Electron transfer-initiated and highly selective photocyclization of N-acyl-α-dehydroarylalaninamides to 3,4-dihydroquinolinone derivatives

Article abstract of DOI:10.3987/COM-04-10242

The irradiation of (Z)-N-acyl-α-dehydroarylalaninamides [(Z)-1] in methanol containing 1,8-diazabicyclo[5.4.0]undec-7-ene gave substituted 3,4-dihydro-2-quinolinones (2) in high yields along with minor amounts of 2-quinolinone (3) and 4,5-dihydrooxazole (

Full text of DOI:10.3987/COM-04-10242

HETEROCYCLES, Vol. 65, No. 1, 2005
117
HETEROCYCLES, Vol. 65, No. 1, 2005, pp.117 - 131
Received, 5th October, 2004, Accepted, 17th November, 2004, Published online, 19th November, 2004
ELECTRON TRANSFER-INITIATED AND HIGHLY SELECTIVE
α
PHOTOCYCLIZATION OF N-ACYL- -DEHYDROARYLALANIN-
AMIDES TO 3,4-DIHYDROQUINOLINONE DERIVATIVES
Kei Maekawa, Kunio Fujita, Katsuyuki Iizuka, Tetsutaro Igarashi, and
Tadamitsu Sakurai*
Department of Applied Chemistry, Faculty of Engineering, Kanagawa University,
Kanagawa-ku, Yokohama 221-8686, Japan
Abstract–The irradiation of (Z)-N-acyl-α-dehydroarylalaninamides [(Z)-1] in
methanol containing 1,8-diazabicyclo[5.4.0]undec-7-ene gave substituted 3,4-
dihydro-2-quinolinones (2) in high yields along with minor amounts of 2-
quinolinone (3) and 4,5-dihydrooxazole (4) derivatives. Analysis of substituent
and tertiary amine base effects on the selectivity of each product showed that 2 and
4 are formed via electron transfer from the amine to the excited-state (E)-1, the
cyclization of which proceeds in competition with this electron transfer to afford 3.
Organic photochemistry has continued to contribute to the development of efficient and selective
transformations for the preparation of complicated molecules which could not have been synthesized by
conventional methods. In recent years much attention is being devoted to the synthetic application of
photoinduced electron transfer (PET) reactions, owing to the fact that many of these reactions enable the
construction of various heterocyclic rings.1 On the other hand, α-dehydroamino acid derivative is one of
the important intermediates for the synthesis of biologically active natural products. Many useful synthetic
methods of α-dehydroamino acid derivatives have been reported but there have been only limited
investigations of the photochemistry of these amino acid derivatives.2,3 Taking into account the fact that
aromatic olefins undergo efficient PET reactions in their excited states,4 it can be expected that substituted α-
dehydroamino acids having the aromatic olefin chromophore are subject to PET reactions. Keeping this
expectation in mind, we embarked on a systematic study toward the characterization of the excited-state
reactivity of N-acyl-α-dehydroamino acids.5–8 In the course of this study we discovered novel
intramolecular and intermolecular ET-initiated photocyclization reactions of substituted N-acyl-α-
dehydronaphthylalaninamides that afford the corresponding 3,4-dihydrobenzo[f]quinolinones.6 Because
many heterocyclic compounds having a dihydroquinolinone ring exhibit pharmacological and physiological
activities, 9 it is of great significance to develop synthetic methods for the construction of this quinolinone
ring.
Very recently we found that the PET reaction of N-(2,4-dimethoxybenzoyl)-α-
dehydronaphthylalaninamide affords selectively the corresponding dihydrobenzoquinolinone derivative.

118
HETEROCYCLES, Vol. 65, No. 1, 2005
Analysis of the quantum yields for the PET reaction led us to conclude that the overall reaction efficiency is
mainly determined by the stability of an initially-formed ion radical pair intermediate, that is, by the relative
rate of back ET in this intermediate.10 In order to extend the synthetic utility of ET-initiated
photocyclization reactions described above and also to develop pharmacologically active heterocyclic
compounds having a structure related to papaverine,11 we synthesized various (Z)-N-acyl-α-
dehydro(methoxy-substituted phenyl)alaninamide derivatives [(Z)-1a–k] and investigated the effects of
substituent and tertiary amine base as an electron donor on the selectivity of each 1-derived photoproduct.
O
NHMe
O
O
NHMe
O
(Z)-1a: R= Me
(Z)-1b: R= i-Pr
(Z)-1c: R= t-Bu
N
R
N
R
(Z)-1d: R= CH Ph
2
H
H
(Z)-1e: R= CH C H F-4
2
6 4
(Z)-1f: R= CH C H Cl-4
2
6 4
(Z)-1j: R= Ph
(Z)-1k: R= C H (OMe) -2,4
(Z)-1g: R= CH C H Cl -3,4
2
6
3
2
6
3
2
MeO
(Z)-1h: R= CH C H (OMe) -3,4
MeO
2
6
3
2
(Z)-1i: R= C H (OMe) -2,4
6
3
2
OMe
The starting (Z)-isomers (1a–k) were prepared by the ring-opening reactions of the corresponding
oxazolones with methylamine in excellent yields.12 After a nitrogen-saturated methanol solution of (Z)-1a
(3.75×10–3 mol dm–3, 200 mL) containing triethylamine (TEA, 0.10 mol dm–3) was irradiated with Pyrex-
filtered light (>280 nm) from a 400 W high-pressure Hg lamp for 10 h at room temperature. Preparative
thin-layer chromatography (silica gel) of the residual solid (that was obtained by evaporating the reaction
mixture to dryness) allowed us to isolate 3-acetylamino-3,4-dihydro-6,7-dimethoxy-1-methyl-2(1H)-
quinolinone (2a, 17% isolated yield) and 3-acetylamino-6,7-dimethoxy-1-methyl-2(1H)-quinolinone (3a,
5%) in addition to (E)-1a (25%). Careful 1H NMR spectral analysis of the product mixture suggested that
NHCOMe
O
NHCOMe
O
hν
N
N
(Z)-1a
+
+
Me
Me
MeOH/TEA
MeO
MeO
OMe
OMe
2a
3a
Me
NHCOMe
CONHMe
O
N
+
CONHMe
MeO
MeO
MeO
OMe
(E)-1a
cis -4a
Scheme 1
there is very little formation of 5-(3,4-dimethoxyphenyl)-2-methyl-4-methylaminocarbonyl-4,5-

HETEROCYCLES, Vol. 65, No. 1, 2005
119
dihydrooxazole (4a). Because the ring-proton signals of this product have larger J4,5 value (10.4 Hz) as
compared to those (J4,5= 6–7 Hz) of the trans-isomer,8,10 4a must be the cis-isomer (Scheme 1). Attempts
to isolate this oxazole derivative from the mixture were unsuccessful owing to its poor yield. The findings
that the photoproducts (2a–4a) are highly stable under the irradiation conditions used and that the area of
1H NMR signals for unknown products is much smaller than that for these photoproducts allowed us
1
to monitor the reaction by means of H NMR spectroscopy in a fair accuracy, as shown in Table 1. The
results in Table 1 demonstrate the rapid production of (E)-1a and the subsequent increase in compositions
for 2a–4a with the decrease of the isomer compositions. In addition to the structure of 2a–4a, this
observation strongly suggests that the excited-state (E)-isomer serves as a precursor of these products. In
previous studies we found that the ET-initiated photocyclization of
(Z)-N-acyl-α-
dehydronaphthylalaninamides gives the corresponding 3,4-dihydrobenzo[f]quinolinone derivatives in high
selectivities (along with minute amounts of 4,5-dihydrooxazoles) via an anion radical intermediate formed
by ET from TEA to the singlet excited-state (E)-isomer.6,10 On the other hand, the irradiation of a
methanol solution of (Z)-N-acyl-α-dehydro(3-methoxyphenyl)alaninamides containing no TEA was found
to afford regioselectively the corresponding 6-methoxy-2-quinolinone derivatives as major
products.7 Thus, these findings reveal that 2a and 4a are the products derived from the PET reaction of
1a which takes place in competition with its photocyclization giving eventually 3a.
Table 1. Relation between irradiation time and composition (%)
of each compound obtained by the irradiation of (Z)-1a in methanol
containing TEA (0.10 mol dm–3) at room temperature
Irradiation time (h)
Compound
0
0.5
3
5
10
100
0
54
42
4
40
42
13
4
39
39
15
6
36
34
21
7
(Z)-1a
(E)-1a
2a
0
0
0
3a
0
0
1
1
2
cis-4a
Taking into account the idea that one simple method to discriminate between these two cyclization pathways
is to employ tertiary amine of a different electron-donating ability, we chose TEA (pKa= 10.6,13 10.814),
N,N-diisopropylethylamine (DPA, pKa= 11.013), and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, pKa=
12.813) and examined the effects of these amines on the photoreactivity of 1a and the selectivity for 2a–4a.
As clearly seen from the results shown in Table 2, the selectivity for 2a is increased with increasing the
electron-donating ability of the amine while the reverse is found for the selectivity for 3a, though the
oxazole derivative (4a) shows a similar selectivity irrespective of the amine examined. In addition to this
product selectivity-amine basicity relationship, the finding that the photoreactivity is also enhanced as the

