Paper
Organic & Biomolecular Chemistry
compounds with biologically relevant stability of metal for 10 h at 65 °C. 1,6-Dibromohexane (0.7 mL, 4.54 mmol) and
complexes.
anhydrous potassium carbonate (0.026 g, 0.189 mmol) were
then added and stirring was continued for 24 h at room temp-
erature. The reaction mixture was transferred to a separatory
funnel and partitioned between dichloromethane (20 mL) and
water (100 mL). A small amount of solid KBr was added to
improve separation of the phases. The organic layer was separ-
Experimental
Synthetic procedures
(7-{2-[3-(Aden-9-yl)propoxy]benzoyl}-16-{2-[3-(N-pyridinium- ated and washed thoroughly with water (5 × 30 mL), dried over
1-yl)propoxy]benzoyl}-5,14-dihydrodibenzo[b,i][1,4,8,11]tetra- anhydrous magnesium sulfate, concentrated to a small volume
azacyclotetradecine bromide) (1). A mixture consisting of and chromatographed on a column of silica gel using dichloro-
adenine (0.266 g, 1.973 mmol), 60% NaH (0.059 g, methane–methanol, (20 : 0.4 v/v) as eluent. The second fraction
1.408 mmol) in anhydrous DMF (5 mL) was stirred for 1 h at was collected from the two orange ones of highest intensity. It
room temperature. Compound a (0.76 g, 0.986 mmol) dis- was evaporated to dryness, dissolved in a small volume of
solved in anhydrous DMF (60 mL) was added and the reaction chloroform and once more chromatographed on a column of
mixture was stirred at 40 °C for 5 min, then for 3 h at room silica gel, using chloroform–methanol (20 : 0.4 v/v) as eluent.
temperature. The reaction mixture was then transferred to a The main fraction was collected, evaporated to dryness and a
separatory funnel and partitioned between dichloromethane solid residue was dissolved in pyridine (5 mL). The mixture
(150 mL) and water (100 mL). The organic layer was separated, was stirred for 7 h at 45 °C, then pyridine was removed under
washed with water (2 × 100 mL), dried over anhydrous mag- diminished pressure and the solid residue was chromato-
nesium sulfate, concentrated to a small volume and chromato- graphed on a column with basic aluminium oxide, using
graphed on a column of silica gel using dichloromethane– dichloromethane–methanol (20 : 2 v/v) as eluent. The main
methanol (40 : 2 v/v) as eluent. The main orange fraction was orange fraction was collected and evaporated to dryness. An
collected and evaporated to dryness. A residue was dissolved in orange microcrystalline product was obtained by slow evapor-
pyridine (6 mL) and stirred for 9 h at 45 °C. the excess of pyri- ation of methylene chloride solution of the crude material
dine was removed under diminished pressure and the residue (0.042 g, 11%).
was chromatographed on a column with basic aluminium
Mp: 194–196 °C. 1H-NMR (300 MHz, DMSO-d6, δ): 0.97–1.28
oxide, using dichloromethane–methanol (20 : 3 v/v) as eluent. (8H, m, aliphatic chain), 1.50 (6H, m, aliphatic chain), 1.64
The main orange fraction was collected, concentrated to a (2H, m, aliphatic chain), 3.86 (2H, t, J = 7 Hz, Hj), 3.95 (4H, m,
small volume and diluted with n-hexane to precipitate an Ha, Ho), 4.40 (2H, t, J = 7.5 Hz, Hf), 7.03–7.19 (14H, m, H1–H4,
orange product (0.144 g, 16%).
