m, ring N-CHn), 3.26–3.84 (14H, m, ring N-CHn), 7.10–7.35
(11H, m, Ar-H) 7.60–7.65 (2H, m, Ar-H), 7.73 (4H, d, J 8.4,
Ar-H); dC 20.0, 21.6, 21.8, 30.8, 46.1, 50.7, 57.5, 64.3, 66.2,
127.2, 127.8, 128.0, 128.2, 129.7, 129.8, 130.4, 134.3, 136.5,
137.8, 143.3, 144.0; m/z (FAB): 809 (23%, M + H), 653 (55,
M ꢂ Ts) (Found: (M + H) 809.3466. C42H57N4O6S3 requires
809.3448).
137.5, 143.5, 144.3; m/z (FAB) 650 (13.5%, M + H); (Found:
M + H 650.2373. C31H44N3O6S6 requires 650.2392).
N,N-Bis(2-[4-methylbenzenesulfonylamino]-3-methylpentyl)-4-
methylbenzenesulfonamide 13b
13b was prepared in an identical manner to 13a to yield colour-
less crystals (5.11 g, 88%), mp 191–192 ꢁC (from ethanol);
N-(1-{N0-[(2-{4-methylbenzenesulfonylamino}-3-methylbutyl]-
aminoethyl}-2-methylpropyl-4-methylbenzenesulfonamide 12a
[a]D ꢂ10.4 (c 0.5, CHCl3); nmax/cmꢂ1 3255, 2957, 2920,
25
2367, 1596, 1453, 1351, 1325, 1306, 1163, 1092, 1039, 1020,
967, 903, 812, 744, 688, 666, 603, 555, 548, 521; dH 0.59 (6H,
d, J 7.2 CH3-CH(CH)-CH2), 0.77–0.94 (8H, m, CH3-CH2
and CH(CH)-CH2-CH3), 1.08–1.24 (2H, m, CH(CH)-CH2-
CH3), 1.55–1.65 (2H, m, CH3-CH(CH)-CH2), 2.39 (6H, s,
Ar-CH3), 2.43 (3H, s, Ar-CH3), 2.70 (2H, dd, J 14.8 and J
5.0, SO2NH-CH2-CH(CH)), 3.04 (2H, dd, J 14.6 and J 8.8,
SO2NH-CH2-CH(CH)), 3.11–3.22 (2H, m, CH2-CH(CH)-
NHSO2), 5.02 (2H, d, J 6.1, CH(CH)-NH-SO2), 7.25 (4H, d,
J 8.0, Ar-H), 7.35 (2H, d, J 8.2, Ar-H), 7.50–7.69 (6H, m,
Ar-H); dC 12.2, 13.8, 21.6, 24.8, 36.1, 48.0, 55.5, 127.3, 127.5,
129.7, 130.3, 135.6, 137.7, 143.5, 144.4; m/z (FAB): 700
(16%, M + Na), 678 (52, M + H) (Found: M + H 678.2694.
C33H48N3O6S3 requires 678.2705)
To a solution of 5a (3.00 g, 5.13 mmol) in glacial acetic acid (60
cm3) was added palladium dispersion on carbon (280 mg, 10%
w/w) and the reaction was stirred under an atmosphere of
hydrogen for 18 hours. The solid was removed by filtration
and the solid washed with ethanol (60 cm3) and ethyl acetate
(60 cm3). The organic phases were combined and the solvents
removed under reduced pressure to yield a yellow oil. The oil
was redissolved in CH2Cl2 and stirred with potassium hydro-
xide solution (60 cm3, 1 M) for 30 min. The layers were seper-
ated and the aqueous layer washed with CH2Cl2 (2 ꢃ 30 cm3).
The organic phases were combined, dried over anhydrous
magnesium sulfate and the solvent removed under reduced
pressure to yield an off-white solid (2.48 g, 97.5%). All spectro-
scopic data were consistent with those previously reported.18
In addition HRMS, found (M + H) 496.2311. C24H38N3O4S2
requires 496.2304.
