ZrOCl2·8H2O on montmorillonite K10 accelerated conjugate addition of amines to α,β-unsaturated alkenes under solvent-free conditions

Article abstract of DOI:10.1016/j.tet.2005.10.006

At room temperature, ZrOCl₂·8H₂O on montmorillonite K10 efficiently catalyzes conjugate addition of amines to a variety of conjugated alkenes such as α,β-unsaturated carbonyl compounds, carboxylic esters, nitriles and amides under solvent-free conditions. The catalyst can be recycled for subsequent reactions without any appreciable loss of efficiency.

Full text of DOI:10.1016/j.tet.2005.10.006

Tetrahedron 62 (2006) 672–677
ZrOCl2$8H2O on montmorillonite K10 accelerated conjugate
addition of amines to a,b-unsaturated alkenes under
solvent-free conditions
*
Mohammed M. Hashemi, Bagher Eftekhari-Sis, Amir Abdollahifar and Behzad Khalili
Department of Chemistry, Sharif University of Technology, PO Box 11365-9516, Tehran, Iran
Received 14 July 2005; revised 20 September 2005; accepted 6 October 2005
Available online 28 October 2005
Abstract—At room temperature, ZrOCl2$8H2O on montmorillonite K10 efficiently catalyzes conjugate addition of amines to a variety of
conjugated alkenes such as a,b-unsaturated carbonyl compounds, carboxylic esters, nitriles and amides under solvent-free conditions. The
catalyst can be recycled for subsequent reactions without any appreciable loss of efficiency.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
reaction conditions in acetonitrile or 1,2-dichloroethane
which are toxic. In some cases, a stoichiometric amount of
Lewis acid such as AlCl3, TiCl4 or SnCl4 are required.4
The development of new synthetic methods leading to
b-amino ketones or their derivatives has attracted much
attention in organic synthesis. These b-amino ketones are
attractive targets for chemical synthesis because of their
prevalence and wide utility. Among the methods for
generating b-amino ketones, the Mannich reaction is a
classic method for the preparation of these derivatives.1
However, due to the drastic reaction conditions and the long
reaction times, the classic Mannich reaction presents serious
disadvantages.1 The approach based on conjugate addition
of amines to a,b-unsaturated carbonyl compounds is one of
the most simple and effective alternative methods for
preparing b-amino ketones.2
The use of zirconium(IV) salts as an efficient Lewis acid for
various transformations, such as electrophilic amination
of activated arenes,5 transthioacetylization of acetals,6
deoxygenation of heterocyclic-N-oxides,7 reduction of
nitro compounds,8 conversion of carbonyl compounds to
1,3-oxathiolanes,9 selective oxidation of primary and
benzylic alcohols,10 synthesis of nitriles from O-arylal-
doximes,11 chemoselective N-nitrosation of secondary
amines,12 Michael reaction of 1,3-dicarbonyls and enones,13
opening of epoxide rings by amines,14 reactions of indole,
1-methylindole, and pyrrole with a,b-unsaturated ketone15
and Friedel-Crafts reactions has been well documented in
the literature.
The Michael reaction, which was discovered many years
ago, has been used as one of the most useful methods for
effecting carbon–carbon bond formation and later has also
been efficiently manipulated for carbon-sulfur and carbon-
nitrogen bond forming processes.2 This reaction is usually
carried out under acid or base catalysis.3 However, to avoid
side reactions, occasionally encountered in the presence of a
strong acid or a base, a number of alternative procedures
have been developed in the past few years and in particular,
various Lewis acid-induced reactions have been reported.4
Unfortunately, many of these procedures often require a
large excess of reagents, long reaction time and drastic
Synthetic chemists have been using highly dispersed
mineral solids with extensive specific areas, for a
considerable time. Many organic reactions have been
devised in which the reagents are deposited on various
inorganic solid supports. These reagents have advantages
over the conventional homogeneous solution techniques:
easy set-up and work-up, mild experimental conditions,
high yields and/or selectivity.16 Montmorillonite K10 had a
great impact in organic synthesis and has offered major
breakthroughs for the fine chemicals manufacturing
industries.17
Keywords: Conjugate addition; Amine; a,b-Unsaturated olefins; Zirconium
oxychloride; Solvent free.
As part of our research on chemical transformations,18 in
this paper we report a simple and environmentally benign
*
Corresponding author. Tel.: C98 21 661 65313; fax: C98 21 660 05718;
e-mail: mhashemi@sharif.edu
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.10.006

