Synthesis of 3-acetyl-4-hydroxy-1-phenylpyridin-2(1H)-one derivatives

Article abstract of DOI:10.1002/jhet.2030

The cyclization of aryl ketone anilides 3 with diethyl malonate to affords 4-hydroxy-6-phenyl-6H-pyrano [3,2-c]-pyridin-2,5-diones 4 in good yields. 3-Acetyl-4-hydroxy-1-phenylpyridin-2(1H)-ones 5 are obtained by ring-opening reaction of 4-hydroxy-6-pheny

Full text of DOI:10.1002/jhet.2030

Month 2014
Synthesis of 3-Acetyl-4-hydroxy-1-phenylpyridin-2(1H)-one Derivatives
a
b
*
B. P. Nikam and T. Kappe
aDepartment of Chemistry, College of Engineering and Polytechnic, Sakharale, Tal. Walwa, Dist. Sangli M.S. 414 415, India
bOrganic Synthesis Group, Institute of Organic Chemistry, Karl-Franzens University of Graz, Heinrichstrabe 28, A-8010
Graz, Austria
*
E-mail: bpnikam@yahoo.co.in
Received November 13, 2012
DOI 10.1002/jhet.2030
Published online in Wiley Online Library (wileyonlinelibrary.com).
The cyclization of aryl ketone anilides 3 with diethyl malonate to affords 4-hydroxy-6-phenyl-6H-pyrano
[3,2-c]-pyridin-2,5-diones 4 in good yields. 3-Acetyl-4-hydroxy-1-phenylpyridin-2(1H)-ones 5 are obtained
by ring-opening reaction of 4-hydroxy-6-phenyl-6H-pyrano[3,2-c]-pyridin-2,5-diones 4 in the presence of
1,2-diethylene glycol. The reaction of 3-acetyl-4-hydroxy-1-phenylpyridin-2(1H)-ones 5 with hydroxyl-
amine hydrochloride produces 4-hydroxy-3-[N-hydroxyethanimidoyl]-1-phenylpyridin-2(1H)-ones 6 from
which 3-alkyloxyiminoacetyl-4-hydroxy-1-phenylpyridin-2(1H)-ones 7 are obtained by reacting with alkyl
bromides or iodides in the presence of anhydrous potassium carbonate with moderate yields. The similar
compounds can be synthesized on refluxing 3-acetyl-4-hydroxy-1-phenylpyridin-2(1H)-ones 5 with
substituted hydroxylamine hydrochloride in the presence of sodium bicarbonate with good yields. Most of
the synthesized compounds are characterized by IR and NMR spectroscopic methods.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
[15]. The degradation of pyranopyridinones in sodium
hydroxide and diethylene glycol yields the 3-acetyl-4-
hydroxy-1-phenylpyridin-2(1H)-ones.
These remarkable importance of 4-hydroxy-pyridin-2-one
derivatives and part of developing new synthetical
compounds enthused us to develop new methods for
the synthesis of 3-acetyl-4-hydroxy-1-phenylpyridin-2
(1H)-one derivatives.
4-Hydroxy-pyridon-2-ones are the important class of
pyridine derivatives. These compounds are found in
natural products having important biological activities such
as flavipucin [1], tenellin [2], mocimycin [3], ilicicolin [4],
and sambutoxin [5]. 4-Hydory-pyridon-2-ones are also
used for the synthesis of nucleotides [6]. Some of them
are showing herbicidal activity [7]. The earlier X-ray
diffraction studies [8–10] have confirmed that 4-hydroxy-
2-pyridones are more stable than 2-hydroxy-4-pyridones.
The synthesis of 4-hydroxy-2-pyridones via condensation
of enamines or azomethines with reactive malonic acid
derivatives has been reported [11,12].
4-Hydroxy-2-pyridones with aliphatic acyl groups in posi-
tion 3 have found much interest because of their biological
properties [13]. A number of methods have been reported
for the acylation of 4-hydroxy-2-pyridinones [14]. To obtain
3-acetyl-4-hydroxy-2-pyridinones, we have adopted the
method in which azomethines are refluxed with two equiva-
lents of diethyl malonate to yield pyranopyridinones. These
pyronopyridones are excellent intermediates in the synthesis
of number of compounds having potential biological activity
RESULTS AND DISCUSSION
The new method for the synthesis of strecker type inter-
mediates 2a–e is introduced. The nitrile compounds 2a–e
(Table 1) are obtained in excellent yields (85–100%) by
adding sodium cyanide to a cooled mixture of ketone 1a–e
and aniline in glacial acetic acid [15]. Elimination of HCN
from 2a–e to yield 3a–e has been accomplished with
potassium hydroxide in refluxing methanol [16]. This
method yields the pure azomethines 3a–e (Table 2), which
can be used for further reactions. The mechanism of this
reaction has been investigated in kinetic study [17]. It has
also been reported that nitrile compounds of type 2a–e
© 2014 HeteroCorporation

B. P. Nikam and T. Kappe
Vol 000
undergo pyrolytic elimination of HCN at 210ꢀC to afford the
azomethines 3a–e [18].
Table 1
Experimental data of nitriles 2.
The azomethines can be condensed with substituted
dialkylmalonates to give 4-hydroxy-2-pyridones in moderate
to good yields [19–21]. The present paper shows that the
condensation of azomethines 3a–e with diethyl malonate
satisfactory yields the substituted 4-hydroxy-6-phenyl-6H-
pyrano[3,2-c]pyridin-2,5-diones 4a–e. Because of lower
reactivity of alkyl malonates, reaction time had to rise to
several hours. A solution of pyranopyridinedione compounds
4a–e with 1,2-diethylene glycol was refluxed with sodium
hydroxide and acidified strongly with hydrochloric acid to
afford the important 3-acetyl-4-hydroxy-1-phenylpyridin-2
(1H)-ones 5a–e (Scheme 1) with good yields.
Yield
(%)
mp (ꢀC)
solvent
Molecular
formula
R
R1
H
2a
2b
2c
Ph
Ph
Ph
85
96
158–160ꢀC
petroleum ether
141–142ꢀC
C15H14N2
C16H16N2
C17H18N2
C12H16N2
C13H18N2
Methyl
Ethyl
H
petroleum ether
100
98
159–160ꢀC
petroleum ether
55–57ꢀC
2d i-Propyl
petroleum ether
2e
i-Butyl
H
92
105–106ꢀC
petroleum ether
The pyridine compounds 5a–e were directly converted
into 3-alkyloxyiminoacetyl-4-hydroxy-1-phenylpyridin-2
(1H)-ones 7a–e or via the conversion into 4-hydroxy-3-
hydroxyliminoacetyl-1-phenylpyridin-2(1H)-ones 6a–e.
