Cerium chloride (CeCl3·7H2O) as a highly efficient catalyst for one-pot three-component Mannich reaction

Article abstract of DOI:10.1590/S0103-50532010001200002

We have demonstrated the use of CeCl₃·7H₂O as highly efficient catalyst for one-pot threecomponent Mannich reaction to afford β-amino carbonyl compounds in good to excellent yield within shorter period of reaction time. The process is mild, efficient, environmentally benign with the use of little amount of catalyst.

Full text of DOI:10.1590/S0103-50532010001200002

J. Braz. Chem. Soc., Vol. 21, No. 12, 2175-2179, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
.
Cerium Chloride (CeCl3 7H2O) as a Highly Efficient Catalyst for One-Pot
Three-Component Mannich Reaction
Mazaahir Kidwai* and Anwar Jahan
Green Chemistry Research Laboratory, Department of Chemistry,
University of Delhi, Delhi, 110007, India
•
Nós demonstramos a utilização de CeCl3 7H2O como catalisador altamente eficiente para
reação de Mannich de três componentes para fornecer compostos β-amino carbonílicos em bons a
excelentes rendimentos em curto período de reação. O processo é brando, eficiente e ambientalmente
amigável com o uso de pequena quantidade de catalisador.
•
We have demonstrated the use of CeCl3 7H2O as highly efficient catalyst for one-pot three-
component Mannich reaction to afford β-amino carbonyl compounds in good to excellent yield
within shorter period of reaction time. The process is mild, efficient, environmentally benign with
the use of little amount of catalyst.
•
Keywords: Mannich reaction, CeCl3 7H2O, aromatic aldehydes, amines, β-amino carbonyl
compounds
Introduction
of Mannich reaction have been developed to overcome
the negative aspect of this classical method. In general,
improved methodologies rely on two-component system
using preformed electrophiles such as imines and
stable nucleophiles such as enolates, enols, ethers and
enamines,13,14 but the preferable route is the use of a one-
pot three-component strategy as it facilitates wide range
of structural variations, but these early three-component
reactions were hampered due to a number of serious
limitations.15
The conventional catalyst for the synthesis of β-amino
carbonyl compounds of aldehydes, ketones and amines
involve mainly organic and mineral acids like proline,16-18
acetic acid,19 p-dodecyl benzene sulfonic acid20 and other
Lewis acids.21,22 They often suffer the drawbacks of
long reaction times, harsh reaction conditions, toxicity
and difficulty in product isolation. While searching for
economical and better catalyst, we thought its worthwhile
to perform a controlled reaction for one-pot three-
component Mannich reaction catalyzed by cerium(III)
Three-component reactions have emerged as a useful
method, since the combination of three-components
to generate new products in a single step is extremely
economical, among the multi-component reaction.1-5
Our research group focuses on finding efficient
chemical transformation using three or more components
in a single step by a catalytic process since it avoids use
of stoichiometric toxic reagents, large amounts of solvents
and expensive purification techniques which is also the
fundamental targets of modern organic synthesis.6
There are many types of three-component reaction
reported in the literature and Mannich reaction is one of
the most important C-C bonds forming reaction. Basically,
Mannich reaction is the synthesis of β-amino carbonyl
compounds and as such is one of the most important
reaction in organic synthesis.7,8 The gaining impetus of
the Mannich reaction has been fuelled by the ubiquitous
nature of nitrogen containing compounds in drugs9 and
natural products.10
•
chloride heptahydrate (CeCl3 7H2O), which has attracted
However, the classical Mannich reaction is plagued
by a number of serious disadvantages with limited
applications.11,12 Therefore, numerous modern versions
considerable attention because of its diverse application as
a promoter in organic synthesis.23
Cerium halides are relatively an effective Lewis acid
catalyst,24 as it is water tolerant, non-toxic, easy to handle,
inexpensive and can be reused without further purification.
*e-mail: kidwai.chemistry@gmail.com

•
2176
Cerium Chloride (CeCl3 7H2O) as a Highly Efficient Catalyst
J. Braz. Chem. Soc.
•
In this work, we have found CeCl3 7H2O as an efficient
catalyst for the synthesis of β-amino carbonyl compounds
at room temperature through a one-pot three-component
reaction of aromatic aldehydes, ketones and aromatic
amines in methanol (Scheme 1). It is also noteworthy to
mention that our environmentally benign reaction does not
generate any toxic waste products.
entry 2). Remarkably, catalyst with high Lewis acidity such
as ZnCl2 andAlCl3 failed to catalyze the reaction efficiently
and resulted in lower yields of the corresponding product
(Table 2).
Table 2. Optimization of various Lewis acids for the Mannich reactiona
entry
Catalyst
CuSO4
time/h
Yield/(%)b
Results and Discussion
1
2
3
4
5
2
2
2
2
2
55
93
40
15
12
•
CeCl3 7H2O
In order to verify the efficient catalytic behavior of
•
CuCl2
ZnCl2
AlCl3
CeCl3 7H2O, a controlled reaction was performed using
benzaldehyde (1 mmol), aniline (1 mmol) and acetophenone
(1 mmol) in methanol (5 mL) at room temperature. In
•
aReaction conditions: acetophenone (1 mmol), benzaldehyde (1 mmol)
and aniline (1 mmol), 3 mol% catalyst; solvent: methanol; r.t. bIsolated
and unoptimized yields.
the absence of CeCl3 7H2O, the reaction resulted in the
formation of a fused product after 8 h at 50 oC (10% yield).
However under same condition by employing 1 mol% of
•
•
CeCl3 7H2O, the reaction afforded expected products up to
A possible mechanism of CeCl3 7H2O catalyzed
94% yield within 4 h of reaction time.
With this optimistic result in hand, we further
investigated the best reaction conditions by using different
Mannich reaction is shown in Scheme 2. The role
of catalyst is the activation of precursors through
coordination leading the desired product in good yield
with less reaction time. First it coordinates with the
carbonyl oxygen of aldehyde and activating it, and then
nucleophilic attack by amine gives I which in turns gets
converted to intermediate imine (II) after dehydration.
