I. Merino et al. / Bioorg. Med. Chem. 14 (2006) 3583–3591
3587
7.79 (d, J = 9.2 Hz, 4H); 13C NMR (100 MHz, CDCl3) d
21.65, 25.33, 28.82, 28.92, 29.34, 29.41, 70.71, 127.89,
129.81, 133.22, 144.63; LREIMS C26H38O6S2 requires
510.21. Found 510 ([M+], 4%), 91 ([C7H7+], 100%);
Anal. Calcd for C26H38O6S2: C, 61.15; H, 7.50; N,
0.00. Found: C, 61.08; H, 7.47; N, 0.00.
at room temperature overnight. The solvent was re-
moved by distillation at reduced pressure. The resulting
brown syrup was purified by column chromatography
with silica gel 50% of which was saturated with NH3
gas (Typical solvent system: dichloromethane/MeOH
(97/3)).
4.1.4. 1,15-Bis-(O-tosyl)pentadecane (5g).25 Yield: 67%;
white powder; mp 72–73 ꢁC; IR (KBr) cmꢁ1 2977,
2923, 2850, 1354, 839, 669; 1H NMR (100 MHz, CDCl3)
d 1.21–1.31 (m, 20H), 1.63 (qn, J = 7.1 Hz, 4H), 2.45 (s,
6H), 4.01 (t, J = 6.6 Hz, 4H), 7.34 (d, J = 8.8 Hz, 4H),
7.79 (d, J = 8.4 Hz, 4H); 13C NMR (100 MHz, CDCl3)
d 21.88, 25.55, 29.04, 29.16, 29.61, 29.72, 29.81, 29.84,
70.95, 128.12, 130.03, 133.42, 144.85; LREIMS
C29H44O6S2 requires 552.26. Found 552 ([M+], 5%), 91
([C7H7+], 100%); Anal. Calcd for C29H44O6S2: C, 63.01;
H, 8.02; N, 0.00. Found: C, 63.12; H, 8.00; N, 0.00.
4.1.8. General procedure for bis-(N-imidazolyl)alkane
hydrochloride salts 2. A solution of bis-(N-imidazolyl)al-
kane 2 (0.5 mmol) in 5 mL of anhydrous THF was
purged with HCl gas for 10–15 s. The solvent was re-
moved under reduced pressure and the hydrochloride
salt of 2 was dried under high vacuum at 70 ꢁC.
4.1.9. 1,9-Bis-(imidazol-1-yl)nonane dihydrochloride (2a).
Yield: 37%; colorless oil; IR (KBr) cmꢁ1 3100, 2930,
2856, 1575, 1457, 629; 1H NMR (400 MHz, DMSO-
d6) d 1.20–1.37 (m, 10H), 1.78 (qn, J = 6.8 Hz, 4H),
4,16 (t, J = 7.0 Hz, 4H), 7.68 (s, 2H), 7,79 (s, 2H), 9,21
(s, 2H); 13C NMR (100 MHz, DMSO-d6) d 26.21,
29.03, 29.43, 30.16, 49.13, 120.12, 122.66, 135.83; LRE-
IMS C15H24N4 (neutral form) requires 260.20. Found
259 ([MꢁH+], 35%), 179 ([Mꢁ(N-methyleneimidaz-
ole)+], 100%); Anal. Calcd for C15H26Cl2N4Æ2H2O: C,
48.78; H, 8.19; N, 15.17. Found: C, 48.99; H, 8.12; N,
14.87.
4.1.5. 1,16-Bis-(O-tosyl)hexadecane (5h).24,26–28. Yield:
90%; white powder; mp 79–81 ꢁC; IR (KBr) cmꢁ1
2977, 2923, 2851, 1358, 838, 670; H NMR (100 MHz,
1
CDCl3) d 1.21–1.31 (m, 22H), 1.63 (qn, J = 7.2 Hz,
4H), 2.45 (s, 6H), 4.02 (t, J = 6.4 Hz, 4H), 7.34 (d,
J = 8.0 Hz, 4H), 7.79 (d, J = 8.0 Hz, 4H); 13C NMR
(100 MHz, CDCl3) d 21.65, 25.34, 28.83, 28.94, 29.40,
29.50, 29.60, 29.64, 70.72, 127.90, 129.80, 133.27,
144.62; LREIMS C30H46O6S2 requires 566.27. Found
566 ([M+], 32%), 91 ([C7H7+], 100%); Anal. Calcd for
C30H46O6S2: C, 63.57; H, 8.18; N, 0.00. Found: C,
63.42; H, 8.25; N, 0.00.
