Synthesis of Acetyl and Iodo Derivatives of 4-Hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-diones and 4-Hydroxy-1-phenylpyridin-2(1H)-ones

Article abstract of DOI:10.1002/jhet.2619

A simple and efficient method has been described for the synthesis of acetyl and iodo derivatives of 4-hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-diones 1 and 4-hydroxy-1-phenylpyridin-2(1H)-ones 5. Compounds 1 with phenyl and alkyl substituent at C(7) and C(8), respectively, can be easily acetylated by refluxing in a mixture of acetic acid and polyphosphoric acid to give 3-acetyl-4-hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-diones 2 in excellent yields. Compounds 1 and 5 can be iodinated with iodine and anhydrous sodium carbonate in boiling dioxane to give 4-hydroxy-3-iodo-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-diones 3 and 4-hydroxy-3-iodo-1-phenylpyridin-2(1H)-ones 6, respectively, in good yields. The structures were confirmed using infrared, nuclear magnetic resonance, and elemental analysis.

Full text of DOI:10.1002/jhet.2619

Month 2016 Synthesis of Acetyl and Iodo Derivatives of 4-Hydroxy-6-phenyl-6H-pyrano
[3,2-c]pyridine-2,5-diones and 4-Hydroxy-1-phenylpyridin-2(1H)-ones
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
bInstitute of Organic Chemistry, Karl-Franzens University of Graz, Heinrichstraße 28, A-8010 Graz, Austria
*
E-mail: bpnikam@yahoo.co.in
Received October 17, 2015
DOI 10.1002/jhet.2619
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A simple and efficient method has been described for the synthesis of acetyl and iodo derivatives of 4-
hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-diones 1 and 4-hydroxy-1-phenylpyridin-2(1H)-ones 5.
Compounds 1 with phenyl and alkyl substituent at C(7) and C(8), respectively, can be easily acetylated
by refluxing in a mixture of acetic acid and polyphosphoric acid to give 3-acetyl-4-hydroxy-6-phenyl-6H-
pyrano[3,2-c]pyridine-2,5-diones 2 in excellent yields. Compounds 1 and 5 can be iodinated with iodine
and anhydrous sodium carbonate in boiling dioxane to give 4-hydroxy-3-iodo-6-phenyl-6H-pyrano[3,2-c]
pyridine-2,5-diones 3 and 4-hydroxy-3-iodo-1-phenylpyridin-2(1H)-ones 6, respectively, in good yields.
The structures were confirmed using infrared, nuclear magnetic resonance , and elemental analysis.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
4-Hydroxy-2-pyridones with aliphatic acyl groups
in position 3 have found much interest because of their
biological properties [29]. Most methods used to intro-
duce acetyl group at position 3 [30]. Best results were
obtained by direct C-acetylation with acetic acid in
polyphosphoric acid according to known methods
[31]. Iodine in presence of sodium carbonate reagents
was used for the iodination [32]. In the present paper,
4-hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-
diones 1 and 4-hydroxy-1-phenylpyridin-2(1H)-ones 5
[33,34] are acetylated and iodinated by a simple and
an efficient method.
The chemistry of 4-hydroxy-2(1H)-pyridone has been
attracting considerable attention because of several rea-
sons. A number of natural products containing this moiety
are available, having various biological properties [1–14].
Because 4-hydroxy-2-pyridones may also exist in their tau-
tomeric 2-hydroxy-4-pyridone form [15–19], this aspect
has found attention. X-ray diffraction studies [18] have
confirmed earlier results [15,16] that N-substituted 4-
pyridones exhibit the infrared frequencies below
1600 cmÀ1 and the 2-pyridone shows the absorption bands
at 1650 cmÀ1
.
4-Hydroxy-2-pyridone has also been used as a base in
the synthesis of nucleosides [20]. The substances
containing 3-acetyl-4-hydroxy-2-pyridone moieties play
important role in agricultural chemistry, whether they are
carbocyclic, oximated, or not [21,22].
4-Hydroxy-2-pyridones are synthesized via condensa-
tion of enamines or azomethines with reactive malonic
acid derivatives (such as carbon suboxide, chlorocarbonyl
ketenes, and bis-2,4,6-trichlorophenyl malonates [23,24].
