4.3.1. Preparation and Characterization of

2-{4-[(4-Bromophenyl)sulfonyl]benzamido}-3-methylbutanoic Acid **5**

The solution of 2.34 g (20 mmol) of *L*-valine in 20 mL (0.80 g, 20 mmol) of 1 N NaOH solution was cooled at 0–5 ◦C in an ice bath and then two other solutions were added simultaneously in droplets under magnetic stirring during half an hour, namely a solution of 7.19 g (20 mmol) of crude 4-[(4-bromophenyl)sulfonyl]benzoyl chloride **4** in 45 mL of anhydrous dichloromethane, and a 2 N NaOH solution (10 mL, 0.80 g, 20 mmol). The reaction mixture was stirred for another 1 h at room temperature and then the separated aqueous phase was acidified with 2 N HCl when a white precipitate appeared. The solid was filtered off at low-pressure, washed thoroughly with distilled water on the filter to remove traces of hydrochloric acid, air-dried, and recrystallized from water when white acicular crystals resulted.

Yield 94% (8.28 g, 18.80 mmol). mp 194–196 ◦C.

UV/VIS (CH3OH) *λ*max nm (log10 *ε*max): 202.6 (4.48); 252.0 (4.20); (CH3CN) *λ*max nm (log10 *ε*max): 196.2 (4.83); 228.2 (4.36); 252.2 (4.57).

FTIR (KBr disc) *<sup>ν</sup>*max cm<sup>−</sup>1: 3347 s (νN–H); 3300–2500 vs (νO–H); 3092 s; 3069 s (νC–H, aromatic); 2966 vs (νasymCH3); 2933 s (νC–H, aliphatic); 2876 s (νsymCH3); 2676 m; 2599 m (combination bands); 1746 vs (νO=C–O); 1635 vs (νO=C–N, amide I); 1599 s; 1573 vs; 1487 s; 1467 s (νC=C, aromatic); 1536 vs (δN–H, amide II); 1324 vs; 1296 vs; 1281 vs (νasymSO2); 1161 vs (νsymSO2); 852 s (γC–H, aromatic); 613 vs; and 575 vs (νC–Br).

1H NMR (300 MHz, DMSO-*d*6) *δ* ppm: 8.73 (d, 1H, H-3, *J* = 8.0 Hz); 8.08 (d, 2H, H-7, H-11, *J* = 8.8 Hz); 8.04 (d, 2H, H-8, H-10, *J* = 8.8 Hz); 7.92 (d, 2H, H-13, H-17, *J* = 8.8 Hz); 7.85 (d, 2H, H-14, H-16, *J* = 8.8 Hz); 4.29 (dd, 1H, H-4, *J* = 8.1, 6.9 Hz); 2.17 (oct, 1H, H-18, *J* = 6.9 Hz); 0.95 (d, 3H, H-19, *J* = 6.9 Hz); and 0.94 (d, 3H, H-20, *J* = 6.9 Hz).

13C NMR (75 MHz, DMSO-*d*6) *δ* ppm: 172.79 (C-5); 165.78 (C-2); 142.66 (C-9); 139.92 (C-12); 139.03 (C-6); 132.96 (C-14, C-16); 129.48 (C-7, C-11); 129.08 (C-8, C-10); 128.22 (C-15); 127.49 (C-13, C-17); 58.43 (C-4); 29.48 (C-18); 19.25 (C-19); and 18.61 (C-20).

Reversed-phase HPLC (CH3OH–H2O 30:70, *V*/*V*; flow rate 1 mL/min; *λ* 250 nm): purity 99.99%; *t*<sup>R</sup> 4.47 min.

Elem. anal. (%) found: C, 49.06; H, 4.11; N, 3.19; and S, 7.28; calcd. for C18H18BrNO5S (*M*r 440.31): C, 49.10; H, 4.12; N, 3.18; and S, 7.28.
