New synthesis of 2,3-diarylacridin-9(10 H)-ones and (E)-2-phenyl-4- styrylfuro[3,2-c]quinolines

Article abstract of DOI:10.1055/s-0030-1258579

A new synthesis of 2,3-diarylacridin-9(10H)-ones and (E)-2-phenyl-4- styrylfuro[3,2-c]quinolines is described. This was accomplished by the Heck reaction of (E)-3-iodo-2-styrylquinolin-4(1H)-ones with styrene, leading to (E,E)-2,3-distyrylquinolin-4(1H)-ones, which when heated at high temperatures, cyclise in two different ways. Electrocyclisation and further in situ oxidation leads to 2,3-diarylacridin-9(10H)-ones and tautomerisation, cyclisation by nucleophilic addition and further in situ oxidation produces (E)-2-phenyl-4-styrylfuro[3,2-c]quinolines. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1258579

LETTER
2565
New Synthesis of 2,3-Diarylacridin-9(10H)-ones and (E)-2-Phenyl-4-
styrylfuro[3,2-c]quinolines
S
ynthesis of 2,3-D
e
iarylacridin
r
-9(10
H
)
a
-ones L. M. Silva, 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 2 August 2010
Several methods for the synthesis of linear furo[2,3-
b]quinolines38 have been reported but, in contrast, synthe-
sis of the isomeric angular furo[3,2-c]quinolines has re-
ceived much less attention.38b,39 Among the methods
Abstract: A new synthesis of 2,3-diarylacridin-9(10H)-ones and
(E)-2-phenyl-4-styrylfuro[3,2-c]quinolines is described. This was
accomplished by the Heck reaction of (E)-3-iodo-2-styrylquinolin-
4(1H)-ones with styrene, leading to (E,E)-2,3-distyrylquinolin-
4(1H)-ones, which when heated at high temperatures, cyclise in two reported for the synthesis of furoquinoline derivatives, a
different ways. Electrocyclisation and further in situ oxidation leads
to 2,3-diarylacridin-9(10H)-ones and tautomerisation, cyclisation
by nucleophilic addition and further in situ oxidation produces (E)-
sition. This is then transformed to the furan ring depend-
2-phenyl-4-styrylfuro[3,2-c]quinolines.
common strategy involves the construction of a quinoline
ring possessing an appropriate carbon chain at the C-3 po-
ing on the presence of an oxygen substituent at the C-2 or
C-4 positions to give linear or angular furoquinolines, re-
spectively. A major drawback of this protocol is that, once
the quinoline ring has been constructed, it is difficult to in-
corporate a carbon chain at C-3 through electrophilic aro-
matic substitution.38
Key words: (E)-2-styrylquinolin-4(1H)-ones, (E)-3-iodo-2-styryl-
quinolin-4(1H)-ones, (E,E)-2,3-distyrylquinolin-4(1H)-ones, 2,3-diaryl-
acridin-9(10H)-ones,
(E)-2-phenyl-4-styrylfuro[3,2-c]quinolines,
Heck reaction, electrocyclisation
In the present communication we report a new synthetic
route to novel 2,3-diarylacridin-9(10H)-ones and (E)-2-
phenyl-4-styrylfuro[3,2-c]quinolines. The approach in-
volves a Heck cross-coupling reaction of (E)-3-iodo-2-
styrylquinolin-4(1H)-ones with styrene leading to the for-
mation of (E,E)-2,3-distyrylquinolin-4(1H)-ones which
are then converted to 2,3-diarylacridin-9(10H)-ones and
furo[3,2-c]quinolines (Schemes 1 and 2).