H12–H15, H26, H26′, H28, H28′, Hu), 7.34 (2H, m, H25, H25′), 7.49
Mp: 164–166 °C. 1H-NMR (300 MHz, DMSO-d6, δ): 2.10 (2H, (2H, m, H27, H27′), 7.85 (1H, s, Hs), 7.97 (1H, s, Hp), 8.05 (2H,
m, Hh), 2.28 (2H, m, Hb), 4.03 (2H, t, J = 6.0 Hz, Hg), 4.12 (4H, m, Hh), 8.44 (4H, m, H7, H9, H18, H20), 8.53 (1H, m, Hi), 8.93
m, Ha, Hi), 4.65 (2H, t, J = 6.9 Hz, Hc), 7.04 (2H, s, Ho), (2H, m, Hg), 14.20 (2H, m, H10, H21). 13C-NMR (75 MHz,
7.08–7.24 (12H, m, H1–H4, H12–H15, H26, H26′, H28, H28′), 7.35 DMSO-d6, δ): 24.8, 24.9, 25.0, 25.6, 28.2, 28.4, 29.1, 30.6 (Cb–
(2H, m, H25, H25′), 7.50 (2H, m, H27, H27′), 7.85 (1H, s, Hm), Ce, Ck–Cn), 42.5 (Co), 60.5 (Cf), 67.7, 67.8 (Ca, Cj), 110.1 (C8,
7.90 (1H, s, Hj), 7.96 (2H, m, He), 8.36 (2H, d, J = 6.5 Hz, {H7, C19), 112.5 (C28, C28′), 115.2 (C1, C4, C12, C15), 118.7 (Cq), 120.8
H9}/{H18, H20}), 8.45–8.52 (3H, m, {H7, H9}/{H18, H20}, Hf), 8.98 (C26, C26′), 126.7 (C2, C3, C13, C14), 128.0 (Ch), 128.7, 128.7 (C24,
(2H, m, Hd), 14.20 (2H, m, H10, H21). 13C-NMR (75 MHz, C24′), 129.4, 129.3 (C25, C25′), 131.5, 131.7 (C27, C27′), 136.1,
DMSO-d6, δ): 29.0 (Ch), 30.0 (Cb), 58.3 (Cc), 65.0 (Ca), 65.2 (Cg), 136.1 (C5, C11, C16, C22), 140.4 (Cp), 144.4 (Cg), 145.4 (Ci), 149.3
109.8, 110.2 (C8, C19), 112.7, 113.0 (C28, C28′), 115.3, 115.4 (C1, (Cr), 152.2 (Cs), 152.5 (C7, C9, C18, C20), 155.2, 155.3 (C29, C29′),
C4, C12, C15), 118.7 (Ck), 121.0, 121.1 (C26, C26′), 126.7 (C2, C3, 155.8 (Ct), 191.6 (C23, C23′). IR (ATR) νmax (cm−1): 1239, 1290,
C13, C14), 127.8 (Ce), 128.6, 128.8 (C24, C24′), 129.2 (C25, C25′), 1308, 1414, 1447, 1485, 1558, 1585, 1652, 1679, 2875, 2931,
131.4, 131.5 (C27, C27′), 136.2, 136.3 (C5, C11, C16, C22), 140.4 3059, 3116, 3242, 3374. MS (ESI) m/z found 908.3. Calc. for
+
(Cj), 144.6 (Cd), 145.4 (Cf), 149.3 (Cl), 152.1 (Cm), 152.4, 152.6 C54H55N10O4 : 907.44. Anal. found: C, 65.62; H, 5.95; N, 14.05.
(C7, C9, C18, C20), 154.8, 155.1 (C29, C29′), 155.7 (Cn), 191.2, Calc. for C54H55N10O4Br: C, 65.65; H, 5.61; N, 14.18%.
191.4 (C23, C23′). IR (ATR) νmax (cm−1): 1254, 1285, 1326, 1414,
(7-(2-Hexoxybenzoyl)-16-{2-[3-(N-pyridinium-1-yl)propoxy]-
1445, 1487, 1557, 1591, 1642, 2876, 2959, 3059, 3203, 3355. MS benzoyl}-5,14-dihydrodibenzo[b,i][1,4,8,11]tetraazacyclotetra-
+
(ESI) m/z found: 823.6. Calc. for C48H43N10O4 : 823.35. Anal. decine bromide) (3). A reaction mixture consisting of com-
found: C, 61.47; H, 4.98; N, 14.71. Calc. for pound c (1 g, 1.892 mmol), 1-bromohexane (0.319 mL,
C48H43N10O4Br·2H2O: C, 61.34; H, 5.04; N, 14.90%.
2.27 mmol) and anhydrous potassium carbonate (0.313 g,
(7-{2-[6-(Aden-9-yl)hexoxy]benzoyl}-16-{2-[6-(N-pyridinium-1- 2.27 mmol) in anhydrous DMF (130 mL) was stirred at 60 °C,
yl)hexoxy]benzoyl}-5,14-dihydrodibenzo[b,i][1,4,8,11]tetraaza- for 3 h. The mixture was cooled down, transferred to a separa-
cyclotetradecine bromide) (2). A reaction mixture consisting of tory funnel and partitioned between chloroform(150 mL) and
compound c (0.2 g, 0.378 mmol), anhydrous potassium car- water (200 mL). A few drops of hydrobromic acid solution were
bonate (0. 104 g, 0.757 mmol) and 9-(6-bromohexyl)adenine added to improve separation of the phases. The organic layer
(0.056 g, 0.189 mmol) in anhydrous DMF (40 mL) was stirred was separated and washed thoroughly with water (7 × 100 mL),
4082 | Org. Biomol. Chem., 2013, 11, 4077–4085
This journal is © The Royal Society of Chemistry 2013