3.2. General Procedure for Quaternization of Esters
The appropriate ester (1.5 mmol) was dissolved in dry acetone. Substituted N-benzyl bromide (1.7 mmol) was slowly added to the solution. The mixture was left at room temperature and after 24 h the crystals were formed. They were washed several times with dry ether and dried under reduced pressure to give the title compounds as white crystals (unless stated otherwise).
3-Acetoyloxy-1-(3-methylbenzyl)quinuclidinium bromide (1). Yield: 41%; m.p. 196.3–197.8 °C; IR (cm−1): 2969 (C-H), 2890 (C-H), 1275 (C=O), 1254 (C-O), 1042 (C-N); 1H-NMR δ: 1.89–2.05 (m, 2H, H5), 2.07 (s, 3H, CH3C=O), 2.15–2.23 (m, 2H, H8), 2.32–2.35 (s, 3H, CH3Bz), 2.38–2.40 (m, 1H, H4),3.62–3.78 (m, 1H, H7), 3.82–3.89 (m, 2H, H6), 3.93–4.04 (m, 1H, H2b), 4.24–4.32 (dd, 1H, H2a), 5.00–5.10 (m, 3H, H3 and CH2Bz), 7.23–7.44 (m, 4H, H2H4H5H6Bz); 13C-NMR δ: 18.39 (C5), 21.28 (C4), 21.29 (CH3Bz), 21,37 (C8), 24.69 (CH3C=O), 52.87 (C6), 53.69 (C7), 59.90 (C2), 66.70 (CH2Bz), 67.16 (C3), 126.63 (C1Bz), 129.06 (C5Bz), 130.45 (C6Bz), 131.33 (C2Bz), 133.75 (C4Bz), 139.13 (C3Bz), 170.02 (C=O). ESMS: m/z (calcd for C17H24NO2+ 274.18) found 274.2.
3-Acetoyloxy-1-(4-methylbenzyl)quinuclidinium bromide (2). Yield: 63%; m.p 174.9–175.6 °C; IR (cm−1): 2945 (C-H), 1720 (C=O), 1241 (C-O), 1025 (C-N); 1H-NMR δ: 1.89–2.00 (m, 2H, H5), 2.08 (s, 3H, CH3C=O), 2.14–2.19 (m, 2H, H8), 2.33 (s, 3H, CH3Bz), 2.35–2.39 (m, 1H, H4), 3.62–3.67 (m, 2H, H7), 3.83–3.86 (m, 2H, H6), 3.93–3.95 (m, 1H, H2b), 4.22–4.29 (m, 1H, H2a), 4.97–5.07 (m, 3H, H3 and CH2Bz), 7.15–7.18 (m, 2H, H3H5Bz), 7.37–7.44 (m, 2H, H2H6Bz); 13C-NMR δ: 17.78 (C5), 20.47 (C4), 20.76 (CH3Bz), 21.37 (C8), 24.23 (CH3C=O), 52.50 (C6), 53.14 (C7), 59.36 (C2), 65.95 (CH2Bz), 66.69 (C3), 123.25 (C1Bz), 129.25 (C3C5Bz), 132.71 (C2C6Bz), 140.13 (C4Bz), 169.76 (C=O). ESMS: m/z (calcd for C17H24NO2+ 274.18) found 274.2.
3-Acetoyloxy-1-(3-bromobenzyl)quinuclidinium bromide (3). Yield: 63%; m.p. 194–196 °C; IR (cm−1): 3050, 2955, 2870, 1720, 1430, 1371, 1244, 1026; 1H-NMR δ: 1.92–2.03 (m, 2H, H5), 2.04–2.09 (s, 3H, CH3C=O), 2.18–2.20 (m, 2H, H8), 2.39–2.40 (m, 1H, H4), 3.70–3.93 (m, 5H, H6, H7 and H2b), 4.33–4.34 (dd, 1H, H2a), 5.08–5.21 (m, 3H, H3 and CH2Bz), 7.36–7.41 (m, 4H, H2H4 H5H6Bz); 13C-NMR δ: 17.89 (C5), 20.51 (C4), 20.90 (C8), 24.15 (CH3C=O), 52.89 (C6), 53.34 (C7), 59.56 (C2), 64.75 (CH2Bz), 66.57 (C3), 122.58 (C1Bz), 128.70 (C3Bz), 130.30 (C6Bz), 131.80 (C5Bz), 133.25 (C4Bz), 135.25 (C2Bz), 169.67 (C=O). ESMS: m/z (calcd for C16H21BrNO2+ 338.08) found 338.2.