120
HETEROCYCLES, Vol. 65, No. 1, 2005
amine basicity is increased substantiates the above suggestion as well as the participation of an ion radical
pair intermediate in the PET reaction of (Z)-1, therefore, leading us to propose Scheme 2. As already
Table 2. Effects of amine basicity on the
Table 3. Effects of DBU concentration on the
conversion of 1a and the selectivity of 2a–4aa
conversion of 1a and the selectivity of 2a–4aa
Selectivity (%)c
Selectivity (%)c
Conversionb
Amine
Conversionb
(%)
DBU
(%)
4a
(mmol dm–3)
4a
2a
61
76
92
3a
29
15
0
2a
3a
44
13
0
TEA
DPA
DBU
45
52
66
10
9
1
3
45
59
71
48
80
92
8
7
8
8
10
a Nitrogen-saturated methanol solutions of (Z)-1a (3.75×10–3 mol dm–3, 10 mL) containing a
given tertiary amine (0.10 mol dm–3 in Table 2) were placed in Pyrex tubes and sealed.
Deaerated solutions were irradiated in parallel for 3 h at room temperature on a merry-go-round
apparatus with Pyrex-filtered light from a 400 W high-pressure Hg lamp.
b Conversion was estimated by the sum of composition for 2a, 3a, and cis-4a.
c Selectivity was evaluated by dividing the composition for each product by the sum of composition
for 2a, 3a, and cis-4a.
hν
ET/TEA
Back ET
(Z)-1a
(E)-1a
(Z)-1a*
(E)-1a*
(Z)-1a
TEA
(Z)-1a
TEA
hν
Me
H
TEA
TEA
NH
Me
N
NHMe
O
O
1) Back ET
2) H shift
O
O
cis-4a
NHMe
ET/TEA
MeO
MeO
OMe
OMe
II
IV
NHCOMe
O
NHCOMe
OH
1) H transfer
2) Back ET
1) Coupling
NHMe
TEA
NMe
2a
2) Tautomerization
TEA 3) H shift
MeO
MeO
OMe
OMe
I
III
NHCOMe
NHCOMe
NHCOMe
OH
O
O
C
C
'In-cage'
reaction
1) H shift
H H abstraction
H
NHMe
N
3a
2) Cyclization
Me 'Out-of-cage'
radicals
NHMe
MeO
MeO
MeO
OMe
OMe
OMe
V
VI
VII
Scheme 2
discussed in the previous paper,10 ET from TEA to the singlet excited-state (E)-1a forms the ion radical pair

HETEROCYCLES, Vol. 65, No. 1, 2005
121
intermediate (I) which may be in equilibrium with the ion radical pair intermediate (II). Hydrogen transfer
from the amide nitrogen to the amide carbonyl oxygen in the intermediate (I) and the subsequent back ET
to TEA cation radical affords TEA and the enol-type biradical (III), the coupling and tautomerization of
which eventually generate dihydroquinolinone derivative (2a) via hydrogen shift. In competition with this
cyclization process, the nucleophilic attack of the N-acetyl carbonyl oxygen anion upon the olefinic carbon
takes place in II to give the cyclized anion radical (IV). Back ET to the TEA cation radical followed by
hydrogen shift affords cis-4a preferentially.8 The observation that the selectivity for 4a is not strongly
dependent on the basicity of the tertiary amine used suggests that the hydrogen-bonding solvation ability of
this amine affects the relative stability of I being equilibrium with the intermediate (II), through which 4a is
formed. On the other hand, an efficient intramolecular ET in the excited-state (E)-isomer is a driving force
for inducing the homolytic C(=O)–NHMe bond cleavage (owing to the so-called “meta effect”15) that gives
the radical pair (V).7 The ‘in-cage’ reaction of this radical pair produces the biradical (VI) while
quinolinone derivative (3a) is obtained by hydrogen abstraction from the acetal (VII) by ‘out-of-cage’
radicals. Because the (Z)-1a*-derived photoproducts such as isoquinoline derivative could not be detected
in the reaction mixture, the ion radical pair, (Z)-1a–• TEA+•, is considered to undergo exclusive back ET
to regenerate (Z)-1a and TEA (Scheme 2).6
As already described, the fact that the photoproducts (2a–4a) are highly stable under the irradiation
conditions makes it possible to estimate the product composition even at greater than 99% conversions of
the starting α-dehydroarylalaninamides (1) and to discuss substituent effects on the selectivities of these
products as well as the synthetic utility of the ET-initiated photocyclization of (Z)-1. Because it is
preferable to minimize the concentration of DBU having a much higher boiling point than that of TEA,16 the
effects of DBU concentration on the conversion (photoreactivity) of 1a and the product selectivity were
explored in nitrogen-saturated methanol (Table 3). The data in Table 3 clearly show that both the
conversion of 1a and the selectivity of dihydroquinolinone derivative (2a) are increased with increasing the
DBU concentration and also this selectivity reaches a nearly constant value at [DBU]= 0.010 mol dm–3. In
addition, the dependence of selectivity for 2a–4a on the DBU concentration is very similar to that of this
selectivity on the basicity of the tertiary amine summarized in Table 2. Hence this finding justifies the
assumption that the hydrogen-bonding solvation of ion radical pair intermediates (I and II) by the amine is
one of the key factors that control the relative stability of these intermediates.
In Table 4 are collected selectivities of the photoproducts (2–4) and isolated yields of 3,4-dihydro-2(1H)-
quinolinones (2a–k). From any starting N-acyl-α-dehydroarylalaninamides we were able to obtain the
desired dihydroquinolinones in high selectivities (71–94%) and also in good isolated yields (57–75%).
Although small amounts of 3 and 4 remain in the reaction mixtures, these two products can be readily
removed by recrystallization from ethanol. Additionally, analysis of N-acyl substituent effects on the
product selectivity revealed that the introduction of bulky aliphatic acyl groups such as i-PrCO, t-BuCO,
and ArCH2CO enhances the selectivity for 3 to some extent while the selectivity for 4 is increased 3–5 times
by the replacement of acetyl by aromatic acyl group. The former finding implies that the bulky acyl group
exerts its steric effect on ET in the excited state to lower the relative rate of this ET, and the increased
contribution of the ion radical pair intermediate (II) in a given reaction system is suggested by the latter

122
HETEROCYCLES, Vol. 65, No. 1, 2005
finding. No formation of expected isoquinoline derivatives in any systems may be due to the exclusive
progress of back ET in the ion radical pair, (Z)-1–• DBU+•, as already described for (Z)-1a.
Table 4. Substituent effects on the selectivity for each product
obtained by the 5h irradiation of (Z)-1 (3.75
×
10–3 mol dm–3) in
methanol containing DBU (10 mmol dm–3) at room temperaturea
Selectivity (%)
Isolated yield
Compound
3
4b
of 2 (%)
2
1a
1b
1c
1d
1e
1f
94
86
82
87
89
91
88
88
82
71
82
0
5
6
4
4
3
5
4
0
0
0
6
9
75
67
74
71
69
62
63
71
69
57
67
12
9
7
6
1g
1h
1i
7
8
18
29
18
1j
1k
a The conversion of 1 was nearly 100%.
b The sum of selectivity for cis- and trans-isomers.
In conclusion, the intermolecular PET reaction of N-acyl-α-dehydro(methoxy-substituted
phenyl)alaninamides in methanol containing a small amount of DBU provides an efficient photochemical
method for synthesizing 3,4-dihydro-2(1H)-quinolinone derivatives containing various substituents in high
yields.
EXPERIMENTAL
General methods
13
1H and C NMR and IR spectra were taken with a JEOL JNM-ECA600 spectrometer and a Shimadzu
IRPrestige-21 infrared spectrophotometer, respectively.
Chemical shifts were determined using
tetramethylsilane as an internal standard. UV absorption spectra were recorded on a Hitachi U-3300
spectrophotometer. Elemental analyses were performed on a Perkin-Elmer PE2400 series II CHNS/O
analyzer. TEA, DPA, and DBU were fractionally distilled from sodium hydroxide. Methanol was
purified according to the standard procedure and freshly distilled prior to use.16 All other reagents used
were obtained from commercial sources and of the highest grade available.

