C. Dardonville et al. / Bioorg. Med. Chem. 10 (2002) 1525–1533
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26.05, 23.81. Anal. calcd for C8H22N6O4S: C, 32.20; H,
7.43; N, 28.17; S, 10.75. Found: C, 32.28; H, 7.70; N,
28.40; S, 10.57.
14.9; LRMS (ES+) m/e 186 (M+H/100%). Anal. calcd
for C10H24N3O2S0.5: C, 51.25; H, 10.32; N, 17.93.
Found: C, 51.01; H, 10.96; N, 17.92.
1,8-Octanediguanidinium sulphate (2). White solid (42%
yield); mp 309–315 ꢃC (lit.:29b 314–317 ꢃC); IR(KBr):
Dodecylguanidinium sulphate (19). A solution of 2 g of
dodecylamine (10.8 mmol, 1 equiv) and 3 g of S-
methylisothiouronium sulphate (10.8 mmol, 1 equiv) in
100 mL of 50% H2O in MeOH was heated at reflux for
3 h. The solution was allowed to cool down to room
temperature and the white solid that precipitated was
rinsed with MeOH and Et2O. The product was recrys-
tallised successively from CH3CN and MeOH. The solid
was rinsed with cold CH3OH and cold Et2O and dried
under vacuum (833 mg). White solid (28%);
3390, 3180, 2950, 2870, 1660, 1485, 1120 cmꢀ1 1H
;
NMR (D2O) d 2.94 (bt, 4H, J=7 Hz); 1.5–1.25 (m, 4H);
1.25–1 (m, 8H); 13C NMR (D2O) d: 158.1, 42.47, 29.38,
29.09, 26.95; MS (ES+) m/e 229 (MH+), 327
(MH+H2SO4). Anal. calcd for C10H26N6SO4: C, 36.80;
H, 8.03; N, 25.75; S, 9.82. Found: C, 37.04; H, 8.31; N,
26.00; S, 9.89.
mp>220 ꢃC dec. (lit.30a 230.5 ꢃC); H NMR (CD3OD/
1
1,9-Nonanediguanidinium sulphate (3). White solid (40%
yield); mp 297–305 ꢃC (lit.29b 302–306 ꢃC dec); IR
(KBr): 3380, 3170, 2950, 2869, 1660, 1620, 1115, 1060
TFA) d 3.1 (t, 2H); 1.5 (m, 2H); 1.35–1.2 (bm, 20H); 0.8
(t, 3H); LRMS (ES+) m/e 228 (M+H/ 100%). Anal.
calcd for C13H30N3O2S0.5: C, 56.48; H, 10.94; N, 15.20.
Found: C, 56.20; H, 11.12; N, 15.34.
1
cmꢀ1; H NMR (400 MHz/CF3COOH/D2O) d 2.15 (t,
4H, J=6.96 Hz); 0.56 (m, 4H); 0.4–0.2 (m, 10H); 13C
NMR (100 MHz/CF3COOH/D2O) d 156.17 (Cq), 40.64
(t, 2JC,D=12.2 Hz), 27.86, 27.64, 27.24, 25.22; MS
(ES+) m/e 243 (MH+), 341 (MH+ H2SO4). Anal. calcd
for C11H28N6SO4: C, 38.81; H, 8.29; N, 24.69. Found:
C, 38.92; H, 8.44; N, 24.56.
2-Aminoimidazoline aliphatic derivatives: general method
A solution of 4.75 mmol of the corresponding diamine
(i, ii, iii, or iv) and 10mmol of 2-methylmercapto-4,5-
dihydroimidazole iodide in 15 mL of dry MeOH was
heated under reflux for 2.5 h. Then, a stream of nitrogen
was bubbled into the solution to remove CH3SH. The
solvent was eliminated under vacuum and the product
was purified by the formation of the corresponding
picrate salt. The crude residue dissolved in 50mL of hot
water was treated with a hot aqueous solution of picric
acid (10mmol) and the resulting mixture was allowed to
stand at room temperature overnight. The yellow
picrate salt that precipitated was washed successively
with H2O, Et2O, and hexane, and then, crystallised from
hot CH3CN. The hydrochloride salts were generated
with Amberlite IRA-400 (Clꢀform) exchange resin. For
this purpose, the picrate salt was dissolved in H2O/THF
(300 mL) and stirred with the resin (previously washed)
overnight. Exchange was complete when the yellow
colour of the solution had disappeared. Then, the resin
was removed by filtration and the solution concentrated
under vacuum. The oily residue was taken up in a little
water, washed twice with AcOEt and filtered through a
Whatman (grade 4) filter. The product was lyophilised
to afford the pure chloride salt.
1,12-Dodecanediguanidinium sulphate (4). White solid
(69% yield); mp 250–254 ꢃC (lit.29b 258–262 ꢃC); IR
1
(KBr): 3401, 2924, 1640, 1119 cmꢀ1; H NMR (D2O/
CF3CO2H) d 2.22 (b, 4H); 0.66 (bm, 4H); 0.37 (bs,
16H); 13C NMR (D2O/CF3CO2H) d: 154.58, 39.3,
26.75, 26.48, 25.88, 23.97; MS (ES+) m/e 285 (MH+),
383 (M+H2SO4). Anal. calcd for C14H34N6O4S: C,
43.96; H, 8.96; N, 21.97. Found: C, 44.08; H, 9.21; N,
22.26.
Octylguanidinium sulphate (17). A solution of 2.073 g of
octylamine (16 mmol, 1 equiv) and 2.72 g of S-methyl-
isothiouronium sulphate (9.6 mmol, 0.6 equiv) in 15 mL
absolute ethanol was heated at 100 ꢃC for 18 h. The
solvent was removed under vacuum and insoluble mat-
ter was filtered off. The crude oil was dissolved in
EtOH/H2O and left in a refridgerator. The solid that
crystallised was rinsed with EtOH, Et2O and dried
under vacuum (1.25 g). White solid (35%); mp>190 ꢃC
dec. (lit.30b 251–252 ꢃC) ; 1H NMR (CD3OD) d 3.1 (bm,
2H); 1.6 (bm, 2H); 1.5–1.2 (bs, 10H); 0.8 (bm, 3H); 13C
NMR (CD3OD) d 159.0; 42.8; 33.4; 30.79; 30.39; 28.22;
24.11; 14.84; LRMS (ES+) m/e 172 (M+H/ 100%).
Anal. calcd for C9H22N3O2S0.5: C, 49.06; H, 10.06; N,
19.07. Found: C, 48.98; H, 10.94; N, 19.27.
N,N0-bis(4,5-Dihydro-1H-imidazol-2-yl)-1,6-hexanedia-
mine (5). The product was isolated from the crude reac-
tion mixture as the iodide salt by precipitation from
MeOH/Et2O: white solid (26%); mp 197–199 ꢃC; IR
Nonylguanidinium sulphate (18). A solution of 2.56 g of
nonylamine (17.9 mmol, 1 equiv) and 3.05 g of S-
methylisothiouronium sulphate (10.74 mmol, 1 equiv) in
15 m absolute ethanol was heated at 100 ꢃC for 18 h.
The solvent was removed under vacuum and insoluble
matter was filtered off. The crude oil was dissolved in
iPrOH/H2O and left in a refridgerator. The solid that
(KBr): 3203, 2906, 1664, 1593, 1473, 1282, 1066 cmꢀ1
;
1H NMR (D2O) d 3.48 (s, 8H); 2.99 (t, 4H, J=6.8 Hz);
1.5–1.25 (m, 4H); 1.25–1.00 (m, 4H); 13C NMR (D2O/
ref DMSO) d 158.86, 41.70, 41.50, 27.16, 24.46; MS
(APCI+): 253 (MH+/100%). Anal. calcd for
C12H26N6I2: C, 28.36; H, 5.16; N, 16.54. Found: C,
28.43; H, 5.02; N, 16.64.
i
crystallised was rinsed with PrOH, Et2O and dried
under vacuum (1.88 g). White solid (45%); mp>220 ꢃC
N,N0 -bis(4,5-dihydro-1H-imidazol-2-yl)-1,8-octanedia-
mine (6). Hydrochloride salt: slightly orange hygro-
scopic gum (40% yield); IR (KBr): 3180, 3060, 2935,
1
dec; H NMR (CD3OD) d 3.15 (bm, 2H); 1.6 (bm, 2H);
1.5–1.2 (bs, 12H); 0.9 (bm, 3H); 13C NMR (CD3OD) d
159.03; 42.84; 33.49; 31.13; 30.9; 30.45; 28.28; 24.17;
2860, 1670, 1600, 1460, 1285, 1050 cmꢀ1 1H NMR
;