The pyridine compounds 5a–e on reaction with hydroxyl
amine hydrochloride in the presence of sodium bicarbonate
yield 4-hydroxy-3-hydroxyliminoacetyl-1-phenylpyridin-2
(1H)-ones 6a–e. The oxime compounds 6a–e on reaction
with alkyl bromides or iodides in the presence of anhydrous
potassium carbonate convert into 3-alkyloxyiminoacetyl-
4-hydroxy-1-phenylpyridin-2(1H)-ones 7a–e with moder-
ate yield. To improve the yield of compounds 7a–e, the
pyridine compounds 5a–e were directly converted into
3-alkyloxyiminoacetyl-4-hydroxy-1-phenylpyridin-2(1H)-
ones 7a–e (Scheme 2) by refluxing with substituted
Table 2
Experimental data of azomethines 3.
Yield
Molecular
formula
R
R1
H
(%)
90
91
81
91
77
mp (ꢀC) solvent
3a
3b
3c
Ph
Ph
Ph
42–43ꢀC
petroleum ether
50–52ꢀC
petroleum ether
K
petroleum ether
K
petroleum ether
K
C14H13
C15H15
C16H17
C11H15
C12H17
N
N
N
N
N
Methyl
Ethyl
H
p30185–187ꢀC
3d i-Propyl
3e i-Butyl
p30153–154ꢀC
H
p30160–162ꢀC
petroleum ether
Scheme 2
Scheme 1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of 3-Acetyl-4-hydroxy-1-phenylpyridin-2(1H)-one Derivatives
4-Hydroxy-6,7-diphenyl-6H-pyrano[3,2-c]pyridine-2,5-dione
(4a). 58 g (50%), mp 293–296ꢀC (DMF); 1H NMR (DMSO): d
6.13 (m, 1, Ar-H), 6.4 (s, 1, Ar-H), 7.00–7.30 (m, 10, Ar-H), 15.0
(d, 1, OH). Anal. Calcd for C20H13NO4 (331.32): C, 72.50; H,
3.95; N, 4.23. Found: C, 72.48; H, 3.94.40; N, 4.22%.
hydroxyl amines in presence of sodium bicarbonate with
better yields.
CONCLUSION
4-Hydroxy-8-methyl-6,7-diphenyl-6H-pyrano[3,2-c]pyridine-
2,5-dione (4b). 45.8 g (70%), mp 271–272ꢀC (acetic acid); IR
(KBr) nmax/cmÀ1: 3060 w, 1725 s, 1670 s, 1600 s, 1550 m,
In conclusion, we have reported an efficient method for
synthesizing variety of substituted 3-acetyl-4-hydroxy-1-
phenylpyridin-2(1H)-ones and its derivatives. The main
practical importance of this reaction is that to report a better
method to synthesize 3-alkyloxyiminoacetyl-4-hydroxy-1-
phenylpyridin-2(1H)-ones.
1
1480 m; H NMR (DMSO): d 1.89 (s, 3, CH3), 5.63 (s, 1, Ar-
CH3), 7.20–7.30 (m, 10, Ar-H). Anal. Calcd for C21H15NO4
(345.35): C, 73.04; H, 4.38; N, 4.06. Found: C, 73.16; H, 4.40;
N, 4.01%.
8-Ethyl-4-hydroxy-6,7-diphenyl-6H-pyrano[3,2-c]pyridine-
2,5-dione (4c).
33.5g (58%), mp 218–219ꢀC (acetic acid); IR
(KBr) nmax/cmÀ1: 3060–2940 w, 1725 s, 1670 s, 1600 w, 1550 s;
1H NMR (DMSO): d 1.00 (t, J=7Hz, 3, CH3), 2.26 (q, J=7.5Hz,
2, CH2), 5.60 (s, 3, Ar-CH3), 7.20–7.40 (m, 10, Ar-H), 13.38 (s, 1,
OH). Anal. Calcd for C22H17NO4 (359.37): C, 73.53; H, 4.77; N,
3.90. Found: C, 73.22; H, 4.87; N, 3.80%.
EXPERIMENTAL
The melting points were determined in open capillary tubes
on a Gallenkamp melting point apparatus, MFB 595. The IR
spectra were recorded on PerkinElmer 298 spectrophotometer
using samples in potassium bromide disks. The 1H NMR
spectra (200 MHz) were obtained on a Varian EM-360
spectrometer at 60 MHz with TMS as an internal standard and
4-Hydroxy-7-isopropyl-6-phenyl-6H-pyrano[3,2-c]pyridine-
2,5-dione (4d).
20 g (31%), mp 205–207ꢀC (acetic acid).
7-tert-Butyl-4-hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-
2,5-dione (4e). 6.2 g (40%), mp 243–244ꢀC (acetic acid); IR
(KBr) nmax/cmÀ1: 2980 w, 1760 s, 1680 s, 1600 w, 1580 m,
1
are given in d units. The solvent for H NMR was DMSO-d6.
Microanalysis was performed on a Carlo Ebra 1106 analyzer.
All reactions were monitored by thin layer chromatography
and carried out on 0.2 mm silica gel 60 F-254 (Merck) plates
using UV light (254 and 366 nm) for detection. Commercially
available (E. Merck) chemicals were used without further puri-
fication. The UV, IR and C, H, and N analysis were carried out
at Institute of Organic Chemistry, Karl-Franzens University,
Graz (Austria).
1
1480 s; H NMR (DMSO): d 1.10 (s, 9, 3CH3), 5.50 (s, 1, Ar-
H), 6.80 (s, 1, Ar-H8), 7.40–7.70 (m, 5, Ar-H), 12.80 (s, 1,
OH). Anal. Calcd for C18H17NO4 (311.33): C, 69.44; H, 5.50;
N, 4.50. Found: C, 69.34; H, 5.44; N, 4.42%.
Synthesis of 3-acetyl-4-hydroxy-1-phenylpyridin-2(1H)-
ones (5a–e).
General method: a solution of 4-hydroxy-6-
phenyl-6H-pyrano[3,2-c]pyridine-2,5-dione 4a–e (0.045 mole)
and 1,2-diethylene glycol (270 mL), and 18 g sodium hydroxide
in 27 mL water was placed in 500 mL round bottom flask and
refluxed with stirring for 1 h. The solution was then cooled and
added to 1.5 L of ice–water. The solution was acidified with
conc. hydrochloric acid to pH = 1. The product was then
filtered, dried, and crystallized to yield respective 3-acetyl-4-
hydroxy-1-phenylpyridin-2(1H)-ones 5a–e. The compounds
5a–e together with their physical constants are listed in the
succeeding text.
