Synthesis and Properties of New Glucocationic Surfactants
chromatography on silica gel using ethyl acetate-petroleum
ether (30:70) as solvent. A white crystalline solid was obtained,
yield 39.97 g (54%).
(C2); 69.9 (C3); 68.8 (C4); 68.5 (OCH2), 67.7 (C5); 61.9 (C6); 29.8
(CH2Br); 20.7 (2 CH3COO); 20.6 (2 CH3COO); FT-IR (KBr)
(cm-1) 2958, 1750, 1434, 1372, 1244, 1038, 904, 834, 756, 694,
602, 554, 524; MS-ESI (m/z) calcd 455, found 477, 479 (M +
Na+). Anal. Calcd for C16H23BrO10: C, 42.21; H 5.09. Found:
C, 42.25; H, 5.06.
Method B. Compound a (0.5 g., 1.02 mM) was dissolved at
25 °C in 25 mL of anhydrous dicholoromethane in a three-
necked flask under Ar. 2-Bromoethanol (0.14 g., 0.079 mL, 1.12
mM) was added dropwise under stirring followed by boron
trifluoride etherate (0.144 g., 0.129 mL, 1.02 mM). The reaction
was left at room temperature. The reaction progress was
monitored by TLC (silica gel, petroleum ether/ethyl acetate
70:30), until the starting material disappeared. The reaction
was quenched by adding a 10% NaCO3 aqueous solution, and
the organic phase was extracted three times with 10% NaCO3
aqueous solution and washed with water to neutrality. The
organic phase was treated with NaSO4 and filtered. The
solvent was removed under reduced pressure, giving a yellow-
brown thick oil.
N-[2-(2,3,4,6-Tetra-O-acetyl-â-D-glucopyranosyl)ethyl]-
N,N-dimethyl-N-octylammonium Bromide (3). In a three-
necked flask, compound 1 (10.49 g, 0.023 mol) was dissolved
in anhydrous ethanol under argon. The mixture was warmed
at reflux, and an ethanolic solution of N,N-dimethyloctylamine
(3.21 g, 0.0204 mol) was added dropwise. After 24 h, a 10%
excess of compound 1 was added, and the reaction was
continued for further 24 h. The solvent was removed in vacuo,
and the resulting viscous oil was purified by flash chromatog-
raphy on basic alumina first with ethyl acetate and subse-
quently with ethyl acetate/methanol 80:20 and 50:50. The
resulting viscous pale yellow syrup solidified on standing and
was further purified from trace of the amine by suspension in
petroleum ether and a small quantity of chloroform, under
stirring. A white powder was finally obtained: yield 70%; mp
95-100 °C; Rf ) 0.05 on silica (MAC methanol/acetic acid/
chloroform 20:10:70); 0.17 on basic alumina (ethyl acetate/
methanol 70:30); [R]25578 ) -12.12 (c ) 0.775, MeOH); 1H NMR
(CDCl3) δ (ppm) 0.86 (t, 3H CH3); 1.30 (m, 10H, 5 CH2); 1.70
(m, 2H, N+-CH2-CH2); 1.95, 2.01, 2.04, 2.07 (4 s, 12H, 4 CH3-
COO); 3.32(s, 3H, N+CH3); 3.35(s, 3H, N+CH3); 3.48 (t, 2H,
N+CH2); 3.80 (m, 1H, H5); 3.94 (ddd, 1H, OCH2CH2aN+), 4.08-
4.22 (m, 4H, OCH2CH2bN+, OCH2aCH2N+, 2H6); 4.33 (dd, 1H,
OCH2bCH2N+); 4.66 (d, 1H, H1, J1,2 ) 8.02 Hz); 4.90 (dd, 1H,
Flash chromatography on column of silica gel and petroleum
ether/ethyl acetate 70:30 as the eluent gave the pure product
(0.33 g., 71% yield), which crystallized immediately from the
eluted fractions: mp 119-120 °C; Rf ) 0.30 on silica (petro-
leum ether/ethyl acetate 70:30); [R]25
) -12.5 (c ) 0.78
578
1
CHCl3); H NMR (CDCl3) δ (ppm) 1.99, 2.01, 2.05, 2.07 (4 s,
12H, 4 CH3COO); 3.44 (m, 2H, CH2Br); 3.69 (ddd, 1H, H5);
3.80 (ddd, 1H, OCH2aCH2Br); 4.11 (dd, 1H, H6a); 4.15 (dd, 1H,
OCH2bCH2Br); 4.24 (dd, 1H, H6b); 4.55 (d, 1H, H1, J1,2 ) 7.69
Hz); 5.00 (dd, 1H, H2); 5.07 (t, 1H, H4); 5.20 (t, 1H, H3); 13C
NMR (CDCl3) δ (ppm) 170.5 (CH3COO); 170.1 (CH3COO);
169.3 (2 CH3COO); 100.9 (C1); 72.5 (C3); 71.8 (C5); 70.9 (C2);
69.7 (OCH2), 68.2 (C4); 61.7 (C6); 29.8 (CH2Br); 20.6 (2 CH3-
COO); 20.5 (2 CH3COO); FT-IR (KBr) (cm-1) 2962, 2884, 1752,
1432, 1370, 1224, 1042, 904, 834, 510; MS-ESI (m/z) calcd 455,
found 477, 479 (M + Na+). Anal. Calcd for C16H23BrO10: C,
42.21; H, 5.09. Found: C, 42.27; H, 5.03.
