Reactivity of 3-iodo-4-quinolones in heck reactions: Synthesis of novel (E)-3-styryl-4-quinolones

Article abstract of DOI:10.1055/s-0029-1219175

A new and efficient route for the synthesis of (E)-N-?methyl-3-styryl-4- quinolones is described. It involves the Heck ?reaction of N-methyl-3-iodo-4- quinolone, which is obtained by consecutive 3-iodination and NH-methylation of the unsubstituted 4-quinolone, with styrene derivatives. It is demonstrated that such a procedure is only efficient when the 3-iodo-4-quinolone has an N-protecting group. In some cases the branched regioisomers N-methyl-3-(1- phenylethenyl)-4-quinolones were also obtained as byproducts. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0029-1219175

462
LETTER
Reactivity of 3-Iodo-4-quinolones in Heck Reactions: Synthesis of
Novel (E)-3-Styryl-4-quinolones
Synthesisof
N
ove
n
l
(
E
)-3-Styry
d
l-4-quinolone
r
s
eia I. S. Almeida, Artur M. S. Silva,* José A. S. Cavaleiro
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal
Fax +351(234)370084; E-mail: artur.silva@ua.pt
Received 10 November 2009
route involves the Heck reaction of 3-iodo-4-quinolones
with styrene derivatives (Scheme 1).
Abstract: A new and efficient route for the synthesis of (E)-N-
methyl-3-styryl-4-quinolones is described. It involves the Heck
reaction of N-methyl-3-iodo-4-quinolone, which is obtained by
consecutive 3-iodination and NH-methylation of the unsubstituted
4-quinolone, with styrene derivatives. It is demonstrated that such a
procedure is only efficient when the 3-iodo-4-quinolone has an N-
protecting group. In some cases the branched regioisomers N-meth-
yl-3-(1-phenylethenyl)-4-quinolones were also obtained as byprod-
ucts.
The Mizoroki–Heck reaction,14 commonly referred as the
Heck reaction, is a highly versatile and useful carbon–
carbon bond-forming methodology using aryl halides as
substrates and nowadays is a keystone in synthetic organic
chemistry.15
Firstly, 4-quinolone (1) was synthesized,16 in good yield
(70%), by reaction of 2¢-aminoacetophenone with methyl
formate in the presence of sodium, at 40 °C (Scheme 1).17
Then, 3-iodo-4-quinolone (2)18 was obtained in good
yield (81%) by a recently reported method for the iodina-
tion of 2-aryl-4-quinolones,19 involving the reaction of 1
with iodine in the presence of sodium carbonate in dry
THF (Scheme 1).20
Key words: 3-iodo-4-quinolones, 3-styryl-4-quinolones, Heck
reaction, N-methylation, iodination
Quinolone ring systems are present in a wide range of nat-
ural products, especially in alkaloids obtained from plants
belonging to the Rutaceae family.1 Therefore, 4-quino-
lones are known by their extensive variety of clinical ap-
plications, such as the treatment of respiratory,
gastrointestinal, and gynaecologic infections, sexually
transmitted diseases, chronic osteomyelitis, prostatitis,
and some skin, bone, and soft tissue infections.2 The
search for new 4-quinolone derivatives has been carried
out to improve the spectrum of antimicrobial activity
against Gram negative as well as Gram positive bacteria.3
In recent years, certain 4-quinolones possessing anti-
tumor, anti-HIV-1 integrase and cannabinoid receptor
agonist–antagonist activities, have been described.4
In the next step to afford (E)-3-styryl-4-quinolone (4), a
range of Heck reaction conditions involving 3-iodo-4-quin-
olone (2) and styrene 3a were explored (Table 1 shows
only pertinent results). In the first attempt, palladium(II)
acetate was used as precatalyst and triphenylphosphine
(Ph3P) as ligand and in situ reducing agent of the precata-
lyst to palladium(0) prior to entering in the Heck catalytic
cycle. Under these conditions, 4 was obtained in low
