Transformation of 1,5-diphenylpentane-1,3,5-trione. The synthesis of substituted (4H)-pyranones, pyridin-4(1H)ones and 4H-pyrano[3,2-c]pyridin-4-ones

Article abstract of DOI:10.3987/COM-07-11252

1,5-Diphenylpentane-1,3,5-trione (1) was transformed by the reaction either with N,N-dimethylformamide dimethyl acetal (DMFDMA) or N,N-dimethylacetamide dimethyl acetal (DMADMA) into (N,N-dimethylamino)-methylidene derivatives 2a,b as intermediates. They

Full text of DOI:10.3987/COM-07-11252

HETEROCYCLES, Vol. 75, No. 4, 2008
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HETEROCYCLES, Vol. 75, No. 4, 2008, pp. 899 - 909. © The Japan Institute of Heterocyclic Chemistry
Received, 26th October, 2007, Accepted, 17th December, 2007, Published online, 18th December, 2007. COM-07-11252
TRANSFORMATION OF 1,5-DIPHENYLPENTANE-1,3,5-TRIONE. THE
SYNTHESIS OF SUBSTITUTED (4H)-PYRANONES, PYRIDIN-4(1H)-
ONES AND 4H-PYRANO[3,2-c]PYRIDIN-4-ONES
Silvo Zupančič, Jurij Svete, and Branko Stanovnik*
Faculty of Chemistry and Chemical Technology, University of Ljubljana,
Aškerčeva 5, P. O. Box 537, 1000 Ljubljana, Slovenia
E-mail: Branko.Stanovnik@fkkt.uni-lj.si
Abstract – 1,5-Diphenylpentane-1,3,5-trione (1) was transformed by the reaction
either with N,N-dimethylformamide dimethyl acetal (DMFDMA) or
N,N-dimethylacetamide dimethyl acetal (DMADMA) into (N,N-dimethylamino)-
methylidene derivatives 2a,b as intermediates. They were converted in the
presence of silica gel into 5-benzoyl-2-phenylpyran-4-one (3a) and its 6-methyl
derivative 3b, while the corresponding 5-benzoyl- 2-phenylpyridin-4(1H)-one (4)
was formed by the reaction with NH4Cl. Compound 3b gave the corresponding
(N,N-dimethylamino)methylidene derivative 5 with DMFDMA, which was
cyclized in aqueous ammonia into 2,5-diphenyl-4H-pyrano[3,2-c]pyridin-4-one
(7). The reaction of 1 with excess of DMFDMA followed by reaction with
ammonia or primary amines yielded 1-substituted 3,5-dibenzoylpyridin-4(1H)-
ones (9a-m).
INTRODUCTION
Substituted pyridin-4(1H)-ones are key structural elements in medicinal chemistry and versatile
intermediates in organic synthesis.1 Many derivatives have been extensively investigated in connection
with the preparation of various alkaloid skeletons.2,3 Pyridin-4(1H)-ones have shown antibacterial,4
antimalarial,5 antineoplastic,6 and other pharmacological activities.
Recently, one step synthesis of 3,5- dibenzoyl-2,6-diphenyl-4-pyrone from the reaction of dibenzoyl-
methane with oxalyl chloride has been described,7 while some other 4-pyranone derivatives have been
prepared from α-oxoketene, generated in situ from 4-ethoxycarbonyl-5-phenyl-2,3-dihydrofuran-2,3-dione
and dibenzoylmethane.7 Condensation reaction of 4-pyranone derivatives with excess primary amines has
provided a series of pyridin-4(1H)-one derivatives.8

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3-Dimethylaminopropenoates and the related enaminones have been demonstrated to be useful reagents in
heterocyclic synthesis,9-16 including preparation of some natural products and their analogs, such as
aplysinopsins,17-20 meridianines,21,22 and dipodazines.23,24 As part of our interest, we have recently
reported an efficient method for the preparation and functionalization of highly substituted
1-aminopyrroline, 1-aminopyrrole, and oxazoline-pyrroline fused system from 1,2-diaza-1,3-butadines
and 3-dimethylaminopropenoates.25 Recently, dialkyl acetonedicarboxylates as compounds with two
activated methylene groups have been used as starting compounds for preparation of mono and
bis(dimethylamino)methylidene intermediates which have been further transformed into 1-substituted
4-oxo-1,4-dihydropyridine-3,5-dicarboxylates,26 2H-pyrazolo[4,3-c]pyridine-7-carboxylates,27 hetero- aryl
substituted pyrazoles,28 heteroaryl substituted pyrimidines,29 and pyrazolo[4,3-d][1,2]diazepine-8-
carboxylates.30,31 In this paper, we report transformations of 1,5-diphenylpentane-1,3,5-trione into
substituted 5-benzoylpyran-4-one, 5-benzoylpyridin-4(1H)-one, 4H-pyrano[3,2-c]pyridin-4-one, and
1-substituted 3,5-dibenzoylpyridin-4(1H)-ones.