HETEROCYCLES, Vol. 65, No. 1, 2005
123
General procedure for the synthesis of (Z)-2-alkyl-4-(methoxy-substituted benzylidene)-
5(4H) -oxazolones and (Z)-2-aryl-4-(methoxy-substituted benzylidene)-5(4H) -oxazolones
N-Acylglycine (0.087 mol), methoxy-substituted benzaldehyde (0.090 mol), and sodium acetate (5.3 g,
0.067 mol) were added to acetic anhydride (50 mL) and the resulting mixtures were heated at 80–85 °C (N-
acetylglycine), 70–80 °C for 1–2 h (N-aroylglycines), and 6–7 h (the other N-acylglycines) with
stirring. The mixtures were cooled with ice and the solids separated out were collected by filtration with
suction and washed with water, a small amount of cold ethanol and then with dry hexane. After the crude
products had been air-dried at room temperature, these were recrystallized from hexane-chloroform to give
yellow crystals (20–50%).
(Z)-4-(3, 4-Dimethoxybenzylidene)-2-methyl-5(4H)-oxazolone: mp 161.0–162.0 °C; IR (KBr):
1
1791, 1659, 1185 cm–1; H NMR (600 MHz, CDCl3): δ 2.38 (3H, s), 3.80 (3H, s), 3.84 (3H, s), 7.09
(1H, d, J= 8.3 Hz), 7.16 (1H, s), 7.75 (1H, dd, J= 1.5, 8.3 Hz), 7.93 (1H, d, J= 1.5 Hz).
(Z)-4-(3, 4-Dimethoxybenzylidene)-2-isopropyl-5(4H)-oxazolone: mp 84.0–85.0 °C; IR
(KBr): 1775, 1655, 1269 cm–1; 1H NMR (600 MHz, CDCl3): δ 1.35 (6H, d, J= 6.9 Hz), 3.92 (1H, qq, J=
6.9, 6.9 Hz), 3.95 (6H, s), 6.91 (1H, d, J= 8.2 Hz), 7.11 (1H, s, He), 7.42 (1H, dd, J=1.4, 8.2 Hz),
8.19 (1H, d, J= 1.4 Hz).
(Z)-2-tert-Butyl-4-(3, 4-dimethoxybenzylidene)-5(4H)-oxazolone: mp 135.0–136.0 °C; IR
(KBr): 1788, 1644, 1263 cm–1; 1H NMR (600 MHz, CDCl3): δ 1.35 (9H, s), 3.95 (6H, s), 6.91 (1H, d,
J= 8.2 Hz), 7.11 (1H, s), 7.45 (1H, dd, J= 8.2, 2.1 Hz), 8.11 (1H, d, J= 2.1 Hz).
(Z)-2-Benzyl-4-(3, 4-dimethoxybenzylidene)-5(4H)-oxazolone: mp 152.0–153.0 °C; IR (KBr):
1
1839, 1797, 1650, 1272 cm–1; H NMR (600 MHz, CDCl3): δ 3.81 (3H, s), 3.93 (3H, s), 3.97 (2H, s),
6.88 (1H, d, J= 8.6 Hz), 7.11(1H, s), 7.27–7.39 (5H, m), 7.40 (1H, dd, J= 2.0, 8.6 Hz), 8.01 (1H, d,
J= 2.0 Hz).
(Z)-4-(3, 4-Dimethoxybenzylidene)-2-(4-fluorobenzyl)-5(4H)-oxazolone: mp 134.0–135.0
1
°C; IR (KBr): 1774, 1653, 1018 cm–1; H NMR (600 MHz, CDCl3): δ 3.83 (3H, s), 3.94 (3H, s), 3.95
(2H, s), 6.89 (1H, d, J= 8.3 Hz), 7.04 (2H, dd, J= 8.3, 8.9 Hz), 7.11 (1H, s), 7.34 (2H, dd, J= 5.5, 8.3
Hz), 7.42 (1H, dd, J= 2.1, 8.3 Hz), 7.98 (1H, d, J= 2.1 Hz).
(Z)-2-(4-Chlorobenzyl)-4-(3, 4-dimethoxybenzylidene)-5(4H)-oxazolone: mp 145.5–146.0
1
°C; IR (KBr): 1800, 1650, 1023 cm–1; H NMR (600 MHz, CDCl3): δ 3.82 (3H, s), 3.94 (3H, s), 3.94
(2H, s), 6.89 (1H, d, J= 8.6 Hz), 7.11 (1H, s), 7.31 (2H, d, J= 8.6 Hz), 7.33 (2H, d, J= 8.6 Hz), 7.41
(1H, d, J= 8.6 Hz), 7.97 (1H, s).

124
HETEROCYCLES, Vol. 65, No. 1, 2005
(Z)-2-(3, 4-Dichlorobenzyl)-4-(3, 4-dimethoxybenzylidene)-5(4H)-oxazolone:
mp
1
132.5–133.5 °C; IR (KBr): 1786, 1651, 1024 cm–1; H NMR (600 MHz, CDCl3): δ 3.84 (3H, s), 3.94
(2H, s), 3.94 (3H, s), 6.90 (1H, d, J= 8.2 Hz), 7.14 (1H, s), 7.22 (1H, dd, J= 2.1, 8.2 Hz), 7.41 (1H,
dd, J= 1.4, 8.2 Hz), 7.44 (1H, d, J= 8.2 Hz), 7.50 (1H, d, J= 2.1 Hz), 7.96 (1H, d, J= 1.4 Hz).
(Z)-2-(3, 4-Dimethoxybenzyl)-4-(3, 4-dimethoxybenzylidene)-5(4H)-oxazolone:
mp
1
157.0–158.0 °C; IR (KBr): 1794, 1650, 1266 cm–1; H NMR (600 MHz, CDCl3): δ 3.85 (3H, s), 3.87
(3H, s), 3.89 (3H, s), 3.91 (2H, s), 3.93 (3H, s), 6.84 (1H, d, J= 8.3 Hz), 6.88 (1H, d, J= 2.0 Hz),
6.89 (1H, d, J= 8.3 Hz), 6.92 (1H, dd, J= 2.0, 8.3 Hz), 7.10 (1H, s), 7.46 (1H, dd, J= 2.0, 8.3 Hz),
7.97 (1H, d, J= 2.0 Hz).
(Z)-4-(3, 4-Dimethoxybenzylidene)-2-(2, 4-dimethoxyphenyl)-5(4H)-oxazolone:
mp
1
181.5–182.0 °C; IR (KBr): 1773, 1601, 1277 cm–1; H NMR (600 MHz, CDCl3): δ 3.90 (3H, s), 3.96
(6H, s), 4.04 (3H, s), 6.56 (1H, d, J= 2.3 Hz), 6.61 (1H, dd, J= 2.3, 8.6 Hz), 6.92 (1H, d, J= 8.3 Hz),
7.13 (1H, s), 7.49 (1H, d, J= 8.3 Hz), 8.02 (1H, d, J= 8.6 Hz), 8.24 (1H, s).
(Z)-4-(3-Methoxybenzylidene)-2-phenyl-5(4H)-oxazolone: mp 103.5–104.0 °C; IR (KBr): 1800,
1
1659, 1200 cm–1; H NMR (600 MHz, CDCl3): δ 3.84 (3H, s), 7.08 (1H, dd, J= 2.4, 7.8 Hz), 7.29 (1H,
s), 7.43 (1H, dd, J= 7.8, 7.8 Hz), 7.63 (2H, dd, J= 7.1, 7.3 Hz), 7.73 (1H, dd, J= 7.1, 7.1 Hz), 7.83
(1H, d, J= 7.8 Hz), 7.93 (1H, d, J= 2.4 Hz), 8.09 (2H, d, J= 7.3 Hz).
(Z)-2-(2, 4-Dimethoxyphenyl)-4-(3-methoxybenzylidene)-5(4H)-oxazolone: mp 142.0–144.0
1
°C; IR (KBr): 1776, 1650, 1296 cm–1; H NMR (600 MHz, CDCl3): δ 3.90 (3H, s), 3.91 (3H, s), 3.98
(3H, s), 6.56 (1H, d, J= 2.0 Hz), 6.62 (1H, dd, J= 2.0, 9.0 Hz), 6.99 (1H, dd, J= 2.0, 7.8 Hz), 7.14
(1H, s), 7.35 (1H, dd, J= 7.8, 7.8 Hz), 7.62 (1H, d, J= 7.8 Hz), 7.99 (1H, d, J= 2.0 Hz), 8.04 (1H, d,
J= 9.0 Hz).
α
General procedure for the synthesis of (Z)-N-acyl- -dehydro(methoxy-substituted
phenyl)alaninamide derivatives [ (Z)-1a–k]
(Z)-2-Alkyl-4-(methoxy-substituted benzylidene)-5(4H)-oxazolone (for 1a–h) or (Z)-2-aryl-4-(methoxy-
substituted benzylidene)-5(4H)-oxazolone (for 1i–k, 0.020 mol) was added to dry chloroform (200 mL)
containing methylamine (40 wt% aqueous solution 1.6 g, 0.021 mol) and the resulting solution was
allowed to stand for 1.0 h with stirring in an ice bath. The reaction mixture was concentrated to dryness
and the resulting residue was dissolved in ethanol and then treated with activated charcoal powder. After
removal of the solvent under reduced pressure, the crystalline solid obtained was recrystallized
from ethanol-hexane affording colorless crystals (50–85%).
(Z)-2-Acetylamino-3-(3, 4-dimethoxyphenyl)-N-methyl-2-propenamide
[(Z)-1a]:
mp
205.0–205.5 °C; IR (KBr): 3303, 1648, 1620 cm–1; 1H NMR (600 MHz, DMSO-d6): δ 2.02 (3H, s), 2.66

