General and efficient one-pot synthesis of N-substituted 7-bromo-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-ones

Article abstract of DOI:10.1007/s10593-016-1856-0

[Figure not available: see fulltext.]A simple and general synthesis of a series of quinoline-based isoindolin-l-ones, namely N-substituted 7-bromo-2,3-dihydro-1H-pyrrolo-[3,4-b]quinolin-1-ones through a one-pot reaction of ethyl 6-bromo-2-(chloromethyl)qu

Full text of DOI:10.1007/s10593-016-1856-0

DOI 10.1007/s10593-016-1856-0
Chemistry of Heterocyclic Compounds 2016, 52(3), 200–205
General and efficient one-pot synthesis of N-substituted
7-bromo-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-ones
Yang Li1, Kai Li1, Wentao Gao1*
1 Institute of Superfine Chemicals, Bohai University,
Jinzhou, 121000, China; е-mail: bhuzh@163.com
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2016, 52(3), 200–205
Submitted January 29, 2016
Accepted March 31, 2016
O
Br
RNH2
N R
71–84%
N
O
AcOH
EtOH
R = Ar, Alk
Br
OEt
CH2Cl
O

N
N
H2N
NH2
n
Br
N
N
O
n
68–77%
N
Br
n = 2–4
A simple and general synthesis of a series of quinoline-based isoindolin-l-ones, namely N-substituted 7-bromo-2,3-dihydro-1H-pyrrolo-
[3,4-b]quinolin-1-ones through a one-pot reaction of ethyl 6-bromo-2-(chloromethyl)quinoline-3-carboxylate with various amines in
refluxing EtOH–AcOH (v/v, 10:1) solvent system was described. A mechanism involving consecutive Williamson-type reaction of the
2-chloromethyl group with amine followed by intramolecular C–N bond cyclization process is proposed.
Keywords: amine, isoindolin-l-one, quinoline, intramolecular cyclization, Williamson-type reaction.
Isoindolin-1-ones constitute an exceptional class of
structural motifs which have been found widely present in
natural products like cichorine1 and vitedoamine,2 and also
in pharmacologically important synthetic molecules such as
indoprofen3 and lenalidomide4 (Fig. 1). Moreover, this
benzolactam system is also used as important synthon to
access various drugs and natural products.5–7 Consequently
attention has been increasingly paid to the use of the
isoindolin-1-one molecular template for further modifi-
cation and functionalization by both organic and medicinal
chemists aiming to find new applications for these
compounds.8–10
On the other hand, functionalized quinolines and their
hetero-fused analogs represent an important class of
organic molecules that have attracted a great deal of
attention from synthetic as well as medicinal chemists.11,12
It is well established that bioactive heterocyclic compounds
when linked with quinoline moiety in fused or bonded
forms usually results in new hybrids with potent pharmaco-
logical properties.13,14 For example, Guo et al. have
recently found that rhodanine derivatives upon bearing a
quinoline moiety are interesting scaffolds for the develop-
ment of novel Gram-positive antibacterial agents.15 Very
recently, a review concerning the chemistry and biological
activity of heterocycle-fused quinolinone derivatives has
been published by Shiro et al.16
Thus, in light of the combination principles for drug
design,17 it would be of synthetic importance to construct
O
O
MeO
HO
HO
Me
NH
NH
OMe
Cichorine
OMe
OH
Vitedoamine A
O
Me
N
CO2H
Indoprofen
O
O
N
O
O
NH
N R
N
NH2
Lenalidomide
Title compound 1
Figure 1. Structures of isoindolin-1-one-containing molecules
and the title compound 1.
009-3122/16/52(3)-0200©2016 Springer Science+Business Media New York
200

Chemistry of Heterocyclic Compounds 2016, 52(3), 200–205
Scheme 1
O
RNH2
Br
5a–l
O
O
N
R
O
O
EtOH–AcOH
10:1 (v/v)
Cl
N
1a–l
Br
Br
OEt
OEt
TMSCl, DMF
100°C, 10 h
O
, 10 h
N
CH2Cl
NHAc
H2N
NH2
N
n
4
Br
3
N
N
O
n
5m–o
PEG-400
rt, 8 h
NBS
N
Br
O
1m–o
a R = Ph (79%), b R = 4-MeC6H4 (82%), c R = 4-EtC6H4 (75%), d R = 4-MeOC6H4 (84%),
e R = 4-(t-Bu)C6H4 (80%), f R = 4-FC6H4 (83%), g R = 4-ClC6H4 (77%), h R = 4-BrC6H4 (74%),
i R = H (71%), j R = Me (76%), k R = Et (82%), l R = CH2Ph (75%),
NHAc
2
m n = 2 (75%), n n = 3 (77%), o n = 4 (68%)
quinoline-based isoindolin-l-one derivatives 1 as shown in
Figure 1, wherein the benzene ring is replaced by quinoline
moiety. A literature survey revealed that there are several
examples reported concerning the synthesis of quinoline-
based isoindolin-l-one derivatives.18–20 For example, Anzini
et al. previously reported the synthesis of 4-phenyl-
quinoline-based isoindolin-l-one through the reaction of
ethyl 6-chloro-2-(chloromethyl)-4-phenylquinoline-3-carb-
oxylate with methylamine.18 In this regard, Cappelli et al.