Synthesis of 2-(phenylamino)-nitriles (2a–e).
General
method: a solution of ketone 1a–e (0.3 mole) and aniline
(33.5 g, 0.36 mole) in 125 mL glacial acetic acid was cooled to
5ꢀC, and then, sodium cyanide (26.7 g) was added portion-wise
with stirring for a period of 1 h. Then, it was stirred for 12 h at
room temperature. It was then poured on ice–water. The product
comes out, which was then filtered, washed with petroleum
ether, and dried in air to yield respective nitriles 2a–e. The
results of this reaction are reported in Table 1.
3-Acetyl-4-hydroxy-1,6-diphenylpyridin-2(1H)-one (5a). 12.96 g
Synthesis of N-alkylidene-benzamines (3a–e).
General
(95%), mp 120–122ꢀC (ethanol).
method: 2-(phenyamino)-nitrile 2a–e (0.3 mole) was boiled in
400 mL of methanol, and then, potassium hydroxide (64.4 g)
dissolved in 500 mL methanol was added through the
condenser. The solution was then heated for 1 h under reflux.
Then, it was diluted with 800 mL water and extracted with
4 Â 500 mL petroleum ether. Organic layer is then dried over
sodium sulfate for overnight and evaporated on rotary vapor
until dryness. The results of this reaction are reported in Table 2.
Synthesis of 4-hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-
3-Acetyl-4-hydroxy-5-methyl-1,6-diphenylpyridin-2(1H)-
one (5b).
22 g (95%), mp 203–204ꢀC (ethanol); IR (KBr)
n
max/cmÀ1: 3030–2930 w, 1675 s, 1620 s, 1600 m, 1550 m;
1H NMR (DMSO): d 1.70 (s, 3, CH3), 2.68 (s, 3, CH3
acetyl), 7.10–7.30 (m, 10, Ar-H). Anal. Calcd for
C20H17NO3 (319.35): C, 75.22; H, 5.37; N, 4.39. Found: C,
75.23; H, 5.33; N, 4.31%.
3-Acetyl-5-ethyl-4-hydroxy-1,6-diphenylpyridin-2(1H)-one
(5c).
15g (90%), mp 163–164ꢀC (ethanol). Anal. Calcd for
2,5-diones (4a–e).
General method: a solution of N-
C21H19NO3 (333.38): C, 75.66; H, 5.75; N, 4.20. Found: C,
75.78; H, 5.70; N, 4.15%.
alkylidene-benzamine 3a–e (0.35 mole) and diethyl malonate
(112 g, 0.7 mole) in diphenyl ether (150 mL) placed in 500 mL
round bottom flask fitted with vigorous distillation column and
distillation assembly. It was then heated to 250–270ꢀC in oil
bath until 75–80 mL of ethanol was collected. It was then
cooled, digested with methanol, filtered, and washed with
methanol and diethyl ether. The solid product was then
crystallized to yield respective 4-hydroxy-6-phenyl-6H-
pyrano[3,2-c]pyridine-2,5-diones 4a–e. Compounds 4a–e
together with their physical constants are listed in the
succeeding text.
3-Acetyl-4-hydroxy-6-isopropyl-1-phenylpyridin-2(1H)-one
(5d).
12.4 g (85%), mp 160–161ꢀC (ethanol).
6-tert-Butyl-3-acetyl-4-hydroxy-1-phenylpyridin-2(1H)-
one (5e).
n
10 g (91%), mp 160–161ꢀC (ethanol); IR (KBr)
1
max/cmÀ1: 2980 w, 1680 s, 1620 s, 1600m, 1520 m; H NMR
(DMSO): d 1.10 (s, 9, 3CH3), 2.50 (s, 3, CH3 acetyl), 6.20 (s, 1,
Ar-H5), 7.30–7.60 (m, 5, Ar-H), 15.43 (s, 1, OH). Anal. Calcd for
C17H19NO3 (285.34): C, 71.56; H, 6.71; N, 4.91. Found: C,
71.78; H, 6.70; N, 4.88%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. P. Nikam and T. Kappe
Vol 000
Synthesis of 4-hydroxy-3-[N-hydroxyethanimidoyl]-1-
phenylpyridin-2(1H)-ones (6a–e). General method:
3-[1-Ethoxyiminoethyl]-4-hydroxy-1,6-diphenylpyridin-2(1H)-
one (7b). A solution of 4-hydroxy-3-[1-(hydroxyimino)ethyl]-
1,6-diphynyl-1,2-dihydropyridin-2-one 6a (3.2g, 0.01 mole), ethyl
iodide (1.56g, 0.01mole), and anhydrous potassium carbonate
(1.38 g, 0.01 mole) in ethanol (50 mL) was refluxed for 6 h. The
solution was then cooled; 25 mL water was added and
neutralized with glacial acetic acid. The solid product separated
on keeping was filtered, washed with EtOH–H2O (2:1), dried,
and crystallized to yield 1.87 g (54%), mp 131–132ꢀC
(ethanol); IR (KBr) nmax/cmÀ1: 3400 w, 3050 w, 1650 m, 1600
w, 1570 s, 1490 s; 1H NMR (DMSO): d 1.30 (t, J = 7 Hz, 3,
CH3), 2.15 (s, 3, CH3 acetyl), 4.15 (q, J = 7 Hz, 2, CH2), 6.08
(s, 1, Ar-H5), 7.10–7.30 (m, 10, Ar-H), 11.70 (s, 1, OH). Anal.
Calcd for C21H20N2O3 (348.4): C, 72.40; H, 5.79; N, 8.04.
Found: C, 72.57; H, 5.74; N, 8.07%.
a
solution of 3-acetyl-4-hydroxy-1-phenylpyridin-2(1H)-one 5a–e
(0.015 mole), hydroxylamine hydrochloride (1.25 g, 0.018 mole),
and sodium bicarbonate (1.51 g, 0.018 mole) was refluxed in
75 mL EtOH–H2O (2:1) mixture for 1 h. On cooling, the product
crystallizes, which was then filtered, dried, and crystallized to yield
respective 4-hydroxy-3-[1-(hydroxyimino)ethyl]-1,6-diphynyl-1,2-
dihydropyridin-2-ones 6a–e. The compounds 6a–e together with
their physical constants are listed in the succeeding text.
4-Hydroxy-3-[1-(hydroxyimino)ethyl]-1,6-diphynyl-1,2-
dihydropyridin-2-one (6a).
4.1 g (86%), mp 228–229ꢀC
(ethanol); IR (KBr) nmax/cmÀ1: 3190 w, 1645m, 1605 w, 1560 w,
1
1400m; H NMR (DMSO): d 2.25 (s, 3, CH3 acetyl), 6.05 (s, 1,
Ar-H5), 7.10–7.30 (m, 10, Ar-H), 11.25 (s, 1, OH). Anal. Calcd
for C19H16N2O3 (320.34): C, 71.24; H, 5.03; N, 8.75. Found: C,
71.53; H, 5.04; N, 8.69%.
3-[1-Benzyloxyiminoethyl]-4-hydroxy-1,6-diphenylpyridin-2
(1H)-one (7c).
A solution of 4-hydroxy-3-[1-(hydroxyimino)
ethyl]-1,6-diphynyl-1,2-dihydropyridin-2-one 6a (3.2 g, 0.01 mole),
benzyl bromide (1.71 g, 0.01mole), and anhydrous potassium
carbonate (1.38g, 0.01 mole) in ethanol (25 mL) was refluxed for
6 h. The solution was then cooled; 25 mL water was added and
neutralized with glacial acetic acid. The solid product separated
on keeping was filtered, washed with EtOH–H2O (2:1), dried, and
crystallized to yield 2.65 g (65%), mp 137–138ꢀC (ethanol); IR
4-Hydroxy-3-[N-hydroxyethanimidoyl]-5-methyl-1,6-
diphenylpyridin-2(1H)-one (6b). 5.38 g (81%), mp 221–222ꢀC
(ethanol); IR (KBr) nmax/cmÀ1: 3170 m, 1640 s, 1600 s, 1550 m,
1490 s; 1H NMR (DMSO): d 1.71 (s, 3, CH3), 2.40 (s, 3, CH3 acetyl),
7.05–7.30 (m, 10, Ar-H). Anal. Calcd for C20H18N2O3 (334.37): C,
71.84; H, 5.43; N, 8.38. Found: C, 71.22; H, 5.41; N, 8.23%.
5-Ethyl-4-hydroxy-3-[N-hydroxyethanimidoyl]-1,6-
diphenylpyridin-2(1H)-one (6c). 2.5 g (72%), mp 208–209ꢀC
(acetic acid); 1H NMR (DMSO): d 0.94 (t, J = 7 Hz, 3, CH3), 2.12
(q, J = 7.5 Hz, 2, CH2), 2.38 (s, 3, CH3 acetyl), 7.00–7.30 (m, 10,
Ar-H), 11.40 (s, 1 OH), 14.0 (s, 1, OH). Anal. Calcd for
C21H20N2O3 (348.4): C, 72.40; H, 5.79; N, 8.04. Found: C,
72.27; H, 5.81; N, 7.97%.
1
(KBr) nmax/cmÀ1: 3060 w, 1660 m, 1570 w, 1500 w; H NMR
(DMSO): d 2.20 (s, 3, CH3 acetyl), 5.15 (s, 2, CH2), 6.05 (s, 1,
Ar-H5), 7.10–7.50 (m, 15, Ar-H), 11.50 (s, 1, OH). Anal. Calcd
for C26H22N2O3 (410.46): C, 76.08; H, 5.40; N, 6.83. Found: C,
76.11; H, 5.53; N, 6.68%.
3-[1-Allyloxyiminoethyl]-4-hydroxy-1,6-diphenylpyridin-2(1H)-
one (7d). A solution of 4-hydroxy-3-[1-(hydroxyimino)ethyl]-
1,6-diphynyl-1,2-dihydropyridin-2-one 6a (3.2g, 0.01 mole), allyl
bromide (1.21 g, 0.01mole), and anhydrous potassium carbonate
(1.38 g, 0.01 mole) in ethanol (25 mL) was refluxed for 6 h. The
solution was then cooled; 25mL water was added and neutralized
with glacial acetic acid. The solid product separated on keeping
was filtered, washed with EtOH–H2O (2:1), dried, and crystallized
to yield 2.53 g (79%), mp 97–98ꢀC (ethanol+ water); IR (KBr)
4-Hydroxy-3-[N-hydroxyethanimidoyl]-1-phenyl-6-(propan-
2-yl)pyridin-2(1H)-one (6d).
5.62 g (53%), mp 194–195ꢀC
(ethanol); IR (KBr) nmax/cmÀ1: 3140-2970 w, 1640 s, 1600 m,
1560 m, 1400 s; 1H NMR (DMSO): d 1.30 (d, J = 8 Hz, 6, 2CH3),
2.25 (s, 3, CH3 acetyl), 2.35 (m, 1, CH), 6.05 (s, 1, Ar-H5),
7.25–7.60 (m, 5, Ar-H), 11.20 (s, 1, OH). Anal. Calcd for
C16H18N2O3 (286.33): C, 67.12; H, 6.34; N, 9.78. Found: C,
67.14; H, 6.35; N, 9.67%.
n
max/cmÀ1: 3080 w, 3060 s, 2920 w, 2870 w, 1650 m, 1610 m,
6-tert-Butyl-4-hydroxy-3-[N-hydroxyethanimidoyl]-1-
1
phenylpyridin-2(1H)-one (6e).
3.5 g (58%), mp 195–196ꢀC
1570 w, 1500s; H NMR (DMSO): d 2.15 (s, 3, CH3 acetyl),
4.61 (d, J = 5 Hz, 2, CH2 allyl), 5.29 (t, J = 7 Hz, 2, CH2), 5.40
(m, 1, CH), 6.05 (s, 1, Ar-H5), 7.10–7.30 (m, 10, Ar-H), 11.65
(s, 1, OH). Anal. Calcd for C22H20N2O3 (360.41): C, 73.32; H,
5.59; N, 7.77. Found: C, 73.52; H, 5.62; N, 7.71%.
(ethanol); IR (KBr) nmax/cmÀ1: 3200-2980 w, 1640 s, 1610 w,
1
1550m, 1490 m, 1370 s, 1030 s; H NMR (DMSO): d 1.04 (s, 9,
3CH3), 2.19 (s, 3, CH3 acetyl), 6.15 (s, 1, Ar-H5), 7.20–7.60
(m, 5, Ar-H), 11.20 (s, 1, OH), 12.90 (s, 1, OH). Anal. Calcd for
C17H20N2O3 (300.35): C, 67.98; H, 6.71; N, 9.33. Found: C,
68.12; H, 6.74; N, 9.20%.
