Anilines as substrates in consecutive four-component synthesis of novel 1-aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1 H)-ones

Article abstract of DOI:10.1055/s-0033-1338574

The consecutive four-component synthesis of 5-acylpyridin-2(1H)-ones initiated by a copper-free alkynylation in a one-pot fashion has been expanded to include considerably less nucleophilic anilines as the amine component in the Michael addition step by altering the solvent system to 1,4-dioxane; 17 examples for the synthesis of 1-aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H) -ones were obtained in moderate to good yields.

Full text of DOI:10.1055/s-0033-1338574

522▌
PAPER
paper
Anilines as Substrates in Consecutive Four-Component Synthesis of Novel
1-Aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-ones
1-Aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-ones
Jan Nordmann, Thomas J. J. Müller*
Institut für Organische Chemie und Makromolekulare Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf,
Germany
Fax +49(211)8114324; E-mail: ThomasJJ.Mueller@uni-duesseldorf.de
Received: 04.10.2013; Accepted after revision: 18.11.2013
Dedicated to Prof. Dr. Klaus Theodor Wanner on the occasion of his 60th birthday
instead of primary aliphatic amines. However, the dimin-
Abstract: The consecutive four-component synthesis of 5-acylpyr-
ished nucleophilicity of anilines should raise the activa-
idin-2(1H)-ones initiated by a copper-free alkynylation in a one-pot
tion barrier for the conjugate addition. Here we report
optimization studies for the diversity-oriented synthesis
fashion has been expanded to include considerably less nucleophilic
anilines as the amine component in the Michael addition step by al-
tering the solvent system to 1,4-dioxane; 17 examples for the syn- of novel 1-aryl-5-benzoyl-3,4-dihydropyridin-2(1H)-
thesis of 1-aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-
ones were obtained in moderate to good yields.
ones in a one-pot fashion and discuss the scope of this
methodology based upon our recently developed copper-
Key words: multicomponent reactions, C–C coupling, alkynes,
heterocycles, palladium
free alkynylation.
O
PdCl2 (1 mol%)
(1-Ad)2PBn⋅HBr (2 mol%)
Et3N (1.1 equiv)
R1
In the vast field of heterocycles, 2-pyridones have attract-
ed attention over the past few decades due to the broad oc-
currence of this structural motif in several alkaloids1 with
medicinal applications, e.g. as pulmonary disease drugs.2–4
Since the pioneering work of P. W. Hickmott in 1971 on
the synthesis of 5-acylpyridin-2(1H)-ones starting from
readily available β-enaminones and α,β-unsaturated acid
chlorides,5 the aza annulation strategy has been continous-
ly developed over the last decades. But it was not until the
early 1990s that the group of J. R. Stille discovered that
changing the solvent system from highly carcinogenic
benzene to the much more Lewis basic tetrahydrofuran
not only gave higher yields, but also enhanced rates under
milder reaction conditions.1c,6 Furthermore, the obstacles
presented by reacting imines and α,β-unsaturated acids
have now been overcome by using acid-activating re-
agents.7 In addition, the aza annulation of maleic anhy-
dride,8 itaconic anhydride,9 and citraconic anhydride8c,d
led to the corresponding five-membered β-lactams or sub-
stituted tetrahydropyridin-2(1H)-ones. Even solid-phase
syntheses have been described.10
CH2Cl2, r.t., 2–22 h
O
R2
N
O
+
R2
then: R3C6H4CH2NH2
40 °C, 20 h
then: CH2=CHCOCl
r.t., 3.5 h
R1
Cl
R3
28 examples
(31–71%)
Scheme 1 Consecutive four-component synthesis of 5-acyl-1-ben-
zyl-3,4-dihydropyridin-2(1H)-ones in a one-pot fashion13
First we set out to examine the formation of the 1-aryl-5-
benzoyl-3,4-dihydropyridin-2(1H)-ones in dichlorometh-
ane as a solvent. Due to its weak coordinating ability it
should be a favorable solvent for the terminal aza annula-
tion step. We recently established that the reaction of one
equivalent of 2-chlorobenzoyl chloride (1a) and one
equivalent of phenylacetylene (2a) under copper-free al-
kynylation conditions furnishes the intermediate alkynone
3a within two hours (monitored by TLC).13 Then 4-fluo-
roaniline (4a) was added to the reaction mixture. We
found that 3a was only quantitatively converted into the
corresponding β-enaminone 5a when the reaction was
conducted at 50 °C for at least 48 hours. Finally, 1.15
equivalents of acryloyl chloride (6) were added and, after
stirring at 50 °C for 3.5 hours, 5-(2-chlorobenzoyl)-1-(4-
fluorophenyl)-6-phenyl-3,4-dihydropyridin-2(1H)-one
(7a) was isolated in 50% yield (Scheme 2).
Nonetheless, very few examples are known in the litera-
ture of the synthesis of 5-acyl-1-aryl-3,4-dihydropyridin-
2(1H)-ones.11 In the past decade we have developed a
multicomponent concept for many classes of heterocycles
in a consecutive one-pot fashion initiated by catalytic ac-
cesses to enones and ynones.12 Therefore, we reasoned
that our recently developed copper-free palladium-cata-
lyzed access to ynones as applied in the synthesis of 5-ac-
ylpyridin-2(1H)-ones in a one-pot fashion (Scheme 1)13
could be extended to anilines in the Michael addition step
Two more aniline derivatives, p-toluidine (4b) and 4-
chloroaniline (4c), were also successfully applied in the
one-pot reaction giving the desired products 7b and 7c in
55% and 44% yields, respectively, when the Michael ad-
dition step was conducted for between 48 and 68 hours
(Scheme 3, Table 1, entries 2 and 3). However the use of
anilines with strongly electron-withdrawing substituents
in the para position, such as 4-aminobenzonitrile (entry 4)
or 4-(trifluoromethyl)aniline (entry 5) only led to the
SYNTHESIS 2014, 46, 0522–0530
Advanced online publication: 10.12.2013
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DOI: 10.1055/s-0033-1338574; Art ID: SS-2013-T0661-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
1-Aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-ones
523
Cl
O
Table 1 Variation of the Aniline 4 in the 4CR Synthesis of 1-Aryl-
5-(2-chlorobenzoyl)-6-phenyl-3,4-dihydropyridin-2(1H)-ones 7 in
Dichloromethanea
PdCl2 (1 mol%)
(1-Ad)2PBn⋅HBr (2 mol%)
Et3N (1.1 equiv)
R1
O
CH2Cl2, r.t., 2 h
Ph
N
F
O
+
Ph
Cl
Entry Aniline 4
2-Pyridone 7
Yieldb
(%)
then: p-FC6H4NH2 (4a)
50 °C, 48 h
then: CH2=CHCOCl (6)
50 °C, 3.5 h
Cl
O
1a (R1 = Cl)
2a
7a (50%)
Ph
N
F
O
coupling
azaannulation
6
1
R3 = 4-FC6H4 4ac
50
F
R1
O
R1
O
HN
4a
aniline addition
7a
Ph
Ph
Cl
O
3a
5c
Scheme 2 Exploration of the synthesis of 5-(2-chlorobenzoyl)-1-(4-
fluorophenyl)-6-phenyl-3,4-dihydropyridin-2(1H)-one in a one-pot
fashion in dichloromethane as a solvent and mechanistic rationale
Ph
N
O
2
R3 = 4-MeC6H4 4bd
55
Me
quantitative formation of the corresponding acryloyl am-
ides, indicating that the Michael addition step prior to aza
annulation had completely failed. 3,5-Dimethoxyaniline
(entry 6) also failed to give the expected dihydropyridin-
2(1H)-one derivative.
7b
Cl
O
Ph
N
O
3
R3 = 4-ClC6H4 4cd
44
PdCl2 (1 mol%)
(1-Ad)2PBn⋅HBr (2 mol%)
Et3N (1.1 equiv)
Cl
O
CH2Cl2, r.t., 2 h
Cl
+
1a
2a
(1.00 equiv) (1.00 equiv)
then: R3NH2 (4)
(1.03 equiv)
50 °C, 48–68 h
then: CH2=CHCOCl (6)
(1.15 equiv)
Ph
N
R3
O
7c
4
5
6
R3 = 4-NCC6H4 4d
R3 = 4-F3CC6H4 4e
R3 = 3,5-(MeO)2C6H3 4f
–
–
–
7
50 °C, 3.5 h
Scheme 3 Variation of the aniline 4 in the 4CR synthesis of 1-aryl-
5-(2-chlorobenzoyl)-6-phenyl-3,4-dihydropyridin-2(1H)-ones 7 in a
one-pot fashion in dichloromethane
a All reactions were carried out on a 2-mmol scale [c0(1) = c0(2) = 1.0
M].
b All yields refer to isolated and purified products.
c The Michael addition step was performed at 50 °C for 48 h.
d The Michael addition step was performed at 50 °C for 68 h.
