Henry reactions have been performed for the first time with suitably activated Mg-Al hydrotalcite as catalyst in quantitative yields in the liquid phase under mild reaction conditions and with low reaction times. Exclusive synthesis of β-nitroalkanols (3) is realised by the compatible basic Bronsted hydroxy sites of the modified hydrotalcite. Reusability with consistent activity and selectivity for a number of cycles is established indicating that the hydrated hydrotalcite employed here is a potentially eco-friendly catalyst which can replace soluble bases in commercial synthesis

Choudary, B. M.

Figueras, F.

Koteswara Rao, K.

Lakshmi Kantam, M.

Venkat Reddy, Ch.

English

Publications of the IAS Fellows

Henry reactions catalysed by
modified Mg–Al hydrotalcite: 
an efficient reusable solid base for selective synthesis of
b-nitroalkanols†
B. M. Choudary,*a M. Lakshmi Kantam,*a Ch. Venkat Reddy,a K. Koteswara Raoa and F. Figuerasb
a Indian Institute of Chemical Technology, Hyderabad-500007, India. E-mail: choudary@iict.ap.nic.in
b Institut de Recherches sur la Catalyse, 2, Avenue Albert Einstein, 69626 Villeurbanne cedex, France
Received 20th May 1999
Summary
Henry reactions have been performed for the first time with suit -
ably activated Mg–Al hydrotalcite as catalyst in quantitative
yields in the liquid phase under mild reaction conditions and with
low reaction times. Exclusive synthesis of b-nitroalkanols (3) is
realised by the compatible basic Brönsted hydroxy sites of the
modified hydrotalcite. Reusability with consistent activity and
selectivity for a number of cycles is established indicating that
the hydrated hydrotalcite employed here is a potentially eco-
friendly catalyst which can replace soluble bases in commercial
synthesis.
Introduction
The design and development of environment-friendly solid
base catalysts to replace soluble bases for C–C bond formation
in organic transformations widely employed in the bulk and
fine chemical industries in order to achieve atomic selectivity
of the desired product and reduce the salts formed as a result of
neutralisation of soluble bases is of intense research activity.1–3
2-Nitroalkanols, the products of the Henry reaction and impor-
tant representatives of C–C bond formation, are ubiquitous mate-
rials extensively used in many important syntheses.4
The greatest challenge in the selective synthesis of 2-nitroalka-
nols among the multiple product options such as polymerization,
aldol olefins and Cannizzaro products, is the selection of
the appropriate base to achieve the most sensitive operation in
the organic synthesis. Further, 2-nitroalkanols formed from 
aryl aldehydes tend to eliminate water to form nitroalkenes5
which readily polymerise. The classical methods for this 
important transformation involving the use of bases such as 
alkali metal hydroxides, carbonates, bicarbonates, alkoxides, 
barium and calcium hydroxide, magnesium and aluminium
ethoxides, a rhodium complex, potassium exchanged zirconium
phosphate and also organic bases such as primary, secondary 
and tertiary amines predominantly give dehydrated products.4
Thus, careful control of the basicity of the reaction medium 
is crucial to achieve better yields of b-nitroalcohols. Such 
efforts require longer reaction times but only give moderate
yields.6,7
Heterogeneous catalysis induced by solid catalysts such as
basic alumina,8 alumina-KF,9 amberlyst6 and phase transfer
catalysis with surfactants10 are the two divergent approaches
applied in an attempt to obtain improved selectivity. The former
approach requires longer reaction times and in some cases
affords condensed olefins.5,11 Although good selectivity has been
achieved in phase transfer reactions, the reaction still requires 
a soluble base, which tends to give salts upon neutralisation at 
the end of the reaction.10 With this background, we envisaged the
use of solid bases in the form of layered double hydroxides
