3.3. Characterization of the Ketoprofen Amino Acid Alkyl-Esters [AAOR][KETO]

¹H-NMR (400.13 MHz) and ¹³C-NMR (100.62 MHz) spectra were recorded in CDCl₃ on a BRUKER DPX-400 Avance III HD spectrometer (Billerica, MA, USA). TMS was used as an internal standard. ATR–FTIR spectra were collected in a Thermo Fisher Scientific Nicolet FTIR 380 FTIR Spectrometer (Waltham, MA, USA) equipped with attenuated total reflectance (ATR) sampling accessory (diamond plate). Spectra were recorded in transmittance mode from 400 to 4000 cm^–1, co–adding 16 interferograms at a resolution of 4 cm^–1. The content of elements, i.e., hydrogen, nitrogen, carbon, and oxygen were determined by CHNS/O elemental analysis. The elemental analysis was performed using a Thermo Scientific™ FLASH 2000 CHNS/O Elemental Analyzer (Waltham, MA, USA). Thermogravimetric analysis was carried out on thermomicrobalance TG 209 F1 Libra^® from NETZSCH (Selb, Germany), in Al₂O₃ crucible. Samples between 5–10 mg were heated from 25 °C to 1000 °C with a heating rate of 10 °C min⁻¹, under air atmosphere (flow rate: air—25 cm³ min⁻¹, nitrogen (as protective gas)—10 cm³ min⁻¹). Phase transformation temperatures were measured using a TA Instruments DSC analyzer model Q-100 (New Castle, DE, USA). Measurements were performed within the temperature range of 0 °C to 100–200 °C (depends on thermal stability), in a nitrogen atmosphere. The heating rate was 10 °C min⁻¹. The sample was loaded on an aluminum pan sealed with a pinhole cap. The specific rotation [α]D₂₀ measurements were determined with an AUTOPOL IV Polarimeter from Rudolph Research Analytical (Hackettstown, NJ, USA) for aqueous solutions of AAILS (c = 0.01 g cm⁻³). The measurements were performed at 20 °C.

The compound was obtained according general procedure in 94.0% yield as white solid. ¹H-NMR (400 MHz, CDCl₃) δ in ppm: 7.71–7.81 (m, 3H, H7, H12, H16); 7.62 (d, J_9,8 = 7.6 Hz, 1H, H9); 7.54–7.60 (m, 2H, H13, H14); 7.44–7.49 (m, 2H, H5, H15); 7.38 (t, J_6,5 = 7.6 Hz, 1H, H6); 6.67 (s, 3H, H22); 4.12–4.18 (m, 2H, H24); 3.68–3.72 (m, 1H, H2); 3.59 (dd, J_20,19 = 4.6 Hz, 1H, H21); 1.69–1.73 (m, 1H, H20); 1.58–1.62 (m, 1H, H19); 1.44–1.51 (m, 4H, H3, H20); 1.24 (t, J_25,24 =7.2 Hz, 3H, H25); 0.85–0.89 (dd, J_17(18),19 = 7.6 Hz, 6H, H17, H18); ¹³C-NMR (100 MHz, CDCl₃) δ in ppm: 196.72 (C1); 178.79 (C23); 173.68 (C10); 142.37 (C8); 137.56 (C11); 132.43 (C4); 131.84 (C5); 130.09 (C14); 129.29 (C12); 128.57 (C16); 128.26 (C9); 128.23 (C6); 61.46 (C24); 51.79 (C21); 46.55 (C2); 42.09 (C20); 24.52 (C19); 22.58 (C18); 21.85 (C17); 18.72 (C3); 14.10 (C25); FTIR: ν (ATR): 2957; 2933; 2872; 1742; 1653; 1597; 1539; 1479; 1456; 1446; 1391; 1362; 1317; 1281; 1252; 1231; 1196; 1172; 1132; 1093; 1074; 1026; 995; 968; 932; 921; 880; 824; 780; 728; 706; 644; 607; 574; 523; 444 cm⁻¹; Elemental analysis: Calc. (%) for C₂₄H₃₁NO₅ (413.51 g mol⁻¹) C (69.71), H (7.56), N (3.39), O (19.35), Found C (69.82), H (7.53), N (3.37), O (19.33).