3-[1-Ethoxyiminoethyl]-4-hydroxy-5-methyl-1,6-diphenylpyridin-
2(1H)-one (7e).
A
solution
of
4-hydroxy-3-[N-
hydroxyethanimidoyl]-5-methyl-1,6-diphenylpyridin-2(1H)-one 6b
(3.34 g, 0.01 mole), ethyl iodide (1.55 g, 0.01 mole), and
anhydrous potassium carbonate (0.7g, 5 mmole) in ethanol
(25 mL) was refluxed for 6 h. The solution was then cooled;
25mL water was added and neutralized with glacial acetic acid.
The solid product separated on keeping was filtered, washed with
EtOH–H2O (2:1), dried, and crystallized to yield 2.5 g (69%), mp
Synthesis of 3-alkyloxyiminoacetyl-4-hydroxy-1-phenylpyridin-
2(1H)-one compounds by reacting with alkyl bromides or iodides
4-Hydroxy-3-(1-methoxyiminoethyl)-1,6-diphenylpyridin-2
(1H)-one (7a).
A solution of 4-hydroxy-3-[1-(hydroxyimino)
ethyl]-1,6-diphynyl-1,2-dihydropyridin-2-one 6a (3.2 g, 0.01 mole),
methyl iodide (1.42 g, 0.01 mole), and anhydrous potassium
carbonate (1.38 g, 0.01 mole) in ethanol (30 mL) was refluxed
for 8 h. The solution was then cooled; 25 mL water was added
and neutralized with glacial acetic acid. The solid product
separated on keeping was filtered, washed with EtOH–H2O
(2:1), dried, and crystallized to yield 1.17 g (50%), mp 116–117ꢀC
(ethanol); IR (KBr) nmax/cmÀ1: 1660 s, 1570m, 1490s, 1390 m;
1H NMR (DMSO): d 2.20 (s, 3, CH3 acetyl), 3.88 (s, 3, CH3),
6.07 (s, 1, Ar-H5), 7.10–7.30 (m, 10, Ar-H). Anal. Calcd for
C20H18N2O3 (334.37): C, 71.84; H, 5.43; N, 8.38. Found: C,
71.33; H, 5.10; N, 8.54%.
1
117–118ꢀC (ethanol); H NMR (DMSO): d 1.31 (t, J = 7 Hz, 3,
CH3), 1.72 (s, 3, CH3), 2.34 (s, 3, CH3 acetyl), 4.22 (q, J = 7 Hz,
2, CH2), 7.10–7.30 (m, 10, Ar-H), 12.95 (s, 1, OH). Anal. Calcd
for C22H22N2O3 (362.42): C, 72.91; H, 6.12; N, 7.73. Found: C,
73.12; H, 6.23; N, 7.63%.
3-[1-Benzyloxyiminoethyl]-4-hydroxy-5-methyl-1,6-
diphenylpyridin-2(1H)-one (7f). A solution of 4-hydroxy-3-[N-
hydroxyethanimidoyl]-5-methyl-1,6-diphenylpyridin-2(1H)-one 6b
(2.39 g, 7 mmole), benzyl bromide (1.26 g, 7 mole), and anhydrous
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of 3-Acetyl-4-hydroxy-1-phenylpyridin-2(1H)-one Derivatives
H2O (2:1) was heated under reflux for 2 h. On cooling, the
product was crystallized, filtered, dried, and recrystallized to
yield 2.70 g (64%), mp 116–117ꢀC (ethanol).
potassium carbonate (1.04 g, 7 mmole) in ethanol (30 mL) was
refluxed for 6 h. The solution was then cooled; 25 mL water was
added and neutralized with glacial acetic acid. The solid product
separated on keeping was filtered, washed with EtOH/H2O (2:1),
dried, and crystallized to yield 1.75 g (58%), mp 116–117ꢀC
3-[1-Allyloxyiminoethyl]-4-hydroxy-5-methyl-1,6-diphenylpyridin-
2(1H)-one (7g). A solution of 3-acetyl-4-hydroxy-5-methyl-1,6-
diphenylpyridin-2(1H)-one 5b (3.19 g, 0.01 mole), allyloxylamine
hydrochloride (1.3g, 12mmole), and sodium bicarbonate (1.01 g,
12mmole) in 45 mL EtOH–H2O (2:1) was heated under reflux for
2 h. On cooling, the product was crystallized, filtered, dried, and
recrystallized to yield 3.10 g (83%), mp 95–96ꢀC (ethanol + water).
3-[1-Ethoxyiminoethyl]-5-ethyl-4-hydroxy-1,6-diphenylpyridin-
2(1H)-one (7h). A solution of 3-acetyl-5-ethyl-4-hydroxy-1,6-
diphenylpyridin-2(1H)-one 5c (3.33g, 10mmole), ethoxylamine
hydrochloride (1.17 g, 12mmole), and sodium bicarbonate
(1.01 g, 12mmole) in 45mL EtOH–H2O (2:1) was heated under
reflux for 1 h. On cooling, the product was crystallized, filtered,
dried, and recrystallized to yield 2.95g (79%), mp 145–146ꢀC
(ethanol+ water); IR (KBr) nmax/cmÀ1: 2980 w, 1650 s, 1605 w,
1
(ethanol); H NMR (DMSO): d 1.67 (s, 3, CH3), 2.37 (s, 3, CH3
acetyl), 5.24 (s, 2, CH2), 7.00–7.50 (m, 15, Ar-H), 12.55 (s, 1,
OH). Anal. Calcd for C27H24N2O3 (424.49): C, 76.40; H, 5.70; N,
6.60. Found: C, 76.86; H, 5.75; N, 6.58%.
3-[1-Allyloxyiminoethyl]-4-hydroxy-5-methyl-1,6-diphenylpyridin-
2(1H)-one (7g).