Acridin-9(10H)-ones and furoquinolines are heterocyclic
compounds widely distributed in plants of the Rutaceae
family.1 Potential applications have been found for some
of them such as being antineoplastic agents2 and antima-
larial drugs.3 Acridin-9(10H)-ones have also presented
other pharmacological properties, such as anticancer,4–6
antimicrobial, antiviral, mutagenic, and cytotoxic activi-
ties.7–17 Certain acridin-9(10H)-one derivatives have been
used as fluorescence probes and as analytical tools in bio-
mimetic chemistry.18–26 The quinoline nucleus is found in
many pharmacologically active antibacterial, anti-inflam-
matory, antiasthmatic, and antihypertensive agents and
also in tyrosine kinase inhibitors.27–30 Additionally, other
quinoline derivatives, including furoquinolines and 2-
styrylquinolines, have shown in vitro activity against cu-
taneous and visceral leishmaniasis, African trypanosomi-
asis, and Chagas disease.30
The Heck reaction has become one of the most useful cat-
alytic carbon–carbon bond-forming processes in organic
synthesis in which an unsaturated halide (or triflate) reacts
with olefins at high temperatures in the presence of a base
and a catalytic amount of Pd(0) to form substituted ole-
fins.40 This reaction seems to be a good strategy to intro-
duce a carbon chain at the C-3 position of the (E)-2-
styrylquinolin-4(1H)-ones. We chose iodine as the halide
substituent of the starting quinolones [(E)-3-iodo-2-
styrylquinolin-4(1H)-ones 2] since iodo derivatives are
the most reactive substrates in the Heck reaction.
Acridin-9(10H)-ones are commonly prepared by the acid-
induced ring closure of N-phenyl anthranilic acids, them-
selves usually obtained from the Ullmann condensation of
anilines with ortho-halogen-substituted benzoic or naph-
thoic acids2,3b,c,5,10,14,31–34 or by the condensation of 3-
amino-2-naphthalenecarboxylic acid with phloro-
glucinol.15a,24,33,35 Other methods involve the intermolecu-
lar nucleophilic coupling of arynes with ortho-
aminobenzoates and subsequent intramolecular nucleo-
philic cyclisation,36 and the anionic N-Fries rearrange-
ment of N-carbamoyl diarylamines to anthranilamides
followed by cyclisation with triflic anhydride.37
Attempts to perform 3-iodination of 1a using iodine in the
presence of triethylamine as base and dichloromethane as
solvent led to the formation of 2a in low yield (40%).
However, (E)-3-iodo-2-styrylquinolin-4(1H)-ones 2a–c
were obtained in high yields (82–95%)41,42 by a recently
reported method for the iodination of quinolin-4(1H)-
ones,43 involving the treatment of 1a–c with iodine in the
presence of sodium carbonate in dry THF at room temper-
ature (Scheme 1). With these substrates in hand, an exten-
sive investigation into the optimal conditions (different
temperatures, catalysts, ligands, solvents, bases, and reac-
tion time) for the Heck reaction of (E)-3-iodo-2-
styrylquinolin-4(1H)-one 2a with styrene (3) was carried
out (Table 1). Based on these results we observed that ex-
SYNLETT 2010, No. 17, pp 2565–2570
x
x
.x
x
.2
0
1
0
Advanced online publication: 23.09.2010
DOI: 10.1055/s-0030-1258579; Art ID: D20910ST
© Georg Thieme Verlag Stuttgart · New York

2566
V. L. M. Silva et al.
LETTER
5'
2'
R1
R1
R1
6'
3'
β
H
N
H
N
H
N
8
5
2
3
9
α
(i)
(ii)
7
6
4
α'
10
I
2"
5"
O
1
O
2
O
β'
3"
4"
3
4
6"
a R = H
b R = OMe
c R = Cl
Scheme 1 Reagents and conditions: (i) I2, Na2CO3, dry THF, r.t., N2; (ii) Heck reaction conditions: Pd catalyst, ligand, base, solvent, N2 (see
Table 1).
tensive degradation occurs when the reaction is performed robenzene, to give 2,3-diarylacridin-9(10H)-ones 5a–c
at 160 °C (not shown), tetrakistriphenylphosphine palladi- (Scheme 2). Under these conditions acridin-9(10H)-ones
um(0) is the best catalyst, and the use of other catalyst 5a–c46,47 were obtained in low yields (16–37%) together
such as Pd(OAc)2 and PdCl2 proved to be unsuccessful with (E)-2-phenyl-4-styrylfuro[3,2-c]quinolines 7a–c48 as
(entries 1–5, Table 1). We also found 5 mol% to be the op- the main product (35–66%). The formation of these fu-
timal amount of catalyst (entries 1 and 2, Table 1). Phos- ro[3,2-c]quinolines can be envisaged by a tautomerisation
phines such as Ph3P or P(o-tolyl)3 are commonly used as of structures 4a–c to 6a–c which, after a nucleophilic at-
ligands in the Heck reaction but we showed that the reac- tack of the hydroxyl oxygen atom to the b-position of the
tion could also be performed in the absence of ligand 3-styryl group and further in situ oxidation, leads to 7a–c.