The intermediate II again activated by the catalyst through
coordination by CeCl3 and then the attack by enol to imine
gives the desired product 4.
Encouraged by these remarkable results, we screened
a variety of aromatic aldehydes and amines having
electron-withdrawing as well as electron-donating groups
and in each case we observed good to excellent yields,
however, when ortho-substituted anilines were used as
substrates, the reaction gave no product probably due to
steric hindrance of ortho-substituents. In the investigation
of various substituted benzaldehydes, it was found that
p-methylbenzaldehyde is the most reactive substrate in the
reaction (Table 3, entry 3). It was observed that the catalyst
had no catalytic activity for the reactions when aliphatic
aldehydes and amines were used as substrate.
•
amounts of CeCl3 7H2O. An increase in the quantity of
•
CeCl3 7H2O from 1 mol% to 3 mol% not only decreased the
reaction time from 4 h to 2 h but also increased the product
yield slightly from 85% to 93%. Thus the use of 3 mol%
•
CeCl3 7H2O is sufficient to push the reaction forward for the
optimum yield of β-amino carbonyl compounds (Table 1).
•
Table 1. Optimization of the concentration of CeCl3 7H2O in the Mannich
reactiona
entry
CeCl3 7H2O/mol%
time/h
Yield/(%)b
•
1
2
3
4
0
1
2
3
8
4
2
2
10
85
90
93
aReaction conditions: acetophenone (1 mmol), benzaldehyde (1 mmol)
b
•
and aniline (1 mmol), x mol% CeCl3 7H2O; solvent methanol; r.t. Isolated
yields.
Further, we have also scrutinized this reaction by
•
employing various Lewis acids such as CuSO4, CeCl3 7H2O,
In order to ascertain the scope and limitation of this
•
•
CuCl2, ZnCl2, and AlCl3 and we found that CeCl3 7H2O
CeCl3 7H2O catalyzed Mannich reaction, we have also
showed the best result among all the catalysts (Table 2,
extended the use of this catalytic systems to the reaction
CHO
NH2
HN
O
O
CeCl3 7H2O (3 mol%)
MeOH, r.t.
Me
+
+
4
1
3
2
•
Scheme 1. CeCl3 7H2O-catalyzed Mannich reaction.

Vol. 21, No. 12, 2010
Kidwai and Jahan
2177
CeCl3
O
H
CeCl3
NH2
O
H
NH2
OH
N
H
I
CeCl3
-H2O
CeCl3
O
HN
CeCl3
O
N
II
4
CH2
O
Me
•
Scheme 2. Proposed mechanism of CeCl3 7H2O catalyzed Mannich reaction.
a
•
Table 3. Synthesis of various β-amino carbonyls using CeCl3 7H2O
O
NHR2
R1
O
CeCl3 7H2O (3 mol%)
MeOH, r.t.
R1CHO + R2NH2
+
R
R
Me
entry
Ketone
R1
R2
time/h
Yield/(%)b
mp/(oC)
TONc
1
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Ph
4-MeC6H4
Ph
2.5
2
2.5
3
96
93
97
91
73
95
92
91
74
76
91
89
85
87
88
90
83
91
•
164-167
168-170
129-130
162-163
184-185
172-173
145-146
135-137
103-104
173-175
118-120
168-170
138-140
146-148
137-138
116-117
133-134
137-138
32
31
32
30
24
31
30
30
31
25
30
29
28
29
29
30
27
30
2
3
4
5
6
7
8
9
Ph
4-MeC6H4
Ph
Ph
Ph
Ph
4-OMeC6H4
4-NO2C6H4
4-ClC6H4
3,4-(Me)2C6H3
Ph
Ph
4-IC6H4
Ph
4-IC6H4
Ph
Ph
Ph
4-MeC6H4
Ph
8
2.5
3.5
3
8
4
5
3
5
5
Ph
4-OMeC6H4
4-NO2C6H4
4-OMeC6H4
4-ClC6H4
Ph
10
11
12
13
14
15
16
17
18
a
p-Methylacetophenone
p-Nitroacetophenone
Cyclohexanone
Ph
Ph
Ph
Ph
3
3.5
4
Cyclohexanone
Cyclohexanone
4-OMeC6H4
Ph
Cyclohexanone
4-ClC6H4
5
b
Reaction conditions: acetophenone (1 mmol), aldehydes (1 mmol) and anilines (1 mmol), 3 mol% CeCl3 7H2O; solvent methanol; r.t. Isolated yields.
cTurnover number (TON).
of cyclohexanone with various aldehydes and amines as
depicted inTable 3. Cyclohexanone showed antiselectivities
determined by 1H NMR analysis of crude products.
Mannich reaction was very sensitive to reaction
temperature. The high temperature could improve the
reaction rate and shorten the reaction time, but favor side
reactions and the oxygenolysis of aldehyde and amine.25
In our investigation for the effect of temperature we found
•
that CeCl3 7H2O efficiently catalyzed the Mannich reaction
at room temperature.

•
2178
Cerium Chloride (CeCl3 7H2O) as a Highly Efficient Catalyst
J. Braz. Chem. Soc.
Table 4. Effect of solvent on the synthesis of β-amino carbonyl ketonesa
Solvent No.
Solvent
entry 1 (Table 3)
Yield/(%)b
entry 7 (Table 3)
time/h
time/h
Yield/(%)b
1
2
3
4
5
6
Ethanol
PEG 200
Methanol
DMF
2
2
2
2
2
2
2
92
90
98
60
55
72
-
2
2
2
2
2
2
2
66
62
70
40
43
55
DMSO
MeCN
7
Solvent Free
-
a
b
•
Reaction conditions: acetophenone (1 mmol), aldehydes (1 mmol) and anilines (1 mmol), 3 mol% CeCl3 7H2O; solvent methanol; r.t. Isolated yields.
