Synthesis of thieno[2,3- c] acridine and furo[2,3- c] acridine derivatives via an iodocyclization reaction and their fluorescence properties and DFT mechanistic studies

Article abstract of DOI:10.1039/c8nj03511c

In this paper, we report the novel synthesis of thieno[2,3-c]acridine and furo[2,3-c]acridine derivatives via an intramolecular iodocyclization reaction. The thieno[2,3-c]acridine derivatives exhibited blue fluorescence in hexane. DFT and time-dependent (TD) DFT studies were carried out. This methodology provided a novel pathway to access thieno[2,3-c]acridine and furo[2,3-c]acridine derivatives via a 6-endo iodocyclization reaction.

Full text of DOI:10.1039/c8nj03511c

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Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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ARTICLE
Synthesis of thieno[2,3-c]acridine and furo[2,3-c]acridine
derivatives via iodocyclization reaction, fluorescence properties
and DFT mechanistic study
Received 00th January 20xx,
Accepted 00th January 20xx
Amol D. Sonawane,a Dinesh R. Garud,b,† Taro Udagawa,a Yasuhiro Kubota,a and Mamoru
DOI: 10.1039/x0xx00000x
Koketsu*,a
www.rsc.org/
In this paper, we report the novel synthesis of thieno[2,3-c]acridine and furo[2,3-c]acridine derivatives via
intramolecular iodocyclization reaction. The thieno[2,3-c] acridine derivatives showed blue fluorescence in hexane. DFT
and time-dependent (TD) DFT studies were carried out. This methodology provided a novel pathway to access
thieno[2,3-c] acridine and furo[2,3-c] acridine derivatives via 6-endo iodocyclization reaction.
Introduction
diverse heterocycles, we disclose here an efficient method for
the synthesis of furo[2,3-c]acridine and thieno[2,3-c]acridine
derivatives via iodocyclization reaction of 3-alkynyl-2-(furan-3-
yl)quinolines and 3-ethynyl-2-(thiophen-3-yl)quinolines,
respectively. Further, we report their density functional theory
(DFT) mechanistic study and fluorescence properties.
Acridines,1
a
nitrogen-containing
heteroaromatic
molecules, are one of the privileged scaffolds possess wide
range of biological activities such as antimicrobial agents,2
antibacterial,3
antimalarial,4
anti-leishmanial
and
antitrypanosomal,5 antiviral,6 antiprion,7 anticancer agents,8
anti-AD,9 anti-inflammatory,10 and analgesic activities.11 In
addition, acridine derivatives have been applied for acute
lymphoblastic leukemia,12 and as a fluorescent indicator for
cell lysosomal dye.13 Recently, quinoline-based BODIPY
showing novel aggregation induced emission (AIE) luminogens
have been synthesized14a. The interesting biological activities
and chemical properties of acridines encouraged synthetic
chemists to develop novel synthetic strategies to access
structurally different acridines.14 However, to the best of our
knowledge, little is known in the literature about furo[2,3-
c]acridines and thieno[2,3-c]acridines.15 In recent years,
molecular iodine mediated iodocyclization reactions has
emerged as an efficient tool to activate a triple bond for
nucleophilic attack.16,17 Our group has shown the efficacy of
iodocyclization reaction to access nitrogen-,18 oxygen-,19
Results and discussion
The starting materials 2-(thiophen-3-yl)-3-carbaldehydes
1a-1d and 2-(furan-3-yl)quinoline-3-carbaldehydes 1e-1h
required for our approach were readily prepared from
corresponding 2-chloroquinoline-3-carbaldehydes with
a
known literature procedure (for detail see the ESI).22 Further,
the (2-(thiophen-3-yl))-3-carbaldehydes 1a-d and 2-(furan-3-
yl)quinoline-3-carbaldehydes 1e-1h were converted to
dibromo olefins by Corey–Fuchs reaction.23 Next, the dibromo
olefins in situ were converted to corresponding alkynes 2a-2h
in 75-87% yields (Table 1, entries 1-8) via dehydrohalogenation
reaction using DBU in DMSO at room temperature.
Furthermore, to study the effect of substitution at the alkyne
part, the synthesized bromoalkyne derivatives 2a-2h were
alkylated by boronic acid coupling reactions with Pd(II)-catalyst
and 2M Na2CO3 in DME to obtain corresponding various
substituted alkynes 3a-3w in 70-90% yields (Table 1, entries 9-
31). The synthesized compounds 1a-1h, 2a-2h and 3a-3w were
characterized by IR, HRMS, 1H NMR and 13C NMR spectral
analysis.
sulphur-,20
and
selenium-containing20a,21
heterocyclic
compounds. Recently, we have shown that the quinoline
fused-heterocycles such as thieno[2,3-b]quinoline and
selenopheno[2,3-b]quinoline can be easily synthesized via
iodocyclization reaction.20a Within an on-going project aimed
at the development of novel approaches to access structurally
Table 1. Synthesis of 3-(alkynyl)-2-(furan-3-yl)quinoline and 3-(alkynyl)-
[a]
Department of Chemistry and Biomolecular Science, Faculty of
Engineering, Gifu University, Gifu 501-1193 Japan; Email:
koketsu@gifu-u.ac.jp
2-(thiophene-3-yl)quinolines.a
[b]
Department of Chemistry, Sir Parashurambhau College, Tilak road,
Pune 411030 India.
†
Affiliated to Savitribai Phule Pune University, Pune 411007 India
(formerly University of Pune).
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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improve the yield of iodocyclization reactioVnie,w AdrtiicflfeeOrnelinnet
reaction conditions were then screened (DTOabI:l1e0.210, 3e9n/tCr8ieNsJ023-51161C).
As shown in Table 2, CH3CN was found to be a suitable solvent
for the iodocyclization and the best result was obtained when
6 equiv of iodine and 6 equiv of NaHCO3 were used in the
reaction (91% yield, entry 7).
Table 2. Optimization conditions for 5-iodo-8-methyl-4-phenylthieno[2,3-
c]acridine (4a).
2 or 3
Entry X
R1
R2
H-
CH3- H-
R3
R4
yield (%)b
1
S
S
S
S
O
O
O
O
S
S
S
S
O
O
O
O
S
S
S
S
O
O
O
O
S
S
S
O
O
O
O
CH3-
H-
H-
Br-
Br-
2a (87%)
2b (79%)
2c (75%)
2d (77%)
2e (75%)
2f (85%)
2g (83%)
2h (78%)
3a (81%)
3b (73%)
3c (75%)
3d (77%)
3e (74%)
3f (78%)
3g (77%)
3h (81%)
3i (72%)
3j (77%)
3k (74%)
3l (70%)
3m (74%)
3n (76%)
3o (70%)
3p (77%)
3q (74%)
3r (72%)
3s (78%)
3t (90%)
3u (83%)
3v (77%)
3w (74%)
2
3
H-
H-
H-
H-
CH3-
H-
Br-
(4a)a
Temp. % yield
E+
(equiv.)
Base
(equiv.)