It has been assumed that only activated enamines derived
from β-ketoesters or 1,3-diketones with NH3 or primary
amines can be condensed with substituted dialkyl
malonates [25], but it is also possible to condense
azomethines with substituted dialkyl malonates to give
4-hydroxy-2-pyridones in moderate to good yields
[26–28].
RESULTS AND DISCUSSION
4-Hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-
diones 1a–e and 3-acetyl-4-hydroxy-1-phenylpyridin-
2(1H)-ones 4a–e were readily synthesized as per the
procedure reported earlier [34]. Compounds 1a–e was
obtained by the reaction of azomethines with diethyl
malonate in diphenyl ether at 250–270°C in moderate
yields (31–70%). The desired products 2a–e and 3a–e
could be obtained from 1a–e, as illustrated in Scheme 1.
Thus, heating of 1a–e in a mixture of acetic acid and
polyphosphoric acid reflux afforded 3-acetyl-4-hydroxy-
6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-diones 2a–e in ex-
cellent yields. 4-Hydroxy-3-iodo-6-phenyl-6H-pyrano
{3,2-c]pyridine-2,5-diones 3a–e were obtained by
© 2016 Wiley Periodicals, Inc.

B. P. Nigam and T. Kappe
Vol 000
Scheme 1. Synthesis of 3-acetyl and 3- iodo (2, 3) derivatives of 4-hy-
droxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-diones 1
Scheme 2. Synthesis of 4-Hydroxy-1-phenylpyridin-2(1H)-ones 5 and its
3-iodo derivatives 6
refluxing 1a–e in a solution of 2 equivalents of I2 in diox-
ane in presence of dry sodium carbonate in good yields
(Table 1).
dioxane. The present method is most valuable in organic
synthesis because of operation simplicity, as well as the
high yield and easy availability of reagents.
3-Acetyl-4-hydroxy-1-phenylpyridin-2(1H)-ones 4a–e
were obtained by refluxing compound 1 in 1,2-diethylene
glycol in the presence of sodium hydroxide in good yields
(85–95%). The cleavage of the acetyl group by treatment
with 90% H2SO4 at 140° results in the formation of 3-
EXPERIMENTAL
All chemicals were purchased from E. Merk (Darm-
stadt/Gemsheim, Germany) and used without purification.
The solvents were dried over appropriate drying agents
and distilled prior to use. All reactions were monitored
by TLC on pre-coated silica gel 60 PF254 (mesh). Spots
were visualized with ultraviolet light. Melting points were
recorded using open glass capillaries on Gallenkamp MFB
595 melting point apparatus (Weiss-Gallenkamp Com-
pany, United Kingdom) and were uncorrected. Infrared
spectra (IR) were recorded on a Perkin-Elmer 298 spectro-
photometer (Waltham, MA) using KBr pellets. Nuclear
magnetic resonance (NMR) spectra were recorded on
Varian Gemini 200MHz spectrometer in dimethyl sulfoxide
(DMSO)-d6 using tetramethylsilane as an internal standard.
CHN analyses were recorded on a Carbon, Hydrogen,
Nitrogen-Automat Carlo Erba 1106 elemental analyzer.
Preparation of 3-acetyl-4-hydroxy-6-phenyl-6H-pyrano
[3,2-c]pyridine-2,5-diones (2a–e): General procedure: The
appropriate 4-hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-
2,5-dione 1 [34] (10mmol) was dissolved in 60mL of
glacial acetic acid at boiling point temperature. Then,
unsubstituted
4-hydroxy-1-phenylpyridin-2(1H)-ones
5a–e [34] as illustrated in Scheme 2 in high yields.
Compounds 5a–e was then iodinated by refluxing in a
solution of 2 equivalents of I2 in dioxane in the presence
of dry sodium carbonate to give 4-hydroxy-3-iodo-1-
phenylpyridin-2(1H)-ones 6a–e in good yields (Table 2).
The structures of the newly obtained compounds were
elucidated on the basis of IR, NMR spectra, and elemen-
tal analysis.
CONCLUSION
A simple and efficient method has been reported for the
synthesis of acetyl and iodo derivatives of 4-hydroxy-6-
phenyl-6H-pyrano[3,2-c]pyridine-2,5-diones and 4-hy-
droxy-1-phenylpyridin-2(1H)-ones. In the present paper,
acetyl derivatives are obtained by refluxing in acetic acid
in the presence of polyphosphoric acid, and the iodo deriv-
atives are obtained by refluxing in a solution of I2 in
Table 1
Preparation of 3-acetyl and 3-iodo (2, 3) derivatives of 4-hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-diones 1.