when using tetrakistriphenylphosphine palladium(0) as
We tried to modify the optimised experimental conditions
catalyst, the expected product being obtained in better
in order to evaluate their effect on the regioselectivity of
yield (entry 13, Table 1). This was a great improvement in
the reaction. Using chloranil to promote the in situ oxida-
the synthesis of 4a since the presence of phosphines often
tion of the formed intermediates the yield of 5a–c and 7a–
c did not improve, and using DDQ as oxidant in refluxing
decalin as solvent led to degradation of starting material.
hamper the isolation and the purification of the product,
and, obviously, the ligand-free synthesis becomes less ex-
pensive. Among the solvents currently used in Heck reac-
Likewise, the use of nitrobenzene as solvent and oxidant
tions (e.g., DMF, NMP, and acetonitrile), acetonitrile
did not improve the yield of the obtained compounds.
proved to be the most appropriate one since the isolation
In order to improve the yield of acridin-9(10H)-ones 5a–
and purification of (E,E)-2,3-distyrylquinolin-4(1H)-one
c we carried out the electrocyclisation of 4a in refluxing
4a was easier and the obtained yield was better (entries 7–
1,2,4-trichlorobenzene in the presence of iodine (10% mol
12, Table 1). Triethylamine proved to be the most suitable
equiv) and p-toluenesulfonic acid (1 mol equiv). Iodine
may play a role in the isomerization of double bonds of 4a
base, and the reaction can be performed in NMP or aceto-
nitrile at 100 °C or reflux, respectively, leading to the for-
with subsequent cyclisation into 5a.49 The acid medium
was used to displace the tautomerism depicted in
Scheme 2 to the quinolone structure 4a which can under-
go electrocyclisation and in situ oxidation to give 5a. Un-
der these conditions, 38% of the desired acridin-9(10H)-
one 5a and 41% of (E)-2-phenyl-4-styrylfuro[3,2-c]quin-
oline 6a were obtained; meaning that we were not able
completely to circumvent the tautomerisation reaction re-
ferred to above.
mation of (E,E)-2,3-distyrylquinolin-4(1H)-one 4a44,45 in
moderate to good yields (53–62%). When we extended
the established conditions to the Heck reaction of (E)-3-
iodo-2-styrylquinolin-4(1H)-ones derivatives 2b,c with
styrene (3) similar results were obtained (entries 16–20,
Table 1).
The next step in our strategy was the electrocyclisation of
(E,E)-2,3-distyrylquinolin-4(1H)-ones 4a–c followed by
in situ oxidation of the adduct, in refluxing 1,2,4-trichlo-
5"
R1
R1
6"
3"
b
R1
3"
2"
2"
H
6
N
4
5
a
N
7
N
3
2
4
5"
(i)
7
6
(i)
4
8
3
9
9
5'
4'
8
1
O
OH
2
O
6'
2'
3'
5'
2'
5
6
7
3'
4'
Scheme 2 Reagents and conditions: (i) 1,2,4-trichlorobenzene (TCB), reflux, N2 or TCB, I2 (10%), PTSA (1 mol equiv), reflux, N2.
Synlett 2010, No. 17, 2565–2570 © Thieme Stuttgart · New York

LETTER
Synthesis of 2,3-Diarylacridin-9(10H)-ones
2567
Table 1 Reaction Conditionsa and Yields in the Heck Reaction of (E)-3-Iodo-2-styrylquinolin-4(1H)-ones 2a–c with Styrene (3)
Entry
Compd
2a
Catalyst (equiv)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.08)
Pd(OAc)2 (0.05)
Pd(OAc)2 (0.05)
Base/solvent
Et3N/NMP
Et3N/NMP
Et3N/NMP
Et3N/NMP
Temp (°C)
100
Time (h)
Yield 4 (%)
1
2
3
4
6
6
8
53
15
–
2a
100
2a
100
2a
r.t.
