W.-Y. Liu et al. / Carbohydrate Research 344 (2009) 1270–1275
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4.89 (s, 1H, OH), 4.35 (s, 1H), 4.15 (q, J 4.3 Hz, 1H), 3.95 (q, J 4.1 Hz,
1H), 3.61–3.64 (m, 1H, CH2), 3.49–3.52 (m, 1H, CH2), 3.31 (s, 2H,
NH2); HRESIMS: calcd for [M+Na]+ C8H13N5NaO5: 282.0814; found:
282.0804.
(d, J 8.7 Hz, 2 ꢁ 1H, ArH), 5.86 (d, J 4.0 Hz, 1H), 5.54 (d, J 5.6 Hz, 1H,
OH), 5.15 (d, J 5.6 Hz, 1H, OH), 4.89 (t, J 5.5 Hz, 1H, OH), 4.41 (q, J
4.8 Hz, 1H), 4.16 (q, J 5.1 Hz, 1H), 3.98 (q, J 4.6 Hz, 1H), 3.82 (s,
3H, OCH3), 3.63–3.68 (m, 1H, CH2), 3.50–3.56 (m, 1H, CH2); 13C
NMR (DMSO-d6, 100 MHz): d 161.4, 156.8, 155.4, 149.3, 145.5,
129.3 (2 ꢁ C), 127.2, 114.8 (2 ꢁ C), 92.4, 86.0, 75.0, 70.3, 61.6,
55.8; HRESIMS: calcd for [M+H]+ C16H20N5O6: 378.1414; found:
378.1404.
4.4. General procedure for the synthesis of ribavirin hydrazone
derivatives
4.4.1. (Z)-N0-Benzylidene-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-
(hydroxymethyl)tetrahydrofuran-2-yl)-1H-1,2,4-triazole-3-
carbohydrazide (7a)
4.4.4. (Z)-1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)-
tetrahydrofuran-2-yl)-N0-(4-(dimethylamino)benzylidene)-1H-
1,2,4-triazole-3-carbohydrazide (7d)
1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-
furan-2-yl)-1H-1,2,4-triazole-3-carbohydrazide
(5)
(530 mg,
1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-
2.04 mmol, theoretical quantity) was added to 7 mL of HOAc, with
stirring and heating until 5 dissolved. Then PhCHO (350 mg,
3.3 mmol) and 12 mL of EtOH were added. The mixture was then
heated to reflux for 0.5 h, at the end of which time it was filtered,
and the solid was washed with 10 mL of EtOH and dried to afford
furan-2-yl)-1H-1,2,4-triazole-3-carbohydrazide
(5)
(530 mg,
2.04 mmol, theoretical quantity) was added to 7 mL of HOAc, with
stirringand heating until 5 dissolved. Then 4-(dimethylamino)benz-
aldehyde (458 mg, 3.07 mmol) and 12 mL of EtOH were added. The
reaction mixture was heated to reflux for 1 h, and then the solvent
was removed on a rotary evaporator. The crude residue was washed
with 1:3 EtOAc–petroleum ether and subsequently purified by col-
umn chromatography (silica gel; 1:2 EtOH–EtOAc) to afford 7d as a
yellow solid: 342 mg (42.8%); mp 228–236 °C; IR (KBr):
3402, 3351, 3322, 3288, 3107, 2934, 2903, 2854, 2820, 1681, 1667,
1599, 1365, 1215, 1181, 1093, 1032, 824, 607, 532 cmꢀ1 1H NMR
(DMSO-d6, 400 MHz): d 11.57 (s, 1H, CONH–N), 8.95 (s, 1H, CH@N
triazole), 8.39 (s, 1H, ArCH@N), 7.52 (d, J 8.7 Hz, 2 ꢁ 1H, ArH), 6.76
(d, J 8.8 Hz, 2 ꢁ 1H, ArH), 5.85 (d, J 3.8 Hz, 1H), 5.53 (d, J 5.5 Hz, 1H,
OH), 5.14 (d, J 5.6 Hz, 1H, OH), 4.89 (t, J 5.5 Hz, 1H, OH), 4.41 (q, J
4.8 Hz, 1H), 4.16 (q, J 5.1 Hz, 1H), 3.98 (q, J 4.5 Hz, 1H), 3.63–3.68
(m, 1H, CH2), 3.50–3.56 (m, 1H, CH2), 2.98 (s, 6H, N(CH3)2); 13C
NMR (DMSO-d6, 100 MHz): d 157.0, 155.1, 152.1, 150.2, 145.4,
129.0 (2 ꢁ C), 121.8, 112.2 (2 ꢁ C), 92.4, 86.0, 75.0, 70.3, 61.6, 40.2
(2 ꢁ C); HRESIMS: calcd for [M+H]+ C17H23N6O5: 391.1730; found:
391.1720.