yields, 20% being the highest yield obtained when using
triethylamine as base, at 150 °C for five hours (Table 1,
entry 1) or by using the Heck–Jeffery reaction condi-
tions,21 at 100 °C for five hours (Table 1, entry 3). On the
other hand, the use of tri(o-tolyl)phosphine (o-TTP) led us
2-Aryl-4-quinolones, also called azoflavones, are well-
known for their significant anticancer activity,5 but some
derivatives also demonstrate other important biological
properties, such as antiviral,6 antibacterial,7 antiplatelet,8
and trypanocidal activities.9 The related 3-aryl-4-quino-
lones (azoisoflavones) have also shown important biolog-
ical properties, such as EGFR tyrosine kinase10 and P-
glycoprotein inhibitory activity,11 good and selective cy-
totoxic activity against human cancer cell lines,12 and also
extremely high antiplatelet potency.8 However, despite
their structural analogy with isoflavones, this group of
compounds have received less attention. In the present
communication we report a new method for the synthesis
of 3-styryl-4-quinolones, a new type of 4-quinolone struc-
turally related to 3-aryl-4-quinolones and with 3-styryl-
chromones.13 The key transformation of this synthetic
Table 1 Heck Reaction of 3-Iodo-4-quinolone 2 with Styrene 3a
Entry
Conditionsa
Yield of Yield of
4 (%) 5 (%)
1
2
Pd(OAc)2, Ph3P, Et3N, 5 h, 150 °C
20
10
–
16
–
Pd(OAc)2, o-TTP, Et3N, 5 h, 100 °C
3
Pd(OAc)2, Ph3P, K2CO3, TBAB, 5 h, 100 °C 20
4b
5
Pd(PPh3)4, Ph3P, Et3N, 5 h, 100 °C
Pd(PPh3)4, o-TTP, Et3N, 5 h, 100 °C
Pd(PPh3)4, Ph3P, Et3N, 5 h, 130 °C
NMP, NaOAc, Pd/C, 140 °C
46
16
28
8
trace
trace
–
6
7
–
a Reactions were performed using 5 equiv of styrene, 0.1 equiv of
ligand, 1 equiv of base and using NMP as solvent.
SYNLETT 2010, No. 3, pp 0462–0466
Advanced online publication: 07.01.2010
DOI: 10.1055/s-0029-1219175; Art ID: D32609ST
1
2.
0
2.
2
0
1
0
b 10% of starting material recovered. o-TTP = tri(o-tolyl)phosphine.
TBAB = tetrabutylammonium bromide.
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Novel (E)-3-Styryl-4-quinolones
463
for the reaction of 2 with styrene 3a; 5 equivalents of sty-
rene, 0.05 equivalents of Pd(PPh3)4, 0.1 equivalents of
Ph3P and 1 equivalent of Et3N in NMP (Table 2, entry 1).
Under these conditions, (E)-N-methyl-3-styryl-4-quino-
lone (7a) was isolated as the main product (55%) and
N-methyl-3-(1-phenylethenyl)-4-quinolone (8a)28 as a
byproduct (14%), with 8% recovery of starting com-
pound. Some changes on the procedure were carried out,
such as increasing the amount of catalyst (Table 2, entry
2), changing the catalyst source from palladium(0) to pal-
ladium(II) (Table 2, entry 3), and the solvent (Table 2, en-
try 4), but the yield of the expected quinolone 7a did not
improve. It is important to note that under all these condi-
tions the byproduct 8a was not found or was found in a
very low yield.
H
N
H
N
8
5
9
2
7
6
β
6'
3'
3
+
5'
4'
10
4
α
O
O
2'
5
4
(iii)
3a
H
N
H
N
NH2
(ii)
(i)
HCO2Me
I
O
O
O
1
2
Me
N
R1
(iv)
Table 2 Heck Reaction of N-Methyl-3-iodo-4-quinolone (6) with
Styrene 3a
R2
Me
O
Conditionsa
Yield of Yieldof
7a (%) 8a (%)
R1
N
Entry
3a–e
7a–e
R2
+
(v)
I
1b
2
Pd(PPh3)4 (0.05 equiv), Ph3P, Et3N, NMP,
5 h, 100 °C
55
42
40
22
14
–
Me
N
O
8
5''
4'' R1
9
6''
2
3
7
6
a: R1 = R2 = H
6
b: R1 = OMe, R2 = H
c: R1 = R2 = OMe
d: R1 = F, R2 = H
e: R1 = H, R2 = NO2
Pd(PPh3)4 (0.05 equiv), Ph3P, Et3N, NMP,
5 h, 100 °C
R2
3''
10
4
1'
2'
2''
5
O
3
PdCl2 (0.05 equiv), Ph3P, Et3N, NMP,
5 h, 100 °C
3
8a–e
Scheme 1 Reagents and conditions: (i) Na, 40 °C, 6 h; (ii) Na2CO3,
I2, dry THF, 6 h; (iii) Heck reaction conditions (Table 1); (iv) MeI,
PS-TBD, 40 °C, dry THF, 3 h; (v) Heck reaction: classical heating
conditions and microwave irradiation (Tables 2,3).