(LDHs) or hydrotalcite like compounds (HTLCs) in view of their
potential usefulness as adsorbents, anion-exchangers and most
importantly as basic catalysts.3,12 LDHs upon thermal decompo-
sition at ca. 450 °C give highly active homogeneous mixed
oxides, which are potential basic catalysts used for a variety 
of organic transformations.13–17 Recently, we reported a modified
method2 for the activation of a hydrotalcite catalyst the basicity
of which was tuned for base catalysed aldol, Knoevenagel and
Michael reactions18,19 in the liquid phase under very mild reaction
conditions. The significance of 2-nitroalkanols in organic 
synthesis4 and our continued interest involving hydrotalcites
prompted us to explore the Henry reaction.
Green Chemistry August 1999 187
CG
The Henry reaction is an important class of C–C bond
forming reaction. It operates under base catalysis condi-
tions to give b-nitro alkanols, important intermediates for
a variety of useful compounds such as amino alcohols.
Difficulties which lead to poor selectivity and thus waste
include dehydration (and possible subsequent reaction of
the nitroalkene formed) and Cannizzaro reaction of the
aldehydic component. This paper describes the applica-
tion of Mg–Al hydrotalcites to the Henry reaction.
Hydrotalcites are mixed oxides, in some ways similar to
clays, but basic rather than acidic, and have found uses as
medium strength base catalysts in recent years. They are
readily prepared, and catalyse several reactions selec-
tively. In the cases described here, they produce a selec-
tive and clean reaction under mild conditions. Catalyst
reuse is also demonstrated. A fully optimised procedure
would require further optimisation of the solvent used to
wash the catalyst, and recovery and recycling of the
excess nitroalkane. DJM
Green Context
† IICT Communication no. 4021.
D
ow
nl
oa
de
d 
on
 0
2 
Fe
br
ua
ry
 2
01
1
Pu
bl
ish
ed
 o
n 
01
 Ja
nu
ar
y 
19
99
 o
n 
ht
tp
://
pu
bs
.rs
c.o
rg
 | d
oi:
10.
103
9/A
904
075
G
View Online
Experimental
Here, we report a convenient and selective synthesis of 2-
nitroalkanols via the Henry reaction,20 Scheme 1, affording 100%
selectivity to b-nitroalcohols (3) in quantitative yields using
modified Mg–Al hydrotalcite.18 Modified Mg–Al hydrotalcite
(Mg/Al ratio = 2.5) was synthesized as follows: an aqueous solu-
tion (0.221 l) containing Mg(NO3)2·6H2O (0.2213 mol) (Aldrich)
and Al(NO3)3·9H2O (0.0885 mol) (Aldrich) was added slowly to
a second solution (0.221 l) containing NaOH (0.7162 mol) and
Na2CO3 (0.2084 mol) in a 1.0 l round-bottom flask under vigor-
ous stirring. The addition took nearly 3 h. Then the contents were
heated to 338 K for 16 h. The precipitate formed was filtered off
and washed with hot distilled water until the pH of the filtrate
was 7. The precipitate was dried in an oven at 353 K for 15 h. The
XRD pattern shows the presence of pure hydrotalcite, with lattice
parameters corresponding to those reported in the literature.3
Scheme 1 Henry reactions between nitromethane and various
substituted aromatic and aliphatic aldehydes.
Table 1 Henry reactions of various substituted aromatic and
aliphatic aldehydes with nitromethane catalysed by MHT
a Determined by 1H NMR,based on starting aldehyde.
b Isolated pure product. c Yield after fifth cycle.
The synthesised Mg–Al hydrotalcite catalyst was first activated
by calcination at to 723 K in a flow of air. The temperature was
raised at a rate of 10 K min21 to 723 K and maintained at this tem-
perature for 8 h. The solid was then cooled in dry nitrogen and
rehydrated at room temperature under a flow of nitrogen gas (6 l
h21) saturated with water vapour for c a . 6 h before use in reactions.
Results and discussion
Results of Henry aldol product synthesis are compiled in Table 1
with modified hydrotalcites showing the best catalytic perfor-
mance. No dehydrated product (4) was observed even after con-
tinuing the reaction for prolonged periods when we deliberately