Time
(h)
4
H-
Br-
Entry Solvent
5
CH3-
H-
H-
Br-
1
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
C2H4Cl2
CH3CN
CH3CN
CH2Cl2
CH3CN
CH3CN
CH2Cl2
CH3CN
CH3Ph
DMSO
DMSO
THF
I2 (2)
NIS (2)
I2 (2)
-
8
rt
rt
87b
58b
75b
46
6
CH3- H-
Br-
2
-
18
12
48
48
12
18
12
12
18
18
18
18
18
18
18
7
H-
H-
H-
H-
CH3-
H-
Br-
3
NaHCO3 (2)
CS2CO3 (6)
-
rt
8
H-
Br-
4
I2 (3)
rt
9
CH3-
H-
H-
Ph-
5
NIS (2)
I2 (6)
70b
60ºC
rt
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
CH3- H-
Ph-
6
NaHCO3 (6)
NaHCO3 (6)
-
89
H-
H-
H-
H-
CH3-
H-
Ph-
7
I2 (6)
rt
91
H-
Ph-
8
I2 (4)
rt
66b
87b
87
78b
NR
NR
Traces
NR
NR
CH3-
H-
H-
Ph-
9
I2 (4)
-
rt
CH3- H-
Ph-
10
11
12
13
14
15
16
I2 (6)
NaHCO3 (3)
NaHCO3 (3)
NaHCO3 (6)
NaHCO3 (6)
NaHCO3 (6)
NaHCO3 (6)
NaHCO3 (6)
rt
H-
H-
H-
H-
CH3-
H-
Ph-
I2 (6)
rt
H-
Ph-
NIS (6)
I2 (6)
rt
p-CH3OC6H4-
p-CH3OC6H4-
p-CH3OC6H4-
p-CH3OC6H4-
p-CH3OC6H4-
p-CH3OC6H4-
p-CH3OC6H4-
p-CH3OC6H4-
p-PhCH2OC6H4-
p-PhCH2OC6H4-
p-PhCH2OC6H4-
p-PhCH2OC6H4-
p-PhCH2OC6H4-
p-PhCH2OC6H4-
p-PhCH2OC6H4-
CH3-
H-
H-
rt
CH3- H-
I2 (6)
rt
H-
H-
H-
H-
CH3-
H-
H-
NIS (6)
I2 (6)
rt
rt
CH3-
H-
H-
CH3- H-
aIsolated Yields; bInseparable mixture of starting and product; NR: No reaction.
H-
H-
H-
H-
H-
H-
H-
CH3-
H-
H-
With the optimized conditions in hand, the scope and
generality of the iodocyclization reaction were further
CH3-
H-
H-
CH3-
H-
extended with other substrates
(Table 3). The alkyl
H-
substitution at the quinoline part and aryl substitution at the
alkynyl part were well tolerated under the present reaction
conditions and the corresponding 5-iodofuro[2,3-c]acridine
and 5-iodothieno[2,3-c]acridine derivatives 4a-4w were
obtained in good yield (table 3, entries 1-23). The 5-
iodothieno[2,3-c]acridine derivatives were obtained slightly in
CH3-
H-
H-
CH3- H-
H-
H-
H-
CH3-
H-
H-
higher yield compared to
5-iodofuro[2,3-c]acridine
aReaction conditions: (i) CBr4, PPh3, DCM, 0oC, 1 h (ii) DBU, DMSO, rt, 1 h (iii)
Phenylboronic acid, 2M Na2CO3, Pd(PPh3)2Cl2, DME, 90oC; bIsolated yields.
derivatives. In contrast, the iodocyclization reaction of
bromoalkynes 2e-2h under the optimized reaction conditions
resulted in the formation of diiodo compounds 5a-5d instead
of cyclized 5-iodothieno[2,3-c]acridine derivatives
4 (for detail
Our study began by examining the iodocyclization reaction
of alkyne 3a which was used as a model compound with 2.0
equiv of iodine in dichloromethane at room temperature
see the ESI). All the synthesized compounds 4a-4w was well
characterized by IR, HRMS, 1H and 13C NMR spectral analysis.
(
Table 2, entry 1). To our surprise, the reaction resulted in the
Table 3. Synthesis of 5-iodofuro[2,3-c]acridine and 5-iodothieno[2,3-
c]acridine derivatives 4 via iodocyclization.a
formation of desired 5-iodo-8-methyl-4-phenylthieno[2,3-
c]acridine 4a in 87% yield along with the unreacted starting
material as an inseparable mixture (Table 2, entry 1). To
2 | J. Name., 2012, 00, 1-3
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View Artioclfe Ontlhinee
Next, to demonstrate the synthetic potential
iodocyclization reaction, the presence of iodine on the 5-
DOI: 10.1039/C8NJ03511C
iodothieno[2,3-c]acridine product 4a allowed us further structural
elaboration, most notable by Suzuki coupling,25 the palladium
catalysed triethylammonium formate reduction of the iodide,26
Heck reaction,27 and alkyne annulation reaction28 to afford the
corresponding diversified quinoline moieties 6a–6d (Scheme 1) in
good to excellent yields.
4
Ga
(kcal/mol)
Entry
X
R1
R2
R3
H-
R4
(% yield)b
1
S
CH3- H-
Ph-
4a (91%)
4b (89%)
4c (84%)
4d (86%)
4e (87%)
4f (80%)
4g (85%)
4h (81%)
4i (89%)
4j (86%)
4k (78%)
4l (88%)
4m (81%)
4n (77%)
4o (73%)
4p (68%)
18.4
18.4
18.2
18.5
17.4
17.8
17.6
17.8
16.6
16.3
16.2
16.9
15.7
15.5
14.8
15.6
16.3
16.8
17.4
15.4
15.2
15.1
15.7
Scheme 1. Functionalization of the 3-iodo-6-methyl-2-phenylthieno[2,3–
b]quinoline 4a.
2
S
H-
H-
H-
CH3- H-
Ph-
3
S
H-
H-
CH3-
Ph-
4
S
H-
H-
Ph-
Ph-
5
O
O
O
O
S
CH3- H-
6
H-
H-
H-
CH3- H-
Ph-
7
H-
H-
CH3-
Ph-
8
H-
H-
Ph-
9
CH3- H-
p-CH3OC6H4-
p-CH3OC6H4-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
S
H-
H-
H-
CH3- H-
S
H-
H-
CH3- p-CH3OC6H4-
S
H-
H-
p-CH3OC6H4-
p-CH3OC6H4-
p-CH3OC6H4-
O
O
O
O
S
CH3- H-
H-
H-
H-
CH3- H-
H-
H-
CH3- p-CH3OC6H4-
Reaction conditions: (a) Phenylboronic acid, Pd(OAc)2, Cs2CO3, DMF, 1100C. (b)
Pd(PPh3)2Cl2, NEt3, HCOOH, DMF, 600C. (c) Methyl acrylate, PPh3, Pd(OAc)2, K2CO3 DMF,
1100C. (d) Diphenylacetylene, Pd(OAc)2, NaOAc, LiCl, DMF, 1000C.
H-
H-
p-CH3OC6H4-
p-PhCH2OC6H4- 4q (77%)
CH3- H-
S
H-
H-
H-
H-
CH3- p-PhCH2OC6H4- 4r (75%)
S
H-
H-
p-PhCH2OC6H4- 4s (81%)
p-PhCH2OC6H4- 4t (71%)
p-PhCH2OC6H4- 4u (70%)
O
O
O
O
CH3- H-
Next, to study the reaction mechanism of iodocyclization of 3 in
detail, we carried out DFT calculations. The calculated relative Gibbs
free energy profile and stationary point structures of the reactions
leading to 4a-4d (X = S and R4 = Ph) are shown in Figure 2, and
those of other reactions are shown in Figures S1 and S3-S6 in the
ESI. These reactions have only one transition state (TS) in ring
closure process, and the elimination of HI proceeds without energy
barrier. The reaction energy profiles of reactions leading to 4a-4d
are similar to each other. For instance, the calculated relative Gibbs
free energies of TS (Ga) are 18.4, 18.4, 18.2, and 18.5 kcal mol-1 in
the reactions leading to 4a-4d, respectively. It should be noted here
that the reactions of oxygen compounds, 4e-4h (X = O and R4 = Ph),
have similar reaction energy profiles to those of 4a-4d (See, Figure
S1 in the ESI). The Ga values of TS in the reactions leading to 4e-4h
(O compounds) are only ~1 kcal mol-1 smaller than those in the
reactions of S compounds. Figure S2 shows the optimized structure
of TS of 4a-4h with the representative interatomic distances. These
representative interatomic distances (RC…C, RC…I, and RI…I) in 4a-4h
are similar to each other. Thus, we can deduce that the reactivity of
the compound depends on the only R4 group on the alkynyl group.
Indeed, the Ga values of TS shown in Table 3 are clearly different
between the reactions, which have different R4 groups.