RESULTS AND DISCUSSION
When 1,5-diphenylpentane-1,3,5-trione (1) was heated under reflux
N,N-dimethylformamide dimethyl acetal (DMFDMA) or N,N-dimethylacetamide dimethyl acetal
(DMADMA) in n-propyl acetate for 1 hour, the corresponding crude (N,N-dimethylamino)-
with an excess of
methylidene-1,5-diphenylpentane-1,3,5-trione (2a) and mono-(N,N-dimethylamino)ethylidene-1,5-
diphenylpentane-1,3,5-trione (2b) were obtained. They were not isolated in pure form. When the reaction
mixture obtained by evaporation of volatile components was purified by column chromatography over
(CHCl3:MeOH = 95:5, silica gel) the corresponding 5-benzoyl-2-phenyl-4H-pyran-4-one (3a) and its
6-methyl derivative 3b were isolated in 33 % and 78 % yields. The cyclization occurred most probably
in the presence of silicagel. Namely, when the crude reaction mixture, obtained by evaporation of volatile
components, was treated with NH4Cl in ethanol at room temperature for 5 h, the corresponding
5-benzoyl-2-phenylpyridin-4(1H)-one (4) was formed in 57 % yield (Scheme 1).
The reaction of pyranone 3b with DMFDMA yielded compound 5. In the last reaction step, compound 5
was converted into 2,5-diphenyl-4H-pyrano[3,2-c]pyridin-4-one (7) by cyclization of compound 5 in
aqueous ammonia. When this reaction was performed in DMF at 80 °C, the dimethylamino group was
substituted with the amino group and subsequently cyclized into the final product (Scheme 2).
The reaction of 1,5-diphenyl-1,3,5-pentanetrione (1) with excess of DMFDMA followed by addition of
amines yielded 1-substituted 3,5-dibenzoyl-4-oxo-1,4-dihydropyridines (2). The reaction of 1,5-diphenyl-

HETEROCYCLES, Vol. 75, No. 4, 2008
901
Me2N
R
Ph
Ph
Ph
Ph
i
O
O
O
O
O
O
1
2a: R=H
b
: R=Me
H
O
R
Me2N
Ph
R
O
Me2N
Ph
Ph
Ph
OH
O
O
O
2"a,b
2´a,b
iii
R=H
ii
H
N
Ph
O
R
Ph
Ph
Ph
O
O
O
O
3a: R=H
4
b
: R=Me
Scheme 1. Reagents and conditions: i for 2a: DMFDMA, n-PrOAc, reflux; for 2b: DMADMA, n-PrOAc,
reflux; ii column chromatography, silica gel; iii NH4Cl, EtOH, rt.
Me
Ph
O
Ph
Me2N
Ph
O
O
Ph
H2N
Ph
O
O
Ph
i
ii
O
O
O
O
3b
6a
5
H2N
O
O
Ph
O
Ph
iii
O
N
Ph
6b
Ph
O
7
Scheme 2. i DMFDMA, n-PrOAc, reflux; ii DMF, NH4OH (25% aq. solution); iii 80 ˚C, 19 h
1,3,5-pentanetrione (1) with excess of DMFDMA afforded bis(N,N-dimethylamino)methylidene
derivatives 8, which were, without purification, followed by addition of amines yielded 1-substituted

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HETEROCYCLES, Vol. 75, No. 4, 2008
3,5-dibenzoylpyridin-4(1H)-ones (9). The reaction of 1,5-diphenyl-1,3,5-pentanetrione with DMFDMA
was carried on in n-propyl acetate as a solvent at reflux temperature for 12 hours and the solvent was
removed by distillation at reduced pressure. The oily residue was dissolved in another solvent and the
cyclization with various amines to form 1-substituted 3,5-dibenzoyl 4-oxo-1,4-dihydropyridines (2) was
performed at reflux temperature of the solvent, usually ethanol. This reaction was catalyzed by addition of
catalytical amount of conc. HCl. (Scheme 3).