1
H2); 5.02 (t, 1H, H4); 5.08 (t, 1H, H3); H NMR (DMSO-d6) δ
(ppm) 0.88 (t, 3H CH3); 1.29 (m, 10H, 5 CH2); 1.66 (m, 2H,
N+-CH2-CH2); 1.95, 2.00, 2.03, 2.04 (4 s, 12H, 4 CH3COO); 3.04
(s, 6H, 2 N+CH3); 3.30 (t, 2H, N+CH2); 3.57 (t, 2H, OCH2CH2N+),
4.03-4.22 (m, 5H, OCH2CH2N+, H5, 2H6); 4.82 (dd, 1H, H2);
4.93-4.97 (m, 2H, H1, H4); 5.29 (t, 1H, H3); 13C NMR (CDCl3)
δ (ppm) 170.4 (CH3COO); 169.7 (CH3COO); 169.3 (2 CH3COO);
100.1 (C1); 72.2 (C3); 72.0 (C5); 70.8 (C2); 67.9 (C4); 66.0
(N+CH2); 63.5 (OCH2), 62.9 (OCH2CH2N+); 61.3 (C6); 51.5 (2
N+CH3); 31.4, 29.0; 28.8; 26.0 (4 CH2); 22.6 (N+CH2CH2); 22.4
(CH2); 20.7 (CH3COO); 20.6 (CH3COO); 20.4 (CH3COO); 20.3
(CH3COO); 13.9 (CH3); 13C NMR (DMSO-d6) δ (ppm) 170.1
(CH3COO); 169.6 (CH3COO); 169.3 (CH3COO); 169.2 (CH3COO);
98.9 (C1); 72.0 (C3); 70.8 (C5); 70.6 (C2); 68.1 (C4); 64.1 (N+CH2);
62.6 (OCH2); 62.2 (OCH2CH2N+); 61.6 (C6); 50.8 (N+CH3); 50.7
(N+CH3); 31.2, 25.8 (4 CH2); 22.1 (N+CH2CH2); 21.8 (CH2); 20.6
(CH3COO); 20.5 (CH3COO); 20.5 (CH3COO); 20.3 (CH3COO);
14.0 (CH3); FT-IR (KBr): cm-1 2928, 2858, 1752, 1438, 1372,
1226, 1166, 1042, 910; MS-ESI: (m/z) calcd 612, found 532
(M - Br). Anal. Calcd for C26H46BrNO10: C, 50.98; H, 7.57; N,
2.29. Found: C, 50.94; H, 7.59; N, 2.32.
2-Bromoethyl-2,3,4,6-tetra-O-acetyl-R-D-glucopyrano-
side (2). Method A. In a first step, the anomeric mixture of
2-bromoethyl-D-glucopyranoside was prepared according to a
literature method.22 This material was directly used in the
synthesis of the compound 2. The anomeric mixture (0.68 g,
2.2 × 10-3 mol) was dissolved in pyridine (4 mL) and added
dropwise in a three-necked flask containing a previously
chilled (0 °C) pyridine (8 mL) solution of acetic anhydride (3.15
mL, 3.33 × 10-2 mol) under stirring. After 80 min, the mixture
was allowed to return to room temperature and reacted for 4
h, when it was quenched with brine (50 mL). The product
separated as an oil, and 15 mL of concd HCl wa added. The
mixture was extracted with dichloromethane, washing the
organic phase with NaHCO3 solution until neutralization was
attained. After drying with Na2SO4, evaporation of the solvent
in vacuo gave a viscous oil which, by flash chromatography
on silica (petroleum ether/ethyl acetate 70:30), furnished a pale
yellow oil, yield (based on starting glucose) 10%.
