5646 J. Am. Chem. Soc., Vol. 119, No. 24, 1997
Hettich and Schneider
[
(1-(4-(Chlorotrimethylammonio)butyl)-1,4,7,10-tetraazacyclodode-
g (10.9 mmol) of methyl bromide in 10 mL of absolute acetonitrile
was added dropwise within 10 min at 0 °C to 1.65 g (5.34 mmol) of
21 in 25 mL of absolute acetonitrile. The ice bath was removed, and
the reaction was stirred at room temperature for 16 h. The liquid was
discarded, and the crystals were stirred with 2 × 30 mL of absolute
ether, filtered, washed with 4 × 10 mL of ether, and dried in vacuo.
Slightly yellow, hygroscopic solid, mp 213 °C. Yield: 1.95 g (4.84
mmol, 91%). C H BrClN O, MW 403.87. Elemental Anal. Calcd:
cane)dichlorocobalt(III)] Chloride (15). As above, 183 mg (0.5
mmol) of 4 was reacted with 181 mg (0.5 mmol) of tris(sodium
carbonato)cobalt(III) trihydrate.33 Violet-blue, hygroscopic crystals, mp
1
4
(
5
83 °C. Yield: 174 mg (0.36 mmol, 72%). C15
H36Cl
4
5
CoN , MW
-
5
87.23. Cobalt content of a 8 × 10 M solution of the complex
AAS): calcd. 4.6 ppm; found 4.0 ppm. UV-data (HCl 37%, λ (nm)):
53 (ꢀ ) 141), 456 (ꢀ ) 37), 385 (ꢀ ) 140), 363 (ꢀ ) 119).
(1-(5-(Chlorotrimethylammonio)pentyl)-1,4,7,10-tetraaza-
cyclododecane)dichlorocobalt(III)] Chloride (16). As above, 190 mg
0.5 mmol) of 5 was reacted with 181 mg (0.5 mmol) of tris(sodium
17
40
2
1
[
C, 50.58; H, 9.98; N, 6.94. Found: C, 48.55; H, 9.23; N, 6.55.
H
NMR (D O, TMSP, δ): 3.59 (t, 2 H, HO-CH ), 1.77-1.35 (m, 16 H,
2
2
(
HO-CH -CH -CH -CH -CH and CH -CH -CH -CH -CH -N(CH ) ),
2
2
2
2
2
2
2
2
2
2
3
2
33
+
+
+
carbonato)cobalt(III) trihydrate. Violet-blue, hygroscopic crystals, mp
85 °C. Yield: 142 mg (0.28 mmol, 57%). C16
3.30 (m, 6 H, CH -N ), 3.04 (s, 6 H, N (CH ) ), 3.11 (s, 9 H, N -
2
3 2
13
1
5
(
5
H38Cl
4
5
CoN , MW
(CH ) ). C NMR (D O, TMSP, δ): 61.67 (HO-CH ), 31.07 (HO-
3
3
2
2
-
5
01.26. Cobalt amount of an 8 × 10 M solution of the complex
CH -CH ), 24.66, 25.38 and 25.23 (HO-CH -CH -CH -CH and
2
2
2
2
2
2
+
+
AAS): calcd. 4.6 ppm; found 4.7 ppm. UV-data (HCl 37%, λ (nm)):
57 (ꢀ ) 209), 456 (ꢀ ) 31), 386 (ꢀ ) 185), 361 (ꢀ ) 141).
(1-(6-(Chlorotrimethylammonio)hexyl)-1,4,7,10-tetraazacyclodode-
(H C) N -(CH ) -CH -CH -(CH ) -N(CH ) ), 21.94 (CH -CH -N -
3
2
2
2
2
2
2
2
+
3
2
2
2
+
(CH ) ), 63.99 and 64.15 ((CH -N
((CH -CH -N (CH ) ), 66.58 ((CH -N (CH ) ), 53.01 (N (CH ) ).