Me2N
Ph
NMe2
Ph
i
Ph
Ph
Ph
ii
O
O
8
O
O
O
1
O
R
N
9 a: R=H
b: R=Me
h: R=4-MeC6H4
i: R=3,5-di-ClC6H3
j: R=pyridin-2-yl
k: R=2-Clpyridin-2-yl
l: R=6-Mepyridin-2-yl
m: R=5-Meisoxazol-3-yl
c: R=CHMe2
d: R=CH2CH2OH
e: R=Ph
f: R=3-BrC6H4
g: R=3-HOC6H4
Ph
O
O
9
O
Scheme 3. i DMFDMA, n-PrOAc, reflux; ii RNH2, reflux
1-Substituted 3,5-dibenzoyl 4-oxo-1,4-dihydropyridines (9) are crystalline compounds and were isolated
by crystallization directly from the reaction mixtures in height yields. It was proved successfully that
1,5-diphenyl-1,3,5-pentanetrione (1) is useful also for the other conversions with DMFDMA.
EXPERIMENTAL
Melting points were taken on a Kofler micro hot stage. The 1H NMR spectra were obtained on a Bruker
Avance DPX 300 (300 MHz) spectrometer in such solvent as DMSO-d6 and CDCl3 with TMS as the
internal standard, MS spectra on an AutoSpecQ spectrometer, IR spectra on a Perkin-Elmer 1310 infrared
spectrophotometer and elemental analyses for C, H and N on a Perkin-Elmer CHN Analyser 2400.
5-Benzoyl-2-phenyl-4H-pyranone (3a). To a solution of 1,5-diphenyl-1,3,5-pentanetrione (666 mg , 2,5
mmol) in n-propyl acetate (5 mL) was added DMFDMA (2 mL, 14,3 mmol) and the mixture was stirred
at rt for 30 min. The reaction mixture was concentrated in vacuum. The residue was chromatographed
o
on a column of silica gel. Elution with CHCl3 : MeOH (98 : 2). Yield 33.3 %; mp 174 - 176 C (from
1
EtOH). IR (KBr, cm–1): 2981, 1735, 1686, 1641, 1580. H NMR (300 MHz, DMSO-d6) δ: 7.16 (s, 1H,
H3), 7.50 – 7.77 (m, 6H, Ph), 7.82 – 8.10 (m, 4H, Ph), 8.66 (s, 1H, H6). 13C NMR (300 MHz, CF3COOH)

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903
δ: 14.1 (OCH2CH3), 14.4 (OCH2CH3) , 42.6, 47.9, 48.6, 59.9 (OCH2CH3), 60.7 (OCH2CH3), 101.1, 159.3,
167.4 (COOEt), 169.2 (COOEt), 189.6 (CO). Anal. Calcd for C18H12O3: C, 78.25; H, 4.38. Found: C,
78.58; H, 4.07.
5-Benzoyl-6-methyl-2-phenyl-4H-pyranone (3b). To a suspension of 1,5-diphenylpentane-1,3,5- trione
(532 mg, 2 mmol) in n-propyl acetate (5 mL) was added DMADMA (0.35 ml, 2,2 mmol) and the mixture
was stirred at reflux temperature for 1 h. The reaction mixture was concentrated in vacuo and 2 mL of
o
EtOH was added. The precipitated product was filtered. Yield 77.9 %; mp 151 - 153 C (from EtOH).
IR (KBr, cm–1): 1649, 1618, 1400, 914, 691. 1H NMR (300 MHz, DMSO-d ) δ: 2.29 (s, 3H, CH3), 7.06 (s,
6
13
1H, H3), 7.50 – 7.77 (m, 6H, Ph), 7.82 – 8.10 (m, 4H, Ph). C NMR (300 MHz, CF3COOH) δ: 17.9,
110.4, 125.86, 126.0, 129.0, 129.1, 129.1, 130.5, 131.7, 134.1, 136.2, 162.9, 163.8, 176.8, 193.6. Anal.
