Multicomponent reactions for facile access to coumarin-fused dihydroquinolines and quinolines: Synthesis and photophysical studies

Article abstract of DOI:10.1039/c4nj00630e

A simple and straightforward method for facile access to coumarin-fused dihydroquinolines (4) has been developed using the microwave-assisted multicomponent reactions of 4-hydroxycoumarin, aldehydes and aromatic amines in water catalyzed by bismuth trifla

Full text of DOI:10.1039/c4nj00630e

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DOI: 10.1039/C4NJ00630E
ARTICLE
Multicomponent reactions (MCRs) for the facile
access of coumarin fused dihydroquinolines
and quinolines: Synthesis and photophysical
studies
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
Mohammed Nasim Khan, Suman Pal, Shaik Karamthulla and Lokman H.
Choudhury*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A simple and straightforward method for the easy access of coumarin fused dihydroquinolines (4) has been
developed using bismuth triflate catalyzed microwave (MW) assisted multicomponent reactions of 4-
hydroxycoumarin, aldehydes and aromatic amines in water. Under solvent free and conventional heating
conditions, the same combination provided the corresponding coumarin fused quinolines (
and rapid method for the conversion of ( ) to ( ) using N-bromosuccinamide with very good yields is also
reported. The single-crystal X-ray crystallographic analysis for one of the product (4q) has revealed that the
products are regioselective and the reactions undergo via 1,2-addition followed by 6 -electrocyclization
instead of Skraup-Doebner-von Miller type reaction. Substituted quinoline carboxylic acid derivatives ( ) were
synthesized selectively from ( by ring opening of coumarin moiety followed by aromatization using
NaOH/DMSO under reflux conditions. Considering the presence of polycyclic conjugated structure of
synthesized and with coumarin moiety, their preliminary photophysical studies were carried out and
promising quantum yields were observed along with maximum quantum yield (Øf = 0.65) for 4j
5). An alternative
4
5

7
4
)
4
5
.
Introduction
antitumor agents.8 Considering the widespread applications of
coumarin fused heterocycles and in continuation of our work on
multicomponent reactions for the easy access of diverse
functionalized9 or polycyclic heterocycles,10 we were interested
in developing a general and versatile method for the synthesis
of coumarin fused dihydroquinoline (CFDQ) and quinoline
(CFQ) derivatives from the readily available starting materials
and to study the photophysical properties of the synthesized
molecules (Figure 1).
Multicomponent reactions (MCRs) have become a very popular
and powerful strategy in modern organic synthesis for the easy
access of complex organic molecules especially heterocycles in
single step.1 The fused polycyclic heterocycles are important
class of organic molecules because of their widespread
applications as pharmaceutical candidates, optical materials and
sensors.2 Coumarin moiety is abundant in various natural as
well as synthetic products having applications in medicinal
chemistry as well as in optoelectronics.3 Coumarin fused
polycyclic heterocycles posses very interesting properties and
therefore development of new methods for the easy access of
these molecules have lot of scope in recent times. E.g. recently,
Yang et al. have reported synthesis of coumarin/pyrrole-fused
heterocycles with their photochemical and redox switching
properties.4
heterocycles
Likewise,
exhibit
coumarin/phenanthridine
interesting photochemical
fused
and
thermochromic properties.5 Red fluorescent dyes based on
coumarin fused rhodamines were synthesized recently and used
for bioimaging in vitro.6 Similarly, synthesis and interesting
photophysical studies on a series of non-symmetrical coumarin-
fused BODIPY has also been reported in the literature.7
Coumarin fused dihydroquinolines have also been reported as
Figure 1 Structural correlation of known coumarin fused polycyclic
molecules with our target molecules.
