Notes
J . Org. Chem., Vol. 64, No. 11, 1999 4171
Sch em e 2a
added, and the reaction mixture was stirred for an additional 2
h. The mixture was concentrated under reduced pressure, and
the residue was dissolved with ethyl acetate (20 mL). The
solution was washed with a saturated aqueous solution of
sodium bicarbonate (5 mL) and with water (3 × 5 mL) and then
dried over sodium sulfate. The mixture was filtered, and the
filtrate was concentrated under reduced pressure. The residue
was subjected to silica gel chromatography [2.5 × 15 cm,
eluent: methanol (1%) in dichloromethane] to give 3a (0.82 g,
80%) as a foam. Compound 3a was used in the following reaction
without further purification.
a
(a) Isopropylamine, EtOH, 4.
Rf (system 2): 0.42; 1H NMR (DMSO-d6): δ 8.0-7.5 (m, 12
H, H-4, H-7 and phenyl), 6.44 (bs, 1 H, OH-2′), 6.11 (d, 1 H,
H-1′, J ) 5.2 Hz), 5.7-5.6 (m, 1 H, H-3′), 4.9 (m, 1 H, H-4′),
4.8-4.6 (m, 3 H, H-2′, H-5′ and H-5′′).
Exp er im en ta l Section
Gen er a l Ch em ica l P r oced u r es. Melting points were de-
termined on a melting point apparatus and are uncorrected.
Silica gel, SilicAR 40-63 µm, 230-400 mesh (Mallinckrodt), was
used for column chromatography. Thin-layer chromatography
(TLC) was performed on prescored SilicAR 7GF plates (Analtech,
Newark, DE). TLC plates were developed in the following solvent
systems: system 1 (35% EtOAc/hexanes, v/v), system 2 (50%
EtOAc/hexanes, v/v), system 3 (10% MeOH/CH2Cl2, v/v). Com-
pounds were visualized by illuminating with UV light (254 nm)
or by treatment with 10% methanolic sulfuric acid followed by
charring on a hot plate. Evaporations were carried out under
reduced pressure (water aspirator) with the bath temperature
not exceeding 50 °C, unless specified otherwise. 1H NMR spectra
were recorded at 300, 360, or 500 MHz. Chemical shifts are
expressed in δ values (ppm) relative to the chemical shift of the
residual DMSO-d5 (δ 2.50 ppm) contained in the solvent DMSO-
d6. All 1H NMR assignments reported were made by homo-
nuclear decoupling experiments. Microanalytical results were
performed by the University of Michigan, Department of Chem-
istry, and are within (0.4% of the theoretical values, unless
otherwise specified. Unless otherwise noted, all materials were
obtained from commercial suppliers.
2,5,6-Tr ich lor o-1-(2-O-acetyl-3,5-di-O-ben zoyl-â-L-xylofu r -
a n osyl)b en zim id a zole (2a ). 2,5,6-Trichlorobenzimidazole22
(500 mg, 2.3 mmol) was suspended in acetonitrile (60 mL), and
the mixture was stirred at 50 °C. BSA (0.83 mL, 3.4 mmol) was
added, and the reaction mixture stirred for an additional 15 min.
Compound 118 (1.0 g, 2.3 mmol) in acetonitrile (10 mL) and
TMSOTf (0.65 mL, 3.4 mmol) were added to the clear solution.
The mixture was allowed to stir at 50 °C for 16 h. The mixture
was concentrated under reduced pressure and the residue
dissolved with ethyl acetate (75 mL). The solution was washed
with a saturated aqueous solution of sodium bicarbonate (10 mL)
and with water (3 × 10 mL) and then dried over anhydrous
sodium sulfate. The mixture was filtered, and the filtrate was
concentrated under reduced pressure. The residue was subjected
to silica gel chromatography [2.5 × 15 cm, eluent: gradient of
methanol (0-1%) in dichloromethane] to give 2a (1.1 g, 80%) as
a foam. Compound 2a was used in the following reaction without
further purification.
2-Br om o-5,6-d ich lor o-1-(3,5-d i-O-b en zoyl-â-L-xylofu r -
a n osyl)ben zim id a zole (3b). The reaction was performed as
described for 3a , using hydrazine hydrate (0.15 mL, 3.0 mmol),
2b (0.65 g, 1.0 mmol), pyridine (7 mL), and acetic acid (1.8 mL)
to give 3b (0.52 g, 85%) as a foam. Compound 3b was used in
the following reaction without further purification.
Rf (system 2): 0.42; 1H NMR (DMSO-d6): δ 8.0-7.4 (m, 12
H, H-4, H-7 and phenyl), 6.43 (d, 1 H, OH-2′, J ) 5.7 Hz), 6.09
(d, 1 H, H-1′, J ) 5.2 Hz), 5.7-5.6 (m, 1 H, H-3′), 4.9 (m, 1 H,
H-4′), 4.8-4.6 (m, 3 H, H-2′, H-5′ and H-5′′).
