Synthesis of Ethano Strapped TBs

Synthesis of Ethano Strapped TBsChapter 3 Synthesis of Ethano Strapped TBs.3.2Experimental Section3.2.1General procedure for the synthesis of ethano-strapped Trgers rear end.The methano-strapped Trgers found (4.24 mmol) and 1,2-dibromoethane (1.60 g, 8.48 mmol, 2.0 eq.) were dissolved in N,N-dim ethyl radicalformamide (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 swear out with water (2 25 mL), dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The crude material was chromatographed (silica gel) to dedicate the desired ethano-strapped Trgers stem turn products.3.3.52,8-Dimethoxy-6H,12H-5,11-ethanodibenzob,f1,5diazocine X(MHK 02-60)ACT check over proton magnetic resonance start with 2,8-dimethoxy Trgers base X (1.20 g, 4.24 mmol), the crude material obtained upon work-up was chromatographed (sil ica gel, dichloromethaneethyl acetate 41) to buckle under X (659 mg, 53%) as an off-white solid. m.p. 185-187 C (lit.ref 186-189 C)1. 1H proton magnetic resonance (400 MHz, CDCl3), 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 be in agreement with those reported in the literature.13.3.42,8-Dibromo-6H,12H-5,11-ethanodibenzob,f1,5diazocine X(MHK 01-120)ACT checked nuclear magnetic resonanceStarting with 2,8-dibromo Trgers 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) 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.23.3.26H,12H-5,11-Ethanodibenzob,f1,5diazocine X(MHK 01-116)ACT checked NMRStarting with unsubstituted methano-strapped Trgers base X (942 mg, 4.24 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane ethyl acetate 41) 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) 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.35.3.20Di-tert-butyl-3,9-dicarbamate-2,8-dimethyl-6H,12H-5,11-ethanodibenzob,f1,5diazocine X (MHK-06-108) Sample has a lot of ethyl acetate in it re-run both 1H and 13C NMRStarting with bis(3,9-tert-butyl-dicarbamate-2,8-dimethyl Trgers base X (5.00 g, 10.42 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethaneethyl acetate 11) 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) 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) 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. arrange C XX H XX N XX %.3.3.38H,16H-7,15-Ethanodinaphtho2,1-b2,1-f1,5diazocine X(MHK 03-72)ACT checked NMR contains an impurity ethano strap region should be symmetricRe-run both 1H and 13C NMR grow crystalsStarting with naphthalene Trgers 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) 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) 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-ethanodibenzob,f1,5diazocine X(MHK 04-50)The spectrum is terrible there is NO way you can claim to have made this compound see meStarting with 2,8-dimethanol Trgers base X (400 mg, 1.42 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethane ethyl acetate 11) to afford X (134 mg, 32%) as a colourless solid. m.p. X-Y C (lit.ref A-B C).2 1H NMR (40 0 MHz, CDCl3) 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) 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. Ishida, Y. Ito, H. Mori, D. Saigo, K., Tetrahedron Lett. 2005, 46, 109-112.3.3.82-Bromo-8-methyl-6H,12H-5,11-ethanodibenzob,f1,5diazocine X(MHK-05-18)ACT checked NMRStarting with 2-bromo-8-methyl Trgers 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) 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) 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-ethanodibenzob,f1,5diazocine 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 peaksStarting with 2-bromo-8-methoxy Trgers base X (500 mg, 1.51 mmol), the crude material obtai ned upon work-up was chromatographed (silica gel, dichloromethaneethyl acetate 21) 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) 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-ethanodibenzob,f1,5diazocine X(MHK-04-30)ACT checked 1H NMR NEED 13C NMRStarting with 2-ethoxycarbonyl-4,8-dim ethyl Trgers base X (500 mg, 1.55 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethaneethyl acetate 41) to afford X (88 mg, 17%) as a pale yellow solid. m.p. 182-185 C. 1H NMR (400 MHz, CDCl3) 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) 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-ethanodibenzob,f1,5diazoci ne 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 ACTStarting with 8-bromo-2-ethoxycarbonyl-4-methyl Trgers base X (5.50 g, 14.21 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethaneethyl acetate 31) to afford X (1.70 mg, 30%) as pale yellow solid. m.p. 196 C. 1H NMR (400 MHz, CDCl3) 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) 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 p pm. 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-ethanodibenzob,f1,5diazocine X(MHK-02-10)Need 1H and 13C NMR where are theseStarting with 1,4,8-trimethyl-2-nitro- Trgers base Y (500 mg, 1.62 mmol), the crude material obtained upon work-up was chromatographed (silica gel, dichloromethaneethyl acetatehexane 411) to afford X (153 mg, 29%) as a yellow solid. m.p. 138-141 C. 1H NMR (400 MHz, CDCl3) 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) 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-ethanodibenzob,f1,5diazocine X(MHK-02-10, MHK04-66 ChromA1)re-run 1H and 13 SpectraStarting with 2,8-dimethyl-4-nitro-Trgers 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 101) to afford Y (120 mg, 23%) as a yellow solid. m.p. 168-170 C. 1H NMR (400 MHz, CDCl3) 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) 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%.References1.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.