A
solution of 4-hydroxy-3-[N-
hydroxyethanimidoyl]-5-methyl-1,6-diphenylpyridin-2(1H)-one 6b
(2.68 g, 8 mmole), allyl bromide (0.96g, 8 mmole), and anhydrous
potassium carbonate (1.10g, 8 mmole) in ethanol (35mL) was
refluxed for 6 h. The solution was then cooled; 25mL water was
added and neutralized with glacial acetic acid. The solid product
separated on keeping was filtered, washed with EtOH–H2O (2:1),
dried, and crystallized to yield 2.3 g (67%), mp 95–96ꢀC
(ethanol + water); IR (KBr) nmax/cmÀ1: 2920 w, 1650 s, 1610 m,
1550m, 1220m; 1H NMR (DMSO): d 1.70 (s, 3, CH3), 2.35
(s, 3, CH3 acetyl), 4.69 (d, J = 5 Hz, 2, CH2allyl), 5.38 (m, 2,
CH2), 6.05 (m, 1, CH), 7.00–7.25 (m, 10, Ar-H), 12.70 (s, 1,
OH). Anal. Calcd for C23H22N2O3 (374.43): C, 73.78; H, 5.92; N,
7.48. Found: C, 73.97; H, 5.99; N, 7.30%.
1
1550 m, 1210s; H NMR (DMSO): d 0.94 (t, J = 7 Hz, 3, CH3
ethyl), 1.30 (t, J = 7 Hz, 3, CH3 ethyloxy), 2.12 (q, J = 7.5Hz, 2,
CH2), 2.33 (s, 3, CH3 acetyl), 4.22 (q, J = 7 Hz, 2, CH2 ethyloxy),
7.00–7.25 (m, 10, Ar-H), 12.95 (s, 1, OH). Anal. Calcd for
C23H24N2O3 (376.45): C, 73.38; H, 6.43; N, 7.44. Found: C,
73.49; H, 6.63; N, 7.12%.
3-[1-Benzyloxyiminoethyl]-5-ethyl-4-hydroxy-1,6-diphenylpyridin-
Synthesis of 3-alkyloxyiminoacetyl-4-hydroxy-1-phenylpyridin-
2(1H)-one compounds by reacting with alkyloxyamino
hydrochlorides
2(1H)-one (7i).
A solution of 3-acetyl-5-ethyl-4-hydroxy-1,6-
diphenylpyridin-2(1H)-one 5c (3.33 g, 0.01 mole), benzyloxylamine
hydrochloride (1.9 g, 12 mmole), and sodium bicarbonate
(1.01 g, 12 mmole) in 45 mL EtOH–H2O (2:1) was heated
under reflux for 1 h. On cooling, the product was crystallized,
filtered, dried, and recrystallized to yield 3.44 g (79%), mp
3-[1-Ethoxyiminoethyl]-4-hydroxy-1,6-diphenylpyridin-2(1H)-
one (7b). A solution of 3-acetyl-4-hydroxy-1,6-diphenylpyridin-
2(1H)-one 5a (4.58 g, 15mmole), ethoxylamine hydrochloride
(1.766g, 18mmole), and sodium bicarbonate (1.51 g, 18mmole)
in 75mL EtOH–H2O (2:1) was heated under reflux for 1 h. On
cooling, the product was crystallized, filtered, dried, and
recrystallized to yield 3.65g (70%), mp 131–132ꢀC (ethanol).
3-[1-Benzyloxyiminoethyl]-4-hydroxy-1,6-diphenylpyridin-2
129–130ꢀC (ethanol + water); IR (KBr)
n : 3060
max/cmÀ1
1
w, 1650 s, 1605 m, 1550 m, 1400 m; H NMR (DMSO): d 0.91
(t, J = 7 Hz, 3, CH3), 2.10 (q, J = 7.5 Hz, 2, CH2), 2.36 (s, 3,
CH3 acetyl), 5.25 (s, 2, CH2 benzyl), 7.00–7.50 (m, 15, Ar-H),
12.57 (s, 1, OH). Anal. Calcd for C28H26N2O3 (438.52): C,
76.69; H, 5.98; N, 6.39. Found: C, 76.56; H, 5.99; N, 6.27%.
3-[1-Allyloxyiminoethyl]-5-ethyl-4-hydroxy-1,6-diphenylpyridin-
(1H)-one (7c).
A
solution of 3-acetyl-4-hydroxy-1,6-
diphenylpyridin-2(1H)-one 5a (4.58 g, 15mmole), benzoxylamine
hydrochloride (2.85 g, 18mmole), and sodium bicarbonate (0.92 g,
10mmole) in 50 mL EtOH–H2O (2:1) was heated under reflux for
1 h. On cooling, the product was crystallized, filtered, dried, and
recrystallized to yield 3.84 g (94%), mp 137–138ꢀC (ethanol).
3-[1-Allyloxyiminoethyl]-4-hydroxy-1,6-diphenylpyridin-2
2(1H)-one (7j).
A solution of 3-acetyl-5-ethyl-4-hydroxy-1,6-
diphenylpyridin-2(1H)-one 5c (3.33 g, 10 mmole), allyloxylamine
hydrochloride (1.31 g, 12mmole), and sodium bicarbonate
(1.01 g, 12mmole) in 45mL EtOH–H2O (2:1) was heated under
reflux for 1 h. On cooling, the product was crystallized, filtered,
dried and recrystallized to yield 2.58g (67%), mp 128–129ꢀC
(ethanol+ water); IR (KBr) nmax/cmÀ1: 3060 w, 1650 s, 1605 w,
(1H)-one (7d).
A solution of 3-acetyl-4-hydroxy-1,6-
diphenylpyridin-2(1H)-one 5a (4.58 g, 15 mmole), allyloxylamine
hydrochloride (1.84 g, 17 mmole), and sodium bicarbonate
(1.43 g, 17mmole) in 45mL EtOH–H2O (2:1) was heated under
reflux for 90min. On cooling, 20 mL water was added. The
product was crystallized. It was then filtered, dried, and
recrystallized to yield 4.86g (98%), mp 97–98ꢀC (ethanol+ water).
3-[1-Ethoxyiminoethyl]-4-hydroxy-5-methyl-1,6-diphenylpyridin-
2(1H)-one (7e). A solution of 3-acetyl-4-hydroxy-5-methyl-1,6-
diphenylpyridin-2(1H)-one 5b (3.19 g, 10 mmole), ethoxylamine
hydrochloride (1.17 g, 12 mmole), and sodium bicarbonate
(1.01 g, 12 mmole) in 45 mL EtOH–H2O (2:1) was heated under
reflux for 90 min. On cooling, the product was crystallized,
filtered, dried, and recrystallized to yield 3.1 g (86%), mp
117–118ꢀC (ethanol).
1
1550 s, 1400 s; H NMR (DMSO): d 0.93 (t, J = 7 Hz, 3, CH3),
2.10 (q, J = 7.5 Hz, 2, CH2), 2.35 (s, 3, CH3 acetyl), 4.70
(d, J = 5.5 Hz, 2, CH2 allyl), 5.35 (m, 2, CH2), 6.05 (m, 1, CH),
7.00–7.30 (m, 10, Ar-H), 12.70 (s, 1, OH). Anal. Calcd for
C24H24N2O3 (388.46): C, 74.21; H, 6.23; N, 7.21. Found: C,
74.44; H, 6.39; N, 6.98%.
