Microwave-enhanced sulphated zirconia and SZ/MCM-41 catalyzed regioselective synthesis of β-amino alcohols under solvent-free conditions

Article abstract of DOI:10.3390/molecules13040977

A solvent-free approach for the regioselective synthesis of β-amino alcohols in shorter reaction times and higher yields, compared to conventional heating is described. It involves microwave (MW) exposure of undiluted reactants in the presence of sulphated zirconia (SZ) or sulphated zirconia over MCM-41 (SZM) as catalyst. Both acid materials can be easily recovered and reused.

Full text of DOI:10.3390/molecules13040977

Molecules 2008, 13, 977-985
molecules
ISSN 1420-3049
© 2008 by MDPI
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Full Paper
Microwave-Enhanced Sulphated Zirconia and SZ/MCM-41
Catalyzed Regioselective Synthesis of β-Amino Alcohols Under
Solvent-Free Conditions
Guillermo Negrón-Silva 1,*, C. Xochitl Hernández-Reyes 1, Deyanira Angeles-Beltrán 1, Leticia
Lomas-Romero 2 and Eduardo González-Zamora 2
1
Departamento de Ciencias Básicas, UAM, Av. San Pablo No 180, C.P. 02200, México D. F.,
México; E-mails: C. X. Hernández-Reyes: floronix@yahoo.com.mx; D. Angeles-Beltrán:
dab@correo.azc.uam.mx
2
Departamento de Química, UAM, Av. San Pablo No 180, C.P. 02200, México D. F., México; E-
mails: L. Lomas-Romero: llr@xanum.uam.mx; E. González Zamora: egz@xanum.uam.mx
* Author to whom correspondence should be addressed; E-mail: gns@correo.azc.uam.mx
Received: 8 April 2008; in revised form: 24 April 2008 / Accepted: 24 April 2008 / Published: 26 April
2008
Abstract: A solvent-free approach for the regioselective synthesis of β-amino alcohols in
shorter reaction times and higher yields, compared to conventional heating is described. It
involves microwave (MW) exposure of undiluted reactants in the presence of sulphated
zirconia (SZ) or sulphated zirconia over MCM-41 (SZM) as catalyst. Both acid materials
can be easily recovered and reused.
Keywords: Sulphated zirconia; amino alcohols; microwaves; regioselective; oxiranes.
Introduction
There is a noticeable growing interest in obtaining solid catalysts that should be able to replace
those commonly used, such as concentrated H2SO4, HCl and triflates, among others, for chemical
transformations because they can be recovered, reused, and are generally innocuous to the
environment. Sulphated zirconia, right from its first reported use in 1979 by Hino and co-workers [1],

Molecules 2008, 13
978
has commanded increasing attention due to its significantly large acidity, which is associated to its
relevant properties such as efficient catalysis of organic reactions. In recent literature, descriptions can
be found of coumarin synthesis through the Pechmann reaction [2], alcohol and amine acylation
reactions [3], Mannich-type reactions between silylated ketones and aldimines [4], xylose to furfural
conversion [5], indole synthesis [6] and the synthesis of β-acetamidocarbonyl compounds [7]. Vicinal
amino alcohols are present in various natural and synthetic biologically active products used for
preparing diabetes treatments, bronco-dilators, anti-inflammatory, anti-hypotensive, anti-depressants,
anti-HIV and anti-malarials [8], in addition to compounds used as catalysts in asymmetric synthesis
[9].
Epoxide aminolysis reactions, normally catalyzed by acids or bases, are an efficient route for
obtaining β-amino alcohols. However, homogeneous catalysis of these reactions is inconvenient, as it
entails the impossibility of reusing the catalyst after the reactions, and in addition, the workup
processes often can be laborious. Recently, we found a description of the reaction performed under
mild conditions in aqueous media [10]. Among the solid materials used to catalyze aminolysis
reactions, one may mention the use of silica gel [11], zeolite NaY [12], alumina [13], copper sulphate-
supported polymer [14], montmorillonite [15], alumina-supported phosphomolybdic acid [16] and acid
resins [17].
Microwave (MW) irradiation, an unconventional energy source, has been used for a variety of
applications including organic synthesis, wherein chemical reactions are accelerated because of
selective absorption of MW energy by polar molecules, non-polar molecules being inert to the MW
dielectric loss [18]. Recently, it has been found that the use of microwave irradiation to assist organic
reactions has considerable advantages over thermal reactions. Reactions that typically require high
temperatures and extended reaction times have been considerably accelerated using microwave
irradiation. The ring-opening of epoxides [19] can be performed in a very short time under microwave
irradiation, compared to the conventional thermal epoxide-opening conditions. The use of microwave
irradiation also eliminated the problems of decomposition of the substrates or products during the
reaction due to prolonged thermal treatment.
Results and Discussion
Our work group has recently shown [20] that MCM-41-supported sulphated zirconia is an efficient
catalyst for the regioselective nucleophilic opening of oxiranes with aniline and benzylamine, under
thermal and solvent-free conditions, which motivated us to study the corresponding microwave
assisted reaction (Scheme 1).
Scheme 1. Aminolysis of oxiranes.
H
N
OH
OH
H
O
R1NH2
+
SZ or SZM
+
N
60°C
2a, R1=Ph
2b, R1=PhCH2
2
R1
solventless
R1
R
R
MW irradiation
R
1
3
4