Conclusions
shift are in d. GC-MS mass spectra were recorded on a
Waters LCT Micromass. The temperature of the reaction
mixture was measured through a non-contact infrared
thermometer (AZ, Mini Gun type, Model 8868).
In conclusion, we have developed a novel and efficient
catalytic method for Mannich reaction of aldehydes, amines
and ketones. We have shown that the reaction proceeds
•
much faster when CeCl3 7H2O is employed as a catalyst
Typical experimental procedure for the synthesis of
compare to uncatalyzed reaction. The most attractive
part of this work is that only small amount of catalyst is
needed for catalyzing the reaction. The simple experimental
procedures, fast reaction rates and easy isolation of products
make this procedure very useful and environment friendly.
In addition, our method does not require expensive reagents
and high temperature for the synthesis of β-amino carbonyl
compounds compared to the traditional protocols and has
broad substrate applicability with ease and much improved
yields.
b-aminocarbonyls
In a 50 mL round bottom flask, acetophenone
(1 mmol), aromatic aldehydes (1 mmol) and aromatic
amines (1 mmol) in MeOH (5 mL) were mixed and stirred
•
at room temperature. To this, CeCl3 7H2O (cerium chloride
heptahydrate) (3 mol%) was added. The progress of
reaction mixture was monitored by TLC (using petroleum
ether/AcOEt = 80:20 as an eluent). After completion of
the reaction, the solid product was collected by filtration
at pump and washed with methanol and water. The crude
product was subjected to purification by recrystalization
using ethanol, was subjected to further purification by
silica gel column chromatography using 15% ethyl
acetate, and 85% petroleum ether as an eluent to yield
the β-amino carbonyl compounds. The structures of all
the products were unambiguously established on the
Experimental
General experimental procedures
All chemicals were purchased from Sigma-Aldrich
and Lancaster and were used as such. All reactions
and purity of β-amino carbonyl compounds were
monitored by thin layer chromatography (TLC) using
aluminium plates coated with silica gel (Merck)
using 20% and 80% petroleum ether as an eluent. The
isolated products were further purified by column
chromatography using silica gel G (particle size
10-40 microns, 300 mesh) purchased from Spectrochem
Pvt. Ltd. Mumbai, India and purified product were
recrystallized. Melting points are determined on
Buchi 530. IR spectra were recorded on Perkin-Elmer
1
basis of their spectral analysis (IR, H NMR and GC/
MS mass spectral data). All the products are known
compounds.
Supplementary Information
Supplementary data are available free of charge at
http://jbcs.sbq.org.br, as PDF file.
Acknowledgment
1
FTIR-1710 spectrophotometer using KBr. H NMR
spectra were recorded on a BrukerAvance Spectrospin 300
(300 MHz) using TMS as internal standard and chemical
Anwar Jahan thanks to University Grants Commission
(UGC), New Delhi, India for Junior Research Fellowship.

Vol. 21, No. 12, 2010
Kidwai and Jahan
2179
References
9. Neves, A. P.; Barbosa, C. C.; Greco, S. J.; Vargas, M. D.;
Visentin, L. C.; Pinheiro, C. B.; Mangrich, A. S.; Barbosa, J.
P.; da Costa, G. L.; J. Braz. Chem. Soc. 2009, 20, 712.
10. Suginome, M.; Uehlin, L.; Murakami, M.; J. Am. Chem. Soc.
2004, 126, 13196; Da Rosa, F.A. F.; Rebelo, R.A.; Nascimento,
M. G.; J. Braz. Chem. Soc. 2003, 14, 11.
1. Wang, H. J.; Ren, X. -Q.; Zhang,Y. -Y.; Zhang, Z. –H; J. Braz.
Chem. Soc. 2009, 20, 1939; Eftekhari-Sis, B.;Abdollahifar,A.;
Hashemi, M. M.; Zirak, M.; Eur. J. Org. Chem. 2006, 5152;
Tewari, N.; Dwivedi, N.; Tripathi, R. P.; Tetrahedron Lett. 2004,
45, 9011; Bienayme, H.; Hulme, C.; Oddon, G.; Schmitt, P.;
Chem. Eur. J. 2000, 6, 3321; Tremblay-Morin, J. -P.; Raeppel,
S.; Gaudette, F.; Tetrahedron Lett. 2004, 45, 3471.
11. For reviews see: Allemann, C.; Gordillo, R.; Clemente, F. R.;
Cheong, P. H. -Y.; Houk, K. N.; Acc. Chem. Res. 2004, 37, 558;
Hayashi,Y.; Tsuboi, W.;Ashimine, I.; Urushima, T.; Shoji, M.;
Sakai, K.; Angew Chem., Ind. Ed. 2003, 42, 3677; Zhang, C.;
Dong, J.; Cheng, T.; Li, R.; Tetrahedron Lett. 2001, 42, 461;
Qian, C.; Gao, F.; Chen, R.; Tetrahedron Lett. 2001, 42, 4673.
12. Kobayashi, S.; Araki, M.;Yasuda, M.; Tetrahedron Lett. 1995,
36, 5773; Manabe, K.; Kobayashi, S.; Tetrahedron Lett. 1999,
40, 3773.
2. Sahu, S. K.;Azam, M.A.; Banerjee, M.; Acharrya, S.; Behera, C.
C.; Si, S.; J. Braz. Chem. Soc. 2008, 19, 963; Khan,A. T.; Parvin,
T.; Choudhury, L. H.; Eur. J. Org. Chem. 2008, 834; Weber,
L.; Illgen, K.; Almstetter, M.; Synlett 1999, 366; Martinez, R.;
Ramon, D. J.;Yus, M.; Tetrahedron Lett. 2005, 46, 8471.
3. Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S.
D.; Keating, T. A.; Acc. Chem. Res. 1996, 29, 123; Zhao, G.;
Jiang, T.; Gao, H.; Han, B.; Huang, J.; Su, D.; Green Chem.
2004, 6, 75; Mironov, M. A.; Ivantsova, M. N.; Tokareva, M.