2 2 3 3 2 3 3 3 3
3
2
2
3
2
3 2
(CH ) ), 50.67 (N (CH ) ), 22.32
+
+
+
[
cane)dichlorocobalt(III)] Chloride (17). As above, 151 mg (0.39
mmol) of 6 was reacted with 141 mg (0.39 mmol) of tris(sodium
carbonato)cobalt(III) trihydrate. Violet-blue, hygroscopic crystals, mp
N-(6-Bromohexyl)-N-(6-aminohexyl)-N,N,N′,N′,N′-pentamethyl-
,6-hexanediyldiammonium Dibromide (23). A solution of 4 mL
1
(
33
45 mmol) of thionyl bromide in 4 mL of absolute toluene was added
dropwise over 30 min to a suspension of 4.5 g (11.2 mmol) of 22 in
0 mL of absolute toluene. After having been stirred 1 h at room
1
5
83 °C. Yield: 152 mg (0.30 mmol, 76%). C17
15.28. Cobalt amount of an 5 × 10 M solution of the complex
H
40Cl
4
CoN
5
, MW
-
5
2
(
5
AAS): calcd. 2.9 ppm; found 2.3 ppm. UV-data (HCl 37%, λ (nm)):
57 (ꢀ ) 191), 457 (ꢀ ) 41), 386 (ꢀ ) 181), 363 (ꢀ ) 147).
(1-[7-(Chlorodimethylammonio)-14-(chlorotrimethylammonio)-
tempature the solution was heated to 80 °C for 1 h and then stirred
again at room tempature for 26 h. The liquid was discarded, and the
brown residue was recrystallized from isopropyl alcohol. The crystals
were filtered, washed with 3 × 30 mL absolute ether and dried in vacuo
[
tetradecyl]-1,4,7,10-tetraazacyclododecane)dichlorocobalt(III)] Chlo-
ride (18). As above, 373 mg (0.62 mmol) of 7 was reacted with 224
mg (0.62 mmol) of tris(sodium carbonato)cobalt(III) trihydrate.33
Violet-blue, hygroscopic crystals, mp 186 °C. Yield: 359 mg (0.53
over P
.43 g (7.95 mmol, 71%). C17
Calcd: C, 39.94; H, 7.69; N, 5.48. Found: C, 40.06; H, 7.17; N, 5.41.
2 5
O . Slightly yellow solid, mp 209 °C (decomposition). Yield:
3
3 2
H39Br N , MW 511.22. Elemental Anal.
mmol, 85%). C25
H
58Cl
5
CoN
M solution of the complex (AAS): calcd. 4.6 ppm; found 4.6
ppm. UV-data (HCl 37%, λ (nm)): 560 (ꢀ ) 158), 454 (ꢀ ) 18), 389
ꢀ ) 127), 360 (ꢀ ) 75).
(1-[7,14-Bis(chlorodimethylammonio)-21-(chlorotrimethylam-
6
, MW 678.97. Cobalt amount of an 8 ×
1
H NMR ((D
H, Br-CH -CH
.36 (m, 6 H, CH
2
O, TMSP, δ): 3.57 (t, 2 H, Br-CH
2
), 1.95-1.42 (m, 16
-CH -CH -N(CH ),
), 3.16 (s, 9 H, N -
2
), 31.80 (Br-CH -
-
5
1
0
2
2
-CH
2
-CH
2
-CH
2
and CH
2
-CH
2
-CH
2
2
2
3 2
)
+
+
+
3
2
-N ), 3.10 (s, 6 H, N (CH
3
)
2
(
13
(
CH
3
)
3
). C NMR (D
2
O, TMSP, δ): 35.17 (Br-CH
2
[
+
2
CH ), 24.74, 26.87 and 25.23 (Br-CH
2
-CH
2
-CH
2
-CH
2
and (H
3
C)
-CH
), 22.32
).