The compound was obtained according general procedure in 94.0% yield as white solid. ¹H-NMR (400 MHz, CDCl₃) δ in ppm: 7.75–7.81 (m, 3H, H7, H12, H16); 7.64 (d, J_9,8 = 7.6 Hz, 1H, H9); 7.53–7.60 (m, 2H, H13, H14); 7.48 (t, J_6,5 = 7.3 Hz, 2H, H5, H15); 7.40 (t, J_6,5 = 7.7 Hz, 1H, H6); 5.75 (s, 3H, H21); 4.02–4.26 (m, 2H, H23); 3.68–3.72 (m, 1H, H2); 3.44 (d, J_20,19 = 4.6 Hz, 1H, H20); 1.98–2.16 (m, 1H, H19); 1.49 (d, J_3,2 = 7.1 Hz, 3H, H3); 1.25 (t, J_24,23 = 7.2 Hz, 3H, H24); 0.88–0.95 (m, 6H, H17, H18); ¹³C-NMR (100 MHz, CDCl₃) δ in ppm: 196.65 (C1); 178.49 (22); 173.58 (C10); 141.64 (C8); 137.72 (C11); 137.54 (C4); 132.45 (C5); 131.76 (C14); 130.10 (C12/C16); 129.31 (C9); 128.79 (C6); 128.37 (C7); 128.28 (C13); 61.17 (C23); 58.95 (C20); 46.00 (C2); 31.39 (C19); 18.72 (C18), 18.52 (C17); 17.29 (C3); 14.21 (C24); FTIR: ν (ATR): 2968; 2929; 2876; 2610; 1741; 1651; 1596; 1574; 1517; 1481; 1463; 1446; 1387; 1361; 1316; 1280; 1257; 1218; 1204; 1180; 1173; 1135; 1107; 1074; 1065; 1053; 1015; 996; 966; 952; 878; 859; 778; 718; 705; 642 cm⁻¹; Elemental analysis: Calc. (%) for C₂₃H₂₉NO₅ (399.48 g mol⁻¹) C (69.15), H (7.32), N (3.51), O (20.03), Found C (69.20), H (7.30), N (3.55), O (20.10).

The compound was obtained according general procedure in 90.0% yield as white solid. ¹H-NMR (400 MHz, CDCl₃) δ in ppm: 7.73–7.83 (m, 3H, H7, H12, H16); 7.61–7.67 (dt, 1H, H9); 7.52–7.60 (m, 2H, H13, H14); 7.47 (t, J_6,5 = 7.6 Hz, 2H, H5, H15); 7.39 (t, J_6,5 = 7.7 Hz, 1H, H6); 5.63 (s, 3H, H21); 4.95–5.12 (m, 2H, H23); 3.66–3.79 (m, 1H, H2); 3.40 (d, J_20,19 = 4.6 Hz, 1H, H20); 2.03–2.12 (m, 1H, H19); 1.49 (d, J_3,2 = 7.2 Hz, 3H, H3); 1.24 (d, J_24,23 = 7.1 Hz, 6H, H24, 25); 0.87–0.95 (dd, 6H, H17, H18); ¹³C-NMR (100 MHz, CDCl₃) δ in ppm: 196.70 (C1); 178.48 (C22); 141.95 (C10); 137.65 (C8); 137.54 (C11); 132.43 (C4); 131.79 (C5); 130.10 (C14); 129.33 (C12/C16); 129.31 (C9); 128.69 (C6); 128.32 (C7); 128.27(C13); 68.90 (C23); 58.90 (C20); 46.21 (C2); 31.30 (C19); 21.76 (C18); 18.65 (C17); 18.60 (C3); 17.26 (C24/C25); FTIR: ν (ATR): 2976; 2933; 2877; 1738; 1660; 1597; 1577; 1558; 1448; 1387; 1358; 1318; 1283; 1233; 1180; 1144; 1105; 1075; 999; 954; 915; 880; 822; 775; 721; 705; 643 cm⁻¹; Elemental analysis: Calc. (%) for C₂₄H₃₁NO₅ (413.51 g mol⁻¹) C (69.71), H (7.57), N (3.39), O (19.35), Found C (69.75), H (7.56), N (3.38), O (19.34).