I.; Mokrushin, V. S.; Tetrahedron Lett. 2005, 46, 3957.
4. Domling, A.; Ugi, I.; Angew. Chem. Int. Ed. 2000, 39, 3168;
Poisson, T.; Tsubogo, T.;Yamashita, Y.; Kobayashi, S.; J. Org.
Chem. 2010, 75, 963; Nanda, K. K.; Trotter, B. W.; Tetrahedron
Lett. 2005, 46, 2025; De, S. K.; Gibbs, R. A.; Tetrahedron Lett.
2004, 45, 7407.
13. Conceicao, T. F.; Bertolino, J. R.; Barra, G. M. O.; Mireski, S.
L.; Joussef, A. C.; Pires, A. T. N; J. Braz. Chem. Soc. 2008, 19,
111; Paixão, M. W.; Braga,A. L.; Ludtke, D. S.; J. Braz. Chem.
Soc. 2008, 19, 813; Trost, B. M.; Terrell, L. R.; J. Am. Chem.
Soc. 2003, 125, 338; Matsunaga, S.; Kumagai, N.; Harada, S.;
Shibasaki, M.; J. Am. Chem. Soc. 2003, 125, 4712.
14. Josephsohn, N. S.; Carswell, E. L.; Snapper, M. L.; Hoveyda,
A. H.; Org. Lett. 2005, 7, 2711; Pilli, R. A.; Robello, L. G.;
Camilo, N. S.; Dupont, J.; Lapis, A. A. M.; da Silveira Neto,
B.A.; Tetrahedron Lett. 2006, 47, 1669; Da Costa, J. S.; Pisoni,
D. S.; da Silva, C. B.; Petzhold, C. L.; Russowsky, D.; Ceschi,
M. A.; J. Braz. Chem. Soc. 2009, 20, 1448.
5. Kazemizadeh, A. R.; Ramazani, A.; J. Braz. Chem. Soc. 2009,
20, 309; Wang, L.; Han, H.; Sheng, J.; Tian, H.; Fan, Z.; Catal.
Commun. 2005, 6, 201; Zhang, Q.; Hui, Y.; Zhou, X.; Lin, L.;
Liu, X.; Feng, X.; Adv. Synth. Catal. 2010, 352, 976.
6. Mizuno, N.; Misono, M.; Chem. Rev. 1998, 98, 199; Kidwai, M.;
Jahan,A.; Bhatnagar, D.; J. Sulf. Chem. 2010, 31, 161; Kidwai,
M.; Jahan, A.; Bhatnagar, D.; J. Chem. Sci. 2010, 122, 607;
Kidwai, M.; Mishra, N. K.; Bhardwaj, S., Jahan, A.; Kumar,
A., Mozumdar, S.; Chem. Cat. Chem. 2010, 2, 1312; Kidwai,
M.; Mishra, N. K.; Bhatnagar, D.; Jahan,A.; Green Chem. Lett.
Rev., in press.
15. Kobayashi, S.; Ishitani, H.; Chem. Rev. 1999, 99, 1069.
16. List, B.; Pojarliev, P.; Biller, W. T.; Martin, H. J.; J. Am. Chem.
Soc. 2002, 124, 827.
17. List, B.; J. Am. Chem. Soc. 2000, 122, 9336.
18. Duthaler, R. O.; Angew. Chem., Int. Ed. 2003, 42, 975.
19. Mogilaiah, K.; Kankaiah, G.; Indian J. Heterocycl. Chem. 2002,
11, 283.
20. Manabe, K.; Mori, Y.; Kobayashi, S.; Tetrahedron 2001, 57,
2537.
7. Belinelo, V. J.; Reis, G. T.; Stefani, G. M.; Ferreira-Alves,
D. L.; Piló-Veloso, D.; J. Braz. Chem. Soc. 2002, 13, 830;
Arend, M.; Westermann, B.; Risch, N.; Angew. Chem., Int.
Ed. 1998, 37, 1044; Shou, W. -G.; Yang , Y. -Y.; Wang, Y. -G.;
Tetrahedron Lett. 2006, 47, 1845; Shi, M.; Cui, S. -C.; Liu, Y.
-H.; Tetrahedron 2005, 61, 4965; Feng, L.; Xu, L.; Lam, K.;
Zhou, Z.; Yip, C. W.; Chan, A. S. C.; Tetrahedron Lett. 2005,
46, 8685.
21. Kobayashi, S.; Hamada, T.; Manabe, K.; J. Am. Chem. Soc.
2002, 124, 5640.
22. Desai, P.; Schildknegt, K.; Agrios, K. A.; Mossman, C.;
Milligan, G. L.; Aube, J; J. Am. Chem. Soc. 2000, 122, 7226.
23. Li, W. -D. Z.; Peng, Y.; Org. Lett. 2005, 7, 3069.
24. Yadav, J. S.; Reddy, B. V. S.; Synlett 2000, 1275; Bartoli,
G.; Bosco, M.; Bellucci, M. C.; Marcantoni, E.; Sambri, L.;
Torregiani, E.; Eur. J. Org. Chem. 1999, 617.
8. Kidwai, M.; Mishra, N. K.; Bansal, V.; Kumar, A.; Mozumdar,
S.; Tetrahedron Lett. 2009, 50, 1355; Izumiseki, A.; Yoshida,
K.; Yanagisawa, A.; Org. Lett. 2009, 11, 5310; Urbaniak, M.;
Iwanek, W.; Tetrahedron 2006, 62, 1508; Ibrahem, I. Cordova,
A.; Tetrahedron Lett. 2005, 46, 2839; Ibrahem, I.; Zou, W.; Xu,
Y.; Cordova, A.; Adv. Synth. Catal. 2006, 348, 211; Dondoni,
A.; Massi, A. A.; Sabbatini, S.; Bertolasi, V.; Tetrahedron Lett.
2004, 45, 2381.
25. Li, Z.; Ma, X.; Liu, J.; Feng, X.; Tian, G.; Zhu,A.; J. Mol. Catal.
A: Chem. 2007, 272, 132.