3-Acetoyloxy-1-(4-bromobenzyl)quinuclidinium bromide (4). Yield: 60%; m.p. 239–241 °C; IR (cm−1): 3050, 2956, 2870 (vs C-H); 1735, 1488,1422, 1363, 1239, 1029; 1H-NMR δ: 1.89–2.02 (m, 2H, H5), 2.04–2.10 (s, 3H, CH3C=O), 2.17–2.21 (m, 2H, H8), 2.38–2.39 (m, 1H, H4), 3.64–3.72 (m, 2H, H7), 3.77–3.95 (m, 3H, H6 and H2b), 4.28–4.29 (dd, 1H, H2a), 5.06–5.07 (m, 3H, H3), 5.14–5.21 (m, 2H, CH2Bz), 7.50–7.52 (m, 2H, H2H6Bz), 7.56–7.58 (m, 2H, H3H5Bz); 13C-NMR δ: 17.87 (C5), 20.47 (C4), 20.88 (C8); 24.15 (CH3C=O), 52.80 (C6), 53.21 (C7), 59.51 (C2), 64.79 (CH2Bz), 66.57 (C3); 124.91(C1Bz), 125.36 (C4Bz), 131.96 (C3C5Bz), 134.47 (C2C6Bz), 169.65 (C=O). ESMS: m/z (calcd for C16H21BrNO2+ 338.08) found 338.2.
3-Benzoyloxy-1-(3-methylbenzyl)quinuclidinium bromide (5). Yield: 89%, m.p. 145.8–146.9 °C; IR (cm−1): 2969 (C-H), 1710 (C=O), 1453 (C=C), 1278 (C-O), 1024 (C-N); 1H-NMR δ: 1.95–2.29 (m, 4H, H5 and H8), 2.32 (s, 3H, CH3Bz), 2.54–2.57 (m, 1H, H4), 3.76–4.13 (m, 5H, H6, H7 and H2b), 4.37–4.47 (m, 1H, H2a), 5.10 (s, 2H, CH2Bz), 5.33–5.36 (m, 1H, H3), 7.19–7.29 (m, 2H, H2H6Bn), 7.39–7.46 (m, 2H, H2H6Bz), 7.53–7.59 (m, 3H, H3H4H5Bn), 8.01–8.04 (m, 2H, H4H5Bz); 13C-NMR δ: 18. 54 (C5), 21.28 (CH3Bz), 21.37 (C8), 24.94 (C4), 53.31 (C6), 53.98 (C7), 59.97 (C2), 66.81 (CH2Bz), 67.79 (C3), 126.69 (C1Bz), 128.81 (C3Bz), 129.08 (C3C5Bn), 128.38 (C10), 129.86 (C2C6Bz), 130.43 (C2C6Bn), 130.43 (C5Bz), 131.29 (C4Bz), 133.82 (C4Bn), 139.31 (C3Bz), 165.40 (C=O). ESMS: m/z (calcd for C22H26NO2+ 336.20) found 336.2.
3-Benzoyloxy-1-(4-methylbenzyl)quinuclidinium bromide (6). Yield: 81%, m.p. 209.6–210.4 °C; IR (cm−1): 2968 (C-H), 2879 (C-H), 1721 (C=O), 1449 (C=C), 1271 (C-O), 1022 (C-N); 1H-NMR δ: 1.95–2.28 (m, 4H, H5 and H8), 2.56 (s, 3H, CH3Ph), 2.52–2.61 (m, 1H, H4), 3.68–4.16 (m, 5H, H6, H7 and H2), 4.32–4.41 (m, 1H, H2), 5.11 (s, 2H, H16), 5.32–5.35 (m, 1H, H3), 7.18–7.23 (m, 2H, H11 and H15), 7.43–7.48 (m, 2H, H18 and H22), 7.51–7.62 (m, 3H, H12, H13 and H14), 8.01–8.04 (m, 2H, H19 and H21); 13C-NMR δ: 18.85 (C5), 21.30 (CH3Bz), 21.38 (C8), 24.98 (C4), 53.35 (C6), 53.93 (C7), 59.99 (C2), 66.68 (CH2Bz), 67.77 (C3), 123.64 (C4Bz), 128.61 (C3C5Bn), 128.76 (C1Bz), 129.87 (C2C6Bz), 129.94 (C2C6Bn), 133.22 (C3C5Bz), 133.73 (C4Bn), 140.92 (C1Bn), 165.51 (C=O). ESMS: m/z (calcd for C22H26NO2+ 336.20) found 336.2.