4
Pd(PPh3)4 (0.05 equiv), Ph3P, Et3N, CH3CN,
5 h, 100 °C
–
a Reactions were performed using 5 equiv of styrene, 0.1 equiv of
ligand, 1 equiv of base in 3 mL of solvent.
b 8% of starting material was recovered.
to obtain compound 5 as the main reaction product
(Table 1, entry 2). However, the optimal experimental
conditions were achieved when palladium(0) was used as
catalyst [Pd(PPh3)4], in the presence of Ph3P as ligand, and
Et3N as base at 100 °C for five hours (Table 1, entry 4).22
Under these reaction conditions, the desired (E)-3-styryl-
4-quinolone (4)23 was obtained in acceptable yield (46%)
and traces of the branched regioisomer 3-(1-phenylethe-
nyl)-4-quinolone (5) were found (Scheme 1).
The beneficial effect of microwave heating in synthetic
organic chemistry is a growing area, since higher yields
and shorter reaction times might be obtained.29 In our case
the Heck reaction of N-methyl-3-iodo-4-quinolone (6)
with styrene 3a under microwave irradiation conditions
allowed us to shortening the reaction time but led to lower
yields than the purely thermal procedure (e.g., 40% being
the highest yield obtained in 1.5 h reaction time).
All tested cross-coupling reaction conditions led to low or
moderate yields of 4 with difficult and time-consuming
purification processes. Furthermore, not only the expect-
ed linear product 4 was obtained but also its branched re-
gioisomer 5. These results led us to conclude that the
reaction proceeds via two pathways, an ionic one leading
to the branched product, and the neutral one, this giving
rise to the linear variant.24
After these studies on the Heck reaction of 3-iodo-4-qui-
nolones 2 and 6 with styrene 3a to afford (E)-3-styryl-4-
quinolones (4) and 7a, we have extended our attention to
the reactions of N-methyl-3-iodo-4-quinolone 6 with dif-
ferent styrenes 3b–e and to the optimization of the synthe-
sis of (E)-N-methyl-3-styryl-4-quinolone derivatives 7b–e.
Attempts to prepare (E)-3-styryl-4-quinolones 7b,c by
treating 6 with styrenes 3b,c using the best conditions es-
tablished in Table 2, were not very successful, the expect-
ed compounds being obtained in poor yields (8b: 15%, 8c:
30%). Even when the amount of catalyst was changed
[from 0.05 to 0.1 equiv of Pd(PPh3)4] and the temperature
(from 100 °C to 130 °C), the results were not better. Con-
sequently, other conditions were attempted by treating 6
with palladium(II) chloride as catalyst, instead of
Pd(PPh3)4, in the presence of Ph3P, Et3N, and using NMP
In order to circumvent these problems we have decided to
protect the NH group of 3-iodo-4-quinolone 2, trying to
avoid possible reactions at the NH group and changing the
reactivity of this 4-quinolone 2. Methylation of 2 with an
excess of methyl iodide in the presence of PS-TBD,25 in
dry THF at 40 °C, led to the formation of N-methyl-3-
iodo-4-quinolone (6)26 in good yield (95%) (Scheme 1).27
In the first attempt to synthesise 3-styryl-4-quinolones
7a–e, we used the optimal conditions established above
Synlett 2010, No. 3, 462–466 © Thieme Stuttgart · New York