Submitted: June 15, 2010
Published online: August 24, 2010

J. Braz. Chem. Soc., Vol. 21, No. 12, S1-S3, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
.
Cerium Chloride (CeCl3 7H2O) as a Highly Efficient Catalyst for One-Pot
Three-Component Mannich Reaction
Mazaahir Kidwai* and Anwar Jahan
Green Chemistry Research Laboratory, Department of Chemistry,
University of Delhi, Delhi, 110007, India
1,3-Diphenyl-3-p-tolylamino-propan-1-one, (1)
7.8 Hz, 2H, Ar-H), 7.21 (d, J 7.38-7.27 (4 Hz, 2H, Ar-H),
A white solid; Rf = 0.70 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3383 (NH), 1698 (CO).
1H NMR (300 MHz, TMS, CDCl3): d 2.47 (s, 3H, -CH3),
3.62-3.45 (m, 2H), 4.47 (t, 1H), 6.91 (d, J 8.5 Hz, 2H, Ar-
H), 6.97 (d, J 7.9, 2H,Ar-H), 7.07-7.03 (m, 2H,Ar-H), 7.15
(d, J 6.3 Hz, 2H,Ar-H), 7.32-7.28 (m, 1H,Ar-H), 7.49-7.46
(m, 2H, Ar-H), 7.69-7.66 (m, 1H, Ar-H), 7.83 (d, J 7.9 Hz,
2H, Ar-H). 13C NMR (75 MHz, CDCl3): d 21.3, 45.5, 56.7,
113.1, 120.5, 122.5, 128.9, 128.3, 130.4, 133.1, 135.3,
144.6, 196.6. m/z (GC-MS, HRMS): 313.362 (M+). Anal.
Calc. for C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C,
82.98; H, 6.81; N, 4.42.
7.41-7.36 (m, 2H, Ar-H), 7.49-7.41 (m, 1H, Ar-H), 7.89
(d, J 8.1 Hz, 2H, Ar-H). C NMR (75 MHz, CDCl3): d
21.7, 42.7, 54.5, 111.4, 119.5, 123.6, 127.4, 128.6, 131.9,
132.3, 135.4, 143.2, 190.6. m/z (GC-MS, HRMS): 317.402
(M+).Anal. Calc. for C22H21NO: C, 83.78; H, 6.71; N, 4.44.
Found: C, 82.85; H, 6.56; N, 4.37.
13
3-(4-Methoxy-phenylamino)-1,3-diphenyl-propan-1-one,
(4)
A white solid; Rf = 0.64 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3385 (NH), 1675 (CO).
1H NMR (300 MHz, TMS, CDCl3): d 3.44-3.39 (m, 2H),
3.58 (s, 3H, -OCH3), 4.86 (t, 1H), 6.51 (d, J 8.6 Hz, 2H,
Ar-H), 6.71 (d, J 8.9, 2H, Ar-H), 6.96-7.05 (m, 1H, Ar-H),
7.15 (d, J 8.3 Hz, 2H,Ar-H), 7.30-7.24 (m, 2H,Ar-H), 7.41-
7.38 (m, 2H,Ar-H), 7.53-7.33 (m, 1H,Ar-H), 7.81 (d, J 7.5
Hz, 2H, Ar-H). 13C NMR (75 MHz, CDCl3): d 46.2, 55.3,
58.2, 115.2, 122.7, 126.2, 127.1, 128.6, 128.8, 128.9, 129.3,
132.5, 138.5, 141.7, 1510.2, 195.6. m/z (GC-MS, HRMS):
332.473 (M+).Anal. Calc. for C22H21NO2: C, 79.73; H, 6.39;
N, 4.23. Found: C, 79.58; H, 6.73; N, 4.37.
1,3-Diphenyl-3-phenylamino-propan-1-one, (2)
A white solid; Rf = 0.68 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3386 (NH), 1671 (CO).
1H NMR (300 MHz, TMS, CDCl3): d 3.47-3.32(m, 2H),
4.98 (t, 1H), 6.51 (d, J 8.0 Hz, 2H, Ar-H), 6.63-6.69 (m,
1H, Ar-H). 7.04-7.00 (m, 2H, Ar-H), 7.20(d, J 6.5 Hz, 2H,
Ar-H), 7.26-7.23(m, 1H, Ar-H), 7.41-7.38 (m, 2H, Ar-H),
7.51-7.45 (m, 1H, Ar-H), 7.57-7.53(m, 2H, Ar-H), 7.84 (d,
J 7.8 Hz, 2H, Ar-H). 13C NMR (75 MHz, CDCl3): d 46.3,
54.2, 115.3, 119.4, 126.4, 128.6, 128.8, 129.5, 132.3, 135.8,
146.2, 197.0. m/z (GC-MS, HRMS): 301.368 (M+). Anal.
Calc. for C20H18NO: C, 83.30; H, 6.29; N, 4.86. Found: C,
82.98; H, 6.15; N, 4.23.
3-(4-Nitro-phenylamino)-1,3-diphenyl-propan-1-one, (5)
A white solid; Rf = 0.48 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3364 (NH), 1627 (CO).
1H NMR (300 MHz, TMS, CDCl3): d 3.67 (d, J 6.8 Hz,
2H), 5.12 (t, 1H), 6.37 (brs, 2H, Ar-H), 6.64 (d, J 6.4,
2H, Ar-H), 7.24-7.20 (m, 1H, Ar-H), 7.38-7.29 (m, 2H,
Ar-H), 7.37 (d, J 7.7 Hz, 2H, Ar-H), 7.67-7.59 (m, 1H,
Ar-H), 8.01 (d, J 7.2 Hz, 2H, Ar-H). 13C NMR (75 MHz,
CDCl3): d 45.2, 53.1, 111.7, 125.9, 126.1, 127.4, 128.9,
128.2, 128.1, 130.5, 132.8, 136.7, 138.6, 140.0, 197.8.
m/z (GC-MS, HRMS): 348.637 (M+). Anal. Calc. for
C21H18N2O3: C, 72.82; H, 5.24; N, 8.09. Found: C, 72.42;
H, 5.76; N, 7.96.