Calcd for C19H14O3: C, 78.61; H, 4.86; N. Found: C, 78.92; H, 4.71.
5-Benzoyl-2-phenylpyridin-4(1H)-one (4). To a solution of 1,5-diphenyl-1,3,5-pentanetrione (1.33 g, 5
mmol) in n-propyl acetate (10 mL) was added DMFDMA (4 mL, 28.5 mmol) and the mixture was stirred
at rt for 30 min. The reaction mixture was concentrated in vacuo. The residue was dissolved in EtOH
(10 mL) and NH4Cl (401 mg, 7.5 mmol) was added. The mixture was stirred at rt for 5 h, cooled and the
precipitate was collected by filtration. Yield 57.3 %, mp 249 - 251 oC (from EtOH). IR (KBr, cm–1): 2981,
1
1735, 1686, 1641, 1580. H NMR (300 MHz, DMSO-d6) δ: 6.6 – 8.3 (m, 12H, Ph, H3,6), 11.8 – 12.2
13
(broad s, 1H, NH). C NMR (300 MHz, CF3CO2H) δ: 14.1 (OCH2CH3), 14.4 (OCH2CH3), 42.6, 47.9,
48.6, 59.9 (OCH2CH3), 60.7 (OCH2CH3), 101.1, 159.3, 167.4 (COOEt), 169.2 (COOEt), 189.6 (CO).
Anal. Calcd for C18H13NO2: C, 78.53; H, 4.76; N, 5.09. Found: C, 78.77; H, 4.84; N, 5.14.
5-Benzoyl-6-[2-(N,N-dimethylamino)ethenyl]-2-phenyl-4H-pyranone (5). To a suspension of
1,5-diphenyl-1,3,5-pentanetrione (532 mg, 2 mmol) in n-propyl acetate (5 mL) was added DMADMA
(0.35 mL, 2,2 mmol) and the mixture was stirred at reflux temperature for 1 h. Then 1,4 mL (10 mmol)
DMFDMA was added and the mixture was stirred additionally at reflux temperature for 16 h. The reaction
mixture was cooled and the precipitated product was collected by filtration. Yield 68.0 %; mp 233 - 241 oC
(from EtOH). IR (KBr, cm–1): 3061, 1675, 1639, 1584, 1542, 1387. 1H NMR (300 MHz, DMSO-d6) δ: 2.50
– 3.00 (broad s, 3H, N(CH3)), 2.80 – 3.40 (broad s, 3H, N(CH3)), 4.75 (d, 1H, CH=CHNMe2, J = 12.6 Hz
(trans)), 6.75 (s, 1H, H3), 7.45 – 7.67 (m, 6H, Ph), 7.66 (d, 1H: CH=CHNMe2, J = 12.6 Hz (trans)), 7.77 –
13
7.83 (m, 2H, Ph), 7.90 - 8.06 (m, 2H, Ph). C NMR (300 MHz, CF3CO2H) δ: 83.7, 109.3, 114.8, 125.9,

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128.6, 128.8, 129.1, 131.0, 131.1, 133.1, 137.7, 148.4, 160.1, 164.1, 176.0, 195.2. Anal. Calcd for
C22H19NO3: C, 76.50; H, 5.54; N, 4.06. Found: C, 76.40; H, 5.63; N, 3.93.