M. M. Hashemi et al. / Tetrahedron 62 (2006) 672–677
673
methodology for the conjugate addition of amines to a,b-
unsaturated esters, nitriles, amides and ketones under
neutral, solvent-free conditions and at room temperature
using ZrOCl2$8H2O on montmorillonite K10 as catalyst.
montmorillonite K10 in the conjugate addition of piperidine
to methylacrylate, respectively.
The conjugate reaction of piperidine with methylacrylate in
the presence of ZrOCl2$8H2O/montmorillonite K10 gave
the conjugate adduct in high yield and in a short time. The
results are summarized in Table 2. The data in Table 2
clearly show that the reaction of different aliphatic amines
and a,b-unsaturated esters give the corresponding b-amino
ester in high yield at room temperature without using any
solvent. Primary amines, such as benzylamine, n-butyl-
amine and cyclohexylamine reacted with a,b-unsaturated
esters to give only the mono-alkylated adduct. No side
product was observed by using excess of the reactants.
When aromatic amines, such as aniline, were added to an
a,b-unsaturated ester or a nitrile (entry 8h, Table 2 and entry
7gg, Table 3), the conjugate adduct was formed in only low
yield. The difference in the reactivity of aromatic amines
shows the chemoselectivity of conjugate addition of
aliphatic amines in this method. Thus, when a mixture of
aniline and piperidine were exposed to excess methylacryl-
ate in the presence of ZrOCl2$8H2O/montmorillonite K10,
the piperidine adduct was obtained as the sole product
(Scheme 2).
2. Results and discussion
Different types of amines (primary and secondary) were
subjected to conjugate addition reactions on the clay-
supported zirconium oxychloride. The overall reaction is as
shown in Scheme 1.
We started to study the conjugate addition catalyzed by
ZrOCl2 supported on the montmorillonite K10 by examin-
ing the conditions required for the reaction involving
piperidine and methylacrylate to afford adduct 1a. A
summary of the results obtained is provided in Table 1.
Entries 1–7 show the effect of various solvents on the yield
of the reaction. Although acetonitrile, dichloromethane and
solvent-free conditions afforded the product in high yields,
we chose solvent-free conditions for economical and
environmental acceptability. Entry 7 describes the yields
of four consecutive additions leading to 1a. In these
experiments the product was isolated by filtration, the
solid residues washed with dichloromethane, and the
remaining catalyst reloaded with fresh reagents for further
runs, follows reactivation (80 8C, vacuum). No decrease in
the yield was observed demonstrating that ZrOCl2/mont-
morillonite K10 can be reused as a catalyst in conjugate
additions. The optimum amount of catalyst (0.15 mmol of
ZrOCl2$8H2O on 0.1 g montmorillonite K10) was deter-
mined from experiments corresponding to entries 7–9.
Entries 10, 11 and 12 show the effect of montmorillonite
K10 and the catalytic effect of ZrOCl2$8H2O/
This method also works well for a,b-unsaturated nitriles,
amides and ketones. Thus, the conjugate addition of
aliphatic amines to these a,b-unsaturated compounds in
the presence of ZrOCl2$8H2O/montmorillonite K10 gave
the corresponding conjugate adducts in high yield and in a
short time. The results are summarized in Table 3. On the
other hand, in the case of a,b-unsaturated aldehydes such as
acrolein, the reaction suffers from regiochemical restriction
caused by competing 1,2- versus 1,4-addition (Scheme 3).
As is well know, iminium salts generally react faster and
R'
R'
ZrOCl2 / Montmorillonite K10
r.t.
R1R2N
R1R2NH
+
R
X
X
R
R = H, Me, Ph;
R' = H, Me;
X = COOMe, CN, COMe, CONH2
Scheme 1.
Table 1. Conjugate addition of piperidine (3 mmol) to methylacrylate (2 mmol) under different conditions
Entry
Solvent
ZrOCl2$8H2O
(mmol)
Montmorillonite K10 (g)
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
H2O
CH2Cl2
CH3CN
THF
EtOH
DMF
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.10
0.20
0.15
0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
60
35
35
45
45
45
30
30
30
60
60
60
34
85
83
52
56
62
84, 80, 79, 80b
65
87
57
48
23
9
10
11
12
0.1
0
0
a Isolated yield.
b Catalyst was used over four runs.

