β-Isocupreidinate?CaAl-layered double hydroxide composites—heterogenized catalysts for asymmetric Michael addition

Article abstract of DOI:10.1016/j.mcat.2019.110675

β-isocupreidinate (β-iCu) anions having well-known structure and catalytic activity in various asymmetric reactions, were incorporated into the interlayer gallery of hydrocalumite (CaAl-LDH) by the partial delamination-restacking method. Silylation of the outer surface of the LDH with trimethyl silane was also employed to avoid the adsorption of β-iCu on the outer surface and to block the basic sites there. The obtained materials were characterized by a range of instrumental methods (X-ray diffractometry, scanning electron microscopy, ATR-IR and grazing incidence IR spectroscopies). The catalytic activities of the composites were tested in the asymmetric Michael addition of β-nitrostyrene and ethyl 2-fluoroacetoacetate. The β-iCu-pillared LDHs proved to be active and recyclable catalysts with very good diastereoselectivities and acceptable and in 2-propanol very good enantioselectivities. The silylated composite retained its activity and diastereoselectivity even in the third repeated run, when heptane was the solvent.

Full text of DOI:10.1016/j.mcat.2019.110675

MolecularCatalysisxxx(xxxx)xxxx
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.elsevier.com/locate/mcat
β-Isocupreidinate‒CaAl-layered double hydroxide
composites—heterogenized catalysts for asymmetric Michael addition
Gábor Vargaa,b,*, Viktória Kozmaa, Vanessza Judit Kolcsára, Ákos Kukoveczc, Zoltán Kónyab,c,d
,
Pál Siposb,e, István Pálinkóa,b,*, György Szὅllὅsif
a Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary
b Materials and Solution Structure Research Group and Interdisciplinary Excellence Centre, Institute of Chemistry, University of Szeged, Aradi Vértanúk tere 1, Hungary
c Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1, Szeged, H-6720, Hungary
d MTA-SZTE Reaction Kinetics and Surface Chemistry Research Group, Rerrich Béla tér 1, Szeged, H-6720, Hungary
e Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, Szeged, H-6720, Hungary
f MTA-SZTE Stereochemistry Research Group, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary
A R T I C L E I N F O
A B S T R A C T
Keywords:
β-isocupreidinate (β-iCu) anions having well-known structure and catalytic activity in various asymmetric re-
actions, were incorporated into the interlayer gallery of hydrocalumite (CaAl-LDH) by the partial delamination-
restacking method. Silylation of the outer surface of the LDH with trimethyl silane was also employed to avoid
the adsorption of β-iCu on the outer surface and to block the basic sites there. The obtained materials were
characterized by a range of instrumental methods (X-ray diffractometry, scanning electron microscopy, ATR-IR
and grazing incidence IR spectroscopies). The catalytic activities of the composites were tested in the asymmetric
Michael addition of β-nitrostyrene and ethyl 2-fluoroacetoacetate. The β-iCu-pillared LDHs proved to be active
and recyclable catalysts with very good diastereoselectivities and acceptable and in 2-propanol very good en-
antioselectivities. The silylated composite retained its activity and diastereoselectivity even in the third repeated
run, when heptane was the solvent.
CaAl-layered double hydroxide
Intercalation of β-isocupreidiniate
XRD
SEM, IR characterizations
Catalysis of asymmetric Michael addition
1. Introduction
Natural cinchona alkaloids and their derivatives are among the most
efficient chiral homogeneous organocatalysts [19–22]. Cinchona alka-
During the last two decades, in the field of asymmetric synthesis,
immense attention has been focused on organocatalysis [1–3]. Due to
environmental considerations and pot, atom and step economic rea-
sons, stereoselective organocatalytic reactions gained important role in
the efficient and rapid generation of complex molecules [4–9]. Orga-
nocatalysts, which have well-known structures, are in many cases easy
to synthesize. As compared to well-established transition metal-con-
taining systems, these catalysts allow the stereoselective preparation of
chiral building blocks free of metal contaminations, which is of para-
mount importance in pharmaceutical processes [1–3,5,10]. Accord-
ingly, due to economic, health and social factors, the utilization of
optically pure compounds produced by organocatalytic pathways, is
dramatically increasing. Chiral organic acids, amines, amino acids, such
as L-proline and oligopeptides were found to be efficient catalysts in
enantioselective oxidations, reductions, and asymmetric CeC bond
formation reactions, such as aldol additions, Mannich, Michael and
Diels-Alder reactions [11–18].
loids are complex molecules containing five stereocentres. The two
rigid units of these molecules, the nucleophilic quinuclidine and the
quinoline moieties are connected through a carbinol bridge (see the
structure of quinine and quinidine in Fig. 1). The hydroxyl group and
substituents on both ring systems allow easy functionalization and fine-
tuning of the catalytic properties of these compounds. Accordingly,
various cinchona derivatives were found to be highly efficient asym-
metric organocatalysts in numerous enantioselective transformations
[19–24]. Aromatic hydroxyl groups are useful hydrogen bond donor
units in bifunctional organocatalysts [25]. The transformation of the
C6′-OMe group in cinchona alkaloids to phenolic hydroxyl leads to
cupreine and cupreidine derivatives, which were used as efficient bi-
functional catalysts [26,27]. Among these types of cinchona derivatives
β-isocupreidine (Fig. 1; the deprotonated version is abbreviated as β-
iCu in the followings) is a privileged representative, which besides
bearing the phenolic hydroxyl group of acidic character, has a rigid
oxazatwistane ring system with low conformational flexibility,
⁎ Corresponding authors at: Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary.
