4.3.2. Preparation and Characterization of

2-{4-[(4-Bromophenyl)sulfonyl]phenyl}-4-isopropyl-4*H*-1,3-oxazol-5-one **6**

An amount of 4.62 g (10.5 mmol) of **5** was suspended under magnetic stirring at room temperature in 50 mL of dry CH2Cl2 and then an equimolar quantity (1.15 mL, 1.06 g, 10.5 mmol) of 4-methylmorpholine was added. A volume of 1 mL (1.14 g, 10.5 mmol) of ethyl chloroformate was added dropwise with continuous stirring to the solution obtained above. The reaction mixture was stirred for an additional 30 min and further poured into 100 mL of ice water. The separated organic phase was washed with 5% NaHCO3 solution, then with distilled water and dried (MgSO4). After concentration under low-pressure, solid product **6** was recrystallized from cyclohexane when white crystals were obtained.

Yield 90% (3.99 g, 9.45 mmol). mp 144–145 ◦C.

UV/VIS (CH3OH) *λ*max nm (log10 *ε*max): 202.6 (4.49); 227.3 (4.14); 252.0 (4.35); (CH3CN) *λ*max nm (log10 *ε*max): 197.1 (4.93); 229.1 (4.48); 252.2 (4.64).

FTIR (KBr disc) *<sup>ν</sup>*max cm<sup>−</sup>1: 3092 m; 3067 w (νC–H, aromatic); 2963 m (νasymCH3); 2930 m (νC–H, aliphatic); 2875 m (νsymCH3); 1825 vs (νC=O); 1650 vs (νC=N); 1599 w; 1573 s; 1469 m (νC=C, aromatic); 1329 vs; 1293 s (νasymSO2); 1243 m (νasymC–O–C); 1160 vs (νsymSO2); 1040 vs (νsymC–O–C); 845 m (γC–H, aromatic); 614 vs; and 574 s (νC–Br).

1H NMR (300 MHz, CDCl3) *δ* ppm: 8.16 (d, 2H, H-7, H-11, *J* = 8.5 Hz); 8.05 (d, 2H, H-8, H-10, *J* = 8.5 Hz); 7.83 (d, 2H, H-13, H-17, *J* = 8.5 Hz); 7.68 (d, 2H, H-14, H-16, *J* = 8.5 Hz); 4.32 (d, 1H, H-4, *J* = 4.7 Hz); 2.40 (septd, 1H, H-18, *J* = 6.9, 4.7 Hz); 1.14 (d, 3H, H-19, *J* = 6.9 Hz); and 0.99 (d, 3H, H-20, *J* = 6.9 Hz).

13C NMR (75 MHz, CDCl3) *δ* ppm: 176.98 (C-5); 160.36 (C-2); 144.89 (C-9); 139.92 (C-12); 132.97 (C-14, C-16); 130.58 (C-6); 129.49 (C-13, C-17); 129.23 (C-15); 128.99 (C-7, C-11); 128.19 (C-8, C-10); 71.04 (C-4); 31.42 (C-18); 18.90 (C-19); and 17.65 (C-20).

GC/EI–MS (70 eV) *m*/*z* (rel. abund. %): 379 (79Br)/381 (81Br) (71.61/100, BP) [M-C3H6]· +; 323/325 (41.31/38.56) [79BrC6H4SO2C6H4CHNH]· +/[81BrC6H4SO2C6H4CHNH]· + or [79BrC6H4SO2C6H4CO]+/[81BrC6H4SO2C6H4CO]+; 207 (29.87); 203 (40.89) [79BrC6H4SO]+; 76 (24.15) [C6H4]· +; 43 (37.71) [C3H7] +; and *t*<sup>R</sup> 36.53 min.

Reversed-phase HPLC (CH3OH–H2O 60:40, *V*/*V*; flow rate 1 mL/min; *λ* 250 nm): purity 94.16%; *t*<sup>R</sup> 4.05 min.

Elem. anal. (%) found: C, 51.24; H, 3.81; N, 3.33; and S, 7.57; calcd. for C18H16BrNO4S (*M*r 422.29): C, 51.19; H, 3.82; N, 3.32; and S, 7.59.

