Straightforward synthesis of photoactive chalcogen functionalized benzimidazo[1,2-a] quinolines

Article abstract of DOI:10.1039/c9nj01948k

A series of new organochalcogen derivatives of benzimidazo[1,2-a]quinolines were synthesized in moderate to excellent yields and in short reaction times from chalcogen benzimidazoles, in a straightforward synthetic procedure, through transition-metal-free cascade reactions involving a sequential intermolecular aromatic nucleophilic substitution (S_NAr), followed by an intramolecular Knoevenagel condensation. Both the sulfur and selenium derivatives presented similar photophysical properties, with absorption maxima located in the UV region (～355 nm) related to spin and symmetry allowed electronic p-p? transitions, and fluorescence emission located in the violet-blue region (～440 nm) with a relatively large Stokes shift (～90 nm). The fluorescence quantum yields were slightly influenced by the chalcogen, with the sulfur derivatives presenting higher values than the selenium analogues, probably due to the intersystem crossing allowed by the selenium atom. Moreover no clear evidence for charge transfer in either compound in the ground and excited states was observed.

Full text of DOI:10.1039/c9nj01948k

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Straightforward Synthesis of Photoactive Chalcogen
Functionalized Benzimidazo[1,2-a]quinolines
Rodrigo Borges da Silva,a Felipe Lange Coelho,a Fabiano Severo Rodembusch,a Ricardo Samuel
Schwab,b Juliana Maria Forain Miolo Schneider,c Daniel da Silveira Rampond and Paulo Henrique
Schneider*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A series of new organochalcogen derivatives of benzimidazo[1,2-a]quinolines were synthesized in moderate to excellent
yields and in short reaction times from chalcogen benzimidazoles, in a straightforward synthetic procedure, through
transition-metal-free cascade reactions involving a sequential intermolecular aromatic nucleophilic substitution (SNAr),
followed by an intramolecular Knoevenagel condensation. Both sulfur and selenium derivatives presented similar
photophysical properties, with absorption maxima located in the UV region (355 nm) related to spin and symmetry
allowed electronic p-p* transitions, and fluorescence emission located in the violet-blue region (440 nm) with relative
large Stokes shift (~90 nm). The fluorescence quantum yields were slightly influenced by the chalcogen, with the sulfur
derivatives presenting higher values than the selenium analogues, probably due to the intersystem crossing allowed by the
selenium atom. Moreover any clear evidence for charge transfer in either compound in the ground and excited states was
observed.
H
O
N
N
NH
Introduction
N
N
N
Heterocyclic compounds containing nitrogen-atoms are found
in many bioactive natural products and pharmaceuticals,
representing important “privileged structures”.1-4 Substituted
benzimidazoles are privileged heterocyclic systems because of
their reactivities, notable chemical properties, and biological
activities. Additionally, their azino-fused derivatives display a
broad spectrum of biological functions such as antiviral,
anticancer, antibacterial and antifungal, etc.5-9 Among fused
benzimidazoles, some benzimidazo[1,2-a]quinolines have been
recently reported to have interesting biological and
N
N
N
N
O
N
H
CN
Antifungal activity
Antimicrobial activity
Antitumor activity
Figure 1. Examples of biologically active benzimidazo[1,2-a]quinolines.
obtaining these compounds. Consequently, the development
of a simple and direct methodology for the synthesis of these
privileged structures, in which a variety of substituents at
different positions can be introduced, remains a significant
challenge in heterocyclic chemistry. The traditional methods
for the synthesis of substituted benzimidazo[1,2-a]quinolines
generally involves an inconvenient multistep synthesis with
the use of a metal catalyst as well as ligands and additives.13-16
Additionally, interest in the chemistry and application of
different selenium-containing compounds as potential
pharmaceuticals,17-21 new materials,22-24 ionic liquids25-28 and
catalysts29-32 has expanded rapidly during the last years. For
instance, the biological and medicinal properties of
organochalcogenides have gained increasing interest, which is
mainly due to their antioxidant,33-36 anti-inflammatory,37-39
anti-HIV40 activities among others. In the same context,
heterocyclic compounds such as substituted benzimidazo[1,2-
a]quinoline derivatives comprise an interesting class of
molecules and they possess interesting electro-optical
properties. Their charge transport capability makes them
attractive candidates for organic light-emitting diodes
(OLEDs).41,42 Align to this fact, chalcogen derivatives have been
pharmacological
activities,
such
as
antimicrobial,10
antifungal,10 antitumor,11,12 among others (Figure 1).
