640 Saidugari et al.
Asian J. Chem.
spectra were recorded with a PE Sciex model API 3000
instrument. All the reactions were carried out under argon
atmosphere.
Synthesis of ethyl 4-hydroxybenzoate (2): To a solution
of compound 2 (2 g, 14.48 mmol) in ethanol (20 mL) was
added sulphuric acid (0.1 mL) and refluxed for 12 h. Ethanol
was evaporated under reduced pressure and the obtained
residue was taken in ethyl acetate (30 mL), washed with 10 %
To a stirred solution of ethyl benzoates (5 mmol) in ethanol
was added hydrazine-hydrate (12.5 mmol) and refluxed for
8 h. The reaction mixture was diluted with ethyl acetate followed
by water. The organic layer was dried over sodium sulphate,
filtered and evaporated to obtain respective benzohydrazides
7a-k.
General procedure for the synthesis of hydrazone
derivatives 8a-k: To a stirred solution of compound 6 (100 mg,
3.2 mmol) in ethanol was added corresponding benzohydrazides
7a-k (3.2 mmol) and refluxed for 1 h. After cooling to room
temperature the precipitated solids were filtered and washed
with minimum quantity of ethanol and dried to obtain hydrazone
derivatives 8a-k in quantitative yields
aq. NaHCO
3
solution (3 × 15 mL) followed by water and brine
SO
solution. The organic layer was separated, dried over Na
2
4
,
filtered and evaporated to afford compound 3. Pale yellow
solid, Yield: 1.7 g, 75 %; m.p.: 114-117 °C.
Synthesis of 4-(hydroxymethyl)phenol (3): To a stirred
mixture of zinc borohydride (3 mmol of BH
4
) and THF (20
(E)-N’-[4-((3-Methyl-4-(methylsulfonyl)pyridin-2-
yl)methoxy)benzylidene]benzohydrazide (8a): White solid;
Yield: 80 %; m.p.: 118-119 °C; H NMR (400 MHz, DMSO-
mL) was added to ethyl 4-hydroxybenzoate (2) (6 mmol) and
refluxed under nitrogen for 4 h. The excess borohydride was
quenched by adding 2 mL of aqueous methanol (50 % v/v).
The solution was saturated with potassium carbonate and the
THF layer was separated. The residue was extracted with THF
1
d ): δ 11.76 (s, 1H), 8.72 (d, J = 5.2 Hz, 1H), 8.40 (s, 1H),
6
7.89 (t, J = 8.8 Hz, 3H), 7.68 (d, J = 10.4 Hz, 2H), 7.59-7.52
(m, 3H), 7.14 (d, J = 10.4 Hz, 2H), 5.42 (s, 2H), 3.34 (s, 3H),
+
and the combined extracts were dried over anhydrous K
2
CO
3
.
2.71 (s, 3H); ESI-MS: m/z, 424 (M+H) .
The solvent was removed under reduced pressure to obtain
alcohol 3. Yield: 0.52 g, 70 %; m.p.: 110-112 °C.
(E)-N’-[4-((3-Methyl-4-(methylsulfonyl)pyridin-2-
yl)methoxy)benzylidene]-3-chlorobenzohydrazide (8b):
1
Synthesis of 4-hydroxybenzaldehyde (4): A mixture of
White solid;Yield: 80 %; m.p.: 82-83 °C; H NMR (400 MHz,
4
-(hydroxymethyl)phenol (3) (7.94 mmol), Cu(OAc)
2
(0.08
DMSO-d ): δ 11.84 (s, 1H), 8.72 (d, J = 6.8 Hz, 1H), 8.40 (s,
6
mmol) and TEMPO (0.08 mmol) in acetonitrile:water was
stirred at room temperature for 3 h. After the completion of
the reaction (monitored by TLC), the reaction mixture was
diluted with dichloromethane. The organic layer was separated
and the aqueous layer was further extracted with dichloro-
methane (2 × 10 mL). The combined organic layer was dried
over sodium sulphate and concentrated to give a residue which
was purified by column chromatography (eluents: petroleum
ether:ethyl acetate = 10:1) to afford aldehyde 4. Yield: 84 %.
m.p.: 114-118 °C.
1H), 7.95 (s, 1H), 7.87 (t, J = 6.0 Hz, 2H), 7.68 (t, J = 11.2 Hz,
2H), 7.54 (t, J = 10.0 Hz, 2H), 7.14 (d, J = 11.6 Hz, 2H), 5.42
(s, 2H), 3.39 (s, 3H), 2.71 (s, 3H); ESI-MS: m/z, 458 (M+H) .