The compound was obtained according general procedure in 93.0% yield as white solid. ¹H-NMR (400 MHz, CDCl₃) δ in ppm: 7.74–7.82 (m, 3H, H7, H12, H16); 7.63–7.68 (dt, 1H, H9); 7.52–7.60 (m, 2H, H13, H14); 7.47 (t, J_6,5 = 7.6 Hz, 2H, H5, H15); 7.41 (t, J_6,5 = 7.7 Hz, 1H, H6); 4.85 (s, 3H, H21); 4.03–4.12 (m, 2H, H23); 3.72–3.79 (m, 1H, H2); 3.42 (d, J_20,19 = 4.7 Hz, 1H, H20); 2.03–2.13 (m, 1H, H19); 1.61–1.69 (m, 2H, H24); 1.51 (d, J_3,2 = 7.1 Hz, 3H, H3); 0.89–0.97 (m, 6H, H17, H18, H25); ¹³C-NMR (100 MHz, CDCl₃) δ in ppm: 196.64 (C1); 178.35 (C10); 174.20 (C22); 141.41 (C8); 137.75 (C11); 137.52 (C4); 132.47 (C5); 131.73 (C14); 130.10 (C12); 129.32 (C9); 128.88 (C6); 128.42 (C7); 128.29 (C13/C15); 66.71 (C23); 59.14 (C20); 45.81 (C2); 31.59 (C19); 21.95 (C24); 18.88 (C18); 18.46 (C17); 17.23 (C3); 10.40 (C25); FTIR: ν (ATR): 2969; 2935; 2879; 1742; 1659; 1597; 1578; 1462; 1448; 1389; 1358; 1318; 1283; 1222; 1179; 1140; 1059; 999; 955; 929; 910; 881; 777; 721; 705; 643; cm⁻¹; Elemental analysis: Calc. (%) for C₂₄H₃₁NO₅ (413.51 g mol⁻¹) C (69.71), H (7.57), N (3.39), O (19.35), Found C (69.74), H (7.55), N (3.37), O (19.33).

Compound was obtained according general procedure in 95.0% yield as white solid. ¹H-NMR (400 MHz, CDCl₃) δ in ppm: 7.75–7.82 (m, 3H, H7,H12, H16); 7.61–7.66 (dt, 1H, H9); 7.53–7.60 (m, 2H, H13, H14); 7.47 (t, J_6,5 = 7.6 Hz, 2H, H5, H15); 7.39 (t, J_6,5 = 7.7 Hz, 1H, H6); 5.62 (s, 3H, H21); 4.05–4.16 (m, 2H, H23); 3.68–3.76 (m, 1H, H2); 3.44 (d, J_20,19 = 4.5 Hz, 1H, H20); 2.04–2.12 (m, 1H, H19); 1.56–1.64 (m, 2H, H24); 1.48 (d, J_3,2 = 7.2 Hz, 3H, H3); 0.87–0.95 (m, 9H, H17, H18, H25, H26); ¹³C-NMR (100 MHz, CDCl₃) δ in ppm: 196.70 (C1); 178.52 (C10); 173.51 (C22); 141.94 (C8); 137.65 (C11); 137.53 (C4); 132.45 (C5); 131.80 (C14); 130.10 (C12); 129.31 (C9); 128.70 (C6); 128.32 (C7); 128.27 (C13/C15); 65.10 (C23); 58.91 (C20); 46.21 (C2); 31.31 (C19); 30.56 (C24); 19.09 (C25); 18.60 (C18); 18.60 (C17); 17.32 (C3); 13.65 (C26); FTIR: ν (ATR): 2964; 2934; 2875; 1742; 1660; 1597; 1578; 1462; 1448; 1389; 1358; 1318; 1283; 1242; 1219; 1179; 1140; 1062; 1021; 999; 954; 881; 779; 721; 705; 643 cm⁻¹; Elemental analysis: Calc. (%) for C₂₅H₃₃NO₅ (427.53 g mol⁻¹) C (70.23), H (7.78), N (3.27), O (18.71), Found C (70.25), H (7.80), N (3.25), O (19.69).

¹H-NMR (400 MHz, CDCl3) δ in ppm: 7.67–7.74 (m, 3H, H9, H16, H12); 7.59–7.61 (dt, 1H, H7); 7.44–7.54 (m, 2H, H4, H5); 7.30–7.42; (m, 3H, H); 3.69–3.79 (m, 1H, H); 1.46 (d, J_2,1 = 7.1 Hz, 3H, H1); ¹³C-NMR (100 MHz, CDCl₃) δ in ppm: 196.56 (C10); 180.24 (1); 140.12 (C8); 137.93 (C11); 137.41 (C4); 132.60 (C5); 131.71 (C14); 130.14 (C12/C16); 129.39 (C9); 129.31 (C6); 128.63 (C7); 128,34 (C13/C15); 45.25 (C2); 18.13 (C3); FTIR: ν (ATR): 2978; 2926; 1697; 1655; 1598; 1576; 1457; 1419; 1370; 1319; 1308; 1285; 1227; 1195; 1175; 1134; 1178; 1063; 1061; 968; 928; 916; 866; 717; 703; 691; 643; 614 cm⁻¹; Elemental analysis: Calc. (%) for C₁₆H₁₄O₃ (254.28 g mol⁻¹) C (75.58), H (5.55), N (0.00), O (18.88), Found C (75.56), H (5.56), N (0.00), O (18.88).