3-Benzoyloxy-1-(3-bromobenzyl)quinuclidinium bromide (7). Yield: 78%; m.p. 140–142 °C; IR (cm−1): 3050, 2966, 2885, 1716, 1450,1409, 1214, 1012; 1H-NMR δ: 1.94–2.27 (m, 4H, H5 and H8), 2.53–2.55 (m, 1H, H4), 3.76–4.09 (m, 5H, H6, H7 and H2b), 4.37–4.45 (dd, 1H, H2a), 5.10 (s, 2H, CH2Bz), 5.33–5.36 (q, 1H, H3), 7.24–7.29 (m, 1H, H4Bn), 7.38–7.78 (m, 6H, H2H3H5H6Bn and H5H6Bz), 7.99–8.01 (d, 2H, H2H4Bz); 13C-NMR δ: 19.95 (C5), 20.10 (C8), 24.90 (C4), 53.07 (C6), 53.58 (C7), 55.21 (C2), 65.68 (CH2Bzl), 67.68 (C3), 123.12 (C1Bz), 128.60 (C1Bn), 129.07 (C3C5Bn), 129.09 (C3Bz), 129.89 (C2C6Bn), 130.82 (C4Bn), 132.30 (C6Bz), 133.70 (C5Bz), 133.81 (C4Bz), 135.72 (C2Bz), 165.56 (C=O). ESMS: m/z (calcd for C21H23BrNO2+ 400.09) found 400.2.
3-Benzoyloxy-1-(4-bromobenzyl)quinuclidinium bromide (8). Yield: 67%; m.p. 84–86 °C; IR (cm−1): 3050, 2963, 2885, 1716, 1409, 1214, 1012; 1H-NMR δ: 2.03–2.27 (m, 4H, H5 and H8), 2.55–2.56 (m, 1H, H4), 3.72–4.05 (m, 5H, H6, H7 and H2b), 4.35–4.45 (dd, 1H, H2a), 5.18 (s, 2H, CH2Bz), 5.33–5.36 (q, 1H, H3), 7.27–7.29 (m, 1H, H4Bn), 7.41–7.59 (m, 6H, H2H3H5H6Bn and H2H6Bz), 7.99–8.01 (d, 2H, H3H5Bz); 13C-NMR δ: 19.39 (C5), 20.10 (C8), 24.89 (C4), 53.07 (C6), 53.74 (C7), 57.53 (C2), 62.16 (CH2Bz), 67.73 (C3), 125.43 (C1Bz), 125.61 (C1Bn), 128.62 (C3C5Bn), 128.70 (C4Bz), 128.73 (C2C6Bz), 129.87 (C2C6Bn), 131.51 (C4Bn), 132.51 (C3C5Bz), 165.56 (C=O). ESMS: m/z (calcd for C21H23BrNO2+ 400.09) found 400.2.
3-Isonicotinoyloxy-1-(3-bromobenzyl)quinuclidinium bromide (9). Yield: 78%; m.p. 251–255 °C; IR (cm−1): 3050, 2963, 2870, 1720, 1468,1406, 1217, 1039; 1H-NMR δ: 1.94–1.95 (m, 2H, H5), 2.10–2.12 (m, 2H, H8), 2.27–2.31 (m, 1H, H4), 3.48–4.19 (m, 5H, H7, H6 and H2b), 4.28–4.30 (dd, 1H, H2a), 4.48–4.51 (m, 2H, CH2Bz), 5.29–5.30 (q, 1H, H3), 7.33 (t, 1H, H5Bz), 7.56–7.70 (m, 2H, H4H6Bz), 7.77–7.78 (m, 1H, H2Bz), 7.89–7.90 (m, 2H, H2H6Py), 8.76–8.77 (m, 2H, H3H5Py); 13C-NMR δ: 17.99 (C5), 20.82 (C8), 24.32 (C4), 52.51 (C6), 53.52(C7), 59.40 (C2), 64.77 (CH2Bz); 68.10 (C3), 122.52 (C2C6Py), 122.73 (C1Py), 128.52 (C1Bz), 130.35 (C3C5Py), 130.78 (C6Bz), 131.33 (C5Bz), 133.21 (C3Bz), 133.38 (C2Bz), 135.23 (C4Bz), 135.54 (C=O). ESMS: m/z (calcd for C20H22BrN2O2+ 401.09) found 401.1.