464
A. I. S. Almeida et al.
LETTER
Table 3 Optimal Heck Reaction Conditions of N-Methyl-3-iodo-4-quinolone (6) with Styrenes 3b–e
Compound
Catalyst
PdCl2
Yields under classical heating conditions(%)aYields under MW condtions (%)b
7b
8b
59
–
36
trace
7c
8c
PdCl2
55
30
trace
7d
8d
PdCl2
56
trace
48
–
7e
8e
Pd(PPh3)4
65
–
45
–
a N-Methyl-3-iodo-4-quinolone (6) was treated with 5 equiv of the appropriate styrene 3b–e, 0.05 equiv of catalyst, 0.1 equiv of Ph3P, and 1
equiv of Et3N, in 3 mL of NMP, at 100 °C for 5 h.
b Reaction performed in closed glass vessels under MW irradiation: 2 min ramp to 100 °C and 1.5 h hold at 100 °C.
as solvent, under classical heating conditions (Table 3). effect of microwave irradiation in the Heck reaction was
The target compounds 7b,c30 were then obtained in good the shortening of the reaction time although the product
yields (55–59%). These conditions were also good for ob- yields are disappointingly lower.
taining (E)-4¢-fluoro-3-styryl-4-quinolone (7d; 56%),
traces of 8d being obtained as a byproduct (Table 3).
When Pd(PPh3)4 was used as catalyst 7d was obtained in
Acknowledgment
Thanks are due to the University of Aveiro, FCT and FEDER for
funding the Organic Chemistry Research Unit and the Project
POCI/QUI/58835/2004. Andreia I. S. Almeida also thanks the FCT
for her PhD Grant (SFRH/BD/40632/2007).
a slight lower yield (50%). On the other hand, compound
7e was obtained in good yield (65%) when using
Pd(PPh3)4 as catalyst, but only in 20% yield when PdCl2
was used. The synthesis of 7b–e were also carried out un-
der microwave irradiation, although the reaction time is
significantly lower (1.5 h instead of 5 h), the expected References and Notes
compounds 7b–e were obtained in lower yields (30–48%,
Table 3).
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All the new synthesized compounds have been character-
ized by NMR spectroscopy. The main features in the 1H
NMR spectra that allows the differentiation of 4 from 5
and of 7a from 8a are the signals due to the vinylic protons
resonances: In compounds 4 and 7a they appear as dou-
blets with a large coupling constant (J = ca. 16 Hz;
d
Ha = 7.27 ppm and dHb = 7.91 ppm for 4 and dHa = 7.19
ppm and dHb = 7.65 ppm for 7a), indicative of a trans con-
figuration; while in the case of 5 and 8a they also appear
as doublets but with small coupling constants (J = ca. 1.7
Hz; dH2¢ = 5.57 and 5.71 ppm for 5 and dH2¢ = 5.64 and
5.78 ppm for 8a) indicative of a geminal coupling. It is im-
portant to notice the high frequency values of the H-2 res-
onance, which appears as singlet at dH = 7.6–8.2 ppm, due
to deshielding effects of the heterocyclic nitrogen atom
(inductive effect) and of the carbonyl group (mesomeric
effect).
In conclusion, a new methodology for the synthesis of
(E)-N-methyl-3-styryl-4-quinolones has been established.
This synthetic route comprises four steps, the synthesis of
the unsubstituted 4-quinolone, followed by its 3-iodina-
tion and NH-methylation, and finally the Heck reaction of
the 3-iodo-N-methyl-4-quinolone thus obtained with sty-
rene derivatives. This Heck procedure is only efficient
when the 3-iodo-4-quinolone has an N-protecting group.
The presence of regioisomeric 3-(1-phenylethenyl)-4-
quinolones as byproducts was observed in some cases, de-
pending on the experimental conditions. The beneficial
Synlett 2010, No. 3, 462–466 © Thieme Stuttgart · New York

LETTER
Synthesis of Novel (E)-3-Styryl-4-quinolones
465
(6) Gatto, B.; Tabarrini, O.; Massari, S.; Giaretta, G.; Sabatini,
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was poured into a sat. Na2S2O3 solution (40 mL). The
organic layer was extracted with EtOAc (3 × 100 mL), dried
over anhyd Na2SO4 and the solvent evaporated to dryness.