H-
H-
H-
CH3- H-
H-
H-
CH3- p-PhCH2OC6H4- 4v (73%)
H- p-PhCH2OC6H4- 4w (69%)
aAll iodocyclization reactions were conducted at room temperature with 6.0 equiv of I2,
6.0 equiv. of NaHCO3 in ACN unless and otherwise stated. bIsolated yields.
Furthermore, the crystal structure of the 5-iodo-8-methyl-
4-phenylthieno[2,3-c]acridine 4a was confirmed by the X-ray
crystallography (see the ESI).24
H12
C29
H13
H6
C30
I2
C25
C18
H14
C31
C15
C12
H2
C28
H11
C11
C20
H5
C14
C17
S3
C24
H8
H9
C27
C10
C13
C19
C21
H3
C22
C16
C23
H4
N4
H10
H1
C26
H7
Fig. 1. X-Ray crystal structure of 5-iodo-8-methyl-4-phenylthieno[2,3-c]acridine
4a (ORTEP diagram). Thermal ellipsoids are drawn at 50% probability level.
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DOI: 10.1039/C8NJ03511C
Figure 2. Relative Gibbs free energy profiles at T = 298 K of the reactions leading to 4a-4d obtained by B3LYP/6-311+G**+Midi!//B3LYP/6-31G*+Midi!
calculations. Solvent effect (Acetonitrile) was taken into account by the SCRF-PCM method.
bands at around 380 nm (λmax: 348–411 nm, ε: 4,200–15,500) and
In recent years, anthracene derivatives emerged as one of
the important blue-light emitting fluorescent dyes and have
widespread applications such as fluorescence sensors29 and organic
light-emitting diodes.30 On the other hand, although 2-
azaanthracene derivatives have been reported to show interesting
fluorescent properties,31 little has been reported on the
fluorescence properties of azaanthracene derivatives. Thus, the
absorption and fluorescence properties of the synthesized
thieno[2,3-c]acridine and furo[2,3-c]acridine derivatives were
studied. The UV-vis absorption spectra of 4a, 4e, and 6a−6d in
hexane are shown in Figure 3. The absorption maximum (λmax) and
molar extinction coefficient (ε) values are listed in Table 4. All the
synthesized compounds showed weak and intense absorption
280 nm (λmax: 266–297 nm, ε: 38,900–72,300), respectively. The
λmax value of furan-fused derivative 4e (399 nm) was slightly red-
shifted compared to that of thiophene-fused derivative 4a (391
nm)32a. The annulation of the naphthalene ring to the thieno[2,3-
c]acridine moiety led to a red shift in the λmax value (6d: 411 nm)
due to the extension of the π-conjugation.
In order to study the experimental absorption spectra, we
carried out time-dependent (TD) DFT calculations on compounds
6a-6d. Table S2 lists the energies of excited states of 6a-6d at their
ground state (S0) equilibrium structures relative to those of the S0
states. The related molecular orbitals are depicted in Figures S8-S11
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32
in the ESI. In the first excited state of 6a-6d, the main contribution
for the excitation is the transition from HOMO to LUMO. The
detailed discussion for the first excited state and the excitations
with the largest oscillator strength are also given in the ESI.
fluorescence probably due to the heavy atom effect. As observed
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DOI: 10.1039/C8NJ03511C
with the absorption spectra, the fluorescence spectra of 6a−6d
were structured. Compound 6a exhibited a mirror image between
the absorption and fluorescence spectra in hexane (Figure 5).
Therefore, the observed two fluorescence peaks of 6a at 415 and
434 nm are probably assigned to the S1,0 → S0,0 and S1,0 → S0,1
transitions, respectively. In accordance with the absorption spectra,
naphthalene-fused derivative 6d showed the most red-shifted
maximum fluorescence wavelength (Fmax) value (Table 4). The
fluorescence quantum yield (f) values of 6a−6d are in the range of
0.04 to 0.09. The relatively lower f value of 6c may be due to the
contribution of the carbonyl group which easily promotes the
intersystem crossing. 33
Summary and Conclusions
In summary, we have developed a synthetic route for the
construction of thieno[2,3-c]acridine and furo[2,3-c]acridine
derivatives via iodocyclization reaction. The structures of the
products were confirmed by IR, NMR, and HRMS, as well as X-
ray diffraction experiments. Thieno[2,3-c] acridine derivatives
Figure 3. UV-Vis absorption spectra in n-hexane.
showed blue fluorescence in hexane (Fmax: 415–430 nm, f
:
0.04–0.09). DFT calculations were also carried out to study the
effect of iodinating reagent and substituents on the reactivity
of the iodocyclization. Finally, the structural elaboration was
done by Suzuki coupling, Heck reaction, dehydroiodination and
alkyne annulation reaction. Further expansion of current
strategies and evaluation of biological activity is in progress.
1
6b
6a
6d
6c
0.5
0
Experimental Section
Experimental General: All solvents and reagents were purchased
from the suppliers and used without further purification. Reactions
were monitored by thin-layer chromatography (TLC) carried out on
silica plates using UV-light or Iodine chamber for visualization.
Column chromatography was performed on silica gel (60−120
mesh) using n-hexane and ethyl acetate as eluents. IR spectra were
400
500
600
Wavelength / nm
Figure 4. Normalized fluorescence spectra in n-hexane.
recorded on
a
JASCO FT/IR-460 Plus spectrophotometer.
Evaporation and condensation was carried out in vacuo. NMR
spectra were recorded with JEOL JNM-ECS 400 spectrometer with
tetramethylsilane as an internal standard. Chemical shifts δ and
coupling constants J are given in ppm (parts per million) and Hz
(hertz), respectively. The following abbreviations were used as
follows: s: singlet, d: doublet, t: triplet and m: multiplet.
Additionally unknown compounds are characterized by HRMS
analysis. All known compounds data are inconsistent with the given
literature reports. Scale up reactions also performed as per the
given general procedure without any deviation. Melting points were
measured by a Yanaco micro melting point apparatus. UV–vis
spectra were taken on
Fluorescence spectra were measured on
a
Hitachi U4100 spectrophotometer.
FP–8600
a
spectrofluorometer. Fluorescence quantum yields were recorded
Figure 5. Normalized absorption and fluorescence spectra of 6a in hexane.
on a Quantaurus–QY.
The fluorescence spectra of compounds 6a−6d in hexane are
shown in Figure 4. Although thieno[2,3-c]acridine derivatives 6a−6d
exhibited fluorescence, iodine derivatives 4a and 4e did not show
General procedure for the synthesis of 5-iodo-8-methyl-4-
phenylthieno[2,3-c]acridine 4a-4w:
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To a stirred solution of 6-methyl-3-(phenylethynyl)-2-(thiophen-3- J = 9.0 Hz, 1H), 7.88 (s, 1H), 7.68-7.73 (m, 3H), 7.55V-7ie.w60Art(icmle,O3nHlin)e,
yl)quinoline 3a (27 mg, 0.083 mmol, 1 equiv.); iodine (126 mg, 7.49-7.51 (m, 2H), 2.61 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ 152.99,
DOI: 10.1039/C8NJ03511C
0.498 mmol, 6 equiv.) and NaHCO3 (41.82 mg, 0.497 mmol, 6 147.66, 144.88, 143.11, 142.22, 139.64, 135.75, 135.07, 133.87,
equiv.) in dry ACN (5 mL) was stirred for 18 h, After completion of 130.15 (2C), 128.78, 128.48 (2C), 128.23, 127.17, 126.98, 126.37,
reaction (monitored by TLC), reaction mixture was quenched by 123.99, 107.34, 99.53, 21.90; HRMS (ESI): m/z = 436.0198 calcd. For
saturated sodium thiosulfate and extracted with ethyl acetate (15 C22H15NOI, found 436.0186 [M+H]+.
