552 Wang et al.
Asian J. Chem.
was heated under reflux and the progress of the reaction
monitored by TLC (CH2Cl2/CH3OH 7:1 silica gel). After dis-
appearance of the starting material (about 8 h), the remaining
solids were removed by filtration and filtrate was cooled to
give compound 1, white solid, yields: 89.5 %. m.p.: 101-102
1
°C. H NMR (300 MHz, CDCl3), δ (ppm): 6.79-6.69 (16H,
dd, C6H4), 4.02 (8H, s, cyclen-CH2CH2O), 3.75 (12H, s, OCH3),
3.27 (8H, s, cyclen-CH2CH2O), 3.13 (16H, s, NCH2CH2N).
13C NMR (75.47 MHz, CDCl3), δ (ppm): 153.78, 153.09,
115.45, 114.73 (C6H4), 67.22 (cyclen-CH2CH2O), 55.74
(OCH3), 54.82 (cyclen-CH2CH2O), 53.66 (NCH2CH2N). MS
(ESI, CH2Cl2/MeOH + 1 %AcOH) m/z (%): 773.5 [M+] (100),
795.50 [M+Na]+ (37). IR (KBr, νmax, cm-1): 3444.2, 2931.5,
2832.9, 1509.8, 1233.7, 1034.9, 827.6.
1,4,7,10-Tetrakis[2-((4-benzyloxy)phenoxy)ethyl]-
1,4,7,10-tetraazacyclododecane (2): To a solution of cyclen
(0.2 g, 1.16 mmol), 2b (1.78 g, 5.8 mmol) in 30 mL CH3CN
was added K2CO3 (0.83 g, 6.0 mmol). The resulting solution
was heated under reflux and the progress of the reaction
monitored by TLC (CH2Cl2/CH3OH 7:1 silica gel). After dis-
appearance of the starting material (about 6 h), the remaining
solids were filtered off and washed several times with deionized
water and CH3OH to yield compound 2, white solid, yields:
90.8 %. m.p.: 139-140 °C. 1H NMR (300MHz, CDCl3), δ
(ppm): 7.38-7.30 (20H, m, C6H5), 6.87-6.77 (16H, dd, C6H4),
4.95 (8H, s, PhCH2), 3.96 (8H, s, cyclen-CH2CH2O), 2.82 (8H,
s, cyclen-CH2CH2O), 2.75 (16H, s, NCH2CH2N). 13C NMR
(75.47MHz, CDCl3), δ (ppm): 153.33, 151.86, 115.46 (C6H4),
137.39, 128.60, 127.93 (C6H5), 70.74 (C6H5CH2O), 67.24
(cyclen-CH2CH2O), 54.83 (cyclen-CH2CH2O), 53.70
(NCH2CH2N). MS (ESI, CH2Cl2/MeOH + 1 % AcOH) m/z
(%): 1078.8 [M+] (6). IR (KBr, νmax, cm-1): 3444.1, 2925.4,
2825.3, 2798.1, 1508.8, 1233.7, 1041.6, 826.0, 760.3, 734.7.
1,4,7,10-Tetrakis[2-((4-ethoxyacyl)phenoxy)ethyl]-
1,4,7,10-tetraazacyclododecae (3): To a solution of cyclen
(0.2 g, 1.16 mmol), 3b (1.58 g, 5.8 mmol) in 30 mL CH3CN
was added K2CO3 (0.83 g, 6.0 mmol). The resulting solution was
heated under reflux and the progress of the reaction monitored
by TLC (CH2Cl2/CH3OH 7:1 silica gel). After disappearance
of the starting material (about 8 h), the remaining solids were
filtered off and washed several times with deionized water
and CH3OH to yield compound 3, white solid, yields: 83.2 %.
m.p.: 130-131 °C. 1H NMR (300 MHz, CDCl3), δ (ppm): 7.95-
Scheme-I: Synthesis of 1b, 2b, 3b and cyclen derivatives 1, 2, 3
18 h), the remaining solids were removed by filtration and
filtrate was cooled to give white solids. The solids were recrys-
tallized in ethanol to yield 1b, white solid, yields: 68.5 %.
m.p.: 50-51 °C. 1H NMR (300 MHz, CDCl3) δ (ppm): 6.88-
6.82 (m, 4H, C6H4), 4.25-4.23 (t, 2H, BrCH2CH2O), 3.77 (s,
3H, CH3O), 3.62-3.60 (t, 2H, BrCH2CH2O).
1-(2-Bromoethoxy)-4-benzyloxybenzene (2b): To a
solution of dibromoethane (56.4 g, 0.3 mol), KOH(10 g, 0.18
mol) in 150 mL EtOH was added to 2a (30 g, 0.15 mol). The
resulting solution was heated under reflux and the progress of
the reaction monitored by TLC (acetone/petroleum ether 1:2
silica gel). After disappearance of the starting material (about
24 h), the remaining solids were removed by filtration and filtrate
was cooled to give white solids. The solids were recrystallized
in ethanol to yield 2b, white solid, yields: 71.1 %. m.p.: 79-80
°C. 1H NMR (300 MHz, CDCl3) δ (ppm): 7.43-7.32 (m, 5H,
C6H5), 6.93-6.84 (m, 4H, C6H4), 5.02 (s, 2H, PhCH2O), 4.26-
4.22 (t, 2H, OCH2CH2Br), 3.63-3.59 (t, 2H, BrCH2CH2O).
Ethyl 4-(2-bromoethoxy) benzoate (3b): To a solution
of dibromoethane (37.6 g, 0.2 mol), K2CO3 (27.6 g, 0.2 mol)
in 100 mL CH3CN was added 3a (10 g, 0.06 mol). The resulting
solution was heated under reflux and the progress of the
reaction monitored by TLC (ethyl acetate/petroleum ether 1:5
silica gel). After disappearance of the starting material (about
22 h), the remaining solids were removed by filtration and the
precipitate was washed several times with CH3CN. The mother
liquor and washings were combined and evaporated to dryness
in a rotavapor. The pale yellow residue was purified by silica
column chromatography using 15:1, petroleum ether/ ethyl
acetate, to yield compound 3b, white solid, yields: 76.4 %.
m.p.: 72-73 °C. 1H NMR (300 MHz, CDCl3) δ (ppm): 8.02-
7.92, (8H, d, C6H2H2ortho-COOEt), 6.85-6.82 (8H, d, C6H2H2meta
-
COOEt), 4.37-4.30 (8H, q, CH3CH2O), 4.05-4.02 (8H, t,
cyclen-CH2CH2O), 2.86-2.84 (8H, t, cyclen-CH2CH2O), 2.74
(16H, s, NCH2CH2N), 1.62-1.35(12H, t, CH3CH2O). 13C NMR
(500 MHz, CDCl3), δ (ppm): 166.40 (COCH2CH3), 162.61,
131.61, 123.08, 114.11 (C6H4), 66.99 (cyclen-CH2CH2O),
60.69 (CH3CH2O), 54.61 (cyclen-CH2CH2O), 53.93
(NCH2CH2N), 14.47 (CH3CH2O). MS (ESI, CH2Cl2/MeOH +
1 % AcOH) m/z (%): 940.7 [M+] (72), 963.7 [M+ Na]+ (100),
979.9 [M+ K] + (5). IR (KBr, νmax, cm-1): 3444.3, 2975.8,
2810.6, 2810.3, 1712.4, 1607.2, 1510.6, 1279.3, 1256.9,
1102.9, 1021.4, 842.3.
7.99 (d, 2H, C6H2H2ortho-COOEt), 6.94-6.91 (m, 2H, C6H2H2meta
COOEt), 4.38-4.36 (t, 2H, BrCH2CH2O), 4.34-4.32 (q, 2H,
CH3CH2O), 3.69-3.63 (t, 2H, BrCH2CH2O), 1.40-1.35 (t, 3H,
CH3CH2O).
-
1,4,7,10-Tetrakis[2-((4-methoxy)phenoxy)ethyl]-
1,4,7,10-tetraazacyclododecane (1): To a solution of cyclen
(0.2 g, 1.16 mmol), 1b (1.34 g, 5.8 mmol) in 30 mL CH3CN
was added K2CO3 (0.83 g, 6.0 mmol). The resulting solution
1,4,7,10-Tetrakis[2-((4-hydroxy)phenoxy)ethyl]-
1,4,7,10-tetraazacyclododecane (4): Compound 2 (0.2 g, 0.19
mmol) dissolved in a mixture of CH2Cl2 (50 mL) and glacial
CH3OH (10 mL) was hydrogenated under 1 atm of H2 in the