HETEROCYCLES, Vol. 65, No. 1, 2005
125
(3H, d, J= 4.8 Hz), 3.76 (3H, s), 3.77 (3H, s), 6.97 (1H, d, J= 8.9 Hz), 7.08 (1H, s), 7.09 (1H, dd, J=
13
1.4, 8.9 Hz), 7.23 (1H, d, J= 1.4 Hz), 7.87 (1H, q, J= 4.8 Hz), 9.35 (1H, s); C NMR (150 MHz,
DMSO-d6): δ 22.9, 26.2, 55.3, 55.5, 111.5, 112.3, 123.2, 126.8, 127.8, 128.3, 148.3, 149.3, 165.4,
169.3; Anal. Calcd for C14H18N2O4: C, 60.42; H, 6.52; N, 10.07. Found: C, 60.04; H, 6.39; N, 9.78.
(Z)-3-(3, 4-Dimethoxyphenyl)-2-isobutyrylamino-N-methyl-2-propenamide [(Z)-1b]: mp
1
205.0–205.5 °C; IR (KBr): 3300, 1651, 1647 cm–1; H NMR (600 MHz, DMSO-d6): δ 1.07 (6H, d, J=
5.9 Hz), 2.65 (3H, d, J= 4.8 Hz), 2.65 (1H, qq, J= 11.0, 5.9 Hz), 3.74 (3H, s), 3.74 (3H, s), 6.93 (1H,
s), 6.95 (1H, d, J= 8.2 Hz), 7.09 (1H, dd, J= 8.2, 2.1 Hz), 7.18 (1H, d, J= 2.1 Hz), 7.73 (1H, q, J= 4.8
13
Hz), 9.24 (1H, s); C NMR (150 MHz, DMSO-d6): δ 19.2 (2C), 26.2, 33.7, 55.5 (2C), 112.9, 114.5,
122.9, 126.9, 127.3, 128.5, 148.3, 149.2, 165.8, 175.7; Anal. Calcd for C16H22N2O4: C, 62.73; H, 7.24;
N, 9.14. Found: C, 62.61; H, 6.85; N, 8.97.
(Z)-3-(3, 4-Dimethoxyphenyl)-N-methyl-2-pivaloylamino-2-propenamide [(Z)-1c]: mp
1
192.0–193.0 °C; IR (KBr): 3296, 1679, 1624 cm–1; H NMR (600 MHz, DMSO-d6): δ 1.20 (9H, s), 2.67
(3H, d, J= 4.8 Hz), 3.75 (6H, s), 6.92 (1H, s), 6.95 (1H, d, J= 8.9 Hz), 7.08 (1H, dd, J= 8.9, 2.1 Hz),
7.19 (1H, d, J= 2.1 Hz), 7.60 (1H, q, J= 4.8 Hz), 8.92 (1H, s); 13C NMR (150 MHz, DMSO-d6): δ 26.1,
27.1(3C), 38.4, 55.5(2C), 111.4, 112.9, 123.0, 127.1, 127.5, 129.1, 148.3, 149.1, 166.2, 177.1; Anal.
Calcd for C17H24N2O4: C, 63.73; H, 7.55; N, 8.74. Found: C, 63.58; H, 7.24; N, 8.86.
(Z)-3-(3, 4-Dimethoxyphenyl)-N-methyl-2-phenylacetylamino-2-propenamide [(Z)-1d]: mp
1
182.5–183.0 °C; IR (KBr): 3291, 1676, 1637 cm–1; H NMR (600 MHz, DMSO-d6): δ 2.65 (3H, d, J=
4.5 Hz), 3.61 (3H, s), 3.64 (2H, s), 3.74 (3H, s), 6.76 (1H, d, J= 8.6 Hz), 6.99 (1H, dd, J= 8.6, 1.7
Hz), 6.99 (1H, s), 7.11 (1H, d, J= 1.7 Hz), 7.24-7.31 (5H, m), 7.88 (1H, q, J= 4.5 Hz), 9.54 (1H, s);
13C NMR (150 MHz, DMSO-d6): δ 26.2, 42.1, 55.3, 55.4, 111.3, 112.9, 122.8, 126.4, 126.6, 127.9,
128.0, 128.2 (2C), 129.3 (2C), 135.6, 148.3, 149.1, 165.5, 169.7; Anal. Calcd for C20H22N2O4: C,
67.78; H, 6.26; N, 7.90. Found: C, 67.49; H, 6.11; N, 7.85.
(Z)-3-(3,4-Dimethoxyphenyl)-2-(4-fluorophenylacetylamino)-N-methyl-2-propenamide
[(Z)-1e]: mp 175.0–175.5 °C; IR (KBr): 3298, 3126, 1660, 1653 cm–1; 1H NMR (600 MHz, DMSO-d6):
δ 2.67 (3H, d, J= 4.8 Hz), 3.64 (2H, s), 3.64 (3H, s), 3.75 (3H, s), 6.79 (1H, d, J= 8.2 Hz), 6.97 (1H,
dd, J= 8.2, 2.0 Hz), 7.02 (1H, s), 7.11 (1H, d, J= 2.0 Hz), 7.14 (2H, dd, J= 8.3, 8.9 Hz), 7.33 (2H, dd,
J= 8.3, 5.5 Hz), 7.91 (1H, q, J= 4.8 Hz), 9.54 (1H, s); 13C NMR (150 MHz, DMSO-d6): δ 26.2, 41.2,
55.3, 55.4, 111.3, 112.9, 114.9 (2C, d, J=22 Hz), 122.8 (2C), 126.6, 127.9, 128.1, 131.8 (2C, d J=
3Hz), 148.3, 149.2, 161.1(1C, d, J= 241 Hz), 165.6, 169.7; Anal. Calcd for C20H21N2O4F: C, 64.51; H,
5.68; N, 7.52. Found: C, 64.25; H, 5.52; N, 7.38.
(Z)-2-(4-Chlorophenylacetylamino)-3-(3,4-dimethoxyphenyl)-N-methyl-2-propenamide
[(Z)-1f]: mp 180.0–180.5 °C; IR (KBr): 3305, 3131, 1673, 1643 cm–1; 1H NMR (600 MHz, DMSO-d6):