chose aryl aldehydes as one of the reactants. The reused catalyst
exhibited consistent activity and selectivity.
Taking the Henry reaction of benzaldehyde with nitromethane
as a model reaction we compared the activity and selectivity of
the modified Mg–Al hydrotalcite catalyst with a variety of solu-
ble and solid bases such as sodium hydroxide, neutral aluminium
oxide, magnesium oxide and diamino-functionalised MCM-4121
under similar reaction conditions (Table 2). The reaction of benz-
aldehyde with nitromethane using magnesium oxide or neutral
aluminium oxide catalyst required longer reaction times and gave
poor yields, while the reaction with diamino-functionalised
MCM-41 yields the nitroalkene as the sole reaction product. The
Henry reaction was slightly sluggish under phase transfer condi-
tions10 using sodium hydroxide as a soluble base. In summary,
the results show that the modified Mg–Al hydrotalcite catalyst is
more active and selective than the other catalysts.
The Henry reaction usually requires Brönsted hydroxy sites to
abstract a proton from an active methylene group of the nitro
compound. X-Ray diffraction studies of the activated hydrotal-
cite show that the layered structure is removed upon calcination
but is restored by rehydration and a meixnerite-like structure is
formed in which OH2 are the compensating anions. These anions
are mobile and therefore basic and catalyse several reactions pro-
ceeding through basic mechanisms such as aldolisation,2,22,23
Knoevenagel18 or Michael reactions.19 From their catalytic prop-
erties it is usually accepted that LDH has a pKb of ca. 11.4–12
and therefore is a base of moderate strength comparable to piperi-
dine.23 The lack of activity of calcined hydrotalcites reiterates
that the reaction of Henry requires Brönsted bases of mild
strength.
The classical mechanism of the Henry reaction6 can therefore
be applied here. The abstraction of a proton from the active meth-
ylene group of the nitro compound gives a carbanion which can
be stabilised by the cationic charge of aluminium in the lattice of
hydrotalcite as suggested in Scheme 2. In this scheme it is sug-
Table 2 Henry reaction between benzaldehyde and
nitromethane using various base catalysts
Yield 
Entry Catalyst t/h (%)a
1 Modified Mg–Al hydrotalcite 0.5 95b
2 Aluminium oxide 12.0 37
3 Magnesium oxide 8.0 51
4 Sodium hydroxide with PTC 2.0 70c
5 Diamino-functionalised MCM-41 3.0 97d
a Determined by 1H NMR, based on starting aldehyde, unless
otherwise stated. b Isolated pure product. c Isolated yield,
using sodium hydroxide with surfactant.10 d Using diamino-
functionalised MCM-41, nitroalkene is the sole product.21
188 Green Chemistry August 1999
D
ow
nl
oa
de
d 
on
 0
2 
Fe
br
ua
ry
 2
01
1
Pu
bl
ish
ed
 o
n 
01
 Ja
nu
ar
y 
19
99
 o
n 
ht
tp
://
pu
bs
.rs
c.o
rg
 | d
oi:
10.
103
9/A
904
075
G
View Online
Scheme 2 A plausible mechanism for the Henry reaction
between nitromethane and benzaldehyde catalysed by modified
Mg–Al hydrotalcite.
gested that this carbanion further adds to the carbonyl compound
to form an intermediate A which, in turn, removes a proton from
water to give the final nitro aldol product. It is of interest that this
aldolisation reaction is very specific towards the nature of the
Brönsted base.2,23 In spite of the large number of basic sites deter-
mined by calorimetric adsorption of CO2, decarbonated hydrotal-
cites are not active, as they do not have any Brönsted hydroxy
groups.
Conclusion
Compatible Brönsted basic hydroxy sites present in the modified
hydrotalcite give rise to selective nitroaldol reactions in excellent
yields over short times more efficiently than methodologies
described earlier. The following advantages are: (a) high cat-
alytic activity under very mild liquid phase conditions, (b) easy
separation of the catalyst by simple filtration, (c) excellent yields
and 100% selectivity of b-nitroalkanols at high rates of reaction,
(d) use of non-toxic and inexpensive materials, (e) recycling of
