Poly(N-bromo-N-ethylbenzene-1,3-disulfonamide) and N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide as efficient reagents for synthesis of quinolines

Article abstract of DOI:10.1016/j.tetlet.2008.12.076

Poly(N-bromo-N-ethylbenzene-1,3-disulfonamide) [PBBS] and N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide [TBBDA] were used as efficient reagents for the synthesis of quinolines in excellent yields from 2-aminoaryl ketones and carbonyl compounds under aqueo

Full text of DOI:10.1016/j.tetlet.2008.12.076

Tetrahedron Letters 50 (2009) 1055–1058
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Tetrahedron Letters
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Poly(N-bromo-N-ethylbenzene-1,3-disulfonamide) and N,N,N0,N0-tetrabromo-
benzene-1,3-disulfonamide as efficient reagents for synthesis of quinolines
*
Ramin Ghorbani-Vaghei , Somayeh Akbari-Dadamahaleh
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
a r t i c l e i n f o
a b s t r a c t
Poly(N-bromo-N-ethylbenzene-1,3-disulfonamide) [PBBS] and N,N,N0,N0-tetrabromobenzene-1,3-disulf-
onamide [TBBDA] were used as efficient reagents for the synthesis of quinolines in excellent yields from
2-aminoaryl ketones and carbonyl compounds under aqueous and solvent-free conditions.
Ó 2008 Elsevier Ltd. All rights reserved.
Article history:
Received 12 October 2008
Revised 9 December 2008
Accepted 16 December 2008
Available online 24 December 2008
Keywords:
Quinolines
2-Aminobenzophenone
Acetylacetone
TBBDA
PBBS
1. Introduction
ylbenzene-1,3-disulfonamide) [PBBS],12 in organic synthesis,12–16 we
report here a convenient method for the preparation of quinolines
Quinolines are an important group of heterocyclic compounds.
Several derivatives have been found to possess useful biological
activities such as antimalarial, antibacterial, anti-asthmatic, anti-
hypertensive, and anti-inflammatory.1 In addition, quinolines are
valuable synthons for the preparation of nano-and meso structures
with enhanced electronic and photonic functions.2 As a result of
their importance as substructures in a broad range of natural and
designed products, significant effort continues to be directed to-
ward the development of new quinoline-based structures and
new methods for their construction.3 Thus, the synthesis of quino-
lines is an important and useful task in organic chemistry. The
Friedländer annulation is a straightforward method for the synthe-
sis of these compounds4 which involves a condensation followed
from 2-aminoarylketones and various ketones in the presence of
TBBDA and PBBS under (i) aqueous and (ii) solvent-free conditions
(Scheme 1). Among the solvents (EtOH, H2O, CH3CN, and toluene)
screened, H2O proved to be the best (Table 1). Under solvent-free con-
ditions, most of the reactions proceeded to afford the corresponding
product in less time, however, the yield was slightly lower.
Substituted quinolines were prepared from appropriate 2-
aminoarylketones and various
a-methylene carbonyl compounds.
2-Aminobenzophenones were converted to quinolines using
TBBDA or PBBS in good to high yields without any by-product for-
mation. The results are presented in Table 2.
N,N,N0,N0-Tetrabromobenzene-1,3-disulfonamide [TBBDA] and
poly(N-bromo-N-ethylbenzene-1,3-disulfonamide) [PBBS] are
inexpensive and non-hazardous reagents. They react under heter-
ogeneous conditions, are conveniently handled, and can be
removed from the reaction mixture by simple filtration.
by a cyclodehydration between 2-aminoarylketones and a-methy-
lene ketones, and is catalyzed by both acids and bases. In recent
years, iodine,5 Lewis acids6 such as ZnCl2, SnCl2, Bi(OTf)3, Ag3P-
W12O40, AuCl3, and CeCl3ꢀ7H2O, a combination of acidic catalysts
and microwave irradiation,7 ionic liquids,8 chlorotrimethylsilane,9
dodecylphosphonic acid,10 and 1-methylimidazolium trifluoroace-
tate,11 have been utilized for this synthesis. However, many of
these procedures suffer from harsh reaction conditions, long reac-
tion times, low yields, difficulties in work-up, and the use of stoi-
chiometric and/or relatively expensive reagents.
In conclusion, we have described an efficient method for the
synthesis of quinolines via Friedländer annulation utilizing TBBDA
and PBBS. This method provides an excellent complement to quin-
oline synthesis and also avoids the use of hazardous acids or bases.
2. Experimental
In continuation of our interest in the application ofN,N,N0,N0-tetrab-
romobenzene-1,3-disulfonamide [TBBDA] and poly(N-bromo-N-eth-
2.1. General procedure for quinoline synthesis using TBBDA
and PBBS in the presence of H2O
2-Aminoarylketone (0.5 mmol), carbonyl compound (0.5 mmol),
and H2O (5 mL) were placed in a 25 mL round-bottomed flask.
* Corresponding author. Tel.: +98 811 8257407; fax: +98 811 8257404.
E-mail address: rgvaghei@yahoo.com (R. Ghorbani-Vaghei).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.12.076

1056
R. Ghorbani-Vaghei, S. Akbari-Dadamahaleh / Tetrahedron Letters 50 (2009) 1055–1058
R2
N
R2
R4
R3
O
O
R1
TBBDA or PBBS
R4
R1
+
R3
solvent-free/ 100 °C
H2O/ reflux or
NH2
Br
N
Br
Br
N
Br
N
Br
N Br
S
S
(
S
S
H2C
CH2
)
n
O
O
O O
O
O
O O
PBBS
TBBDA
Scheme 1.
Table 1
Reaction times and yields of 1-(2-methyl-4-phenylquinoline-3-yl)ethanone using TBBDA in various solvents
Entry
Product
Solvent
Time (h)
10
Yield (%)
66
Ph
O
O
O
O
1
Toluene
N
Ph
2
3
4
CH3CN
EtOH
H2O
10
74
92
94
N
Ph
6
N
Ph
4
N
Table 2
Synthesis of various quinolines using TBBDA and PBBS in H2O and under solvent-free conditions
Entry 2-Aminoaryl ketone Ketone
Product
TBBDA(H2O)
PBBS(H2O)
TBBDA (solvent-free)
PBBS (solvent-free)
Ref.
10
Time (h) Yielda (%) Time(h) Yielda (%) Time (h) Yielda (%) Time (h) Yielda (%)
Ph
Ph
O
O
O
1
4
94
6
91
2.5
90
4
84
O
NH2
N
Ph
Ph
O
O
2
3
4.5
6
94
86
7
87
80
3.5
4
90
82
5
86
84
10
10
NH2
Ph
N
Ph
O
8.5
6.5
O
NH2
N
Ph
Ph
N
O
Cl
O
O
Cl
4
5
94
7
90
3
92
4.5
83
10
O
NH2

R. Ghorbani-Vaghei, S. Akbari-Dadamahaleh / Tetrahedron Letters 50 (2009) 1055–1058
1057
Table 2 (continued)
Entry 2-Aminoaryl ketone Ketone
Product
TBBDA(H2O)
PBBS(H2O)
TBBDA (solvent-
free)
PBBS (solvent-free) Ref.
Time
(h)
Yielda
(%)
Time(h) Yielda
(%)
Time
(h)
Yielda
(%)
Time
(h)
Yielda
(%)
Ph
N
Ph
O
Cl
Cl
Cl
Cl
5
6
4
95
6.5
92
2.5
91
83
4
83
10
6e
O
NH2
O
Cl
Cl
Cl
O
O
7.5
87
10
81
5
7
80
Cl
Cl
O
NH2
N
O
Cl
7
8
8
6
84
91
10.5
80
85
6
82
8.5
81
6e
O
NH2
N
Ph
Ph
O
O
O
COOH
9
—
—
O
OEt
NH2
N
Ph
Ph
O
O
COOH
Ph
9
10
11
6.5
92
92
94
8.5
9.5
9
87
85
87
—
—
—
—
—
—
O
OMe
NH2
N
Ph
O
COOH
Cl
Cl
Cl
Cl
7
O
OE
t
NH2
N
Ph
Ph
O
O
COOH
7
O
OMe
N
NH2
a
Products were characterized from their physical properties, by comparison with authentic samples, and by spectroscopic methods.
TBBDA (0.25 g, 0.45 mmol) or PBBS (0.25 g) was added to the solu-
tion with stirring. The reaction was heated at reflux and after
completion [Table 2, monitored by TLC (5:1, n-hexane/acetone)],
the flask was cooled to room temperature, and the precipitated sul-
fonamide was removed by filtration. Dichloromethane (10 mL) was
added and the organic layer was separated and dried (Na2SO4). Evap-
oration of the solvent under reduced pressure followed by purifica-
tion by preparative thin layer chromatography afforded the pure
quinoline.
C17H13O2N (entries 8 and 9): mp 215–218 °C; IR (KBr):
2700 (COOH), 1706 (CO), 1654 (C@N) cmꢁ1
m
3350–
;
1H NMR [CDCl3, FT-90
MHz]: d 12.63 (s, 1H, COOH), 7.50–7.00 (m, 9H, aromatic), 2.28 (s,
3H, CH3); 13C NMR [CDCl3, FT-90 MHz]: d 31.80, 116.67, 120.04,
123.07, 127.10, 128.69, 129.16, 131.54, 132.40, 134.47, 138.42,
149.46, 152.20, 201.84; MS (m/z) 262 (M+). Anal. Calcd for
C17H13O2N: C, 77.56; H, 4.94; N, 5.32%. Found: C, 77.77; H, 4.89; N, 5.12.
C17H12O2NCl (entries 10 and 11): mp 269–272 °C; IR (KBr):
m
3400–2700 (COOH), 1716 (CO), 1649 (C@N) cmꢁ1; 1H NMR [CDCl3,
FT-90 MHz]: d 12.90 (s, 1H, COOH), 7.46–7.24 (m, 8H, aromatic),
2.24 (s, 3H, CH3); 13C NMR [CDCl3, FT-90 MHz]: d 31.60, 118.16,
121.01, 126.60, 126.80, 128.90, 131.78, 133.81, 135.20, 136.83,
144.70, 146.40, 147.90, 200.20; MS (m/z) 297 (M+). Anal. Calcd
for C17H12O2NCl: C, 68.57; H, 4.03; N, 4.70%. Found: C, 68.14; H,
4.21; N, 5.02.
2.2. General procedure for quinoline synthesis using TBBDA
and PBBS under solvent-free conditions
A mixture of the 2-aminoarylketone (0.5 mmol), carbonyl com-
pound (0.5 mmol), and TBBDA (0.25 g, 0.45 mmol) or PBBS (0.25 g)
was placed in a test-tube at 100 °C and stirred. After completion of
the reaction [Table 2, monitored by TLC (5:1, n-hexane/acetone)],
CH2Cl2 (10 mL) was added, and the precipitated sulfonamide was
removed by filtration. Evaporation of the solvent under reduced
pressure followed by purification by preparative thin layer chro-
matography afforded the pure quinoline.
Acknowledgment
We are thankful to Bu-Ali Sina University, Center of Excellence
in Development of Chemical Methods (CEDCM), for financial
support.

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