 and 55.83. MS (m/z): 519.11 (M+).
N-(4- [1, 5-diphenyl-1H-pyrazol-3-yl] phenyl) acridin-9-amine (6b)
Brownish black crystals yield 61%, mp 205-207°C. IR (KBr, υ, cm –1 ): 3100-3000 (Ar C-H), 1600 and 1496 (Ar C = C), 1273 (C-N), 750 (Ar C-H).). 1 H NMR (CDCl 3 ) δ ppm: 4.11 (s, 1H, NH), 8.02-6.51 (m, 22H, Ar-H). 13 C NMR: 129.18, 129.64, 126.28, 124.52, 114.73, 149.25, 114.68, 148.32, 126.38, 126.33, 129.68, 129.15, 116.76, 128.43, 123.16, 128.28, 153.64, 106.08, 144.52, 127.48, 127.48, 133.16, 120.18, 129.43, 120.12, 129.73, 129.5, 126.29. MS (m/z): 489.28 (M + 1).
2-(3-[4-[acridin-9-ylamino] phenyl]-1-phenyl-1H-pyrazol-5-yl) phenol (6c)
Brick red crystals yield 64%, mp 290-292°C. IR (KBr, υ, cm –1 ): 3400 (N-H), 3250 (O-H), 3088-3018 (Ar C-H), 1589 and 1506 (Ar C = C), 1273 (C-N), 1251 (C-O), 750 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.10 (s, 1H, NH), 5.08 (s, 1H, OH) 8.02-6.45 (m, 21H, Ar-H). 13 C NMR: 129.12, 129.74, 126.31, 124.62, 114.83, 149.65, 114.78, 148.36, 126.78, 126.73, 129.72, 129.12, 116.66, 128.33, 123.21, 128.28, 153.72, 106.02, 144.52, 120.58, 155.41, 116.36, 120.58, 129.93, 120.22, 129.38, 129.42, 126.34, 139.65. MS (m/z): 505.31 (M + 1).
N-(4-[5-[furan-2-yl]-1-phenyl-1H-pyrazol-3-yl] phenyl) acridin-9-amine (6d)
Orange crystals yield 60%, mp 298-300°C. IR (KBr, υ, cm–1 ): 3323 (N-H), 3090-3022 (Ar C-H), 1599 and 1489 (Ar C = C), 1273 (C-N), 1220 and 1165 (C-O), 754 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.12 (s, 1H, NH), 8.03-6.31 (m, 20H, Ar-H). 13 C NMR: 129.21, 129.72, 126.33, 124.53, 114.69, 149.65, 114.65, 148.42, 126.52, 126.63, 129.66, 129.16, 116.82, 128.26, 123.18, 128.35, 152.74, 107.15, 152.57, 107.08, 127.06, 157.61, 107.32, 105.03, 142.93, 120.24, 129.35, 129.46, 126.25, 139.72. MS (m/z): 479.68 (M + 1).
4-(3-[4-[acridin-9-ylamino] phenyl]-1-phenyl-1H-pyrazol-5-yl) phenol (6e)
Brick red crystals yield 63%, mp 295-297°C. IR (KBr, υ, cm –1 ): 3250 (N-H), 3090 (O-H), 3070-3018 (Ar C-H), 1589 and 1506 (Ar C = C), 1273 (C-N), 1251 (C-O), 750 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.02 (s, 1H, NH), 5.08 (s, 1H, OH), 8.03-6.48 (m, 20H, Ar-H). 13 C NMR: 129.07, 129.59, 126.25, 124.38, 114.92, 149.25, 114.65, 148.73, 126.32, 126.43, 129.59, 129.06, 143.22, 116.68, 128.33, 123.21, 128.42, 153.66, 106.04, 144.48, 128.88, 116.37, 158.44, 116.41, 128.79, 120.23, 120.28, 126.38, 129.43, 139.67. MS (m/z): 505.32 (M + 1).
N-(4-[5-[4-[dimethylamino] phenyl]-1-phenyl-1H-pyrazol-3-yl] phenyl) acridin-9-amine (6f)
Brick red crystals yield 56%, mp 284-286°C. IR (KBr, υ, cm –1 ): 3254 (N-H), 3086-3000 (Ar C-H), 1589 and 1506 (Ar C = C), 1273 (C-N), 1251 and 1163 (C-O), 750 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 4.11 (s, 1H, NH), 8.02-6.55 (m, 21H, Ar-H). 13 C NMR: 129.11, 129.81, 126.34, 124.53, 114.69, 148.28, 114.73, 149.75, 126.28, 126.23, 129.71, 129.21, 143.13, 116.91, 128.38, 123.14, 128.37, 153.74, 106.24, 144.47,122.63, 128.43, 114.76, 149.49, 114.41, 128.36, 120.28, 120.21, 126.31, 129.29, 40.27, 139.67, 40.25. MS (m/z): 532.27 (M + 1).