the catalyst and (f) zero emission of pollutants. The present cat-
alytic system is thus a potential alternative to soluble bases.
Acknowledgements
This work was carried out as part of the Indo-French co-opera-
tive programme, funded by IFCPAR (Project No. IFC/1106-
2/96/2460).
References
1 Y. V. Subba Rao, D. V. De Vos and P. A. Jacobs, Angew.
Chem., Int. Ed, Engl., 1997, 36, 2661.
2 K.Koteswara Rao, M. Gravelle, J. Sanchez and F. Figueras,
J. Catal., 1998, 173, 115.
3 F. Cavani, F. Trifiro and A. Vaccari, Catal. Today, 1991, 11,
173.
4 G. Rosini, in Comprehensive Organic Synthesis, vol. 2, ed.
C. H. Heathcock, ch. 1.10 p. 321, ed. B. M. Trost and 
I. Fleming, Pergamon Press, Oxford, 1991, and references
therein. 
5 B. P. Bandager, M. B. Zirange and P. P. Wandgaokar, Synlett,
1996, 149; G. Rosini, R. Ballini, M. Petrini and P. Sorrenti,
Synthesis, 1985, 515.
6 R. Ballini, G. Bosica and P. Forconi, Tetrahedron, 1996, 52,
1677.
7 U. Contantino, M. Curini, F. Marmottini, O. Rosati and
E. Pisani, Chem. Lett., 1994, 2215.
8 G. Rosini, R. Ballini and P. Sorrenti, Synthesis, 1983, 1014.
9 J.-M. Melot, F. Texier-Boullet and A. Foucaud, Tetrahedron
Lett., 1986, 27, 493.
10 R. Ballini and G. Bosica, J. Org. Chem., 1997, 62, 425.
11 R. Ballini, R. Castagnani and M. Petrinini, J. Org. Chem.,
1992, 57, 2160.
12 W. T. Reichle, J. Catal., 1985, 94, 547; J. G. Nunan,
P. B. Himelfarb, R. G. Herman, K. Klier, C. E. Bogdan and
G. W. Simmons, Inorg. Chem. , 1989, 28, 3868; C. Busetto,
G. Delpiero, G. Manara, F. Trifiro and A. Vaccari, J. Catal.,
1984, 85, 260.
13 E. Suzuki and Y. Ono, Bull. Chem. Soc. Jpn., 1988, 61, 1008.
14 E. Suzuki, M. Okamoto and Y. Ono, J. Mol. Catal., 1990, 61,
283.
15 C. Cativiela, F. Figueras, J. I. Garcia, J. A. Mayoral and
M. Zurbano, Synth. Commun., 1995, 25, 1745.
16 C. Cativiela, F. Figueras, J. M. Fraile, J. I. Garcia and
J. A. Mayoral, Tetrahedron Lett., 1995, 36, 4125.
17 W. T. Reichle, US Pat., 4 458 026, 1984 to Union Carbide.
18 M. Lakshmi Kantam, B. M. Choudary, Ch. Venkat Reddy,
K. Koteswara Rao and F. Figueras, Chem. Commun. , 1998,
1033.
19 B. M. Choudary, M. Lakshmi Kantam, Ch. Venkat Reddy,
K. Koteswara Rao and F. Figueras, J. Mol. Catal., in press.
20 Representative procedure: To a mixture of nitromethane (10
mmol) and benzaldehyde (2 mmol), 0.2 g of catalyst was
added at room temperature and stirring was continued until
completion of the reaction, as monitored by TLC. The cata-
lyst was filtered off, washed with dichloromethane (10 ml 3
3) and the filtrate concentrated under reduced pressure. The
crude product was purified by column chromatography (sil-
ica gel, 60–120 mesh; hexane–ethyl acetate 98+2 v/v) to give
PhCH(OH)CH2NO2 (0.317 g, 95% yield). The product was
characterised by comparison of its NMR and IR spectra with
those reported in the literature. 10
21 M. Lakshmi Kantam and P. Sreekanth, Catal. Lett., 1999, 57,
227.
22 D. Tichit, M. H. Lhouty, A. Guida, B. Chiche, F. Figueras,
A. Auroux and E. Garrone, J. Catal., 1995,151, 50.
23 F. Figueras, D. Tichit, M. Bennani Nasiri and R. Ruiz, in
Catalysis of Organic Reactions, ed. F. E. Herkes, Marcel
Dekker, New York, 1998, pp. 37–49.
Paper 9/04075G
Green Chemistry August 1999 189
D
ow
nl
oa
de
d 
on
 0
2 
Fe
br
ua
ry
 2
01
1
Pu
bl
ish
ed
 o
n 
01
 Ja
nu
ar
y 
19
99
 o
n 
ht
tp
://
pu
bs
.rs
c.o
rg
 | d
oi:
10.
103
9/A
904
075
G
View Online
D
ow
nl
oa
de
d 
on
 0
2 
Fe
br
ua
ry
 2
01
1
Pu
bl
ish
ed
 o
n 
01
 Ja
nu
ar
y 
19
99
 o
n 
ht
tp
://
pu
bs
.rs
c.o
rg
 | d
oi:
10.
103
9/A
904
075
G
View Online


Henry reactions catalysed by modified Mg-Al hydrotalcite: an efficient reusable solid base for selective synthesis of β-nitroalkanols

http://repository.ias.ac.in/6753/1/6753.pdf

Henry reactions catalysed by modified Mg-Al hydrotalcite: an efficient reusable solid base for selective synthesis of β-nitroalkanols

Abstract

Similar works

Full text

Available Versions

Publications of the IAS Fellows