E-mail addresses: gabor.varga5@chem.u-szeged.hu (G. Varga), palinko@chem.u-szeged.hu (I. Pálinkó).
https://doi.org/10.1016/j.mcat.2019.110675
Received 16 September 2019; Received in revised form 9 October 2019; Accepted 16 October 2019
2468-8231/©2019ElsevierB.V.Allrightsreserved.
Pleasecitethisarticleas:GáborVarga,etal.,MolecularCatalysis,https://doi.org/10.1016/j.mcat.2019.110675

G. Varga, et al.
MolecularCatalysisxxx(xxxx)xxxx
Fig. 1. Structures of the cinchona alkaloids quinine, quinidine and β-isocupreidine.
increased basicity and nucleophilicity. β-iCuH displays appreciable
catalytic performance in several asymmetric organocatalytic reactions,
such as Morita-Baylis-Hillman reactions, direct aminations, allylic nu-
cleophilic substitutions as well as Michael additions [28–32].
fully or partially hydrated anions [54–56]. The interlayer anions can be
Cl–, NO3–, CO32–, etc. or various organic anions.
Recently, LDHs were used for the immobilization of β-iCu [32].
However, due to the large dimensions of the cinchona alkaloid deri-
vatives surface-anchored LDH-supported organocatalyst was only ob-
tained. In the present work, β-iCu was incorporated among the layers of
the LDH exclusively, and the activity and selectivity of this LDH–β-iCu
composites were studied in the Michael addition of ethyl 2-fluor-
oacetoacetate (2) to trans β-nitrostyrene (1). The partial delamination-
restacking method was successfully used to intercalate the organoca-
talyst exclusively into the interlayer gallery of the LDHs. The as-pre-
pared composites and those recovered following several catalytic cycles
were characterized by a range of instrumental techniques.
In spite of these attractive features, organocatalysts have been rarely
used in industry, which may be related to their insufficient activity
under the desired conditions and the difficulties in catalyst separation
and recycling [33]. By immobilization of chiral organocatalysts onto/
into solid supports, the above-mentioned drawbacks can be diminished
or even eliminated. Thus, catalytic materials, which are separable from
the reaction mixture, recyclable, adaptable to various reaction condi-
tions and efficient in the continuous production of chiral compounds,
may be obtained [34,35]. Despite their advantages, the anchored chiral
organocatalysts have gained little attention. This is due to the often-
decreased enantioselectivities obtained using such materials, as com-
pared with their homogeneous counterparts. Another reason might be
their significantly reduced activity, due to the less accessible active sites
of the catalysts and the slow diffusion of the reactants and products to
and from these sites determined by the structure and morphology of the
support [36]. Deactivation or leaching of the immobilized catalysts
from the solid surfaces should also be solved in order to obtain efficient,
recyclable materials [36,37].
2. Experimental part
2.1. Materials
All chemicals used in the preparation of the inorganic-organic
composites, reagents, solvents of analytical grade applied in the test
reaction were purchased from Merck and Sigma-Aldrich and were used
as received without further purification. The literature-based prepara-
tion of β-iCuH has been described previously [32].
Accordingly, besides the immobilization methods, utilizing the
surface modification of metals, metal oxides as well as resins [38–42],
novel procedures have appeared employing mesoporous materials and
clays as solid supports for chiral catalysts [43–46]. The latter sub-
stances, due to their sterically confined environments, may give the
opportunity to increase the enantioselectivity. However, the im-
mobilization of the chiral organocatalysts into the interlayer space of
the anionic or cationic clays has been seldom reported, even though
various methods have been successfully applied to immobilize orga-
nocatalysts between the layers of layered double hydroxides, which
showed outstanding activity in various reactions. Among the rare ex-
amples, the anionic forms of proline and other amino acids have been
incorporated into hydrotalcite or brucite-like layers, and these com-
posites proved to be efficient enantioselective catalysts in en-
antioselective aldol and asymmetric Michael additions [47–51].
The group of brucite-like materials or layered double hydroxides
(LDH) is a family of natural and synthetic substances with a general
2.2. Syntheses
The CaAl-LDH (hereafter referred to as LDH) was prepared by the
co-precipitation method, via addition of 3.0 M NaOH solution to a
vigorously stirred and N2-blanketed CaCl2×6H2O/AlCl3×6H2O solu-
tion with 2:1 M ratio at room temperature. The suspension was filtered
and dried for 24 h at 60 °C and kept in a desiccator under N2 until use.