126
HETEROCYCLES, Vol. 65, No. 1, 2005
δ 2.66 (3H, d, J= 4.8 Hz), 3.63 (2H, s), 3.64 (3H, s), 3.74 (3H, s), 6.76 (1H, d, J= 8.2 Hz), 6.92 (1H,
dd, J= 8.2, 1.8 Hz), 7.01 (1H, s), 7.10 (1H, d, J= 1.8 Hz), 7.33 (2H, d, J= 8.2 Hz), 7.38 (2H, d, J= 8.2
13
Hz), 7.91 (1H, q, J= 4.8 Hz), 9.54 (1H, s); C NMR (150 MHz, DMSO-d6): δ 26.2, 41.4, 55.3, 55.4,
111.3, 113.0, 122.7, 126.6, 127.8, 128.1 (3C), 131.2 (3C), 134.6, 148.2, 148.2, 165.4, 169.4; Anal.
Calcd for C20H21N2O4Cl: C, 61.78; H, 5.44; N, 7.20. Found: C, 61.59; H, 5.15; N, 6.96.
(Z)-2-(3,4-Dichlorophenylacetylamino)-3-(3,4-dimethoxyphenyl)-N-methyl-2-
1
propenamide [(Z)-1g]: mp 173.5–174.0 °C; IR (KBr): 3308, 2977, 1652, 1646 cm–1; H NMR (600
MHz, DMSO-d6): δ 2.67 (3H, d, J= 4.8 Hz), 3.66 (2H, s), 3.66 (3H, s), 3.75 (3H, s), 6.76 (1H, d, J=
8.3 Hz), 6.94 (1H, dd, J= 1.4, 8.3 Hz), 7.03 (1H, s), 7.09 (1H, d, J= 1.4 Hz), 7.30 (1H, dd, J= 1.4, 8.2
Hz), 7.57 (1H, d, J= 1.4 Hz), 7.59 (1H, d, J= 8.2 Hz), 7.94 (1H, q, J= 4.8 Hz), 9.56 (1H, s); 13C NMR
(150 MHz, DMSO-d6): δ 26.2, 41.0, 55.3, 55.4, 111.2, 113.1, 122.6, 126.6, 127.7, 128.4, 129.2, 128.9,
130.3, 130.7, 131.4, 136.8, 148.3, 149.2, 165.4, 169.0; Anal. Calcd for C20H20N2O4Cl2: C, 56.75; H,
4.76; N, 6.62. Found: C, 56.50; H, 4.47; N, 6.75.
(Z)-3-(3,4-Dimethoxyphenyl)-2-(3,4-dimethoxyphenylacetylamino)-N-methyl-2-
1
propenamide [(Z)-1h]: mp 180.5–181.0 °C; IR (KBr): 3275, 2964, 1640, 1621 cm–1; H NMR (600
MHz, DMSO-d6): δ 2.66 (3H, d, J= 4.8 Hz), 3.56 (2H, s), 3.63 (3H, s), 3.71 (3H, s), 3.74 (3H, s), 3.74
(3H, s), 6.73 (1H, d, J= 8.3 Hz), 6.83 (1H, dd, J= 1.7, 8.3 Hz), 6.91 (1H, d, J= 8.3 Hz), 6.92 (1H, dd,
J= 2.0, 8.3 Hz), 6.93 (1H, d, J= 1.7 Hz), 7.01 (1H, s), 7.11 (1H, d, J= 2.0 Hz), 7.87 (1H, q, J= 4.8
13
Hz), 9.45 (1H, s); C NMR (150 MHz, DMSO-d6): δ 26.2, 41.9, 55.3 (2C), 55.4, 55.6, 111.0, 111.7,
113.0, 113.2, 121.3, 122.7, 126.7, 128.0 (3C), 147.6, 148.2, 148.5, 149.1, 165.6, 170.0; Anal. Calcd
for C22H26N2O6: C, 63.76; H, 6.32; N, 6.76. Found: C, 63.47; H, 6.09; N, 6.96.
(Z)-2-(2,4-Dimethoxybenzoylamino)-3-(3,4-dimethoxyphenyl)-N-methyl-2-propenamide
[(Z)-1i]: mp 184.0–184.5 °C; IR (KBr): 3350, 3332, 1632, 1620 cm–1; 1H NMR (600 MHz, DMSO-d6):
δ 2.68 (3H, d, J= 4.6 Hz), 3.57 (3H, s), 3.76 (3H, s), 3.85 (3H, s), 3.93 (3H, s), 6.68 (1H, dd, J= 2.3,
9.2 Hz), 6.72 (1H, d, J= 2.3 Hz), 6.96 (1H, d, J= 8.6 Hz), 7.05 (1H, s), 7.15 (1H, d, J= 8.6 Hz), 7.22
13
(1H, s), 7.86 (1H, d, J= 9.2 Hz), 7.89 (1H, d, J= 4.6 Hz), 9.38 (1H, s); C NMR (150 MHz, DMSO-
d6): δ 26.3, 55.0, 55.4, 55.6, 56.2, 98.5, 105.9, 111.5, 112.2, 114.2, 123.0, 126.9, 127.1, 128.1, 132.8,
148.3, 149.2, 158.9, 163.4, 163.5, 165.6; Anal. Calcd for C21H24N2O6: C, 62.99; H, 6.04; N, 7.00.
Found: C, 62.83; H, 6.17; N, 6.86.
(Z)-2-Benzoylamino-3-(3-methoxyphenyl)-N-methyl-2-propenamide
[(Z)-1j]:
mp
181.5–182.5 °C; IR (KBr): 3244, 1635 cm–1; 1H NMR (600 MHz, DMSO-d6): δ 2.69 (3H, d, J= 4.9 Hz),
3.59 (3H, s), 6.86 (1H, dd, J= 2.4, 7.3 Hz), 7.11 (1H, d, J= 7.9 Hz), 7.16 (1H, s), 7.27 (1H, d, J= 2.4
Hz), 7.28 (1H, dd, J= 7.9, 7.9 Hz), 7.51 (2H, dd, J= 7.3, 7.9 Hz), 7.58 (1H, dd, J= 7.3, 7.9 Hz), 8.02
(2H, d, J= 7.3 Hz), 8.08 (1H, q, J= 4.9 Hz), 9.91 (1H, s); 13C NMR (150 MHz, DMSO-d6): δ 26.2, 54.7,
113.9, 114.5, 122.0, 127.8 (2C), 128.2 (2C), 128.9, 129.4, 130.2, 131.6, 133.5, 135.5, 159.0, 165.2,