160
24
2
–
–
5
6
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2c
2c
2c
PdCl2 (0.05)
Et3N/NMP
Et3N/DMF
Et3N/MeCN
Et3N/NMP
Et3N/NMP
Et3N/DMF
Et3N/NMP
Et3N/MeCN
Et3N/MeCN
K2CO3/NMP
NaOAc/NMP
Et3N/NMP
Et3N/MeCN
Et3N/NMP
Et3N/MeCN
Et3N/MeCN
100
6
6
6
3
6
3
3
5
4
6
4
3
4
6
4
4
–
9
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(OAc)2 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
Pd(PPh3)4 (0.05)
100
7
reflux
130
31
14
40
41
13
60
62
28
–
8
9
100
10
11
12
13
14
15
16
17
18
19
20
130
130
reflux
reflux
100
130
100
67
65
60
45
58
reflux
100
reflux
reflux
a Reaction conditions: 0.1 equiv of the ligand Ph3P was used in entries 1–8 and 14–17, P(o-tolyl)3 in entries 9–12 and 18 and no ligand in entries
13, 17, and 20.
Based on this last result, a stronger acid was used with the The electrocyclization of derivatives 4b,c under the opti-
intention of shifting the equilibrium completely to the for- mized conditions of refluxing 1,2,4-trichlorobenzene in
mation of the oxo form 4 and consequently avoid the for- the presence of iodine (10% mol equiv) and p-toluene-
mation of 6. However, using trifluoroacetic acid (1 + 0.5 sulfonic acid (1 mol equiv), led to a significant increase in
mol equiv) instead of p-toluenesulfonic acid (1 mol equiv) the yield for compounds 5b,c (Table 2).
we obtained, after seven hours of reaction, 39% of 7a,
26% of 5a and degradation products.
Table 2 Reaction Conditions and Yields in the Synthesis of 2,3-Diarylacridin-9(10H)-ones 5a–c and (E)-2-Phenyl-4-styrylfuro[3,2-c]quin-
olines 7a–c
Conditions
TCBa reflux
TCB reflux
TCB reflux
Compound
R
Time (h)
Yield of 5 (%)
Yield of 7 (%)
a
b
c
H
24
24
24
22
37
16
66
35
51
OMe
Cl
TCB reflux, I2 (10%), PTSA (1 equiv)
TCB reflux, I2 (10%), PTSA (1 equiv)
TCB reflux, I2 (10%), PTSA (1 equiv)
a
b
c
H
OMe
Cl
7
4.5
5
38
35
40
41
44
56
a TCB = 1,2,4-Trichlorobenzene; PTSA = p-toluenesulfonic acid.
Synlett 2010, No. 17, 2565–2570 © Thieme Stuttgart · New York

2568
V. L. M. Silva et al.
LETTER
All the synthesised compounds have been characterized
by NMR, MS, and elemental analysis. The most notice-
able features in the 1H spectra of (E)-3-iodo-2-styrylquin-
olin-4(1H)-ones 2a–c are the absence of the singlet
corresponding to the resonance of H-3 which confirms the
substitution at this position and the singlet due to the res-
onance of the NH proton at dH = 11.88–11.99 ppm for 2a–
c. The coupling constants 3JHa–Hb = ca. 16 Hz indicates a
trans configuration for the vinylic system. The resonances
assigned to H-b/C-b (d, dH = 7.50–7.55 ppm/dC = 135.8–
137.1 ppm) appear at high frequency values than those of
H-a/C-a (d, dH = 7.28–7.43 ppm/dC = 123.9–127.2 ppm)
due to the mesomeric deshielding effect of the carbonyl
group. The assignment of proton resonances in the spectra
of (E,E)-2,3-distyrylquinolin-4(1H)-ones 4a–c is not easy
because almost all the signals appear in the aromatic re-
gion of the spectrum due to the symmetry of the mole-
cules, except the resonance of H-5 which appears as a
double doublet or in some cases as a doublet at higher fre-
quencies (dH = 8.16–8.17 ppm) due to the anisotropic and
mesomeric deshielding effect of the carbonyl group.
Based on the connectivities found in the HMBC and
HSQC spectra of 4a–c it was possible to assign the reso-
nances of H-a, H-b, H-a¢ and H-b¢. The coupling con-
stants of these two vinylic systems (J = ca. 16 Hz) indicate
their trans configurations.