(E)-N’-[4-((3-methyl-4-(methylsulfonyl)pyridin-2-
yl)methoxy)benzylidene]-3-nitrobenzohydrazide (8c):
+
White solid; Yield: 84 %; m.p.: 128-129 °C; IR (KBr, νmax
,
-1
cm ): 3445, 3317, 3083, 3034, 2989, 2926, 2909, 1668, 1605,
1568, 1557, 1530, 1509, 1479, 1421, 1349, 1301, 1238, 1170,
1131, 1063, 1027, 1009, 960, 891, 834, 817, 807, 766, 724,
1
713, 670, 588, 567, 533, 465; H NMR (400 MHz, DMSO-
Synthesis of 4-[(3-methyl-4-(methylsulfonyl)pyridin-2-
yl)methoxy]benzaldehyde (6): To a stirred solution of aldehyde
d ): δ 12.08 (s, 1H), 8.75 (t, J = 3.6 Hz, 2H), 8.44 (s, 1H), 8.35
6
(d, J = 10.4 Hz, 2H), 7.85 (t, J = 6.0 Hz, 2H), 7.71 (d, J = 11.2
Hz, 2H), 7.16 (d, J = 11.2 Hz, 2H), 5.43 (s, 2H), 3.40 (s, 3H),
4
(1 g, 8.2 mmol) in DMF (7 mL) was added potassium carbonate
+
(1.36 g, 9.84 mmol) followed by compound 5 (1.8 g, 8.2 mmol)
2.71 (s, 3H); ESI-MS: m/z, 469 (M+H) .
and heated to 80 °C for 3 h. The reaction mixture was cooled
to room temperature and then poured into cold water to obtain
pale yellow solid, which was filtered and dried at the pump to
afford compound 6. Yield: 88 %. m.p.: 106-107 °C. White
(E)-N’-[4-((3-Methyl-4-(methylsulfonyl)pyridin-2-
yl)methoxy)benzylidene]-4-methoxybenzohydrazide (8d):
-1
White solid;Yield: 86 %; m.p.: 91-92 °C; IR (KBr, νmax, cm ):
3444, 3251, 3074, 3039, 3021, 3004, 2962, 2924, 2836, 1654,
1607, 1575, 1548, 1507, 1464, 1419, 1410, 1370, 1315, 1293,
1252, 1235, 1211, 1170, 1138, 1108, 1061, 1028, 1010, 970,
-1
solid; Yield: 84 %; m.p.: 100-101 °C; IR (KBr, νmax, cm ):
3
1
1
6
445, 3086, 3063, 3007, 2954, 2927, 2839, 2754, 1682, 1598,
509, 1470, 1416, 1404, 1367, 1304, 1260, 1238, 1219, 1164,
133, 1119, 1025, 999, 963, 888, 857, 836, 798, 765, 748,
960, 917, 889, 843, 827, 815, 802, 760, 671, 647, 621, 587,
1
566, 535, 465; H NMR (400 MHz, DMSO-d
6
): δ 11.64 (s,
1
71, 616, 588, 562, 534, 519, 511, 466; H MR (400 MHz,
1H), 8.74 (s, 1H), 8.40 (s, 1H), 7.89 (d, J = 10.0 Hz, 4H), 7.67
(d, J = 7.2 Hz, 1H), 7.14 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 9.2
Hz, 2H), 5.41 (s, 2H), 3.83 (s, 3H), 3.40 (s, 3H), 2.71 (s, 3H);
DMSO-d
6
): δ 9.90 (s, 1H), 8.72 (d, J = 6.4 Hz, 1H), 7.88 (t, J
=
12.0 Hz, 3H), 7.22 (d, J = 11.2 Hz, 2H), 5.50 (s, 2H), 3.88
+
+
(
s, 3H), 2.74 (s, 3H); ESI-MS: m/z, 306.35 (M + H) .
ESI-MS: m/z, 454 (M+H) .
General procedure for the synthesis of benzohydrazides
a-k [12,13]:A mixture of benzoic acid (6.42 mmol), catalytic
(E)-N’-[4-((3-Methyl-4-(methylsulfonyl)pyridin-2-
yl)methoxy)benzylidene]-3,4,5-trimethoxybenzohydrazide
(8e): Pale yellow solid; Yield: 86 %; m.p.: 128-129 °C; IR
7
quantity of conc. H SO in ethanol was heated to reflux for 10
2
4
-1
h. The reaction mixture was diluted with ethyl acetate followed
by water. The organic layer was washed with saturated
(KBr, νmax, cm ): 3444, 3251, 3074, 3039, 3021, 3004, 2962,
2924, 2836, 1654, 1607, 1575, 1548, 1507, 1464, 1419, 1410,
1370, 1315, 1293, 1252, 1235, 1211, 1170, 1138, 1108, 1061,
1028, 1010, 970, 960, 917, 889, 843, 827, 815, 802, 760, 671,
NaHCO followed by water and brine solution. The organic
3
layer was dried over sodium sulphate, filtered and evaporated
to obtain respective ethyl benzoates.
1
647, 621, 587, 566, 535, 465; H NMR (400 MHz, DMSO-