R
R1
Compound no.
mp (°C)
Yield (%)
Compound no.
mp (°C)
Yield (%)
Ph
Ph
Ph
i-Propyl
t-Butyl
H
Me
Et
H
2a
2b
2c
2d
2e
240–241
245–246
198–199
249–250
263–264
98
98
91
81
96
3a
3b
3c
3d
3e
206–208
253–254
226–227
201–202
223–224
70
69
93
78
71
H
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Acetyl and Iodo Derivatives of 4-Hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-
diones and 4-Hydroxy-1-phenylpyridin-2(1H)-ones
Table 2
Preparation of 4-hydroxy-1-phenylpyridin-2(1H)-ones 5 and its 3-iodo derivatives 6.
R
R1
Compound no.
mp (°C)
Yield (%)
Compound no.
mp (°C)
Yield (%)
Ph
Ph
Ph
i-Propyl
t-Butyl
H
Me
Et
H
5a
5b
5c
5d
5e
304–305
303–304
280–281
211–212
225–226
91
93
86
91
85
6a
6b
6c
6d
6e
250–252
197–198
208–209
224–225
232–233
94
88
60
80
68
H
20mL polyphosphoric acid was added dropwise with
stirring, and the mixture was further refluxed for 15min.
The resulting hot solution was then poured in ice water.
The residual solid obtained was filtered, dried, and
recrystallized from acetic acid to give the corresponding
derivative 2. Physical data and yields are listed in Table 1.
3-Acetyl-4-hydroxy-6,7-diphenyl-6H-pyrano[3,2-c]pyridine-2,5-
dione (2a). IR (KBr, cmÀ1): 3080, 1755, 1680, 1610, 1560,
7-tert-Butyl-3-acetyl-4-hydroxy-6-phenyl-6H-pyrano[3,2-c]
pyridine-2,5-dione (2e).
IR (KBr, cmÀ1): 3060–2960,
1750, 1690, 1600, 1560, 1400. 1H-NMR (200 MHz,
DMSO-d6) δ (ppm): 1.12 (s, 9H, 3 ÀCH3), 2.56 (s,
3H, ÀCH3), 6.67 (s, 1H, Ar-H), 7.35–7.60 (m, 5H,
Ar-H). 13C-NMR (200 MHz, DMSO-d6)
δ (ppm):
197.8, 183.2, 158.4, 157.2, 154.9, 110.7, 99.3, 88.1,
37.3, 27.5, 27.5, 27.4, 25.9. Anal. Calcd for
C20H19NO5 (353.37): C 67.98, H 5.42, N 3.96%.
Found: C 68.08, H 5.46, N 3.92%.
4-Hydroxy-3-iodo-6,7-diphenyl-6H-pyrano[3,2-c]pyridine-
2,5-diones (3a–e). General procedure: The appropriate
1
1500, 1400. H-NMR (200MHz, DMSO-d6) δ (ppm): 2.59
(s, 3H, ÀCH3); 6.68 (s, 1H, Ar-H), 7.20–7.40 (m, 10H, Ar-
H). 13C-NMR (200 MHz, DMSO-d6) δ (ppm): 198.9, 182.6,
163.1, 158.2, 155.4, 145.3, 111.1, 99.6, 92.2, 26.7. Anal.
Calcd for C22H15NO5 (373.36): C 70.77, H 4.05, N 3.75%.
Found: C 70.48, H 4.11, N 3.64%.
compound
1 (20 mmol) was dissolved in 30 mL
aqueous solution prepared by dissolving dry sodium
carbonate (4.2 g, 40 mmol) with stirring. To this
mixture, solution of I2 (6 g, 40 mmol) in 30 mL
dioxane was added till the color of iodine persists on
solution. This mixture was then refluxed for 1 h,
cooled, and acidified with conc. hydrochloric acid. The
solid product obtained was filtered, dried, and
recrystallized from acetic acid to give the
corresponding derivative 3. Physical data and yields
are listed in Table 1.
3-Acetyl-4-hydroxy-8-methyl-6,7-diphenyl-6H-pyrano[3,2-c]
pyridine-2,5-dione (2b).