1-Phenyl-3-phenylamino-3-p-tolyl-propan-1-one, (3)
A white solid; Rf = 0.61 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3387(NH), 1667(CO). 1H NMR
(300 MHz, TMS , CDCl3): d 2.27 (s, 3H, -CH3), 3.45-3.31
(m, 2H), 4.82 (t, 1H), 6.75 (d, J 8.1 Hz, 2H, Ar-H), 6.83-
6.91 (m, 1H, Ar-H), 7.08-7.04 (m, 2H, Ar-H), 7.10 (d, J
*e-mail: kidwai.chemistry@gmail.com

•
S2
Cerium Chloride (CeCl3 7H2O) as a Highly Efficient Catalyst
J. Braz. Chem. Soc.
3-(4-Chloro-phenylamino)-1,3-diphenyl-propan-1-one, (6)
A white solid; Rf = 0.79 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3325 (NH), 1654 (CO).
1H NMR (300 MHz, TMS, CDCl3): d 3.54-3.37 (m, 2H),
4.91 (t, 1H), 6.35 (d, J 8.4 Hz, 2H, Ar-H), 6.68 (d, J 8.1,
2H, Ar-H), 7.11 (d, J 6.6 Hz, 2H, Ar-H), 7.28-7.22 (m,
2H, Ar-H), 7.34-7.31 (m, 2H, Ar-H), 7.42-7.38 (m, 2H,
Ar-H), 7.51-7.47 (m, 1H, Ar-H), 7.86 (d, J 7.8 Hz, 2H,
Ar-H). 13C NMR (75 MHz, CDCl3): d 44.08, 55.1, 116.4,
122.5, 125.7, 127.3, 128.4, 128.7, 129.3, 133.6, 137.5,
140.6, 197.4. m/z (GC-MS, HRMS): 335.832 (M+). Anal.
Calc. for C21H18ClNO: C, 75.11; H, 5.40; N, 4.17. Found:
C, 75.41; H, 5.36; N, 4.31.
2H, Ar-H), 7.59-7.55 (m, 2H, Ar-H), 7.65 (d, J 7.5 Hz, 2H,
Ar-H), 7.87 (d, J 8.0 Hz, 2H, Ar-H), 8.16 (d, J 9.6 Hz, 2H,
Ar-H). C NMR (75 MHz, CDCl3): d 46.4, 54.1, 112.8,
116.8, 123.4, 128.2, 128.4, 128.6, 129.3, 132.6, 137.6,
140.2, 143.6, 146.4, 198.4. m/z (GC-MS, HRMS): 346.381
(M+). Anal. Calc. for C21H18N2O3: C, 72.82; H, 5.24; N,
8.09. Found: C, 72.92; H, 5.13; N, 8.16.
13
3-(4-Bromo-phenyl)-1-phenyl-3-phenylamino-propan-1-
one, (10)
A white solid; Rf = 0.59 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3385(NH), 1670(CO). 1H NMR
(300 MHz, TMS, CDCl3): d 3.41 (d, J 5.6, 2H), 3.69 (s, 3H,
-OCH3), 4.91 (t, 1H), 6.48 (d, J 7.6 Hz, 2H, Ar-H), 6.70 (d,
J 6.9 Hz, 2H, Ar-H), 7.04 (d, J 6.7 Hz, 2H, Ar-H), 7.33 (d,
J 7.6 Hz, 2H, Ar-H), 7.46-7.41 (m, 2H, Ar-H), 7.58-7.54
(m, 1H, Ar-H), 7.90 (d, J 6.7 Hz, 2H, Ar-H). 13C NMR
(75 MHz, CDCl3): d 47.2, 54.4, 56.8, 112.8, 113.9, 86.8,
127.8, 128.3, 128.1, 138.6, 132.9, 134.2, 137.7, 160.7,
197.8. m/z (GC-MS, HRMS): 457.348 (M+). Anal. Calc.
for C22H20NO2: C, 57.78; H, 4.41; N, 3.06. Found: C, 57.92;
H, 4.33; N, 3.17.
3-(3,4-Dimethyl-phenylamino)-1,3-diphenyl-propan-1-
one, (7)
A white solid; Rf = 0.73 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3410(NH), 1702(CO). 1H NMR
(300 MHz, TMS, CDCl3): d 2.35 (s, 6H, -CH3), 3.10 (d,
J 6.1, 2H), 4.56 (t, 1H), 6.28 (s, 1H, Ar-H), 6.29 (d, J 6.8
Hz, 2H, Ar-H), 6.65 (d, J 8.1, 2H, Ar-H), 7.05-7.11 (m,
1H, Ar-H), 7.28 (d, J 6.7 Hz, 2H, Ar-H), 7.31-7.28 (m, 2H,
Ar-H), 7.34-7.30 (m, 2H, Ar-H), 7.49-7.42 (m, 1H, Ar-H),
7.93 (d, J 7.8 Hz, 2H, Ar-H). 13C NMR (75 MHz, CDCl3):
d 17.3, 42.4, 55.7, 115.4, 123.2, 126.5, 128.6, 128.7, 129.7,
129.8, 131.3, 137.4, 141.4, 192.5. m/z (GC-MS, HRMS):
327.432 (M+).Anal. Calc. for C23H23NO: C, 83.85; H, 7.04;
N, 4.25. Found: C, 82.89; H, 7.18; N, 4.10.
3-(4-Chloro-phenyl)-1-phenyl-3-phenylamino-propan-1-
one, (11)
A white solid; Rf = 0.70 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3382(NH), 1690(CO). 1H NMR
(300 MHz, TMS, CDCl3): d 3.48 (d, J 5.8 Hz, 2H), 5.18
(t, 1H), 6.60 (d, J 6.2 Hz, 2H, Ar-H), 6.68-6.73 (m, 1H,
Ar-H), 7.07-7.12 (m, 2H, Ar-H), 7.28 (d, J 7.6 Hz, 2H,
Ar-H), 7.52 (d, J 8.1 Hz, 2H, Ar-H), 7.60-7.67 (m, 2H, Ar-
H), 7.71-7.76 (m, 1H, Ar-H), 7.96 (d, J 9.1 Hz, 2H, Ar-H).