The silylated CaAl-LDH (abbreviated as Sil-LDH) were prepared by a
modified co-precipitation method. 6.5 g of CaCl2×6H2O and 3.6 g of
AlCl3×6H2O were dissolved in 100 cm3 of distilled water (solution A).
5.0 cm3 trimethylchlorosilane dissolved in 50 cm3 ethanol was acti-
vated by 20% aqueous ammonia solution (solution B). At room tem-
perature, solution B was added dropwise to solution A and the mixture
was stirred at pH∼13 (set by 3 M NaOH) overnight. The mixture was
aged at 80 °C for 12 h. The resulting slurry was filtered, washed with
distilled water several times and dried at 60 °C.
formula of [M(II)1-xM(III)x(OH)2](Yn−
)x/n × yH2O, where M(II) and M
(III) represent divalent and trivalent metal ions, respectively, and Yn− is
the anion situated between the layers [52]. The divalent and trivalent
metal cations found in layered double hydroxides belong mainly to the
third and fourth periods of the periodic table of elements (divalent
cations: Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+; trivalent cations:
Al3+, Mo3+, Fe3+, Co3+, Cr3+, Ga3+) [53]. The ionic radii are mostly
in the range of 0.65–0.80 Å for divalent cations and 0.62–0.69 Å for the
trivalent ones (there are some exceptions like Al: 0.50 Å and Ba:
1.49 Å). Tetravalent cations such as Zr4+ and Sn4+ can also be in-
corporated into the layers. The LDHs consist of hexagonal-shaped
brucit-like sheets having positive charge due to partial substitution of
M2+ with M3+. The uniformly dispersed positive charge is balanced by
The CaAl–β-iCu-LDH (LDH–β-iCu in the followings) and its silylated
derivative (Sil-LDH–β-iCu) were produced by the partial delamination
method. The previously synthesized chloride-containing (Sil-)LDH
(0.5 g) was partially delaminated in an EtOH/DMF 30/70 (vol./vol.)
mixture (15 cm3) by 240-min-long ultrasonic irradiation under inert
atmosphere. The reaction mixture was stirred at room temperature for
96 h followed by the addition of 10 cm3 of 4 × 10–3 M β-iCuH depro-
tonated with 0.15 M NaOH (aqueous) solution. The slurry was cen-
trifuged (3000 rpm) for 15 min and decanted. A fresh solution of β-
isocupreidinate (β-iCu) was added to the solid material again, and the
treatment was repeated twice. After the last step, the solid product was
filtered, washed with EtOH and dried at 40 °C overnight.
2

G. Varga, et al.
MolecularCatalysisxxx(xxxx)xxxx
All operations were performed under N2 blanket to avoid carbona-
tion of the layers and thus the interlayer space by airborne CO2.
2.3. Characterization techniques
For detection of X-ray diffraction (XRD) patterns, a Rigaku XRD-
MiniFlex II instrument utilizing Cu Kα radiation (λ = 0.15418 nm) with
40 kV accelerating voltage at 30 mA was applied. The morphologies of
the samples were studied with a scanning electron microscope (SEM,
Hitachi S-4700, accelerating voltages of 10–18 kV).
The combination of two different IR techniques was used for de-
tecting the spatial arrangement of the anionic form of β-iCu. The in-
strument for acquiring the spectra was a BIO-RAD Digilab Division FTS-
65A/896 FT-IR spectrophotometer with 4 cm–1 resolution. The
4000–600 cm–1 wavenumber range was recorded, but the most relevant
1850–600 cm–1 range was displayed and discussed. 256 scans were
collected for each spectrum. The spectra of each sample were taken
using a single reflection diamond ATR accessory and the grazing in-
cidence (GIRA-FTIR) technique (detecting organic material on the
surface of the LDH) [56].
Fig. 2. XRD patterns of A: LDH; B: β-iCu-intercalation (dehydration-rehydra-
tion); C: β-iCu-intercalation (direct anion exchange); D: LDH–β-iCu (delami-
nation-restacking); E: Sil-LDH; F: Sil-LDH–β-iCu (delamination-restacking).
2.4. Catalytic test: general procedure
distance as the parent LDH. These two composites exhibited interlayer
distances close to 0.75 nm. Considering the large dimensions of the β-
iCu, the failure in direct intercalation was not surprising.
The test reactions were carried out in 4 cm3 glass vials using mag-
netic stirring (800 rpm) in a refrigerator set to −20 °C. In a typical
experiment, the given amount of catalyst was suspended in 1 cm3 sol-
vent followed by addition of 0.25 mmol 1. To the cooled slurry,
0.5 mmol 2 was added, and the reaction was started by turning on the
stirrer. Following the given reaction time, the catalyst was centrifuged,
the solid material was washed twice with solvent. The unified organic
solution was checked for leached out organocatalyst by IR spectro-
scopy. Following the drying of the organic phase over Na2SO4, the
products were analysed by gas chromatography. The remaining solid
material was dried at room temperature, and reused in successive runs
using identical reaction conditions.
