4
Tetrahedron
phenyl-1H-pyrazol-5-amine (1a), 4-chlorobenzaldehyde (2a),
In summary, we reported carbonaceous material as solid acid
catalyzed three-component reaction leading to synthesis of
pyrazoloisoquinoline and pyrazolopyridine derivatives in good
yield. The simple experimental and work-up procedures, high
yield, recovery, and reusability of metal-free solid acid
heterogeneous catalyst render it an attractive approach for the
generation of different potential biological and pharmaceutical
compounds.
and cyclohexanone (3a) were carried out in the presence of C-
SO3H (10 mg) with TLC monitoring for the formation of
intermediates (Scheme 2). Firstly, a mixture of 1a and 2a were
o
treated in the presence of C-SO3H (10 mg) at 60 C in water for
about 3 hours. To our delight, the compound 5 was obtained with
good yield (73%), which could further react with compound 3a
and give goal product 4a. However, when 1a and 3a were mixed
under the optimized conditions, an intermediate 7 was isolated in
65% yield along with intermediate 6 (18%). Intermediate 6 could
further be transformed to the final product 4a under the
optimized reaction conditions. In addition, when a mixture of 2a
and 3a were treated in the presence of C-SO3H (10 mg),
Acknowledgments
We are grateful for financial support from the research project
of undergraduate of Shaoxing University. We are also grateful to
Shaoxing University for spiritual support.
compound 2,6-bis((E)-4-chlorobenzylidene)cyclohexan-1-one
was given, which can not give goal product 4a by subsequent
reaction.
References and notes
O
1.
2.
(a) Stein, R. G.; Beil, J. H.; Singh, T. J. Med. Chem. 1970, 13,
153-155; (b) Smirnoff, P.; Crenshaw, R. R. Antimicrob.
Agents Chemother. 1977, 11, 571-573; (c) Selvi, S. T.;
Nadaraj, V.; Mohan, S.; Sasi, R.; Hema, M. Bioorg. Med.
Chem. 2006, 14, 3896-3903.
N
CHO
C
N
3a
N
Ph
SO3H
N
NH2
+
N
Cl
Ph
1a
5
Cl
2a
(a) Beutner, G. L.; Kuethe, J. T.; Kim, M. M.; Yasuda, N. J.
Org. Chem. 2009, 74, 789-794; (b) Meiners, B. A.; Salama, A.
I. Eur. J. Pharmacol. 1982, 78, 315-322; (c) Lynck, B.; Khan,
M.; Teo, H.; Pedrotti, F. Can. J. Chem. 1988, 66, 420-428; (d)
Manetti, F.; Schenone, S.; Bondavalli, F.; Brullo, C.; Bruno, O.;
Ranise, A.; Mosti, L.; Menozzi, G.; Fossa, P.; Trincavelli, M.
L.; Martini, C.; Martinelli, A.; Tintori, C.; Botta, M. J. Med.
Chem. 2005, 48, 7172-7185; (e) Hamblin, J. N.; Angell, T. D.
R.; Ballantine, S. P.; Cook, C. M.; Cooper, A. W. J.; Dawson,
J.; Delves, C. J.; Jones, P. S.; Lindvall, M.; Lucas, F. S.;
Mitchell, C. J.; Neu, M. Y.; Ranshaw, L. E.; Solanke, Y. E.;
Somers, D. O.; Wiseman, J. O. Bioorg. Med. Chem. Lett. 2008,
18, 4237-4241; (f) Chen, Y. L. WO9534563 A1, 1995 [Chem.
Abstr. 1995, 124, 232447].
CHO
Cl
C SO3H
2a
O
N
NH2
Cl
N
N
N
N
Ph
N
+
NH2
Ph
N
Ph
6
4a
1a
3a
C SO3H
N
N
N
Ph
7
Scheme 2. Control experiment.
On the basis of these experiments, the possible mechanism for
3.
(a) Afghan, A.; Baradarani, M. M.; Joule, J. A. ARKIVOC
2009, 20-30; (b) Paul, S.; Gupta, M.; Gupta, R.; Loupy, A.