4.1.10. 1,10-Bis-(imidazol-1-yl)decane dihydrochloride
(2b). Yield: 45%; white powder; mp 132–134 ꢁC; IR
1
(KBr) cmꢁ1 3068, 3022, 2932, 2857, 1545, 865, 636; H
NMR (400 MHz, DMSO-d6) d 1.15–1.25 (m, 12H),
1.77 (qn, J = 6.8 Hz, 4H), 4.16 (t, J = 7.0 Hz, 4H), 7.68
(d, J = 1.2 Hz, 2H), 7.79 (d, J = 1.2 Hz, 2H), 9.18 (s,
2H); 13C NMR (100 MHz, DMSO-d6) d 26.24, 29.03,
29.47, 30.15, 49.10, 120.14, 122.63, 135.87; LREIMS
C16H26N4 (neutral form) requires 274.22. Found 273
([MꢁH+], 51%), 193 ([Mꢁ(N-methyleneimidazole)+],
100%); Anal. Calcd for C16H28Cl2N4: C, 55.33; H,
8.13; N, 16.13. Found: C, 55.09; H, 8.12; N, 15.74.
4.1.6. 1-Bromo-13-(O-tosyl)tridecane (7e). A solution of
13-bromotridecanol-1 6e (2.5 mmol), N-methylmorpho-
line (5.0 mmol), and p-tosyl chloride (2.6 mmol) in
25 mL of anhydrous THF was stirred at room tempera-
ture for 2 days. The solvent was then removed under re-
duced pressure, and the mixture was dissolved in
dichloromethane, washed with 1 N NaHCO3 (3·
50 mL), 1 N HCl (3· 50 mL), and deionized water (3·
50 mL), respectively. The organic phase was dried with
anhydrous Na2SO4, filtered, and concentrated under re-
duced pressure. The resulting mixture was purified by
column chromatography (hexanes/ethyl acetate 3:1) to
give 7e in 45% yield; white powder; mp 44–45 ꢁC; IR
(KBr) cmꢁ1 2920, 2953, 1597, 1354, 846, 665; 1H
NMR (400 MHz, CDCl3) d 1.21–1.27 (m, 16H), 1.42
(qn, J = 7.2 Hz, 2H), 1.63 (qn, J = 7.0 Hz, 2H), 1.85
(qn, J = 7.2 Hz, 2H), 2.45 (s, 3H), 3.41 (t, J = 6.8 Hz,
2H), 4.02 (t, J = 6.4 Hz, 2H), 7.34 (d, J = 8.2 Hz, 2H),
7.79 (d, J = 8.6 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 21.65, 25.32, 28.16, 28.76, 28.81, 28.91, 29.37, 29.42,
29.45, 29.50, 29.53, 32.83, 34.10, 70.71, 127.89, 129.79,
133.22, 144.62; LREIMS C20H33BrO3S requires
434.13. Found 435 ([M+], 30%), 433 ([M+], 30%), 263
([MꢁTsO+], 99%), 261 ([MꢁTsO+], 100%); Anal. Calcd
for C20H33BrO3S: C, 55.42; H, 7.67; N, 0.00; Found: C,
55.58; H, 7.71; N 0.00.
4.1.11. 1,11-Bis-(imidazol-1-yl)undecane dihydrochloride
(2c). Yield: 43%; white powder; mp 138–139 ꢁC; IR
1
(KBr) cmꢁ1 3392, 2928, 2856, 1576, 1547, 764, 628; H
NMR (400 MHz, DMSO-d6) d 1.15–1.25 (m, 14H),
1.77 (qn, J = 7.0 Hz, 4H), 4.17 (t, J = 7.0 Hz, 4H), 7.68
(d, J = 1.6 Hz, 2H), 7.79 (d, J = 1.6 Hz, 2H), 9.21 (s,
2H); 13C NMR (100 Hz, DMSO-d6) d 26.23, 29.06,
29.57, 30.12, 49.14, 120.43, 122.65, 135.85; LREIMS
C17H28N4 (neutral form) requires 288.23. Found 287
([MꢁH+], 51%), 207 ([Mꢁ(N-methylenelimidazole)+],
100%); Anal. Calcd for C17H30Cl2N4ÆH2O: C, 53.82;
H, 8.50; N, 14.77. Found: C, 53.68; H, 8.49; N, 14.38.
4.1.12. 1,12-Bis-(imidazol-1-yl)dodecane dihydrochloride
(2d). Yield: 32%; white powder; mp 127–129 ꢁC; IR
(KBr) cmꢁ1 2923, 2854, 1472, 662; 1H NMR
(400 MHz, DMSO-d6) d 1.15–1.25 (m, 16H), 1.72 (qn,
J = 7.2 Hz, 4H), 4.05 (t, J = 7.2 Hz, 4H), 7.31 (d,
J = 1.6 Hz, 2H), 7.50 (d, J = 1.6 Hz, 2H), 8.48 (s, 2H);
13C NMR (100 MHz, DMSO-d6) d 26.47, 29.13, 29.58,
29.67, 30.64, 48.29, 121.41, 124.22, 136.74; LREIMS
C18H30N4 (neutral form) requires 302.25. Found 301
([MꢁH+], 92%), 221 ([Mꢁ(N-methyleneimidazole)+],
4.1.7. General procedure for bis-(N-imidazolyl)alkanes 2.
A mixture of bis-tosylalkane 5, dibromoalkane 8, or
tosylbromoalkane 7 (2.0 mmol) and imidazole sodium
salt (4.4 mmol) in 15 mL of anhydrous DMF was stirred