described this type of synthesis involving the reaction of
ethyl 2-chloromethylquinoline-3-carboxylate with aniline
or 4-chloroaniline.19 Recently, Bose et al. also reported a
similar synthesis by using both S-phenylalaninol and
R-phenethylamine as substrates in refluxing acetonitrile.20
Although some achievements have been made, these
reports are of individual and scattered syntheses, and no
efforts have been made to develop a general synthetic
approach. As such, the development of a more general
method towards such compounds is of significant interest.
Thus, we wish to report a general synthesis of quinoline-
based isoindolin-l-one, namely, N-substituted 7-bromo-
2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-ones 1 through
the one-pot reaction of ethyl 6-chloro-2-(chloromethyl)-
quinoline-3-carboxylate with various amines.
We have been engaged in exploring the reactivity and
synthetic applications of 2-halomethylquinoline-3-carbox-
aldehyde derivatives as an ideal starting material for the
flexible synthesis of a large range of quinoline derivatives.
In recent papers we have reported on the reaction of
2-halomethylquinoline with phenols,21,22 salicylaldehy-
des,23 aromatic aldehydes,24 and quinolin-8-ols25 for the
synthesis of novel heterocycle-containing quinolines. Building
on the evolving expertise, we envisaged that reacting ethyl
6-bromo-2-(chloromethyl)quinoline-3-carboxylate (4) with
various amines 5 might produce the corresponding
quinoline-based isoindolin-l-one derivatives through a
cascade Williamson-type condensation reaction and
subsequent intramolecular C–N bond cyclization in a single
synthetic operation. Thus, according to that the first stage
in this strategy involved the preparation of the substrate 4,
which could be easily obtained via Friedländer annulation
reaction of N-(4-bromo-2-formylphenyl)acetamide (3) with
ethyl 4-chloro-3-oxobutanoate according to the method
described in the literature,26 using chlorotrimethylsilane
(TMSCl) as a promoter and water-acceptor agent (Scheme 1).
In our synthesis, the C-6 position of the quinoline ring was
occupied by a derivatizable bromo group in consideration
of the fact that the functional group could provide ample
opportunity for further synthetic manipulation, for example,
for cross-coupling reactions, and thus would make the
targeted products particularly appealing.
Subsequently, our attention was transferred to the reac-
tion of ethyl 6-bromo-2-(chloromethyl)quinoline-3-carboxy-
late (4) with a series of aromatic amines for building the
desired isoindolin-l-one system. At this stage, we first took
up the synthesis of 7-bromo-2-phenyl-2,3-dihydro-1H-pyrrolo-
[3,4-b]quinolin-1-one (1a). Our initial investigation was
conducted using ethanol as solvent in accordance with the
reaction conditions described in the literature.19 However,
the result was less satisfactory, and the expected pyrrolo-
[3,4-b]quinolin-1-one 1a was obtained in a moderate yield
of 61% (Table 1, entry 1). Accordingly, to further improve
the yield of this synthetic approach, various solvents were
Table 1. Reaction conditions and yields
of N-phenylpyrrolo[3,4-b]quinolin-1-one 1a*
Entry
Solvent
EtOH
Temperature, °C
Time, h
24
Yield, %
1
2
3
4
5
6
7
8
61
50
42
33
29
0


MeOH
CHCl3
24
24

DMF
85
85
24
Dioxane
H2O
24
24

Solvent-free
rt
3
0
EtOH–AcOH
(20:1, v/v)
10
67





9
EtOH–AcOH
(15:1, v/v)
10
10
12
24
74
79
67
44
10
11
12
EtOH–AcOH
(10:1, v/v)
EtOH–AcOH
(5:1, v/v)
EtOH–AcOH
(2:1, v/v)
* Reaction conditions: compound 4 (0.5 mmol), aniline 5a (0.5 mmol),
solvent (5 ml).