13C NMR (75 MHz, CDCl3): d 47.9, 53.7, 111.5, 115.3,
128.1, 128.6, 128.7, 128.9, 129.6, 131.8, 136.5, 141.1,
144.5, 196.6. m/z (GC-MS, HRMS): 337.416 (M+). Anal.
Calc. for C21H18ClNO: C, 75.11; H, 5.40; N, 4.17. Found:
C, 75.32; H, 5.67; N, 4.23.
3-(4-Methoxy-phenyl)-1-phenyl-3-phenylamino-propan-
1-one, (8)
A white solid; Rf = 0.67 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3401(NH), 1679(CO). 1H NMR
(300 MHz, TMS, CDCl3): d 3.47-3.40 (m, 2H), 3.62 (s, 3H,
-OCH3), 4.96 (t, 1H), 6.47 (d, J 8.1 Hz, 2H, Ar-H), 6.52 (t,
1H, Ar-H), 6.90-6.86 (m, 2H, Ar-H), 7.23 (d, J 8.2 Hz, 2H,
Ar-H), 7.33-7.28 (m, 2H, Ar-H), 7.44-7.41 (m, 2H, Ar-H),
7.54-7.51 (m, 1H, Ar-H), 7.89 (d, J 7.5 Hz, 2H, Ar-H).
13C NMR (75 MHz, CDCl3): d 47.6, 54.2, 56.2, 113.2,
113.9, 116.4, 128.6, 128.1, 127.9, 129.4, 132.9, 134.2,
137.7, 160.2, 198.2. m/z (GC-MS, HRMS): 331.423 (M+).
Anal. Calc. for C22H21NO2: C, 79.73; H, 6.39; N, 4.23.
Found: C, 79.64; H, 6.48; N, 4.31.
3-(4-Iodo-phenylamino)-1,3-diphenyl-propan-1-one, (12)
A white solid; Rf = 0.63 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3383(NH), 1669(CO). 1H NMR
(300 MHz, TMS, CDCl3): d 3.34 (m, 2H), 4.64 (t, 1H),
6.24 (d, J 7.0 Hz, 2H, Ar-H), 6.96 (d, J 8.1 Hz, 2H, Ar-H),
7.06-7.02 (m, 1H,Ar-H), 7.14-7.10 (m, 2H,Ar-H), 7.25 (d,
J 6.3 Hz, 2H, Ar-H), 7.34-7.29 (m, 2H, Ar-H), 7.45-7.42
(m, 1H, Ar-H), 7.83 (d, J 8.1 Hz, 2H, Ar-H). 13C NMR
(75 MHz, CDCl3): d 46.4, 55.3, 113.2, 126.2, 126.4, 127.8,
128.5, 128.7, 128.9, 132.3, 132.5, 137.5, 138.8, 142.8,
198.2. m/z (GC-MS, HRMS): 346.382 (M+). Anal. Calc.
for C21H18INO: C, 59.03; H, 4.25; N, 3.28. Found: C, 59.12;
H, 4.17; N, 3.34.
3-(4-Nitro-phenyl)-1-phenyl-3-phenylamino-propan-1-
one, (9)
A white solid; Rf = 0.54 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3372 (NH), 1681 (CO).
1H NMR (300 MHz, TMS, CDCl3): d 3.52 (d, J 6.1 Hz,
2H), 5.13 (t, 1H), 6.52 (d, J 6.5 Hz, 2H, Ar-H), 6.66-6.70
(m, 1H, Ar-H), 7.07-7.11 (m, 2H, Ar-H), 7.48-7.43 (m,

Vol. 21, No. 12, 2010
Kidwai and Jahan
S3
3-Phenyl-3-phenylamino-1-p-tolyl-propan-1-one, (13)
2-(phenyl-p-tolylamino-methyl)-cyclohexanone, (16)
A white solid; Rf = 0.74 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3380(NH), 1670(CO). 1H NMR
(300 MHz, TMS, CDCl3): d 2.42 (s, 3H, -CH3), 3.45 (d,
J 5.9 Hz, 2H), 4.93 (t, 1H), 6.43 (d, J 7.8 Hz, 2H, Ar-H),
6.58 (m, 1H, Ar-H). 6.98 (m, 2H, Ar-H), 7.11 (d, J 6.4 Hz,
2H, Ar-H), 7.27-7.19 (m, 3H, Ar-H), 7.43 ( d, 7.8 Hz, 2H,
Ar-H), 7.86 (d, J 7.2 Hz, 2H, Ar-H); 13C NMR (75 MHz,
CDCl3): d 20.7, 44.2, 52.3, 109.2, 113.5, 124.2, 126.3,
127.3, 127.5, 128.1, 128.4, 131.5, 140.2, 141.7, 194.3.
m/z (GC-MS, HRMS): 316.374 (M+). Anal. Calc. for
C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C, 83.92;
H, 6.61; N, 4.37.
A white solid; Rf = 0.62 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3406(NH), 1702(CO). 1H NMR
(300 MHz, TMS, CDCl3, syn/anti = 34:66): d 1.33-1.89 (m,
6H), 2.14 (s, 3H, -CH3), 2.36-2.57 (m, 2H), 2.97-3.04 (m,
1H), 4.52 (d, 0.34H, J 5.2 Hz), 4.52 (d, 0.66H, J 6.8 Hz),
4.77 (brs, 1H), 6.45 (d, J 7.5 Hz, 2H, Ar-H), 6.84 (d, J 8.2
Hz, 2H,Ar-H), 7.02-7.18 ( m, 1H,Ar-H), 7.32-7.42 (m, 2H,
13
Ar-H), 7.62 (d, J 7.1 Hz, 2H, Ar-H). C NMR (75 MHz,
CDCl3): d 21.0, 23.2, 25.7, 32.9, 43.3, 55.1, 57.3, 113.3,
127.6, 126.8, 126.4, 127.1, 128.9, 140.4, 142.5, 209.2. m/z
(GC/MS, HRMS): 296.106 (M+).Anal. Calc. for C20H23NO:
C, 81.87; H, 7.90; N, 4.77. Found: C, 81.69; H, 7.56; N, 4.13.