4.3.3. General Procedure for the Preparation of 2-Acylamino Ketones **7a**,**b** and Their Characterization

To a solution of raw 2-{4-[(4-bromophenyl)sulfonyl]phenyl}-4-isopropyl-4*H*-1,3-oxazol-5-one **6** (2.11 g, 5 mmol) in 25 mL of anhydrous arene (i.e., benzene and toluene, respectively), 2.00 g (15 mmol) of anhydrous aluminum trichloride were added portion-wise with magnetic stirring at room temperature. The reaction mixture was stirred for a further 20 h until hydrogen chloride emission ceased and then poured into 100 mL of ice water acidified with 5 mL of 37% HCl. A precipitate was obtained, which was isolated by filtration, washed on the filter with cold distilled water, and further with a cold ethanol/distilled water (1:1, *V*/*V*) mixture. The aqueous filtrate was extracted with CH2Cl2 (2 × 15 mL), then the organic phase was washed with distilled water, dried (Na2SO4), and concentrated to dryness by vacuum distillation, when the second fraction of **7** was isolated. Purification of the crude product by recrystallization from ethanol afforded colorless crystals.

4-[(4-Bromophenyl)sulfonyl]-*N*-(3-methyl-1-oxo-1-phenylbutan-2-yl)benzamide **7a**

Compound **7a** was synthesized by the reaction of **6** with benzene (25 mL, 21.85 g, 279.7 mmol).

Yield 80% (2.00 g, 4.00 mmol). mp 164–166 ◦C.

UV/VIS (CH3OH) *λ*max nm (log10 *ε*max): 202.6 (4.49); 252.0 (4.19); (CH3CN) *λ*max nm (log10 *ε*max): 198.0 (5.03); 250.2 (4.77).

FTIR (KBr disc) *<sup>ν</sup>*max cm<sup>−</sup>1: 3301 s (νN–H); 3089 m; 3061 m; 3040 m (νC–H, aromatic); 2962 m (νasymCH3); 2931 m (νC–H, aliphatic); 2872 m (νsymCH3); 1655 vs (νO=C–O and νO=C–N, amide I; overlapped); 1597 m; 1574 s; 1483 m; 1469 m; 1448 m (νC=C, aromatic); 1528 s (δN–H, amide II); 1323 vs; 1289 s (νasymSO2); 1161 vs (νsymSO2); 854 m (γC–H, aromatic); 615 vs; and 580 s (νC–Br).

1H NMR (300 MHz, DMSO-*d*6) *δ* ppm: 8.99 (d, 1H, H-3, *J* = 8.0 Hz); 8.05 (m, 6H, H-7, H-8, H-10, H-11, H-22, H-26); 7.91 (d, 2H, H-13, H-17, *J* = 8.5 Hz); 7.84 (d, 2H, H-14, H-16, *J* = 8.5 Hz); 7.64 (br t, 1H, H-24, *J* = 7.6 Hz); 7.53 (br t, 2H, H-23, H-25, *J* = 7.6 Hz); 5.38 (t, 1H, H-4, *J* = 7.7 Hz); 2.28 (m, 1H, H-18); 0.92 (d, 3H, H-19, *J* = 7.1 Hz); and 0.90 (d, 3H, H-20, *J* = 7.1 Hz).

13C NMR (75 MHz, DMSO-*d*6) *δ* ppm: 199.19 (C-5); 165.57 (C-2); 142.76 (C-9); 139.88 (C-12); 138.78 (C-6); 136.17 (C-21); 133.44 (C-24); 132.94 (C-14, C-16); 129.48 (C-13, C-17); 129.04 (C-7, C-11); 128.82 (C-23, C-25); 128.24 (C-22, C-26); 128.22 (C-15); 127.53 (C-8, C-10); 59.23 (C-4); 29.50 (C-18); 19.72 (C-19); and 18.36 (C-20).

Reversed-phase HPLC (CH3OH–H2O 60:40, *V*/*V*; flow rate 1 mL/min; *λ* 250 nm): purity 92.02%; *t*<sup>R</sup> 4.35 min.

Elem. anal. (%) found: C, 57.63; H, 4.41; N, 2.81; and S, 6.40; calcd. for C24H22BrNO4S (*M*r 500.40): C, 57.60; H, 4.43; N, 2.80; and S, 6.41.

4-[(4-Bromophenyl)sulfonyl]-*N*-[3-methyl-1-oxo-1-(*p*-tolyl)butan-2-yl]benzamide **7b**

Compound **7b** was synthesized by the reaction of **6** with toluene (25 mL, 21.63 g, 234.8 mmol).

Yield 86% (2.21 g, 4.30 mmol). mp 154–155 ◦C.

UV/VIS (CH3OH) *λ*max nm (log10 *ε*max): 202.6 (4.47); 255.5 (4.18); (CH3CN) *λ*max nm (log10 *ε*max): 197.8 (5.01); 254.8 (4.78).