674
M. M. Hashemi et al. / Tetrahedron 62 (2006) 672–677
Table 2. Conjugate addition of amines to a,b-unsaturated esters catalyses by ZrOCl2$8H2O/montmorillonite K10 under solvent-free conditions
Entry
1a
Amines
Ester
Product
Yield (%)a (time, min)b
84 (30)4f
COOMe
NH
N
COOMe
COOMe
COOMe
COOMe
NH
2b
96 (30)4f
N
O
O
NH
3c
76 (35)20
N
COOMe
COOMe
NH
4d
5e
6f
82 (30)4f
86 (30)27
87 (30)21
N
COOMe
COOMe
COOMe
H
Ph
NH2
COOMe
COOMe
Ph
N
H
N
NH2
H
7g
8h
n-BuNH2
89 (30)27
COOMe
COOMe
N
n-Bu
COOMe
COOMe
H
N
PhNH2
29 (180)27
Ph
Ph
Ph
Ph
NH
COOEt
N
9i
79 (30)4f
88 (35)4f
74 (30)4f
COOEt
COOEt
Ph
Ph
O
O
NH
COOEt
COOEt
N
N
10j
11k
NH
COOEt
COOEt
COOEt
Ph
Ph
Ph
Ph
H
Ph
NH2
Ph
N
COOEt
COOEt
12l
80 (35)22
85 (40)23
H
N
NH2
13m
Ph
Ph
H
N
COOEt
14n
n-BuNH2
86 (35)26
n-Bu
COOEt
Ph
NH
15o
16p
17q
18r
19s
20t
82 (35)27
88 (30)27
84 (30)20
73 (35)27
80 (30)27
82 (35)27
N
N
COOMe
COOMe
COOMe
NH
COOMe
COOMe
COOMe
COOMe
O
O
NH
N
N
COOMe
NH
COOMe
COOMe
H
Ph
NH2
Ph
N
n-BuNH2
H
N
n-Bu
COOMe
COOEt
COOEt
COOEt
COOMe
COOEt
NH
84 (25)4f
89 (30)20
57 (35)4f
N
N
N
21u
22v
23w
O
COOEt
COOEt
O
NH
NH
a Isolated yields.
b References.

M. M. Hashemi et al. / Tetrahedron 62 (2006) 672–677
675
Table 3. Conjugate addition of amines to a,b-unsaturated nitriles, amides and ketones catalyses by ZrOCl2$8H2O/montmorillonite K10 under solvent-free
condition
Entry
1aa
Amine
Ethylenic compound
Product
Yield (%)a (time, min)b
94 (15)4b
CN
NH
N
N
CN
CN
CN
CN
NH
2bb
3cc
98 (30)4b
O
O
O
NH
98 (20)21b
N
CN
CN
NH
4dd
75 (10)27
N
CN
CN
CN
H
N
5ee
6ff
89 (15)27
93 (15)27
32 (120)26
Ph
NH2
CN
CN
Ph
H
N
n-BuNH2
n-Bu
H
N
PhNH2
CN
7gg
Ph
CN
NH2
NH
8hh
9ii
87 (30)28
90 (35)24
83 (35)26
86 (35)26
N
CONH2
O
NH2
O
O
NH
N
CONH2
CONH2
O
NH2
H
Ph
NH2
Ph
N
10jj
11kk
O
NH2
H
n-BuNH2
N
n-Bu
CONH2
O
O
NH
N
12ll
72 (25)4b
86 (30)4a
O
O
O
NH
N
N
13mm
O
O
O
O
NH
14nn
15oo
73 (25)25
94 (75)27
O
O
H
N
Ph
PhNH2
a Isolated yields.
b References.
1a
COOMe
N
ZrOCl2 / Montmorillonite K10
r.t, 30 min
NH
100%
+ PhNH2
3 mmol
+
COOMe
2 mmol
H
8h
COOMe
N
3 mmol
Ph
0%
Scheme 2.
H
H
N
ZrOCl2 / Montmorillonite K10
r.t
NH +
N
O
N
iminium salt
Scheme 3.

676
M. M. Hashemi et al. / Tetrahedron 62 (2006) 672–677
more regioselectively than the corresponding carbonyl
compounds.19 Thus, in the a,b-unsaturated iminium salt,
the hard electrophilic character of the N-linked carbon atom
is enhanced, that 1,2-attack by a second molecule of amine
takes place almost exclusively.
with methylacrylate for four times (entry 7, Table 1) and no
decrease in the yield was observed.
References and notes
3. Conclusion
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unsaturated olefins by using the ZrOCl2$8H2O/montmor-
illonite K10. Due to the stability of the catalyst under the
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4. Experimental
4.1. General
NMR spectra were recorded on a Bruker ACF 500.
IR spectra were measured using a Perkin Elmer 781
spectrometer. Column chromatography was performed on
silica gel, Merck grade 60. CH2Cl2 was distilled before use.
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