Synthesis of Ethano Strapped TBs

Synthesis of Ethano Strapped TBs Chapter 3 Synthesis of Ethano Strapped TBs. 3.2  Experimental Section 3.2.1  General procedure for the synthesis of ethano-strapped Trà ¶gers base. The methano-strapped TrÓ §gers base (4.24 mmol) and 1,2-dibromoethane (1.60 g, 8.48 mmol, 2.0 eq.) were dissolved in N,N-dimethylformamide (5 mL) and lithium carbonate (1.41 g, 19.08 mmol, 4.5 eq.) was added to the mixture which was stirred and heated at 110  °C for 3 days.   The mixture was cooled and suspended in ethyl acetate (100 mL) and then washed with water (2 25 mL), dried over anhydrous magnesium sulfate, filtered and evaporated to dryness.   The crude material was chromatographed (silica gel) to afford the desired ethano-strapped Trà ¶gers base products. 3.3.5  2,8-Dimethoxy-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X(MHK 02-60)ACT checked NMR Starting with 2,8-dimethoxy TrÓ §gers base X (1.20 g, 4.24 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane:ethyl acetate 4:1) to afford X (659 mg, 53%) as an off-white solid.   m.p. 185-187  °C (lit.ref 186-189  °C)1.   1H NMR (400 MHz, CDCl3), ÃŽ ´ 3.55-3.61 (4H, m, CH2-CH2), 3.68 (6H, s, OCH3), 4.37 (2H, d, J = 17.2 Hz, CH2), 4.55 (2H, d, J = 17.2 Hz, CH2), 6.43 (2H, d, J = 2.8 Hz, ArH), 6.62 (2H, dd, J = 2.8, 8.6 Hz, ArH), 7.07 (2H, d, J = 8.6 Hz, ArH).   The data are in agreement with those reported in the literature.1 3.3.4  2,8-Dibromo-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X(MHK 01-120)ACT checked NMR Starting with 2,8-dibromo TrÓ §gers base X (1.65 g, 4.24 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane) to afford X (750 mg, 45%) as an off-white solid.   m.p. 220  °C.   1H NMR (400 MHz, CDCl3) ÃŽ ´ 3.47-3.59 (4H, m, CH2-CH2), 4.35 (2H, d, J = 17.4 Hz, CH2), 4.53 (2H, d, J = 17.4 Hz, CH2), 6.96 (2H, d, J = 8.4 Hz, ArH), 7.04 (2H, d, J = 2.1 Hz, ArH), 7.17 (2H, dd, J = 2.1, 8.4 Hz, ArH).   The data are in agreement with those reported in the literature.2 3.3.2  6H,12H-5,11-Ethanodibenzo[b,f][1,5]diazocine X(MHK 01-116)ACT checked NMR Starting with unsubstituted methano-strapped TrÓ §gers base X (942 mg, 4.24 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane: ethyl acetate 4:1) to afford X (505 mg, 51%) as an off-white solid.   m.p. 169-171  °C (lit.3 174  °C).   1H NMR (400 MHz, CDCl3) ÃŽ ´ 3.53-3.68 (4H, m, CH2-CH2), 4.46 (2H, d, J = 17.2 Hz, CH2), 4.61 (2H, d, J = 17.2 Hz, CH2), 6.89-6.96 (4H, m, ArH), 7.03-7.08 (2H, m, ArH), 7.09-13 (2H, m, ArH).   