FTIR (KBr disc) *<sup>ν</sup>*max cm<sup>−</sup>1: 3281 s (νN–H); 3086 m; 3058 m; 3037 m (νC–H, aromatic); 2962 m (νasymCH3); 2929 m (νC–H, aliphatic); 2868 m (νsymCH3); 1655 vs (νO=C–O and νO=C–N, amide I; overlapped); 1606 m; 1572 s; 1483 m; 1467 m (νC=C, aromatic); 1530 s (δN–H, amide II); 1325 s; 1305 m; 1287 m (νasymSO2); 1161 vs (νsymSO2); 858 m (γC–H, aromatic); 617 s; and 576 s (νC–Br).

1H NMR (300 MHz, DMSO-*d*6) *δ* ppm: 8.94 (d, 1H, H-3, *J* = 8.0 Hz); 8.06 (d, 2H, H-7, H-11, *J* = 8.8 Hz); 8.03 (d, 2H, H-8, H-10, *J* = 8.8 Hz); 7.95 (d, 2H, H-22, H-26, *J* = 8.2 Hz); 7.91 (d, 2H, H-13, H-17, *J* = 8.8 Hz); 7.84 (d, 2H, H-14, H-16, *J* = 8.8 Hz); 7.33 (d, 2H, H-23, H-25, *J* = 8.2 Hz); 5.36 (t, 1H, H-4, *J* = 7.7 Hz); 2.36 (s, 3H, CH3); 2.27 (m, 1H, H-18); 0.92 (d, 3H, H-19, *J* = 7.4 Hz); and 0.89 (d, 3H, H-20, *J* = 7.4 Hz).

13C NMR (75 MHz, DMSO-*d*6) *δ* ppm: 198.57 (C-5); 165.47 (C-2); 143.89 (C-24); 142.72 (C-9); 139.88 (C-12); 138.81 (C-6); 133.61 (C-21); 132.92 (C-14, C-16); 129.44 (C-13, C-17); 129.34 (C-23, C-25); 129.00 (C-7, C-11); 128.36 (C-22, C-26); 128.18 (C-15); 127.49 (C-8, C-10); 59.05 (C-4); 29.56 (C-18); 21.12 (CH3); 19.71 (C-19); and 18.33 (C-20).

Reversed-phase HPLC (CH3OH–H2O 60:40, *V*/*V*; flow rate 1 mL/min; *λ* 250 nm): purity 99.99%; *t*<sup>R</sup> 4.95 min.

Elem. anal. (%) found: C, 58.34; H, 4.69; N, 2.71; and S, 6.21; calcd. for C25H24BrNO4S (*M*r 514.43): C, 58.37; H, 4.70; N, 2.72; and S, 6.23.

4.3.4. General Procedure for the Preparation of 2,5-Disubstituted 4-Isopropyl-1,3-oxazoles **8a**,**b** and Their Characterization

A mixture of 10 mmol of crude **7** and 20 mL (33.40 g, 217.8 mmol) of phosphoryl trichloride was heated under reflux during 4 h. The excess phosphoryl trichloride was evaporated under reduced pressure. The resulting oily residue was cooled, treated with an ice water mixture, and extracted with 2 × 20 mL CH2Cl2. The organic phase was separated and washed with 5% NaHCO3 solution, then with distilled water and dried (Na2SO4). The solvent was evaporated off under vacuum. Purification of the resulting solid was performed by recrystallization from ethanol when colorless crystals of **8** were obtained.

2-{4-[(4-Bromophenyl)sulfonyl]phenyl}-4-isopropyl-5-phenyl-1,3-oxazole **8a**

Compound **8a** was synthesized from 5.00 g (10 mmol) of 2-acylamino ketone **7a**.

Yield 94% (4.53 g, 9.39 mmol). mp 165–167 ◦C.

UV/VIS (CH3OH) *λ*max nm (log10 *ε*max): 202.6 (4.48); 249.3 (4.10); 333.9 (4.13); (CH3CN) *λ*max nm (log10 *ε*max): 196.2 (4.95); 248.6 (4.56); 335.6 (4.64).

FTIR (KBr disc) *<sup>ν</sup>*max cm<sup>−</sup>1: 3092 m; 3063 m; 3041 w (νC–H, aromatic); 2963 s (νasymCH3); 2930 m (νC–H, aliphatic); 2869 m (νsymCH3); 1602 m (νC=N); 1588 m; 1574 s; 1543 w; 1494 m; 1471 m; 1446 m (νC=C, aromatic); 1323 vs; 1293 m (νasymSO2); 1280 m (νasymC–O–C); 1155 vs (νsymSO2); 1099 s (νsymC–O–C); 844 m (γC–H, aromatic); 617 s; and 568 s (νC–Br).