mL). The solvent was evaporated under reduced pressure to afford 5-Iodo-9-methyl-4-phenylfuro[2,3-c]acridine (4f)
a
crude residue. The crude was purified by silica gel Yield: 80%; Melting point: 219-2200C; IR (neat): 3059, 3017, 1609,
chromatography using n-hexane/ethyl acetate (97:3) as eluent to 1576, 1560, 1467, 1442, 1418, 1398, 1157, 1002, 890, 759, 719,
afford 4a (34 mg). Yield: 91%; Melting point: 228-2300C; IR (neat): 701, 643, 480 cm-1; 1H-NMR (400 MHz, CDCl3) δ 9.19 (s, 1H), 8.10 (s,
3052, 2915, 2182, 1585, 1551, 1491, 1353, 1314, 1139, 1029, 968, 1H), 8.00 (d, J = 8.5 Hz, 1H), 7.71 (dd, J = 6.3, 1.8 Hz, 2H), 7.54-7.60
913, 888, 815, 710, 694, 632, 532, 467 cm-1; 1H-NMR (400 MHz, (m, 3H), 7.49-7.51 (m, 2H), 7.43 (d, J = 6.7 Hz, 1H), 2.65 (s, 3H); 13C-
CDCl3) δ 9.01 (s, 1H), 8.43 (d, J = 5.4 Hz, 1H), 8.16 (d, J = 9.0 Hz, 1H), NMR (100 MHz, CDCl3) δ 153.16, 149.08, 144.83, 143.74, 142.79,
7.78 (s, 1H), 7.60 (dd, J = 8.8, 2.0 Hz, 1H), 7.46-7.50 (m, 4H), 7.39 141.67, 139.64, 134.72, 130.18 (2C), 128.77, 128.66, 128.47 (2C),
(dd, J = 7.4, 2.0 Hz, 2H), 2.53 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ 128.37, 127.09, 125.84, 125.41, 123.92, 107.35, 99.67, 22.44; HRMS
147.43, 144.02, 143.93, 142.36, 141.45, 141.20, 137.37, 135.97, (ESI): m/z = 436.0198 calcd. For C22H15NOI, found 436.0190 [M+H]+.
133.60, 129.40 (2C), 128.83, 128.76 (2C), 128.56, 127.53, 127.36, 5-Iodo-10-methyl-4-phenylfuro[2,3-c]acridine (4g)
126.91, 126.79, 124.54, 99.21, 21.94; HRMS (ESI): m/z = 451.9970 Yield: 85%; Melting point: 148-1490C; IR (neat) 3146, 2866, 1602,
calcd. For C22H15NSI, found 451.9980 [M+H]+.
5-Iodo-9-methyl-4-phenylthieno[2,3-c]acridine (4b)
1575, 1518, 1502, 1452, 1243, 1178, 1013, 999, 835, 821, 753, 740,
1
694, 619 cm-1; H-NMR (400 MHz, CDCl3) δ 9.19 (s, 1H), 7.95 (d, J =
Yield: 89%; Melting point: 145-1470C; IR (neat): 3111, 3048, 2936, 8.5 Hz, 1H), 7.67-7.73 (m, 3H), 7.57 (dd, J = 9.0, 6.7 Hz, 3H), 7.47-
1626, 1601, 1587, 1550, 1489, 1443, 1363, 1143, 1033, 907, 871, 7.52 (m, 3H), 3.01 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ 152.97,
748, 714, 702, 659, 632, 577 cm-1; 1H-NMR (400 MHz, CDCl3) δ 9.14 148.09, 144.78, 142.94, 142.68, 139.65, 136.73, 134.95, 130.31,
(s, 1H), 8.51 (d, J = 5.4 Hz, 1H), 8.11 (s, 1H), 8.00 (d, J = 8.5 Hz, 1H), 130.20 (2C), 128.76, 128.46 (2C), 127.06, 126.67, 126.08, 125.72,
7.54-7.58 (m, 4H), 7.43-7.48 (m, 3H), 2.65 (s, 3H); 13C-NMR (100 124.50, 107.43, 99.32, 18.30; HRMS (ESI): m/z = 436.0198 calcd. For
MHz, CDCl3) δ 148.87, 144.62, 143.92, 142.65, 142.07, 141.41, C22H15NOI, found 436.0178 [M+H]+.
140.87, 137.29, 129.43 (2C), 128.86, 128.83, 128.77 (2C), 128.14, 5-Iodo-4-phenylfuro[2,3-c]acridine (4h)
127.43, 127.28, 126.38, 125.76, 124.59, 99.30, 22.42; HRMS (ESI): Yield: 81%; Melting point: 168-1700C; IR (neat): 3057, 3026, 1607,
m/z = 451.9970 calcd. For C22H15NSI, found 451.9950 [M+H]+.
5-Iodo-10-methyl-4-phenylthieno[2,3-c]acridine (4c)
1524, 1441, 1356, 1333, 1212, 1175, 1053, 905, 880, 812, 716, 701,
1
562 cm-1; H-NMR (400 MHz, CDCl3) δ 9.26 (s, 1H), 8.34 (d, J = 8.5
Yield: 84%; Melting point: 118-1190C; IR (neat): 3023, 2962, 2911, Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.83-7.87 (m, 1H), 7.73 (q, J = 2.2
2027, 1617, 1588, 1560, 1495, 1439, 1361, 1142, 1076, 1069, 892, Hz, 2H), 7.49-7.62 (m, 6H); 13C-NMR (100 MHz, CDCl3) δ 153.19,
884, 810, 753, 712, 692, 637, 629, 528 cm-1; 1H-NMR (400 MHz, 148.79, 144.93, 143.73, 143.19, 139.56, 135.27, 130.99, 130.15
CDCl3) δ 9.05 (s, 1H), 8.49 (d, J = 5.4 Hz, 1H), 7.87 (d, J = 8.1 Hz, 1H), (2C), 128.83, 128.77, 128.63, 128.49 (2C), 127.05, 126.30, 125.88,
7.51-7.62 (m, 5H), 7.41-7.46 (m, 3H), 2.97 (s, 3H); 13C-NMR (100 124.01, 107.43, 99.53; HRMS (ESI): m/z = 422.0042 calcd. For
MHz, CDCl3) δ 147.69, 143.91, 143.41, 142.21, 141.06 (2C), 137.84, C21H13NOI, found 422.0034 [M+H]+.
136.88, 130.14, 129.45 (2C), 128.83, 128.76 (2C), 127.34, 127.22, 5-Iodo-4-(4-methoxyphenyl)-8-methylthieno[2,3-c]acridine (4i)
126.52, 126.40, 125.90, 124.68, 99.07, 18.35; HRMS (ESI): m/z = Yield: 89%; Melting point: 198-2000C; IR (neat): 3103, 2959, 2926,
451.9970 calcd. For C22H15NSI, found 451.9949 [M+H]+.
5-Iodo-4-phenylthieno[2,3-c]acridine (4d)
1792, 1604, 1587, 1574, 1509, 1489, 1439, 1353, 1245, 1172, 1134,
1
1025, 894, 835, 821, 813, 720, 689, 470 cm-1; H-NMR (400 MHz,
Yield: 86%; Melting point: 131-1330C; IR (neat): 3101, 3055, 2924, CDCl3) δ 9.10 (s, 1H), 8.51 (d, J = 5.4 Hz, 1H), 8.24 (d, J = 8.5 Hz, 1H),
1791, 1732, 1618, 1587, 1548, 1491, 1439, 1360, 1323, 1138, 1128, 7.87 (s, 1H), 7.69 (dd, J = 8.8, 2.0 Hz, 1H), 7.57 (d, J = 5.4 Hz, 1H),
1031, 897, 884, 776, 766, 755, 721, 628, 530, 469 cm-1; 1H-NMR 7.41 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H), 3.93 (s, 3H), 2.61 (s,
(400 MHz, CDCl3) δ 9.20 (s, 1H), 8.53 (d, J = 5.4 Hz, 1H), 8.35 (d, J = 3H); 13C-NMR (100 MHz, CDCl3) δ 159.85, 147.37, 144.03, 142.83,
8.5 Hz, 1H), 8.11 (d, J = 7.6 Hz, 1H), 7.85 (t, J = 7.0 Hz, 1H), 7.56-7.63 141.47, 140.95, 137.23, 136.45, 135.95, 133.56, 130.71 (2C),
(m, 5H), 7.47 (dd, J = 7.4, 2.0 Hz, 2H); 13C-NMR (100 MHz, CDCl3) δ 128.56, 127.53, 127.33, 127.03, 126.80, 124.58, 114.04 (2C), 99.88,
148.56, 144.59, 143.84, 142.77, 142.45, 141.37, 137.33, 130.79, 55.42, 21.94; HRMS (ESI): m/z = 482.0076 calcd. For C23H17NOSI,
129.38 (2C), 128.94, 128.89, 128.79 (2C), 128.55, 127.47, 127.42, found 482.0064 [M+H]+.
