Methods
All of the melting points were determined in open capillary tubes on a Gallenkamp melting point apparatus (London, UK). These data have been presented as the uncorrected values. Ultraviolet (UV) spectra were recorded on a JNWAY 6505 UV/vis spectrometer (Staffordshire, UK) in dimethylformamide (DMF). IR spectra were recorded as KBr disks on a PerkinElmer RXIFTIR spectrometer (Waltham, MA, USA). 1H NMR spectra were measured on a Varian Gemini 300 MHz spectrometer (Palo Alto, CA, USA). Chemical shifts (δ) have been expressed in ppm downfield from TMS, which was used as an internal standard. 1H NMR spectra were recorded in DMSO-d
6 and the coupling constants (J) reported in Hz. Mass spectra were recorded on a Shimadzu GC–MS QP 1000 EX system (Tokyo, Japan) operating at 70 eV. All of the reactions were monitored by thin-layer chromatography (TLC) using aluminum TLC sheets coated with silica gel F254 (Merck, Darmstadt, Germany). TLC was also used to assess the purity of the synthesized compounds.
General procedure for the mechanochemical formation of azlactones 2a–i
A mixture of glycine (1.0 mmol), aromatic aldehyde (1.0 mmol), benzoyl chloride (1.0 mmol) and fused sodium acetate (1.0 mmol) was mixed in a porcelain mortar and pestle in the presence of a few drops of acetic anhydride for a few minutes (Table 1). Upon completion of the reaction, as determined by TLC, the reaction mixture turned to a yellow solid, which was washed with cold water and recrystallized from ethanol to give the desired azlactone. The structures of the azlactones were confirmed based on a comparison of their m.p., mixed. m.p., TLC, IR, UV, 1H NMR and MS data with those from the literature.
General procedure for the conventional formation of azlactones 2a-i
A mixture of N-benzoyl glycine (hippuric acid) (1.2 mmol), aromatic aldehyde (1.0 mmol), acetic anhydride (3.0 mmol) and fused sodium acetate (1.5 mmol) was heated on a hot plate to liquefaction, and the resulting mixture was then heated on a water path for 2 h. Upon completion of the reaction, as determined by TLC, the mixture was cooled to room temperature and treated with EtOH (5 ml) [27, 28, 40]. The ethanolic mixture was then held in a refrigerator at 4°C overnight, and the resulting precipitate was collected by filtration. The solid product was then washed with hot water and air-dried at room temperature for 2 h before being recrystallized from ethanol to give the corresponding azlactones 2a–i.
4-Benzylidene-2-phenyl-5(4H)-oxazolone (2a)
UV (DMF): λmax 300 (log ε = 3.95) nm. IR (KBr): 1793, 1768 (C=O), 1652 (C=N), 1594 (C=C).1H NMR (300 MHz, DMSO-d
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): δ 7.35 (s, 1H, CH=C), 7.33–7.75 (m, 6H, Ar–H), 8.13 (d, 2H, J = 7.5 Hz), 8.30 (d, 2H, J = 7.8 Hz). MS (ESI) m/z (%): 249 (M+, 100).
(E/Z)-4-(4-Methoxybenzylidene)-2 phenyl-5(4H)-oxazolone (2b)
UV (DMF): λmax 290 (log ε = 3.93) nm.IR (KBr): 1788, 1769 (C=O), 1653 (C=N), 1600 (C=C).1H NMR (300 MHz, DMSO-d
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): δ 3.88 (s, 3H, CH3), 7.11 (d, 2H, J = 9.0 Hz), 7.64 (d, 2H, J = 7.5 Hz), 7.69 (d, 1H, J = 6.9 Hz), 8.11 (d, 2H, J = 6.9 Hz), 8.30 (d, 2H, J = 9.0 Hz). For the E-isomer (71 %): 7.33 (s, 1H, CH=C), for the Z-isomer (29 %): 7.60 (s, 1H, CH=C). MS (ESI) m/z (%): 279 (M+, 88), 105 (100).
(E/Z)-4-(4-Chlorobenzylidene)-2-phenyl-5(4H)-oxazolone (2c)
UV (DMF): λmax 252 (log ε = 4.00) nm.IR (KBr): 1795, 1766 (C=O), 1653 (C=N), 1585 (C=C). 1H NMR (300 MHz, DMSO-d
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): δ 7.50 (d, 1H, J = 7.5 Hz), 7.61 (d, 1H, J = 8.7 Hz), 7.66 (d, 1H, J = 7.5 Hz), 7.73 (d, 1H, J = 7.5 Hz), 7.94 (d, 1H, J = 7.5 Hz), 8.14 (d, 2H, J = 7.5 Hz), 8.33 (d, 2H, J = 8.7 Hz). For the E-isomer (86 %): 7.37 (s, 1H, CH=C), for the Z-isomer (14 %): 7.47 (s, 1H, CH=C). MS (ESI) m/z (%): 285 (M+. + 2, 30), 283 (M+, 90), 105 (100).