This journal is © The Royal Society of Chemistry 2013
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4-Hydroxycoumarin is one of the widely explored and biscoumarin. In case of imidazole as well as acetic acid as
readily available substrate in organic synthesis.11 It is also one catalyst (Table 1, entries 4 and 5) the yield for 4j was not
View Article Online
of the very important building block for the construction of satisfactory as like L-proline. So we focused our attention to
DOI: 10.1039/C4NJ00630E
coumarin fused polycyclic molecules. Very recently we have use other acidic catalysts such as protic acid HCl and
developed a few MCRs involving 4-hydroxycoumarin for the CF3COOH and also Lewis acids such as InCl3 and metal
preparation of diverse heterocycles.12 In continuation of our triflates (Metal = Cu, Ag, Yt, Sc and Bi) were screened and the
work on exploration of various readily available substrates in results are summarized in Table 1 (entries: 6-13). From the
MCRs, we were interested in exploring 4-hydroxycoumarin Table 1, we realized that among all the screened catalysts
along with aromatic amines as a 1,3-binucleophile to form a Bi(OTf)3 provided the maximum yield in water under reflux
CFDQ moiety by reacting with aldehydes. From the literature it conditions. Next, various solvents were screened in presence of
is evident that aromatic amines acting as 1,3-binucleophile in Bi(OTf)3 as catalyst at reflux temperature. To our surprise we
multicomponent reactions is still limited and only few methods observed that the reaction predominantly gives unwanted
are known.13 Thus, there is lot of scope to explore this biscoumarin 6a along with traces of 4j and 5j in organic
reactivity pattern of aromatic amines in MCRs. Initially, we solvents such as acetonitrile, ethanol, tetrahydrofuran and
presumed that the combination of 4-hydroxycoumarin, toluene (Table 1, entries 14-17).
aldehydes and aromatic amines will provide either
shown in scheme 1.
4
or 4' as
From this study, we realized water as the best solvent for
this MCR. It is noteworthy to mention that, when the same
reaction was performed under the influence of Microwave
OH
NH2
o
irradiation at 130 C in water and Bi(OTf)3 as catalyst, within
+
+
R2 CHO
O
O
R1
15 minutes the desired CFDQ 4j was observed in good yields
(Table 1, entry 18). The variation in catalyst loading was also
checked to see the impact on yields and time. In case of 5 mol%
R1
R2
R1
o
catalyst loading and MW irradiation at 130 C for 15 minutes
HN
NH
R2
70% of the desired product along with considerable amount of
biscoumarin a side product (Table 1, entry 19) was isolated. By
increasing the catalyst loading up to 15 mol% keeping other
parameters same, no significant change in yield was observed.
From the optimization studies we have observed that, reaction
temperatures, type of solvent and catalyst are very much
important for the success of this type of MCRs. Interestingly,
the same set of substrates under solvent free and MW
O
4
O
O
O
4'
via-Skraup-Doebner-Von
Miller type reaction
6p‐electrocyclization
via-
Scheme
1 Possible regioisomers from the reaction of 4-
hydroxycoumarin, aldehydes and aromatic amines
Results and discussion
o
conditions at 140 C in the presence of 10 mol% Bi(OTf)3
provided biscoumarin 6a in 87% yield along with trace amount
for 4j and 5j. To our surprise, the same reaction under neat and
conventional heating conditions at 140 C provided coumarin
fused quinoline (CFQ) 5c in 90% yield along with traces
amount of 4j and 6a (Table 1, entry-23).
Synthesis of CFDQ (4) and CFQ (5) :
For the preliminary investigation, reaction of 4-
hydroxycoumarin, 4-bromobenzaldehyde and 4-methylaniline
was chosen as model reaction. Interestingly, in absence of any
catalyst and water as reaction medium, even after 24h of
stirring at room temperature, we did not observe any desired
three component product. Under the reflux and catalyst free
conditions, the same combination provided 87% of biscoumarin
o
With the optimized conditions in hand, we turned our
attention to investigate the scope and general applicability of
this methodology by carrying out the synthesis of CFDQ, a
tetracyclic heterocycles using different aldehydes and aromatic
amines (Table 2). We found that a series of substituted aromatic
aldehydes tethered with either electron-withdrawing or
electron-donating groups produced CFDQ derivatives in good
to excellent yields (Table 2, entries 2-4, 8-9, 12 and 16-17).
