Aziridine Ring Cleavage by Nucleophiles in Epimino Derivatives of 1,6-Anhydro-β-D-hexopyranoses
Table 7. Carbon-13 chemical shifts (100 MHz) of N-benzylamino derivatives 12, 14؊15, 19Ϫ22, 26Ϫ28 and 33Ϫ36 in CDCl3
Compound C-1 C-2 C-3 C-4 C-5 C-6 OCH2C6H5 NCH2C6H5 C6H5
FULL PAPER
12
101.87 57.32 58.25 76.83 73.96 65.50 71.63
103.78 23.85 58.72 77.32 75.14 65.92 71.36
101.37 60.44 40.50 78.42 74.75 65.84 71.92
100.20 76.34 58.95 57.32 74.86 66.48 72.41
51.30
51.34
50.86
50.73
51.28
51.31
50.09
139.54, 137.13, 128.63(2), 128.52(2),
128.16(2), 127.85(2), 127.22(2)
137.92, 137.32. 128.66(2), 128.38(2),
128.31(2), 128.21, 128.07(2), 127.17
136.88(2), 128.73(2), 128.68(2), 128.57(2),
128.02(2), 127.82, 127.65
139.49, 137.04, 128.62(2), 128.53(2),
128.21, 128.11(2), 128.02(2), 127.22
140.07, 137.42, 128.65(2), 128.38(2),
128.24, 128.21(2), 128.17(2),127.14
140.01, 137.45, 128.64(2), 128.29(2),
128.28(2), 128.21, 128.12(2), 127.07
128.87, 128.85, 128.71(2), 128.39,
128.26(2), 128.17(2), 127.72(2), 127.33
132.02, 128.62(2), 128.32(2), 127.54
139.55, 128.59(2), 127.98(2), 127.39
130.49, 129.63, 129.16, 128.39,
14
15
19[a]
20
99.90
99.99
75.99 57.97 52.92 76.11 64.54 72.86
75.08 58.51 34.92 77.61 65.13 72.71
21[a]
22
100.58 77.32 40.25 59.29 74.35 66.34 72.57
26[a]
27
28
102.37 69.84 60.12 61.38 74.60 66.10
100.90 71.12 59.79 55.73 75.04 63.45
103.58 71.26 62.44 45.42 78.83 68.22
-
-
-
52.74
52.18
51.87
128.07, 127.29
33
34
35
102.27 66.74 59.18 77.55 75.34 65.95 70.80
103.62 24.59 59.75 77.93 75.34 66.06 70.67
102.44 54.40 58.71 78.60 74.83 65.34 71.25
100.26 29.62 52.41 77.62 74.68 65.29 71.09
52.26
52.23
53.81
52.06
139.48, 137.22, 128.54(2), 128.45(2),
128.27(2), 127.89(2), 127.83, 127.35
139.49, 137.21, 128.55(2), 128.43(2),
128.30(2), 127.92(2), 127.79, 127.32
139.93, 137.69, 128.52(2), 128.48(2),
128.41(2), 127.90(2), 127.69, 127.15
129.45, 128.43(2), 127.78(2), 127.32
36[a]
[a]
At 125.7 MHz
and NH4Br (600 mg, 6.1 mmol), after 23 h of reflux. A mixture of
isomeric bromo derivatives 33 and 35 was formed, and the indi-
vidual compounds were separated by column chromatography on
silica gel (50 g, solvent mixture S3). 33: Yield 14.4 mg (29%) of
colourless oil. [α]D ϭ ϩ 37.1 (c ϭ 0.28, CHCl3). HR MS (FAB)
analysis found m/z ϭ 404.0783 [Mϩ ϩ H], C20H23BrNO3 requires
404.0861. 35: Yield 12.2 mg (28%) of colourless oil. [α]D ϭ Ϫ27.5
(c ϭ 0.24, CHCl3). HR MS (FAB) analysis found m/z ϭ 404.0745
[Mϩ ϩ H], C20H23BrNO3 requires 404.0861. In addition, 15 mg
(30%) of epimine 8 was isolated.
46.7 mmol), after 7 h of reflux. Yield 538 mg (94%), [α]D ϭ Ϫ19
(c ϭ 0.8 CHCl3). HR MS (FAB) analysis found m/z ϭ 367.1785
[Mϩ ϩ H], C20H23N4O3 requires 367.1770.