IR (KBr, cmÀ1): 3060, 1750,
1680, 1550, 1490. 1H-NMR (200 MHz, DMSO-d6) δ
(ppm): 1.84 (s, 3H, ÀCH3), 2.56 (s, 3H, ÀCH3), 7.20–
7.40 (m, 10H, Ar-H). 13C-NMR (200 MHz, DMSO-d6) δ
(ppm): 198.8, 183.2, 162.9, 157.9, 154.8, 135.8, 110.9,
105.1, 99.7, 26.8, 7.6. Anal. Calcd for C23H17NO5
(387.38): C 71.31, H 4.42, N 3.62%. Found: C 71.49, H
4.38, N 3.55%.
3-Acetyl-8-ethyl-4-hydroxy-6,7-diphenyl-6H-pyrano[3,2-c]
pyridine-2,5-dione (2c).
4-Hydroxy-3-iodo-6,7-diphenyl-6H-pyrano[3,2-c]pyridine-
2,5-dione (3a). IR (KBr, cmÀ1): 3060, 1760, 1750, 1670,
1610, 1450, 1300. 1H-NMR (200MHz, DMSO-d6) δ
(ppm): 6.95 (s, 1H, Ar-H), 7.20–7.50 (m, 10H, Ar-H).
13C-NMR (200MHz, DMSO-d6) δ (ppm): 206.1, 160,
157.2, 153.8, 144.9, 111.2, 95.3, 45.8. Anal. Calcd for
C20H12INO4 (457.22): C 52.54, H 2.65, N 3.06%. Found:
C 52.76, H 2.72, N 3.13%.
IR (KBr, cmÀ1): 3060–2880,
1750, 1680, 1540, 1490, 1450. 1H-NMR (200 MHz,
DMSO-d6) δ (ppm): 1.00 (t, J = 7 Hz, 3H, ÀCH3),
2.24 (q, J = 7.5 Hz, 2H, ÀCH2), 2.56 (s, 3H, ÀCH3),
7.20–7.30 (m, 10H, Ar-H). 13C-NMR (200 MHz,
DMSO-d6) δ (ppm): 198.7, 183.7, 162.5, 156.9, 154.4,
134.7, 110.2, 109.7, 99.7, 26.8, 12.5,12.1. Anal. Calcd
for C24H19NO5 (401.41): C 71.81, H 4.77, N 3.49%.
Found: C 71.67, H 4.72, N 3.41%.
4-Hydroxy-3-iodo-8-methyl-6,7-diphenyl-6H-pyrano[3,2-c]
pyridine-2,5-dione (3b).
IR (KBr, cmÀ1): 3060, 1715,
3-Acetyl-4-hydroxy-7-isopropyl-6-phenyl-6H-pyrano[3,2-c]
pyridine-2,5-dione (2d).
1670, 1550, 1480, 1380. 1H-NMR (200 MHz,
DMSO-d6) δ (ppm): 1.89 (s, 3H, ÀCH3), 7.20–7.40
(m, 10H, Ar-H). 13C-NMR (200 MHz, DMSO-d6) δ
(ppm): 207.1, 160, 157.1, 153.8, 135.4, 109.8, 105.7,
45.4, 7.5. Anal. Calcd for C21H14INO4 (471.24): C
53.52, H 2.99, N 2.97%. Found: C 53.54, H 3.12, N
2.92%.
8-Ethyl-4-hydroxy-3-iodo-6,7-diphenyl-6H-pyrano[3,2-
c]pyridine-2,5-dione (3c). IR (KBr, cmÀ1): 2980, 1740,
1665, 1550, 1470, 1390, 1290, 1160. 1H-NMR
IR (KBr, cmÀ1): 3070–2930,
1750, 1680, 1570, 1480, 1400. 1H-NMR (200 MHz,
DMSO-d6) δ (ppm): 1.15 (d, J = 7 Hz, 6H, 2 ÀCH3),
2.45 (m, 1H, ÀCH), 2.59 (s, 3H, ÀCH3), 6.75 (s, 1H,
Ar-H), 7.40–7.70 (m, 5H, Ar-H). 13C-NMR (200 MHz,
DMSO-d6) δ (ppm): 197.9, 193, 184, 161.7, 157.3,
154.1, 110.9, 99.2, 91.7, 28.7, 26.5, 19.4. Anal. Calcd
for C19H17NO5 (339.34): C 67.25, H 5.05, N 4.13%.