2,3′-O-An h yd r o-5,6-d ich lor o-1-(â-L-lyxofu r a n osyl)b en z-
im id a zole (7). Triflic anhydride (0.37 mL, 2.2 mmol) in a
solution of dichloromethane (4.5 mL) was added to a solution of
3a (820 mg, 1.5 mmol) in a mixture of dichloromethane (7.5 mL)
and pyridine (0.75 mL). The reaction was stirred at 0 °C and
monitored by TLC (system 1). After 30 min, water (1.5 mL) was
added, and the temperature of the reaction mixture was
increased to 40 °C. After an additional 15 h of stirring, the
mixture was diluted with dichloromethane (10 mL) and water
(10 mL). The organic extract was washed with water (5 mL),
dried over anhydrous sodium sulfate, and filtered, and the
filtrate was evaporated to dryness. The residue was subjected
to silica gel chromatography [2.5 × 15 cm, eluent: gradient of
methanol (0-2%) in dichloromethane] to give one major com-
pound [Rf (system 2): 0.40, 590 mg] as a foam. 1H NMR (DMSO-
d6): δ 7.9-7.5 (m, 12 H, phenyls, H-4 and H-7), 6.61 (d, 1 H,
H-1′, J ) 5.4 Hz), 6.27 (t, 1 H, H-2′, J ) 5.5 Hz), 5.88 (t, 1 H,
H-3′, J ) 5.5 Hz), 4.9 (m, 1 H, H-4′), 4.6-4.5 (m, 1 H, H-5′),
4.3-4.2 (m, 1 H, H-5′′). This foam was dissolved in a solution of
ethanol and water (9:1, v/v, 20 mL), and sodium carbonate (0.45
g, 4.2 mmol) was added. The reaction mixture was stirred 4 days,
and then acetic acid (1 mL) was added and the mixture
evaporated to dryness. Water (10 mL) and ethyl acetate (20 mL)
were added to the residue. The organic extract was washed with
water (2 × 5 mL), dried over sodium sulfate, and filtered, and
the filtrate was evaporated to dryness. The residue was sus-
pended in boiling dichloromethane, (10 mL) and methanol was
added until complete dissolution had occurred. Compound 7 (200
mg, 43%) crystallized from this solution.
Rf (system 1): 0.20; 1H NMR (DMSO-d6): δ 8.1-7.5 (m, 12
H, phenyl, H-4 and H-7), 6.37 (d, 1 H, H-1′, J ) 5.3 Hz), 5.9 (m,
1 H, H-3′), 5.6-5.5 (m, 1 H, H-2′), 5.0-4.9 (m, 1 H, H-4′), 4.8-
4.7 (m, 2 H, H-5′,5′′), 2.12 (s, 3 H, acetyl).
2-Br om o-5,6-d ich lor o-1-(2-O-a cetyl-3,5-d i-O-ben zoyl-â-L-
xylofu r a n osyl)ben zim id a zole (2b). The reaction was per-
formed as described for 2a , using 2-bromo-5,6-dichlorobenzim-
idazole13 (530 mg, 2.0 mmol), BSA (0.73 mL, 3.0 mmol),
compound 118 (0.88 g, 2.0 mmol), and TMSOTf (0.58 mL, 3.0
mmol) to give 2b (1.1 g, 83%) as a foam. Compound 2b was used
in the following reaction without further purification.
Mp: 255-257 °C (decomp); Rf (system 3): 0.18; 1H NMR
(DMSO-d6): δ 7.96 and 7.62 (2 s, 2 H, H-4 and H-7), 6.36 (d, 1
H, OH-2′, J ) 2.9 Hz), 6.18 (d, 1 H, H-1′, J ) 4.0 Hz), 5.04 (t, 1
H, H-3′, J ) 2.9 Hz), 5.01 (t, 1 H, OH-5′, J ) 5.4 Hz), 4.7 (m, 1
H, H-2′), 4.4 (m, 1 H, H-4′), 3.5-3.4 (m, 1 H, H-5′), 3.4-3.3 (m,
1 H, H-5′′); Anal. Calcd for C12H10Cl2N2O4: C, 45.45; H, 3.18;
N, 8.83. Found: C, 45.08; H, 3.15; N, 8.74. Compound 7 (0.12 g,
40%) was also obtained from 3b (0.55 g, 0.9 mmol). Structure
and absolute stereochemistry of 7 was determined by X-ray
crystallography.
5,6-Dich lor o-2-isopr opylam in o-1-(â-L-lyxofu r an osyl)ben z-
im id a zole (8). Compound 7 (150 mg, 0.47 mmol) was dissolved
in ethanol (3.3 mL). Isopropylamine (2.0 mL, 24 mmol) was
added, the flask was sealed, and the reaction mixture was stirred
at 70 °C for one week. At this time, the reaction was checked by
TLC (system 3). Because only a partial reaction had occurred,
the reaction mixture was stirred at 80 °C for an additional week.
The mixture was then evaporated to dryness, and the residue
was dissolved in ethyl acetate (20 mL) and water (5 mL). The
organic extract was washed with water (2 × 5 mL), dried over
Na2SO4, and filtered, and the filtrate was evaporated to dryness.
The residue was subjected to silica gel chromatography [2.5 ×
15 cm, eluent: methanol (6%) in dichloromethane]. Fractions
Rf (system 2): 0.45; 1H NMR (DMSO-d6): δ 8.1-7.5 (m, 12
H, phenyl, H-4 and H-7), 6.33 (d, 1 H, H-1′, J ) 5.3 Hz), 5.9 (m,
1 H, H-3′), 5.6-5.5 (m, 1 H, H-2′), 5.0-4.9 (m, 1 H, H-4′), 4.8-
4.7 (m, 2 H, H-5′,5′′), 2.12 (s, 3 H, acetyl).
2,5,6-Tr ich lor o-1-(3,5-d i-O-b en zoyl-â-L-xylofu r a n osyl)-
ben zim id a zole (3a ). Hydrazine hydrate (0.27 mL, 5.5 mmol)
was added to a solution of 2a (1.1 g, 1.8 mmol) in a mixture of
pyridine (12.6 mL) and acetic acid (3.2 mL). After stirring the
mixture at room temperature for 20 h, acetone (4.1 mL) was
(22) Hinkley, J . M.; Porcari, A. R.; Walker, J . A., II; Swayze, E. E.;
Townsend, L. B. Synth. Commun. 1998, 28, 1703-1712.