2
N -
moniochloride)hemicosane]-1,4,7,10-tetraazacyclododecane)dichlo-
rocobalt(III)] Chloride (19). As above, 511.6 mg (0.63 mmol) of 8
was reacted with 226 mg (0.63 mmol) of trisodium triscarbonatocobalt-
+
(
CH
N (CH
(CH -CH
2
)
2
-CH
2
-CH
2
-(CH
2
)
2
-N (CH
3
)
3
), 21.93 and 21.84 (CH
2
2
-
+
+
+
3 2
) ), 64.09 and 63.93 ((CH
2
-N (CH
-N (CH
3
)
2
), 50.67 (N (CH
)
3 2
+
+
+
(
2
2
-N (CH
3
)
3
), 66.61 ((CH
2
3
)
3
), 53.04 (N (CH
3
)
3
3
3
(
III) trihydrate. Violet-blue, very hygroscopic crystals. Yield: 414
N-6-Bis(dimethylamino)hexyl-N,N,N′,N′,N′-pentamethyl-1,6-hex-
mg (0.50 mmol, 79%). C35 CoN , MW 866.09. Cobalt amount
H
76Cl
6
7
-
4
anediyldiammonium Dibromide (24). 6-(N,N,N-Trimethylammonio)-
hexyl bromide31 (4.82 g, 15.9 mmol) in 60 mL of absolute acetonitrile
was added dropwise within 1 h to a solution of 10.95 g (63.3 mmol)
of 1,6-bis(dimethylamino)hexane in 70 mL of absolute acetonitrile. The
solution was refluxed for 24 h, cooled to room temperature, and filtered.
The solvent was evaporated and dried in vacuo. The residue was stirred
with 3 × 100 mL ether, and the crystals were filtered, washed with 3
× 50 mL ether and dried in vacuo. White crystals, mp 171 °C.
of an 1 × 10 M solution of the complex (AAS): calcd. 5.8 ppm;
found 5.8 ppm. UV-data (HCl 37%, λ (nm)): 557 (ꢀ ) 173), 454 (ꢀ
)
19), 389 (ꢀ ) 138), 360 (ꢀ ) 89).
(N,N′-Bis[6-(1-(1,4,7,10-tetraazacyclododecane))hexyl]-N,N′-bis-
dimethylamino)hexylchlorodiammonio)bis(dichloro)cobalt(III)]
[
(
Dichloride (20). As above, 432.3 mg (0.51 mmol) of 10 was reacted
with 371.4 mg (0.51 mmol) of tris(sodium carbonato)cobalt(III)
33
trihydrate. Violet-blue, hygroscopic crystals, mp 191 °C. Yield: 480
mg (0.44 mmol, 87%). C38 Co 10, MW 1084.66. Cobalt amount
2 3
Yield: 5.59 g (11.8 mmol, 73%). C19H45Br N , MW 475.39. Elemen-
H
86Cl
8
2
N
-
4
tal Anal. Calcd: C, 48.00; H, 9.54; N, 8.84. Found: C, 48.14; H,
of an 1 × 10 M solution of the complex (AAS): calcd. 11.6 ppm;
1
9
.46; N, 8.78. H NMR (D
2 3 2
O, TMSP, δ): 2.20 (s, 6 H, N(CH ) ),
found 10.3 ppm. UV-data (HCl 37%, λ (nm)): 560 (ꢀ ) 360), 454 (ꢀ
2
CH
6
4
CH
.34 (t, 2 H, (CH
3
)
3
2
)N-CH
-CH
2
), 1.86-1.74 and 1.55-1.34 (m, 16 H,
)
52), 389 (ꢀ ) 300), 360 (ꢀ ) 198).
+
+
(
2
)
4
-CH
2
-N (CH
)
2
2
-(CH
2
+
)
4
), 3.29 (m, 6 H, N -CH
2
), 3.06 (s,
O, TMSP, δ):
), 26.25, 26.07, 25.54, 25.27
Synthesis of the Alkylating Agents. N-(6-Hydroxyhexyl)-N,N,N′,N′-
+
13
H, N (CH
3
)
2
), 3.13 (s, 9 H, N (CH
3
)
3
). C NMR (D
2
tetramethylhexylammonium Chloride (21). 1,6-Bis(dimethylamino)-
hexane (14.06 g, 81.6 mmol) and 2.45 mL (18.3 mmol) of chlorohex-
anol in 100 mL of absolute acetonitrile were refluxed 28 h. After
cooling to room tempature, absolute ether was added until turbidity
occurred. The reaction mixture was cooled to -20 °C. The liquid
was decanted and discarded. The slightly yellow solid was stirred with
3.94 (N(CH
3
)
2
), 58.43 (CH
)
3 2
)N-CH
-CH
2
+
(
2
-CH
-N (CH
2
-CH
2
-CH
2
-CH
2
-N (CH
3
)
2
2
-CH
-N (CH
2
-CH
2
-CH
2
), 21.95 (CH
2
-
+
+
+
CH
2
)
3 2
), 64.27 and 63.99 (CH
2
3
)
2
), 50.71 (N (CH
3
)
2
),
).