The residue was recrystallized from CH2Cl2–light PE to give
3-iodoquinolin-4 (1H)-one (2, 454.6 mg, 81%), as a yellow
solid.
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S.-C. Bioorg. Med. Chem. 1998, 6, 1657.
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T. Synthesis 1987, 70.
(22) Optimized Experimental Procedure
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2125.
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H.-L. ChemMedChem 2008, 3, 1077.
A mixture of 3-iodoquinolin-4 (1H)-one (2, 50 mg, 0.18
mmol), Ph3P (4.7 mg, 0.018 mmol), Et3N (25.1 mL, 0.18
mmol), tetrakis(triphenylphosphine)palladium(0) (10.4 mg,
0.009 mmol), and styrene 3a (103.4 mL, 0.9 mmol) in NMP
(3 mL) was stirred at 100 °C for 5 h, under a nitrogen
atmosphere. After this period, the reaction mixture was
poured into H2O (40 mL) and ice (30 g). The organic layer
was extracted with EtOAc (3 × 100 mL) and washed with
H2O (100 mL). After initial purification by TLC using a
(3:1) mixture of CH2Cl2–acetone, the solvent was evapor-
ated to dryness and the residue recrystallized from CH2Cl2–
light PE to give (E)-3-styrylquinolin-4 (1H)-one(4) as a
yellow solid (20.5 mg, 46%). Traces of product 5 were found
and 10% (5 mg) of the starting material was recovered.
(23) Physical Data of (E)-3-Styrylquinolin-4 (1H)-one (4)
Mp 269–270 °C. 1H NMR (300.13 MHz, CD3OD): d = 7.23
(m, 1 H, H-4¢), 7.27 (d, 1 H, J = 16.2 Hz, H-a), 7.38 (m, 3 H,
H-6, H-3¢,5¢), 7.63 (m, 4 H, H-7, H-8, H-2¢,6¢), 7.91 (d, 1 H,
J = 16.2 Hz, H-b), 8.24 (s, 1 H, H-2), 8.36 (dd, 1 H, J = 8.4,
0.9 Hz, H-5), 11.11 (s, 1 H, NH) ppm. 13C NMR (75.47
MHz, CD3OD): d = 118.6 (C-3), 118.9 (C-8), 124.2 (C-6),
124.7 (C-a), 126.8 (C-5, C-2¢,6¢), 126.7 (C-10), 127.5 (C-4¢),
128.2 (C-b), 129.4 (C-3¢,5¢), 132.2 (C-7), 138.8 (C-2), 139.8
(C-9), 139.8 (C-1¢) 176.6 (C-4) ppm. ESI+-MS: m/z (%) =
248 (100) [M + H]+. Anal. Calcd (%) for C17H13NO (247.3):
C, 82.57; H, 5.30; N, 5.66. Found: C, 82.47; H, 5.22; N, 5.62.
(24) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2.
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100, 3009. (b) Knowles, J. P.; Whiting, A. Org. Biomol.
Chem. 2007, 5, 31.
(16) Physical Data for Quinolin-4 (1H)-one (1)
Mp 196–197 °. 1H NMR (300.13 MHz, DMSO-d6): d = 6.35
(d, 1 H, J = 7.2 Hz, H-3), 7.43 (ddd, 1 H, J = 7.8, 7.7, 0.8 Hz,
H-6), 7.59 (d, 1 H, J = 8.1 Hz, H-8), 7.72 (ddd, 1 H, J = 8.1,
7.8, 1.3 Hz, H-7), 7.99 (d, 1 H, J = 7.2 Hz, H-2), 8.26 (d, 1
H, J = 7.7 Hz, H-5) ppm. 13C NMR (75.47 MHz, DMSO-d6):
d = 109.8 (C-3), 119.5 (C-8), 125.3 (C-6), 126.1 (C-5), 126.7
(C-10), 133.6 (C-7), 141.5 (C-2, C-9), 180.8 (C-4) ppm.
ESI+-MS: m/z (%) = 146 (100) [M + H]+. ESI+-HRMS: m/z
calcd for [C9H7NO + H]+: 146.0606; found: 146.0604.