Found: C 67.45, H 5.01, N 4.04%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. P. Nigam and T. Kappe
Vol 000
(200 MHz, DMSO-d6) δ (ppm): 1.01 (t, J = 7 Hz, 3H,
ÀCH3), 2.29 (q, J = 7.5 Hz, 2H, ÀCH2), 7.20–7.40 (m,
10H, Ar-H), 14.42 (s, 1H, ÀOH). 13C-NMR (200 MHz,
DMSO-d6) δ (ppm): 205.8, 160, 157.2, 153.9, 134.7,
111.2, 109.4, 45.4, 12.8, 12.2. Anal. Calcd for
C22H16INO4 (485.27): C 54.45, H 3.32, N 2.89%.
Found: C 54.24, H 3.34, N 2.80%.
5-Ethyl-4-hydroxy-1,6-diphenylpyridin-2(1H)-one (5c). IR
1
(KBr, cmÀ1): 3060–2940, 1630, 1600, 1550, 1490. H-
NMR (200MHz, DMSO-d6) δ (ppm): 0.91 (t, J = 7Hz,
3H, ÀCH3), 2.05 (q, J= 7.5 Hz, 2H, ÀCH2), 5.85 (s, 1H,
Ar-H), 7.00–7.30 (m, 10H, Ar-H), 11.00 (s, 1H, ÀOH).
13C-NMR (200MHz, DMSO-d6) δ (ppm): 175.4, 160.5,
134.4, 134.2, 132.4, 106.5, 98.7, 12.4, 12.3. Anal. Calcd
for C19H17NO2 (291.34): C 78.33, H 5.88, N 4.81%.
Found: C 78.11, H 5.86, N 4.63%.
4-Hydroxy-3-iodo-7-isopropyl-6-phenyl-6H-pyrano[3,2-
c]pyridine-2,5-dione (3d).
IR (KBr, cmÀ1): 3100–2980,
1740, 1665, 1600, 1570, 1450, 1290. 1H-NMR
(200MHz, DMSO-d6) δ (ppm): 1.11 (s, 3H, ÀCH3),
1.15 (s, 3H, ÀCH3), 2.46 (m, 1H, ÀCH), 6.88 (s, 1H,
Ar-H), 7.45–7.70 (m, 5H, Ar-H). 13C-NMR (200MHz,
DMSO-d6) δ (ppm): 205.2, 160, 156.7, 153.8, 151.2,
110.6, 91.5, 45.3, 28.7, 19.2, 19.2. Anal. Calcd for
C17H14INO4 (423.20): C 48.25, H 3.33, N 3.31%.
Found: C 48.40, H 3.39, N 3.27%.
7-ter-Butyl-4-hydroxy-3-iodo-6-phenyl-6H-pyrano[3,2-c]
pyridine-2,5-dione (3e). IR (KBr, cmÀ1): 2980, 1630,
1600, 1570, 1490, 1380, 1080. 1H-NMR (200 MHz,
DMSO-d6) δ (ppm): 1.05 (s, 9H, 3 ÀCH3), 6.28 (s,
1H, Ar-H), 7.20–7.50 (m, 5H, Ar-H). 13C-NMR
(200 MHz, DMSO-d6) δ (ppm): 205.3, 161.1, 157.9,
156.8, 153.9, 109.8, 88.5, 45.4, 37.4, 27.4, 27.5,
4-Hydroxy-6-isopropyl-1-phenylpyridine-2(1H)-one (5d). IR
(KBr, cmÀ1): 3050–2990, 1660, 1600, 1550, 1490. 1H-
NMR (200MHz, DMSO-d6) δ (ppm): 1.02 (d, J=8Hz, 6H,
2 ÀCH3), 2.37 (m, 1H, ÀCH), 5.55 (d, J=2.5Hz, 1H, Ar-
H), 5.80 (d, J= 2.5Hz, 1H, Ar-H), 7.15–7.65 (m, 5H, Ar-H),
10.64 (s, 1H, ÀOH). 13C-NMR (200 MHz, DMSO-d6) δ
(ppm): 160.2, 158.9, 150.8, 98.7, 91.5, 29.3, 19.3, 19.2.