Method B: Anomerization of Compound 1. Compound
1 (3 g, 6.59 mmol) was introduced in a three-necked round-
bottom flask, dissolved in 20 mL of dichloromethane, and
stirred under argon at room temperature. Anhydrous ferric
chloride (5.3 g., 32.7 mmol) was quickly added to the reaction.
The black solution was allowed to react overnight and quenched
with water (20 mL). The organic phase was extracted three
times with water, dried with CaCl2, and evaporated, giving a
dark brown oil. Flash chromatography on silica with petroleum
ether/ethyl acetate 70:30 gave a colorless oil that solidified on
prolonged standing. A white solid paste was obtained: yield
0.91 g (30%); Rf ) 0.21 on silica (petrol ether/ethyl acetate 70:
30); [R]25578 ) +112.52 (c ) 0.558, CHCl3); 1H NMR (CDCl3) δ
(ppm) 1.99, 2.00, 2.06, 2.07 (4 s, 12H, 4 CH3COO); 3.49 (t, 2H,
CH2Br); 3.82, 3.97 (2 sym quintets, 2H, OCH2CH2Br), 4.08-
4.11 (m, 2H, H5+H6a); 4.20-4.24 (m, 1H, H6b); 4.83 (dd, 1H,
H2); 5.04 (t, 1H, H4); 5.13 (d, 1H, H1, J1,2 ) 3.8 Hz); 5.47 (t,
1H, H3); 13C NMR (CDCl3) δ (ppm) 170.6 (CH3COO); 170.2
(CH3COO); 170.0 (CH3COO); 169.6 (CH3COO); 96.0 (C1); 70.8
N-[2-(2,3,4,6-Tetra-O-acetyl-â-D-glucopyranosyl)ethyl]-
N,N-dimethyl-N-dodecylammonium Bromide (4). The
same procedure described for product 3 was applied, giving a
white powder: yield 60%; mp 90-93 °C; Rf ) 0.05 on silica
(MAC 20:10:70); 0.22 on basic alumina (ethyl acetate/methanol
1
70:30); [R]25 ) -11.68 (c ) 0.78, MeOH); H NMR (DMSO-
578
d6) δ (ppm) 0.87 (t, 3H CH3); 1.26 (m, 18H, 9 CH2); 1.65 (m,
2H, N+-CH2-CH2); 1.95, 2.00, 2.03, 2.04 (4 s, 12H, 4 CH3COO);
3.04(s, 6H, 2 N+CH3); 3.30 (t, 2H, N+CH2); 3.57 (t, 2H,
OCH2CH2N+); 4.03-4.22 (m, 5H, OCH2CH2N+, H5, 2H6); 4.82
(dd, 1H, H2); 4.93-4.97 (m, 2H, H1, H4); 5.29 (t, 1H, H3); 13C
NMR (DMSO-d6) δ (ppm) 170.1 (CH3COO); 169.6 (CH3COO);
169.3 (CH3COO); 169.2 (CH3COO); 99.0 (C1); 71.9 (C3); 70.8
(C5); 70.7 (C2); 68.1 (C4); 64.1 (N+CH2); 62.6 (OCH2), 62.2
(OCH2CH2N+); 61.6 (C6); 50.8 (N+CH3); 50.7 (N+CH3); 31.4-
25.8 (8 CH2); 22.2 (N+CH2CH2); 21.8 (CH2); 20.6 (CH3COO);
20.5 (2 CH3COO); 20.3 (CH3COO); 14.0 (CH3); FT-IR (KBr)
(cm-1) 2926, 2856, 1751, 1464, 1372, 1224, 1042, 908; MS-ESI
(m/z) calcd 668, found 588 (M - Br). Anal. Calcd for C30H54-
NO10Br: C, 53.89; H, 8.14; N, 2.09. Found: C, 53.83; H, 8.19;
N, 2.04.
J. Org. Chem, Vol. 70, No. 24, 2005 9865