Tetrahedron Lett. 2001, 42, 3827-3829; (c) Mali, J. R.; Pratap,
U. R.; Jawale, D. V.; Mane, R. A. Tetrahedron Lett. 2010, 51,
3980-3982; (d) Wang, S.-L.; Liu, Y.-P.; Xu, B.-H.; Wang, X.-
H.; Jiang, B.; Tu, S.-J. Tetrahedron 2011, 67, 9417-9425; (e)
Jiang, B.; Liu, Y.-P.; Tu, S.-J. Eur. J. Org. Chem. 2011, 3026-
3035; (f) Quiroga, J.; Mejia, D.; Insuasty, B.; Abonia, R.;
Nogueras, M.; Sanchez, A.; Cobo, J.; Low, J. N. Tetrahedron
2001, 57, 6947-6953; (g) Drizin, I.; Altenbach, R. J.; Buckner,
S. A.; Whiteaker, K. L.; Scott, V. E.; Darbyshire, J. F.; Jayanti,
V.; Henry, R. F.; Coghlan, M. J.; Gopalakrishnan, M.; Carroll,
W. A. Bioorg. Med. Chem. 2004, 12, 1895-1904; (h) Quiroga,
J.; Portilla, J.; Serrano, H.; Abonia, R.; Insuasty, B.; Nogueras,
M.; Cobo, J. Tetrahedron Lett. 2007, 48, 1987-1990.
the formation of pyrazoloisoquinoline and pyrazolopyridine
derivatives in the presence of carbonaceous material catalyst is
shown in Scheme 3. Presumably, the compound 1a was firstly
condensed with aldehyde 2 to afford intermediate A. Then, the
condensed intermediate A undergoes a [4+2] cycloaddition with
the enol form 3’, which is in equilibrium with cyclicketone 3 in
the presence of carbonaceous material, to give radical
intermediate B, which further forms intermediate C. Finally,
intramolecular aromatization followed by elimination of H2O
from the intermediate C affords the desired product 4.
Ar
4.
5.
Scharff, P. Carbon. 1998, 36, 481-486.
N
N
H2O
N
Ph
(a) Makowski, P.; Demir-Cakan, R.; Antonietti, M.;
Goettmann, F.; Titirici. M. M. Chem. Commun. 2008, 999-
1001; (b) Watanabe, M.; Aizawa, Y.; Iida, T.; Aida, T. M.;
Levy, C.; Sue, K. Carbohydr Res. 2005, 340, 1925-1930; (c)
Hu, Y. S.; Demir-Cakan, R.; Titirici, M. M.; Muller, J. O.;
Schlogl, R.; Antonietti, M. Angew. Chem., Int. Ed. 2008, 47,
1645-1649.
H
O
OH
A
[4+2]
n
n
Cycloaddition
3
3'
N
NH2
N
Ph
Ar
H
6.
(a) Nakajima, K.; Okamura, M.; Kondo, J. N.; Domen, K.;
Tatsumi, T.; Hayashi, S. Chem. Mater. 2009, 21, 186-193; (b)
Budarin, V.; Luque, R.; Macquarrie, D. J.; Clark, J. H. Chem.
Eur. J. 2007, 13, 6914-6919; (c) Toda, M.; Takagaki, A.;
Okamura, M.; Kondo, J. N.; Domen, K.; Hayashi, S. Nature
2005, 438, 178; (d) Hara, M.; Yoshida, T.; Takagaki, A.;
Takata, T. J.; Kondo, N.; Domen, K. Angew. Chem., Int. Ed.
2004, 43, 2955-2958; (e) Comerford, J. W.; Clark, J. H.;
Macquarrie, D. J.; Breeden, S. W. Chem. Commun. 2009,
2562-2564.
O
1a
2
HO
N
N
Ph
Ar
N
Aromatization
- H2O
n
B
n
HO
Ar
N
N
Ar
N
N
N
N
Ph
7.
8.
Heravi, M. M.; Hashhemi, E.; Beheshtiha, Y. S.; Kamjou, K.;
Toolabi, M.; Hosseintash, N. J. Mol. Catal. A: Chem. 2014,
392, 173-180.
C
Ph
Scheme 3. Proposed mechanism for the synthesis of pyrazoloisoquinoline
and pyrazolopyridine derivatives using solid acid catalyst.
4
(a) Sania, Y. M.; Dauda, W. M. A. W.; Aziz, A. R. A. Appl.
Catal. A: Gen. 2014, 470, 140-161; (b) Chehardoli, G.;
Zolfigol, M. A.; Faal-Rastgar, T.; Mallakpour, S.; Ghorbani-