N-(4-[5- [2, 4-dichlorophenyl]-1-phenyl-1H-pyrazol-3-yl] phenyl) acridin-9-amine (6 g)
Orange crystals yield 59%, mp 230-232°C. IR (KBr, υ, cm –1 ): 3335 (N-H), 3100-3000 (Ar C-H), 1583 and 1506 (Ar C = C), 1259 (C-N), 750 (Ar C-H). 1 H NMR (CDCl 3 ) δ ppm: 3.98 (s, 1H, NH), 8.06-6.47 (m, 20H, Ar-H). 13 C NMR: 129.22, 129.74, 126.28, 124.61, 114.78, 148.93, 114.69, 148.34, 126.39, 126.42, 129.67, 129.18, 143.33, 116.86, 128.41, 123.08, 128.28, 153.69, 106.24, 144.47,128.13, 133.67, 130.92, 135.67, 127.56, 130.36, 120.31, 120.25, 126.36, 129.35. MS (m/z): 557.22 (M + 1).
In this study, the title compounds 4a-g, 5a-g and 6a-g was prepared according to the procedure outlined in the scheme [Figure 1]. 9-chloroacridine 2 was substituted with 4-amino acetophenone under microwave irradiation gave 1-(4-[acridin-9-ylamino] phenyl) ethanone 3. The compound 3 was then reacted with corresponding aromatic aldehydes (Ar-CHO) in the presence of ethylene glycol and piperidine under microwave irradiation gave chalcones 4a-g . Cyclization of 4a-g with hydrazines (R-NH-NH 2 ) in the presence of absolute ethanol at reflux under microwave irradiation afforded pyrazole substituted 9-anilinoacridines 5a-g and 6a-g in good yields.
Figure 1: Synthetic scheme for compounds
The chemical structure of the synthesized compounds was elucidated by IR, 1 H NMR and 13 C NMR and Mass spectral data. According to the IR spectral data, 4a-g showed the C = O peaks at 1600-1700 cm–1 region, which are disappeared for compounds 5a-g and 6a-g. The NH bands of 5a-g were observed in the region 3300-3400 cm –1 . In the 1 H NMR spectra of 5a-g, the NH proton of pyrazole ring was observed as a broad singlet at about 13.00-13.85 ppm. However, in 6a-g , it was not appeared due to phenyl substitution. All other aromatic and aliphatic protons of the compounds were observed at the expected regions. 13 C NMR of the compounds gave prominent signals provide further evidence for their structures. Mass spectra of all the synthesized compounds showed M + /M ++1 peaks in agreement with their molecular formula.
The newly synthesized compounds 4a-g, 5a-g, and 6a-g had been tested for their anti-microbial activity against Bacillus subtilis lis (G0 + ve), Escherichia More Details coli (G + ve) and Candida albicans by means of the cup and plate method in accordance with the experimental procedures previously described. [18] The results are summarized in the [Table 1].
Table 1: Antimicrobial activity of synthesized compounds 4a‑g, 5a‑g and 6a‑g
From the results obtained, it is obvious that most of the compounds showed promising activity against bacteria and fungi. The compounds 4b, 5a, 5d, 6b, and 6e showed significant inhibition effect on the growth of bacteria like B. subtilis and E. coli at the concentration of 25 μg/ml. However, all compounds have showed significant inhibition effect on the growth of bacteria like B. subtilis and E. coli at the concentration of 50 μg/ml. The compounds 4b, 5a, 5d, 6b, and 6e showed significant inhibition effect on the growth of fungi like C. albicans at the concentration of 50 μg/ml. However, all compounds have showed significant inhibition effect on the growth of C. albicans at the concentration of 100 μg/ml. The Minimum Inhibitory Concentration of compound 5a is 14.5 μg/ml, compound 5d is 12.5 μg/ml and compound 6e is 11 μg/ml. The 5 th position of pyrazole ring was substituted with p-methoxy phenyl, p-hydroxy phenyl and furan group increases the anti-bacterial activity. The ortho substituted phenyl and p-dimethyl amino phenyl group at 5 th position of pyrazole ring decreases the anti-bacterial activity.
A series of novel 9-anilinoacridines have been designed and synthesized. The anti-microbial activities of the synthesized compounds were evaluated. Among these compounds 4b, 5a, 5d, 6b, and 6e showed good anti-microbial activity and emerged as potential molecules for further development. With this set of analogs, we are now in a position to investigate the multiple biological activities for these compounds.
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Kalirajan R
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Jubie S
Sankar S
chalcone
microwave synthesis
pyrazole