2,5-Diphenyl-4H-pyrano[3,2-c]pyridin-4-one (7). To a solution of 345 mg (1 mmol) of
5-benzoyl-6-[2-(dimethylamino)ethenyl]-2-phenyl-4H-pyranone (5) in DMF (5 mL) was added 0.15 mL
25 % NH4OH (2.0 mmol) and one drop of conc. HCl and the mixture was stirred at 80 oC for19 h. The
reaction mixture was cooled and the precipitated product was collected by filtration. Yield 45.8 %; mp 195
- 197 oC (from EtOH). IR (KBr, cm–1): 3060, 1660, 1651, 1359, 690. 1H NMR (300 MHz, DMSO-d6) δ:
7.06 (s, 1H, H3), 7.36 – 7.77 (m, 8H, Ph), 7.78 (d, 1H, H7), J = 6.0 Hz), 8.10 – 8.15 (m, 2H, Ph), 8.82 (d, 1H,
H8), J = 6.0 Hz) 13C NMR (300 MHz, CF3COOH) δ: 109.8, 112.3, 116.8, 126.3, 127.1, 128.1, 129.2, 129.3,
130.4, 132.0, 140.3, 151.5, 160.4, 161.1, 162.4, 176.1. Anal. Calcd for C20H13NO2: C, 80.25; H, 4.38; N,
4.68. Found: C, 80.31; H, 4.23; N, 4.42.
General procedure for preparation of 1-substituted 3,5-dibenzoylpyridin-4(1H)-ones (9a-m)
The suspension of 1,5-diphenyl-1,3,5-pentanetrione (532 mg, 2 mmol) in n-propyl acetate (5 mL) was
stirred at reflux temperature for several h. The reaction mixture was concentrated in vacuo and the residue
was dissolved in EtOH (5 mL). Then 2.4 mmol of the corresponding amine and one drop of conc. HCl
were added and the mixture was stirred at reflux temperature to complete the reaction. The mixture was
then cooled and the precipitated product was collected by filtration. In this manner, the following
compounds were prepared:
3,5-Dibenzoylpyridin-4(1H)-one (9a). This compound was prepared using ammonia refluxing for 2 h.
Yield 48 %; mp 331-332 °C (from EtOH). IR (KBr, cm–1): 3422, 1667, 1633, 1538, 1267, 593. 1H NMR
(300 MHz, DMSO-d6) δ: 7.48 (m, 4H, H3,5 (Ph)), 7.59 (m, 2H, H4 (Ph)), 7.78 (m, 4H, H2,6 (Ph)), 8.09 (s,
13
2H, H2,6), 11,50 – 12.50 (broad s, 1H, NH). C NMR (300 MHz, DMSO-d6) δ: 128.28, 129.02, 129.88,
132.90, 137.12, 140.03, 173.46, 194.22. Anal. Calcd for C19H13NO3: C, 75.24; H, 4.32; N, 4.62. Found: C,
75.53; H, 4.28; N, 4.91.
3,5-Dibenzoyl-1-methylpyridin-4(1H)-one (9b). This compound was prepared using methylamine in
EtOH at rt for 1 h. Yield 73 %; mp 215-217 °C (from EtOH). IR (KBr, cm–1): 3060, 1660, 1650, 1586,
1178. 1H NMR (300 MHz, DMSO-d ) δ: 3.80 (s, 3H: CH3), 7.48 (m, 4H, H3,5 (Ph)), 7.59 (m, 2H, H4 (Ph)),
6
7.78 (m, 4H, H2,6 (Ph)), 8.16 (s, 2H, H2,6). 13C NMR (300 MHz, DMSO-d6) δ: 43.49, 128.31, 129.05,

HETEROCYCLES, Vol. 75, No. 4, 2008
905
129.99, 133.01, 137.03, 144.01, 172.42, 193.90. Anal. Calcd for C20H15NO3: C, 75.70; H, 4.76; N, 4.41.
Found: C, 75.75; H, 4.81; N, 4.45.
3,5-Dibenzoyl-1-isopropylpyridin-4(1H)-one (9c). This compound was prepared using isopropylamine
in EtOH refluxing for 5 h. Yield 38 %; mp 252-254 °C (from EtOH). IR (KBr, cm–1): 3083, 1662, 1582,
1
1172. H NMR (300 MHz, DMSO-d6) δ: 1.46 (d, 6H, CH3, J = 6.6 Hz), 4.48 (q, 1H: CH, J = 6.6 Hz),
7.50 (m, 4H, H3,5 (Ph)), 7.59 (m, 2H, H4 (Ph)), 7.80 (m, 4H; H2,6 (Ph)), 8.29 (s, 2H, H2,6). 13C NMR (300
MHz, DMSO-d6) δ: 21.9, 58.6, 128.3, 129.1, 130.4, 133.0, 137.0, 140.7, 172.8, 194.0. Anal. Calcd for
C22H19NO3: C, 76.50; H, 5.54; N, 4.06. Found: C, 76.76; H, 5.48; N, 4.31.