201

Chemistry of Heterocyclic Compounds 2016, 52(3), 200–205
Scheme 2
applied to promote this transformation. The results
summarized in Table 1 show that the choice of the solvent
was critical for this reaction. These attempts using MeOH,
CHCl3, DMF, THF, and dioxane as solvent were unfruitful,
and no further improvement of the yields was observed
(entries 2–5). Upon switching the solvent to H2O or solvent-
free conditions, no desired product was detected (entries 6, 7),
and the starting materials were recovered unchanged. After
many attempts, we were delight to find that the use of
EtOH–AcOH solvent system described in the literature27
afforded a significant amelioration in our synthesis (entry 9),
and the most striking yield (79%) was obtained when the
volume ratio of EtOH–AcOH was 10:1 (entry 10). Due to
the good yield obtained and in order to retain the simplicity
of the procedure, no further optimization in the reaction
conditions was necessary and the above-mentioned
conditions were chosen for the following work.
Thereafter, we investigated the scope and limitations by
extending the reaction to various aromatic amines 5b–h for
building differently substituted analogs as shown in
Scheme 1. Our results demonstrated that the reaction pro-
ceeded smoothly with aromatic amines and the expected
products 1b–h were obtained in good yields ranging from
74 to 84%. Moreover, in this series of reactions the effect
of substitution groups is not very strong; both the electron-
donating (e.g., Me, Et, OMe, t-Bu) and slightly electron-
withdrawing groups (e.g., F, Cl, Br) worked well, showing
little distinction. However, it is noteworthy that when a
strong electron-withdrawing groups such as NO2 and CN
were present, the reaction scarcely proceeded and the
desired product was detected in negligible amount that did
not warrant isolation. A possible reason is that the presence
of the strong electron-withdrawing group might render the
aromatic amines highly electron-deficient and thus retard
the reaction process.
To the best of our knowledge, all the newly synthesized
quinoline-based isoindolin-l-ones 1a–o have never been
reported and their structures were easily confirmed by their
spectroscopic and analytical data, which were in good
agreement with the compounds expected (see
Experimenta). The IR spectrum of compound 1a exhibited
the disappearance of the ester carbonyl group at 1711 cm–1,
and the appearance of the lactam C=O stretching frequency
at a decreased wave number of 1685 cm–1, which were
clear evidence for cyclization having occurred. The main
1
feature of the H NMR spectrum of compound 1a was the
presence of a singlet sharp line at 5.65 ppm, readily
recognizable as arising from methylene protons, supporting
the signal of its 13C NMR spectrum at 51.7 ppm. Moreover,
the presence of 9 aromatic protons in the range of the
aromatic region of 7.51–9.55 ppm exactly matches its
structure as well. Further, the structure assigned to
compound 1a was fully supported by its elemental analysis,
which established its molecular formula in accordance with
the suggested molecular structure. The other synthesized
compounds exhibited similar spectral characteristics,
except the substituents, which exhibited characteristic
signals with appropriate chemical shifts.
On the basis of the obtained results, a mechanistic pro-
posal portraying the probable sequence of events for the
formation of the title compounds 1 is outlined in Scheme 2.
The one-pot reaction might start with the nucleophilic
attack of amine 5 to 2-(chloromethyl)quinoline 4 to give
the intermediate A, which undergoes subsequent intramole-
cular nucleophilic cyclization in the presence of acetic acid
with participation of the nitrogen atom and the ester C=O
group to form a five-membered cyclic system B. At this
point, we reason that the presence of the catalytic amount
of acetic acid might play an important role in pushing the
cyclization reaction forward, though the detailed pathway
remains to be elucidated. Importantly, it is pertinent to note
that this type of acetic acid-promoted intramolecular
cyclization has been already reported by Hu et al.27,28 But
in both literatures no detailed mechanistic studies were
carried out to explain the catalytic activity of acetic acid,
and at the current stage there is no consensus of opinion
regarding the role of acetic acid. After this cyclization, the
elimination of an equivalent of EtOH led to the formation
of pyrrolo[3,4-b]quinolin-1-one ring. The whole reactions
Further, due to the simplicity of the one-pot synthesis,
we decided to extend its scope to some aliphatic amines 5i–l
and aliphatic diamines 5m–o with the aim of diversifying
our work on new quinoline-based isoindolin-l-one deriva-
tives. To our delight, these amines were equally amenable
to the reaction process without any experimental diffi-
culties, successfully furnishing the corresponding pyrrolo-
[3,4-b]quinolin-1-ones 1i–o in comparable yields of 68–
82% (Scheme 1).
202

Chemistry of Heterocyclic Compounds 2016, 52(3), 200–205
occurred effectively in one pot. It is worthy to mention that
ethyl 6-bromo-2-(chloromethyl)quinoline-3-carboxylate (4)
(0.328 g, 1.0 mmol) and the respective amine 5a–l
(1.0 mmol) or diamine 5m–o (0.5 mmol) in EtOH–AcOH
(10 ml, 10:1 v/v) solvent system was stirred at refluxing
temperature for 10 h. After the reaction was complete
(monitored by TLC), the reaction mixture was cooled to
room temperature and the solvent was removed under
reduced pressure. The residue was purified by column
chromatography on silica gel using hexane–EtOAc, 9:1, as
eluent, giving the pure products 1a–o.
an example that is particularly relevant to the present
discussion is described in the literature,29 wherein
7-isopropyl-1-methylazulen-4-amine undergoes intra-
molecular ring annulation reactions with ester group at
position 3 to yield tricyclic δ-lactams with the elimination
of ethanol without the need for a catalyst.
In summary, we have provided an easy access to bio-
logically intriguing quinoline-based isoindolin-l-ones in
one-pot synthesis in relatively environmentally benign
EtOH–AcOH solvent system. These newly synthesized
compounds would likely possess significant biological
activities and could also be potentially applied as useful
synthetic building blocks for the development of biolo-
gically and pharmaceutically important drugs. Currently,
the studies concerning their application are underway.
7-Bromo-2-phenyl-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-
1-one (1a). Mp 252–254°C. IR spectrum, ν, cm–1: 3053,
2939, 1685 (C=O), 1609 (C=N). 1H NMR spectrum,
δ, ppm (J, Hz): 5.65 (2H, s, CH2); 7.51–7.64 (5H, m,
H Ph); 8.36 (1H, d, J = 8.0, H Quino); 8.46 (1H, d, J = 8.0,
H Quino); 8.71 (1H, s, H Quino); 9.55 (1H, s, H Quino).
13C NMR spectrum, δ, ppm: 51.7; 121.5; 123.1; 126.3;
127.1; 128.9; 129.6; 129.7; 132.9; 134.7; 137.4; 141.8;
142.9; 156.6; 164.0. Mass spectrum, m/z (Irel, %): 340
[M+H]+ (100). Found, %: C 60.47; H 3.10; N 8.45.
C17H11BrN2O. Calculated, %: C 60.20; H 3.27; N 8.26.
7-Bromo-2-(4-methylphenyl)-2,3-dihydro-1H-pyrrolo-
[3,4-b]quinolin-1-one (1b). Mp 266–267°C. IR spectrum,
Experimental
IR spectra were recorded on a Shimadzu FTIR-8400S
infrared spectrophotometer using samples in thin layer.
1H and 13C NMR spectra were recorded on a Brucker
Avance II 400 spectrometer (400 and 100 MHz, respecti-
vely) in CDCl3 using TMS as internal standard. (The
abbreviation H Quino corresponds to the protons of the
quinoline ring.) Mass spectra were obtained on a Finnigan-
MAT 8430 mass spectrometer (electron ionization, 70 eV).
The elemental analyses were performed using an Elementar
Vario EL-III element analyzer. The progress of reactions
was monitored by thin layer chromatography (TLC) on
silica gel GF254 using petroleum ether–EtOAc, 4:1, as
eluent. Melting points (uncorrected) were determined by
using WRS-1B melting points apparatus. All chemicals
(AR graded) were commercially available and used without
further purification.
1
ν, cm–1: 3044, 2964, 1679 (C=O), 1619 (C=N). H NMR
spectrum, δ, ppm (J, Hz): 2.15 (3H, s, CH3); 5.31 (2H, s,
CH2); 7.10 (2H, d, J = 7.6, H Ar); 7.21 (2H, d, J = 7.6,
H Ar); 8.07 (1H, d, J = 8.4, H Quino); 8.42 (1H, s, H Quino);
8.47 (1H, d, J = 8.4, H Quino); 9.24 (1H, s, H Quino).
13C NMR spectrum, δ, ppm: 18.9; 51.7; 121.6; 123.0;
126.9; 129.2; 129.3; 130.0; 131.7; 136.9; 138.6; 138.9;
140.2; 142.7; 156.5; 163.9. Mass spectrum, m/z (Irel, %):
354 [M+H]+ (100). Found, %: C 60.99; H 3.88; N 8.11.
C18H13BrN2O. Calculated, %: C 61.21; H 3.71; N 7.93.
7-Bromo-2-(4-ethylphenyl)-2,3-dihydro-1H-pyrrolo-
[3,4-b]quinolin-1-one (1c). Mp 248–250°C. IR spectrum,
Synthesis of ethyl 6-bromo-2-(chloromethyl)quinoline-
3-carboxylate (4). N-(4-Bromo-2-formylphenyl)acetamide
(3) (4.84 g, 20 mmol) and ethyl 4-chloro-3-oxobutanoate
(3.3 g, 20 mmol) were placed in a 50-ml reaction kettle and
dissolved in DMF (20 ml). To the solution thus obtained,
TMSCl (8.7 g, 80 mmol) was carefully added dropwise.
The kettle was sealed and heated at 100°C for 10 h. After
cooling, the kettle was opened and the mixture was poured
into H2O (1000 ml) and the mixture thus obtained was
allowed to stand at room temperature in ultrasonic bath for
1 h. The resulting precipitate was filtered off and purified
by column chromatography on silica gel using hexane–
EtOAc, 10:1, as eluent, affording the pure product 4 in
64% yield. Mp 127–130°C. IR spectrum, ν, cm–1: 1711
1
ν, cm–1: 3046, 2960, 1681 (C=O), 1613 (C=N). H NMR
spectrum, δ, ppm (J, Hz): 1.08 (3H, t, J = 7.6, CH3CH2);
2.53 (2H, q, J = 7.6, CH3CH2); 5.39 (2H, s, CH2); 7.20 (2H,
d, J = 7.6, H Ar); 7.30 (2H, d, J = 7.6, H Ar); 8.12 (1H, d,
J = 8.4, H Quino); 8.23 (1H, d, J = 8.4, H Quino); 8.48
(1H, s, H Quino); 9.31 (1H, s, H Quino). 13C NMR spectrum,
δ, ppm: 13.4; 27.7; 51.8; 110.0; 121.4; 123.2; 126.1; 127.0;
129.0; 129.6; 131.9; 132.7; 137.2; 141.6; 142.7; 146.7;
156.7; 164.0. Mass spectrum, m/z (Irel, %): 368 [M+H]+
(100). Found, %: C 62.32; H 3.97; N 7.75. C19H15BrN2O.
Calculated, %: C 62.14; H 4.12; N 7.63.
7-Bromo-2-(4-methoxyphenyl)-2,3-dihydro-1H-pyrrolo-
[3,4-b]quinolin-1-one (1d). Mp 269–271°C. IR spectrum,
1
1
(C=O), 1609, 1583, 1558, 1478, 1440, 1072. H NMR
ν, cm–1: 3037, 2984, 1671 (C=O), 1618 (C=N). H NMR
spectrum, δ, ppm (J, Hz): 1.48 (3H, t, J = 7.2, OCH2CH3);
4.50 (2H, q, J = 7.2, OCH2CH3); 5.28 (2H, s, CH2Cl); 7.91
(1H, d, J = 8.4, H Quino); 8.05 (1H, d, J = 8.4, H Quino);
8.10 (1H, s, H Quino); 8.75 (1H, s, H Quino). 13C NMR
spectrum, δ, ppm: 14.2; 45.9; 62.2; 119.4; 122.1; 124.1;
127.8, 130.4; 130.6; 135.7; 140.1; 156.0; 165.1. Found, %:
C 47.75; H 3.62; N 4.11. C13H11BrClNO2. Calculated, %:
C 47.52; H 3.37; N 4.26.
spectrum, δ, ppm (J, Hz): 3.94 (3H, s, OCH3); 5.51 (2H, s,
CH2); 7.11 (2H, d, J = 7.6, H Ar); 7.54 (2H, d, J = 7.6,
H Ar); 8.24 (1H, d, J = 8.4, H Quino); 8.35 (1H, d, J = 8.4,
H Quino); 8.61 (1H, s, H Quino); 9.43 (1H, s, H Quino).
13C NMR spectrum, δ, ppm: 56.0 (2C); 116.1; 122.2;
122.6; 125.9; 128.8; 130.5; 131.4; 133.7 (2C); 138.1;
138.3; 142.6; 143.6; 157.3; 159.2; 164.3. Mass spectrum,
m/z (Irel, %): 370 [M+H]+ (100). Found, %: C 58.68;
H 3.63; N 7.44. C18H13BrN2O2. Calculated, %: C 58.56;
H 3.55; N 7.59.
Synthesis of 7-bromo-2,3-dihydro-1H-pyrrolo[3,4-b]-
quinolin-1-ones 1a–o (General method). A mixture of
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Chemistry of Heterocyclic Compounds 2016, 52(3), 200–205
7-Bromo-2-[4-(tert-butyl)phenyl]-2,3-dihydro-1H-
C 50.06; H 2.82; N 10.78. C11H7BrN2O. Calculated, %:
pyrrolo[3,4-b]quinolin-1-one (1e). Mp 255–257°C.
C 50.22; H 2.68; N 10.65.
IR spectrum, ν, cm–1: 3042, 2945, 1674 (C=O), 1614
7-Bromo-2-methyl-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-
1-one (1j). Mp 192–193°C. IR spectrum, ν, cm–1: 3034,
2934, 1694 (C=O), 1634 (C=N). 1H NMR spectrum,
δ, ppm (J, Hz): 3.24 (3H, s, CH3); 5.00 (2H, s, CH2); 8.07
(1H, d, J = 8.4, H Quino); 8.21 (1H, d, J = 8.4, H Quino);
8.46 (1H, s, H Quino); 9.23 (1H, s, H Quino). 13C NMR
spectrum, δ, ppm: 24.1; 46.1; 116.4; 121.2; 121.7; 124.5;
127.8; 132.1; 136.6; 137.3; 151.9; 159.9. Mass spectrum,
m/z (Irel, %): 278 [M+H]+ (100). Found, %: C 52.22;
H 3.34; N 9.86. C12H9BrN2O. Calculated, %: C 52.01;
H 3.27; N 10.11.
1
(C=N). H NMR spectrum, δ, ppm (J, Hz): 1.37 (9H, s,
(CH3)3C); 5.60 (2H, s, CH2); 7.52 (2H, d, J = 7.6, H Ar);
7.63 (2H, d, J = 7.2, H Ar); 8.32 (1H, d, J = 8.4, H Quino);
8.43 (1H, d, J = 8.4, H Quino); 8.68 (1H, s, H Quino); 9.51
(1H, s, H Quino). 13C NMR spectrum, δ, ppm: 29.6; 34.2;
52.0; 110.0; 121.6; 122.9; 126.3; 126.8; 127.2; 129.8;
131.8; 132.9; 137.4; 141.8; 142.8; 153.7; 156.8; 164.5.
Mass spectrum, m/z (Irel, %): 396 [M+H]+ (19), 260
[M–Br–(CH3)3C]+ (100). Found, %: C 64.00; H 4.89; N 6.91.
C21H19BrN2O. Calculated, %: C 63.81; H 4.84; N 7.09.
7-Bromo-2-(4-fluorophenyl)-2,3-dihydro-1H-pyrrolo-
[3,4-b]quinolin-1-one (1f). Mp 234–236°C. IR spectrum,
7-Bromo-2-ethyl-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-
1-one (1k). Mp 237–238°C. IR spectrum, ν, cm–1: 3048,
2960, 1681 (C=O), 1631 (C=N). 1H NMR spectrum,
δ, ppm (J, Hz): 1.25 (3H, t, J = 7.2, CH2CH3); 3.65 (2H, q,
J = 7.2, CH2CH3); 4.65 (2H, s, CH2); 7.98 (1H, d, J = 8.4,
H Quino); 8.03 (1H, d, J = 8.4, H Quino); 8.47 (1H, s,
H Quino); 8.69 (1H, s, H Quino). 13C NMR spectrum,
δ, ppm: 13.6; 37.0; 50.8; 120.0; 125.4; 128.9; 131.2; 131.4;
132.1; 134.6; 148.0; 156.9; 162.2. Mass spectrum, m/z (Irel, %):
292 [M+H]+ (100). Found, %: C 53.85; H 3.90; N 9.54.
C13H11BrN2O. Calculated, %: C 53.63; H 3.81; N 9.62.
2-Benzyl-7-bromo-2,3-dihydro-1H-pyrrolo[3,4-b]-
quinolin-1-one (1l). Mp 257–259°C. IR spectrum, ν, cm–1:
1
ν, cm–1: 3034, 2895, 1666 (C=O), 1611 (C=N). H NMR
spectrum, δ, ppm (J, Hz): 5.57 (2H, s, CH2); 7.20 (2H, t,
J = 7.6, H Ar); 7.61 (2H, t, J = 7.6, H Ar); 8.29 (1H, d,
J = 8.4, H Quino); 8.40 (1H, d, J = 8.4, H Quino); 8.66
(1H, s, H Quino); 9.49 (1H, s, H Quino). 13C NMR
spectrum, δ, ppm: 51.7; 110.0; 116.4; 116.6; 121.5; 124.8;
125.2; 125.3; 126.3; 126.9; 129.7; 132.8; 137.4; 141.8;
142.9; 156.5; 163.9. Mass spectrum, m/z (Irel, %): 358
[M+H]+ (100). Found, %: C 57.42; H 3.12; N 7.92.
C17H10BrFN2O. Calculated, %: C 57.17; H 2.82; N 7.84.
7-Bromo-2-(4-chlorophenyl)-2,3-dihydro-1H-pyrrolo-
[3,4-b]quinolin-1-one (1g). Mp 223–225°C. IR spectrum,
1
3054, 2973, 2921, 1675 (C=O), 1632 (C=N). H NMR
1
ν, cm–1: 3035, 2938, 1681 (C=O), 1609 (C=N). H NMR
spectrum, δ, ppm (J, Hz): 4.57 (2H, s, CH2Ph); 4.87 (2H, s,
CH2); 7.30–7.37 (5H, m, H Ph); 8.18 (1H, d, J = 8.4,
H Quino); 8.30 (1H, d, J = 8.4, H Quino); 8.60 (1H, s,
H Quino); 9.41 (1H, s, H Quino). 13C NMR spectrum,
δ, ppm: 46.0; 51.4; 120.1; 124.9; 127.7; 128.0; 128.1;
128.4; 128.9; 129.4; 131.1; 131.8; 132.0; 132.1; 132.2;
137.3; 148.1; 161.9. Mass spectrum, m/z (Irel, %): 354
[M+H]+ (100). Found, %: C 61.01; H 3.77; N 8.06.
C18H13BrN2O. Calculated, %: C 61.21; H 3.71; N 7.93.
2,2'-(Ethane-1,2-diyl)bis(7-bromo-2,3-dihydro-1H-
spectrum, δ, ppm (J, Hz): 5.66 (2H, s, CH2); 7.57 (2H, d,
J = 8.0, H Ar); 7.68 (2H, d, J = 7.6, H Ar); 8.37 (1H, d,
J = 8.4, H Quino); 8.48 (1H, d, J = 8.4, H Quino); 8.73
(1H, s, H Quino); 9.57 (1H, s, H Quino). 13C NMR
spectrum, δ, ppm: 51.2; 112.8; 115.6; 121.6; 123.8; 126.4;
126.9; 129.8; 132.9 (2C); 133.5; 135.0; 137.5; 141.9; 142.9;
156.4; 163.8. Mass spectrum, m/z (Irel, %): 376 [M+H]+
(30), 374 [M+H]+ (100). Found, %: C 54.40; H 2.60; N 7.64.
C17H10BrClN2O. Calculated, %: C 54.65; H 2.70; N 7.50.
7-Bromo-2-(4-bromophenyl)-2,3-dihydro-1H-pyrrolo-
[3,4-b]quinolin-1-one (1h). Mp 240–241°C. IR spectrum,
pyrrolo[3,4-b]quinolin-1-one)
(1m). Mp >300°C.
IR spectrum, ν, cm–1: 3074, 2977, 1675 (C=O), 1629
1
1
ν, cm–1: 3028, 2946, 1672 (C=O), 1608 (C=N). H NMR
(C=N). H NMR spectrum, δ, ppm (J, Hz): 3.71 (4H, d,
spectrum, δ, ppm (J, Hz): 5.65 (2H, s, CH2); 7.61 (2H, d,
J = 8.4, H Ar); 7.72 (2H, d, J = 8.0, H Ar); 8.37 (1H, d,
J = 8.8, H Quino); 8.48 (1H, d, J = 8.4, H Quino); 8.73
(1H, s, H Quino); 9.56 (1H, s, H Quino). 13C NMR
spectrum, δ, ppm: 51.2; 111.3; 113.6; 121.7; 122.5; 124.0;
126.5; 127.1; 129.9; 133.0; 133.1; 134.2; 137.6; 142.0;
143.1; 156.5; 163.8. Mass spectrum, m/z (Irel, %): 419
[M+H]+ (100), 417 [M+H]+ (92). Found, %: C 48.63;
H 2.52; N 6.79. C17H10Br2N2O. Calculated, %: C 48.84;
H 2.41; N 6.70.
J = 7.2, 2CH2); 5.28 (4H, s, 2CH2N); 8.30 (2H, d, J = 8.4,
H Quino); 8.48 (2H, d, J = 8.4, H Quino); 8.72 (2H, s,
H Quino); 9.46 (2H, s, H Quino). 13C NMR spectrum,
δ, ppm: 40.4; 49.2; 110.6; 113.4; 116.3; 119.1; 122.2;
126.3; 130.2; 133.5; 157.2; 162.1. Mass spectrum, m/z (Irel, %):
553 [M+H]+ (100). Found, %: C 52.52; H 2.84; N 10.34.
C24H16Br2N4O2. Calculated, %: C 52.20; H 2.92; N 10.15.
2,2'-(Propane-1,3-diyl)bis(7-bromo-2,3-dihydro-1H-
pyrrolo[3,4-b]quinolin-1-one)
(1n).
Mp
>300°C.
IR spectrum, ν, cm–1: 3067, 2952, 1669 (C=O), 1617
1
7-Bromo-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-one
(C=N). H NMR spectrum, δ, ppm (J, Hz): 2.33–2.40 (2H,
(1i). Mp 263–265°C. IR spectrum, ν, cm–1: 3412 (NH),
m, CH2); 3.98 (4H, t, J = 7.2, 2CH2); 5.28 (4H, s, 2CH2N);
8.23 (2H, d, J = 8.4, H Quino); 8.37 (2H, d, J = 8.4,
H Quino); 8.61 (2H, s, H Quino); 9.38 (2H, s, H Quino).
13C NMR spectrum, δ, ppm: 25.1; 40.3; 49.3; 115.5; 121.3;
126.1; 129.5; 132.7; 137.1; 141.6; 142.4; 157.0; 164.9.
Mass spectrum, m/z (Irel, %): 567 [M+H]+ (100). Found, %:
C 53.46; H 3.25; N 10.13. C25H18Br2N4O2. Calculated, %:
C 53.03; H 3.20; N 9.89.
1
3042, 2956, 1684 (C=O), 1615 (C=N). H NMR spectrum,
δ, ppm (J, Hz): 5.34 (2H, s, CH2); 8.38 (1H, d, J = 8.0,
H Quino); 8.51 (1H, d, J = 8.4, H Quino); 8.75 (1H, s,
H Quino); 8.97 (1H, s, H Quino); 9.59 (1H, s, NH).
13C NMR spectrum, δ, ppm: 40.1; 110.8; 116.5; 122.2;
127.0; 130.3; 133.8; 138.4; 142.8; 144.3; 162.7. Mass
spectrum, m/z (Irel, %): 264 [M+H]+ (100). Found, %:
204

Chemistry of Heterocyclic Compounds 2016, 52(3), 200–205
11. Balasubramanian, M.; Keay, J. G. In Comprehensive
2,2'-(Butane-1,4-diyl)bis(7-bromo-2,3-dihydro-1H-
pyrrolo[3,4-b]quinolin-1-one) (1o). Mp >300°C. IR spectrum,
Heterocyclic Chemistry II; Katritzky, A. R.; Rees, C. W.;
Scriven, E. F. V., Eds.; Pergamon Press: Oxford, 1996, Vol. 5,
chap. 5.06, p. 245.
1
ν, cm–1: 3041, 2637, 1689 (C=O), 1608 (C=N). H NMR
spectrum, δ, ppm (J, Hz): 1.93–1.99 (4H, m, 2CH2); 3.93
(4H, t, J = 7.2, 2CH2); 5.24 (4H, s, 2CH2N); 8.24 (2H, d,
J = 8.4, H Quino); 8.32 (2H, d, J = 8.4, H Quino); 8.44
(2H, s, H Quino); 9.35 (2H, s, H Quino). 13C NMR spectrum,
δ, ppm: 24.4; 43.5; 51.2; 118.3; 121.5; 126.7; 129.2; 136.8;
138.6; 138.8; 142.4; 156.9; 162.3. Mass spectrum, m/z (Irel, %):
581 [M+H]+ (100). Found, %: C 54.06; H 3.73; N 9.38.
C26H20Br2N4O2. Calculated, %: C 53.82; H 3.47; N 9.66.
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available online at http://link.springer.com/journal/10593.
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