Molecules 2008, 13
979
Once the catalyst has been spent, it can be recovered by filtration reactivated by regeneration at 550
°C for one hour. The reactivated samples treated this way displayed the XRD traces shown in Figure 1,
where the initial pattern corresponds to as-received sulphated zirconia (SZ); the recovered samples that
were used again are labelled SZFC for one cycle, SZSC for a second cycle and SZTC for a third cycle.
It can be observed that formation of the monoclinic phase takes place after the first reactivation, while
for the other reactivation cycles, the monoclinic: tetragonal phase proportion was maintained.
Figure 1. XRD traces of sulphated zirconia after reactivation cycles.
The diffraction patterns corresponding to the as-prepared SZ/MCM-41 (SZM), and those of the
SZ/MCM-41 recovered after a first cycle (SZMFC), a second cycle (SZMSC) and a third cycle
(SZMTC) are shown in Figure 2, which shows that reactivation destroys the MCM-41 phase, because
its corresponding peak did appear at 2θ = 2.5.
Figure 2. XRD traces of sulphated zirconia over MCM-41 after reactivation cycles.
The textural properties of the sulphated zirconia and the SZ/MCM-41, and those of the reactivated
catalysts, shown in Table 1 indicate that the texture of the catalytic material recovered after heating for
1 h at 550 °C, did not undergo significant changes.

Molecules 2008, 13
980
Table 1. Textural properties of the catalysts.
Specific area /
(m2·g-1)
105.73
107.84
86.82
Pore volume /
(cc·g-1)
0.12
Pore size /
(Å)
Sample
SZ
42.79
55.90
63.04
54.59
27.19
24.95
29.00
27.03
SZFC
0.15
SZSC
0.13
SZTC
SZM
96.83
0.13
554.21
580.88
415.72
431.29
0.40
SZMFC
SZMSC
SZMTC
0.39
0.33
0.29
The experimental results related to Scheme 1 are presented and compared in Table 2 (3/4 yield,
refers to Scheme 1). They show that the use of the microwave radiation at 60°C (initial power 50W)
did not catalyze the reaction. However, if the latter is carried out in the presence of sulphated zirconia
or sulphated zirconia supported on MCM-41 the reaction is catalyzed and a significant decrease of the
reaction times becomes obvious, as compared to those measured during thermal treatment. Two cases
can be mentioned as examples: in entry 1 in Table 2, using only microwaves and no catalyst, no
product formation is observed. Using microwaves, 75% of product 3 is obtained with SZ and 70% of
product 3 is obtained with SZM, and no product 4 is formed in both cases. In entry 2, using only
microwaves and no catalyst, no product formation is observed. Using microwaves and SZ 68% of
product 3 is obtained and no product 4, and with SZM 64% of product 3 and 19% of product 4 are
obtained, for an 84% overall yield. Reaction times for both entries are shorter than thermal treatment
ones.
Table 2. Yields (%) (3/4 refers to Scheme 1), calculated using GC-FID and compared
with published data [20].
MW
Amine Time
(min)
3/4 yielda 3/4 yieldb 3/4 yieldc 60 oC 3/4 yieldd 3/4 yielde
Entry
Epoxide
No cat.
(%)
0
SZ
(%)
75/0
SZM
(%)
Time
(min)
30
SZ
(%)
74/0
SZM
(%)
1
2
3
2a
2a
2b
10
70/0
23/0
O
Cl
20
0
1
68/0
78/0
64/19
40/0
300
360
61/20
82/0
63/0
35/0
O
120
O