Anal. Calcd for C14H15NO2 (229.27): C 73.34, H 6.59, N
6.11%. Found: C 73.27, H 6.48, N 6.05%.
6-tert-Butyl-4-hydroxy-1-phenylpyridin-2(1H)-one (5e).
IR
(KBr, cmÀ1): 3050–2980, 1640, 1600, 1540, 1480. 1H-
NMR (200 MHz, DMSO-d6) δ (ppm): 1.06 (s, 9H, 3
ÀCH3), 5.58 (d, J= 2.5 Hz, 1H, Ar-H), 6.05 (d, J=2Hz.
1H, Ar-H), 7.10–7.50 (m, 5H, Ar-H), 10.62 (s, 1H, ÀOH).
13C-NMR (200MHz, DMSO-d6) δ (ppm): 160.3, 158.7,
157.9, 98.5, 88.7, 37.7, 27.4, 27.3, 27.5. Anal. Calcd for
C15H17NO2 (243.30): C 74.05, H 7.04, N 5.76%. Found: C
74.28, H 6.90, N 5.61%.
27.3. Anal. Calcd for C18H16INO4 (437.23):
C
49.45, H 3.69, N 3.20%. Found: C 49.22, H 3.85,
N 3.25%.
4-Hydroxy-1,6-diphenylpyridin-2-(1H)-ones (5a–e) [26]:
4-Hydroxy-3-iodo-1,6-diphenylpyridin-2(1H)-ones (6a–e):
General procedure:
A
reaction mixture of the
General procedure: The appropriate compound
5
appropriate
3-acetyl-4-hydroxy-1,6-diphenylpyridin-
(15 mmol) was dissolved at room temperature in 50mL
aqueous solution prepared by dissolving dry sodium
carbonate (3.2 g, 30mmol) with stirring. To this mixture,
solution of I2 (4 g, 30mmol) prepared by dissolving in
25mL dioxane was added till the color of iodine persists
on solution. The mixture was then refluxed for 30min
(5a–b) or 1 h (5c–e) at 50°, cooled and acidified with
dilute hydrochloric acid or glacial acetic acid. A solid
product obtained was filtered, dried, and recrystallized
from acetic acid to give the corresponding derivative 6.
Physical data and yields are listed in Table 2.
2(1H)-one 4 (0.042 mol) and 70 mL sulfuric acid (90%)
was placed in Erlenmeyer flask and stirred at 140° for
20 min. It was then cooled and added to ice water and
stirred. A solid obtained was filtered, washed with
water, and recrystallized from ethanol to give the
corresponding derivative 5. Physical data and yields are
listed in Table 2.
4-Hydroxy-1,6-diphenylpyridin-2-(1H)-one (5a). IR (KBr,
cmÀ1): 3060–2960, 1660, 1600, 1550, 1490. 1H-NMR
(200 MHz, DMSO-d6) δ (ppm): 5.34 (s, 1H, Ar-H),
7.00–7.40 (m, 11H, Ar-H), 11.15 (s, 1H, ÀOH).
13C-NMR (200 MHz, DMSO-d6) δ (ppm): 160.3, 159.4,
145.1, 132.5, 98.2, 95.7. Anal. Calcd for C17H13NO2
(263.29): C 77.55, H 4.98, N 5.32%. Found: C 77.37, H
5.13, N 5.24%.
4-Hydroxy-3-iodo-1,6-diphenylpyridin-2(1H)-one (6a). IR
1
(KBr, cmÀ1): 3000, 1645, 1625, 1490, 1410. H-NMR
(200 MHz, DMSO-d6) δ (ppm): 6.05 (s, 1H, Ar-H), 7.10–
7.30 (m, 10H, Ar-H), 11.70 (s, 1H, ÀOH). 13C-NMR
(200 MHz, DMSO-d6) δ (ppm): 201.8, 157.9, 145.2,
95.4, 48.3. Anal. Calcd for C17H12INO2 (389.19): C
52.46, H 3.11, N 3.60%. Found: C 52.29, H 3.15, N
3.67%.