Despite the importance of these compounds, there are
only few reports that merge together a study concerning the
structure-activity relationships of substituted benzimidazo[1,2-
a]quinolines. In fact, this may be due to the difficulty in
a. Instituto de Química, Departamento de Química Orgânica, Universidade Federal
do Rio Grande do Sul, UFRGS, Av. Bento Gonçalves, 9500, CEP 91501-970, Porto
Alegre, RS, Brazil. E-mail: paulos@iq.ufrgs.br
b. Departamento de Química, Universidade Federal de São Carlos – UFSCar, Rodovia
Washington Luís, km 235 - SP-310, São Carlos, São Paulo, 13565-905, Brazil.
c. Departamento de Farmacociências, Universidade Federal de Ciências da Saúde de
Porto Alegre (UFCSPA). Rua Sarmento Leite, 245 - Porto Alegre, Rio Grande do
Sul, Brasil - CEP 90050-170
d. Laboratory of Polymers and Molecular Catalysis (LAPOCA), Department of
Chemistry, Federal University of Paraná–UFPR, P. O. Box 19032, Curitiba, PR,
81531-990, Brazil
† Electronic Supplementary Information (ESI) available: Experimental procedures,
characterization data. See DOI: 10.1039/x0xx00000xAddress here.
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Table 1. Synthesis of chalcogen 1H-benzimidazoles 5a-k.a
intensively studied in the development of organic materials
with technological interest.43-49
View Article Online
DOI: 10.1039/C9NJ01948K
H
H
N
N
(4)
RYYR , NaBH4
In this way, taking into account the biological and
technological roles of organochalcogen compounds and a
broad spectrum of fused benzimidazole properties, the
unification of these two moieties might result in the
construction of novel compounds with improved activities.
With these criteria in mind, and in consonance with our
continued interest in the synthesis of organoselenium
compounds,50-53 we designed a selenium-containing precursor
(5), for an efficient approach, with the formation of two new
bonds, for the synthesis of benzimidazo[1,2-a]quinolines
containing organochalcogens. To the best of our knowledge,
this is the first report of the synthesis of these chalcogen-
functionalized fused heterocycles. The cascade process
proceeded through an initial intermolecular aromatic
nucleophilic substitution (SNAr) of chalcogen benzimidazoles 5
with substituted 2-fluorobenzaldehydes 6, followed by the
intramolecular Knoevenagel condensation, first described by
Yokomatsu and co-workers (Scheme 1).54 In addition, we also
dedicate our efforts to study experimentally the photophysics
of these compounds in the ground and excited states by UV-
Vis, and fluorescence emissions spectroscopies, aiming to
better understand the deactivation channels in these
compounds.
N
Br
THF/EtOH
reflux, 24 h
N
Y
R
3
5a-k
Diorganyl dichalcogenides
Product
Entry
4
(RY)2
5
Yield (%)b
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
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30
31
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41
42
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44
45
46
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50
51
52
53
54
55
56
57
58
59
60
1
2
4a
4b
4c
4d
4e
4f
(PhSe)2
(4-MePhSe)2
(4-MeOPhSe)2
(2-MeOPhSe)2
(4-ClPhSe)2
(3-CF3PhSe)2
(2,4,6-MePhSe)2
(BuSe)2
5a
5b
5c
5d
5e
5f
81
54
44
58
60
58
52
68
43
62
69
3
4
5
6
7
4g
4h
4i
5g
5h
5i
8
9
(PhS)2
10
11
4j
(4-MeOPhS)2
(3-CF3PhS)2
5j
4k
5k
a
All reactions were performed in the presence of 2-(bromomethyl)-1H-
benzo[d]imidazole 3 (1.0 mmol), diorganyl dichalcogenides 4 (0.5 mmol) and
THF/EtOH (3:1) under nitrogen atmosphere. b Isolated yields.
The reaction was tolerant to a variety of electron-donating
and electron-withdrawing substituents at the aromatic ring of
the diaryl diselenides, allowing for the preparation of a series
of selanyl-1H-benzimidazoles 5a-f in moderate and good yields
(entries 1-6). Even when the sterically hindered dimesityl
diselenide 4g was applied, a good yield was obtained and the
product 5g was obtained in 52 % yield (entry 7). We could also
prepare an analogous compound with an aliphatic chain,
through the reaction with dibutyl diselenide 4h, under the
standard reaction conditions, leading to the formation of the
expected product 5h in moderate yield (entry 8). The reaction
is also efficient with a sulfur nucleophile, which results in the
thio-1H-benzimidazoles 5i-k in good yields (entries 9-11). With
this variety of chalcogen-1H-benzimidazoles 5a-k, we turned
our attention toward the SNAr/Knoevenagel cyclization domino
Results and discussion
Synthesis
As the starting point of this study, we focused on an
efficient way to prepare the precursors, chalcogen 1H-
benzimidazoles 5a-k (Table 1). This was conveniently achieved
in a short synthetic sequence involving the introduction of the
respective organochalcogen moiety in the 2-(bromomethyl)-
1H-benzo[d]imidazole 3 framework, through the reaction with
a nucleophilic organyl chalcogenolate. Thus, the nucleophilic
organyl chalcogenolates were generated in situ from the
corresponding diorganyl dichalcogenides 4a-k by reduction
with NaBH4.
reaction,
using
2-[(phenylselanyl)methyl]-1H-benzo[d]
imidazole 5a and 2-fluorobenzaldehyde 6a as model substrates
to optimize the reaction conditions (Table 2), in the presence
of Cs2CO3 in DMF.
O
H
N
Br
HO
NH2
NH2
N
Under these reaction conditions, the desired product 7a
was obtained in 76% yield (entry 1) after 8h at 120oC.
Increasing the reaction time did not improve the reaction
yields (entries 2-3). When the amount of 2-
fluorobenzaldehyde 6a was reduced from 1.2 mmol to 1.0
mmol, a decrease in the yield of product 7a was observed
(entry 4). We next evaluated the effect of the base for this
cascade reaction, and in order to accomplish that, five
reactions were performed in the presence of different bases,
such as Et3N, DBU, K2CO3, K2HPO4 and Na2CO3 (entries 5-9).
However, all tested bases afforded inferior yields when
compared to Cs2CO3 (entry 9). Different solvents were also
investigated in this domino reaction. When the reaction was
2
4
RYYR (
)
N
Y
R
N
H
Br
HCl (4 mol.L-1
7.5 h
)
Y = S, Se
3
5
1
O
F
H
R1
6
N
Y
R
N
R1
7
Scheme 1. Synthesis of substituted benzimidazo[1,2-a]quinolines 7.
2 | J. Name., 2012, 00, 1-3
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Table 2. Optimization of the metal-free cascade synthesis of organochalcogen
resulted from the formation of significant amounts of by-
products. We also prove the generality of our method, and the
View Article Online
DOI: 10.1039/C9NJ01948K
derivatives.a
reaction
between
2-((phenylthio)methyl)-1H-
Reaction
Conditions
N
N
F
O
SePh
H
N
benzo[d]imidazole 5i and 2-fluorobenzaldehydes bearing
electron-donating or withdrawing substituents worked well
under the optimal conditions, leading to the formation of the
desired products 7f-h in excellent yield (entries 6-8).
H
+
N
SePh
5a
6a
7a
Entry
Base
Solvent
Temp (°C)
Time (h)
Yield (%)b
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 3. Investigation on the scope of the 2-fluorobenzaldehydes.a
1
2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Et3N
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
120
120
120
120
120
120
120
120
120
120
80
8
24
48
8
76
74
H
N
F
O
N
N
YPh
Cs2CO3, DMF
80 °C, 8 h
3
77
H
+
N
YPh
4
66c
nrd
R1
1
5
8
R1
5
6
7
2
3
6
DBU
8
Trace
Entry
1H-benzimidazole
Aldehyde
Productb
7
K2CO3
8
69
nrd
nrd
nrd
N
SePh
F
O
H
N
8
KHPO4
Na2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
8
N
H
9
8
1
N
Se
5a
10
11
12
13
14
15
16
17
18
Toluene
MeCN
Ethanol
1,2-DCE
DMSO
DMF
8
6a
7a (77%)
8
Trace
nrd
N
N
SePh
80
8
F
O
H
N
80
8
Trace
60
H
6b
2
3
N
Se
120
140
80
8
5a
CF3
F
8
70
CF3
7b (73%)
DMF
8
77
N
N
SePh
H
DMF
80
4
68
76e
O
N
DMF
80
8
H
N
Se
Br
5a
6c
aAll reactions were carried out in the presence of 2-[(phenylselanyl)methyl]-1H-
benzo[d] imidazole 5a (1.0 mmol), 2-fluorobenzaldehyde 6a (1.2 mmol), and base
(3.0 mmol) in the indicated time and solvent (5 mL) unless otherwise stated.
bIsolated yield. c2-fluorobenzaldehyde 6a (1.0 mmol). dNo reaction. eCs2CO3 (4.0
mmol).
Br
7c (58%)
N
N
SePh
H
N
F
O
MeO
H
4
5
6
7
8
N
Se
MeO
5a
6d
carried out with Cs2CO3, upon switching the solvent from DMF
to toluene, acetonitrile, ethanol or 1,2-dichloroethane, the
desired product 7a was not observed or only traces were
formed (entries 10-13). On the other hand, the product was
also obtained in DMSO, albeit in moderate yield (entry 14).
The domino reaction is affected by the reaction temperature,
and after several experiments, we have established 80°C as the
ideal reaction temperature. Finally, reducing the reaction time
to 4 hours or increasing the amount of the base did not
improve the reaction yields (Table 2, entries 17 and 18). Based
on these results, the optimal conditions for the domino
reaction were with 3.0 eq. of Cs2CO3 in DMF at 80°C for 8h.
To explore the scope and limitation of this method, after
determining the optimal conditions, we explored first the
influence of the substituents on the 2-fluorobenzaldehydes
(Table 3). For this purpose, 2-[(phenylselanyl)methyl]-1H-
benzo[d] imidazole 5a was reacted with a variety of 2-
7d (58%)
N
N
SePh
H
N
F
O
F
H
N
Se
F
5a
6e
7e (31%)
N
N
SPh
H
N
F
O
H
N
S
5i
6b
CF3
CF3
7f (79%)
N
SPh
H
N
F
O
N
H
N
S
5i
Br
6c
Br
7g (85%)
N
SPh
H
F
O
N
N
fluorobenzaldehydes
6 bearing an electron-donating or
MeO
H
N
S
withdrawing substituent on the aromatic ring, affording the
corresponding 6-(phenylselanyl)benzimidazo[1,2-a]quinolines
7a-d in good yields (entries 1-4). However, only the 2-
fluorobenzaldehyde bearing the electron-withdrawing
substituent -F, was a surprisingly poor substrate, furnishing the
desired product 7e with low yield (entry 5). This low yield
MeO
5i
6d
7h (82%)
aAll reactions were carried out in the presence of 5a and 5i (1.0 mmol), aromatic
aldehydes 6 (1.2 mmol), and Cs2CO3 (3.0 mmol) in DMF (5 mL) at 80 °C. bIsolated
yield.
This journal is © The Royal Society of Chemistry 20xx
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The possibility of performing this domino reaction with
other chalcogen 1H-benzimidazoles 5b-k was also investigated,
as shown in Table 4. Thus, we examined the reaction of 2-
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4
5
6
7
8
Table 4. Investigation on the scope of the chalcogen 1H-benzimidazoles 5b-k.a
View Article Online
DOI: 10.1039/C9NJ01948K
H
N
F
O
N
N
YPh
Cs2CO3, DMF
+
H
80 °C, 8 h
N
YPh
fluorobenzaldehyde 6a with
a
variety of selanyl-1H-
Y= Se, S
R= aryl, alkyl
R1
7
benzimidazoles bearing electron-donating (–CH3 and –OCH3)
and electron withdrawing (-CF3 and -Cl) substituents, affording
the respective products 7i-r in moderate and good yields
(entries 1-6). Moreover, selanyl-1H-benzimidazoles 5h
containing an alkyl chain, also undergoes the desired
transformation as show for the formation of the desired
product 7o (entry 7). Due to the success obtained with the
5
6
Entry
1H-benzimidazole
Aldehyde
Productb
N
H
N
Se
9
F
O
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
H
N
Se
1
5b
5c
6a
7i (78%)
N
H
N
Se
OMe
F
O
preparation
of
the
6-(phenylselanyl)benzimidazo[1,2-
N
H
a]quinolines, we decided to extend our studies to thio-1H-
benzimidazoles, bearing a neutral, electron-donating and -
withdrawing substituents. By using our standard protocol, the
corresponding products 7p-r were obtained in good yield
(entries 8-10) The results revealed some influence of the
electronic effect on the chalcogen benzimidazo[1,2-
a]quinolines 7i-r. For example, the chalcogen benzimidazo[1,2-
a]quinolines bearing a neutral substituent 7a and 7p, gave
higher yields than chalcogen benzimidazo[1,2-a]quinolines
2
N
Se
OMe
6a
7j (42%)
H
N
N
Se
N
F
O
O
H
N
Se
MeO
5d
3
4
5
6
6a
7k (48%)
N
N
Se
Cl
H
N
F
O
bearing
electron-donating
and
electron-withdrawing
H
N
Se
Cl
5e
5f
substituents.
6a
7l (47%)
Photophysics
N
Se
H
N
F
O
N
The photophysical investigation of the chalcogen
functionalized benzimidazo[1,2-a]quinolines is shown in Figure
2. The relevant data obtained from this investigation are
summarized in Tables 5 and 6 for sulfur and selenium
derivatives, respectively. Figure 2 (a-d) presents the absorption
spectra of these compounds taking the chalcogen, the solvent
and the substituents into account. In this discussion,
compounds 7p and 7a were chosen as model for sulfur and
selenium derivatives, respectively. It is worth mentioning that
the additional compounds presented quite similar
photophysical behavior (data not shown, see supporting
information). It can be observed for both set of compounds,
sulfur and selenium analogues, a structured absorption spectra
with maxima located around 355 nm. The presence of vibronic
structure on the UV-Vis spectra suggests that these
compounds present upper potential energy curve appreciably
displaced horizontally, from the lower due to greater
equilibrium bond lengths because electronically excited states
usually have more antibonding character than electronic
ground states.55 The absorption spectra of compound 7p
(Figure 2a) show a wavenumber spacing of about 1382 cm-1,
where values around 1290 cm-1 can be found for compound 7a
(Figure 2c), similar to those found for some aromatic
hydrocarbons.56 This result indicates that the sulfur analogues
present higher energy values between the vibrational levels
than the selenium ones. Additionally, the intensity of the
vibronic structure of the absorption spectra indicates, for all
studied compounds, that the most probable electronic
transition is usually 01 and in few examples 02, but not at
all the pure electronic transition 00 (Figure 2b and 2d). This
last observation, the less probable transition ascribed as 00
CF3
N
H
Se
6a
CF3
7m (41%)
N
N
Se
H
N
F
O
H
N
Se
5g
6a
7n (78%)
N
Se
F
O
H
N
N
H
7
N
Se
6a
5h
7o (68%)
N
S
H
N
F
F
O
N
H
H
N
8
9
S
5i
6a
7p (65%)
N
S
OMe
O
H
N
N
N
S
S
OMe
6a
5j
7q (42%)
N
N
S
H
N
F
O
CF3
N
H
10
5k
CF3
6a
7r (45%)
aAll reactions were carried out in the presence of 1H-benzimidazoles 5b-k (1.0
mmol), 2-fluorobenzaldehyde 6a (1.2 mmol), and Cs2CO3 (3.0 mmol) in DMF (5
mL) at 80 °C for 8 h. bIsolated yield.
indicates that, for these compounds the internuclear distances
in the ground and excited states are not equal. Most probable
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-1
electronic transitions ascribed as 01 or 02 indicates that  values for all studied compounds (104 M-1·cm ), as well as
View Article Online
8
the excited electronic state presents
a
larger nuclear the calculated radiative rate constant (10DOs-I1:)10in.1d0i3c9a/tCe9NspJ0in19a4n8dK
1
separation than in the ground state. In addition, it can also be symmetry allowed - * electronic transitions, that usually
observed that the solvent seems do not influence the ranges values to e (102-106 M-1·cm-1) and ke (105-109 s-1). The
0
0
absorption maxima location, where an almost absent pure radiative lifetime (t0) was also obtained as 1/ke , with
solvatochromism is observed (Figure 2a and 2c). Similarly, the similar magnitude (ns) for all compounds, indicating that after
chalcogen also seems not to play a significant role on the radiation
absorption
the
chalcogen
functionalized
ground state properties of these compounds (Figure 2b and benzimidazo[1,2-a]quinolines populate the same excited state.
2d). On the other hand, the substituents presented a more
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significant influence on the location of the absorption maxima
Table 5. Photophysical data of sulfur functionalized benzimidazo[1,2-a]quinolines,
of the sulfur containing compounds than the selenium
where  is the molar extinction coefficient (x104 M-1·cm-1), abs and em are the
analogues (Tables 5 and 6).
absorption and emission maxima (nm), ST is the Stokes shift (nm/cm-1), and FL is the
0
The photophysical data in the ground state also allowed
total quantum yield (%), fe is the calculated oscillator strength, ke is the calculated
radiative rate constant (108 s-1) and 0 is the calculated pure radiative lifetime (ns).
obtaining the oscillator strength (fe) and the radiative rate
0
0
#
Solvent
abs

em
ST
FL
fe
ke
0
constant for emission (ke ) applying the well-known Strickler-
Berg equation (Equation 1).57
1,4-Dioxane 354 1.87 446 92/5827 1.1 0.276 2.20 4.54
DCM
353 1.64 450 97/6106 0.9 0.231 1.85 5.40
350 1.45 465 115/7066 0.4 0.281 2.29 4.36
푓푒 = 4.32 × 10 ―9∫휀(푣)푑푣,
(Equation 1)
7f
Ethanol
Acetonitrile 351 1.19 452 101/6366 0.3 0.196 1.59 6.30
PBS 361 1.30 450 89/5479 4.2 0.279 2.14 4.68
1,4-Dioxane 358 0.75 445 87/5461 3.4 0.105 0.82 12.20
In Equation (1), the integral is the area under the
absorption curve, which corresponds to a single electron
oscillator. Equally, the radiative rate constant for emission can
be related to the extinction coefficient for absorption from
Equation (2).58
DCM
358 0.91 445 87/5461 2.9 0.131 1.03 9.75
356 1.01 450 94/5868 0.8 0.125 0.99 10.11
7g
7p
7r
Ethanol
푘0푒 ≈ 2.88 × 10 ―9푣2∫휀(푣)푑푣
, (Equation 2)
0
Acetonitrile 356 1.17 450 94/5868 0.3 0.167 1.32 7.58
PBS 366 1.20 455 89/5344 2.1 0.279 2.08 4.81
1,4-Dioxane 353 1.57 439 86/5550 7.2 0.238 1.91 5.25
DCM
352 1.63 440 88/5682 5.3 0.267 2.15 4.65
350 1.32 450 100/6349 1.3 0.228 1.86 5.37
Ethanol
Acetonitrile 350 1.23 440 90/5844 2.1 0.209 1.70 5.87
PBS 361 0.95 448 87/5379 3.6 0.183 1.41 7.10
1,4-Dioxane 352 1.22 442 90/5785 4.2 0.242 1.95 5.13
DCM
352 1.19 440 88/5682 3.9 0.209 1.69 5.93
350 0.74 437 87/5688 2.5 0.142 1.16 8.60
Ethanol
Acetonitrile 350 0.81 450 100/6349 1.7 0.136 1.11 9.02
PBS 361 0.47 455 94/5723 2.5 0.099 0.76 13.10
The normalized fluorescence emission spectra of the
chalcogen functionalized benzimidazo[1,2-a]quinolines are
shown in Figure 3. The emission curves were obtained by
exciting the compounds at the respective absorption maxima
wavelengths (abs). The data from fluorescence emission
spectroscopy are also summarized in Tables 5 and 6.
Despite the vibronic structure on the UV-Vis spectra, the
fluorescence spectroscopy presents broad structureless
emission spectra, with maxima located in the violet-blue
region with relative large Stokes shift (Figure 3). The absence
of the mirror effect in these compounds indicates that the
energy spacing between the vibrational levels and the Franck-
Condon factors are different in S0 and S1.Error! Bookmark not
defined. Once again, changes on the chalcogen seem do not
affect the photophysics of these compounds, since quite
Figure 2. UV-Vis absorption spectra of (a) sulfur derivative 7p in different organic
solvents (10-5 M), (b) sulfur containing compounds in dichloromethane (10-5 M), (c)
selenium derivative 7a in different organic solvents (10-5 M) and (d) selenium
containing compounds in dichloromethane (10-5 M).
From the Strickler–Berg relation, values for the oscillator
strength, fe ranges 0.087-0.349 (Table 5), which corroborates
with electronic dipole-allowed transitions, as expected (fe10-
3-1).59 Moreover, the obtained molar absorptivity coefficient
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similar emission maxima location was observed for all
compounds. Although the emission maxima changes
depending on the solvent, any clear tendency was observed,
discarding a solvatochromic effect in redshifted emission if
compared to other solvents, which can be associated to
specific interactions afforded by this solvent with the
fluorophore, lowering its excited state energy.60 The studied
compounds, even containing fused aromatic rings, which
provide significant structural rigidity, present relatively low
fluorescence quantum yield (FL) values (Tables 5 and 6).
View Article Online
DOI: 10.1039/C9NJ01948K
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Table 6. Photophysical data of selenium functionalized benzimidazo[1,2-a]quinolines,
where  is the molar extinction coefficient (x104 M-1·cm-1), abs and em are the
absorption and emission maxima (nm), ST is the Stokes shift (nm/cm-1), and FL is the
0
total quantum yield (%), fe is the calculated oscillator strength, ke is the calculated
radiative rate constant (108 s-1) and 0 is the calculated pure radiative lifetime (ns).
0
#
Solvent
fe
ke
abs
em ST FL
0

1,4-Dioxane 354 1.27 438 84 0.28 0.192 1.53 6.53
DCM
Ethanol
Acetonitrile
PBS
354 2.03 440 86 0.12 0.301 2.40 4.16
352 0.74 470 118 0.88 0.116 0.93 10.71
352 1.17 450 98 0.16 0.162 1.30 7.67
365 1.08 443 78 0.91 0.232 1.75 5.73
7a
1,4-Dioxane 354 1.10 445 91 0.26 0.180 1.43 6.98
DCM
Ethanol
Acetonitrile
PBS
354 1.63 445 91 0.17 0.239 1.91 5.23
352 0.92 455 103 0.58 0.123 0.99 10.08
352 1.24 440 88 0.12 0.167 1.35 7.42
365 0.95 446 81 0.48 0.195 1.46 6.84
7b
7c
7i
Figure 3. Fluorescence emission spectra of (a) sulfur derivative 7a in different organic
solvents (10-5 M), (b) sulfur containing compounds in dichloromethane (10-5 M), (c)
selenium derivative 7p in different organic solvents (10-5 M) and (d) selenium
containing compounds in dichloromethane (10-5 M).
1,4-Dioxane 360 0.70 444 84 0.37 0.118 0.91 10.96
DCM
Ethanol
Acetonitrile
PBS
359 1.97 445 86 0.12 0.266 2.07 4.84
357 0.77 445 88 0.28 0.118 0.93 10.77
357 1.23 442 85 0.10 0.168 1.32 7.60
370 0.77 453 83 0.85 0.153 1.12 8.95
The results from the two sets of compounds (S and Se) may
be probably related to triplet state population via intersystem
crossing (ISC) after radiation absorption. In this sense, this
pathway disfavors the deactivation between states of the
same multiplicity or even photoinduced electron transfer (PET)
that can take place from the organoyl selenide group to the
quinoline moiety. In addition, it can be observed that the
sulfur based compounds showed slightly higher FL values than
the selenium analogues. In this context, it is believed that spin-
orbit coupling is even more favored for selenium derivatives
due to the electronic characteristics of this chalcogen.
In order to exploit the obtained low fluorescence quantum
yield values, mainly for the substituted quinolines, an
additional experiment based on the selenium oxidation was
performed. In this sense, the photophysical behaviour in the
excited state of a model compound 7a bearing a phenyl
bonded to the chalcogen, was investigated in presence of an
oxidizing agent. It could be observed that right after addition
of 20 equiv. of benzoyl peroxide to a solution of 7a (10-5 M)
any change was observed in the fluorescence emission spectra
(Figure 4). However, an increase in fluorescence intensity was
observed over time, starting after 5 minutes and reaching 5
times the initial intensity value after 210 minutes. It is worth
mentioning that at this time range (210 minutes) the UV-Vis
spectra presented quite the same profile, suggesting that any
chemical transformation occurred in the fluorophore. In this
way, the observed changes on the fluorescence intensity after
addition of benzoyl peroxide can probably be related to
1,4-Dioxane 354 1.02 445 91 0.32 0.154 1.23 8.11
DCM
Ethanol
Acetonitrile
PBS
354 1.11 445 91 0.19 0.167 1.33 7.51
352 1.03 464 112 1.07 0.141 1.14 8.79
352 1.01 447 95 0.17 0.142 1.14 8.74
363 0.60 443 80 0.79 0.121 0.92 10.88
1,4-Dioxane 354 1.54 435 81 0.45 0.226 1.80 5.54
DCM
Ethanol
Acetonitrile
PBS
354 1.85 440 86 0.23 0.310 2.48 4.04
352 1.13 455 103 0.62 0.166 1.34 7.48
352 1.20 442 90 0.22 0.182 1.47 6.81
366 0.77 445 79 0.63 0.183 1.37 7.32
7k
7l
1,4-Dioxane 354 1.28 440 86 0.40 0.182 1.45 6.88
DCM
Ethanol
Acetonitrile
PBS
354 1.84 445 91 0.23 0.279 2.23 4.49
352 0.71 455 103 0.45 0.108 0.87 11.44
352 1.03 442 90 0.33 0.144 1.16 8.61
362 0.67 440 78 0.53 0.115 0.88 11.36
1,4-Dioxane 354 1.03 425 71 0.59 0.139 1.11 8.99
DCM
Ethanol
Acetonitrile
PBS
354 2.67 425 71 0.17 0.349 2.79 3.59
352 1.07 435 83 0.36 0.125 1.01 9.93
352 1.28 420 68 0.15 0.160 1.29 7.73
362 1.03 430 68 0.95 0.199 1.52 6.59
7n
7o
1,4-Dioxane 353 1.16 440 87 0.71 0.182 1.46 6.85
DCM
Ethanol
Acetonitrile
PBS
354 2.43 425 71 0.46 0.393 3.14 3.19
352 0.69 458 106 3.41 0.097 0.78 12.78
352 1.16 425 73 0.30 0.144 1.16 8.62
362 0.52 436 74 0.35 0.087 0.66 15.06
6 | J. Name., 2012, 00, 1-3
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deactivation of fluorescence quenching mechanisms related to
ARTICLE
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General procedure for preparation of chalcogen 1H-
benzimidazoles 5a-k.
View Article Online
DOI: 10.1039/C9NJ01948K
the chalcogen atom since the oxidation of selenium and the
deactivation of photoinduced electron transfer (PET) process
have already been determined in selenium containing BODIPY
derivatives.61-63 Based on these results, the synthesized
selenium-quinolines present potential application for peroxide
sensing in solution. In order to confirm our hypothesis, a
control experiment was performed. Compound 7a was
oxidized with MCPBA, and the product was analyzed by 77Se
NMR; we could clearly observe the oxidation product
ArSe(O)Ph (data not shown, see supporting information).
Under an argon atmosphere, sodium borohydride (0.028 g,
0.75 mmol,) was added to a solution of the diorganyl
dichalcogenides (4) (0.5 mmol) in THF (7.5 mL). EtOH (2.5 mL)
was then dropwise added and the clear solution formed was
stirred at room temperature for 20 min. After this time a
9
solution of the 2-(bromomethyl)-1H-benzo[d]imidazole
3
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(0.211 g, 1.0 mmol) in THF was added dropwise, and the
reaction mixture was heated at reflux for 24 h. The solution
was washed with NH4Cl(aq.) (2 x 30 mL) and extracted with
CH2Cl2 (3 x 20 mL). The combined organic layers were dried
over MgSO4, filtered, and concentrated under vacuo. The
crude product was purified by silica gel chromatography
(eluent: hexane/ethyl acetate).
General
procedure
for
the
preparation
of
6-
(phenylselenyl)benzo[4,5] imidazo[1,2-a]quinoline 7a-r.
A mixture of 2-fluorobenzaldehyde 6a (0.148 g, 1.2 mmol), 2-
[(phenylselenyl)methyl]-1H-benzo[d]imidazole 5a (0.287 g, 1.0
mmol), and Cs2CO3 (0.325g, 3.0 mmol) in DMF (5.0 mL) was
stirred at 80 °C for 8 h. After the end of the reaction, the
mixture was cooled to room temperature and diluted with
water. The resulting mixture was extracted with ethyl acetate.
The combined organic layer was washed with water, dried
over MgSO4 and the solvent was removed under vacuo. The
residue was purified by silica gel chromatography (eluent:
Figure 4. (a) UV-Vis and (b) fluorescence emission spectra of compound 7a (10-5 M) in
presence of benzoyl peroxide (10-5 M) observed at different time (0-210 minutes).
hexane/ethyl
acetate
=
9/1)
to
afford
6-
(phenylselenyl)benzo[4,5]imidazo[1,2-a]quinoline 7a in 77 %
Conclusions
yield.
In summary, we report an efficient way to prepare a wide
range of substituted chalcogen-1H-benzimidazoles 5a-k. The
products were obtained in good to excellent yields, making
them suitable for the synthesis of more complex structures. In
this way, we provided a simple and efficient method for the
synthesis of wide range of substituted chalcogen-
benzimidazo[1,2-a]quinolines 7a-s, without using any
transition metal catalysts, through a cascade reaction between
the substituted chalcogen-1H-benzimidazoles 5a-k and 2-
fluoroarylaldehydes 6 substrates. The corresponding products
were obtained in moderate to excellent yields and in a
relatively short reaction time. These compounds presented
absorption in the UV region related to spin and symmetry
allowed electronic -* transitions and fluorescence emission
located in the violet-blue regions with relative large Stokes
shift. The compounds did not show significant
solvatochromism in either the ground or the excited state.
Moreover, changes on the chalcogen seem not affect the
absorption or the emission maxima location. The fluorescence
quantum yields were slightly tailored by the chalcogen, with
the sulfur derivatives presenting higher values than the
selenium analogues, due to quenching mechanisms presented
by selenium. These properties were investigated showing that
a peroxide oxidation can enhance fluorescence emission and,
thus, extend the employment for other analytes sensoring.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We are grateful to Coordenação de Aperfeiçoamento de
Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001,
CNPq, INCT-CMN, FAPERGS and FAPESP (2013/06558-3) for
financial and technical support.
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DOI: 10.1039/C9NJ01948K
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Graphical Abstract