Heteroaromatic aldehyde such as thiophene-2-carbaldehyde
(Table 2, entry 13) also underwent this multicomponent
reaction smoothly to provide the corresponding CFDQ in good
yield. Aliphatic aldehyde such as formaldehyde was also tested
and was found to be suitable in this multicomponent reaction to
obtain the desired product (Table 2, entry 15). Similarly, the
variability of aromatic amines were also tested under the same
reaction conditions. All the synthesized compounds were fully
characterized using IR, 1H and 13C NMR and elemental
analysis. The structures of these CFDQs were further confirmed
6
within 24h from the condensation of two molecules of 4-
hydroxycoumarin with the aldehyde. Interestingly, use of L-
proline (10 mol%) in the model reaction provided desired
CFDQ (4j) 25% along with the 70% biscoumarin (6a) (Table 1,
entry 3). Both the isolated compounds 4j and 6a were
1
characterized by, IR, H and 13C NMR as well as elemental
analysis. The presence of one singlet at 5.21 ppm and a broad
singlet at 9.73 ppm indicates the presence of a benzylic proton
(CH) and a NH proton respectively. In 13C NMR the benzylic
carbon appeared at 40.7 ppm. The possibility of formation of 4'
type product as shown in scheme 1, was ruled out due to the
absence of doublet for benzylic proton and the lower than the
expected 13C NMR value of benzylic carbon. Next, we turned
our attention to explore various catalysts to achieve the
optimum yield for 4j by minimizing the formation of unwanted
2 | J. Name., 2012, 00, 1‐3
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by recording the single crystal XRD of one the product (4q) as
shown in Figure 2.
View Article Online
DOI: 10.1039/C4NJ00630E
Table 1 Optimization of the Reaction Conditions for the Synthesis of 4j
CH3
CH3
O
HO
OH
CHO
NH2
OH
O
HN
N
O
O
Catalyst
+
+
+
+
Solvent /
Solvent free
MW
O
Br
O
O
O
O
Br
O
Br
Br
2
CH3
3
1
6a
4j
5j
Entry
catalyst
(10 mol %)
reaction conditions
yielda (%)
4j
yielda (%)
5j
yielda (%)
6a
1.
2.
3.
4.
5.
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
----
----
H2O, rt, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
H2O, reflux, 24 h
CH3CN, reflux, 24 h
EtOH, reflux, 24 h
THF, reflux, 24 h
Toluene, reflux, 24 h
nil
Traces
25
30
30
10
Traces
15
20
15
58
55
65
Traces
Traces
Traces
Traces
86
nil
81
87
70
60
60
85
95
74
75
78
20
30
30
95
97
90
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
90
L-proline
Imidazole
CH3COOH
HCl
CF3COOH
InCl3
Cu(OTf)3
Ag(OTf)3
Yt(OTf)3
Sc(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
82
Traces
20
Traces
15
87
H2O, MW, 130 oC, 15 min
H2O, MW, 130 oC, 15 min
H2O, MW, 130 oC, 15 min
H2O, MW, 100 oC, 15 min
Neat, MW, 140 oC, 15 min
Neat, 140 oC, 2 h
Bi(OTf)3 ( 5 mol %)
Bi(OTf)3 ( 15 mol %)
Bi(OTf)3
70
87
78
Traces
Traces
Bi(OTf)3
Bi(OTf)3
Traces
Reaction conditions: 4-Hydroxycoumarin (0.5 mmol), aldehyde (0.5 mmol), aromatic amine (0.5 mmol), catalyst (10 mol%) and
solvent. ayields of isolated product w.r.t ‘1’
.
and NBS in stoichimetric amount (1 equiv.) were screened in
After the successful demonstration of the generality and different solvents. When 4j was refluxed with HNO3 in water
applicability of this method for the synthesis of a wide range of for 10h, only trace amount of the 5j was formed. Similarly,
CFDQs (4a-4s), next we wanted to prepare some CFQ so that KMnO4 and H2O2 gave only 20% and 10% respectively for the
we can study the photophysical properties of both the CFDQ same reaction time in water at reflux conditions. Interestingly,
and the CFQ derivatives and compare their relative quantum when CAN was employed in acetonitrile at room temperature
yields. Using the procedure of Table 1 (entry 23) the reaction of 86% of the desired product 5j was formed. The best result was
aromatic amines with 4-hydroxycoumarin and aldehydes in the obtained with 1.0 eqv. NBS in THF at room temperature and
o
presence of Bi(OTf)3 under neat conditions at 140 C provided 99% yield was isolated within 2 min. NBS with other solvents
the corresponding aromatized CFQ as the major product. Some such as, DCM and DMSO was also tested and the isolated
of the corresponding CFQ derivatives (5e, 5h, 5j, 5l, 5m, 5n yields were 96% and 98% respectively with long reaction time.
and 5q) were synthesized using this method under neat Hence, the best optimized condition to obtain 5j from 4j was
conditions and the results are summarized in Table 3 (Method NBS/THF at room temperature. Using this optimized condition
A). Although this method is an effective method for the direct other CFQs were prepared and the results are summarized in
synthesis of CFQ derivatives, we realized that the long reaction Table 3 (Method B).
time (2-4 hours) and the tedious purification process may be
Next, to explore the diversity of the process and to
avoided if we synthesize the fused CFDQ by our MW-H2O achieve different functionalized quinolines from the same
method in presence of Bi(OTf)3 and then convert to the starting materials, we attempted to open the cyclic ester of the
corresponding quinoline using a rapid and clean method. Thus coumarin moiety both from the CFDQ (
4
) and CFQ (
5) to
an alternate and time effective method was looked for and achieve the corresponding quinoline scaffolds (
7
) bearing
initially 4j was chosen to find a suitable condition for carboxylic acid at the 3-position in the quinoline ring. From the
conversion to the corresponding 5j. In this direction a wide literature we realized that quinoline-3-carboxylates or
range of reagents such as HNO3, KMnO4, H2O2, CAN, BDMS
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7
3
87
3
98
4q
5q
quinoline-3-carboxamide are promising drug candidates and act
as sweet flavor modifiers.14
aIsolated yields, Method A (neat reaction): 4-hydroxycoumarin
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(1.0 mmol), aldehyde (1.0 mmol), aromatic amine (1.0 mmol)
DOI: 10.1039/C4NJ00630E
and Bi(OTf)3 (0.1mmol), at 140 oC heating; Method B: CFDQs
(1.0 mmol), NBS (1.0 mmol) in THF (5ml) at room
temperature.
Table 2 Synthesis of 7-phenyl-7,12-dihydro-6
b
H
-chromeno[4,3-
]quinolin-6-onea
R2
OH
NH2
HN
Bi(OTf)3 (10 mol %)
H2O/MW
CHO
R1
+
+
Considering the importance of these types of functionalized
quinolines, initially we took 4h for the conversion to the
corresponding 7h by ring opening of coumarin moiety followed
R1
O
O
O
O
R2
1
2
4
3
by aromatization.
Using NaOH in DMSO at 140 oC we
Ent
ry
R1
R2
produ
time
yieldb
(%)
82
89
87
90
87
88
89
88
92
92
89
93
93
90
94
89
92
90
observed the best result for this conversion. Similarly, 7q was
also synthesized from 4q using same strategy in good yields. It
is noteworthy to mention that when similar strategy for the
ct
(min)
12
10
15
15
10
15
16
16
16
12
10
18
10
15
10
14
5
1
2
3
4
5
6
7
8
C6H5-
H
H
H
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
4-OMe-C6H4-
4-CN- C6H4-
4-Br- C6H4-
C6H5-
4-CN- C6H4-
4-Br- C6H4-
conversion of product
5 to 7 were tried the reaction failed
(Scheme 2). This may be due to thermodynamically less stable,
flexible ring which leads to facile cleavage of the coumarin ring
4-OMe-
4-OMe-
4-OMe-
in case of
4. We believe that in this method initially ring
opening of the coumarin followed by oxidation of
dihydroquinoline moiety takes place to form the desired
compounds.
3-OMe-C6H4- 4-OMe-
9
3-NO2-C6H4-
4-Br- C6H4-
3-NO2-C6H4-
4-OMe-
4-Me-
4-Me-
10
11
12
13
14
15
16
17
18
4j
4k
4l
R1
R
R1
2,4-Cl- C6H3- 4-Me-
R
N
R1
COOH
HN
N
O
2-Thiophene
C6H5-
4-Me-
4-Br-
4-Br-
3-Br--
3,4-OMe
3,4-(-
4m
4n
4o
4p
4q
4r
NaOH/DMSO
NaOH/DMSO
R
140 o
24h
C
140 oC
24h
H
O
O
O
HO
4-Cl-C6H4-
4-Me-C6H4-
C6H5-
5
4
7
7h : R = 3-OMe-C6H4-, R1= 4-OMe- ; yield: 54%
7q : R = 4-Me-C6H4-, R1= 3,4-OMe- ; yield : 60%
8
O(CH2)2-
O)-
4(piperidin-
1-yl)-
Scheme 2 Selective synthesis of 3-quinolinecarboxylic acid
derivatives from 4.
19
20
4-Br-C6H4-
C6H5-
4s
4t
10
20
91
0
4-NO2-
Mechanism
aReaction conditions: 4-Hydroxycoumarin (0.5 mmol),
aldehyde (0.5 mmol), aromatic amine (0.5 mmol), Bi(OTf)3
The proposed mechanism for the formation of CFDQ (4) has
been described in Scheme 3a. We believe initially, aromatic
o
(0.05 mmol) and H2O (1 ml) were heated in MW at 130 C.
bIsolated yields.
amine
which 4-hydroxycoumarin undergoes nucleophilic addition to
form an unstable intermediate . The side product forms
when another equivalent of 4-hydroxycoumarin reacts with the
intermediate . The formation of minimizes when the rate of
reaction of aromatic amine is faster than the nucleophilic
addition of 4-hydroxycoumarin to the intermediate . The
aromatic amine can undergo either 1, 2- or 1,4-addition to . In
3 condense with aldehyde 2 to form a Schiff base A, to
B
6
Table 3 Synthesis of 7-phenyl-6
H
-chromeno[4,3-
b
]quinolin-6-
R2
R2
one
4-Hydroxycoumarin
C
6
N
O
HN
Bi(OTf)3
+
NBS (1.0 eqv.) / THF
Aromatic amine
rt
Neat
C
+
Method A
Method B
O
Aldehyde
O
O
R1
R1
C
5
4
case of 1,4-addition obeying Skraup-Doebner-von Miller
process15 the expected product is 4'. However, from the the X-
ray crystal structure of one of the CFDQ (4q) (Figure 2) we
have realized that the observed product 4q possibly formed by a
entry substrate
product
Method A
time yielda
Method B
time
yielda
(h)
3
(%)
86
88
85
90
88
90
(min)
2
2
2
2
(%)
98
99
99
99
97
99
1,2-addition of aromatic amine with the intermediate
of aza-Michael addition followed by 6electrocyclization and
isomerisation to yield product ( ). We are not sure whether in
C instead
1
2
3
4
5
6
4e
4h
4j
4l
4m
4n
5e
5h
5j
5l
5m
5n
3.5
4
4
2
3
2
this MCR, Bi(OTf)3 in water medium acting as a source of in
situ triflic acid or as Lewis acid. In the literature most of the
methods have assumed that in water medium Bi(OTf)3 acts as a
5
1.5
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source of triflic acid which actually catalyzes various may be explained via the formation of
4
and followed by free-
reactions.16 It is also reported that (BiOTf)3 can be stabilized in radical mechanism involving Bi(III)/Bi(0) as shown in scheme
View Article Online
DOI: 10.1039/C4NJ00630E
water and acts as Lewis acid in the presence of basic ligand.17 3b. To know the role of bismuth in this reaction, compound 4e
o
Thus we believe that both the Bi(III) ion and triflic acid may be was heated at 140 C without adding any oxidant under open
helping at a time in this case for the formation of
A
,
B, C and air. Even after 6 hours we did not observe any conversion from
D
intermediates. In case of neat and conventional heating 4e to 5e.Thus the possibility of aerial oxidation can be ruled
conditions, the observed major product is CFQ (5) which
out.
OH
OH
O
R
O
R1
O
HN
R
NH2
O
NH
O
O
R
+
NH2
+
R
H
O
O
R1
3
2
1
R1
A
R1
B
C
1
1,2-addition of 3
X
1,4-addition of 3
OH
HO
R1
R
R1
O
NH
N
O
O
O
O
R
R
O
6
O
O
O
E
D
- H2O
R1
R1
R1
NH
N
R
HN
isomerization
R
O
R
O
O
O
4'
O
O
4
via-Skraup-Doebner-
von-Miller type reaction
4
via- 6electrocyclization
Not observed
Scheme 3a Proposed mechanism for the formation of CFDQ (4)
Scheme 3b Plausible mechanism for the formation of CFQ (
5
) from CFDQ (
4
) using Method-A: one-pot neat condition in
presence of Bi(OTf)3.
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could not study the UV-Vis and fluorescent property of 4j in
nonpolar solvents. Similar to 4j, we have also screened the
UV-Vis and fluorescence properties of the other synthesized
CFDQs and the results are summarized in Table 4 (see
Supporting Information). From these graphs for 4j, we have
found that UV-Vis and fluorescence spectra appeared around
345-357 nm and 422-441 nm respectively in different
solvents. The emission band for 4j appears at 422 nm in
CHCl3 solvent. On the other hand a large red-shift, low
energy band was observed both in MeOH and dipolar aprotic
DMSO solvents at 440 nm and 441 nm respectively.
Similarly, from Figure 3a, the absorption band for 4j was
observed at 357 nm for DMSO and a large blue shift was
observed at 345 nm in CHCl3.
From the Table 4 (see Supporting Information) we have
observed that the quantum yields of other compounds were in
the range of Øf = 0.00-0.59. Quantum yield above 50 % was
observed for 4b, 4c, 4d, 4g and 4l as 0.56 in MeOH, 0.58 in
DMSO, 0.59 in THF, 0.56 in THF and 0.55 in DMSO
respectively.
Figure 2 ORTEP plot of compound 4q (CCDC 997125)
.
o
Next, Compound 4e was heated at 140 C in the presence of 10
mol% Bi(OTf)3 under solvent-free conditions and within 2 hours,
the corresponding 5e was obtained in 30% yield. The less
conversion as compared to one pot three component method may
be due to inhomogeneous mixing of the catalyst under solvent free
conditions. From the literature it is understood that Bi(III)
compounds can be used for various oxidative reactions including
aromatization reactions.18 Thus we also presume that the
conversion of 4 to 5 takes place via a radical mechanism involving
Bi(III)/Bi(0).
It is interesting to note that, the CFDQs polycyclic
heterocycle fluorophores (4) becomes less fluorescent and in
most cases non-fluorescent when converted to their
corresponding CFQs analogues (5) (see Supporting
Information, Table 4, 5e-5q). A representative picture of 4j
and 5j in DMSO under the influence of UV at 366 nm is
Photophysical Properties
0.10
In recent time, search for organic molecules with high
quantum yield has been the subject of intense study owing to
their demands for organic light-emitting diodes (OLED),
biological markers, functional organic devices and sensors,
organic rectifiers as well as in dyes.19 Fluorophores embedded
with donor-acceptor that connected to a rigid π-system
DMSO
MeOH
CH3CN
DCM
THF
CHCl3
0.05
believes to prevent non-radiative decay.20 CFDQs (
4) bearing
an electron withdrawing group at 3-position possess such
structural features. Considering these features we were
interested to see the optical behaviour of the synthesized
CFDQs containing D-π-A (Donar-π system-Acceptor) push
pull system.
0.00
350
400
Initially, UV-Vis and fluorescence behaviour of compound
4j was investigated at room temperature in different polar
protic and aprotic solvents such as DMSO, THF, DCM,
CH3CN, MeOH and CHCl3 (Figures 3a and 3b, for details:
see Supporting Information) w.r.t. quinine sulphate
dihydrate21, interestingly we observed very good quantum
yield (Øf = 0.65) in DMSO. Because of solubility problem we
Wavelength (nm)
Figure 3a UV-Vis spectra of compound 4j in different
solvents (10-5 M; 25 oC)
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Page 7 of 9
Journal Name
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same combination under solvent-free and conventional
heating conditions provides coumarin fused quininolines (
5
)
View Article Online
in one pot. Alternatively, coumarin fuDseOdI: 1q0u.1i0n3o9l/iCne4Ns J500h6a3v0Ee
also been synthesized using N-bromosuccinamide as an
oxidizing agent at room temperature. We also have developed
1.0
0.8
0.6
0.4
0.2
0.0
DMSO
MeOH
CH3CN
DCM
THF
CHCl3
a
new route for the synthesis of substituted 3-
quinolinecarboxylic acid derivatives in a two step process by
hydrolysis of the coumarin ring followed by simultaneous
aerobic oxidation of 4. The fluorescence property studies of
the synthesized coumarin fused tetracyclic heterocycles in
different solvents shows that some of the fused
dihydroquinolines (
4
)
are highly fluorescent with good
quantum yields that may become a promising fluorescent
probe. A comparative study on fluorescent property for some
of the
4 with its analogues showed that 4 are more fluorescent
400
450
500
550
than the corresponding 5.
Wavelength (nm)
Figure 3b Fluorescence Spectra of compound 4j in different
solvents [10-5M; 25 oC; slit = 1/1]
Experimental
Methods and materials
.
All reagents were used without further purification and
procured from the commercial sources. Microwave irradiation
was carried out with Initiator 2.5 Microwave Synthesizers
from Biotage, Uppsala, Sweden. Shimadzu FTIR
spectrophotometer was used for recording IR spectra. 1H
NMR and 13C NMR spectra were recorded on a Jeol 500,
Varian 400 and Bruker 300/400/500 MHz spectrometers in
CDCl3 and DMSO-d6 using TMS as internal reference.
Elemental analyses were carried out in a Perkin Elmer 2400
automatic CHN analyzer or Elementer Vario EL III. X-ray
crystallographic analysis was performed with a Siemens
Figure 4 CFDQ (4j) and CFQ (5j) in DMSO[10-5M] at UV
366 nm.
shown in the Figure 4. This clearly indicates that the
fluorescence intensity shrink in case of aromatized CFQs.
Form the table 4, we also observed that both a highest stoke’s
shift of about 10094 in CHCl3 and a lowest stoke’s shift of
about 2300 in THF was observed for 4s.
SMART CCD and
a Siemens P4 diffractometer. All
compounds were characterized by their melting points, 1H
NMR and 13C NMR spectra and elemental analysis. The UV-
Vis absorption spectra were recorded on Shimadzu UV-Vis
spectrophotometer UV-2550 and fluorescence spectra was
The absorption maxima, emission maxima and
fluorescence quantum yield depends on various factors such
as structure of the molecule, nature of the solvent, probe-
probe interaction, probe-solvent interaction, temperature, pH
and concentration etc.22 In this investigation we have
observed that fluorescence quantum yield of these types of
coumarin fused polycyclic heterocycles are dependent on the
types of the substituent groups as well as solvent medium
used. Considering the above behaviours, we believe that these
coumarin fused polycyclic heterocycles may find some
recorded
at
Horiba
Jobin
Yuon
fluoromax-4
spectrofluorometer.
General procedure for the synthesis of CFDQ (4).
A mixture of aldehyde (0.5 mmol), aromatic amine (0.5
mmol), 4-hydroxycoumarin (0.5 mmol) and Bi(OTf)3 (0.05
mmol) in water (1.0 ml) was taken in a sealed 0.5-2.0 ml vial
containing a Teflon coated magnetic stirring bar and was
o
irradiated at 130 C for an appropriate time mentioned in the
potential application as
luminescence material.
a new fluorescent probes or
table 2, using a microwave reactor. The resulting mixture was
cool down to 50 C by air flow. The water was decanted and
o
1-2 ml glacial acetic acid was added to the reaction mixture
and stirred for 5 min to obtain the precipitate. The solid
precipitate was filtered under suction and dried. The obtained
solid was found pure enough for further characterization.
Conclusions
In conclusion, the present work describes an efficient one-pot
multicomponent strategy for the synthesis of coumarin fused
dihydroquinolines
(
4
)
from the reaction of 4-
General procedure for the synthesis of CFQ (5).
Method-A (one-pot neat condition)
A mixture of aldehyde (1.0 mmol), aromatic amine (1.0
mmol), 4-hydroxycoumarin (1.0 mmol) and Bi(OTf)3 (0.1
hydroxycoumarin, aldehydes and aromatic amines using an
environmentally benign readily available bismuthtriflate as a
catalyst in water medium under microwave irradiation. The
This journal is © The Royal Society of Chemistry 2012
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New Journal of Chemistry
Page 8 of 9
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mmol) was taken in a 10 ml round bottom flask fitted with a *Corresponding author. Tel.: +91 612 2552038; Fax: +91 612
reflux condenser in an open air and was heated at 140 oC. The 2277383
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progress of the reaction was monitored by TLC. After E-mail address: lokman@iitp.ac.in
completion of the reaction, reaction mixture was cooled down
DOI: 10.1039/C4NJ00630E
Electronic Supplementary Information (ESI) available:
†
to room temperature. To this mixture 1-2 ml glacial acetic [Experimental general, UV-Vis and Fluorescence data,
1
acid was added and stirred to obtain the precipitate. The solid spectroscopic data for all compounds, scanned H NMR and
precipitate was filtered and washed with methanol under 13C NMR spectra of all compounds]. See DOI:
suction and dried. The crude product was dissolved in 20 ml 10.1039/b000000x/
dichloromethane and aqueous workup was carried out using
0.05N NaOH solution to remove the by-product biscoumarin. 1 (
Finally the compounds were purified by recrystallization from Soc. Rev. 2013, 42, 4948; (
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Acknowledgments
8 (a) Z. Chen, W. Su, J. Bi, X. Ye, Z. S. Faming, 2012, CN
102584841 A 20120718; (b) Z. Chen, J. Bi, W. Su, Chin. J.
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Authors are grateful to the Department of Science and
Technology, India for the financial support with Sanction No.
SR/FT/CS-042/2009 and IIT Patna for carrying out this work.
M.N.K. and S.K are thankful to CSIR New Delhi, for their
Senior Research Fellowships. S.P. is thankful to UGC for
SRF. We are also grateful to Bose Institute Kolkata, IIT
Kanpur and SAIF-Panjab University Chandigarh for
providing analytical facilities. SAIF-IIT Madras is gratefully
acknowledged for single crystal X-ray diffraction studies.
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Department of Chemistry, Indian Institute of Technology
Patna, Bihar-800013, India
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