HETEROCYCLES, Vol. 65, No. 1, 2005
127
165.7; Anal. Calcd for C18H18N2O3: C, 69.66; H, 5.85; N, 9.03. Found: C, 69.76; H, 5.52; N, 9.03.
(Z)-2-(2,4-Dimethoxybenzoylamino)-3-(3-methoxyphenyl)-N-methyl-2-propenamide
[(Z)-1k]: mp 150.5–151.5 °C; IR (KBr): 3308, 3300, 1650, 1632 cm–1; 1H NMR (600 MHz, DMSO-d6):
δ 2.69 (3H, d, J= 4.9 Hz), 3.67 (3H, s), 3.85 (3H, s), 3.90 (3H, s), 6.68 (1H, dd, J= 2.5, 7.9 Hz), 6.72
(1H, d, J= 2.5 Hz), 6.90 (1H, dd, J= 1.8, 8.6 Hz), 6.93 (1H, s), 7.14 (1H, d, J= 1.8 Hz), 7.16 (1H, d,
J= 7.9 Hz), 7.30 (1H, dd, J= 7.9, 8.6 Hz), 7.84 (1H, d, J= 7.9 Hz), 7.98 (1H, q, J= 4.9 Hz), 9.49 (1H,
13
s); C NMR (150 MHz, DMSO-d6): δ 54.9, 55.6, 56.1 (2C), 98.5, 106.0, 114.1, 114.2 (2C), 121.7,
125.2, 129.6, 130.8, 132.8, 135.6, 158.9, 159.2, 163.3, 163.5, 165.5; Anal. Calcd for C20H22N2O5: C,
64.85; H, 5.99; N, 7.56. Found: C, 64.76; H, 6.01; N, 7.74.
General procedure for the irradiation of (Z)-1a–k
In order to examine the irradiation time dependence of the product distribution and composition, a methanol
solution of (Z)-1 (3.75×10–3 mol dm–3, 200 mL) containing TEA (0.10 mol dm–3), placed in a Pyrex
vessel, was irradiated under nitrogen at rt with Pyrex-filtered light from a 400 W high-pressure Hg lamp
(internal irradiation). At suitable time intervals, an aliquot (5 mL) of the solution was pipetted off and
1
concentrated to dryness in vacuo. The resulting residue was dissolved in DMSO-d6 and subjected to H
NMR spectral analysis. The composition was estimated from the area ratio of a given 1H NMR signal for
each compound. The remaining solution containing TEA was concentrated to dryness in vacuo and the
resulting residue was subjected to preparative thin layer chromatography over silica gel. The mixed
solvents of chloroform and ethyl acetate were used as developing solvents.
On the other hand, a nitrogen-saturated methanol solution of (Z)-1 (3.75×10–3 mol dm–3, 500 mL)
containing DBU (0.010 mol dm–3), placed in a Pyrex vessel, was irradiated for 5 h with Pyrex-filtered light
from a 400 W high-pressure Hg lamp at room temperature. After 5 h irradiation, an appropriate amount of
the solution (5 mL) being irradiated was pipetted off and concentrated to dryness in vacuo giving the residue
1
which was subjected to H NMR spectral analysis in DMSO-d6. The remaining solution was concentrated
to dryness under reduced pressure and the resulting residue was subjected to column chromatography over
silica gel (230 mesh, Merck) eluting with chloroform-ethyl acetate. For the purpose of isolating the
photoproducts, preparative TLC plate (silica gel) was also used. Physical and spectroscopic data of
purified 3,4-dihydroquinolinones (2a–k), quinolinone (3a), and (E)-1a are as follows. Attempts
to isolate other quinolinones and (E)-isomers were not made.
3-Acetylamino-3, 4-dihydro-6, 7-dimethoxy-1-methyl-2(1H)-quinolinone (2a): mp 165.0–
166.0 °C (EtOH); IR (KBr): 3318, 1679, 1636 cm–1; 1H NMR (600 MHz, DMSO-d6): δ 1.91(3H, s), 2.76
(1H, dd, J= 6.2, 15.1 Hz), 2.91 (1H, dd, J= 14.5, 15.1 Hz), 3.29 (3H, s), 3.74 (3H, s), 3.80 (3H, s),
13
4.38 (1H, ddd, J= 6.2, 8.3, 14.5 Hz), 6.74 (1H, s), 6.90 (1H, s), 8.18 (1H, d, J= 8.3 Hz); C NMR
(150 MHz, DMSO-d6): δ 22.6, 30.0, 30.8, 48.5, 55.6, 55.9, 101.4, 112.4, 115.6, 132.9, 144.3, 148.0,
167.9, 169.2; Anal. Calcd for C14H18N2O4: C, 60.42; H, 6.52; N, 10.07. Found: C, 60.38; H, 6.41; N,
9.97.

128
HETEROCYCLES, Vol. 65, No. 1, 2005
3, 4-Dihydro-6, 7-dimethoxy-3-isobutyrylamino-1-methyl-2(1H)-quinolinone (2b):
mp
1
179.0–180.0 °C (EtOH); IR (KBr): 3334, 1691, 1638 cm–1; H NMR (600 MHz, DMSO-d6): δ 1.03 (3H,
d, J= 6.1 Hz), 1.05 (3H, d, J= 6.9 Hz), 2.49 (3H, qq, J= 6.1, 6.9 Hz), 2.79 (1H, dd, J= 6.2, 15.1 Hz),
2.87 (1H, dd, J= 14.5, 15.1 Hz), 3.29 (3H, s), 3.73 (3H, s), 3.80 (3H, s), 4.38 (1H, ddd, J= 6.2, 7.6,
13
14.5 Hz), 6.74 (1H, s), 6.91 (1H, s), 8.03 (1H, d, J= 7.6 Hz); C NMR (150 MHz, DMSO-d6): δ 19.5
(2C), 30.0, 30.7, 33.9, 48.2, 55.9 (2C), 101.4, 112.4, 115.7, 133.0, 144.3, 148.0, 168.0, 176.1; Anal.
Calcd for C16H22N2O4: C, 62.73; H, 7.24; N, 9.14. Found: C, 62.35; H, 7.11; N, 9.05.
3, 4-Dihydro-6, 7-dimethoxy-1-methyl-3-pivaloylamino-2(1H)-quinolinone
(2c):
mp
1
179.0–180.0 °C (EtOH); IR (KBr): 3325, 1676, 1639 cm–1; H NMR (600 MHz, DMSO-d6): δ 1.15 (9H,
s), 2.83 (1H, dd, J= 14.5, 15.1 Hz), 2.91 (1H, dd, J= 6.2, 15.1 Hz), 3.29 (3H, s), 3.73 (3H, s), 3.80
13
(3H, s), 4.38 (1H, ddd, J= 6.2, 7.6, 14.5 Hz), 6.74 (1H, s), 6.91 (1H, s), 7.60 (1H, d, J= 7.6 Hz); C
NMR (150 MHz, DMSO-d6): δ 27.3 (3C), 30.0, 30.4, 38.0, 48.4, 55.9 (2C), 101.4, 112.4, 115.9, 133.0,
144.3, 148.0, 168.0, 176.1; Anal. Calcd for C17H24N2O4: C, 63.73; H, 7.55; N, 8.74. Found: C, 63.46;
H, 7.22; N, 8.61.
3, 4-Dihydro-6, 7-dimethoxy-1-methyl-3-phenylacetylamino-2(1H)-quinolinone (2d): mp
1
192.0–193.0 °C (EtOH); IR (KBr): 3288, 1677, 1628 cm–1; H NMR (600 MHz, DMSO-d6): δ 2.75 (1H,
dd, J= 6.2, 15.1 Hz), 2.86 (1H, dd, J= 14.4, 15.1 Hz), 3.52 (2H, s), 3.67 (3H, s), 3.74 (3H, s), 4.35
(1H, ddd, J= 6.2, 7.6, 14.4 Hz), 6.70 (1H, s), 6.86 (1H, s), 7.16–7.19 (1H, m), 7.24–7.26 (4H, m),
13
8.34 (1H, d, J= 7.6 Hz); C NMR (150 MHz, DMSO-d6): δ 30.1, 30.7, 42.1, 48.6, 55.9, 56.0, 101.5,
112.5, 115.6, 126.3, 128.2 (2C), 129.0 (2C), 133.0, 136.3, 144.4, 148.1, 167.8, 170.1; Anal. Calcd for
C20H22N2O4: C, 67.43; H, 6.28; N, 7.86. Found: C, 67.78; H, 6.26; N, 7.90.
3,4-Dihydro-6,7-dimethoxy-3-(4-fluorophenylacetylamino)-1-methyl-2(1H) -quinolinone
1
(2e): mp 202.0–203.0 °C (EtOH); IR (KBr): 3352, 1684, 1640 cm–1; H NMR (600 MHz, DMSO-d6): δ
2.78 (1H, dd, J= 6.2, 15.1 Hz), 2.91 (1H, dd, J= 14.4, 15.1 Hz), 3.31 (3H, s), 3.53 (2H, s), 3.71 (3H,
s), 3.79 (3H, s), 4.38 (1H, ddd, J= 6.2, 7.5, 14.4 Hz), 6.74 (1H, s), 6.90 (1H, s), 7.13 (2H, dd, J= 8.9,
9.0 Hz), 7.33 (2H, dd, J= 6.2, 9.0 Hz), 8.34 (1H, d, J= 7.5 Hz); 13C NMR (150 MHz, DMSO-d6): δ 30.1,
30.7, 48.6, 55.9, 56.0, 79.1, 101.5, 112.4, 114.8 (2C, d, J= 22 Hz), 115.6, 130.8 (2C, d, J= 7 Hz),
132.4, 133.0, 144.3, 148.1, 160.9 (1C, d, J= 241 Hz), 167.8, 170.0; Anal. Calcd for C20H21N2O4F: C,
64.51; H, 5.68; N, 7.52. Found: C, 64.25; H, 5.54; N, 7.31.
3-(4-Chlorophenylacetylamino)-3,4-dihydro-6,7-dimethoxy-1-methyl-2(1H) -quinolinone
(2f): mp 202.0–203.0 °C (EtOH); IR (KBr): 3346, 1681, 1643 cm–1; 1H NMR (600 MHz, DMSO-d6): δ
2.77 (1H, dd, J= 6.1, 15.1 Hz), 2.91 (1H, dd, J= 14.4, 15.1 Hz), 3.29 (3H, s), 3.53 (2H, s), 3.71 (3H,
s), 3.78 (3H, s), 4.38 (1H, ddd, J= 6.1, 8.3, 14.4 Hz), 6.73 (1H, s), 6.89 (1H, s), 7.31 (2H, d, J= 8.2
13
Hz), 7.35 (2H, d, J= 8.2 Hz), 8.43 (1H, d, J= 8.3 Hz); C NMR (150 MHz, DMSO-d6): δ 30.1, 30.7,
41.3, 48.6, 55.9, 56.0, 101.5, 112.4, 115.6, 128.1 (2C), 130.9 (2C), 131.1, 133.0, 135.3, 144.3, 148.1,