7a as a white solid: 568 mg (79.8%); mp 245–249 °C; IR (KBr):
m
3457, 3368, 3326, 3129, 2930, 1694, 1545, 1229, 1084 cmꢀ1 1H
;
NMR (DMSO-d6, 400 MHz): d 11.91 (s, 1H, CONH–N), 8.98 (s, 1H,
CH@N triazole), 8.57 (s, 1H, ArCH@N), 7.70–7.72 (2 ꢁ 1H, ArH),
7.45–7.48 (3 ꢁ 1H, ArH), 5.87 (d, J 4.0 Hz, 1H), 5.55 (d, J 5.6 Hz,
1H, OH), 5.15 (d, J 5.5 Hz, 1H, OH), 4.89 (t, J 5.5 Hz, 1H, OH), 4.41
(q, J 4.8 Hz, 1H), 4.16 (q, J 5.1 Hz, 1H), 3.98 (q, J 4.6 Hz, 1H),
3.64–3.69 (m, 1H, CH2), 3.51–3.56 (m, 1H, CH2); 13C NMR
(DMSO-d6, 100 MHz): d 156.1, 155.0, 148.9, 144.9, 134.1, 130.1,
128.7 (2 ꢁ C), 127.1 (2 ꢁ C), 91.9, 85.4, 74.4, 69.7, 61.0. HRESIMS:
calcd for [M+H]+ C15H18N5O5: 348.1308; found: 348.1304.
m 3463,
;
4.4.2. (Z)-N0-(Benzo[d][1,3]dioxol-5-ylmethylene)-1-((2R,3R,4S,-
5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1H-1,
2,4-triazole-3-carbohydrazide (7b)
1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-
furan-2-yl)-1H-1,2,4-triazole-3-carbohydrazide (5) (514 mg, 1.98
mmol, theoretical quantity) was added to 6 mL of HOAc, with stir-
ring and heating until 5 dissolved. Then benzo[d][1,3]dioxole-5-
carbaldehyde (358 mg, 2.38 mmol) and 25 mL of EtOH were added.
The reaction mixture was heated to reflux for 2 h, and then the sol-
vent was removed on a rotary evaporator. The crude residue was
washed with 1:3 EtOAc–petroleum ether and subsequently,
purified by column chromatography (silica gel; 1:2 EtOH–EtOAc)
to afford 7b as a white solid: 357 mg (61.7%); mp 190–199 °C; IR
4.4.5. (Z)-1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)-
tetrahydrofuran-2-yl)-N0-(furan-2-ylmethylene)-1H-1,2,4-triazole-
3-carbohydrazide (7e)
Compound 7e was prepared from furan-2-carbaldehyde
(318 mg, 3.3 mmol) using the same procedure as described for
7d. Purification by column chromatography resulted in 7e as a
white solid: 461 mg (66.8%); mp 243–246 °C; IR (KBr):
3258, 3222, 3127, 2951, 2881, 1670, 1621, 1328, 1250, 1126,
1078, 1031, 766, 649, 596 cmꢀ1 1H NMR (DMSO-d6, 400 MHz): d
m 3419,
(KBr):
m
3451, 3354, 3327, 3284, 3122, 2936, 2910, 1765,
;
;
1689 cmꢀ1
1H NMR (DMSO-d6, 400 MHz): d 11.87 (s, 1H, CONH–
11.93 (s, 1H, CONH–N), 8.97 (s, 1H, CH@N triazole), 8.46 (s, 1H,
ArCH@N), 7.84 (s, 1H, ArH), 6.92 (d, J 3.0 Hz, 1H, ArH), 6.63 (s,
1H, ArH), 5.86 (d, J 3.7 Hz, 1H), 5.54 (d, J 5.6 Hz, 1H, OH), 5.15 (d,
J 5.5 Hz, 1H, OH), 4.89 (t, J 5.2 Hz, 1H, OH), 4.40 (q, J 4.6 Hz, 1H),
4.16 (q, J 5.1 Hz, 1H), 3.98 (q, J 4.4 Hz, 1H), 3.64–3.69 (m, 1H,
CH2), 3.50–3.56 (m, 1H, CH2); 13C NMR (DMSO-d6, 100 MHz): d
156.6, 155.5, 149.8, 145.8, 145.5, 139.0, 114.2, 112.7, 92.4, 86.0,
75.0, 70.3, 61.6; HRESIMS: calcd for [M+H]+ C13H16N5O6:
338.1101; found: 338.1098.