(2S,6S)-2,6-Bis(1-methylethyl)-1,4,7-tris(4-methylbenzene-
sulfonyl)-1,4,7-triazacyclononane 14a
N-(1-{N0-[(2-{4-methylbenzenesulfonylamino}-3-methylpentyl]-
aminoethyl}-2-methylbutyl-4-methylbenzenesulfonamide 12b
Tosylamide 13a (4.50 g, 6.93 mmol), ethylene glycol 1,2-dito-
lyl-4-sulfonic acid ester (3.34 g, 9.01 mmol) and caesium carbo-
nate (6.77 g, 20.79 mmol) were dissolved in dry acetonitrile (10
cm3) and refluxed under nitrogen for 6 d. The resulting white
solid was filtered off and washed with acetonitrile (10 cm3).
The solvent was removed from the combined filtrates and
the resulting yellow semisolid was recrystallised from acetoni-
trile to yield macrocycle 14a (3.00 g, 64%) as colourless crys-
12b was prepared in an identical manner to 12a to yield a yel-
25
low solid (4.84 g, 95%), mp 99–101 ꢁC; [a]D ꢂ2.2 (c 0.5,
CHCl3); nmax/cmꢂ1: 3291, 3168, 2360, 2338, 1596, 1457,
1419, 1326, 1156, 1092, 1076, 1017, 952, 856, 816, 700, 655,
571, 547, 496, 436; dH 0.70 (6H, d, J 6.9, CH3-CH(CH)-
CH2), 0.77 (6H, t, J 7.3, CH2-CH3), 0.83–1.07 (2H, m, CH-
CH(CH2)-CH3), 1.18–1.31 (2H, m, CH-CH(CH2)-CH3),
1.33–1.50 (2H, m, CH-CH(CH2)-CH3), 2.18 (2H, dd, J 12.6
and J 4.0, NH-CH2-CH(CH)), 2.34 (2H, dd, J 12.9 and J
7.9, NH-CH2-CH(CH)), 2.41 (6H, s, Ar-CH3), 3.02–3.08
(2H, m, CH2-CH(CH)-NHSO2), 7.28 (4H, d, J 8.1, Ar-H),
7.75 (4H, d, J 8.1, Ar-H); dC 11.8, 14.4, 21.6, 25.7, 37.1,
48.2, 56.8, 127.2, 129.7, 138.1, 143.3; m/z (FAB): 524 (100%,
M + H); (Found: M + H 524.2631. C26H42N3O4S2 requires
524.2617).
25
tals, mp 214–215 ꢁC (from acetonitrile); [a]D ꢂ7.4 (c 0.5,
CHCl3); nmax/cmꢂ1 2964, 2360, 1597, 1452, 1395, 1336, 1305,
1154, 1089, 1018, 972, 909, 843, 815, 730, 714, 697, 665, 649,
633, 574, 549; dH 0.35 (6H, br s, CH(CH3)2), 0.85 (6H, d, J
6.0, CH(CH3)2), 0.93–1.16 (2H, bm, CH(CH3)2), 2.38 (6H, s,
Ar-CH3), 2.45 (3H, s, Ar-CH3), 3.04–3.29 (4H, m, ring-CHn),
3.30–3.48 (2H, m, ring-CHn), 3.53–3.88 (4H, m, ring-CHn),
7.26 (4H, d, J 8.3, Ar-H), 7.35 (2H, d, J 8.3, Ar-H), 7.67–
7.72 (6H, m, Ar-H); dC (Bruker AMX400, 100.6 MHz) 20.0,
20.4, 21.8, 28.2, 45.6, 51.7, 64.5, 127.2, 127.6, 128.1, 129.7,
129.8, 143.4, 143.9; m/z: 698 (52, M + Na), 676 (65, M + H),
520 (69%, M ꢂ Ts) (Found: M + H 676.2575. C33H46N3O6S3
requires M + H 676.2549).
N,N-Bis(2-[4-methylbenzenesulfonylamino]-3-methylbutyl)-4-
methylbenzenesulfonamide 13a
p-Toluenesulfonyl chloride (462 mg, 2.42 mmol) and 12a (1.00
g, 2.02 mmol) were dissolved in dry CH2Cl2 (20 cm3) under
nitrogen. Triethylamine (613 mg, 6.06 mmol) and DMAP (49
mg, 0.4 mmol) were added and the yellow solution stirred
for 12 h. The solvent was removed under reduced pressure
and the resulting yellow oil stirred with H2O (20 cm3) for 1
h. The water was decanted and the remaining yellow semi-solid
recrystallised from EtOH to give 13a (1.00 g, 76%) as colour-
(2S,6S)-2,6-Bis(1-methylpropyl)-1,4,7-tris(toluene-4-sulfonyl)-
1,4,7-triazacyclononane 14b
13b was prepared in identical manner to 13a to give colourless
crystals of 14b (4.40 g, 53%), mp 95–97 ꢁC (from acetonitrile);
25
[a]D +24.1 (c 0.5, CHCl3); Found: C, 59.8; H, 7.0; N, 6.0.
25
less crystals, mp 205–207 ꢁC (from ethanol), [a]D ꢂ30.4 (c
C35H49N3O6S3 requires: C, 59.7; H, 7.0; N, 6.0%; nmax/cmꢂ1
3203, 2963, 2931, 1596, 1453, 1381, 1340, 1303, 1112, 1151,
1112, 1088, 979, 962, 891, 855, 816, 736, 715, 696, 664, 649,
631, 574, 544; dH 0.55–0.64 (8H, m), 0.77–0.80 (8H, m),
0.91–1.06 (2H, m, CH3-CH(CH)-CH2), 2.39 (6H, s, Ar-CH3),
2.44 (3H, s, Ar-CH3), 3.19–3.72 (8H, m, ring-CHn), 3.75–
3.92 (2H, bm, ring-CHn) 7.25 (4H, d, J 8.3, Ar-H), 7.34 (2H,
d, J 8.0, Ar-H), 7.73–7.66 (6H, m, Ar-H); dC 11.6, 15.7, 21.6,
26.7, 35.8, 46.1, 48.7, 63.3, 127.5, 127.8, 129.8, 129.9, 137.7,
143.6, 143.7; m/z (FAB): 726 (32%, M + Na), 704 (39,
M + H) (Found M + H 704.2850. C35H50N3O6S3 requires
704.2862).
0.5, CHCl3); Found C, 57.8; H, 6.8; N, 6.5. C31H43N3O6S3
requires C, 57.3; H 6.7; N, 6.5%; nmax/cmꢂ1 3244, 2958,
1597, 1454, 1353, 1320, 1160, 1127, 1092, 1037, 1019, 964,
891, 813, 737, 665, 617, 587, 553, 513, 460; dH 0.55 (6H, d, J
7.2, CH(CH3)2), 0.71 (6H, d, J 6.9, CH(CH3)2), 1.65–1.85
(2H, m, CH(CH3)2), 2.39 (6H, s, Ar-CH3), 2.43 (3H, s, Ar-
CH3), 2.87–3.02 (4H, m, SO2N-CH2-CH(CH)), 3.08–3.19
(2H, m, CH2-CH(CH)-NHSO2), 5.07 (2H, d, J 6.6, CH-NH-
SO2), 7.25 (4H, d, J 8.0, Ar-H), 7.33 (2H, d, J 8.0, Ar-H),
7.65 (2H, d, J 8.3, Ar-H), 7.72 (4H, d, J 8.3, Ar-H); dC 16.5,
17.9, 21.6, 28.4, 51.0, 57.1, 127.3, 127.6, 129.7, 130.1, 134.6,
1058
New J. Chem., 2002, 26, 1054–1059