Products of the catalytic reactions were identified on the basis of
their mass spectra measured on Agilent Techn. 6890 N GC-5973 inert
MSD system (GC-MSD) equipped with HP-1MS 60 m × 0.25 mm i.d.
capillary column [32]. Conversions, diastereomeric ratios and en-
antioselectivities were calculated based on quantitative analysis carried
out using Agilent 7890A GC System equipped with flame ionization
detector (FID) and Hydrodex-g-TBDAc 30 m × 0.25 mm (Macherey-
Nagel GmbH) chiral capillary column, which allowed the separation of
all four ethyl 2-acetyl-2-fluoro-4-nitro-3-phenylbutanoate (3) Michael-
adduct stereoisomers [30] using decane as internal standard.
Experiments repeated three times showed that the reproducibility of
product composition was within 1%.
Accordingly, only the delamination-restacking (Fig. 2D) method
seems to give material having the anionic form of the cinchona alkaloid
immobilized between the layers (abbreviated as LDH–β-iCu). Based on
the XRD pattern of this material, two reaction products are formed
following the intercalation process. In the pattern of LDH–β-iCu in
Fig. 2D, a series of reflections corresponding to d values of 1.08 (001),
0.54 (002) and 0.27 (003) nm indicated the layered structure with the
basal spacing of 1.08 nm. The large interlayer distance confirmed that
β-iCu could be introduced into the interlayer region of the restacked
LDH. The calculated basal spacing can be ascribed to vertically oriented
anions in the interlayer space (the dimensions of β-iCu:
0.782 nm × 0.494 nm × 1.007 nm, the interlayer distance is
1.08 nm – 0.234 nm = 0.846 nm). The interlayer-modified structure
exhibited a turbostatic disorder as can be seen from the increased in-
tensity of the 001 reflection compared to the relatively low intensities
of the 002 and 003 reflections [57,58]. This effect may occur because of
the increase in the 2D character of the material with extensive charge
separation and hydration. On the other hand, beside the 1.08 nm-phase,
a small amount of the 0.75 nm-phase was also present, which can be
interpreted in two ways. Either a single phase is formed in which cer-
tain layers contain chloride anions while others contain β-iCu, i.e. sta-
ging occurred, or two different phases were produced, one of which
only contained chloride between the layers, while the other with in-
creased interlayer distance contained β-iCu [59].
Previous studies reported that LDHs behaved as actual catalysts in
Michael or nitro Michael reactions due to their basic character, which is
ascribed to the Brønsted basic sites, i.e. surface OH groups [60,61].
Therefore, in order to examine the catalytic activity of the surface OH
groups and the incorporated organocatalyst separately, surface-sily-
lated LDH was also synthesized and intercalated with the anionic form
of the cinchona alkaloid. The XRD diffraction pattern of Sil-LDH is
displayed in Fig. 2E. In the XRD diffractogram of this material, exactly
the same reflections are observed as in that of the parent LDH corre-
sponding to the same d values of 0.75 (001) and 0.38 (002) nm. The
broadened peaks indicate decreased crystallinity of the silylated ma-
terial. Doubled 002 reflections are also observed attributed to the sig-
nificantly changed hydration of the structure. Starting from the sily-
lated product, a novel intercalated composite was also synthesized.
Fig. 2F verifies that the synthesis was successful, furthermore, reflec-
tions characteristic to the starting material could not be observed. Its
Bragg reflections could also be indexed considering a hexagonal lattice
3. Results and discussions
3.1. Silylation and intercalation
In order to find the optimal intercalation conditions of β-iCu into
LDH, various synthesis methods were examined. Fig. 2 shows the XRD
patterns of the pure chloride-containing LDH (A) and its β-iCu modified
derivatives. The XRD patterns of LDHs are usually indexed on the basis
of a rhombohedral unit cell, which is analogous to the chloride-con-
taining hydrocalumite. The interlayer distances were calculated on the
basis of Bragg’s law. Fig. 2B indicates that the intercalation of the
cinchona alkaloid was not successful by the reconstruction (dehydra-
tion-rehydration) method, because the layered structure was not re-
stored. It is known that molecules, which cannot be intercalated by the
reconstruction method, could sometimes be introduced between the
layers by applying either the direct anion exchange or the delamina-
tion-restacking methods. However, as it is seen in Fig. 2C, the XRD
pattern of the LDH modified by anion exchange had the same interlayer
3

G. Varga, et al.
MolecularCatalysisxxx(xxxx)xxxx
Fig. 3. SEM images of A: LDH–β-iCu; B: Sil-LDH–β-iCu.
with rhombohedral symmetry, similarly to the precursor. The calcu-
lated interlayer distance (1.5 nm) increased relative to that of the pre-
cursor (0.75 nm), clearly indicating that the intercalation was suc-
cessful.
In order to provide further evidence for the successful transforma-
tion of the parent LDH through intercalation and/or silylation, the as-
prepared products were investigated by SEM (Fig. 3). The SEM image of
the LDH–β-iCu showed the formation of a material with hexagonally-
shaped platelet-like particles (Fig. 3A) confirming the LDH-like struc-
ture of the intercalated system [62]. Crystal particles with less regular
shapes and smaller particles are observed in the image of Sil-LDH–β-iCu
indicating that surface modification influenced the morphology as well
as the particles sizes [63].
Since one of the aims of the work is the intercalation of the orga-
nocatalyst solely into the interlayer space, determination of the position
of the incorporated β-iCu in the LDH–β-iCu was carried out. A com-
parative IR study was proven to be efficient for determining the local
position of the intercalant within the LDH. The ATR-FTIR detection is
an available method for observing changes in the bulk as well as on the
surface with the predominance of signals originating from the struc-
tures of the bulk [64]. As one can see in Fig. 4A, the characteristic
vibrations of the interlayer nitrate ions and surface-bound carbonate
ions, such as ν3(interlayer NO3–) ∼ 1349 cm–1, ν3(surface CO32–) ∼
1415 cm–1, appeared [65]. The vibration bands at 1650 and 785 cm–1
were assigned as β(OH) (bending mode) of the water and O–Al–O
stretching mode of the LDH structure, respectively [66,66]. On the
other hand, since the GIRA-FTIR method has surface-sensitive character
[67], significantly altered spectrum is observable in Fig. 4B. The posi-
tions of the overlapped and broadened peaks are identical to those of
Therefore, due to the absence of inert atmosphere, the carbon dioxide
adsorbed and transformed to carbonate ions on the surface, which can
be clearly identified by GIRA-FTIR. As far as the intercalated composite
is concerned, beside the above-mentioned absorption bands of carbo-
nate and nitrate ions, new vibrations appeared at 1668 and 1581 cm–1
indicating the presence of the anionic form of the cinchona alkaloid
(Fig. 4C) [69]. New bands were identified as bending vibration modes
of the hydroxyl and amino groups related to β-iCu. The observed sig-
nificant shifts (1610 → 1668 cm–1) can be ascribed to the interaction of
β-iCu with the layer of the LDH host [70,71]. However, based on the
GIRA-FTIR measurements, the surface of the composite (Fig. 4D) was
similar to that of the parent LDH.
The silylated derivatives of the composites were also studied by
both IR techniques (Fig. 5). The characteristic vibrations of the LDH
disappeared following silylation, which is consistent with literature
results [72,73]. Some of the vibrations related to the trimethyl silane
group appeared in all these materials identified as SieOeM stretching
vibrations at ∼1000 and 1100 cm–1. The intense peaks at about 1210,
840 and 760 cm–1 can be assigned to the bending, rocking and
stretching vibrations of Si–Me, respectively, corresponding to –Si(Me)X–
units from trimethyl silane [74]. The broadened peaks at about 1350
and 1450 cm–1 were assigned as nitrate and carbonate ions distorted
during the silylation process, which highly influenced the hydration
state of the LDH [75,76]. After intercalation, the above-assigned vi-
brations such as hydroxyl vibrations appeared indicating the successful
inclusion of the anionic form of the cinchona alkaloid. GIRA-FTIR
spectrum of the intercalated system resembled the spectrum of the non-
intercalated composite.
On the basis of IR measurements, it can be stated that β-iCu is
overwhelmingly resides among the layers of the LDH in both compo-
sites.
the vibrational modes of the free carbonate ions located at ν3(surface)
∼
1430 cm–1, ν2(surface) ∼ 890 cm–1 and ν4(surface) ∼ 690 cm–1 [68].
Fig. 4. IR spectra of A: LDH (ATR-FTIR); B: LDH (GIRA-FTIR); C: LDH–β-iCu
(ATR-FTIR); D: LDH–β-iCu (GIRA-FTIR); E: Na-β-iCu (ATR-FTIR).
Fig. 5. IR spectra of: A: Sil-LDH (ATR-FTIR); B: Sil-LDH (GIRA-FTIR); C: Sil-
LDH–β-iCu (ATR-FTIR); D: Sil-LDH–β-iCu (GIRA-FTIR).
4

G. Varga, et al.
MolecularCatalysisxxx(xxxx)xxxx
Fig. 6. Possible structures for LDH–β-iCu (A) and Sil-LDH–β-iCu based on XRD and ATR- and GIRA-FTIR measurements.
Scheme 1. The Michael addition of ethyl 2-fluoroacetoacetate
(2) to trans β-nitrostyrene (1).
Table 1
Table 2
Results of the Michael addition catalysed by the unmodified CaAl-LDH, β-iCu as
homogeneous catalyst and β-iCu intercalated in non-silylated and silylated
CaAl-LDHa.
Results of the Michael addition over the reused β-iCu intercalated in non-sily-
lated and silylated CaAl-LDHa.
catalyst
nr. of reuse
solvent
conv (%)b
drb
ee (%)c
Entry
catalyst
solvent
conv (%)b
drb
ee (%)c
LDH–β-iCu
1
2
1
1
2
1
2
3
2-propanol
2-propanol
DCE
toluene
toluene
heptane
heptane
heptane
83
< 4
43
> 99
65
> 99
> 99
98
66/34
53/47
78/22
74/26
73/27
67/33
66/34
66/34
88; 77
10; 12
19; 18
16; 21
10; 12
10; 6
7; 4
1
2
3
4
5
6
7
8
–
DCE
DCE
< 1
99
72
89
94
–
–
Sil-LDH–β-iCu
Sil-LDH–β-iCu
β-iCu
85/15
–
98; 96
–
29; 26
22; 26
3; 4
95; 82
28; 24
22; 28
19; 11
97; 94
CaAl-LDH
LDH–β-iCu
LDH–β-iCu
LDH–β-iCu
LDH–β-iCu
Sil-LDH–β-iCu
Sil-LDH–β-iCu
Sil-LDH–β-iCu
Sil-LDH–β-iCu
heptane
DCE
toluene
heptane
2-propanol
DCE
toluene
heptane
2-propanol
83/17
73/27
65/35
75/25
80/20
73/27
67/33
78/22
Sil-LDH–β-iCu
90
4; 2
> 99
> 99
> 99
> 99
> 99
a
Reaction conditions: catalyst 20 mg, 0.25 mmol of 1, 0.5 mmol of 2, 1 cm3
9
10
11
solvents, −20 °C, 22 h.
b
Conversions (conv) and diastereomeric ratios (dr) determined by GC-FID.
Enantiomeric excesses (ee), the configuration of the excess enantiomers
c
a
Reaction conditions: catalyst 20 mg, 0.25 mmol of 1, 0.5 mmol of 2, 1 cm3
were assigned based on previous studies and GC-FID analysis as 2R,3R and
2S,3R [32].
solvents, −20 °C, 22 h.
b
Conversions (conv) and diastereomeric ratios (dr) determined by GC-FID.
Enantiomeric excesses (ee), the configuration of the excess enantiomers
c
were assigned based on previous studies and GC-FID analysis as 2R,3R and
2S,3R [32].
Possible structures for the non-silylated and silylated intercalated
LDHs, mainly for helping visualisation, are given in Fig. 6A and B, re-
spectively.
3.2. Catalytic behaviour of the materials
The composite materials obtained, LDH–β-iCu and Sil-LDH–β-iCu,
were tested as catalysts in the Michael addition of 2 to 1 (Scheme 1).
Results obtained in various solvents are summarized in Table 1.
The obtained diastereomeric ratios and enantiomeric excess values
confirmed that these composites catalysed the Michael addition, and
the catalysts were the chiral solid hybrid materials. The material pre-
pared by the inclusion of the anionic form of the cinchona alkaloid in
the parent LDH provided lower conversions in every solvent tested than
those obtained using the silylated composite. A possible explanation of
this activity difference may be the decreased hydrophilicity of the in-
terlamellar space following silylation, which favours the migration of
Fig. 7. XRD patterns of A: used (in toluene, 2 times) and B: as-prepared LDH–β-
iCu; C: used (in heptane, 4 times) and D: as-prepared Sil-LDH–β-iCu.
5

G. Varga, et al.
MolecularCatalysisxxx(xxxx)xxxx
the reactants and the products to/from the chiral active sites. It is
known that cinchona alkaloids have rich conformational behaviour,
due to rotations around the C8‒C9 and C9‒C4′ axes [20–23,77]. Al-
though in the isocinchona alkaloids the former is hindered, rotation
around the C9‒C4′ bond still allows the formation of some conformers
[78]. However, the similar (quite high) diastereomeric ratios (dr) and
(the moderate) enantiomeric excess (ee) values obtained with both the
LDH–β-iCu and Sil-LDH–β-iCu (except in heptane) indicated similar
arrangement of the immobilized β-isocupreidinate.
Declaration of Competing Interest
None.
Acknowledgements
This work was supported by the Hungarian Government and the
European Union through grant GINOP-2.3.2-15-2016-00013. G. Varga
thanks for the postdoctoral fellowship under the grant PD 128189.
The dr and ee values were calculated the following way:
References
dr = [c(S,S) – c(R,R)]/[c(R,S) – c(S,R)],
[1] A. Berkessel, H. Groger, Asymmetric Organocatalysis: From Biomimetic Concepts to
Applications in Asymmetric Synthesis, Wiley-VCH, Weinheim, 2005.
[2] B. List, K. Maruoka, Science of Synthesis: Asymmetric Organocatalysis, Thieme,
Stuttgart, 2012.
[3] P.I. Dalko, Comprehensive Enantioselective Organocatalysis: Catalysts, Reactions
and Applications Vols. 1–3 Wiley-VCH, Weinheim, 2013.
ee = 100 × [c(S,S) – c(R,R]/[c(S,S) + c(R,R)] and 100 × [c(R,S) – c
(S,R)]/[c(R,S) + c(S,R)]
where c(S,S), c(R,R), c(R,S) and c(S,R) are the concentrations of the
Michael adducts, and there were no other products.
[4] G.L. Hua, C. Li, X.F. Wang, L.Q. Lu, J.R. Chen, W.J. Xiao, Enantioselective synthesis
of chromans with a quaternary stereogenic centre through catalytic asymmetric
cascade reactions, ACS Catal. 1 (2011) 221–226.