Also employing various Lewis acids, such as indium(III)
triflate,14 silver(I) acetate,15 silver(I) tetrafluoroborate,16
and Amberlyst®,16,17 which have already been successful-
ly used as catalysts in addition reactions of amines to dou-
ble and triple bonds, in the Michael addition step proved
to be unsuccessful at a temperature range from room tem-
perature to 50 °C. Furthermore, the addition of triflic
acid18 in the Michael addition step did not show any rate
enhancement.
The reaction of 1a, 2a, 4-chloroaniline (4c), and 6 furnish-
ing 7c was chosen as the model reaction for the optimiza-
tion of the solvent (Scheme 4, Table 2).
PdCl2 (1 mol%)
(1-Ad)2PBn⋅HBr (2 mol%)
solvent, Et3N (1.1 equiv), r.t., t1
1a
+
2a
7c
Therefore, we questioned whether dichloromethane was
still the most appropriate solvent to fulfill all prerequisites
of the complete sequence. Firstly, the copper-free al-
kynylation has to occur at reasonable rates. Secondly, a
broader range of anilines 4 should undergo the Michael
addition at higher rates. And thirdly, the reaction time of
the terminal aza annulation step should be comparably
fast to the reaction in dichloromethane.
then: p-ClC6H5NH2 (4c), T2, t2
then: CH2=CHCOCl (6), T3, t3
Scheme 4 Model reaction for the optimization the one-pot coupling–
addition–aza-annulation synthesis of 5-acyl-1-aryl-6-phenyl-3,4-di-
hydropyridin-2(1H)-ones 7
Dichloromethane was chosen for comparison (Table 2,
entry 1). 1,2-Dichloroethane has a similar polarity to di-
chloromethane and can be utilized at higher reaction tem-
peratures, although, its acute toxicity19 rather prohibits its
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 522–530

524
J. Nordmann, T. J. J. Müller
PAPER
Table 2 Variation of the Aniline 4 in the 4CR Synthesis of 1-Aryl-5-(2-chlorobenzoyl)-6-phenyl-3,4-dihydropyridin-2(1H)-ones 7 in Dichlo-
romethanea
Entry
Solvent
Sonogashira coupling
Michael addition
Aza annulation
Yieldb (%) of 7c
T1
t1
T2
t2
T3
t3
1
2
3
4
5
6
CH2Cl2
DCE
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
2 h
50 °C
80 °C
80 °C
80 °C
100 C
100 °C
68 h
22 h
21 h
50 h
46 h
38 h
50 °C
70 °C
60 °C
60 °C
70 C
70 °C
3.5 h
4 h
44
39
2.5 h
1.5 h
1 h
MeCN
MeCN
MeCN
1,4-dioxane
3.5 h
16 h
3.5 h
3.5 h
48c
44
1 h
58c
46
9 h
a All reactions were carried out on a 2-mmol scale [c0(1a) = c0(2a) = 1.0 M].
b All yields refer to isolated and purified products.
c Not pure: product was isolated in a mixed fraction with N-(4-chlorophenyl)acrylamide.
O
use in practical and safe syntheses. Using 1,2-dichloroeth-
ane the alkynylation at room temperature is complete after
PdCl2 (1 mol%)
(1-Ad)2PBn⋅HBr (2 mol%)
R1
O
Et3N (1.1 equiv)
2.5 hours, the Michael addition proceeds at 80 °C within
22 hours, and the aza annulation at 70 °C for 4 hours to
give 7c in 39% yield (entry 2). With acetonitrile as the sol-
vent, the alkynylation was complete within one hour and
the enaminone was formed at 80 °C within 21 hours (entry
3). Although the aza annulation was complete at 60 °C
within 3.5 hours and the product was isolated in 48%
yield, it was still contaminated with the corresponding ac-
ryloyl anilide arising from residual aniline from the in-
complete Michael addition.
1,4-dioxane, r.t., 19 h
Ph
N
O
+
2a
Cl
then: p-ClC6H4NH2 (4c)
120 °C, 48 h
then: CH2=CHCOCl (6)
70 °C, 3.5 h
Cl
1b (R1 = H)
7d (52%)
Scheme 5 Optimized conditions for the four-component synthesis of
5-benzoyl-1-(4-chlorophenyl)-6-phenyl-3,4-dihydropyridin-2(1H)-
one (7d) in 1,4-dioxane as a solvent
O
Prolonged heating in the Michael addition step did not
give a higher isolated yield in comparison to the reaction
in dichloromethane (entry 4). Increasing the reaction tem-
peratures for the Michael and aza annulation steps led to
higher yields, yet the isolated product 7c was contaminat-
ed with the acryloyl anilide (entry 5). Changing the sol-
vent to 1,4-dioxane was accompanied by a longer reaction
time for the alkynylation, however, comparable reaction
times and temperatures for the Michael addition and the
aza annulation finally gave a comparable yield for the
pure isolated product 7c as with acetonitrile as a solvent
(entry 6).
PdCl2 (1 mol%)
(1-Ad)2PBn⋅HBr (2 mol%)
Et3N (1.1 equiv)
1,4-dioxane, r.t., 19 h
Ph
N
R3
O
1b
+
2a
then: R3NH2 (4)
120 °C, 48 h
then: CH2=CHCOCl (6a)
70 °C, 3.5 h
7
Scheme 6 Variation of anilines 4 in the 4CR synthesis of 1-aryl-5-
benzoyl-6-diphenyl-3,4-dihydropyridin-2(1H)-ones 7 in 1,4-dioxane
Notably, attention should be turned towards the Michael
addition, which previously failed for anilines 4 with
strongly electron-withdrawing groups in the para position
and bulky substituents in the meta position with dichloro-
methane as the solvent for the one-pot reaction (Table 1,
entries 4–6). Benzoyl chloride (1b), phenylacetylene (2a),
and acryloyl chloride (6a) were kept constant as the reac-
tion partners (Scheme 6). The synthesized 1-aryl-5-ben-
zoyl-6-diphenyl-3,4-dihydropyridin-2(1H)-ones 7 were
all obtained in moderate to good yields (10–65%) and the
Using benzoyl chloride (1b) and phenylacetylene (2a), 4-
chloroaniline (4c), and acryloyl chloride (6) as the sub-
strates, with alkynylation at room temperature for 19
hours, Michael addition at 120 °C for 48 hours, and aza
annulation at 70 °C for 3.5 hours gave an isolated yield of
5-benzoyl-1-(4-chlorophenyl)-6-phenyl-3,4-dihydropyri-
din-2(1H)-one (7d) of 52% (Scheme 5).
structures were unambiguously assigned by H and 13C
NMR spectroscopy, mass spectrometry, and combustion
analysis.
1
With this solvent (1,4-dioxane) and optimized conditions
for the coupling–addition–aza annulation sequence with
4-chloroaniline (4c) as the amino component in hand, we
then examined the scope of the aniline in respect of elec-
tronic and steric factors while keeping constant benzoyl
chloride (1b), phenylacetylene (2a), and acryloyl chloride
(6) as the partners (Scheme 6, Table 3).
The newly established reaction sequence (Table 3) in 1,4-
dioxane as a solvent is particularly advantageous for ani-
lines 4 with electron-donating or weakly electron-with-
drawing substituents in the para position (entries 1, 3, 6–
8, and 12). The corresponding 5-acylpyridin-2(1H)-ones
Synthesis 2014, 46, 522–530
© Georg Thieme Verlag Stuttgart · New York

PAPER
1-Aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-ones
525
7 were isolated in analytically pure form in overall yields try 16). However, even the optimized reaction sequence
between 49% and 65% after column chromatography. reaches its limits when the pKa values of the conjugated
This matches with an average yield of at least 79% per re- acids of the anilines 4 drop below 3.6. For the latter, all
action step.
isolated yields fall below 40%, due to incomplete Michael
additions under the given reaction conditions. For in-
stance, 4-(trifluoromethyl)aniline (4e), an extremely elec-
tron-poor aniline (pKa 2.77), gives the dihydropyridone
7q in only 10% isolated yield (entry 14). The major prod-
uct of the transformation of this aniline is the correspond-
ing acryloyl anilide, which was identified unambiguously
by NMR spectroscopy and mass spectrometry.