4-(4-(Dimethylamino)benzylidene)-2-phenyl-5(4H)-oxazolone (2d)
UV (DMF): λmax 290 (log ε = 3.98) nm. IR (KBr): 1758, 1763 (C=O), 1646 (C=N), 1605, 1580 (C=C).1H NMR (300 MHz, DMSO-d
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): δ 3.07 (s, 6H, 2CH3), 6.83 (d, 2H, J = 9.0 Hz), 7.33 (s, 1H, CH=C), 7.58–7.66 (m, 3H), 8.06 (d, 2H, J = 6.6 Hz), 8.17 (d, 2H, J = 8.7 Hz). MS (ESI): m/z (%): 292 (M+, 91), 105 (100).
4-(4-Nitrobenzylidene)-2-phenyl-5(4H)-oxazolone (2e)
UV (DMF): λmax 252 (log ε = 4.00) nm.IR (KBr): 1750, 1686 (C=O), 1620 (C=N), 1585 (C=C). 1H NMR (300 MHz, DMSO-d
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): δ 7.26–7.58 [m, 6H, (5Ar–H + 1CH=C), 7.74 (d, 2H, J = 7.5 Hz), 7.88 (d, 2H, J = 7.2 Hz). MS (ESI) m/z (%): 294.15 (M+, 0.5), 105 (100).
4-(2-Chlorobenzylidene)-2-phenyl-5(4H) oxazolone (2f)
UV (DMF): λmax 300 (log ε = 3.95) nm. IR (KBr): 1794, 1772 (C=O), 1687, 1652 (C=N), 1601 (C=C). 1H NMR (300 MHz, DMSO-d
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): δ 7.46 (s, 1H, CH=C), 7.50 (d, 2H, J = 7.8 Hz), 7.57–7.67 (m, 3H), 7.94 (d, 2H, J = 7.2 Hz), 8.15 (d, 1H, J = 6.9 Hz), 8.88 (d, 1H, J = 8.1 Hz). MS (ESI) m/z (%): 285 (M+.+2, 7), 283 (M+, 21), 105 (100).
4-(2-Bromobenzylidene)-2-phenyl-5(4H)-oxazolone (2 g)
UV (DMF): λmax 297 (log ε = 3.96) nm.IR (KBr): 1794, 1770 (C=O), 1650 (C=N), 1583, 1552 (C=C); 1H NMR (300 MHz, DMSO-d
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): δ 7.40–7.51(m, 2H), 7.57–7.67 (m, 3H, (2Ar–H + 1CH=C)), 7.74 (d, 1H, J = 7.5 Hz), 7.80 (d, 1H, J = 8.1 Hz), 7.94 (d, 1H, J = 7.2 Hz), 8.14 (d, 1H, J = 7.2 Hz), 8.86 (d, 1H, J = 8.1 Hz). MS (ESI) m/z (%): 328 (M+, 5.6), 330 (M+ + 2, 4.8), 327 (27.3), 329 (26.9), 248 (59), 105 (100).
4-(3,4-Dimethoxybenzylidene)-2-phenyl-5(4H)-oxazolone (2 h)
UV (DMF): λmax 280 (log ε = 3.62) nm.IR (KBr): 1789, 1766 (C=O), 1649 (C=N), 1596, 1578 (C=C). 1H NMR (300 MHz, DMSO-d
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): δ 3.86 (s, 3H, OMe), 3.88 (s, 3H, OCH3), 7.13 (d, 1H, J = 8.7 Hz), 7.32 (s, 1H, CH=C), 7.60–7.73 (m, 3H), 7.81 (d, 1H, J = 9.0 Hz), 8.08–8.14 (m, 3H). MS (ESI) m/z (%): 309.15 (M+, 6.0), 105 (100).
2-Phenyl-4-(3-phenylallylidene)-5(4H)-oxazolone (2i)
UV (DMF):λmax 300 (log ε = 3.95) nm.IR (KBr): 1785, 1747 (C=O), 1640 (C=N), 1595, 1574 (C=C). 1H NMR (300 MHz, DMSO-d
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): δ 7.27 (d, 1H, CH=C, J = 11.4 Hz), 7.36–7.42 (m, 4H, Ar–H), 7.57–7.68 (m, 7H, (6 Ar–H + 1 CH=C)), 8.08 (d, 1H, CH=C, J = 12.0 Hz). MS (ESI) m/z (%): 275.10 (M+, 12.57), 105 (100).