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. Vera L. M. Silva also thanks the FCT for a
Post-Doctoral grant (SFRH/BPD/27098/2006).
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In conclusion we have established a new methodology for
the synthesis of new 2,3-diarylacridin-9(10H)-ones 5a–c
and (E)-2-phenyl-4-styrylfuro[3,2-c]quinolines 7a–c.
This is a straightforward methodology which involves
only three steps; the C-3 iodination of (E)-2-styrylquino-
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Synlett 2010, No. 17, 2565–2570 © Thieme Stuttgart · New York

LETTER
Synthesis of 2,3-Diarylacridin-9(10H)-ones
2569
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(41) Optimized Experimental Procedure for the Synthesis of
(E)-3-Iodo-2-styrylquinolin-4(1H)-ones 2a–c
Na2CO3 (0.064 g, 0.61 mmol) and I2 (0.15 g, 0.61 mmol)
were added to a solution of the appropriate (E)-2-styryl-
quinolin-4(1H)-one 1a–c (0.40 mmol) in anhyd THF (25
mL). The mixture was stirred, protected from the daylight (to
avoid the E/Z isomerisation), at r.t. until complete
consumption of the starting material (4–5 h) and then poured
into an aq sat. solution of Na2S2O3. The solid obtained was
filtered, washed with H2O and crystallised from EtOH. (E)-
3-Iodo-2-styrylquinolin-4(1H)-ones 2a–c were obtained as
yellow solids (2a, 211.7 mg, 93%; 2b, 201.7 mg, 82%; 2c,
236.2 mg, 95%).
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(42) Analytical Data for (E)-3-Iodo-2-styrylquinolin-4(1H)-
one (2a)
Mp 194–197 °C. 1H NMR (300.13 MHz, DMSO-d6):
d = 7.39 (ddd, 1 H, J = 8.0, 6.8, 1.2 Hz, H-6), 7.43 (d, 1 H,
J = 16.4 Hz, H-a), 7.45–7.57 (m, 3 H, H-3¢,4¢,5¢), 7.55 (d, 1
H, J = 16.4 Hz, H-b), 7.70–7.76 (m, 3 H, H-7, H-2¢,6¢), 7.80
(d, 1 H, J = 8.4 Hz, H-8), 8.11 (dd, 1 H, J = 8.0, 1.2 Hz, H-
5), 11.97 (s, 1 H, NH) ppm. 13C NMR (75.47 MHz, DMSO-
d6): d = 87.5 (C-3), 118.3 (C-8), 120.8 (C-10), 124.0 (C-6),
125.5 (C-5), 126.4 (C-a), 127.4 (C-2¢,6¢), 129.2 (C-3¢,5¢),
129.7 (C-4¢), 132.3 (C-7), 135.0 (C-1¢), 137.1 (C-b), 139.4
(C-9), 147.6 (C-2), 173.4 (C-4) ppm. MS (ESI+): m/z (%) =
374 (100) [M + H]+, 396 (12) [M + Na]+, 769 (3) [2 M +
Na]+. Anal. Calcd (%) for C17H12INO (373.19): C, 54.71; H,
3.24; N, 3.75. Found: C, 55.10; H, 3.17; N, 3.77.
(43) (a) Plisson, C.; Chenault, J. Heterocycles 1999, 51, 2627.
(b) Mphalele, M. J.; Nwamadi, M. S.; Mabeta, P. J.
Heterocycl. Chem. 2006, 43, 255. (c) Almeida, A. I. S.;
Silva, A. M. S.; Cavaleiro, J. A. S. Synlett 2010, 462.
(44) Optimized Experimental Procedure for the Heck
Reaction of (E)-3-Iodo-2-styrylquinolin-4(1H)-one 2a–c
with Styrene: Synthesis of (E,E)-2,3-distyrylquinolin-
4(1H)-ones 4a–c
Styrene (138.8 mL, 1.6 mmol) was added to a mixture of the
appropriate (E)-3-iodo-2-styrylquinolin-4(1H)-one 2a–c
(0.24 mmol), tetrakis(triphenylphosphine)palladium(0)
(13.94 mg, 1.2 × 10–2 mmol), and Et3N (33.4 ml, 0.24 mmol)
in MeCN (6 mL). The mixture was heated at reflux until
consumption of the starting material, which was confirmed
by TLC (Table 1). The mixture was then poured into H2O,
extracted with CHCl3, and dried over anhyd Na2SO4. The
solvent was evaporated and the residue dissolved in CH2Cl2
and purified by TLC using a mixture of EtOAc–light PE
(3:2) as eluent. The (E,E)-2,3-distyrylquinolin-4(1H)-ones
4a–c were obtained as yellow solids in good yields (4a, 52.2
mg, 62%; 4b, 55.0 mg, 65%; 4c, 49.3 mg, 58%).