126.85, 126.11, 124.65, 99.14; HRMS (ESI): m/z = 451.9813 calcd. 5-Iodo-4-(4-methoxyphenyl)-9-methylthieno[2,3-c]acridine (4j)
For C21H13NSI, found 437.9796 [M+H]+.
5-Iodo-8-methyl-4-phenylfuro[2,3-c]acridine (4e)
Yield: 86%; Melting point: 218-2200C; IR (neat): 3104, 3084, 2954,
1629, 1608, 1585, 1513, 1361, 1289, 1248, 1170, 1141, 1030, 903,
Yield: 87%; Melting point: 248-2500C; IR (neat): 3126, 3057, 1607, 886, 831, 796, 725, 717, 578, 525 cm-1; 1H-NMR (400 MHz, CDCl3) δ
1574, 1551, 1524, 1441, 1356, 1333, 1211, 1053, 905, 880, 812, 9.14 (s, 1H), 8.50 (d, J = 5.4 Hz, 1H), 8.11 (s, 1H), 8.00 (d, J = 8.5 Hz,
716, 701, 533 cm-1; 1H-NMR (400 MHz, CDCl3) δ 9.17 (s, 1H), 8.25 (d, 1H), 7.56 (d, J = 5.4 Hz, 1H), 7.42 (dd, J = 13.9, 8.5 Hz, 3H), 7.09 (d, J
6 | J. Name., 2012, 00, 1-3
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= 8.5 Hz, 2H), 3.93 (s, 3H), 2.65 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ 136.69, 134.64, 131.87, 131.53 (2C), 130.24, 12V7ie.0w3A,rtic1le2O6n.6lin6e,
DOI: 10.1039/C8NJ03511C
159.84, 148.79, 144.61, 143.13, 142.08, 141.35, 140.62, 137.15, 126.16, 125.67, 124.41, 114.20, 113.84, 107.44, 99.81, 55.42, 18.30;
136.43, 130.73 (2C), 128.83, 128.14, 127.40, 127.24, 126.50, HRMS (ESI): m/z = 466.0304 calcd. For C23H17NO2I, found 466.0304
125.75, 124.63, 114.04 (2C), 99.96, 55.42, 22.40; HRMS (ESI): m/z = [M+H]+.
482.0076 calcd. For C23H17NOSI, found 482.0053 [M+H]+.
5-Iodo-4-(4-methoxyphenyl)furo[2,3-c]acridine (4p)
5-Iodo-4-(4-methoxyphenyl)-10-methylthieno[2,3-c]acridine (4k)
Yield: 68%; Melting point: 234-2350C; IR (neat): 2923, 2836, 1719,
Yield: 78%; Melting point: 222-2240C; IR (neat): 3098, 3084, 2929, 1575, 1544, 1516, 1504, 1438, 1285, 1244, 1025, 881, 830, 792,
1607, 1587, 1572, 1511, 1460, 1275, 1244, 1173, 1026, 1013, 892, 761, 748, 603 cm-1; 1H-NMR (400 MHz, CDCl3) δ 9.28 (s, 1H), 8.34 (d,
1
831, 721, 544, 506 cm-1; H-NMR (400 MHz, CDCl3) δ 9.08 (s, 1H), J = 9.0 Hz, 1H), 8.13 (d, J = 8.5 Hz, 1H), 7.86 (t, J = 7.2 Hz, 1H), 7.74
8.50 (d, J = 5.4 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 6.7 Hz, (dd, J = 9.0, 1.8 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.46 (d, J = 8.5 Hz,
1H), 7.53 (d, J = 4.9 Hz, 1H), 7.38-7.47 (m, 3H), 7.08 (d, J = 8.5 Hz, 2H), 7.11 (d, J = 9.0 Hz, 2H), 3.93 (s, 3H); 13C-NMR (100 MHz, CDCl3)
2H), 3.92 (s, 3H), 2.99 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ 159.84, δ 159.91, 153.42, 148.73, 144.87, 143.76, 143.19, 134.99, 131.79,
147.65, 143.45, 142.73, 142.24, 140.83, 137.72, 136.89, 136.43, 131.48 (2C), 130.93, 128.77, 128.61, 127.06, 126.44, 125.87,
130.75 (2C), 130.10, 127.81, 127.36, 127.19, 126.42, 125.88, 123.91, 113.88 (2C), 107.43, 100.01, 55.42; HRMS (ESI): m/z =
124.72, 114.03 (2C), 99.70, 55.42, 18.33; HRMS (ESI): m/z = 452.0148 calcd. For C22H15NO2I, found 452.0175 [M+H]+.
482.0076 calcd. For C23H17NOSI, found 482.0057 [M+H]+.
4-(4-(Benzyloxy)phenyl)-5-iodo-8-methylthieno[2,3-c]acridine (4q)
5-Iodo-4-(4-methoxyphenyl)thieno[2,3-c]acridine (4l)
Yield: 77%; Melting point: 220-2210C; IR (neat): 3116, 2896, 2922,
Yield: 88%; Melting point: 212-2140C; IR (neat): 3086, 2926, 2851, 1733, 1605, 1582, 1550, 1509, 1453, 1376, 1244, 1172, 1022, 819,
1605, 1586, 1573, 1510, 1492, 1452, 1362, 1288, 1247, 1172, 1030, 795, 731, 696, 634, 492 cm-1; H-NMR (400 MHz, CDCl3) δ 9.12 (s,
1
835, 748, 717, 698, 619, 469 cm-1; 1H-NMR (400 MHz, CDCl3) δ 9.20 1H), 8.52 (d, J = 5.4 Hz, 1H), 8.25 (d, J = 9.0 Hz, 1H), 7.89 (s, 1H), 7.70
(s, 1H), 8.52 (d, J = 5.4 Hz, 1H), 8.34 (d, J = 8.5 Hz, 1H), 8.11 (d, J = (d, J = 9.0 Hz, 1H), 7.58 (d, J = 5.4 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H),
8.5 Hz, 1H), 7.85 (t, J = 7.2 Hz, 1H), 7.57-7.63 (m, 2H), 7.41 (d, J = 8.5 7.39-7.46 (m, 5H), 7.17 (d, J = 8.5 Hz, 2H), 5.18 (s, 2H), 2.62 (s, 3H);
Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H), 3.93 (s, 3H); 13C-NMR (100 MHz, 13C-NMR (100 MHz, CDCl3) δ 159.17, 147.38, 144.04, 142.81,
CDCl3) δ 159.89, 148.50, 144.59, 143.24, 142.45 (2C), 141.13, 141.50, 140.93, 137.25, 136.86, 136.70, 135.97, 133.58, 130.76
137.20, 136.36, 130.70 (3C), 128.92, 128.54, 127.42 (2C), 126.95, (2C), 128.76 (2C), 128.56, 128.24, 127.81 (2C), 127.54, 127.35,
126.08, 124.68, 114.06, 99.80, 55.43; HRMS (ESI): m/z = 467.9919 127.04, 126.81, 124.59, 114.88 (2C), 99.85, 70.23, 21.94; HRMS
calcd. For C22H15NOSI, found 467.9909 [M+H]+.
5-Iodo-4-(4-methoxyphenyl)-8-methylfuro[2,3-c]acridine (4m)
(ESI): m/z = 558.0389 calcd. For C29H21NOSI, found 558.0405
[M+H]+.
Yield: 81%; Melting point: 218-2190C; IR (neat): 3048, 2970, 1633, 4-(4-(Benzyloxy)phenyl)-5-iodo-10-methylthieno[2,3-c]acridine
1578, 1472, 1395, 1363, 1219, 1084, 1010, 971, 923, 822, 772, 756, (4r)
561 cm-1; H-NMR (400 MHz, CDCl3) δ 9.16 (s, 1H), 8.23 (d, J = 8.5 Yield: 75%; Melting point: 175-1760C; IR (neat): 3034, 2892, 2955,
1
Hz, 1H), 7.88 (s, 1H), 7.68-7.74 (m, 3H), 7.45 (d, J = 8.1 Hz, 2H), 7.11 1724, 1604, 1588, 1494, 1449, 1361, 1246, 1171, 1107, 1035, 1025,
(d, J = 8.5 Hz, 2H), 3.93 (s, 3H), 2.61 (s, 3H); 13C-NMR (100 MHz, 760, 734, 716, 693, 621, 531, 499 cm-1; 1H-NMR (400 MHz, CDCl3) δ
CDCl3) δ 159.87, 153.18, 147.61, 144.81, 143.13, 142.16, 135.69, 9.11 (s, 1H), 8.53 (d, J = 5.4 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.66 (d, J
134.77, 133.77, 131.87, 131.48 (2C), 128.24, 127.16, 126.97, = 6.7 Hz, 1H), 7.37-7.56 (m, 9H), 7.16 (d, J = 8.5 Hz, 2H), 5.16 (s, 2H),
126.48, 123.92, 113.85 (2C), 107.34, 100.02, 55.41, 21.90; HRMS 3.00 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ 159.15, 147.70, 143.49,
(ESI): m/z = 466.0304 calcd. For C23H17NO2I, found 466.0294 [M+H]+. 142.72, 142.29, 140.81, 137.75, 136.91, 136.86, 136.67, 130.80
5-Iodo-4-(4-methoxyphenyl)-9-methylfuro[2,3-c]acridine (4n)
(2C), 130.14, 128.77 (2C), 128.25, 127.83 (2C), 127.40, 127.23,
Yield: 77%; Melting point: 188-1900C; IR (neat): 3020, 2963, 1025, 126.70, 126.44, 125.92, 124.72, 114.86 (2C), 99.69, 70.22, 18.34;
1604, 1476, 1459, 1441, 1242, 1215, 1176, 1140, 958, 903, 756, 668 HRMS (ESI): m/z = 558.0389 calcd. For C29H21NOSI, found 558.0402
cm-1; 1H-NMR (400 MHz, CDCl3) δ 9.21 (s, 1H), 8.11 (s, 1H), 8.02 (d, J [M+H]+.
= 8.5 Hz, 1H), 7.72 (dd, J = 9.6, 2.0 Hz, 2H), 7.44-7.46 (m, 3H), 7.11 4-(4-(Benzyloxy)phenyl)-5-iodothieno[2,3-c]acridine (4s)
(d, J = 9.0 Hz, 2H), 3.93 (s, 3H), 2.66 (s, 3H); 13C-NMR (100 MHz, Yield: 81%; Melting point: 169-1710C; IR (neat): 3034, 2920, 2214,
CDCl3) δ 159.86, 153.38, 149.01, 144.77, 143.75, 142.79, 141.60, 1620, 1603, 1583, 1549, 1508, 1453, 1360, 1240, 1175, 1009, 1001,
134.45, 131.86, 131.50 (2C), 128.64, 128.37, 127.08, 125.96, 919, 910, 832, 734, 725, 715, 698, 632, 509 cm-1; 1H-NMR (400 MHz,
125.42, 123.83, 113.86 (2C), 107.38, 100.17, 55.41, 22.44; HRMS CDCl3) δ 9.22 (s, 1H), 8.53 (d, J = 5.4 Hz, 1H), 8.35 (d, J = 8.5 Hz, 1H),
(ESI): m/z = 466.0304 calcd. For C23H17NO2I, found 466.0300 [M+H]+. 8.13 (d, J = 8.1 Hz, 1H), 7.86 (t, J = 7.2 Hz, 1H), 7.58-7.64 (m, 2H),
5-Iodo-4-(4-methoxyphenyl)-10-methylfuro[2,3-c]acridine (4o)
7.52 (d, J = 7.2 Hz, 2H), 7.37-7.46 (m, 5H), 7.18 (d, J = 8.5 Hz, 2H),
Yield: 73%; Melting point: 205-2060C; IR (neat): 3019, 2839, 1718, 5.17 (s, 2H); 13C-NMR (100 MHz, CDCl3) δ 159.20, 148.52, 144.62,
1606, 1454, 1441, 1419, 1397, 1355, 1248, 1215, 1157, 1133, 1034, 143.21, 142.49, 141.10, 137.22, 136.84, 136.61, 130.76 (3C),
1
913, 893, 833, 756, 651 cm-1; H-NMR (400 MHz, CDCl3) δ 9.17 (s, 128.93, 128.77 (2C), 128.56, 128.25, 127.82 (2C), 127.45 (2C),
1H), 7.94 (d, J = 8.5 Hz, 1H), 7.66-7.73 (m, 3H), 7.47 (t, J = 9.2 Hz, 126.97, 126.09, 124.69, 114.89 (2C), 99.78, 70.23; HRMS (ESI): m/z
3H), 7.10 (d, J = 9.0 Hz, 2H), 3.92 (s, 3H), 3.00 (s, 3H); 13C-NMR (100 = 544.0232 calcd. For C28H19NOSI, found 544.0223 [M+H]+.
MHz, CDCl3) δ 159.86, 153.17, 147.99, 144.69, 142.89, 142.66, 4-(4-(Benzyloxy)phenyl)-5-iodo-8-methylfuro[2,3-c]acridine (4t)
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Yield: 71%; Melting point: 195-1960C; IR (neat): 3031, 3009, 2914, using n-hexane/ethyl acetate (97:3) as eluent to afford 5a (21 mg).
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0
DOI: 10.1039/C8NJ03511C
2174, 1722, 1602, 1578, 1547, 1517, 1292, 1219, 1173, 1052, 1021, Yield: 58%; Melting point: 103-105 C; IR (neat): 3020, 2977, 1593,
912, 836, 819, 760, 747, 732, 694, 535 cm-1; 1H-NMR (400 MHz, 1556, 1514, 1487, 1215, 1166, 1159, 1087, 931, 874, 826, 669, 622,
CDCl3) δ 9.16 (s, 1H), 8.23 (d, J = 8.5 Hz, 1H), 7.87 (s, 1H), 7.67-7.73 594 cm-1; H-NMR (400 MHz, CDCl3) δ 7.93-8.00 (m, 3H), 7.54-7.60
1
(m, 3H), 7.35-7.51 (m, 7H), 7.18 (d, J = 8.5 Hz, 2H), 5.16 (s, 2H), 2.60 (m, 3H), 7.13 (d, J = 1.8 Hz, 1H), 2.55 (s, 3H); 13C-NMR (100 MHz,
(s, 3H); 13C-NMR (100 MHz, CDCl3) δ 159.18, 153.16, 147.60, 144.82, CDCl3) δ 146.99, 146.37, 143.41, 143.17, 138.85, 137.08, 135.78,
143.13, 142.18, 136.89, 135.70, 134.73, 133.80, 132.12, 131.55 133.19, 129.12, 126.54, 126.34, 110.90, 110.77, 103.81, 61.30,
(2C), 128.77 (2C), 128.23 (2C), 127.78 (2C), 127.16, 126.98, 126.48, 21.72; HRMS (ESI): m/z = 565.8114 calcd. For C16H11NOBrI2, found
123.92, 114.66 (2C), 107.35, 100.02, 70.20, 21.91; HRMS (ESI): m/z 565.8138 [M+H]+.
= 542.0617 calcd. For C29H21NO2I, found 542.0626 [M+H]+.
(E)-3-(2-Bromo-1,2-diiodovinyl)-2-(furan-3-yl)-7-methylquinoline
4-(4-(Benzyloxy)phenyl)-5-iodo-9-methylfuro[2,3-c]acridine (4u)
(5b)
Yield: 70%; Melting point: 190-1920C; IR (neat): 3031, 2920, 2851, Yield: 43%; Sticky; IR (KBr): 2970, 2922, 1709, 1625, 1573, 1550,
1738, 1598, 1515, 1500, 1352, 1231, 1207, 997, 904, 830, 741, 689, 1514, 1452, 1215, 1159, 1054, 1007, 874, 806, 756, 706, 667, 594
1
1
646, 587, 511, 473, 464 cm-1; H-NMR (400 MHz, CDCl3) δ 9.22 (s, cm-1; H-NMR (400 MHz, CDCl3) δ 7.96-7.99 (m, 2H), 7.88 (s, 1H),
1H), 8.11 (s, 1H), 8.03 (d, J = 8.5 Hz, 1H), 7.73 (dd, J = 9.9, 2.2 Hz, 7.68-7.71 (m, 1H), 7.54 (d, J = 1.8 Hz, 1H), 7.38 (d, J = 8.5 Hz, 1H),
2H), 7.37-7.52 (m, 8H), 7.19 (d, J = 9.0 Hz, 2H), 5.17 (s, 2H), 2.66 (s, 7.12 (d, J = 9.0 Hz, 1H), 2.56 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ
3H); 13C-NMR (100 MHz, CDCl3) δ 159.17, 153.37, 149.05, 144.78, 147.95, 143.57, 143.18, 141.43, 138.10, 136.19, 135.49, 129.38,
143.78, 142.80, 141.62, 136.90, 134.41, 132.12, 131.55 (2C), 128.76 128.43, 127.39, 125.70, 124.38, 110.94, 103.89, 61.42, 22.15; HRMS
(2C), 128.65, 128.38, 128.21, 127.77 (2C), 127.09, 125.97, 125.43, (ESI): m/z = 565.8114 calcd. For C16H11NOBrI2, found 565.8123
123.86, 114.66 (2C), 107.37, 100.13, 70.20, 22.43; HRMS (ESI): m/z [M+H]+.
= 542.0617 calcd. For C29H21NO2I, found 542.0620 [M+H]+.
(E)-3-(2-Bromo-1,2-diiodovinyl)-2-(furan-3-yl)-8-methylquinoline
4-(4-(Benzyloxy)phenyl)-5-iodo-10-methylfuro[2,3-c]acridine (4v)
(5c)
Yield: 73%; Melting point: 165-1670C; IR (neat): 3146, 2911, 2866, Yield: 59%; Melting point: 82-840C; IR (neat): 2954, 2920, 1614,
1717, 1602, 1575, 1518, 1502, 1352, 1243, 1178, 1013, 999, 835, 1592, 1572, 1513, 1573, 1410, 1377, 1215, 1066, 1040, 1004, 932,
821, 753, 740, 694, 619, 588 cm-1; 1H-NMR (400 MHz, CDCl3) δ 9.21 923, 874, 792, 710, 667, 593 cm-1; 1H-NMR (400 MHz, CDCl3) δ 7.97-
(s, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.69-7.75 (m, 3H), 7.47 (td, J = 16.5, 8.01 (m, 2H), 7.54-7.65 (m, 3H), 7.42 (t, J = 7.6 Hz, 1H), 7.21-7.25
7.8 Hz, 8H), 7.19 (d, J = 9.0 Hz, 2H), 5.18 (s, 2H), 3.01 (s, 3H); 13C- (m, 1H), 2.84 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ 146.63, 146.15,
NMR (100 MHz, CDCl3) δ 159.17, 153.18, 148.05, 144.72, 142.95, 143.62, 143.11, 138.44, 137.47, 136.62, 135.93, 130.83, 126.85,
142.71, 136.91, 136.72, 134.64, 132.13, 131.57 (2C), 130.27, 128.76 126.20, 125.68, 111.05, 103.92, 61.34, 17.85; HRMS (ESI): m/z =
(2C), 128.21, 127.76 (2C), 126.68, 126.21, 125.70, 124.43, 115.18, 565.8114 calcd. For C16H11NOBrI2, found 565.8133 [M+H]+.
114.66 (2C), 107.45, 99.77, 70.21, 18.28; HRMS (ESI): m/z = (E)-3-(2-Bromo-1,2-diiodovinyl)-2-(furan-3-yl)quinoline (5d)
542.0617 calcd. For C29H21NO2I, found 542.0613 [M+H]+.
Yield: 51%; Sticky; IR (KBr): 2963, 2928, 1726, 1618, , 1591, 1545,
4-(4-(Benzyloxy)phenyl)-5-iodofuro[2,3-c]acridine (4w)
1513, 1484, 1418, 1215, 1158, 1053, 1005, 936, 873, 783, 667, 593
Yield: 69%; Melting point: 177-1780C; IR (neat): 3142, 2969, 1663, cm-1; H-NMR (400 MHz, CDCl3) δ 8.01-8.11 (m, 3H), 7.73-7.82 (m,
1
1603, 1574, 1519, 1503, 1355, 1219, 1175, 1048, 1025, 1002, 831, 2H), 7.52-7.56 (m, 2H), 7.14 (d, J = 9.4 Hz, 1H); 13C-NMR (100 MHz,
1
773, 739, 697, 591 cm-1; H-NMR (400 MHz, CDCl3) δ 9.25 (s, 1H), CDCl3) δ 147.90, 143.67, 143.24, 138.88, 136.48, 135.77, 130.83,
8.33 (d, J = 9.0 Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.82-7.86 (m, 1H), 129.46, 127.76, 127.06, 126.32, 125.63, 110.81, 103.58, 61.53;
7.72 (dd, J = 8.1, 1.8 Hz, 2H), 7.57-7.61 (m, 1H), 7.34-7.51 (m, 7H), HRMS (ESI): m/z = 551.7982 calcd. For C15H9NOBrI2, found 551.7957
7.17-7.20 (m, 2H), 5.16 (s, 2H); 13C-NMR (100 MHz, CDCl3) δ 159.23, [M+H]+.
153.38, 148.73, 144.87, 143.75, 143.17, 136.90, 134.94, 132.05, General procedure for the synthesis of 8-Methyl-4,5-
131.56 (2C), 130.93, 128.77 (3C), 128.62, 128.23, 127.77 (2C), diphenylthieno[2,3-c]acridine (6a)
127.05, 126.42, 125.87, 123.94, 114.70 (2C), 107.45, 100.01, 70.22; To a solution of 5-iodo-8-methyl-4-phenylthieno[2,3-c]acridine 4a
HRMS (ESI): m/z = 528.0461 calcd. For C28H19NO2I, found 528.0455 (30 mg, 0.075 mmol, 1 equiv.) the phenyl boronic acid (11.9 mg,
[M+H]+.
0.097 mmol, 1.3 equiv.) in 5 ml DMF, Pd(OAc)2 (1.7 mg, 1 mol %),
General procedure and spectral data for the synthesis of (E)-3-(2- Cs2CO3 (73.08 mg, 0.224 mmol, 3 equiv.) were added. The resulting
bromo-1,2-diiodovinyl)-2-(furan-3-yl)-6-methylquinoline 5a-5d:
mixture was then heated at 1100C for 12 h. The solvent was
To a stirred solution of (E)-3-(2-bromo-1,2-diiodovinyl)-2-(furan-3- removed under reduced pressure, the residue was extracted with
yl)-6-methylquinoline 2a (20 mg, 0.064 mmol, 1 equiv.) and iodine ethyl acetate: brine; the crude was purified by silica gel
(97.6 mg, 0.384 mmol, 6 equiv.); NaHCO3 (32.3 mg, 0.384 mmol, 6 chromatography using n-hexane/ethyl acetate (95:5) as eluents to
equiv.) in dry ACN (5 mL) was stirred for 18 h, After completion of afford 6a (18 mg). Yield: 67%; Melting point: 257-259ºC; IR (neat):
reaction (monitored by TLC), reaction mixture was quenched by 3054, 3022, 2979, 1738, 1601, 1586, 1574, 1550, 1439, 1373, 1310,
1
saturated sodium thiosulfate and extracted with ethyl acetate (20 1123, 1027, 911, 894, 820, 808, 744, 696, 633, 536, 469 cm-1; H-
mL). Solvent was evaporated under reduced pressure to afford a NMR (400 MHz, CDCl3) δ 8.61 (d, J = 5.4 Hz, 1H), 8.41 (s, 1H), 8.24
crude residue. The crude was purified by silica gel chromatography (d, J = 8.5 Hz, 1H), 7.61-7.65 (m, 3H), 7.25-7.32 (m, 10H), 2.53 (s,
8 | J. Name., 2012, 00, 1-3
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3H); 13C-NMR (100 MHz, CDCl3) δ 146.74, 144.88, 143.28, 139.37, The mixture was allowed to cool to room temperature, diluted with
View Article Online
ethyl acetate (15 mL); dried over sodium sulfate, and filtered. The
solvent was removed under reduced pressure and the residue was
DOI: 10.1039/C8NJ03511C
138.04, 136.71, 135.20, 134.93, 134.18, 133.64, 133.02, 131.68
(2C), 130.08 (2C), 128.88, 128.15 (2C), 128.01 (2C), 127.56, 127.17,
purified by column chromatography using n-hexane: ethyl acetate
126.90, 126.47, 126.35, 125.75, 124.80, 21.79; HRMS (ESI): m/z =
(95:5) as eluent to afford 6d (28 mg). Yield: 84%; Melting point:
402.1316 calcd. For C28H20NS, found 402.1344 [M+H]+.
General procedure for the synthesis of 8-Methyl-4-
274-2760C; IR (neat): 3052, 2917, 2850, 1582, 1548, 1515, 1473,
1388, 1293, 1081, 1071, 924, 821, 807, 752, 727, 716, 698, 656,
1
639, 551 cm-1; H-NMR (400 MHz, CDCl3) δ 9.40 (d, J = 8.5 Hz, 1H),
phenylthieno[2,3-c]acridine (6b)
8.67 (d, J = 5.4 Hz, 1H), 8.23 (s, 1H), 8.09 (d, J = 9.0 Hz, 1H), 7.71-
7.81 (m, 3H), 7.52-7.58 (m, 2H), 7.26 (d, J = 8.5 Hz, 3H), 7.13-7.19
(m, 5H), 7.07 (d, J = 6.3 Hz, 2H), 6.95 (s, 1H), 2.44 (s, 3H); 13C-NMR
(100 MHz, CDCl3) δ 145.85, 145.79, 143.07, 139.59, 138.71, 138.28,
137.63 (2C), 137.57, 137.50, 134.98, 132.95, 132.42, 131.67 (2C),
131.40 (2C), 129.10, 128.40 (2C), 128.13, 127.95, 127.67 (2C),
127.16, 127.08 (2C), 126.90, 126.59 (2C), 126.35, 126.02, 125.03
(2C), 123.58, 21.76; HRMS (ESI): m/z = 502.1629 calcd. For C36H24NS,
found 502.1611 [M+H]+.
To
a
solution of the corresponding 5-iodo-8-methyl-4-
phenylthieno[2,3-c]acridine 4a (34 mg, 0.075 mmol, 1 equiv.) the
formic acid (5.68 mml, 0.150 mmol, 2 equiv.) in 5 ml DMF, Pd
(PPh3)2Cl2 (2.64 mg, 0.5 mol %), NEt3 (31.54 mml, 0.226 mmol, 3
equiv.) were added. The resulting mixture was then heated at 60ºC
for 12 h. The solvent was removed under reduced pressure, the
residue was extracted with ethyl acetate: brine and purified by silica
gel column chromatography using n-hexane: ethyl acetate (95:5) as
eluent to afford 6b (21 mg). Yield: 86%; Melting point: 146-1480C; IR
(neat): 3098, 3048, 2970, 1633, 1600, 1578, 1547, 1472, 1395,
1363, 1219, 1084, 1010, 971, 957, 923, 822, 772, 756, 715, 694, 561
cm-1; 1H-NMR (400 MHz, CDCl3) δ 8.59-8.65 (m, 2H), 8.23 (d, J = 9.0
Hz, 1H), 7.83 (d, J = 7.2 Hz, 2H), 7.75 (d, J = 4.9 Hz, 2H), 7.64 (t, J =
4.9 Hz, 2H), 7.52 (dt, J = 26.0, 7.3 Hz, 3H), 2.58 (s, 3H); 13C-NMR (100
MHz, CDCl3) δ 147.19, 144.94, 140.93, 140.06, 137.89, 135.47,
135.42, 134.99, 132.88, 129.23, 128.97 (2C), 128.51 (3C), 126.80,
126.42, 126.14, 125.48, 124.78, 123.5, 21.90; HRMS (ESI): m/z =
326.1003 calcd. For C22H16NS, found 326.0984 [M+H]+.
Conflicts of interest
“There are no conflicts to declare”.
Acknowledgements
This study was supported by JSPS KAKENHI Grant Number
17550099 (to MK) and 16K17851 (to TU). Portion of these
computations was performed at Research Center for Computational
Science (RCCS), Okazaki. Author ADS thankful to Masayuki Ninomiya
for help in elemental analysis characterization.
General procedure for the synthesis of Methyl (E)-3-(8-methyl-4-
phenylthieno[2,3-c]acridin-5-yl)acrylate (6c)
To
a
solution of the corresponding 5-iodo-8-methyl-4-
phenylthieno[2,3-c]acridine 4a (30 mg, 0.066 mmol, 1 equiv.) and
the methyl acrylate (11.4 mg, 0.133 mmol, 2 equiv.) in 4 ml DMF; Pd
(OAc)2 (0.7 mg, 0.5 mol %), PPh3 (17.4 mg, 0.066 mmol, 1 equiv.)
and K2CO3 (18.4 mg, 0.133 mmol, 2 equiv.) were added. The
resulting mixture was then heated under nitrogen atmosphere for
12 h. The solvent was removed under reduced pressure, the residue
was extracted with ethyl acetate and purified by silica gel column
chromatography using hexane: ethyl acetate (97:3) as eluent to
afford 6c (21 mg). Yield: 78%; Melting point: 170-1720C; IR (neat):
2948, 2916, 1712, 1702, 1633, 1587, 1503, 1428, 1375, 1315, 1288,
Supporting Information:
Experimental procedures, characterization data for the new
1
compounds, and copies of H and 13C NMR spectra. This material is
available free of charge via the Internet at http://pubs.rsc.org.
Notes and references
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1258, 1170, 1160, 988, 898, 819, 738, 718, 703, 640, 467 cm-1; H-
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New Journal of Chemistry
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DOI: 10.1039/C8NJ03511C
Synthesis of thieno[2,3-c]acridine and furo[2,3-c]acridine derivatives via
iodocyclization reaction, fluorescence properties and DFT mechanistic study
In this paper, we report the novel synthesis of thieno[2,3-c] acridine and furo[2,3-c] acridine
derivatives via intramolecular iodocyclization reaction. The thieno[2,3-c] acridine derivatives
showed blue fluorescence in hexane. DFT and time-dependent (TD) DFT studies were carried
out. This methodology provided a novel pathway to access thieno[2,3-c] acridine and furo[2,3-
c] acridine derivatives via 6-endo iodocyclization reaction.