HETEROCYCLES, Vol. 65, No. 1, 2005
129
167.7, 169.7; Anal. Calcd for C20H21N2O4Cl: C, 61.78; H, 5.44; N, 7.20. Found: C, 61.78; H, 5.30; N,
7.41.
3-(3,4-Dichlorophenylacetylamino)-3,4-dihydro-6,7-dimethoxy-1-methyl-2(1H) -
1
quinolinone (2g): mp 177.0–178.0 °C (EtOH); IR (KBr): 3325, 1683, 1635 cm–1; H NMR (600 MHz,
DMSO-d6): δ 2.79 (1H, dd, J= 6.1, 15.2 Hz), 2.92 (1H, dd, J= 14.4, 15.2 Hz), 3.30 (3H, s), 3.58 (2H,
s), 3.72 (3H, s), 3.79 (3H, s), 4.37 (1H, ddd, J= 6.1, 8.2, 14.4 Hz), 6.75 (1H, s), 6.91 (1H, s), 7.30
13
(1H, dd J= 2.1, 8.2 Hz), 7.58 (1H, d, J= 8.2 Hz), 7.59 (1H, d, J= 2.1 Hz), 8.99 (1H, d, J= 8.2 Hz); C
NMR (150 MHz, DMSO-d6): δ 30.1, 30.6, 48.7, 55.9, 56.0, 101.5, 112.4, 115.6, 129.1, 129.5, 130.3,
130.7, 131.1 (2C), 137.4, 144.4, 148.1, 167.7, 169.3; Anal. Calcd for C20H20N2O4Cl2: C, 56.75; H,
4.76; N, 6.62. Found: C, 56.50; H, 4.65; N, 6.44.
3,4-Dihydro-6,7-dimethoxy-3-(3,4-dimethoxyphenylacetylamino)-1-methyl-2(1H) -
1
quinolinone (2h): mp 191.0–192.0 °C (EtOH); IR (KBr): 3290, 1642, 1618 cm–1; H NMR (600 MHz,
DMSO-d6): δ 2.75 (1H, dd, J= 6.2, 15.1 Hz), 2.90 (1H, dd, J= 14.4, 15.1 Hz), 4.37 (1H, ddd, J= 6.2,
7.6, 14.4 Hz), 6.73 (1H, s), 6.80 (1H, d, J= 7.6 Hz), 6.86 (1H, d, J= 7.6 Hz), 6.89 (1H, s), 6.95 (1H,
13
s), 8.28 (1H, d, J= 7.6 Hz); C NMR (150 MHz, DMSO-d6): δ 30.1, 30.7, 41.8, 48.6, 55.4, 55.5, 55.9,
56.0, 101.5, 111.8, 112.5, 112.9, 115.6, 121.0, 128.6, 133.0, 144.3, 147.5, 148.0, 148.5, 167.8,
170.3; Anal. Calcd for C22H26N2O6: C, 63.76; H, 6.32; N, 6.76. Found: C, 63.67; H, 5.99; N, 6.61.
3,4-Dihydro-6,7-dimethoxy-3-(2,4-dimethoxybenzoylamino)-1-methyl-2(1H) -
1
quinolinone (2i): mp 203.5–205.0 °C (EtOH); IR (KBr): 3372, 1643, 1605 cm–1; H NMR (600 MHz,
DMSO-d6): δ 2.80 (1H, dd, J= 5.7, 14.9 Hz), 3.30 (1H, dd, J= 14.3, 14.9 Hz), 3.34 (3H, s), 3.76 (3H,
s), 3.81 (3H, s), 3.84 (3H, s), 3.97 (3H, s), 4.49 (1H, ddd, J= 5.2, 5.7, 14.3 Hz), 6.68 (1H, dd, J= 2.3,
9.2 Hz), 6.71 (1H, d, J= 2.3 Hz), 6.80 (1H, s), 6.96 (1H, s), 7.94 (1H, d, J= 9.2 Hz), 8.81 (1H, d, J=
5.2 Hz); 13C NMR (150 MHz, DMSO-d6): δ 30.3, 30.7, 49.6, 55.6, 55.9, 56.0, 56.3, 98.7, 101.7, 106.0,
112.5, 113.7, 116.0, 132.7, 132.8, 144.5, 148.1, 159.0, 163.2, 163.8, 168.0; Anal. Calcd for
C21H24N2O6: C, 62.67; H, 6.51; N, 6.96. Found: C, 62.46; H, 6.39; N, 6.84.
3-Benzoylamino-3, 4-dihydro-6-methoxy-1-methyl-2(1H)-quinolinone (2j): mp 127.0–127.5
1
°C (EtOH); IR (KBr): 3279, 1676, 1630 cm–1; H NMR (600 MHz, DMSO-d6): δ 3.01 (1H, dd, J= 5.5,
14.8 Hz), 3.14 (1H, dd, J= 14.4, 14.8 Hz), 3.29 (3H, s), 3.75 (3H, s), 4.68 (1H, ddd, J= 5.5, 8.2, 14.4
Hz), 6.88 (1H, dd, J= 2.7, 8.9 Hz), 6.92 (1H, d, J= 2.7 Hz), 7.08 (1H, d, J= 8.9 Hz), 7.51 (2H, dd, J=
6.9, 6.9 Hz), 7.57 (1H, dd, J= 6.9, 6.9 Hz), 7.90 (2H, d, J= 6.9 Hz), 8.70 (1H, d, J= 8.2 Hz); 13C NMR
(150 MHz, DMSO-d6): δ 30.0, 31.2, 48.6, 55.3, 112.5, 113.9, 116.1, 125.7, 127.3 (2C), 128.3 (2C),
131.4, 133.1, 134.0, 154.9, 166.1, 167.7; Anal. Calcd for C18H18N2O3: C, 69.66; H, 5.85; N, 9.03.
Found: C, 69.35; H, 5.88; N, 8.84.