(17) Optimized Experimental Procedure
Sodium (0.4 g, 8.70 mmol) was added to a solution of
2¢-aminoacetophenone (1 mL, 8.23 mmol) in an excess of
methyl formate (23 mL), and the reaction mixture was
stirred at 40 °C, under a nitrogen atmosphere. After 6 h,
MeOH (10 mL) was added to the reaction mixture to destroy
the remaining sodium and the mixture was poured into H2O
(60 mL) and ice (30 g). The organic layer was extracted with
EtOAc (4 × 100 mL), dried over anhyd Na2SO4, and the
solvent evaporated to dryness. The residue was taken in
acetone and purified by chromatography column using a
(3:2) mixture of acetone–CH2Cl2 as eluent. The solvent was
evaporated to dryness, and the residue was recrystallized
from CH2Cl2–light PE to give quinolin-4 (1H)-one (1) as a
yellowish solid (836.5 mg, 70%).
(26) Physical Data for 1-Methyl-3-iodoquinolin-4 (1H)-one
(6)
Mp 177–178 °C. 1H NMR (300.13 MHz, DMSO-d6): d =
3.00 (s, 3 H, NCH3), 7.47 (ddd, 1 H, J = 7.8, 6.8, 1.2 Hz, H-
6), 7.70 (d, 1 H, J = 9.0 Hz, H-8) 7.79 (ddd, 1 H, J = 9.0, 6.8,
1.6 Hz, H-7), 8.32 (dd, 1 H, J = 7.8, 1.6 Hz, H-5) ppm. 13
C
NMR (75.47 MHz, DMSO-d6): d = 40.8 (NCH3), 80.3 (C-3),
117.3 (C-8), 124.3 (C-10), 125.0 (C-6), 127.5 (C-5), 132.9
(C-7), 141.4 (C-9), 150.2 (C-2), 173.8 (C-4) ppm. ESI+-MS:
m/z (%) = 286 (100) [M + H]+, 308 (67) [M + Na]+. ESI+-
HRMS: m/z calcd for [C10H8INO + H]+: 285.9729; found:
285.9728.
(18) Physical Data for 3-Iodoquinolin-4 (1H)-one (2)
Mp 217–218 °C. 1H NMR (300.13 MHz, DMSO): d = 7.38
(ddd, 1 H, J = 8.2, 7.6, 1.1 Hz, H-6), 7.58 (d, 1 H, J = 8.1 Hz,
H-8), 7.69 (ddd, 1 H, J = 8.1, 7.6, 1.3 Hz, H-7), 8.10 (d, 1 H,
J = 8.2 Hz, H-5), 8.52 (s, 1 H, H-2), 12.24 (s, 1 H, NH) ppm.
13C NMR (74.47 MHz, DMSO): d = 80.7 (C-3), 118.5 (C-8),
122.5 (C-10), 124.1 (C-6), 125.5 (C-5), 131.9 (C-7), 139.6
(C-9), 144.8 (C-2), 173.0 (C-4) ppm. ESI+-MS: m/z (%) =
272 (100) [M + H]+, 294 (21) [M + Na]+. ESI+-HRMS: m/z
calcd for [C9H6INO + H]+: 271.9572; found: 271.9579.
(19) Mphahlele, M. J.; Nwamadi, M.; Mabeta, P. J. Heterocycl.
Chem. 2006, 43, 255.
(27) Optimized Experimental Procedure
A mixture of 3-iodoquinolin-4 (1H)-one (2, 200 mg, 0.74
mmol), PS-TBD (1.39 mmol/1 g, 1.33 g, 1.85 mmol) and
MeI (0.47 mL, 7.4 mmol) in fresh dry THF (40 mL) was
stirred at r.t. for 3 h. After this period, the reaction mixture
was poured into a mixture of H2O (100 mL) and Et3N (8 mL)
and neutralized with HCl (10%). The PS-TBD was filtered
off, and the organic layer was extracted with EtOAc (3 × 150
mL), dried over anhyd Na2SO4, and the solvent evaporated
to dryness. The product 1-methyl-3-iodoquinolin-4 (1H)-
one (6) was recrystallized from CH2Cl2–light PE and
obtained as a yellow solid (200.4 mg, 95%).