The data are in agreement with those reported in the literature.3 5.3.20Di-tert-butyl-3,9-dicarbamate-2,8-dimethyl-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X (MHK-06-108)   Sample has a lot of ethyl acetate in it re-run both 1H and 13C NMR Starting with bis(3,9-tert-butyl-dicarbamate-2,8-dimethyl TrÓ §gers base X (5.00 g, 10.42 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane:ethyl acetate 1:1) to afford X (2.67 g, 52% with 7% methano strapped as a impurity) as a pale brown solid.   m.p. X-Y  °C.   1H NMR (400 MHz, CDCl3) ÃŽ ´ 1.49 (18H, s, Boc CH3), 2.03 (6H, s, CH3), 3.50-3.60 (4H, m, CH2-CH2), 4.40 (2H, d, J = 17.1 Hz, CH2), 4.48 (2H, d, J = 17.1 Hz, CH2), 6.08 (2H, s, ArH), 6.67 (2H, s, ArH), 7.56 (2H, br s, NH).   13C NMR (100 MHz, CDCl3) ÃŽ ´ 17.1, 28.3, 54.9, 58.5, 80.2, 120.3, 128.4, 130.3, 132.0, 134.9, 148.8, 152.9 ppm.   FTIR 1049 (m), 1182 (s), 1230 (m), 1709 (s, C=O), 2900 (m), 2972 (m), 3295(bs), cm-1.   Anal. Calcd for C28H38N4O4:   C 67.99; H 7.74; N 11.33.   Found C XX; H XX; N XX %. 3.3.38H,16H-7,15-Ethanodinaphtho[2,1-b][2,1-f][1,5]diazocine X(MHK 03-72)ACT checked NMR contains an impurity ethano strap region should be symmetric Re-run both 1H and 13C NMR grow crystals! Starting with naphthalene TrÓ §gers base X (500 mg, 1.55 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane) to afford X (113 mg, 22%) as an off-white solid.   m.p. 224-227  °C.   1H NMR (400 MHz, CDCl3) ÃŽ ´ 3.75-3.97 (4H, m, CH2-CH2), 4.90 (2H, d, J = 17.5 Hz, CH2), 5.44 (2H, d, J = 17.5 Hz, CH2), 7.27-7.37 (4H, m, ArH), 7.41-7.48 (2H, m, ArH), 7.51 (2H, app. d, J = 8.6 Hz, ArH), 7.67 (2H, app. d, J = 8.0 Hz, ArH), 7.82 (2H, d, J = 8.5 Hz, ArH).   13C NMR (100 MHz, CDCl3) ÃŽ ´ 55.2, 55.7, 122.3, 124.4, 126.0, 127.3, 127.5, 128.3, 128.6, 131.5, 132.5, 148.5 ppm.   FTIR 828 (s), 927 (s), 1137 (m), 1209 (m), 1469 (m), 2360 (m), 2900 (m), 2959 (m) cm-1.   Anal. Calcd for C24H20N2:   C 85.68; H 5.99; N 8.33.   Found C 85.73; H 5.68; N 8.59%. 3.3.72,8-Dimethanol-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X(MHK 04-50)The spectrum is terrible there is NO way you can claim to have made this compound see me Starting with 2,8-dimethanol TrÓ §gers base X (400 mg, 1.42 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane: ethyl acetate 1:1) to afford X (134 mg, 32%) as a colourless solid.   