1-(4-Nitro-phenyl)-3-phenyl-3-phenylamino-propan-1-
one, (14)
(2-(4-Methoxy-phenyl)-phenylamino-methyl)-
cyclohexanone, (17)
A white solid; Rf = 0.49 (petroleum ether/AcOEt
= 80:20); IR (KBr) nmax/cm-1: 3400 (NH), 1678 (CO).
1H NMR (300 MHz, TMS, CDCl3): d 3.44-3.57 (m, 2H),
5.10 (t, 1H), 6.48 (d, J 6.2 Hz, 2H, Ar-H), 6.69-6.63 (m,
2H,Ar-H). 6.80-6.83 ( m, 1H,Ar-H), 7.14 (d, J 7.6 Hz, 2H,
Ar-H), 7.23-7.26 (m, 1H, Ar-H), 7.31-7.35 (m, 2H, Ar-H),
7.62 (d, J 6.3 Hz, 2H, Ar-H); 7.92 (d, J 7.2 Hz, 2H, Ar-H).
13C NMR (75 MHz, CDCl3): d 46.2, 53.4, 110.1, 114.9,
122.7, 123.5, 126.1, 127.9, 128.3, 128.8, 142.6, 141.3,
151.8, 196.4. m/z (GC-MS, HRMS): 346.217 (M+). Anal.
Calc. for C21H18N2O3: C, 72.82; H, 5.24; N, 8.09. Found:
C, 72.96; H, 5.34; N, 8.11.
A white solid; Rf = 0.69 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3332(NH), 1690(CO). 1H NMR
(300 MHz, TMS, CDCl3, syn/anti = 42:58): d 1.68-1.93 (m,
6H), 2.42-2.47 (m, 2H), 2.72-2.76 (m, 1H), 3.89 (s, 3H,
OCH3), 4.08 (d, 0.58H, J 7.3 Hz), 4.63 (d, 0.42H, J 4.4 Hz),
4.71 (br, s, 1H), 6.64-6.61 (m, 1H,Ar-H), 6.68 (d, J 8.3 Hz,
2H,Ar-H), 7.10-7.03 ( m, 2H,Ar-H), 7.16 (d, J 7.6 Hz, 2H,
Ar-H), 7.27 (d, J 8.4 Hz, 2H, Ar-H); 13C NMR (75 MHz,
CDCl3): d 20.8, 23.2, 27.8, 30.9, 41.3, 57.2, 56.3, 113.1,
117.2, 126.8, 128.6, 128.8, 136.4, 138.2, 147.0, 212.7. m/z
(GC/MS, HRMS): (M+). Anal. Calc. for C20H23NO2: C,
77.64; H, 7.49; N, 4.53. Found: C, 77.43; H, 7.58; N, 4.59.
2-(Phenyl-phenylamino-methyl)-cyclohexanone, (15)
A white solid; Rf = 0.68 (Petroleum Ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3390 (NH), 1690 (CO).
1H NMR (300 MHz, TMS, CDCl3, syn/anti = 48:52): d
1.25-1.76 (m, 6H), 2.28-2.44 (m, 2H), 2.73-2.78 (m, 1H),
4.62 (d, 0.52H, J 7.6 Hz), 4.70 (brs, 1H), 4.79 (d, 0.48H,
J 4.8 Hz), 6.37 (d, J 7.3 Hz, 2H, Ar-H), 6.51-6.63 (m,
1H, Ar-H), 7.02-7.07 (m, 2H, Ar-H), 7.19-7.26 (m, 1H,
Ar-H), 7.29-7.37 (m, 2H, Ar-H), 7.60 (d, J 7.8 Hz, 2H,
Ar-H). 13C NMR (75 MHz, CDCl3): d 23.2, 24.5, 28.3,
36.7, 52.1, 57.4, 108.6, 113.5, 123.1, 127.5, 128.9, 138.6,
140.4, 203.8. m/z (GC/MS, HRMS): 283.329 (M+). Anal.
Calc. for C19H21NO: C, 81.68; H, 7.58; N, 5.01. Found:
C, 81.34; H, 7.45; N, 5.23.
(2-(4-Chloro-phenylamino)-phenyl-methyl)-
cyclohexanone, (18)
A yellowish solid; Rf = 0.73 (petroleum ether/AcOEt =
80:20); IR (KBr) nmax/cm-1: 3378 (NH), 1674 (CO).
1H NMR (300 MHz, TMS, CDCl3, syn/anti = 28:72): d
1.60-1.92 (m, 6H), 2.28-2.31 (m, 2H), 2.65-2.61 (m, 1H),
4.10 (d, 0.72H, J 8.2 Hz), 4.30 (d, 0.28H, J 4.1 Hz), 4.56
(brs, 1H), 6.58 (d, J 7.3 Hz, 2H, Ar-H), 6.98 (d, J 8.7 Hz,
2H, Ar-H), 7.22-7.17 ( m, 1H, Ar-H), 7.41-7.48 (m, 2H,
Ar-H), 7.56 (d, J 8.9 Hz, 2H, Ar-H). 13C NMR (75 MHz,
CDCl3): d 24.9, 25.1, 28.7, 40.1, 54.6, 57.3, 112.6 120.1,
124.9, 128.1, 138.6, 140.5, 210.4. m/z (GC/MS, HRMS):
344.281 (M+). Anal. Calc. for C19H20ClNO: C, 72.72; H,
6.42; N, 4.46. Found: C, 72.68; H, 6.32; N, 4.41.