Molecules 2008, 13
981
Table 2. Cont.
MW 3/4 yieldb 3/4 yieldc 3/4 yieldd 60 oC 3/4 yielde 3/4 yieldf
Entry
Epoxide
Aminea Time
No cat.
(%)
0
SZ
(%)
SZM
(%)
Time
(min)
300
SZ
(%)
SZM
(%)
(min)
4
2a
30
65/15
64/12
63/13
55/0
O
O
5
6
2b
2a
150
20
4
0
72/0
82/0
46/0
83/0
300
300
81/0
97/0
54/0
84/0
O
7
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
170
10
0
0
66/0
95/0
95/0
4/92
61/23
85/0
77/0
95/0
83/0
86/0
85/0
85/0
89/0
11/0
86/0
47/0
5/85
23/9
77/4
44/0
80/0
70/0
77/0
55/0
80/0
70/0
300
300
300
60
71/0
93/0
83/0
0/96
53/31
81/0
87/0
86/0
87/0
76/0
77/0
76/0
85/0
14/0
99/0
45/0
5/91
55/25
83/0
81/0
81/0
52/0
57/0
51/0
59/0
82/0
O
8
O
9
120
10
0
O
10
11
12
13
14
15
16
17
18
19
0
O
180
110
120
10
11
2
360
300
300
30
O
O
O
12
0
O
O
O
O
O
20
11
2
30
O
O
30
60
50
36
0
60
O
O
O
O
10
60
O
O
20
9
60
O
a
b
c
2a = aniline; 2b = benzylamine; MW radiation-assisted reaction without catalyst; MW
assisted reaction with SZ; d MW assisted reaction with SZM; e Solvent-free reaction at 60 °C with
SZ [20]; f Solvent-free reaction at 60 °C with SZM [20].

Molecules 2008, 13
982
In order to assess the catalytic activity of the reactivated materials, these were used in the test
reaction given in entry 15 in Table 2, using 2,3-epoxy-3-phenoxypropane as substrate and benzylamine
(2b) as nucleophile, under the same conditions previously described. It was noted that their activity
was maintained, as shown in Table 3: regardless of the reactivation process of the SZ/MCM-41, a
destruction of the MCM-41 occurs.
Table 3. Catalytic activity of reactivated catalysts. (3/4 yield refers to Scheme 1).
MW Time
(min)
20
3/4 Yield (%)
SZ
3/4 Yield (%)
SZM
Calcination
1st
2nd
3rd
77/0
76/0
20
79/0
68/0
20
65/0
70/0
Conclusions
When the aminolysis reaction takes place mainly through microwave assistance, the yields are
typically lower than 5 %, although entries 11, 13, 15, 17 and 19 gave yields of 11, 12, 11, 36 and 9 %,
respectively. Entries 1, 2, 4, 6, 7, 8, 9, 10, 14 and 18 did not afford any reaction products. The
application of microwave irradiation in conjunction with the use of sulphated zirconia and SZ/MCM-
41, under solvent-free conditions, enables the regioselective synthesis of β-amino alcohols, thus
providing a unique chemical processes with special attributes such as enhanced reaction rates, higher
yields, and the associated ease of manipulation. The catalyst can be easily recovered and reused for at
least three cycles without any significant decreases in yield and regioselectivity. It is worthwhile to
mention that the reactions where the SZ/MCM-41 was used, microwave irradiation destroyed the
characteristic structure of MCM-41 though its activity was maintained even after three reaction cycles,
which indicates that catalytic activity depends on the presence of the sulphated zirconia, be it
tetragonal or monoclinic.
Experimental
General
The sulphated zirconia was characterized using a Phillips X´Pert Instrument diffractometer with Cu
Kα, and nitrogen physisorption was measured at -196 °C with a Micromeritics ASAP 2020. The
reaction products were analyzed using an HP-5 column on a Hewlett Packard model 6890 Gas
Chromatograph equipped with a model 5973 mass detector system, with the oven programmed from
70-200°C (10°C/min) for 4 min then 200-280°C (10°C/min) for 3 min, inj. 250ºC, det. 280 °C; the
detector was set in the Chemical Ionization mode using methane as reactive gas.

Molecules 2008, 13
983
Synthesis of sulphated zirconia supported on MCM-41
Preparation of the sulphated zirconia supported on MCM-41 (SZM) has been already described.
[20] Siliceous MCM-41 (300 mg) were mixed with zirconium sulphate (15 mL) in methanol (1 wt %
S), the heterogeneous mixture was stirred 14 h. Then, the impregnated solid was dried for 6 days at 50
°C and finally calcined at 660 °C for 3 h in air flow.
General experimental procedure for β-amino alcohol synthesis
A mixture of oxirane 1 (186 mg, 1.0 mmol), aniline (2a) or benzylamine (2b) (93 mg or 107 mg,
1.1 mmol), and sulphated zirconia or sulphated zirconia on MCM-41 (50 mg) were introduced into a
pressurised reaction tube (10 mL) equipped with a magnetic stirrer, which was irradiated at 60 °C
(initial power 50 W) for 10 min in a self tuning single mode CEM Labmate® microwave synthesizer.
After completion of the reaction, the mixture was cooled rapidly to room temperature, passing
compressed nitrogen through the microwave cavity for 5 min. The catalyst was then recovered by
filtration and the organic product was dried under reduced pressure. All products were identified by
comparison with the previously described physical and spectroscopic data of the corresponding β-
amino alcohols [20].
Acknowledgements
The authors would like to thank Consejo Nacional de Ciencia y Tecnología, CONACYT (project
59417) for financial support of this work. GNS, LLR and EGZ thank the SNI for the distinction of
their membership and the stipend received.
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Sample Availability: Samples of the compounds are available from the authors.
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