3-Isonicotinoyloxy-1-(4-bromobenzyl)quinuclidinium bromide (10). Yield: 78%; m.p. 119–121 °C; IR (cm−1): 3050, 2953, 2870, 1731, 1462,1409, 1214, 1012; 1H-NMR δ: 1.92–2.33 (m, 4H, H5 and H8), 2.57–2.58 (m, 1H, H4), 3.50–4.24 (m, 5H, H6, H7 and H2b), 4.32–4.51 (dd, 1H, H2a), 5.25 (s, 2H, CH2Bz), 5.29–5.41 (q, 1H, H3), 7.47–7.66 (m, 4H, H2H3H4H5Bz), 7.89–7.91 (m, 2H, H2H6Py), 8.78–8.80 (m, 2H, H3H5Py); 13C-NMR δ: 18.47 (C5), 21.30 (C8), 24.05 (C4), 53.06 (C6), 53.61 (C7), 59.78 (C2), 65.33 (CH2Bz), 68.33 (C3), 119.46 (C2C6Py), 125.69 (C1Py), 131.95 (C2C6Bz), 134.49 (C3C5Bz), 136.03 (C1Bz); 144.13 (C4Bz), 151.03 (C3C5Py), 164.38 (C=O). ESMS: m/z (calcd for C20H22BrN2O2+ 401.09) found 401.1.
3-Phthaloyloxy-1-(3-methylbenzyl)quinuclidinium bromide (11). Yield: 49%, yellow viscous oil; IR (cm−1): 3344 (O-H), 2923 (C-H), 1721 (C=O), 1488 (C=C), 1284 (C-O), 1039 (C-N); 1H-NMR δ: 0.88–0.99 (m, 2H, H5), 1.20–1.48 (m, 2H, H8), 1.80–2.15 (m, 1H, H4), 2.32–2.40 (CH3Bz), 3.38–3.97 (m, 5H, H6, H7 and H2b), 4.65–4.71(m, 1H, H2a), 5.17–5.24 (s, 2H, CH2Bz), 5.29–5.36 (s, 1H, H3), 7.08–7.31 (m, 4H, H3H4H5H6Pht), 7.56–8.25 (m, 4H, H2H4H5H6Bz); 13C-NMR δ: 13.36 (CH3Bz), 18.05 (C5), 20.62 (C8), 21.23 (C4), 26.22 (C6), 29.98 (C7), 64.05 (C3), 67.53 (CH2Bz), 67.83 (C2), 125.49 (C2Bz), 128.41–129.29 (C2C4C5C6Bz), 130.55 (C1Pht), 130.89–131.97 (C3C4C5C6Pht), 132.75 (C1Bz), 135.17 (C2Pht), 138.35 (C3Bz), 168.09 (COOH), 171.03 (C=O). ESMS: m/z (calcd for C23H26NO4+ 380.19) found 380.3.
3-Phthaloyloxy-1-(4-methylbenzyl)quinuclidinium bromide (12). Yield: 81%, yellow viscous oil; IR (cm−1): 3419 (O-H), 2957 (C-H), 1722 (C=O), 1458 (C=C), 1285 (C-O), 1039 (C-N); 1H-NMR δ: 1.77–1.87 (m, 4H, H5 and H8), 2.27–2.35 (m, 1H, H4), 2.28 (s, 3H, CH3Bz), 3.45–3.52 (m, 5H, H6, H7 and H2b), 3.94–3.90 (m, 1H, H2a), 4.84 (s, 2H, CH2Bz), 4.51 (q, 1H, H3); 7.11–7.16 (m, 4H, H2H3H5H6Bz), 7.27–7.36 (m, 2H, H4H5Pht), 7.45–7.52 (m, 2H, H3H6Pht), 8.19–8.24 (m, 1H, COOH); 13C-NMR δ: 17.97 (C5), 21.23 (C4), 21.57 (C8), 26.92 (CH3Bz), 53.27 (C7), 54.36 (C6), 63.77 (C2), 64.09 (C3), 67.63 (CH2Bz), 123.44 (C1Bz), 129.93 (C3C6Pht), 131.04 (C2C3C5C6Bz), 132.43 (C4Pht), 132.88 (C5Pht), 134.11 (C1C2Pht), 140.89 (C4Bz), 170.95 (C=O, COOH). ESMS: m/z (calcd for C23H26NO4+ 380.19) found 380.3.