[5] T. Shi, Z. Guo, H. Yu, J. Xie, Y. Zhong, W. Zhu, Atom‐economic synthesis of opti-
cally active Warfarin anticoagulant over a chiral MOF organocatalyst, Adv. Synth.
Catal. 355 (2013) 2538–2543.
[6] R. Bharti, R. Parvin, One‐pot synthesis of highly functionalized tetrahydropyridines:
a camphor sulfonic acid catalysed multicomponent reaction, J. Heterocyclic Chem.
52 (2015) 1806–1811.
[7] V.J. Lillo, J.M. Saá, Towards enzyme‐like, sustainable catalysis: switchable, highly
efficient asymmetric synthesis of enantiopure Biginelli dihydropyrimidinones or
hexahydropyrimidinones, Chem. Eur. J. 22 (2016) 17182–17186.
[8] H. Wei, M. Bao, K. Dong, L. Qiu, B. Wu, W. Hu, X. Xu, Enantioselective oxidative
cyclization/Mannich addition enabled by gold (I)/chiral phosphoric acid co-
operative catalysis, Angew. Chem. Int. Ed. 57 (2018) 17200–17204.
[9] Gy. Szőllősi, Asymmetric one-pot reactions using heterogeneous chemical catalysis:
recent steps towards sustainable processes, Catal. Sci. Technol. 8 (2018) 389–422.
[10] F. Xu, M. Zacuto, N. Yoshikawa, R. Desmond, S. Hoerrner, T. Itoh, M. Journet,
G.R. Humphrey, C. Cowden, N. Strotman, P. Devine, Asymmetric synthesis of tel-
cagepant, a CGRP receptor antagonist for the treatment of migraine, J. Org. Chem.
75 (2010) (2010) 7829–7841.
[11] W. Notz, F. Tanaka, C.F. Barbas, Enamine-based organocatalysis with proline and
diamines: the development of direct catalytic asymmetric aldol, Mannich, Michael,
and Diels−Alder reactions, Acc. Chem. Res. 37 (2004) 580–591.
[12] X. Yu, W. Wang, Organocatalysis: asymmetric cascade reactions catalysed by chiral
secondary amines, Org. Biomol. Chem. 6 (2008) 2037–2046.
The low ee values obtained with LDH–β-iCu in heptane could be due
to the difficult approach of the reactants to the chiral sites found in a
hydrophilic environment, thus the surface basic centres of the inorganic
material only catalysed the reaction. Upon reuse, the activity as well as
the ee values decreased (Table 2). It is to be noted that Sil-LDH–β-iCu
could keep its activity in four uses in heptane, and the diastereomer
ratio did not decrease either. These results are quite probably origi-
nated in the largely hydrophobic environment due to the solvent as well
as the silylated composite. The ee value decreased during the repeated
runs even on this catalyst.
The enantioselectivites were found to be quite good in 2-propanol.
We think that this solvent partially replaced the interlayer water mo-
lecules, and created an environment in which the accessibility of the
chiral centres of the alkaloid modifier was increased. The other solvents
either could not replace the interlayer water molecules or even if they
partially could, the new environment was not advantageous for ex-
posing the chiral centres to the incoming reactants.
The catalysts were recovered from the reaction mixtures by cen-
trifuging the slurries and washing the solids before their X-ray dif-
fractograms were registered. Substances with high crystallinities were
obtained (Fig. 7). The (001) reflections of these materials (Fig. 7A and
C) indicate that the recovered substances kept their layered structure.
The basal distance of the major phase was 1.04 nm and that of the
minor phase was ∼0.90 nm. Even this latter value was larger than that
found for the parent LDH (0.75 nm). The major phase contained β-iCu
immobilized between the layers. Change in the hydration degree of the
interlayer gallery and/or the rearrangement of the interlayer region due
to the conformational transition of the alkaloid may explain the lower
interlamellar distance. Leaching of the organocatalyst was not observed
either from the silylated or the non-silylated composites.
[13] R. Mahrwald, Enantioselective Organocatalyzed Reactions I, Enantioselective
Oxidation, Reduction, Functionalization and Desymmetrization, Springer,
Dordrecht, 2011.
[14] R. Mahrwald, R, Enantioselective Organocatalyzed Reactions II, Asymmetric C‒C
Bond Formation Processes, Springer, Dordrecht, 2011.
[15] M. Tsakos, C.G. Kokotos, Primary and secondary amine-(thio)ureas and squar-
amides and their applications in asymmetric organocatalysis, Tetrahedron 69
(2013) 10199–10222.
[16] Y.L. Sun, L. Wei, M. Shi, Applications of chiral thiourea‐amine/phosphine orga-
nocatalysts in catalytic asymmetric reactions, ChemCatChem 9 (2017) 718–727.
[17] S. Nießing, C. Janiak, Studies on catalytic activity of MIL-53 (Al) and structure
analogue DUT-5 (Al) using bdc-and bpdc-ligands functionalized with L-proline in a
solid-solution mixed-linker approach, Mol. Catal. 467 (2019) 70–77.