Table 3 Variation of the Aniline 4 in the 4CR Synthesis of 1-Aryl-
5-(2-chlorobenzoyl)-6-phenyl-3,4-dihydropyridin-2(1H)-ones 7 in
1,4-Dioxanea
Entry
Aniline 4
2-Pyridone Yieldb
7
(%)
1
2
R3 = 4-ClC6H4 4c
7d
7e
7f
52
34
63
38
12
63
49c
60
54
43
49
65
22
10
36
46
41
In conclusion we have successfully revisited our recently
published one-pot, four-component reaction for the syn-
thesis of 5-acylpyridin-2(1H)-ones in dichloromethane as
the solvent. By altering the solvent system to 1,4-dioxane,
various substituted anilines are now well tolerated under
the optimized reaction conditions and furnish the desired
1-aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-ones
7 in moderate to good yields. The key step of this diversi-
ty-orientated synthesis is the generation of the intermedi-
ate β-enaminones, which failed for electron-deficient and
sterically hindered anilines when dichloromethane was
used as the solvent. Undoubtedly, this novel four-compo-
nent approach is well suited for the easy access to libraries
of 5-acyl-1-aryl-3,4-dihydropyridin-2(1H)-ones, which
have remained almost unknown in literature to date.
R3 = 3-ClC6H4 4g
3
R3 = 4-FC6H4 4a
4
R3 = 3-FC6H4 4h
7g
7h
7i
5
R3 = 2-FC6H4 4i
6
R3 = Ph 4j
7
R3 = 4-Me2NC6H4 4k
R3 = 4-MeOC6H4 4l
R3 = 3-MeOC6H4 4m
R3 = 2-MeOC6H4 4n
R3 = 3,5-(MeO)2C6H3 4f
R3 = 4-MeC6H4 4b
R3 = 3,5-F2C6H3 4o
R3 = 4-F3CC6H4 4e
R3 = 1-naphthyl 4p
R3 = 4-hydroxy-1-naphthyl 4q
R3 = anthracen-1-yl 4r
7j
8
7k
7l
9
10
11
12
13
14
15
16
17
7m
7n
7o
7p
7q
7r
7s
7t
1
The H, 13C, and 135-DEPT spectra were recorded on a Bruker
AVIII-300 or Bruker Avance III-600 spectrometer. CDCl3 was used
as a solvent. The resonance of CDCl3 was locked as internal stan-
dard (CDCl3: 1H δ = 7.26, 13C δ = 77.0). The EI mass spectra were
measured on a Finnigen MAT 8200 spectrometer and the GC mass
spectra were measured on a GCMS-QP2010 S spectrometer from
Shimadzu. IR spectra were obtained on Shimadzu IRAffinity-1.
The melting points (uncorrected) were measured on a Büchi Melt-
ing Point B-540. Combustion analyses were carried out on Perkin
Elmer Series II Analyzer 2400 in the microanalytical laboratory of
the Institut für Pharmazeutische und Medizinische Chemie at the
Heinrich-Heine-Universität Düsseldorf.
a All reactions were carried out on a 2-mmol scale [c0(1) = c0(2) = 1.0
M].
b All yields refer to isolated and purified products.
c Hydrochloride salt of the product was formed during the aza annu-
lation, therefore Et3N was added to the eluent upon column chroma-
tography.
1-Aryl-5-(2-chlorobenzoyl)-6-phenyl-3,4-dihydropyridin-
2(1H)-ones 7a–c; General Procedure
PdCl2 (3.5 mg, 0.02 mmol, 1 mol%) and di(1-adamantyl)ben-
zylphosphonium bromide (18.9 mg, 0.04 mmol, 2 mol%) were
placed in a dry Schlenk tube under an argon atmosphere and anhyd
CH2Cl2 (2 mL) was added. 2-Chlorobenzoyl chloride (1a, 360 mg,
2.00 mmol), phenylacetylene (2a, 209 mg, 2.00 mmol), and reagent
grade Et3N (0.30 mL, 2.15 mmol) were added to the mixture, which
was then stirred at r.t. for 2 h until complete conversion (monitored
by TLC). Then substituted anilines (2.05 mmol) were added and the
mixture was stirred for 48–68 h at 50 °C (oil bath). The mixture was
allowed to cool to r.t. and acryloyl chloride (0.2 mL, 2.3 mmol) was
successively added. After stirring for 3.5 h at 50 °C in an oil bath,
EtOH (1 mL) was subsequently added and stirring was continued
for 15 min. The solvents were removed in vacuo and the residue was
purified by flash chromatography (silica gel, n-hexane–EtOAc) to
give the desired products.
Compound 7j (entry 7) was isolated in the lowest yield in
this series since the formed hydrochloride salt hampered
its isolation by chromatography. Furthermore, sterically
more demanding amines m-anisidine (4m) and o-anisi-
dine (4n) were employed equally well under these opti-
mized reaction conditions (entries 9 and 10). Likewise
3,5-dimethoxyaniline (4f) was successfully reacted (entry
11); this reaction failed completely when dichlorometh-
ane was the solvent (Table 1, entry 6). In addition annulat-
ed ring systems such as 1-naphthylamine (4p), 4-
aminonaphthalen-1-ol (4q) (as the hydrochloride salt),
and 1-aminoanthracene (4r) were employed in the reac-
tion sequence (entries 15–17). Although acryloyl chloride
(6) reacted to a small extent with the free OH group of the
naphthol of the 4-aminonaphthalen-1-ol moiety, the de-
5-(2-Chlorobenzoyl)-1-(4-fluorophenyl)-6-phenyl-3,4-dihydro-
pyridin-2(1H)-one (7a)
Yellow solid; yield: 406 mg (50%); mp 124 °C.
IR (diamond): 3155 (w), 3061 (w), 2974 (w), 1690 [ν (C=O), s],
1618 [ν (C=O), s], 1510 (s), 1356 (s), 1221 [δ (C–F), s], 1194 (s),
sired product 7s was still isolated in 46% overall yield (en- 1167 (s), 1148 cm–1 (s).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 522–530

526
J. Nordmann, T. J. J. Müller
PAPER
1H NMR (300 MHz, CDCl3): δ = 2.89–3.11 (m, 4 H), 6.74–6.95 (m,
10 H), 6.95–7.01 (m, 3 H).
5-Benzoyl-1-(4-chlorophenyl)-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7d); Typical Procedure
PdCl2 (3.5 mg, 0.02 mmol, 1 mol%) and di(1-adamantyl)ben-
zylphosphonium hydrobromide (18.9 mg, 0.04 mmol, 2 mol%)
were placed in a dry Schlenk tube under an argon atmosphere and
anhyd 1,4-dioxane (2 mL) was added. Benzoyl chloride (1b, 284
mg, 2.00 mmol), phenylacetylene (2a, 209 mg, 2.00 mmol), and re-
agent grade Et3N (0.30 mL, 2.15 mmol) were added to the mixture,
and stirring at r.t. was continued for 19 h until complete conversion
(monitored by TLC). Then, 4-chloroaniline (4c, 267 mg, 2.05
mmol) was added and the mixture was stirred for 48 h at 120 °C (oil
bath). The mixture was allowed to cool to r.t. and acryloyl chloride
(0.2 mL, 2.3 mmol) was successively added. After stirring at 70 °C
(oil bath) for 3.5 h, EtOH (1 mL) was subsequently added and stir-
ring was continued for 15 min. The solvents were removed in vacuo
and the residue was purified by flash chromatography (silica gel, n-
hexane–EtOAc, 5:1) to give compound 7d as a pale fawn/yellowish
solid; yield: 403 mg (52%); mp 158 °C.
13C NMR (75 MHz, CDCl3): δ = 23.4 (CH2), 32.1 (CH2), 115.6 (d,
J = 22.9 Hz, 2 CH), 120.7 (Cquat), 126.3 (CH), 127.6 (2 CH), 128.9
(CH), 129.6 (CH), 130.0 (CH), 130.2 (2 CH), 130.7 (CH), 130.8
(Cquat), 131.1 (d, J = 8.7 Hz, 2 CH), 133.1 (Cquat), 133.8 (d, J = 3.4
Hz, Cquat), 139.9 (Cquat), 150.1 (Cquat), 161.3 (d, J = 247.7 Hz, Cquat),
171.1 (Cquat), 196.1 (Cquat).
MS (EI+): m/z (%) = 407.2 ([M+(Cl37)], 19), 405.2 ([M+(Cl35)], 51),
370.2 ([M+ – Cl], 57), 328.2 ([M+ – C2H2ClO], 41), 310.1
([M+(Cl35) – C6H4F], 1), 294.2 ([M+ – C6H4Cl], 6), 266.1 ([M+ –
C7H4ClO], 43), 198.1 ([M+ – C11H8ClO2], 60), 141.1 ([M+(Cl37) –
C17H13FNO], 32), 139.1 ([M+(Cl35) – C17H13FNO], 98), 113.1
([M+(Cl37) – C18H13FNO2], 27), 111.1 ([M+(Cl35) – C18H13FNO2],
94), 95.1 ([M+ – C18H13ClNO2], 100).
Anal. Calcd for C24H17ClFNO2 (405.9): C, 71.03; H, 4.22; N, 3.45.
Found: C, 70.90; H, 4.36; N, 3.62.
IR (diamond): 3057 (w), 3032 (w), 1701 [ν (C=O), s], 1638 [ν
(C=O), s], 1595 (m), 1614 (s), 1491 (s), 1346 (s), 1325 (s), 1281 (s),
1192 (s), 1165 (s), 1142 cm–1 (s).
1H NMR (300 MHz, CDCl3, r.t.): δ = 2.86–3.01 (m, 4 H), 6.84–6.98
(m, 7 H), 7.08–7.14 (m, 2 H), 7.15–7.22 (m, 2 H), 7.27–7.34 (m, 1
H), 7.57–7.63 (m, 2 H).
13C NMR (75 MHz, CDCl3, r.t.): δ = 24.7 (CH2), 32.5 (CH2), 120.8
(Cquat), 128.0 (2 CH), 128.1 (2 CH), 128.7 (2 CH), 128.9 (CH),
129.0 (2 CH), 130.2 (2 CH), 130.2 (2 CH), 132.5 (CH), 132.8
(Cquat), 133.6 (Cquat), 136.7 (Cquat), 137.5 (Cquat), 145.7 (Cquat), 170.7
(Cquat), 197.5 (Cquat).
MS (EI+): m/z (%) = 387.0 ([M+(Cl35)], 14), 180.9 ([M+(Cl35) –
C15H10O], 16), 128.9 ([M+(Cl37) – C18H16O2], 29), 126.9 ([M+(Cl35)
– C18H16O2], 88), 104.9 ([M+ – C17H13ClNO], 100), 76.9 ([M+ –
C18H13ClNO2], 36).
5-(2-Chlorobenzoyl)-6-phenyl-1-(p-tolyl)-3,4-dihydropyridin-
2(1H)-one (7b)
Yellow solid; yield: 445 mg (55%); mp 174 °C.
IR (diamond): 3061 (w), 3032 (w), 2909 (w), 1690 [ν (C=O), s],
1614 [ν (C=O), s], 1354 (s), 1190 (s), 1165 (s), 1146 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.15 (s, 3 H), 2.87–3.13 (m, 4 H),
6.79 (td, J = 5.6, 3.4 Hz, 5 H), 6.83–6.94 (m, 5 H), 6.95–7.01 (m, 3
H).
13C NMR (75 MHz, CDCl3): δ = 21.1 (CH3), 23.5 (CH2), 32.2
(CH2), 120.4 (Cquat), 126.2 (CH), 127.4 (2 CH), 128.7 (CH), 129.2
(2 CH), 129.3 (2 CH), 129.6 (CH), 130.0 (CH), 130.2 (2 CH), 130.6
(CH), 130.8 (Cquat), 133.4 (Cquat), 135.2 (Cquat), 137.3 (Cquat), 140.0
(Cquat), 150.6 (Cquat), 171.2 (Cquat), 196.2 (Cquat).
MS (EI+): m/z (%) = 403.2 ([M+(Cl37)], 18), 401.1 ([M+(Cl35)], 52),
366.2 ([M+ – Cl], 47), 324.2 ([M+ – C2H2ClO], 32), 290.1 ([M+ –
C6H4Cl], 4), 262.1 ([M+ – C7H4ClO], 47), 194.1 ([M+ – C11H8ClO2],
38), 141.1 ([M+(Cl37) – C18H16NO], 22), 139.1 ([M+(Cl35) –
C18H16NO], 68), 113.1 ([M+(Cl37) – C19H16NO2], 16), 111.0
([M+(Cl35) – C19H16NO2], 47), 91.1 ([M+ – C18H13ClNO2], 100).
Anal. Calcd for C24H18ClNO2 (387.9): C, 74.32; H, 4.68; N, 3.61.
Found: C, 74.52; H, 4.77; N, 3.67.
5-Benzoyl-1-(3-chlorophenyl)-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7e)
Fawn/yellowish solid; yield: 265 mg (34%); mp 192 °C.
Anal. Calcd for C25H20ClNO2 (401.9): C, 74.71; H, 5.02; N, 3.49.
Found: C, 74.91; H, 5.29; N, 3.47.
IR (diamond): 3073 (w), 2980 (w), 2970 (w), 2945 (w), 1707 [ν
(C=O), s], 1634 [ν (C=O), s], 1348 (s), 1329 (s), 1283 (s), 1194 (s),
1173 (s), 1144 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.86–3.02 (m, 4 H), 6.85–6.96 (m,
6 H), 6.99–7.10 (m, 3 H), 7.14–7.24 (m, 2 H), 7.27–7.35 (m, 1 H),
7.57–7.64 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 24.7 (CH2), 32.5 (CH2), 120.9
(Cquat), 127.3 (CH), 127.4 (CH), 127.9 (2 CH), 128.2 (2 CH), 128.9
(CH), 129.1 (2 CH), 129.4 (CH), 129.4 (CH), 130.2 (2 CH), 132.5
(CH), 133.5 (Cquat), 134.0 (Cquat), 137.5 (Cquat), 139.2 (Cquat), 145.6
(Cquat), 170.6 (Cquat), 197.5 (Cquat).
5-(2-Chlorobenzoyl)-1-(4-chlorophenyl)-6-phenyl-3,4-dihydro-
pyridin-2(1H)-one (7c)
Yellow solid; yield: 371 mg (44%); mp 185 °C.
IR (diamond): 3057 (w), 1688 [ν (C=O), s], 1616 [ν (C=O), s], 1352
(s), 1192 (s), 1148 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.91–3.09 (m, 4 H), 6.75–6.96 (m,
8 H), 6.96–7.03 (m, 3 H), 7.04–7.10 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 23.5 (CH2), 32.1 (CH2), 120.9
(Cquat), 126.3 (CH), 127.7 (2 CH), 128.8 (2 CH), 129.1 (CH), 129.6
(CH), 130.1 (CH), 130.2 (2 CH), 130.7 (2 CH), 130.8 (CH), 130.8
(Cquat), 133.0 (Cquat), 133.3 (Cquat), 136.4 (Cquat), 139.8 (Cquat), 149.8
(Cquat), 171.0 (Cquat), 196.1 (Cquat).
MS (EI+): m/z (%) = 387.1 ([M+(Cl35)], 9), 127.1 ([M+(Cl35) –
C18H16O2], 4), 105.1 ([M+ – C17H13ClNO], 47), 77.1 ([M+
C18H13ClNO2], 100).
–
MS (EI+): m/z (%) = 423.1 ([M+(Cl37)], 23), 421.1 ([M+(Cl35)], 33),
388.1 ([M+(Cl37) – Cl], 14), 386.2 ([M+(Cl35) – Cl], 42), 346.1
([M+(Cl37) – C2H2ClO], 10), 344.1 ([M+(Cl35) – C2H2ClO], 26),
312.0 ([M+(Cl37) – C6H4Cl], 2), 310.1 ([M+(Cl35) – C6H4Cl], 5),
284.1 ([M+(Cl37) – C7H4ClO], 9), 282.1 ([M+(Cl35) – C7H4ClO], 25),
242.1 ([M+(Cl37) – C9H9ClNO], 6), 240.1 ([M+(Cl35) – C9H9ClNO],
16), 141.0 ([M+(Cl37) – C17H13ClNO], 26), 139.1 ([M+(Cl35) –
C17H13ClNO], 82), 113.0 ([M+(Cl37) – C18H13ClNO2], 34), 111.0
([M+(Cl35) – C18H13ClNO2], 100).
Anal. Calcd for C24H18ClNO2 (387.9): C, 74.32; H, 4.68; N, 3.61.
Found: C, 74.48; H, 4.68; N, 3.49.
5-Benzoyl-1-(4-fluorophenyl)-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7f)
Yellow solid; yield: 470 mg (63%); mp 184 °C.
IR (diamond): 3075 (w), 3024 (w), 1703 [ν (C=O), s], 1626 (m),
1611 [ν (C=O), s], 1508 (s), 1350 (s), 1288 (s), 1217 (s), 1194 cm–1
(s).
Anal. Calcd for C24H17Cl2NO2 (422.3): C, 68.26; H, 4.06; N, 3.32.
Found: C, 68.07; H, 4.14; N, 3.35.
1H NMR (300 MHz, CDCl3): δ = 2.86–3.02 (m, 4 H), 6.78–6.94 (m,
7 H), 6.94–7.02 (m, 2 H), 7.15–7.22 (m, 2 H), 7.27–7.33 (m, 1 H),
7.56–7.63 (m, 2 H).
Synthesis 2014, 46, 522–530
© Georg Thieme Verlag Stuttgart · New York

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1-Aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-ones
527
13C NMR (75 MHz, CDCl3): δ = 24.7 (CH2), 32.5 (CH2), 115.5 (d,
J = 22.9 Hz, 2 CH), 120.5 (Cquat), 127.9 (2 CH), 128.1 (2 CH), 128.8
(CH), 129.1 (2 CH), 130.2 (2 CH), 130.6 (d, J = 8.7 Hz, 2 CH),
132.4 (CH), 133.7 (Cquat), 134.0 (d, J = 3.4 Hz, Cquat), 137.6 (Cquat),
146.0 (Cquat), 161.1 (d, J = 247.3 Hz, Cquat), 170.8 (Cquat), 197.6
(Cquat).
MS (EI+): m/z (%) = 371.2 ([M+], 9), 342.1 ([M+ – CO], 2), 328.2
([M+ – C2H2O], 2), 266.2 ([M+ – C7H5O], 2), 198.1 ([M+ – C12H11F],
10), 105.1 ([M+ – C17H13FNO], 42), 95.1 ([M+ – C18H14NO], 22),
77.1 ([M+ – C18H13FNO2], 100).
13C NMR (75 MHz, CDCl3): δ = 24.8 (CH2), 32.6 (CH2), 120.4
(Cquat), 127.2 (CH), 127.7 (2 CH), 128.1 (2 CH), 128.5 (2 CH),
128.6 (CH), 129.1 (4 CH), 130.3 (2 CH), 132.3 (CH), 133.9 (Cquat),
137.8 (Cquat), 138.1 (Cquat), 146.4 (Cquat), 170.8 (Cquat), 197.7 (Cquat).
MS (EI+): m/z (%) = 353.3 ([M+], 17), 310.3 ([M+ – C2H2O], 4),
296.3 ([M+ – C3H4O], 2), 276.3 ([M+ – C6H5], 2), 248.2 ([M+ –
C7H5O], 7), 180.2 ([M+ – C11H10O2], 14), 105.1 ([M+ – C17H14NO],
32), 93.1 ([M+ – C18H14O2], 5), 77.1 ([M+ – C18H14NO2], 100).
Anal. Calcd for C24H19NO2 (353.4): C, 81.56; H, 5.42; N, 3.96.
Found: C, 81.49; H, 5.36; N, 3.99.
Anal. Calcd for C24H18FNO2 (371.4): C, 77.61; H, 4.88; N, 3.77.
Found: C, 77.59; H, 4.92; N, 3.75.
5-Benzoyl-1-[4-(dimethylamino)phenyl]-6-phenyl-3,4-dihydro-
pyridin-2(1H)-one (7j)
Yellow solid; yield: 390 mg (49%); mp 233 °C.
5-Benzoyl-1-(3-fluorophenyl)-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7g)
Yellow solid; yield: 280 mg (38%); mp 183 °C.
IR (diamond): 3096 (w), 3051 (w), 2887 (w), 2814 (w), 1694 [ν
(C=O), s], 1614 [ν (C=O), s], 1522 (s), 1352 [ν (Ar-NR2), s], 1327
[ν (Ar-NR2), s], 1290 (s), 1190 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.81 (s, 6 H), 2.92 (s, 4 H), 6.41–
6.48 (m, 2 H), 6.80–6.87 (m, 5 H), 6.90–6.97 (m, 2 H), 7.13–7.21
(m, 2 H), 7.23–7.32 (m, 1 H), 7.53–7.63 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 24.8 (CH2), 32.7 (CH2), 40.5 (2
CH3), 112.0 (2 CH), 119.7 (Cquat), 126.8 (Cquat), 127.6 (2 CH), 128.0
(2 CH), 128.4 (CH), 129.0 (2 CH), 129.5 (2 CH), 130.4 (2 CH),
132.1 (CH), 134.2 (Cquat), 138.1 (Cquat), 147.3 (Cquat), 149.2 (Cquat),
171.3 (Cquat), 198.0 (Cquat).
IR (diamond): 3082 (w), 3067 (w), 3026 (w), 1699 [ν (C=O), s],
1633 (s), 1595 [ν (C=O), s], 1350 (s), 1288 (s), 1196 (s), 1175 (s),
1153 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.85–3.02 (m, 4 H), 6.72–6.83 (m,
3 H), 6.84–6.89 (m, 3 H), 6.90–6.97 (m, 2 H), 7.09 (td, J = 8.3,
6.4 Hz, 1 H), 7.15–7.24 (m, 2 H), 7.27–7.34 (m, 1 H), 7.58–7.64 (m,
2 H).
13C NMR (75 MHz, CDCl3): δ = 24.7 (CH2), 32.6 (CH2), 114.3 (d,
J = 21.0 Hz, CH), 116.7 (d, J = 23.1 Hz, CH), 120.9 (Cquat), 124.8
(d, J = 3.2 Hz, CH), 127.9 (2 CH), 128.2 (2 CH), 128.8 (CH), 129.1
(2 CH), 129.5 (d, J = 9.1 Hz, CH), 130.1 (2 CH), 132.5 (CH), 133.6
(Cquat), 137.5 (Cquat), 139.5 (d, J = 9.9 Hz, Cquat), 145.7 (Cquat), 162.3
(d, J = 247.1 Hz, Cquat), 170.6 (Cquat), 197.5 (Cquat).
MS (EI+): m/z (%) = 371.3 ([M+], 10), 342.3 ([M+ – CO], 2), 328.3
([M+ – C2H2O], 2), 266.2 ([M+ – C7H5O], 2), 198.1 ([M+ – C12H11F],
8), 105.1 ([M+ – C17H13FNO], 45), 95.1 ([M+ – C18H14NO], 27),
77.1 ([M+ – C18H13FNO2], 100).
HRMS (ESI): m/z [M + H]+ calcd for C26H25N2O2: 397.19105;
found: 397.19116.
5-Benzoyl-1-(4-methoxyphenyl)-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7k)
Yellow solid; yield: 459 mg (60%); mp 172 °C.
IR (diamond): 3057 (w), 2967 (w), 2907 (w), 2841 (w), 1690 [ν
(C=O), s], 1634 (s), 1618 (s), 1508 (s), 1362 (s), 1296 (s), 1248 (s),
1200 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.85–3.00 (m, 4 H), 3.66 (s, 3 H),
6.62–6.69 (m, 2 H), 6.82–6.88 (m, 3 H), 6.89–6.95 (m, 4 H), 7.14–
7.22 (m, 2 H), 7.23–7.35 (m, 1 H), 7.56–7.62 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 24.8 (CH2), 32.6 (CH2), 55.4
(CH3), 113.8 (2 CH), 120.1 (Cquat), 127.7 (2 CH), 128.1 (2 CH),
128.6 (CH), 129.0 (2 CH), 130.0 (2 CH), 130.3 (2 CH), 130.8
(Cquat), 132.2 (CH), 133.9 (Cquat), 137.9 (Cquat), 146.7 (Cquat), 158.2
(Cquat), 171.1 (Cquat), 197.8 (Cquat).
MS (EI+): m/z (%) = 384.1 ([M+], 25), 383.1 ([M+], 100), 382.1
([M+], 84), 354.0 ([M+ – CO], 10), 340.0 ([M+ – C2H2O], 8), 306.0
([M+ – C6H5], 3), 278.0 ([M+ – C7H5O], 16), 236.0 ([M+ – C9H7O2],
9), 210.0 ([M+ – C11H9O2], 21), 107.9 ([M+ – C18H14NO2], 7), 104.9
([M+ – C18H16NO2], 29), 77.0 ([M+ – C19H16NO3], 22).
Anal. Calcd for C24H18FNO2 (371.4): C, 77.61; H, 4.88; N, 3.77.
Found: C, 77.83; H, 4.96; N, 3.80.
5-Benzoyl-1-(2-fluorophenyl)-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7h)
Yellow solid; yield: 91 mg (12%); mp 183 °C.
IR (diamond): 3024 (w), 2841 (w), 1703 [ν (C=O), s], 1614 [ν
(C=O), s], 1354 (s), 1331 (s), 1294 (s), 1271 (s), 1186 (s), 1136
cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.87–3.04 (m, 4 H), 6.83–6.89 (m,
3 H), 6.89–7.01 (m, 5 H), 7.03–7.11 (m, 1 H), 7.16–7.23 (m, 2 H),
7.27–7.33 (m, 1 H), 7.57–7.63 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 24.8 (CH2), 32.2 (CH2), 116.0 (d,
J = 20.1 Hz, CH), 120.0 (Cquat), 124.1 (d, J = 3.7 Hz, CH), 126.2 (d,
J = 13.0 Hz, Cquat), 127.8 (2 CH), 128.1 (2 CH), 128.9 (CH), 129.1
(2 CH), 129.6 (d, J = 8.4 Hz, CH), 129.7 (2 CH), 130.8 (CH), 132.3
(CH), 133.4 (Cquat), 137.8 (Cquat), 146.4 (Cquat), 158.0 (d,
J = 249.8 Hz, Cquat), 170.2 (Cquat), 197.5 (Cquat).
Anal. Calcd for C25H21NO3 (383.4): C, 78.31; H, 5.52; N, 3.65.
Found: C, 78.07; H, 5.44; N, 3.68.
5-Benzoyl-1-(3-methoxyphenyl)-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7l)
Yellow solid; yield: 413 mg (54%); mp 174 °C.
MS (EI+): m/z (%) = 370.3 ([M+], 8), 328.1 ([M+ – C2H2O], 2),
266.2 ([M+ – C7H5O], 2), 198.2 ([M+ – C12H11F], 7), 105.1 ([M+ –
C17H13FNO], 39), 95.1 ([M+ – C18H14NO], 9), 77.1 ([M+
C18H13FNO2], 100).
–
IR (diamond): 3055 (w), 2978 (w), 2970 (w), 2949 (w), 1695 [ν
(C=O), s], 1614 [ν (C=O), s], 1589 (s), 1354 (s), 1285 (s), 1194 (s),
1179 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.87–3.01 (m, 4 H), 3.64 (s, 3 H),
6.55 (t, J = 2.2 Hz, 1 H), 6.59 (ddd, J = 8.3, 2.5, 0.9 Hz, 1 H), 6.63
(ddd, J = 7.9, 1.9, 1.0 Hz, 1 H), 6.82–6.88 (m, 3 H), 6.91–6.97 (m,
2 H), 7.04 (t, J = 8.1 Hz, 1 H), 7.15–7.22 (m, 2 H), 7.26–7.33 (m, 1
H), 7.57–7.63 (m, 2 H).
Anal. Calcd for C24H18FNO2 (371.4): C, 77.61; H, 4.88; N, 3.77.
Found: C, 77.39; H, 5.12; N, 3.84.
5-Benzoyl-1,6-diphenyl-3,4-dihydropyridin-2(1H)-one (7i)
Yellow solid; yield: 445 mg (63%); mp 175 °C.
IR (diamond): 2990 (w), 2967 (w), 2889 (w), 1697 [ν (C=O), s],
1624 (m), 1611 (m), 1595 (m), 1352 cm–1 (s).
13C NMR (75 MHz, CDCl3): δ = 24.8 (CH2), 32.6 (CH2), 55.4
(CH3), 113.1 (CH), 115.0 (CH), 120.4 (Cquat), 121.6 (CH), 127.7 (2
CH), 128.1 (2 CH), 128.6 (CH), 129.1 (2 CH), 129.1 (CH), 130.2 (2
1H NMR (300 MHz, CDCl3): δ = 2.85–3.02 (m, 4 H), 6.80–6.87 (m,
3 H), 6.89–6.96 (m, 2 H), 6.98–7.07 (m, 3 H), 7.10–7.23 (m, 4 H),
7.26–7.33 (m, 1 H), 7.57–7.65 (m, 2 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 522–530

528
J. Nordmann, T. J. J. Müller
PAPER
CH), 132.3 (CH), 133.8 (Cquat), 137.7 (Cquat), 139.1 (Cquat), 146.3
(Cquat), 159.6 (Cquat), 170.7 (Cquat), 197.8 (Cquat).
1H NMR (300 MHz, CDCl3): δ = 2.17 (s, 3 H), 2.86–3.01 (m, 4 H),
6.82–6.97 (m, 9 H), 7.14–7.23 (m, 2 H), 7.26–7.32 (m, 1 H), 7.56–
7.62 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 21.1 (CH3), 24.8 (CH2), 32.6
(CH2), 120.2 (Cquat), 127.7 (2 CH), 128.1 (2 CH), 128.5 (CH), 128.8
(2 CH), 129.1 (2 CH), 129.2 (2 CH), 130.3 (2 CH), 132.3 (CH),
133.9 (Cquat), 135.4 (Cquat), 137.0 (Cquat), 137.8 (Cquat), 146.6 (Cquat),
170.9 (Cquat), 197.8 (Cquat).
MS (EI+): m/z (%) = 384.2 ([M+], 18), 383.2 ([M+], 75), 382.2
([M+], 74), 354.2 ([M+ – CO], 8), 340.2 ([M+ – C2H2O], 16), 306.1
([M+ – C6H5], 5), 278.1 ([M+ – C7H5O], 24), 236.1 ([M+ – C9H7O2],
12), 210.1 ([M+ – C11H9O2], 22), 107.1 ([M+ – C18H14NO2], 12),
105.1 ([M+ – C18H16NO2], 65), 77.0 ([M+ – C19H16NO3], 100).
Anal. Calcd for C25H21NO3 (383.4): C, 78.31; H, 5.52; N, 3.65.
Found: C, 78.33; H, 5.36; N, 3.62.
MS (EI+): m/z (%) = 367.1 ([M+], 100), 366.1 ([M+], 94), 338.1
([M+ – CO], 11), 324.1 ([M+ – C2H2O], 17), 290.1 ([M+ – C6H5], 4),
262.1 ([M+ – C7H5O], 20), 194.0 ([M+ – C11H9O2], 31), 104.9 ([M+
5-Benzoyl-1-(2-methoxyphenyl)-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7m)
Yellow solid; yield: 328 mg (43%); mp 135 °C.
– C18H16NO], 30), 91.0 ([M+ – C18H14NO2], 19), 77.0 ([M+
C19H16NO2], 19).
–
IR (diamond): 3065 (w), 2997 (w), 2980 (w), 1678 [ν (C=O), s],
Anal. Calcd for C25H21NO2 (367.4): C, 81.72; H, 5.76; N, 3.81.
Found: C, 81.54; H, 5.90; N, 3.67.
1643 [ν (C=O), s], 1360 (s), 1333 (s), 1292 (s), 1254 (s), 1194 cm–1
(s).
1H NMR (300 MHz, CDCl3): δ = 2.85–3.03 (m, 4 H), 3.75 (s, 3 H),
6.66 (dd, J = 8.3, 1.2 Hz, 1 H), 6.73 (td, J = 7.6, 1.3 Hz, 1 H), 6.78–
6.85 (m, 3 H), 6.92–7.00 (m, 3 H), 7.05 (ddd, J = 8.2, 7.5, 1.7 Hz, 1
H), 7.18 (ddt, J = 8.3, 6.6, 1.2 Hz, 2 H), 7.24–7.31 (m, 1 H), 7.56–
7.61 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 24.9 (CH2), 32.3 (CH2), 55.6
(CH3), 111.5 (CH), 119.1 (Cquat), 120.3 (CH), 127.1 (Cquat), 127.2 (2
CH), 128.0 (2 CH), 128.6 (CH), 129.0 (2 CH), 129.3 (CH), 129.9 (2
CH), 130.8 (CH), 132.0 (CH), 133.8 (Cquat), 138.3 (Cquat), 147.8
(Cquat), 154.8 (Cquat), 170.5 (Cquat), 197.9 (Cquat).
MS (EI+): m/z (%) = 384.2 ([M+], 19), 383.2 ([M+], 71), 382.2
([M+], 66), 354.3 ([M+ – CO], 6), 340.2 ([M+ – C2H2O], 13), 306.2
([M+ – C6H5], 5), 278.2 ([M+ – C7H5O], 26), 236.2 ([M+ – C9H7O2],
8), 210.1 ([M+ – C11H9O2], 16), 108.1 ([M+ – C18H14NO2], 16),
105.1 ([M+ – C18H16NO2], 84), 77.1 ([M+ – C19H16NO3], 100).
5-Benzoyl-1-(3,5-difluorophenyl)-6-phenyl-3,4-dihydropyri-
din-2(1H)-one (7p)
Yellow solid; yield: 169 mg (22%); mp 227 °C.
IR (diamond): 3082 (w), 3057 (w), 2970 (w), 1697 [ν (C=O), s],
1593 [ν (C=O), s], 1435 (w), 1352 (s), 1283 (s), 1190 (s), 1175
cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.85–3.00 (m, 4 H), 6.52 (tt,
J = 8.8, 2.3 Hz, 1 H), 6.56–6.65 (m, 2 H), 6.89–6.98 (m, 5 H), 7.17–
7.24 (m, 2 H), 7.29–7.36 (m, 1 H), 7.59–7.63 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 24.6 (CH2), 32.5 (CH2), 103.1 (t,
J = 25.3 Hz, CH), 112.5–113.0 (m, 2 CH), 121.5 (Cquat), 128.1 (2
CH), 128.2 (2 CH), 129.1 (2 CH), 130.0 (2 CH), 132.6 (2 CH),
133.3 (Cquat), 137.3 (Cquat), 140.3 (t, J = 12.4 Hz, Cquat), 145.0
(Cquat), 162.3 (d, J = 248.8 Hz, Cquat), 162.5 (d, J = 249.0 Hz, Cquat),
170.4 (Cquat), 197.3 (Cquat).
Anal. Calcd for C25H21NO3 (383.4): C, 78.31; H, 5.52; N, 3.65.
Found: C, 78.10; H, 5.45; N, 3.57.
MS (EI+): m/z (%) = 389.1 ([M+], 100), 388.1 ([M+], 89), 360.1
([M+ – CO], 14), 346.0 ([M+ – C2H2O], 23), 312.0 ([M+ – C6H5], 7),
284.0 ([M+ – C7H5O], 11), 216.0 ([M+ – C11H10O2], 33), 112.9 ([M+
– C18H14NO2], 15), 104.9 ([M+ – C17H12F2NO], 76), 77.0 ([M+ –
C18H12F2NO2], 41).
5-Benzoyl-1-(3,5-dimethoxyphenyl)-6-phenyl-3,4-dihydropyri-
din-2(1H)-one (7n)
Orange solid; yield: 406 mg (49%); mp 180 °C.
Anal. Calcd for C24H17F2NO2 (389.4): C, 74.03; H, 4.40; N, 3.60.
Found: C, 73.78; H, 4.61; N, 3.52.
IR (diamond): 3021 (w), 2978 (w), 2936 (w), 1659 [ν (C=O), s],
1599 (s), 1360 (s), 1290 (s), 1196 (s), 1161 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.86–3.00 (m, 4 H), 3.62 (s, 6 H),
6.15 (t, J = 2.2 Hz, 1 H), 6.19 (d, J = 2.2 Hz, 2 H), 6.83–6.90 (m, 3
H), 6.93–7.01 (m, 2 H), 7.18 (ddt, J = 8.2, 6.6, 1.2 Hz, 2 H), 7.26–
7.32 (m, 1 H), 7.57–7.62 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 24.7 (CH2), 32.7 (CH2), 55.5 (2
CH3), 99.7 (CH), 107.8 (2 CH), 120.4 (Cquat), 127.7 (2 CH), 128.1
(2 CH), 128.7 (CH), 129.1 (2 CH), 130.2 (2 CH), 132.3 (CH), 133.8
(Cquat), 137.7 (Cquat), 139.6 (Cquat), 146.2 (Cquat), 160.4 (2 Cquat),
170.6 (Cquat), 197.8 (Cquat).
5-Benzoyl-6-phenyl-1-[4-(trifluoromethyl)phenyl]-3,4-dihydro-
pyridin-2(1H)-one (7q)
Pale fawn solid; yield: 86 mg (10%); mp 180 °C.
IR (diamond): 3071 (w), 2959 (w), 1703 [ν (C=O), s], 1634 [ν
(C=O), s], 1609 (s), 1350 (s), 1319 (s), 1296 (s), 1271 (s), 1169 (s),
1159 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 2.88–3.03 (m, 4 H), 6.84–6.95 (m,
5 H), 7.12–7.24 (m, 4 H), 7.28–7.35 (m, 1 H), 7.37–7.43 (m, 2 H),
7.60–7.64 (m, 2 H).
MS (EI+): m/z (%) = 414.3 ([M+], 28), 413.3 ([M+], 100), 412.3
([M+], 96), 385.2 ([M+ – CO], 3), 370.2 ([M+ – C2H2O], 18), 336.2
([M+ – C6H5], 8), 308.2 ([M+ – C7H5O], 26), 281.1 ([M+ – C8H5O2],
12), 280.2 ([M+ – C8H5O2], 11), 266.2 ([M+ – C9H7O2], 17), 240.2
([M+ – C11H9O2], 16), 207.1 ([M+ – C15H10O], 26), 137.2 ([M+ –
13C NMR (75 MHz, CDCl3): δ = 24.7 (CH2), 32.5 (CH2), 121.4
(Cquat), 123.7 (d, J = 269.4 Hz, Cquat), 125.6 (q, J = 3.7 Hz, 2 CH),
128.1 (2 CH), 128.2 (2 CH), 129.0 (d, J = 32.8 Hz, Cquat), 129.0
(CH), 129.1 (2 CH), 129.3 (2 CH), 130.0 (2 CH), 132.6 (CH), 133.4
(Cquat), 137.4 (Cquat), 141.4 (Cquat), 145.3 (Cquat), 170.6 (Cquat), 197.4
(Cquat).
MS (EI+): m/z (%) = 422.1 ([M+], 19), 421.2 ([M+], 80), 392.1 ([M+
– CO], 13), 378.1 ([M+ – C2H2O], 21), 364.2 ([M+ – C3H4O], 7),
344.1 ([M+ – C6H5], 6), 316.1 ([M+ – C7H5O], 10), 288.1 ([M+ –
C9H9O], 9), 248.1 ([M+ – C11H9O2], 39), 145.1 ([M+ – C18H14NO2],
35), 105.1 ([M+ – C18H13F3NO], 95), 77.1 ([M+ – C19H13F3NO2],
100).
C18H14NO2], 9), 107.1 ([M+ – C19H18NO3], 14), 105.1 ([M+
C19H18NO3], 91), 77.1 ([M+ – C20H18NO4], 97).
–
Anal. Calcd for C26H23NO4 (413.5): C, 75.53; H, 5.61; N, 3.39.
Found: C, 75.35; H, 5.60; N, 3.28.
5-Benzoyl-6-phenyl-1-(p-tolyl)-3,4-dihydropyridin-2(1H)-one
(7o)
Yellow solid; yield: 479 mg (65%); mp 208 °C.
Anal. Calcd for C25H18F3NO2 (421.4): C, 71.25; H, 4.31; N, 3.32.
Found: C, 71.04; H, 4.37; N, 3.35.
IR (diamond): 3069 (w), 2961 (w), 1695 [ν (C=O), s[, 1614 [ν
(C=O), s], 1352 (s), 1327 (s), 1287 (s), 1192 cm–1 (s).
Synthesis 2014, 46, 522–530
© Georg Thieme Verlag Stuttgart · New York

PAPER
1-Aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-ones
529
5-Benzoyl-1-(naphthalen-1-yl)-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7r)
13C NMR (150 MHz, CDCl3): δ = 25.1 (CH2), 32.7 (CH2), 119.8
(Cquat), 121.4 (CH), 124.1 (CH), 125.9 (CH), 126.1 (CH), 127.2 (2
CH), 127.3 (CH), 128.1 (2 CH), 128.1 (CH), 128.2 (CH), 128.6
(CH), 128.7 (CH), 129.0 (2 CH), 129.1 (CH), 129.2 (Cquat), 129.8 (2
CH), 131.8 (Cquat), 132.1 (Cquat), 132.1 (Cquat), 132.2 (CH), 133.3
(Cquat), 134.7 (Cquat), 138.1 (Cquat), 147.8 (Cquat), 170.8 (Cquat), 197.7
(Cquat).
Pale fawn solid; yield: 290 mg (36%); mp 178 °C.
IR (diamond): 3053 (w), 2997 (w), 2974 (w), 1684 [ν (C=O), s],
1638 [ν (C=O), s], 1358 (s), 1296 (s), 1196 cm–1 (s).
1H NMR (600 MHz, CDCl3): δ = 3.05–3.22 (m, 4 H), 6.60–6.66 (m,
2 H), 6.70 (t, J = 7.7 Hz, 1 H), 6.83–6.88 (m, 2 H), 7.18–7.21 (m, 2
H), 7.23 (dd, J = 7.4, 1.3 Hz, 1 H), 7.27–7.31 (m, 2 H), 7.44 (ddd,
J = 8.0, 6.8, 1.2 Hz, 1 H), 7.56 (ddd, J = 8.3, 6.8, 1.3 Hz, 1 H), 7.60–
7.64 (m, 3 H), 7.72 (d, J = 8.5 Hz, 1 H), 7.82–7.86 (m, 1 H).
13C NMR (150 MHz, CDCl3): δ = 24.9 (CH2), 32.6 (CH2), 119.6
(Cquat), 122.6 (CH), 124.9 (CH), 126.1 (CH), 127.0 (CH), 127.1 (2
CH), 128.0 (2 CH), 128.3 (CH), 128.5 (CH), 128.6 (CH), 128.6
(CH), 129.0 (2 CH), 129.9 (CH), 130.9 (Cquat), 132.2 (2 CH), 133.3
(Cquat), 134.1 (Cquat), 134.6 (Cquat), 138.1 (Cquat), 147.7 (Cquat), 170.7
(Cquat), 197.8 (Cquat).
MS (EI+): m/z (%) = 454.1 ([M+], 19), 453.1 ([M+], 57), 418.1
([M+], 24), 424.1 ([M+ – CO], 3), 410.0 ([M+ – C2H2O], 6), 376.0
([M+ – C6H5], 3.8), 347.0 ([M+ – C7H5O], 6), 320.0 ([M+ – C9H9O],
7), 282.9 ([M+ – C11H9O2], 88), 247.0 ([M+ – C15H10O], 55), 219.0
([M+ – C17H14O], 18) 192.9 ([M+ – C18H14O2], 100), 177.9 ([M+ –
C18H14NO2], 20), 104.9 ([M+ – C25H18NO], 56), 76.9 ([M+
C26H18NO2], 25);
–
HRMS (ESI): m/z [M + H]+ calcd for C32H24NO2: 454.18016;
found: 454.17979.
MS (EI+): m/z (%) = 403.2 ([M+], 56), 402.2 ([M+], 48), 374.2 ([M+
– CO], 5), 360.2 ([M+ – C2H2O], 10), 346.2 ([M+ – C3H4O], 3),
298.2 ([M+ – C7H5O], 10), 270.2 ([M+ – C8H5O2], 8), 256.2 ([M+ –
Acknowledgment
C9H7O2], 11), 127.1 ([M+ – C18H14NO2], 62), 105.1 ([M+
C21H16NO], 74), 77.1 ([M+ – C22H16NO2], 100).
–
The authors cordially thank B. Sc. Sebastian Gawin for experimen-
tal assistance and the Fonds der Chemischen Industrie for support.
Anal. Calcd for C28H21NO2 (403.5): C, 83.35; H, 5.25; N, 3.47.
Found: C, 83.12; H, 5.32; N, 3.46.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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5-Benzoyl-1-(4-hydroxynaphthalen-1-yl)-6-phenyl-3,4-dihy-
dropyridin-2(1H)-one (7s)
Pale beige solid; yield: 385 mg (46%); mp 204 °C.
References
IR (diamond): 3308 (w), 3291 (w), 3254 (w), 3231 (w), 1667 [ν
(C=O), s], 1639 [ν (C=O), s], 1354 [ν + δ (Ar-OH), s], 1333 [ν + δ
(Ar-OH), s], 1279 (s), 1198 cm–1 (s).
1H NMR (600 MHz, CDCl3): δ = 3.00–3.05 (m, 1 H), 3.06–3.10 (m,
2 H), 3.12–3.18 (m, 1 H), 6.09 (d, J = 8.0 Hz, 1 H), 6.57 (t,
J = 7.7 Hz, 2 H), 6.61–6.67 (m, 1 H), 6.72–6.78 (m, 2 H), 6.79 (d,
J = 8.0 Hz, 1 H), 6.96 (s, 1 H), 7.16 (t, J = 7.7 Hz, 2 H), 7.24–7.28
(m, 1 H), 7.30 (dd, J = 8.3, 6.8 Hz, 1 H), 7.49 (ddd, J = 8.2, 6.7,
1.2 Hz, 1 H), 7.55–7.59 (m, 2 H), 7.66 (d, J = 8.4 Hz, 1 H), 7.81 (d,
J = 8.2 Hz, 1 H).
13C NMR (150 MHz, CDCl3): δ = 24.7 (CH2), 32.6 (CH2), 108.2
(CH), 119.8 (Cquat), 121.9 (CH), 122.8 (CH), 124.9 (CH), 125.1
(Cquat), 125.8 (Cquat), 127.1 (2 CH), 127.2 (CH), 128.0 (2 CH), 128.6
(CH), 128.6 (CH), 129.0 (2 CH), 129.9 (2 CH), 131.4 (Cquat), 132.3
(CH), 133.1 (Cquat), 138.0 (Cquat), 147.7 (Cquat), 152.3 (Cquat), 171.9
(Cquat), 198.0 (Cquat).
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MS (EI+): m/z (%) = 420.1 ([M+], 28), 419.1 ([M+], 100), 418.1
([M+], 80), 390.1 ([M+ – CO], 9), 376.1 ([M+ – C2H2O], 15), 362.1
([M+ – C3H4O], 6), 342.1 ([M+ – C6H5], 3), 314.1 ([M+ – C7H5O],
9), 286.1 ([M+ – C9H9O], 9), 276.0 ([M+ – C10H7O], 5), 249.0 ([M+
– C11H9O2], 21), 246.0 ([M+ – C11H9O2], 28), 233.0 ([M+
C11H7NO2], 12), 159.0 ([M+ – C18H16O2], 51), 158.0 ([M+
C18H16O2], 13), 104.9 ([M+ – C21H16NO2], 40), 77.0 ([M+
C22H16NO3], 21).
–
–
–
HRMS (ESI): m/z [M + H]+ for calcd C28H22NO3: 420.15942;
found: 420.15947.
1-(Anthracen-1-yl)-5-benzoyl-6-phenyl-3,4-dihydropyridin-
2(1H)-one (7t)
Pale beige solid; yield: 369 mg (41%); mp 115 °C.
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1624 [ν (C=O), m], 1354 (m), 1290 (s), 1194 cm–1 (s).
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2 H), 6.65 (tt, J = 7.7, 1.4 Hz, 1 H), 6.80–6.90 (m, 2 H), 7.18–7.24
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Synthesis 2014, 46, 522–530
© Georg Thieme Verlag Stuttgart · New York