3,5-Dibenzoyl-1-(2-hydroxyethyl)pyridin-4(1H)-one (9d). This compound was prepared using
2-ethanolamine in EtOH refluxing for 3h. Yield 53 %; mp 205-207 °C (from i-PrOH). IR (KBr, cm–1):
1
3382, 3052, 1665, 990. H NMR (300 MHz, DMSO-d6) δ: 3.73 (m, 2H, NCH2), 4.11 (m, 2H: CH2OH),
5.15 (t, 1H: OH, J = 5.4 Hz), 7.50 (m, 4H: 2 × H3,5 (Ph)), 7.60 (m, 2H: 2 × H4 (Ph)), 7.80 (m, 4H: 2 × H2,6
(Ph)), 8.16 (s, 2H: H2,6). 13C NMR (300 MHz, DMSO-d ): δ 58.6, 60.0, 128.3, 129.1, 129.8, 133.0, 137.1,
6
143.6, 172.7, 193.9. Anal. Calcd for C21H17NO4: C, 72.61; H, 4.93; N, 4.03. Found: C, 72.99; H, 5.02; N,
3.80.
3,5-Dibenzoyl-1-phenyl-pyridin-4(1H)-one (9e). This compound was prepared using aniline in EtOH
refluxing for 15 h. Yield 61 %; mp 226-228 °C (from EtOH). IR (KBr, cm–1): 3056, 1667, 1644, 1589,
1
1244. H NMR (300 MHz, DMSO-d6) δ: 7.40 – 7.80 (m, 9H, Ph), 7.72 (m, 2H , H4 (Ph)), 7.88 (m, 4H;
H2,6 (Ph)), 8.42 (s, 2H; H2,6). 13C NMR (300 MHz, DMSO-d ) δ: 123.3, 128.4, 128.6, 129.3, 129.9, 130.5,
6
133.2, 136.9, 141.5, 142.2, 172.9, 193.4. Anal. Calcd for C25H17NO3: C, 79.14; H, 4.52; N, 3.69. Found:
C, 79.42; H, 4.36; N, 3.61.
1-(3-Bromophenyl)-3,5-dibenzoylpyridin-4(1H)-one (9f). This compound was prepared using
3-bromoaniline in EtOH refluxing for 5 h. Yield 63 %; mp 236-239 °C (from EtOH). IR (KBr, cm–1):
1670, 1642, 1590, 1529, 1243. 1H NMR (300 MHz, DMSO-d6) δ: 7.40 – 7.80 (m, 9H, Ph), 7.85 – 7.91 (m,
13
4H, (Ph)), 8.05 (m, 1H, Ph), 8.45 (s, 2H, H2,6). C NMR (300 MHz, DMSO-d6) δ: 122.2, 122.6, 126.5,
128.4, 129.3, 130.4, 131.4, 131.6, 133.3, 136.8, 141.3, 143.3, 173.0, 193.3. Anal. Calcd for C25H16BrNO3:
C, 65.52; H, 3.52; N, 3.06. Found: C, 65.80; H, 3.49; N, 2.68.

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3,5-Dibenzoyl-1-(3-hydroxyphenyl)pyridin-4(1H)-one (9g). This compound was prepared using
3-hydroxyaniline in EtOH refluxing for 5 h. Yield 57 %; mp 280-282 °C (from MeCN). IR (KBr, cm–1):
3283, 1669, 1606, 1521, 1202. 1H NMR (300 MHz, DMSO-d ) δ: 6.90 (ddd, 1H, H6 or H4 (Ar), J1 = 8.1
6
Hz, J2 = 2.4 Hz, J3 = 2.1 Hz), 7.05 (dd, 1H, H2 (Ar), J1 = 2.4 Hz, J2 = 2.4 Hz), 7.09 (ddd, 1H, H6 or H4
(Ar), J1 = 8.1 Hz, J2 = 2.4 Hz, J3 = 2.1Hz), 7.37 (dd, 1H, H5 (Ar), J1 = 8.1 Hz, J2 = 8.1Hz), 7.50 (m, 4H,
H3,5 (Ph)), 7.60 (m, 2H, H4 (Ph)), 7.87 (m, 4H, H2,6 (Ph)), 8.36 (s, 2H, H2,6), 10.09 (broad s, 1H, OH). 13C
NMR (300 MHz, DMSO-d6) δ: 110.3, 113.6, 115.7, 128.4, 129.3, 130.4, 130.8, 133.2, 136.9, 141.4,
143.3, 158.5, 172.9, 193.4. Anal. Calcd for C25H17NO4: C, 75.94; H, 4.33; N, 3.54. Found: C, 76.45; H,
4.45; N, 3.24.