(20) Optimized Experimental Procedure
A mixture of quinolin-4 (1H)-one (1, 300 mg, 2.07 mmol),
Na2CO3 (329 mg, 3.11 mmol), and iodine (789 mg, 3.11
mmol) in dry THF (20 mL) was stirred at r.t. for 6 h, under a
nitrogen atmosphere. After this period, the reaction mixture
(28) Physical Data for 1-Methyl-3-(1-phenylvinyl)quinolin-4
(1H)-one (8a)
1H NMR (300.13 MHz, CDCl3): d = 3.81 (s, 3 H, NCH3),
Synlett 2010, No. 3, 462–466 © Thieme Stuttgart · New York

466
A. I. S. Almeida et al.
LETTER
5.65 (d, 1 H, J = 1.7 Hz, H-2¢), 5.78 (d, 1 H, J = 1.7 Hz, H-
2¢), 7.31 (m, 3 H, H-3¢¢,4¢¢,5¢¢), 7.44 (m, 4 H, H-6, H-8, H-
2¢¢,6¢¢), 7.55 (s, 1 H, H-2), 7.70 (ddd, 1 H, J = 7.8, 7.4, 1.6
Hz, H-7), 8.52 (dd, 1 H, J = 8.3, 1.6 Hz, H-5) ppm. 13C NMR
(75.47 MHz, CDCl3): d = 40.7 (NCH3), 115.1 (C-8), 116.6
(C-2¢), 122.4 (C-3), 123.8 (C-6), 127.1 (C-10), 127.2 (C-
2¢¢,6¢¢), 127.5 (C-4¢¢), 127.7 (C-5), 128.3 (C-3¢¢,5¢¢), 132.0
(C-7), 140.0 (C-9), 141.3 (C-1¢¢), 143.5 (C-2), 143.8 (C-1¢),
176.2 (C-4) ppm. ESI+-HRMS: m/z calcd for [C18H15NO +
H]+: 262.1232; found: 262.1226.
(30) Physical Data for (E)-3-(4-Methoxystyryl)-1-
methylquinolin-4 (1H)-one (7b)
Mp 134.7–135.0 °C. 1H NMR (300.13 MHz, CDCl3): d =
3.82 (s, 3 H, OCH3), 3.83 (s, 3 H, NCH3), 6.87 (d, 2 H,
J = 8.7 Hz, H-2¢,6¢), 7,01 (d, 1 H, J = 16.3 Hz, H-a), 7.38 (m,
2 H, H-6, H-8), 7,44 (d, 2 H, J = 8.7 Hz, H-3¢,5¢), 7.56 (d, 1
H, J = 16.3 Hz, H-b), 7.65 (ddd, 1 H, J = 7.8, 7.4, 1.4 Hz, H-
7), 7.69 (s, 1 H, H-2), 8.52 (d, 1 H, J = 7.5 Hz, H-5) ppm. 13
C
NMR (75.47 MHz, CDCl3): d = 40.9 (OCH3), 55.3 (NCH3),
114.0 (C-3¢,5¢), 115.2 (C-8), 118.8 (C-3), 120.4 (C-a), 123.8
(C-6), 126.5 (C-10), 127.2 (C-5), 127.5 (C-2¢,6¢), 127.8 (C-
b), 131.0 (C-1¢), 131.7 (C-7), 139.2 (C-9), 141.6 (C-2), 158.9
(C-4¢), 176.1 (C-4) ppm. ESI+-MS: m/z (%) = 292 (100) [M
+ H]+, 314 (10) [M + Na]+. ESI+-HRMS: m/z calcd for
[C19H17NO2 + H]+: 292.1338; found: 292.1335.
(29) (a) Loupy, A. Microwaves in Organic Synthesis; Wiley-
VCH: Weinheim, 2002. (b) Kappe, C. O. Angew. Chem. Int.
Ed. 2004, 43, 6250. (c) Arvela, R. K.; Leadbeater, N. E.
J. Org. Chem. 2005, 70, 1786. (d) Kappe, C. O.; Dallinger,
D. Nat. Rev. Drug Discovery 2006, 5, 51.
Synlett 2010, No. 3, 462–466 © Thieme Stuttgart · New York

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