1H NMR (300 MHz, CDCl3) *δ* ppm: 8.22 (d, 2H, H-7, H-11, *J* = 8.8 Hz); 8.00 (d, 2H, H-8, H-10, *J* = 8.8 Hz); 7.82 (d, 2H, H-13, H-17, *J* = 8.8 Hz); 7.65 (d, 2H, H-14, H-16, *J* = 8.8 Hz); 7.64

(dd, 2H, H-22, H-26, *J* = 7.4, 1.4 Hz); 7.48 (br t, 2H, H-23, H-25, *J* = 7.4 Hz); 7.37 (tt, 1H, H-24, *J* = 7.4, 1.4 Hz); 3.29 (sept, 1H, H-18, *J* = 6.9 Hz); and 1.36 (d, 6H, H-19, H-20, *J* = 6.9 Hz).

13C NMR (75 MHz, CDCl3) *δ* ppm: 157.78 (C-2); 145.47 (C-5); 144.19 (C-4); 141.71 (C-12); 140.56 (C-9); 132.80 (C-14, C-16); 132.33 (C-6); 129.29 (C-13, C-17); 129.01 (C-23, C-25); 128.81 (C-21); 128.78 (C-15); 128.39 (C-24); 128.26 (C-7, C-11); 127.09 (C-8, C-10); 126.25 (C-22, C-26); 26.10 (C-18); and 22.07 (C-19, C-20).

Reversed-phase HPLC (CH3OH–H2O 70:30, *V*/*V*; flow rate 1 mL/min; *λ* 335 nm): purity 98.95%; *t*<sup>R</sup> 5.97 min.

Elem. anal. (%) found: C, 59.71; H, 4.18; N, 2.91; and S, 6.67; calcd. for C24H20BrNO3S (*M*r 482.39): C, 59.76; H, 4.18; N, 2.90; and S, 6.65.

2-{4-[(4-Bromophenyl)sulfonyl]phenyl}-4-isopropyl-5-(*p*-tolyl)-1,3-oxazole **8b**

Compound **8b** was synthesized from 5.14 g (10 mmol) of 2-acylamino ketone **7b**. Yield 91% (4.52 g, 9.10 mmol). mp 215–217 ◦C.

UV/VIS (CH3OH) *λ*max nm (log10 *ε*max): 202.6 (4.48); 249.3 (4.11); 337.4 (4.09); (CH3CN) *λ*max nm (log10 *ε*max): 195.3 (4.96); 249.5 (4.59); 340.1 (4.64).

FTIR (KBr disc) *<sup>ν</sup>*max cm<sup>−</sup>1: 3091 m; 3069 w; 3028 w (νC–H, aromatic); 2963 m (νasymCH3); 2925 m (νC–H, aliphatic); 2869 m (νsymCH3); 1601 m (νC=N); 1592 m; 1574 m; 1545 w; 1508 m; 1471 m (νC=C, aromatic); 1322 s; 1292 m (νasymSO2); 1280 m (νasymC–O–C); 1156 vs (νsymSO2); 1097 s (νsymC–O–C); 846 m (γC–H, aromatic); 617 s; and 568 s (νC–Br).

1H NMR (300 MHz, CDCl3) *δ* ppm: 8.21 (d, 2H, H-7, H-11, *J* = 8.5 Hz); 8.00 (d, 2H, H-8, H-10, *J* = 8.5 Hz); 7.82 (d, 2H, H-13, H-17, *J* = 8.5 Hz); 7.65 (d, 2H, H-14, H-16, *J* = 8.5 Hz); 7.53 (d, 2H, H-22, H-26, *J* = 8.2 Hz); 7.28 (d, 2H, H-23, H-25, *J* = 8.2 Hz); 3.26 (sept, 1H, H-18, *J* = 6.9 Hz); 2.41 (s, 3H, CH3); and 1.35 (d, 6H, H-19, H-20, *J* = 6.9 Hz).

13C NMR (75 MHz, CDCl3) *δ* ppm: 157.52 (C-2); 145.69 (C-5); 143.63 (C-4); 141.57 (C-12); 140.61 (C-9); 138.48 (C-24); 132.80 (C-14, C-16); 132.43 (C-6); 129.70 (C-23, C-25); 129.29 (C-13, C-17); 128.76 (C-15); 128.25 (C-7, C-11); 127.03 (C-8, C-10); 126.22 (C-22, C-26); 126.01 (C-21); 26.08 (C-18); 22.07 (C-19, C-20); and 21.47 (CH3).

Reversed-phase HPLC (CH3OH–H2O 70:30, *V*/*V*; flow rate 1 mL/min; *λ* 335 nm): purity 99.99%; *t*<sup>R</sup> 7.32 min.

Elem. anal. (%) found: C, 60.52; H, 4.46; N, 2.81; and S, 6.48; calcd. for C25H22BrNO3S (*M*r 496.42): C, 60.49; H, 4.47; N, 2.82; and S, 6.46.