130
HETEROCYCLES, Vol. 65, No. 1, 2005
3,4-Dihydro-3-(2,4-dimethoxybenzoylamino)-6-methoxy-1-methyl-2(1H) -quinolinone
1
(2k): mp 160.5–161.5 °C (EtOH); IR (KBr): 3394, 1650, 1611 cm–1; H NMR (600 MHz, DMSO-d6): δ
3.35 (1H, dd, J= 5.5, 15.1 Hz), 2.89 (1H, dd, J= 15.1, 14.4 Hz), 3.32 (3H, s), 3.76 (3H, s), 3.84 (3H,
s), 3.97 (3H, s), 4.50 (1H, ddd, J= 5.5, 7.9, 14.4 Hz), 6.68 (1H, dd, J= 2.1, 8.9 Hz), 6.71 (1H, d, J=
2.8 Hz), 6.89 (1H, dd, J= 2.8, 8.9 Hz), 6.94 (1H, d, J= 2.1 Hz), 7.11 (1H, d, J= 8.9 Hz), 7.94 (1H, d,
13
J= 8.9 Hz), 8.81 (1H, d, J= 7.9 Hz); C NMR (150 MHz, DMSO-d6): δ 30.1, 31.3, 49.3, 55.3, 55.5,
56.2, 98.7, 106.0, 112.6, 113.7, 113.9, 116.4, 125.9, 132.7, 133.0, 155.1, 159.0, 163.3, 163.9, 167.8;
Anal. Calcd for C20H22N2O5: C, 64.85; H, 5.99; N, 7.56. Found: C, 64.66; H, 5.81; N, 7.67.
3-Acetylamino-6, 7-dimethoxy-1-methyl-2(1H)-quinolinone (3a): mp 195.0–196.0 °C (EtOAc);
1
IR (KBr): 3377, 1688, 1636 cm–1; H NMR (600 MHz, DMSO-d6): δ 2.17 (3H, s), 3.74 (3H, s), 3.81
13
(3H, s), 3.91 (3H, s), 6.99 (1H, s), 7.26 (1H, s), 8.59 (1H, s), 9.33 (1H, s); C NMR (150 MHz,
DMSO-d6): δ 24.1, 30.2, 55.7, 55.8, 98.1, 109.5, 113.1, 120.4, 125.6, 130.6, 145.2, 150.2, 156.7,
169.3; Anal. Calcd for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14. Found: C, 60.88; H, 5.56; N, 9.86.
1
(E)-1a: mp 142.5–143.0 °C (EtOAc); IR (KBr): 3275, 1686, 1643, 1624 cm–1; H NMR (600 MHz,
DMSO-d6): δ 1.93 (3H, s), 2.57 (3H, d, J= 4.8 Hz), 3.69 (3H, s), 3.73 (3H, s), 6.72 (1H, s), 6.75 (1H,
dd, J= 2.1, 8.3 Hz), 6.86 (1H, d, J= 2.1 Hz), 6.97 (1H, d, J= 8.3 Hz), 7.97 (1H, d, J= 4.8 Hz), 9.50
13
(1H, s); C NMR (150 MHz, DMSO-d6): δ 23.3, 25.8, 55.3, 55.4, 111.2, 111.6, 115.4, 120.8, 127.9,
131.8, 147.8, 148.2, 165.5, 168.0; Anal. Calcd for C14H18N2O4: C, 60.42; H, 6.52; N, 10.07. Found: C,
60.40; H, 6.40; N, 9.97.
ACKNOWLEDGMENT
This research was partially supported by a “High-Tech Research Project” from the Ministry of
Education, Sports, Culture, Science and Technology, Japan.
REFERENCES
1. P. S. Mariano and J. L. Stavinoha, ‘Synthetic Organic Photochemistry,’ ed. by W. M. Horspool,
Plenum Press, New York, 1984, pp. 145–257.
2. C. Shin, Y. Yonezawa, and M. Ikeda, Bull. Chem. Soc. Jpn., 1986, 5 9, 3573; C. Shin, N. Takahashi,
and Y. Yonezawa, Chem. Pharm. Bull., 1990, 38, 2020; U. Schmidt, H. Griesser, V. Leitenberger, A.
Lieberknecht, R. Mangold, R. Meyer, and B. Riedl, Synthesis, 1992, 487; F. Effenberger, J.
Kuehlwein, M. Hopf, and U. Stelzer, Liebigs Ann. Chem., 1993, 1303; P. M. T. Ferreira, H. L. S.
Maia, and L. S. Monteiro, Tetrahedron Lett., 1998, 39, 9575; P. M. T. Ferreira, H. L. S. Maia, L. S.
Monteiro, and J. Sacramento, Tetrahedron Lett., 2000, 41, 7437; H. Sai, T. Ogiku, and H.
Ohmizu, Synthesis, 2003, 201.
3. C. Shin, Y. Nakajima, T. Haga, and Y. Sato, Bull. Chem. Soc. Jpn., 1986, 59, 3917; Y. Sato, Y.
Nakajima, and C. Shin, Heterocycles, 1992, 3 3, 589.
4. F. D. Lewis, Acc. Chem. Res., 1979, 1 2, 152; F. D. Lewis and G. D. Reddy, J. Am. Chem. Soc. ,

HETEROCYCLES, Vol. 65, No. 1, 2005
131
1989, 111, 6465; F. D. Lewis, G. D. Reddy, and D. M. Bassani, J. Am. Chem. Soc., 1993, 115,
6468; F. D. Lewis, D. M. Bassani, and G. D. Reddy, J. Org. Chem., 1993, 58, 6390; F. D. Lewis, D.
Reddy, D. M. Bassani, S. Schneider, and M. Gahr, J. Am. Chem. Soc., 1994, 116, 597; F. D. Lewis,
D. M. Bassani, E. L. Burch, B. E. Cohen, J. A. Engleman, G. D. Reddy, S. Schneider, W. Jaeger, P.
Gedeck, and M. Gahr, J. Am. Chem. Soc., 1995, 117, 660.
5. K. Kubo, S. Yaegashi, K. Sasaki, T. Sakurai, and H. Inoue, Tetrahedron Lett., 1996, 37, 5917; K.
Kubo M. Koshiba, H. Hoshina, and T. Sakurai, Heterocycles, 1998, 4 8, 25; H. Hoshina, K. Kubo,
A. Morita, and T. Sakurai, Tetrahedron, 2000, 56, 2941; H. Hoshina, H. Tsuru, K. Kubo, T. Igarashi,
and T. Sakurai, Heterocycles, 2000, 5 3, 2261.
6. T. Sakurai, Y. Morioka, K. Maekawa, and K. Kubo, Heterocycles, 2000, 53, 271; K. Maekawa, T.
Igarashi, K. Kubo, and T. Sakurai, Tetrahedron, 2001, 57, 5515; T. Motohashi, K. Maekawa, K.
Kubo, T. Igarashi, and T. Sakurai, Heterocycles, 2002, 5 7, 269.
7. K. Maekawa, H. Kajiwara, Y. Iseya, T. Igarashi, and T. Sakurai, Heterocycles, 2003, 6 0, 637.
8. K. Maekawa, T. Sasaki, K. Kubo, T. Igarashi, and T. Sakurai, Tetrahedron Lett., 2004, 4 5, 3663.
9. G. R. Martinez, K. A. M. Walker, D. R. Hirschfeld, J. J. Bruno, D. S. Yang, and P. J. Maloney, J.
Med. Chem., 1992, 35, 620; C. D. Jones, J. E. Audia, D. E. Lawhorn, L. A. McQuaid, B. L.
Neubauer, A. J. Pike, P. A. Pennington, N. B. Stamm, R. E. Toomey, and K. S. Hirsch, J. Med.
Chem., 1993, 36, 421; T. Nishikawa, M. Omura, T. Iizuka, I. Saito, and S. Yoshida, Arzneim.-
Forsch./Drug Res., 1996, 46, 875; Y. Oshiro, S. Sato, N. Kurahashi, T. Tanaka, T. Kikuchi,
K. Tottori, Y. Uwahodo, and T. Nishi, J. Med. Chem., 1998, 41, 658; Y. Oshiro,
Y. Sakurai, S. Sato, N. Kurahashi, T. Tanaka, T. Kikuchi, K. Tottori, Y. Uwahodo, T. Miwa, and T.
Nishi, J. Med. Chem., 2000, 43, 177; I. Butenschön, K. Möller, and W. Hönsel, J. Med. Chem.,
2001, 44, 1249; K. G. Rosauer, A. K. Ogawa, C. A. Willoughby, K. P. Ellsworth, W. M. Geissler,
R. W. Myers, Q. Deng, K. T. Chapman, G. Harris, and D. E. Moller, Bioorg. Med. Chem. Lett.,
2003, 1 3, 4385.
10. K. Maekawa, A. Shinozuka, M. Naito, T. Igarashi, and T. Sakurai, Tetrahedron, 2004, 6 0, 10293.
11. H. Hoshina, K. Maekawa, K. Taie, T. Igarashi, and T. Sakurai, Heterocycles, 2003, 6 0, 1779.
12. Y. S. Rao and R. Filler, Synthesis, 1975, 749; B. Rzeszotarska, J. Karolak-Wojciechowska, M. A.
Broda, Z. Galdecki, B. Trzezwinska, and A. E. Koziol, Int. J. Peptide Protein Res., 1994, 4 4, 313.
13. These
pKa
values
were
calculated
using
Advanced
Chemistry
Development
(ACD/Labs) Software Solaris Ver. 4.67 (Registry Numbers: TEA, 121-44-8; DPA, 7087-68-5; DBU,
6674-22-2).
14. ‘Handbook of Tables for Organic Compound Identification,’ 3rd edn., ed. by Z. Rappoport, The
Chemical Rubber Co., Ohio, 1968, p. 439.
15. H. E. Zimmerman and V. R. Sandel, J. Am. Chem. Soc., 1963, 85, 915; H. E. Zimmerman, J. Am.
Chem. Soc., 1995, 117, 8988; H. E. Zimmerman, J. Phys. Chem. A, 1998, 102, 5616.
16. J. A. Riddick, W. B. Bunger, and T. K. Sakano, ‘Organic Solvents,’ 4th ed. Wiley, Chichester,
1986.