+
+
+
22.34 (CH
2
-CH
2
-N (CH
3 3
) ), 66.64 (CH
2
-N (CH
3
)
3
), 53.07 (N (CH
)
3 3
N,N,N′,N′-Tetramethyl-N-(6-hydroxyhexyl)-N′-(6-(bromotrime-
3
× 40 mL ether and dried in vacuo. Colorless, hygroscopic crystals,
mp 67 °C. Yield: 4.21 g (13.6 mmol, 75%). C16
O, MW
08.94. Elemental Anal. Calcd: C, 62.21; H, 12.07; N, 9.07.
thylammonio)hexyl)-1,6-hexanediyldiammonium Bromide Chloride
(25). A suspension of 5.3 g (11.36 mmol) of 24 in 15.5 g (113 mmol)
of chlorohexanol was heated 2 h to 90 °C, giving a clear solution after
10 min. After cooling to room tempature, 80 mL of ether was added
slowly. The liquid was decanted and discarded. The residue was stirred
with 2 × 100 mL of ether, filtered, washed with 3 × 50 mL ether, and
H37ClN
2
3
1
Found: C, 60.17; H, 11.62; N, 8.48. H NMR (D
t, 2 H, HO-CH ), 1.70-1.31 (m, 16 H, HO-CH -CH
and CH -CH -CH
.25 (t, 2 H, CH
N(CH
). 13C NMR (D
CH -CH ), 24.86, 25.41, 25.96 and 26.19 (HO-CH
2
O, TMSP, δ): 3.55
(
2
2
2
-CH
2
-CH
2
-CH
2
+
2
2
2
-CH
-N(CH
2
-CH
2
-N(CH
3
)
2
2
), 3.22 (m, 4 H, CH -N (CH
3 2
) ),
+
2
2
3
)
2
), 2.98 (s, 6 H, N (CH
3
)
2
), 2.11 (s, 6 H,
), 31.12 (HO-
dried in vacuo over P
g (10.5 mmol, 93%). C25
Calcd: C, 49.06; H, 9.56; N, 6.87. Found: C, 49.24; H, 9.54; N, 6.65.
2
O
5
. Colorless crystals, mp 202 °C. Yield: 6.44
3
)
2
2
O, TMSP, δ): 61.72 (HO-CH
-CH
), 21.91 (CH
2
H58Br
2
ClN O, MW 612.01. Elemental Anal.
3
2
2
+
2
2
-CH
2
-CH
-CH
), 40.05 ((CH
).
2
and
-N -
+
1
(
H
3
C)
2
N -(CH
), 64.12 ((CH
), 58.41 ((CH
2
)
2
-CH
2
-CH
2
-(CH
), 50.69 (N (CH
), 43.89 (N(CH
2
)
2
-N(CH
3
+
)
2
2
2
H NMR (D
2
+
O, TMSP, δ): 3.59 (t, 2 H, HO-CH
2
), 1.84-1.35 (m, 24
), 3.05 (s, 12 H,
+
+
(CH
3
)
2
2
-N (CH
)
3 2
3
)
2
2
2
-CH -
H, (CH
N (CH
(HO-CH
CH -CH
3
)
2
N -CH
), 3.10 (s, 9 H, N (CH
), 31.10 (HO-CH -CH
-CH ), 21.97 ((CH
2
-(CH
2
)
4
), 3.29 (m, 10 H, N -CH
2
+
+
13
N(CH
3
)
2
2
-N(CH
3
)
2
3
)
2
)
3 2
3 3
) ). C NMR (D
2
O, TMSP, δ): 61.69
+
N,N-Dimethyl-N-(6-hydroxyhexyl)-N′,N′,N′-(trimethylamino)-1,6-
hexanediyldiammonium Bromide Chloride (22). A solution of 1.0
2
2
2
), 24.67 and 25.32 ((CH
3
)
2
N -CH
2
+
-
+
2
2
2
3
)
2
N -CH
2
2
-CH ), 63.95 and 64.16 ((CH
3
)
2
N -