(45) Analytical Data of (E,E)-2,3-Distyrylquinolin-4(1H)-one
(4a)
Mp 207–208 °C. 1H NMR (500.13 MHz, DMSO-d6):
d = 7.24 (t, 1 H, J = 7.6 Hz, H-4¢¢), 7.32–7.39 (m, 5 H, H-6,
H-8, H-2¢,6¢, H-a¢), 7.41 (t, 1 H, J = 7.5 Hz, H-4¢), 7.48 (t, 2
H, J = 7.5 Hz, H-3¢,5¢), 7.52 (d, 1 H, J = 16.4 Hz, H-b), 7.56
(d, 2 H, J = 7.6 Hz, H-2¢¢,6¢¢), 7.67 (dt, 1 H, J = 8.0, 1.2 Hz,
H-7), 7.70 (d, 1 H, J = 16.4 Hz, H-a), 7.78 (t, 2 H, J = 7.6
(36) (a) Rudas, M.; Nyerges, M.; Toke, L.; Pete, B.;
Groundwater, P. W. Tetrahedron Lett. 1999, 40, 7003.
(b) Zhao, J.; Larock, R. C. J. Org. Chem. 2007, 72, 583.
Synlett 2010, No. 17, 2565–2570 © Thieme Stuttgart · New York

2570
V. L. M. Silva et al.
LETTER
d = 7.15–7.17 (m, 2 H, H-2¢,6¢), 7.21–7.32 (m, 9 H, H-
Hz, H-3¢¢,5¢¢), 7.85 (d, 1 H, J = 16.0 Hz, H-b¢), 8.17 (dd, 1 H,
J = 8.1, 1.2 Hz, H-5), 11.69 (br s, NH) ppm. 13C NMR
(125.77 MHz, DMSO-d6): d = 115.4 (C-3), 118.6 (C-8),
121.3 (C-a), 122.4 (C-10), 123.1 (C-a¢), 124.4 (C-6), 125.2
(C-5), 126.1 (C-2¢¢,6¢¢), 127.0 (C-4¢¢), 127.5 (C-3¢¢,5¢¢), 128.7
(C-3¢,5¢), 129.0 (C-2¢,6¢), 129.2 (C-4¢), 131.0 (C-b¢), 131.6
(C-7), 135.7 (C-b,1¢), 136.4 (C-1¢¢), 138.6 (C-9), 145.5 (C-
2), 175.9 (C-4). MS (ESI+): m/z (%) = 350 (100) [M + H]+.
HRMS (ESI+): m/z calcd for [C25H20NO + H]+: 350.15394;
found: 350.15345.
3¢,4¢,5¢, H-2¢¢,3¢¢,4¢¢,5¢¢,6¢¢, H-7), 7.55 (s, 1 H, H-4), 7.58 (d,
1 H, J = 8.0 Hz, H-5), 7.77 (ddd, 1 H, J = 8.0, 7.0, 1.1 Hz, H-
6), 8.20 (s, 1 H, H-1), 8.26 (dd, 1 H, J = 8.0, 1.1 Hz, H-8),
11.92 (s, 1 H, NH) ppm. 13C NMR (125.77 MHz, DMSO-
d6): d = 117.5 (C-5), 118.9 (C-4), 119.6 (C-9a), 120.7 (C-7),
121.3 (C-8a), 126.1 (C-4¢), 126.6 (C-8), 127.5 (C-4¢¢), 127.6
(C-1), 128.1 (C-3¢¢,5¢¢), 128.2 (C-3¢,5¢), 129.3 (C-2¢,6¢),
129.6 (C-2¢¢,6¢¢), 133.5 (C-2), 133.6 (C-6), 140.1 and 140.2
(C-1¢ and C-1¢¢), 140.4 (C-4a), 141.0 (C-4b), 145.4 (C-3),
176.5 (C-9). HRMS (ESI+): m/z calcd for [C25H18NO + H]+:
348.1383; found: 348.1384.
(46) Optimized Experimental Procedure for the Synthesis of
2,3-Diarylacridin-9(10H)-ones 5a–c and (E)-2-phenyl-4-
styrylfuro[3,2-c]quinolines 7a–c
(48) Analytical Data of (E)-2-Phenyl-4-styrylfuro[3,2-
c]quinoline (7a)
Iodine (1.82 mg, 7.15 × 10–3 mmol) and PTSA (1.36 mg,
7.15 × 10–2 mmol) were added to a solution of the
Mp 154–156 °C. 1H NMR (300.13 MHz, DMSO-d6):
d = 7.41 (t, 1 H, J = 7.0 Hz, H-4¢¢), 7.48–7.55 (m, 1 H, H-4¢),
7.53 (t, 1 H, J = 7.0 Hz, H-3¢¢,5¢¢), 7.61 (t, 2 H, J = 7.6 Hz,
H-3¢,5¢), 7.70 (dd, 1 H, J = 7.7, 7.4 Hz, H-8), 7.78 (ddd, 1 H,
J = 8.0, 7.7, 1.3 Hz, H-7), 7.89 (d, 1 H, J = 17.4 Hz, H-a),
7.91 (d, 2 H, J = 7.0 Hz, H-2¢¢,6¢¢), 8.08 (d, 1 H, J = 17.4 Hz,
H-b), 8.11 (d, 2 H, J = 7.6 Hz, H-2¢,6¢), 8.15 (d, 1 H, J = 8.0
Hz, H-6), 8.25 (s, 1 H, H-3), 8.39 (dd, 1 H, J = 7.4, 1.3 Hz,
H-9) ppm. 13C NMR (125.77 MHz, DMSO-d6): d = 101.6
(C-3), 115.7 (C-9a), 119.8 (C-9), 120.9 (C-3a), 124.7 (C-
2¢,6¢), 125.4 (C-a), 126.8 (C-8), 127.6 (C-2¢¢,6¢¢), 128.9,
129.06 and 129.12 (C-3¢¢,4¢¢,5¢¢, C-1¢, C-4¢, C-7), 129.26 (C-
3¢,5¢), 129.32 (C-6), 135.2 (C-b), 136.2 (C-1¢¢), 145.0 (C-5a),
150.0 (C-4), 154.9 (C-2), 155.7 (C-9b) ppm. HRMS (ESI+):
m/z calcd for [C25H18NO + H]+: 348.1383; found: 348.1378.
(49) (a) Wyman, G. M. Chem. Rev. 1955, 55, 625.
(b) Yamashita, S. Bull. Chem. Soc. Jpn. 1961, 34, 487.
appropriate (E,E)-2,3-distyrylquinolin-4(1H)-one 4a–c
(7.15 × 10–2 mmol) in 1,2,4-trichlorobenzene (3 mL), and
the mixture was refluxed (see Table 2 for reaction time).
After cooling the reaction mixture was purified by column
chromatography using light PE as eluent to remove the
1,2,4-trichlorobenzene. Then, the mixture was removed
from the column using CH2Cl2 as eluent and was purified by
TLC using a mixture of EtOAc–light PE (3:2) as eluent. Two
main compounds were isolated in each case: That with the
lower Rf value corresponded to the 2,3-diarylacridin-
9(10H)-ones 5a–c which were isolated as yellow
compounds in moderate yields (5a, 9.4 mg, 38%; 5b, 8.7 mg,
35%; 5c, 9.9 mg, 40%); and that with higher Rf value
corresponded to (E)-2-phenyl-4-styrylfuro[3,2-c]quinolines
7a–c obtained as yellow compounds also in moderate yields
(7a, 10.2 mg, 41%; 7b, 10.9 mg, 44%; 7c, 13.9 mg, 56%).
(47) Analytical Data of 2,3-Diphenylacridin-9(10H)-one (5a)
Mp 283–284 °C. 1H NMR (300.13 MHz, DMSO-d6):
Synlett 2010, No. 17, 2565–2570 © Thieme Stuttgart · New York

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