N), 8.98 (s, 1H, CH@N triazole), 8.46 (s, 1H, ArCH@N), 7.28 (d, J
1.2 Hz, 1H, ArH), 7.14 (dd, J 8.1 Hz, 1.6 Hz, 1H, ArH), 6.99 (d, J
8 Hz, 1H, ArH), 6.09 (s, 2H, O–CH2–O), 5.85 (d, J 3.9 Hz, 1H), 5.60
(d, J 5.5 Hz, 1H, OH), 5.21 (d, J 5.5 Hz, 1H, OH), 4.94 (t, J 5.5 Hz,
1H, OH), 4.40 (q, J 4.8 Hz, 1H), 4.15 (q, J 5.0 Hz, 1H), 3.97 (q, J
4.6 Hz, 1H), 3.63–3.68 (m, 1H, CH2), 3.50–3.55 (m, 1H, CH2); 13C
NMR (DMSO-d6, 100 MHz): d 156.8, 155.5, 149.7, 149.3, 148.5,
145.5, 129.0, 124.1, 108.9, 105.5, 102.1, 92.5, 86.0, 72.0, 70.3,
61.6; HRESIMS: calcd for [M+H]+ C16H18N5O7: 392.1206; found:
392.1205.
4.4.6. (Z)-1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)-
tetrahydrofuran-2-yl)-N0-(2-hydroxybenzylidene)-1H-1,2,4-
triazole-3-carbohydrazide (7f)
4.4.3. (Z)-1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)-
tetrahydrofuran-2-yl)-N’-(4-methoxybenzylidene)-1H-1,2,4-
triazole-3-carbohydrazide (7c)
Compound 7c was prepared from 4-methoxybenzaldehyde
(427 mg, 3.13 mmol) using the same procedure as described for
7a. Purification of the solid resulted in 7c as a white solid:
1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-
furan-2-yl)-1H-1,2,4-triazole-3-carbohydrazide (5) (530 mg, 2.04
mmol, theoretical quantity) was added to 7 mL of HOAc, with stir-
ring and heating until 5 dissolved. Then 2-hydroxybenzaldehyde
(542 mg, 4.43 mmol) and 12 mL of EtOH were added. The reaction
mixture was heated to reflux for 4 h, and then the solvent was re-
moved on a rotary evaporator. The crude residue was washed with
1:3 EtOAc–petroleum ether and subsequently purified by column
chromatography (silica gel; 1:2 EtOH–EtOAc) to afford 7f as a
608 mg (78.7%); mp 241–244 °C; IR (KBr):
m
3445, 3345, 3134,
2964, 2928, 1698, 1604, 1254, 1081, 850, 682 cmꢀ1
;
1H NMR
(DMSO-d6, 400 MHz): d 11.76 (s, 1H, CONH–N), 8.96 (s, 1H, CH@N
triazole), 8.49 (s, 1H, ArCH@N), 7.65 (d, J 8.7 Hz, 2 ꢁ 1H, ArH), 7.02