4-Hydroxy-5-methyl-1,6-diphenylpyridin-2(1H)-one (5b). IR
(KBr, cmÀ1): 3060–2950, 1640, 1610, 1540, 1480. H-
1
NMR (200 MHz, DMSO-d6) δ (ppm): 1.68 (s, 3H,
ÀCH3), 5.88 (s, 1H, Ar-H), 7.00–7.30 (m, 10H, Ar-H),
11.05 (s, 1H, ÀOH). 13C-NMR (200 MHz, DMSO-d6)
δ (ppm): 175.3, 160.1, 135.5, 134.2, 132.5, 105.4,
98.5, 7.2. Anal. Calcd for C18H15NO2 (277.32): C
77.96, H 5.45, N 5.05%. Found: C 77.81, H 5.43, N
4.94%.
4-Hydroxy-3-iodo-5-methyl-1, 6-diphenylpyridin-2(1H)-one
(6b). IR (KBr, cmÀ1): 3060–2920, 1630, 1600, 1560,
1
1490. H-NMR (200MHz, DMSO-d6) δ (ppm): 1.76 (s,
3H, ÀCH3), 7.00–7.30 (m, 10H, Ar-H), 10.40 (s, 1H,
ÀOH). 13C-NMR (200 MHz, DMSO-d6) δ (ppm): 202.1,
158.6, 135.3, 105.6, 48.6, 6.3. Anal. Calcd for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Acetyl and Iodo Derivatives of 4-Hydroxy-6-phenyl-6H-pyrano[3,2-c]pyridine-2,5-
diones and 4-Hydroxy-1-phenylpyridin-2(1H)-ones
[9] Southon, I. W.; Buckingham, J. Dictionary of Alkaloids, 1st
C18H14INO2 (403.21): C 53.62, H 3.50, N 3.47%. Found:
C 53.59, H 3.62, N 3.39%.
ed.; Chapman and Hall: London, 1989 I-00015, 560; B-00056, p. 135.
[10] Matsumoto, M.; Minato, H. Tetrahedron Lett 1976, 20, 3827.
[11] Wat, C. K.; Malones, A. G.; Smith, D. G.; Wright, J. L. C.;
Vining, L. C. Can J Chem 1977, 55, 4090.
[12] (a) Ando, K.; Matsuura, I.; Nawata, Y.; Endo, H.; Sasaki, H.;
Okutomi, T.; Saeki, T.; Tamura, G. J Antibiot 1976, 31, 533; (b) Nawata,
Y.; Matsuura, I.; Ando, K.; Iitaka, Y. Acta Crystallogr Sec C 1990, 46, 515.
[13] (a) Trecourt, F.; Mallet, M.; Mongin, F.; Queguiner, G. J Het-
erocyclic Chem 1995, 32, 1117; (b) Cutler, H. G.; Jacyno, J. M. Agric
Biol Chem 1991, 55, 2629; (c) Wiiliams, D. R.; Bremmer, M. L.; Brown,
D. L.; Antuono, J. D. J Org Chem 1985, 50, 2807.
[14] The Merk Index; 10th Edn.; Merck & Co Inc.: Rahway, New
Jersey, 1996; No. 6308, pp 1068.
[15] Katritzky, A. R.; Jones, R. A. J Chem Soc 1960, Part X, 2947.
[16] Bellamy, L. J.; Rogasch, P. E. Spectrochim Acta 1969, 16, 30.
[17] Fabian, W. Z Naturforsch B Anorg Chem Org Chem 1979,
348, 266, 871.
[18] Knops, H. J.; Born, L. Tetrahedron Lett 1983, 24, 2973.
[19] Shapiro, M. J.; Kolpak, M. X.; Lemke, T. L. J Org Chem 1984,
49, 187.
[20] (a) Cook, P. D.; Day, R. T.; Robins, R. K. J Heterocyclic
Chem 1977, 14, 1295; (b) Stone, R. L. Tetrahedron Lett 1977, 46,
4017; (c) McNamara, D. J.; Cook, P. D.; Allen, L. B.; Kehoe, M. J.;
Holland, C. S.; Teepe, A. G. J Med Chem 1990, 33, 2006.
[21] Iwataki, I.; Draber, W.; Fujita, T. Rational Approaches to
Structure, Activity and Ecotoxicology of Agrochemicals; CRC Press:
Boca Raton, FL, 1992; 397.
[22] Kappe, T.; Schnell, B. J Heterocyclic Chem 1996, 33, 663.
[23] Kappe, T.; Ajili, S.; Stadlbauer, W. J Heterocyclic Chem 1988,
25, 463.