3,5-Dibenzoyl-1-(4-methylphenyl)pyridin-4(1H)-one (9h). This compound was prepared using
p-toluidine in EtOH refluxing for 2 h. Yield 56 %; mp 245-246 °C (from EtOH). IR (KBr, cm–1): 1667,
1
1643, 1590, 1244, 694. H NMR (300 MHz, DMSO-d6) δ: 2.38 (s, 3H: CH3), 7.37 (d, 2H, Ar), 7.50 (m,
4H; H3,5 (Ph)), 7.60 (m, 4H; H4 (Ph), Ar), 7.87 (m, 4H, H2,6 (Ph)), 8.37 (s, 2H, H2,6). 13C NMR (300 MHz,
DMSO-d6) δ: 20.5, 123.0, 128.4, 129.2, 130.2, 130.5, 133.2, 136.9, 138.3, 139.9, 141.5, 172.81, 193.4.
Anal. Calcd for C26H19NO3: C, 79.37; H, 4.87; N, 3.56. Found: C, 79.79; H, 4.75; N, 3.65.
3,5-Dibenzoyl-1-(3,4-dichlorophenyl)pyridin-4(1H)-one (9i). This compound was prepared using
3,4-dichloroaniline in EtOH refluxing for 2 h. Yield 62 %; mp 245-247 °C (from MeCN). IR (KBr, cm–1):
1641, 1597, 1525, 1236. 1H NMR (300 MHz, DMSO-d ) δ: 7.52 (m, 4H, H3,5 (Ph)), 7.64 (m, 2H, H4 (Ph)),
6
7.75 (dd, 1H, H6 (Ar), J1 = 8.7 Hz, J2 = 2,7 Hz), 7.87 (m, 5H, H2,6 (Ph), H5 (Ar)), 8.15 (d, 1H, H2 (Ar), J2 =
13
2.7 Hz), 8.45 (s, 2H, H2,6). C NMR (300 MHz, DMSO-d6) δ: 123.9, 125.9, 128.4, 129.2, 130.4, 131.2,
131.4, 132.0, 133.3, 136.8, 141.3, 141.6, 173.0, 193.3. Anal. Calcd for C25H15Cl2NO3: C, 66.98; H, 3.37;
N, 3.12. Found: C, 67.46; H, 3.23; N, 2.92.
3,5-Dibenzoyl-1-(2-pyridyl)pyridin-4(1H)-one (9j). This compound was prepared using
2-aminopyridine in EtOH refluxing for 3 h. Yield 42 %; mp 216-218 °C (from EtOH). IR (KBr, cm–1):
1644, 1592, 1245, 961. 1H NMR (300 MHz, DMSO-d ) δ: 7.52 (m, 5H, H3,5 (Ph), H5 (Het)), 7.64 (m, 2H,
6
H4 (Ph)), 7.87 (m, 4H, H2,6 (Ph)), 8.01 (broad d, 1H, H3 (Het), J = 8.4 Hz), 8.11 (ddd, 1H, H4 (Het), J1 =
8.4 Hz, J2 = 7.5 Hz,), 8.61 (ddd, 1H, H6 (Het), J1 = 4.8 Hz, J2 = 1.8 Hz, J3 = 0.6 Hz), 8.89 (s, 2H, H2,6).
13C NMR (300 MHz, DMSO-d6) δ: 114.5, 123.6, 128.5, 129.2, 130.2, 133.3, 136.8 138.5, 140.3, 148.7,
151.0, 173.7, 193.4. Anal. Calcd for C24H16N2O3: C, 75.78; H, 4.24; N, 7.36. Found: C, 75.87; H, 4.11; N,
7.30.

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1-(2-Chloro-3-pyridyl)-3,5-dibenzoylpyridin-4(1H)-one (9k). This compound was prepared using
3-amino-2-chloropyyridine in EtOH refluxing for 5 h. Yield 34%; mp 251-253 °C (from MeCN). IR (KBr,
1
cm–1): 1636, 1596, 1415, 1272. H NMR (300 MHz, DMSO-d ) δ: 7.53 (m, 4H, H3,5 (Ph)), 7.63 (m, 2H,
6
H4 (Ph)), 7.70 (dd, 1H, H5 (Het), J1 = 7.8 Hz, J2 = 4.8 Hz), 7.86 (m, 4H, H2,6 (Ph)), 8.38 (s, 2H, H2,6), 8.38
(dd, 1H, H4 (Het), J1 = 7.8 Hz, J2 = 1.8 Hz), 8.60 (dd, 1H, H6 (Het), J1 = 4.8 Hz, J2 = 1.8 Hz). 13C NMR
(300 MHz, DMSO-d6) δ: 124.4, 128.5, 129.2, 130.1, 133.4, 136.4, 136.7, 138.0, 142.9, 146.5, 150.6,
172.9, 193.0. Anal. Calcd for C24H15ClN2O3: C, 69.49; H, 3.64; N, 6.75. Found: C, 69.57; H, 3.69; N,
7.00.
3,5-Dibenzoyl-1-(6-methyl-2-pyridyl)pyridin-4(1H)-one (9l). This compound was prepared using
2-amino-6-methylpyridine in EtOH refluxing for 3 h. yield 48 %; mp 244-246 °C (from EtOH/MeCN).
1
IR (KBr, cm–1): 1644, 1585, 1439, 1297. H NMR (300 MHz, DMSO-d ) δ: 2.56 (s, 3H: CH3), 7.40 (d,
6
1H H5 (Het), J = 7.8 Hz), 7.51 (m, 4H, H3,5 (Ph)), 7.63 (m, 2H, H4 (Ph)), 7.79 (d, 1H, H3 (Het), J = 8.4
13
Hz), 7.86 (m, 4H, H2,6 (Ph)), 7.99 (dd, 1H, H4 (Het), J1 = 8.4 Hz, J2 = 7.8 Hz), 8.86 (s, 2H, H2,6). C
NMR (300 MHz, DMSO-d6): δ 23.7, 111.3, 122.9, 128.4, 129.2, 130.2, 133.3, 136.8, 138.4, 140.4,
150.35, 158.0, 173.7, 193.5. Anal. Calcd for C25H18N2O3:C, 76.13; H, 4.60; N, 7.10. Found: C, 76.30; H,
4.72; N, 7.35.
3,5-Dibenzoyl-1-(5-methyl-3-isoxazolyl)pyridin-4(1H)-one (9m). This compound was prepared using
3-amino-5-methylisooxazole in EtOH refluxing for 3 h. Yield 38 %; mp 218-222 °C (from
i-PrOH/MeCN). IR (KBr, cm–1): 3324, 3166, 1741, 1716, 1662, 1335. 1H NMR (300 MHz, DMSO-d6) δ:
2.50 (s, 3H, CH3), 7.07 (s, 1H, H4 (Het)), 7.51 (m, 4H, H3,5 (Ph)), 7.63 (m, 2H, H4 (Ph)), 7.89 (m, 4H, H2,6
(Ph)), 8.58 (s, 2H, H2,6). 13C NMR (300 MHz, DMSO-d ) δ: 12.5, 95.3, 128.5, 129.3, 130.6, 133.5, 136.6,
6
138.1, 160.6, 173.3, 192.8. Anal. Calcd for C23H16N2O4: C, 71.87; H, 4.20; N, 7.29. Found: C, 72.09; H,
4.28; N, 7.18.
ACKNOWLEDGEMENTS
The financial support from the Slovenian Research Agency, Slovenia through grants P0-0502-0103,
P1-0179, and J1-6689-0103-04 is gratefully acknowledged. Financial support by the pharmaceutical
companies LEK-SANDOZ, Ljubljana, and KRKA, Novo Mesto, is fully appreciated.
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