1,6-Anhydro-3-azido-2-O-benzyl-4-benzylamino-3,4-dideoxy-β-D-
glucopyranose (19): This compound was prepared from 4 (200 mg,
0.62 mmol), NaN3 (180 mg, 2.77 mmol) and NH4Cl (1 g,
18.7 mmol), after 8.5 h of reflux. Yield 203 mg (88%). [α]D ϭ Ϫ62.4
(c ϭ 0.48, CHCl3). IR (CHCl3): ν˜ ϭ 2100 [ν(N3)], 3332 [ν(NH)]
cmϪ1. HR MS (FAB) analysis found m/z ϭ 367.1842 [Mϩ ϩ H],
C20H23N4O3 requires 367.1770.
1,6-Anhydro-4-O-benzyl-3-benzylamino-2-iodo-2,3-dideoxy-β-D-
1,6-Anhydro-4-azido-3-benzylamino-3,4-dideoxy-β-
nose (26): This compound was prepared from
D
-glucopyra-
(160 mg,
glucopyranose (34): This compound was prepared from 8 (50 mg,
0.15 mmol), Bu4NI (300 mg, 0.8 mmol) and NH4I (300 mg,
2.1 mmol), after 19 h of reflux. Yield 52 mg (68%) of colourless oil.
[α]D ϭ ϩ23.1 (c ϭ 1.19, CHCl3). HR MS (FAB) analysis found
m/z ϭ 452.0736 [Mϩ ϩ H], C20H23INO3 requires 452.0723.
6
0.67 mmol), NaN3 (180 mg, 2.77 mmol) and NH4Cl (1 g,
18.7 mmol), after 7.5 h of reflux. Yield 166 mg (87.8%). [α]D ϭ Ϫ24
(c ϭ 0.46, CHCl3). IR (CHCl3): ν˜ ϭ 2102 [ν(N3)], 3342 [ν(NH)],
3560 [ν(OH)] cmϪ1. HR MS (FAB) analysis found m/z ϭ 277.1300
[Mϩ ϩ H], C13H17N4O3 requires 277.1301.
General Procedure for Treatment of Epimines 2, 4 and 6 with Azide:
A solution of benzylepimine 2, 4 or 6, sodium azide and ammo-
nium chloride in 2-methoxyethanol (10 mL) and water (2 mL) was
heated under reflux for given time. After the mixture had cooled
to room temp., the reaction solvents were evaporated to dryness (at
70Ϫ80 °C) and the solid residue was extracted with chloroform (70
mL). The extract was dried with Na2SO4, and the solvents were
evaporated to leave a brown oil. This oil was dissolved in toluene
(10 mL, for 12 and 19) or in dichloromethane (30 mL, for 26),
stirred with charcoal and filtered through a short (3 cm) column of
silica gel to remove coloured impurities. After concentration, the
filtrate gave a colourless, uncrystallizable oil, which was dried in a
vacuum dessicator over P2O5. The 1H and 13C NMR spectra are
summarized in Tables 4 to 7.
1,6-Anhydro-2-azido-4-O-benzyl-2,3-dideoxy-3-tosylamino-β-D-
glucopyranose (32): Epimine 7 (50 mg, 0.13 mmol), lithium azide
(60 mg, 1.23 mmol) and ammonium trifluoroacetate (35 mg,
0.27 mmol) were dissolved in DMSO (4 mL) and heated with stir-
ring at 110 °C for 19 h. After consumption of epimine 7, the reac-
tion mixture was cooled to room temp. and poured onto crushed
ice (30 mL). The separated solid was filtered off and air-dried.
Crude product 32 (48 mg, 87%) was recrystallised from a methanol/
diethyl ether/petroleum ether mixture to afford pure 32 (38.5 mg,
70%), m.p. 146Ϫ147 °C. [α]D ϭ ϩ129.4 (c ϭ 0.17, CHCl3). IR
(CHCl3): ν˜ ϭ 2101 [ν(N3)], 3375 [ν(NH)], 1343 [ν(SO2)], 1164
[ν(SO2)] cmϪ1. C20H22N4O5S (430.5): calcd. C 55.80, H 5.15, N
13.02, S 7.45; found C 55.76, H 5.20, N 12.68, S 7.23.
1,6-Anhydro-3-azido-4-O-benzyl-2-benzylamino-2,3-dideoxy-β-D-
glucopyranose (12): This compound was prepared from 2 (500 mg,
General Procedure for Treatment of Epimines 2, 4, 6 and 8 with
1.67 mmol), NaN3 (440 mg, 6.77 mmol) and NH4Cl (2.5 g,
Hydrobromic Acid: Epimine 2, 4, 6 or 8 was dissolved in ethanol
Eur. J. Org. Chem. 2002, 2449Ϫ2459
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