3-[1-Ethoxyiminoethyl]-4-hydroxy-6-isopropyl-1-phenylpyridin-
2(1H)-one (7k). A solution of 3-acetyl-4-hydroxy-6-isopropyl-1-
phenylpyridin-2(1H)-one 5d (2.71 g, 10 mmole), ethoxylamine
hydrochloride (1.17 g, 0.012 mole), and sodium bicarbonate
(1.01g, 12mmole) in 50mL EtOH–H2O (2:1) was heated under
reflux for 2 h. On cooling, the product was crystallized, filtered,
dried and recrystallized to yield 1.58 g (50%), mp 107–108ꢀC
(ethanol + water); IR (KBr) nmax/cmÀ1: 3040–2980 w, 1660 s,
3-[1-Benzyloxyiminoethyl]-4-hydroxy-5-methyl-1,6-
diphenylpyridin-2(1H)-one (7f).
A solution of 3-acetyl-4-
1
hydroxy-5-methyl-1,6-diphenylpyridin-2(1H)-one 5b (3.19 g,
10 mmole), bezyloxylamine hydrochloride (1.9 g, 12 mmole),
and sodium bicarbonate (1.01 g, 12 mmole) in 45 mL EtOH–
1620 s, 1590 s, 1400 s; H NMR (DMSO): d 1.05 (d, J=7Hz, 6,
2CH3), 1.25 (t, J=7Hz, 3, CH3 ethyloxy), 2.11 (s, 3, CH3 acetyl),
2.35 (m, 1, CH), 4.10 (q, J=7Hz, 2, CH2), 6.05 (s, 1, Ar-H5),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. P. Nikam and T. Kappe
Vol 000
7.20–7.60 (m, 5, Ar-H), 11.05 (s, 1, OH). Anal. Calcd for
C18H22N2O3 (314.38): C, 68.77; H, 7.05; N, 8.91. Found: C,
68.76; H, 7.11; N, 8.82%.
6-tert-Butyl-3-[1-allyloxyiminoethyl]-4-hydroxy-1-phenylpyridin-2
(1H)-one (7p). A solution of 6-tert-butyl-3-acetyl-4-hydroxy-1-
phenylpyridin-2(1H)-one 5e (2.85g, 10mmole), allyloxylamine
hydrochloride (1.24 g, 11mmole), and sodium bicarbonate
(0.93 g, 11mmole) in 45mL EtOH–H2O (2:1) was heated under
reflux for 1 h. On cooling, the product was crystallized, filtered,
dried, and recrystallized to yield 2.4 g (47%), mp 118–119ꢀC
(ethanol+ water); IR (KBr) nmax/cmÀ1: 2080 w, 1650 s, 1605 w,
1570 m, 1550m, 1490 w; 1H NMR (DMSO): d 1.04 (s, 9, 3CH3),
2.10 (s, 3, CH3 acetyl), 4.58 (d, J = 5.5 Hz, 2, CH2 allyl), 5.26
(m, 2, CH2), 6.00 (m, 1, CH), 6.18 (s, 1, Ar-H5), 7.20–7.50 (m, 5,
Ar-H), 11.50 (s, 1, OH). Anal. Calcd for C20H24N2O3 (340.42):
C, 70.57; H, 7.11; N, 8.23. Found: C, 70.95; H, 7.17; N, 7.90%.
3-[1-Benzyloxyiminoethyl]-4-hydroxy-6-isopropyl-1-phenylpyridin-
2(1H)-one (7l). A solution of 3-acetyl-4-hydroxy-6-isopropyl-1-
phenylpyridin-2(1H)-one 5d (2.71g, 0.01mole), benzyloxylamine
hydrochloride (1.92 g, 12 mmole), and sodium bicarbonate
(1.01 g, 12 mmole) in 45mL EtOH:H2O (2:1) was heated under
reflux for 2 h. On cooling, the product was crystallized, filtered,
dried, and recrystallized to yield 2.5 g (67%), mp 127–128ꢀC
(ethanol + water); IR (KBr) nmax/cmÀ1: 3040 w, 2980 m, 2930–
2880 w, 1660 s, 1520 s, 1500 w, 1400 s; 1H NMR (DMSO):
d 1.00 (d, J = 7 Hz, 6, 2CH3), 2.15 (s, 3, CH3 acetyl), 2.35
(m, 1, CH), 5.15 (s, 2, CH2), 6.00 (s, 1, Ar-H5), 7.20–7.60
(m, 10, Ar-H), 11.60 (s, 1, OH). Anal. Calcd for
C23H24N2O3 (376.45): C, 73.38; H, 6.48; N, 7.44. Found: C,
73.26; H, 6.39; N, 7.29%.
Acknowledgment. Dr. B. P. Nikam thanks the Austrian Academic
Exchange Service, Austria for granting postdoctorate fellowship.
3-[1-Allyloxyiminoethyl]-4-hydroxy-6-isopropyl-1-phenylpyridin-
2(1H)-one (7m).
A solution of 3-acetyl-4-hydroxy-6-
REFERENCES AND NOTES
isopropyl-1-phenylpyridin-2(1H)-one 5d (2.47 g, 9 mmole),
allyloxylamine hydrochloride (1.12 g, 10 mmole), and sodium
bicarbonate (1.01 g, 12 mmole) in 50 mL EtOH:H2O (2:1)
was heated under reflux for 2 h. On cooling, the product was
crystallized, filtered, dried, and recrystallized to yield 1.5 g
[1] White, P. S.; Findlay, J. A.; Tam, H. J.; Can J Chem 1978, 56, 1904.
[2] Williams, D. R.; Bremmer, M. L.; Brown, D. L.; Antuono,
J. D. J Org Chem 1985, 50, 2807.
[3] The Merck Index, 10th Edn, Merck & Co. Inc. N. J., 1976; vol
6083, 891.
[4] Matsumoto, M.; Minato, H. Tetrahedron Lett 1976, 17(42), 3827.
[5] Kim, J. C.; Lee, Y. W.; Tamura, H.; Yashizawa, T. Tetra-
hedron Lett 1995, 36, 1047.
[6] Eiden, F.; Gren, G. Liebigs Ann Chem 1971, 304, 723; Cook,
P. D.; Day, R. T. J. Heterocyclic Chem. 1977, 14, 1295; Robins, M. J.;
Kaneko, C.; Kaneko, M. Canedian J Chem 1981, 59, 3356.