[24] Kappe, T. In Encyclopedia of Reagents for Organic Synthesis
(EROS); Paquette L. A. Ed.; Use of Carbon Suboxide, 2, 996-997; Use of
Chlorocarbonyl Ketenes, 2, 1098-1100; Use of Magic Malonates,
AMIEns, “Bis-(2,4,6-trichlorophenyl)-malonates” Wiley: Chichester, 1995;
Vol 1, 577-579.
5-Ethyl-4-hydroxy-3-iodo-1,6-diphenylpyridin-2(1H)-one
(6c). IR (KBr, cmÀ1): 3050–2930, 1640, 1600, 1560,
1
1490. H-NMR (200 MHz, DMSO-d6) δ (ppm): 0.90 (t,
J = 7 Hz, 3H, CH3), 2.17 (q, J = 7 Hz, 2H, ÀCH2), 7.00–
7.40 (m, 10H, Ar-H), 10.21 (s, 1H, ÀOH). 13C-NMR
(200 MHz, DMSO-d6) δ (ppm): 201.9, 157.8, 134.3,
109.5, 48.5, 12.7, 11.5. Anal. Calcd for C19H16INO2
(417.24): C 54.69, H 3.87, N 3.36%. Found: C 54.63,
H 4.06, N 3.23%.
4-Hydroxy-3-iodo-6-isopropyl-1-phenylpyridin-2(1H)-one
(6d). IR (KBr, cmÀ1): 3040–2870, 1630, 1600, 1550,
1430. 1H-NMR (200 MHz, DMSO-d6) δ (ppm): 1.01
(d, J = 6.5 Hz, 6H, 2 ÀCH3), 2.36 (m, 1H, ÀCH), 6.05
(s, 1H, Ar-H), 7.20–7.60 (m, 5H, Ar-H), 11.50 (s,
1H, ÀOH). 13C-NMR (200 MHz, DMSO-d6) δ (ppm):
201.7, 157.8, 150.8, 91.4, 48.3, 29.1, 19.3, 19.2.
Anal. Calcd for C14H14INO2 (355.17): C 47.34, H
3.97, N 3.94%. Found: C 47.50, H 4.11, N 3.92%.
6-ter-Butyl-4-hydroxy-3-iodo-1-phenylpyridin-2(1H)-one
(6e). IR (KBr, cmÀ1): 3020–2860, 1630, 1600, 1570,
1390. 1H-NMR (200 MHz, DMSO-d6) δ (ppm): 1.02
(s, 9H, 3 ÀCH3), 6.26 (m, 1H, Ar-H), 7.22–7.47 (m,
5H, Ar-H), 11.41 (s, 1H, ÀOH). 13C-NMR (200 MHz,
DMSO-d6) δ (ppm): 203.1, 159.1, 157.9, 87.9, 48.6,
37.8, 27.6, 27.5, 27.4. Anal. Calcd for C15H16INO2
(369.20): C 48.80, H 4.37, N 3.79%. Found: C 48.97,
H 4.37, N 3.77%.
[25] (a) Prelog, V.; Szpilfogel, S. Helv Chem Acta 1945, 28,
648; (b) Schrőtter, E.; Niedrich, H.; Schick, H. Pharmazie 1984,
39, 155.
[26] Bohdal, U. Ph. D. Thesis, Karl Franzens University of Graz,
1992.
[27] Roschger, P. Ph.D. Thesis, Karl Franzens University of Graz,
1988.
Acknowledgment. Dr. B. P. Nikam thanks to the Austrian
Academic Exchange Service, Austria, for a postdoctorate
fellowship.
[28] Kafka, S.; Kappe, T. Monatsh Chem 1997, 128, 1019.
[29] (a) Ukita, C.; Mizuno, D. Chem Pharm Bull 1960, 8, 1016; (b)
Ukita, C.; Mizuno, D.; Tamura, T.; Yamakawa, T.; Nojima, S. J Chem
Pharm Soc Jap 1951, 71, 234; 1960, 8, 1016; (c) Wat, C. K.; Innes, A.
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otics 1985, 38, 145; (f) Tanabe, Y.; Miyakodo, M.; Ohno, N.; Yoshioka,
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mann, J.; Wamhoff, H. Liebigs Ann Chem 1974 1287; (f) Vul’fson, N. S.;
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet