o-Benzenedisulfonimide as a reusable Br?nsted acid catalyst for an efficient and facile synthesis of quinolines via Friedla?nder annulation

Article abstract of DOI:10.1016/j.tetlet.2010.02.139

The synthesis of quinolines via Friedl?nder annulation was carried out in the presence of catalytic amount of o-benzenedisulfonimide as Br?nsted acid organocatalyst; the reaction conditions were mild and the yields of the target products were good. The or

Full text of DOI:10.1016/j.tetlet.2010.02.139

Tetrahedron Letters 51 (2010) 2342–2344
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Tetrahedron Letters
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o-Benzenedisulfonimide as a reusable Brønsted acid catalyst for an efficient
and facile synthesis of quinolines via Friedländer annulation
Margherita Barbero, Stefano Bazzi, Silvano Cadamuro, Stefano Dughera *
Dipartimento di Chimica Generale e Chimica Organica, Università di Torino, C.so Massimo d’Azeglio 48, 10125 Torino, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of quinolines via Friedländer annulation was carried out in the presence of catalytic
amount of o-benzenedisulfonimide as Brønsted acid organocatalyst; the reaction conditions were mild
and the yields of the target products were good. The organocatalyst was easily recovered and purified,
ready to be used in further reactions.
Received 8 February 2010
Revised 18 February 2010
Accepted 22 February 2010
Available online 26 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Homogeneous catalysis
Quinoline
Brønsted acid
o-Aminoarylketone
a-Methyleneketone
Quinolines and their derivatives are very important com-
pounds1 that show a broad range of biological activities such as
ammonium nitrate,21 GdCl
used; however, some of these procedures are complicated by harsh
reaction conditions, use of harmful organic solvents, low yields,
and difficulties in the work-up procedures.
3
Á6H
2 3
O,22 and BiCl 23) were widely
2
3
anti-bacterial,4 anti-asth-
anti-malarial,
anti-inflammatory,
5
6
matic, and anti-hypertensive . In addition, quinolines are advan-
tageously employed in the fields of bioorganic and industrial
organic chemistries.
7
We have recently reported the use of o-benzenedisulfonimide
(1, Fig. 1) in catalytic amounts as a safe, nonvolatile, and noncorro-
sive Brønsted acid in some acid-catalyzed organic reactions such as
8
Probably, quinolines represent a major class of heterocycles and
a significant number of preparations have been known since the
2
4,25
24–26
28
24,25
etherification,
esterification,
acetalization,
Ritter reac-
1
27
late 1800s; quinolines have generally been synthesized by well-
tion, Nazarov electrocyclization, disproportionation of dialkyl
2
9
30
known classical syntheses such as Skraup, Doebner-von Miller,
diarylmethyl ethers, and Hosomi–Sakurai reaction under very
mild and selective conditions. This organocatalyst, highly soluble
in both organic solvents and water, is easily recovered and purified
from the reaction mixture, owing to its complete solubility in
water, and it is ready to be used in further reactions with economic
and ecological advantages.
1
Friedländer, Pfitzinger, Conrad-Limpach, and Combes.
9
Among them, the Friedländer annulation appears to be still one
of the simplest and direct approaches for the synthesis of quino-
lines. The Friedländer protocol consists typically of the reactions
between aromatic o-aminoketones or aldehydes and another car-
bonylic compound with an activated
a
-methylene group. The reac-
The synthesis of 1 has been described for the first time in 1920s
2
4
tion can be promoted by acid or base catalysis or by heating;
however, under basic or thermal conditions sometimes the reac-
tion between 2-aminobenzophenone and simple ketones or b-keto
and recently modified. The key intermediate is o-benzenedisulfo-
nyl chloride, which can be prepared starting from o-benzenedi-
sulfonic acid dipotassium salt, anthranilic acid, 2-aminobenzene-
sulfonic acid, and 1,2-bis(methylsulfanyl)benzene. Nowadays, both
o-benzenedisulfonyl chloride and 1 are commercially available from
Sigma–Aldrich and Qventas, respectively.
9
esters fails. In general, better yields of quinolines were achieved
9
9
under acid catalysis. Several acid catalysts such as Brønsted acids
10
11
(
recent examples are hydrochloric acid in water, sulfamic acid,
1
2
13
sulfuric acid, dodecylphosphonic acid, PEG-supported sulfonic
1
4
15
acid, propylsulfonic silica, sulfonic acid-functionalized ionic
liquids, and oxalic acid ), and Lewis acids9 (recent examples
1
6
17
SO
NH
SO2
2
3 4 4 4
are Zr(NO ) or Zr(HSO )
,18 Lewis acid ionic liquid, LASC, ceric
19
20
1
*
Corresponding author. Tel.: +39 (11) 6707645; fax: +39 (11) 6707642.
E-mail address: stefano.dughera@unito.it (S. Dughera).
Figure 1. o-Benzenedisulfonimide (1).
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.139

M. Barbero et al. / Tetrahedron Letters 51 (2010) 2342–2344
2343
O
Y
THF, or EtOH) and in the presence of 5 mol % of 1, did not complete
even after long time (48 h). Performing the same reaction in H O,
O
R
2
Y
1 (cat)
the yield of 6b was only 72% after 24 h. Note that the reactions be-
tween 2b and 3a–c or 5a–c took place usually slower (Table 1; en-
tries 4–6, 10–12). Moreover, by using the less reactive 3a, the
products 4a and 4d were obtained in lower yields and longer
times; it was also necessary to use 10 mol % of 1 (Table 1; entries
1 and 4). It must be stressed that the presence of a strong elec-
tron-withdrawing group influenced the progress of the reaction:
reacting 2d with 5b, it was necessary to use 10 mol % of 1 for the
completion of the reaction (Table 1; entry 14).
+
Me
CH2R
NH2
N
4
Me
2
3
2
a
b
Y
3
a
b
c
R
4
a
b
c
d
e
f
Y
R
Ph
Me
Ph
Ph
Ph
Me
Me
COOEt
COMe
COOEt
COMe
Me
Me
Me
Me
COOEt
COMe
O
Furthermore, 1 was recovered in excellent yields (about 90%),
simply by evaporating under reduced pressure aqueous layer and
washings. The recovered 1 was reused as catalyst in other two con-
secutive reactions between 2a and 5b. The results are listed in
Table 2: the reaction time increased, but the yields of 6b and the
recovery of 1 were always good.
In conclusion, we have proposed a mild, easy, and efficient
method for the synthesis of quinolines through Friedländer annu-
lation in the presence of o-benzenedisulfonimide (1) as a reusable
homogeneous catalyst. The advantages of performing the Friedlän-
der reaction in the presence of 1 as catalyst can be summarized as
follows: (1) use of a safe, nonvolatile, noncorrosive Brønsted acid;
O
Y
X
Y
1 (cat)
X
W
Z
NH2
(
CH2)n
N
2
5
6
2
a
b
c
d
e
X
Y
5
a
b
c
Z
6
X
H
H
H
H
H
H
Y
n
1
2
2
1
2
2
2
2
2
W
H
H
Cl
Ph
Me
Ph
CH
a
b
c
d
e
f
Ph
Ph
Ph
Me
Me
Me
CH
2
2
2
2
2
CH -CH
2
CH
CO
CH
CH -CO
NO Ph
2
2
2
Cl
2-ClC H
CH
6
4
CO
g
h
i
Cl Ph
NO2 Ph
CH2
CH2
(
2) high yields of recovering of 1 at the end of the reactions simply
Cl 2-ClC H
CH
6
4
2
evaporating aqueous washings; (3) the target products 4 and 6 are
obtained generally in excellent yields under easy and mild reaction
conditions; and (4) the reactions are carried out under solvent free
conditions with economic benefits.
Scheme 1. Friedländer synthesis of quinolines 4 and 6.
In the light of these shortcomings, in this Letter we wish to pro-
pose a simple and efficient quinoline synthesis via Friedländer
annulation in the presence of 1 as reusable Brønsted acid catalyst.
Various 2-aminobenzophenones 2a, c–e and 2-aminoacetophe-
none (2b) were reacted at 80 °C with a number of carbonyl com-
Table 2
Consecutive reactions with 1
Run
Time (h)
Yield (%) of 6aa,b
Recovery (%) of 1
pounds 3a–c or 5a–c bearing one activated
a-methylene group,
usually in the presence of 5 mol % of 1 in order to synthesize quin-
olines 4a–f or 6a–i (Scheme 1); the results are listed in Table 1.
The target products 4a–f and 6a–i were obtained in good to
excellent yields (15 examples: average yield 90%) reacting either
cyclic or acyclic ketones, diketones, b-ketoester under mild, easy,
and solvent-free conditions. Interestingly, the reaction between
92,c 101 mg
1
2
3
6
6
8
100
92
90
3
1
d
88,
89 mg
90, 80 mg
a
b
c
The reactions were performed at 80 °C, under solvent-free conditions.
Yields refer to the pure and isolated product.
The recovered 1 was used as catalyst in entry 2.
The recovered 1 was used as catalyst in entry 3.
d
2
a and 5b, carried out at reflux in an organic solvent (MeCN,
Table 1
Synthesis of quinolines 4 or 6
Entry
Reactants
Products and yieldsa,b,c (%)
1%
Time (h)
Quinolines 4 or 6
Lit. mp (°C)
Mpd (°C)
32
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
2a 3a
2a 3b
2a 3c
2b 3a
2b 3b
2b 3c
2a 5a
2a 5b
2a 5c
2b 5a
2b 5b
2b 5c
2c 5b
2d 5b
2e 5b
4a, 90d
4b, 93
4c, 95
10
5
5
10
5
5
5
5
5
5
5
5
5
10
5
28
3
4
48
16
16
4
6
4
48
24
16
4
147–148
100–101
110–111
109–110
Waxy solid
Viscous oil
130–131
136–137
155–156
60–61
78–79
68–69
162–164
143–144
151–152
144
97
33
1133
3
e
34
4d, 55
110
Oil
Oil
3
3
4
4
5
4e, 85
4f, 92
6a, 90
128–1303
f
34
6b,100
137
151–153
60
2
3
2
2
0
4
0
3
4
6c,100
6d, 83
6e, 100
6f, 100
6g, 95
1
1
1
1
1
1
78
78
1633
e
36
6h, 80
8
4
—
6i, 92
15333
a
b
c
d
e
f
The reactions were performed at 80 °C under solvent-free conditions.
Yields refer to the pure and isolated products.
Structures and purity of all the products were confirmed by comparison of their physical (mp) and spectral data with those reported in the literature.
Crystallization solvent: MeOH.
After 48 h, the reaction carried out with 5 mol % of 1 was not complete.
2
After 48 h, the reactions carried out at reflux in MeCN, THF, or EtOH were not complete. In H O the reaction time was 24 h and the yield of 6b was 72% (1.86 g).

2
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2
2. Prabhakar Reddy, P.; China Rayu, B.; Madhusudana Rao, J. J. Chem. Res. 2008, 12,
79–682.
3. Jia, C. S.; Wang, G. W. Lett. Org. Chem. 2006, 3, 289–291.
Acknowledgments
6
2
This work was supported by Ministero dell’Università e della
Ricerca and by University of Torino.
24. Barbero, M.; Cadamuro, S.; Dughera, S.; Venturello, P. Synlett 2007,
2209–2212.
2
2
5. Barbero, M.; Cadamuro, S.; Dughera, S.; Venturello, P. Synthesis 2008, 1379–
388.
6. Barbero, M.; Cadamuro, S.; Dughera, S.; Venturello, P. Synthesis 2008, 3625–
632.
1
References and notes
3
1
.
.
Kouznetsov, V. V.; Vargas Méndez, L. Y.; Meléndez Gómez, C. M. Curr. Org.
Chem. 2005, 9, 141–161. and references cited therein.
(a) Larsen, R. D.; Corley, E. G.; King, A. O.; Carrol, J. D.; Davis, P.; Verhoeven, T.
R.; Reider, P. J.; Labelle, M.; Gauthier, J. Y.; Xiang, Y. B.; Zamboni, R. J. J. Org.
Chem. 1996, 61, 3398–3405; (b) Chauhan, P. M. S.; Srivastava, S. K. Curr. Med.
Chem. 2001, 8, 1535–1542.
27. Barbero, M.; Bazzi, S.; Cadamuro, S.; Dughera, S. Eur. J. Org. Chem. 2009, 430–
436.
28. Barbero, M.; Cadamuro, S.; Deagostino, A.; Dughera, S.; Larini, P.; Occhiato, G.;
Prandi, C.; Tabasso, S.; Venturello, P.; Vulcano, R. Synthesis 2009, 2260–2266.
29. Barbero, M.; Bazzi, S.; Cadamuro, S.; Dughera, S.; Ghigo, G. Eur. J. Org. Chem.
2009, 4346–4351.
2
3
.
(a) Roma, G.; Braccio, M. D.; Grossi, G.; Mattioli, F.; Ghia, M. Eur. J. Med. Chem.
30. Barbero, M.; Bazzi, S.; Cadamuro, S.; Dughera, S.; Piccinini, C. Synthesis 2010,
315–319.
31. 9-Phenyl-1,2,3,4-tetrahydroacridine (6b): representative procedure for the
2
000, 35, 1021–1035; (b) Kalluraya, B.; Sreenivasa, S. Farmaco 1998, 53, 399–
4
04.
4
.
.
Chen, Y. L.; Fang, K. G.; Sheu, J. Y.; Tsu, S. L.; Tzeng, C. C. J. Med. Chem. 2001, 44,
374–2377.
preparation of quinolines 4 and 6: o-Benzenedisulfonimide (1; 5 mol %;
2
110 mg, 0.5 mmol) was added to a mixture of 2-aminobenzophenone (2a;
1.97 g, 10 mmol) and cyclohexanone (5b; 1.18 g, 12 mmol). The mixture was
stirred at 80 °C. The reaction was monitored by GC and GC–MS until the
complete disappearance of 2a (6 h). The reaction mixture was poured into
5
Dube, D.; Blouin, M.; Brideau, C.; Chan, C. C.; Desmarais, S.; Ethier, D.;
Falgueyret, J. P.; Friesen, R. W.; Girard, M.; Girard, Y.; Guay, J.; Riendeau, D.;
Tagari, P.; Young, R. N. Bioorg. Med. Chem. Lett. 1998, 8, 1255–1260.
Ferrarini, P. L.; Mori, C.; Badawneh, M.; Calderone, V.; Greco, R.; Manera, C.;
Martinelli, A.; Nieri, P.; Saccomanni, G. Eur. J. Med. Chem. 2000, 35, 815–826.
Saito, I.; Sando, S.; Nakatami, K. Bioorg. Med. Chem. 2001, 9, 2381–2385.
Jenekhe, S. A.; Lu, L.; Alam, M. M. Macromolecules 2001, 34, 7315–7324.
Marco-Contelles, J.; Perez-Mayoral, E.; Samadi, A.; do Carmo Carreiras, M.;
Soriano, E. Chem. Rev. 2009, 109, 2652–2671. and references cited therein.
6
.
ethyl acetate–H
extracted with ethyl acetate (2 Â 50 ml). The combined organic extracts were
washed with H SO . After solvent removal
O (2 Â 50 ml) and dried over Na
under reduced pressure, the crude residue was the virtually pure (GC, GC–MS,
2
O (100 ml, 1:1). The aqueous layer was separated and
7.
8.
9.
2
2
4
1
13
H NMR, C NMR) title compound 6b, pale brown solid; yield: 100% (1.46 g).
The aqueous layer and the aqueous washings were collected and evaporated
1
1
1
0. Wang, G. W.; Jia, C. S.; Dong, Y. W. Tetrahedron Lett. 2006, 47, 1059–1063.
1. Yadav, J. S.; Purushothama Rao, P.; Sreenu, D.; Srinivasa Rao, R.; Naveen Kumar,
V.; Nagaiah, K.; Prasad, A. R. Tetrahedron Lett. 2005, 46, 7249–7253.
under reduced pressure. After removal of the water, virtually pure ( H NMR) o-
benzenedisulfonimide (1) was recovered (101 mg, 92% yield).
32. Mp are reported in: (a) Yadav, J. S.; Reddy, B. V. S.; Premlatha, K. Synlett 2004,
963–966; NMR data are reported in: (b) Zhang, Z.; Tan, J.; Wang, Z. Org. Lett.
2008, 10, 173–175.
33. Yadav, J. S.; Reddy, B. V. S.; Sreedhar, P.; Srinivasa Rao, R.; Nagaiah, K. Synthesis
2004, 2381–2385.
12. Strekowski, L.; Czarny, A.; Lee, H. J. Fluorine Chem. 2000, 104, 281–284.
13. Ghassamipour, S.; Sardarian, A. R. Tetrahedron Lett. 2009, 50, 514–519.
14. Zhang, X. L.; Wang, Q. Y.; Sheng, S. R.; Wang, Q.; Liu, X. L. Synth. Commun. 2009,
3
9, 3293–3304.
1
5. Garella, D.; Barge, A.; Upadhyaya, D.; Rodriguez, Z.; Palmisano, G.; Cravotto, G.
Synth. Commun. 2010, 40, 120–128.
34. Palimkar, S. S.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. J. Org.
Chem. 2003, 68, 9371–9378.
1
1
6. Akbari, J.; Heydari, A.; Kalhor, H. R.; Kohan, S. A. J. Comb. Chem. 2010, 12, 137–140.
7. Dabiri, M.; Baghbanzadeh, M.; Nikcheh, M. S. Monatsh. Chem. 2007, 138, 1249–
35. Larock, R. C.; Kishan Reddy, C. J. Org. Chem. 2002, 67, 2027–2033.
36. 7-Nitro-9-phenyl-1,2,3,4-tetrahydroacridine (6h) is known in the literature;37
however, no physical and spectral data are reported. EI–MS, m/z (%) = 304
1
252.
8. Zolfigol, M. A.; Salehi, P.; Ghaderi, A.; Shiri, M. Catal. Commun. 2007, 8, 1214–
218.
+
1
1
1
[M ,100]. H NMR (200 MHz, CDCl
7.58–7.47 (m, 3H), 7.18–7.01 (m, 2H), 3.18–3.11 (m, 2H), 2.60–2.25 (m, 2H),
1.89–1.86 (m, 2H), 1.79–1.77 (m, 2H); 13C NMR (50 MHz, CDCl
): d 163.4,
3
): d 8.28–8.21 (m, 2H), 8.01 (d, J = 9.05 Hz),
1
9. (a) Karthikeyan, G.; Perumal, P. T. J. Heterocycl. Chem. 2004, 41, 1039–1041; (b)
Zhou, T.; Lin, J. L.; Chen, Z. C. Lett. Org. Chem. 2008, 5, 47–50.
3
148.2, 148.0, 144.7, 135.1, 130.6, 129.9, 128.8, 128.7, 128.4, 125.5, 122.7, 121.7,
34.3, 27.9.4, 22.5, 22.3.
2
2
0. Zhang, L.; Wu, J. Adv. Synth. Catal. 2007, 349, 1047–1051.
1. (a) Sridharan, V.; Ribelles, P.; Ramos, M. T.; Menendez, J. C. J. Org. Chem. 2009,
37. Kamal, A.; Reddy, K. S.; Khan, M. N. A.; Shetty, R. V. C. R. N. C.;
Ahmed, S. K.; Kumar, K. P.; Murthy, U. S. N. Lett. Drug Des. Discov.
2007, 8, 580–586.
74, 5715–5718; (b) Subhas Bose, D.; Idrees, M.; Jakka, N. M.; Venkateswara Rao,
J. J. Comb. Chem. 2010, 12, 100–110.