m.p. X-Y  °C (lit.ref A-B  °C).2   1H NMR (400 MHz, CDCl3) ÃŽ ´ 1.76 (2H, br s, OH), 3.46-3.64 (4H, m, CH2-CH2), 4.43 (2H, d, J = 17.3 Hz, CH2), 4.47 (2H, s, CH2OH), 4.56 (2H, d, J = 17.2 Hz, CH2), 6.89 (2H, app. s, ArH), 7.02 (2H, dd, J = 1.5, 8.1 Hz, ArH), 7.07 (2H, d, J = 8.0 Hz, ArH), 7.26 (2H, s, ArH).   13C NMR (100 MHz, CDCl3) ÃŽ ´ 54.6, 59.1, 64.8, 126.1, 127.5, 128.1, 136.7, 137.2, 149.6 ppm.   FTIR 750 (s), 884 (s), 1105 (m), 1195 (m), 1328 (m), 1491 (d), 1622 (s), 1701 (s, C=O), 2852 (m), 2893 (bs), 2946 (m) cm-1.   Anal. Calcd for C18H20N2O2:   C 72.95; H 6.80; N 9.45.   Found C XX; H XX; N XX %.   See me is this compound in the literature(NOT charactrised in letreature)   1.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã ‚  Ã‚   Ishida, Y.; Ito, H.; Mori, D.; Saigo, K., Tetrahedron Lett. 2005, 46, 109-112. 3.3.82-Bromo-8-methyl-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X(MHK-05-18)ACT checked NMR Starting with 2-bromo-8-methyl TrÓ §gers base X (1.30 g, 4.12 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane) to afford X (1.00 g, 73%) as an off-white solid.   m.p. 209-212  °C.   1H NMR (400 MHz, CDCl3) ÃŽ ´ 2.19 (3H, s, CH3), 3.47-3.62 (4H, m, CH2-CH2), 4.37 (2H, app. d, J = 17.1 Hz, CH2), 4.53 (1H, d, J = 17.2 Hz, CH2), 4.54 (1H, d, J = 17.2 Hz, CH2), 6.71 (1H, app. s, ArH), 6.86-6.91 (1H, m, ArH), 6.97 (1H, d, J = 8.3 Hz, ArH), 6.99 (1H, d, J = 7.9 Hz, ArH), 7.03 (1H, d, J = 2.1 Hz, ArH), 7.15 (1H, dd, J = 2.1, 8.3 Hz, ArH).   13C NMR (100 MHz, CDCl3) ÃŽ ´ 20.7, 54.70, 54.74, 58.7, 59.0, 117.5, 127.7, 128.1, 129.1, 129.7, 130.1, 131.4, 134.4, 136.0, 139.2, 147.2, 149.5 ppm.   FTIR 863 (s), 944 (m), 1090 (m), 1219 (s), 1341 (s), 1476 (s), 1518 (s), 2901 (m), 2954 (m) cm-1.   Anal. Calcd for C17H17BrN2:   C 62.02; H 5.20; N 8.51.   Found C 62.29; H 5.12; N 8.68%. 3.3.92-Bromo-8-methoxyl-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X(MHK-04-34)ACT checked NMRReplot 13C with expansions of all picked peaks and show ACTMay need to re-run 13C with more scans not sure about some peaks Starting with 2-bromo-8-methoxy TrÓ §gers base X (500 mg, 1.51 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane:ethyl acetate 2:1) to afford X (180 mg, 35%) as a pale brown solid.   m.p. 156-157  °C.   1H NMR (400 MHz, CDCl3) 3.50-3.60 (4H, m, CH2-CH2), 3.68 (3H, s, OCH3), 4.34 (1H, d, J = 17.3 Hz, CH2), 4.37 (1H, d, J = 17.2 Hz, CH2), 4.52 (1H, d, J 17.3 Hz, CH2), 4.54 (1H, d, J = 17.2 Hz, CH2), 6.42 (1H, d, J = 2.9 Hz, ArH), 6.63 (1H, dd, J = 2.9, 8.6 Hz, ArH), 6.98 (1H, d, J = 8.4 Hz, ArH), 7.01-7.06 (2H, m, ArH), 7.16 (1H, dd, J = 2.0, 8.4 Hz, ArH).   13C NMR (100 MHz, CDCl3) ÃŽ ´ 54.7, 54.8, 55.2, 58.8, 59.2, 112.8, 113.3, 117.6, 128.8, 129.7, 130.2, 131.5, 137.5, 139.0, 149.4, 156.6, 165.6 ppm.   FTIR 805 (m), 846 (m), 1025 (s), 1066 (s), 1278 (s), 1469 (s), 1487 (m), 1594 (m), 2359 (m), 2900 (m) cm-1.   Anal. Calcd for C17H17BrN2O:   C 59.14; H 4.96; N 8.11.   Found C 59.26; H 4.72; N 8.08%. 3.3.102-Ethoxycarbonyl-4,8-dimethyl-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X(MHK-04-30)ACT checked 1H NMR NEED 13C NMR Starting with 2-ethoxycarbonyl-4,8-dimethyl TrÓ §gers base X (500 mg, 1.55 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane:ethyl acetate 4:1) to afford X (88 mg, 17%) as a pale yellow solid.   m.p. 182-185  °C.   1H NMR (400 MHz, CDCl3) ÃŽ ´ 1.32 (3H, t, J = 7.1 Hz, CH3), 2.17 (3H, s, CH3), 2.38 (3H, s, CH3), 3.54-3.66 (4H, m, CH2-CH2), 4.20-4.33 (3H, m, CH2), 4.49 (1H, d, J = 17.4 Hz, CH2), 4.50 (1H, d, J = 17.2 Hz, CH2), 4.60 (1H, d, J = 17.2 Hz, CH2), 6.69 (1H, app. s, ArH), 6.85-6.89 (1H, m, ArH), 7.02-7.09 (1H, m, ArH), 7.46 (1H, app. s, ArH), 7.65 (1H, app. s, ArH).   13C NMR (100 MHz, CDCl3) ÃŽ ´ 14.3, 17.8, 20.7, 54.7, 55.4, 55.4, 59.3, 60.6, 126.1, 127.8, 128.1, 129.0, 130.0, 134.3, 135.5, 136.5, 137.0, 147.2, 152.8, 166.5 ppm.   FTIR 776 (s), 833 (s), 905 (m), 1025 (s), 1215 (s), 1293 (s), 1497 (s), 1709 (s, C=O), 2900 (m) cm-1.   Anal. Calcd for C21H24N2O2:   C 74.97; H 7.19; N 8.33.   Found C 74.72; H 7.25; N 8.41 %. 2.3.118-Bromo-2-ethoxycarbonyl-4-methyl-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X (MHK-05-22)ACT checked NMRNeed to re-run 13C with more scans insufficient aryl peakssections of 1H MR should go in thessi with discussion see ACT Starting with 8-bromo-2-ethoxycarbonyl-4-methyl TrÓ §gers base X (5.50 g, 14.21 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane:ethyl acetate 3:1) to afford X (1.70 mg, 30%) as pale yellow solid.   m.p. 196  °C.   1H NMR (400 MHz, CDCl3) ÃŽ ´ 1.33 (3H, t, J = 7.1 Hz, CH3), 2.36 (3H, s, CH3), 3.54-3.64 (4H, m, CH2-CH2), 4.21 (1H, d, J = 17.5 Hz, CH2), 4.24-4.34 (2H, 2 x overlapping q, J = 7.1 Hz, CH2-CH3), 4.47 (1H, d, J = 17.3 Hz, CH2), 4.49 (1H, d, J = 17.4 Hz, CH2), 4.57 (1H, d, J = 17.3 Hz, CH2), 6.97 (1H, d, J = 8.4 Hz, ArH), 7.01 (1H, d, J = 2.2 Hz, ArH), 7.15 (1H, dd, J = 2.2, 8.4 Hz, ArH), 7.44-7.46 (1H, m, ArH), 7.65-7.67 (1H, m, ArH).   13C NMR (100 MHz, CDCl3) ÃŽ ´ 14.3, 17.8, 54.6, 55.0, 55.2, 59.1, 60.7, 117.6, 126.3, 128.0, 129.9, 130.2, 130.3, 131.2, 135.6, 136.6, 139.1, 149.2, 152.3, 166.4 ppm.   FTIR 827 (s), 927 (s), 1023 (m), 1150 (s), 1387 (s), 1412 (m), 11470 (s), 1704 (s, C=O), 2360 (m), 2900 (m) cm -1.   Anal. Calcd for C20H21BrN2O2:   C 59.86; H 5.27; N 6.98.   Found C 59.76; H 5.19; N 7.21%. 3.3.121,4,8-Trimethyl-2-nitro-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X(MHK-02-10)Need 1H and 13C NMR where are these!!! Starting with 1,4,8-trimethyl-2-nitro- TrÓ §gers base Y (500 mg, 1.62 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane:ethyl acetate:hexane 4:1:1) to afford X (153 mg, 29%) as a yellow solid.   m.p. 138-141  °C.   1H NMR (400 MHz, CDCl3) ÃŽ ´ 2.20 (6H, s, CH3), 2.36 (3H, s, CH3), 3.54-3.64 (4H, m, CH2-CH2), 4.33 (1H, d, J = 17.5 Hz, CH2), 4.36 (1H, d, J = 17.6, CH2), 4.50 (1H, d, J = 17.5 Hz, CH2), 4.65 (1H, d, J = 17.6 Hz, CH2), 6.75 (1H, app. s, ArH), 6.89 (1H, app.d, J = 7.9 Hz, ArH), 7.01 (1H, d, J = 8.0 Hz, ArH), 7.40 (1H, s, ArH).   13C NMR (100 MHz, CDCl3) ÃŽ ´ 14.7, 17.8, 20.7, 54.1, 54.9, 55.7, 57.2, 124.1, 125.0, 127.9, 128.3, 128.6, 128.8, 134.2, 134.6, 136.5, 136.8, 147.2, 152.4 ppm.   FTIR 819 (m), 1053 (s), 1185 (m), 1280 (s), 1369 (m), 1497 (m), 2359 (m), 2900 (m), 2987 (m) cm-1.   Anal. Calcd for C19H21N3O2:   C 70.57; H 6.55; N 12.99.   Found C 70.52; H 6.28; N 12.69%. 3.3.142,8-Dimethyl-4-nitro-6H,12H-5,11-ethanodibenzo[b,f][1,5]diazocine X(MHK-02-10, MHK04-66 ChromA1)re-run 1H and 13 Spectra Starting with 2,8-dimethyl-4-nitro-Trà ¶gers base X (500 mg, 1.69 mmol) and 1with heating for 5 days,the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane: ethyl acetate 10:1) to afford Y (120 mg, 23%) as a yellow solid.   m.p. 168-170  °C.   1H NMR (400 MHz, CDCl3) ÃŽ ´ 2.20 (3H, s, CH3), 2.21 (3H, s, CH3), 3.42-3.63 (4H, m, CH2-CH2), 4.44 (1H, d, J = 17.6 Hz, CH2), 4.50 (2H, app. s, CH2), 4.62 (1H, d J = 17.6 Hz, CH2), 6.79 (1H, app. s, ArH), 6.87-6.94 (2H, m, ArH), 7.02 (1H, d, J = 8.0 Hz, ArH), 7.11 (1H, app. s, ArH).   13C NMR (100 MHz, CDCl3) ÃŽ ´ 20.5, 20.7, 54.4, 56.0, 58.0, 59.4, 122.0, 127.5, 128.1, 129.4, 132.2, 134.6, 135.4, 136.0, 139.4, 140.8, 146.9, 150.5 ppm.   FTIR 836 (m), 884 (m), 1021 (m), 1171 (s), 1371 (m), 1521 (s), 2910 (m), cm-1.   Anal. Calcd for C18H19N3O2:   C 69.88; H 6.19; N 13.58.   Found C 69.67; H 6.24; N 13.43%. References 1.Hamada, Y.; Mukai, S., Tetrahedron: Asymmetry 1996, 7, 2671-2674. 2.Ishida, Y.; Ito, H.; Mori, D.; Saigo, K., Tetrahedron Lett. 2005, 46, 109-112. 3.Faroughi, M.; Try, A. C.; Turner, P., Acta Crystallogr., Sect. E: Struct. Rep. Online 2008, 64, o458.