[7] Knops, H. J.; Eue, L.; Schmidt, R. R.; Bayer, A. G. German
Often 1984, DE 3.210.598, Chem Abstr 100, 4412j.
(51%), mp 97–98ꢀC (ethanol + water); IR (KBr) nmax/cmÀ1
:
3070 w, 1650 s, 1605 m, 1400 s, 1200 m; 1H NMR (DMSO):
d 1.05 (d, J = 7 Hz, 6, 2CH3), 2.15 (s, 3, CH3 acetyl), 2.35
(m, 1, CH), 4.60 (d, 2, CH2 allyl), 5.25 (d, J = 7 Hz, 2,
CH2), 5.38 (m, 1, CH), 6.02 (s, 1, Ar-H5), 7.20–7.60 (m, 5,
Ar-H), 11.50 (s, 1, OH). Anal. Calcd for C19H22N2O3
(326.39): C, 69.92; H, 6.79; N, 8.58. Found: C, 69.70; H,
6.81; N, 8.43%.
6-tert-Butyl-3-[1-ethoxyiminoethyl]-4-hydroxy-1-phenylpyridin-
2(1H)-one (7n). A solution of 6-tert-butyl-3-acetyl-4-hydroxy-
1-phenylpyridin-2(1H)-one 5e (2.85 g, 0.01 mole), ethoxylamine
hydrochloride (1.19 g, 0.012 mole), and sodium bicarbonate
(0.93 g, 0.011 mole) in 50 mL EtOH–H2O (2:1) was heated under
reflux for 1 h. On cooling, the product was crystallized, filtered,
dried, and recrystallized to yield 2.4 g (73%), mp 107–108ꢀC
(ethanol + water); IR (KBr) nmax/cmÀ1: 3080 w, 3020 w,
2980 s, 1650 s, 1570 s, 1490 m, 1410 m; 1H NMR (DMSO): d
1.05 (s, 9, 3CH3), 1.23 (t, J = 7 Hz, 3, CH3), 2.07 (s, 3, CH3
acetyl), 4.10 (q, J = 7 Hz, 2, CH2), 6.19 (s, 1, Ar-H5), 7.20–7.50
(m, 5, Ar-H), 11.60 (s, 1, OH). Anal. Calcd for C19H24N2O3
(328.41): C, 69.49; H, 7.37; N, 8.53. Found: C, 69.43; H, 7.34;
N, 8.46%.
[8] Katritzky, A. R.; Jones, R. A. J Chem Soc 1960, Part X, 2947.
[9] Bellamy, L. J.; Rogasch, R. E. SpectrochimActa 1969, 16, 30.
[10] Knops, H. J.; Born, L. Tetrahedron Lett 1983, 24, 2973.
[11] Kappe, T.; Ajili, M.; Stadlbaner, W. J Heterocyclic Chem
1988, 25, 463.
[12] Kappe, T., In Encyclopedia of Reagents in Organic Synthesis
(EROS); Pacquette, L. A. Ed.; Wiley, Chichester New York Brisbane
Toronto Singapore; Use of Carbon Suboxide, vol. 2, pp 996–997; Use of
Chlorocarbonyl Ketenes, vol. 2, pp 1098–1100; Use of Magic Malonates,
AMEns, Bis-(2,4,6-trichlorophenyl)-malonates, 1995; vol. 1, pp 577–579.
[13] Cutler, H. G.; Jacyno, J. M. Agric Biol Chem 1991, 55, 2629.
[14] (a) Ziegler, E.; Wildtgrube, G.; Junek, H. Motash Chem 1956,
87, 439; (b) Kappe, T.; Linnau, Y. Monatsh Chem 1983, 114, 349;
(c) Effenberger, F.; Muck, A. O.; Bessey, E. Chem Ber 1980, 113 2086;
(d) Jamkhandi, P. S.; Rajgopal, S. Monatsh Chem 1968, 99, 1390;
(e) Matzat, N.; Wamhoff, H.; Korte, F. Chem Ber 1969, 102, 3122;
(f) Stephen, J. F.; Marcus, E. J Org Chem 1969, 34, 2764; (g) Khetri,
H. N.; Hamdi, M.; Speziale, Y.; J Hetrocycl Chem 1990, 27, 1401;
(h) Faber, K.; Kappe, T. J Hetrocycl Chem 1984, 21, 1881; (i) Roschger,
P.; Stadlebauer, W. Liebigs Ann Chem 1990, 821; (j) Roschger, P., Fiala,
W.; Stadlebauer, W. J Hetrocycl Chem 1992, 29, 225.
6-tert-Butyl-3-[1-benzyloxyiminoethyl]-4-hydroxy-1-
phenylpyridin-2(1H)-one (7o). A solution of 6-tert-butyl-3-acetyl-
4-hydroxy-1-phenylpyridin-2(1H)-one 5e (2.85 g, 10 mmole),
benzyloxylamine hydrochloride (1.4 g, 11 mmole), and sodium
bicarbonate (0.93 g, 11 mmole) in 50 mL EtOH–H2O (2:1) was
heated under reflux for 2 h. On cooling, the product was
crystallized, filtered, dried, and recrystallized to yield 2.6 g
[15] Kappe, T. Farmaco 1999, 54, 309.
[16] Landor, S. R.; Sonola, O. O.; Tatchell, A. R. J Chem Soc
Perkin Trans 1978, 1, 605.
[17] Cho, B. R.; Oh, Y. C.; Lee, S. H.; Park, Y. J. J Org Chem
1996, 61, 5656.
(67%), mp 127–128ꢀC (ethanol + water); IR (KBr) nmax/cmÀ1
:
2980 m, 1650 s, 1580 m, 1360 s, 1010 s; 1H NMR (DMSO): d
1.03 (s, 9, 3CH3), 2.12 (s, 3, CH3 acetyl), 5.13 (s, 2, CH2), 6.15
(s, 1, Ar-H5), 7.20–7.50 (m, 10, Ar-H), 11.43 (s, 1, OH). Anal.
Calcd for C24H26N2O3 (390.47): C, 73.82; H, 6.71; N, 7.17.
Found: C, 74.63; H, 6.79; N, 7.01%.
[18] Dew, E. N.; Richie, P. D. Chem Ind 1969, 51.
[19] Bohdal, U. Thesis, Karl Franzens University of Graz 1992.
[20] Roschger, P. Thesis, Karl Franzens University of Graz 1988.
[21] Kafka, S.; Kappe, T. Monatsh Chem 1990, 128, 1019.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet