Synthesis of 1,8-Pyridine-Capped 5,12-Dioxocyclams
J. Am. Chem. Soc., Vol. 122, No. 21, 2000 5041
Pyridine-Capped (+)-(Methyl)(methoxy)dioxocyclam (9). In a
100-mL round-bottom flask equipped with a condenser, 120 mg (0.26
mmol) of (S,+)-(methyl)(methoxy)dioxocyclam (8) was dissolved in
50 mL of CH3CN. To this solution was added 220 mg (2.08 mmol, 8
equiv) of Na2CO3, and the turbid mixture was then heated at reflux for
1 h. Next, 70 mg (0.26 mmol) of solid 2,6-bis(bromomethyl)pyridine
was added. After 6 days at reflux, the reaction mixture was filtered
through a pad of Celite and the solvent was removed in vacuo. The
resulting yellow oil was purified by flash column chromatography, first
by eluting (5:95 MeOH/CH2Cl2) to remove the dioxocyclam 8 and then
with 5:95 Et3N/CH2Cl2 to yield, after a saturated Na2CO3 wash to
remove the Et3N, 65 mg (0.12 mmol, 45%) of the capped dioxocyclam
(9) as a clear wax. X-ray quality crystals of 9 were generated by slow
diffusion of water into methanol, mp 187 °C (MeOH/H2O), [R]21D +57°
6 days at reflux, the cooled reaction mixture was filtered through a
pad of Celite and the solvent was removed in vacuo. The resulting
yellow oil was crystallized from CHCl3 to yield 25 mg (0.026 mmol,
1
24%) of 13 as white powder. H NMR (CD3OD): δ 8.47 (t, 2H, J )
8.1 Hz), 7.80 (d, 4H, J ) 7.7), 7.31 (s, 4H), 4.28 (dd, 8H, J ) 7.3,
18.3 Hz), 3.81 (m, 8H), 3.45 (d, 4H, J ) 15.7 Hz), 3.00 (d, 4H, J )
13.2 Hz), 2.98 (d, 4H, J ) 15.4 Hz), 2.82 (d, 4H, J ) 13.5 Hz) 2. 29
(m, 4H), 1.46 (s, 12H), 1.38 (s, 12H), 1.30 (s, 12H). 13C NMR: δ
175.7, 154.7, 148.3, 125.2, 85.8, 68.0, 65.6, 63.2, 62.3, 55.9, 34.5, 29.7,
26.1, 21.4. IR (neat): ν 1664 (CdO) cm-1. MS (HR FAB): MW
calculated for C52H83N10O8, 975.6395; found, 975.6379 (∆ ) 1.7 ppm)
(M + 1).
Pyrazine-Bridged S-(Methyl)(methoxy)bis-dioxocyclam (15). In
a 100-mL round-bottom flask equipped with a condenser, 259 mg (0.56
mmol) of (S,+)-(methyl)(methoxy)dioxocyclam ((+)8) was dissolved
in 50 mL of CH3CN. To this solution was added 238 mg (2.25 mmol,
8.0 equiv) of Na2CO3, and this turbid solution was heated to reflux.
Next, 56 mg (0.21 mmol, 2 equiv) of tetrakis(bromomethyl)pyrazine
was added. The solution was allowed to stir at reflux for 6 days, after
which the reaction mixture was filtered through a pad of Celite and
the solvent was removed in vacuo. The resulting yellow oil was purified
by flash column chromatography, first by eluting (5:95 MeOH/CH2-
Cl2) to remove the dioxocyclam (8) and then with 5:95 Et3N/CH2Cl2
to yield, after a saturated Na2CO3 wash to remove the Et3N, 59 mg
(0.17 mmol, 10%) of the bridged bis-dioxocyclam (15) as a clear wax.
1
(c ) 1.03, CHCl3). H NMR: δ 8.56 (bs, 2H), 7.56 (t, 1H, J ) 7.7
Hz), 6.86 (d, 2H, J ) 7.7 Hz), 3.72 (dd, 4H, J ) 14.4, 10.9 Hz), 3.71
(s, 6H), 3.27 (s 6H), 3.14 (dd, 4H, J ) 11.0, 4.0 Hz) 3.16 (d, 2H, J )
15.0 Hz), 3.12 (d, 2H, J ) 12.8 Hz), 2.91(d, 2H, J ) 13.1 Hz), 2.78
(d, 2H, J ) 15.0 Hz), 1.54 (s, 6H), 1.12 (s, 6H). 13C NMR: δ 175.1,
172.0, 158.6, 136.1, 119.5, 82.4, 65.9, 62.7, 61.9, 61.4, 52.1, 50.1, 21.6,
19.3. IR (neat): ν 1738, 1648 (CdO) cm-1. MS (HR FAB): MW
calculated for C27H42N5O8, 564.3033; found, 564.3030 (∆ ) 0.8 ppm)
(M + 1). The structure of 5a was determined by X-ray analysis, and
the results of the study are presented in the Supporting Information.
m-Xylene-Capped centro-(Methyl)(methoxy)dioxocyclam (10). In
a 100-mL round-bottom flask equipped with a condenser, 100 mg (0.26
mmol) of centro-(methyl)(methoxy)dioxocyclam (4a) was dissolved
in 45 mL of CH3CN, along with 100 mg (1.04 mmol, 4.0 equiv) of
Na2CO3. This turbid solution was heated to reflux, followed by the
addition of 68 mg (0.26 mmol, 1 equiv) of R,R′-dibromo-m-xylene.
The solution was allowed to stir at reflux for 4 days, after which the
reaction mixture was filtered through a pad of Celite and the solvent
was removed in vacuo. The resulting yellow oil was purified by radial
chromatography (CHCl3 to 5% MeOH/CHCl3) and then crystallized
from toluene to yield 37 mg (0.078 mmol 30%) of a white powder. 1H
NMR: δ 9.21 (bs, 1H), 7.45 (bs, 1H), 7.08 (t, 1H, J ) 7 Hz), 6.8 (m,
2H), 5.9 (bs, 1H), 4.0 (d, 1H, J ) 13.8 Hz), 3.78 (dd, 2H, J ) 20.9,
17.2 Hz), 3.78 (d, 2H, J ) 7.7 Hz), 3.11 (m, 3H), 3.06 (s, 3H), 2.90 (s,
2H), 2.84 (d, 1H, J ) 14.6 Hz), 2.34 (d, J ) 12.7 Hz), 1.70 (m, 1H),
X-ray quality crystals of 15 were generated by slow diffusion of water
1
into methanol, mp 160 °C dec, [R]21 +20.4° (c ) 1.0, CHCl3). H
D
NMR (CDCl3, -10 °C): δ 9.34 (s, 2H), 7.49 (s, 2H), 4.30 (d, 2H, J
) 12.1 Hz), 4.03 (d, 2H, J ) 10.5 Hz), 3.83 (d, 2H, J ) 10.5 Hz),
3.75 (s, 6H), 3.70 (s, 6H), 3.47 (m, 4H), 3.28 (s, 6H), 3.25 (m, 8H),
3.09 (d, 2H, J ) 15.4 Hz), 3.00 (m, 4H), 2.86 (d, 2H, J ) 12.5 Hz),
2.77 (d, 2H, J ) 15.3 Hz), 2.46 (d, 2H, J ) 14.3 Hz), 2.00 (s, 6H),
1.29 (s, 6H), 1.13 (s, 6H), 1.05 (s, 6H). 13C NMR: δ 174.6, 174.5,
173.5, 172.4, 150.3, 150.0, 81.9, 79.0, 77.4, 68.6, 66.1, 62.2, 61.5, 59.7,
57.3, 56.9, 56.1, 52.8, 52.5, 51.2, 25.7, 23.7, 18.6, 17.5. IR (neat): ν
1741, 1667 (CdO) cm-1. The structure of 14 was determined by X-ray
analysis, and the results of the study are presented in the Supporting
Information.
Pyrazine-Bridged centro-(Methyl)(methoxy)bis-dioxocyclam (20
and 22). In a 100-mL three-neck flask equipped with a condenser, 247
mg (0.66 mmol, 2.0 equiv) of centro-(methyl)(methoxy)dioxocyclam
(4a) was dissolved in 50 mL of CH3CN. To this solution was added
280 mg (2.64 mmol, 8.0 equiv) of Na2CO3, and this turbid solution
was heated to reflux. Next, 50 mg (0.33 mmol) of tetrakis(bromo-
methyl)pyrazine was added. The solution was allowed to stir at reflux
for 6 days, after which the reaction mixture was filtered through a pad
of Celite and the solvent was removed in vacuo. The resulting yellow
oil was recrystallized from MeOH/H2O. The first crop of crystals
yielded 30 mg of capped monomer. The mother liquor was allowed to
evaporate, and a second crop of crystals was collected (177 mg, 0.20
1.35 (s, 6H), 1.34 (s, 3H), 1.27 (s, 3H), 1.21 (s, 3H), 1.08 (s, 3H). 13
C
NMR: δ 173.7, 172.9, 142.2, 140.3, 131.8, 127.1, 122.5, 122.5, 83.0,
82.9, 72.5, 69.1, 67.9, 63.1, 62.7, 62.5, 55.1, 53.3, 51.5, 49.8, 30.4,
28.1, 27.6, 24.6, 20.6, 20.3. MS (HR FAB): MW calculated for
C26H43N4O4, 475.3284; found, 475.3278 (∆ ) 1.2 ppm) (M + 1).
Bis-Capped meso-(C3)-Bis-dioxocyclam (12). In a 50-mL round-
bottom flask equipped with a condenser, 70 mg (0.09 mmol) of meso-
(C3)-bis-dioxocyclam (11) was dissolved in 20 mL of CH3CN. To this
solution was added 75 mg (0.72 mmol, 8.0 equiv) of Na2CO3, and this
turbid solution was heated to reflux. Next, 47 mg (0.18 mmol, 2 equiv)
of 2,6-bis(bromomethyl)pyridine was added. The solution was allowed
to stir at reflux for 5 days, after which the reaction mixture was filtered
through a pad of Celite and the solvent was removed in vacuo. The
resulting yellow oil was dissolved in 20 mL of CH2Cl2 and washed 3
times with 10 mL of water. The CH2Cl2 was dried with Na2SO4, and
the solvent was removed in vacuo. The resulting clear wax was
crystallized by slow diffusion of Et2O into CH2Cl2 to yield 50 mg (0.051
1
mmol, 61%) as a 3:4 mixture of diasteriomers. H NMR (400 MHz,
CDCl3, -30 °C): δ 9.91 (s, 2H), 9.77 (s, 2H), 8.53 (s, 2H), 8.37 (s,
2H), 5.24 (d, 2H, J ) 12.5 Hz), 5.20 (d, 2H, J ) 12.8 Hz), 4.25 (d,
2H, J ) 11.7 Hz), 4.14 (d, 2H, J ) 11.7 Hz), 3.63 (d, 2H, J ) 11.7
Hz), 3.46 (d, 2H, J ) 11.7 Hz), 3.37 (m, 8H), 3.16 (d, 2H, J ) 13.6
Hz), 3.00 (m, 8H), 2.84 (d, 2H, J ) 14.4 Hz), 2.82 (d, 2H, J ) 13.6
Hz), 2.62 (m, 8H), 2.15 (d, 2H, J ) 14.0 Hz), 2.03 (d, 2H, J ) 14.0
Hz), 1.52 (s, 12H), 1.49 (s, 12H), 1.28 (s, 6H), 1.27 (s, 6H), 1.24 (s,
12H), 1.18 (s, 6H), 1.14 (s, 6H), 1.02 (s, 6H), 1.01 (s, 6H). 13C NMR:
δ 171.3, 171.2, 170.1, 169.5, 151.5, 150.7, 150.5, 149.3, 81.0, 80.8,
80.3, 79.8, 70.2, 66.6, 66.0, 63.9, 63.4, 63.1, 62.6, 58.6, 53.4, 53.3,
53.1, 51.1, 51.0, 50.8, 28.6, 28.3, 27.6, 27.2, 25.7, 24.9, 19.7, 19.3,
1
mmol, 58%) of 11 as white powder, mp > 250 °C. H NMR: δ 7.81
(bs, 4H), 7.38 (t, 2H, J ) 7.3 Hz), 6.75 (d, 4H, J ) 7.3), 3.74 (s, 8H),
3.54 (dt, 4H, J ) 5.9, 10.3 Hz), 3.36 (dt, 4H, J ) 5.1, 10.3 Hz), 3.10
(d, 4H, J ) 15.0 Hz), 2.77 (d, 4H, J ) 15.0), 2.70 (dd, 8H, J ) 13.3,
7.7 Hz), 1.97 (m, 2H), 1.83 (m 2H), 1.30 (s, 12H), 1.19 (s, 12H), 1.17
(s, 12H). 13C NMR: δ 172.6, 158.7, 135.9, 118.8, 84.1, 68.5, 66.6,
66.3, 60.9, 54.1, 33.3, 28.6, 25.3, 21.1. IR (neat): ν 1651 (CdO) cm-1
.
18.9, 18.9. IR (neat): ν 1671 (CdO) cm-1
.
Anal. Calcd for C52H82N10O8: C, 64.04; H, 8.47; N, 14.36. Found: C,
64.37; H, 8.35; N, 14.39.
Cu(II) Complex of centro-(Methyl)(benzyloxy)-capped Dioxocy-
clam (20). To 5 mL of CH2Cl2 in a pressure tube was added 70 mg
(0.11 mmol) of 5b along with 187 mg (0.55 mmol, 5.0 equiv) of Cu-
(BF4)2‚6H2O and 76 mg (0.55 mmol, 5.0 equiv) of K2CO3. The pressure
tube was capped, and the reaction was heated to 65 °C for 2 days. The
green reaction mixture was then filtered through a pad of Celite, and
the solvent was removed in vacuo. The resulting green tar was dissolved
in CH2Cl2, and the organic layer was extracted with water. During the
Bis-Capped D2-Symmetric (C3)-Bis-dioxocyclam (14). In a 50-
mL round-bottom flask equipped with a condenser, 83 mg (0.11 mmol)
of D2-symmetric (C3)-bis-dioxocyclam (13) was dissolved in 20 mL
of CH3CN. To this solution was added 75 mg (0.42 mmol, 4.0 equiv)
of Na2CO3, and this turbid solution was heated to reflux. Next, 56 mg
(0.21 mmol, 2 equiv) of 2,6-bis(bromomethyl)pyridine was added. After