[18] J. Xu, J. Pang, D. Feng, X. Ma, Jorgensen–hayashi organocatalyst/Brønsted acid-
tethered multifunctional polymeric nanospheres for complex asymmetric multi-
component/multicatalysed organocatalysis: heterogeneous Michael/Michael/aldol
organocascade and [4+ 2] cycloaddition reactions, Mol. Catal. 443 (2017)
139–147.
4. Conclusions
[19] K. Kacprzak, J. Gawroński, Cinchona alkaloids and their derivatives: versatile cat-
alysts and ligands in asymmetric synthesis, Synthesis (2001) 961–998.
[20] C.E. Song, Cinchona Alkaloids in Synthesis and Catalysis, Ligands, Immobilization
and Organocatalysis, Wiley-VCH, Weinheim, 2009.
It was shown that the inclusion of these bulky anionic cinchona
alkaloids into the interlamellar space was possible by the delamination-
restacking method. Furthermore, the silylated derivatives of these
composites have also been synthesized. The composites were char-
acterised by several methods (XRD, two IR techniques, SEM), and it was
proven that the organocatalyst was between the layers, indeed.
Materials containing immobilized β-iCu were tested as catalysts in the
asymmetric Michael addition of a C-nucleophile to β-nitrostyrene. In
general, the diastereoselectivities were high, the enantioselectivities
were acceptable in most cases and very good using 2-propanol as sol-
vent. There was no leaching of β-iCu during the reactions; however,
rearrangement of intercalated organocatalyst may have occurred
during the reactions explaining the decreasing enantioselectivity in the
repeated runs.
[21] T. Marcelli, H. Hiemstra, Cinchona alkaloids in asymmetric organocatalysis,
Synthesis (2010) 1229–1279.
[22] M.S. Ullah, S. Itsuno, Synthesis of cinchona alkaloid squaramide polymers as bi-
functional chiral organocatalysts for the enantioselective Michael addition of β-
ketoesters to nitroolefins, Mol. Catal. 438 (2017) 239–244.
[23] E.M.O. Yeboah, S.O. Yeboah, G.S. Singh, Recent applications of cinchona alkaloids
and their derivatives as catalysts in metal-free asymmetric synthesis, Tetrahedron
67 (2011) 1725–1762.
[24] P.J. Boratyński, Dimeric cinchona alkaloids, Mol. Divers. 19 (2015) 385–422.
[25] P. Chauhan, S.S. Chimni, Aromatic hydroxyl group – a hydrogen bonding activator
in bifunctional asymmetric organocatalysis, RSC Adv. 2 (2012) 737–758.
[26] T. Marcelli T, J.H. van Maarseveen, H. Hiemstra, Cupreines and cupreidines: an
emerging class of bifunctional cinchona organocatalysts, Angew. Chem. Int. Ed. 45
(2006) 7496–7504.
[27] L.A. Bryant, R. Fanelli, A.J.A. Cobb, Cupreines and cupreidines: an established class
of bifunctional cinchona organocatalysts, Beilstein J. Org. Chem. 12 (2016)
6

G. Varga, et al.
MolecularCatalysisxxx(xxxx)xxxx
[53] G.R. Williams, D. O’Hare, Towards understanding, control and application of
layered double hydroxide chemistry, J. Mater. Chem. 16 (2006) 3065–3074.
[54] G. Varga, Á. Kukovecz, Z. Kónya, L. Korecz, Sz. Muráth, Z. Csendes, G. Peintler,
S. Carlson, P. Sipos, I. Pálinkó, Mn (II)–amino acid complexes intercalated in CaAl-
layered double hydroxide – well-characterized, highly efficient, recyclable oxida-
tion catalysts, J. Catal. 335 (2016) 125–134.
[55] F. Zhang, L. Zhao, H. Chen, S. Xu, D.G. Evans, X. Duan, Corrosion resistance of
superhydrophobic layered double hydroxide films on aluminum, Angew. Chem. Int.
Ed. 47 (2008) 2466–2469.
[56] Y. Zhao, F. Li, R. Zhang, D.G. Evans, X. Duan, Preparation of layered double-hy-
droxide nanomaterials with a uniform crystallite size using a new method involving
separate nucleation and aging steps, Chem. Mater. 14 (2002) 4286–4291.
[57] X.Y. Jin, K.J. Kim, H.S. Lee, Grazing incidence reflection absorption Fourier
transform infrared (GIRA-FTIR) spectroscopic studies on the ferroelectric behavior
of poly (vinylidene fluoride–trifluoroethylene) ultrathin films, Polymer 46 (2005)
12410–12415.
429–443.
[28] Y. Iwabuchi, M. Nakatani, N. Yokoyama, S.J. Hatakeyama, S.J, Chiral amine-cata-
lysed asymmetric Baylis-Hillman reaction: a reliable route to highly en-
antiomerically enriched (α-methylene-β-hydroxy) esters, J. Am. Chem. Soc. 121
(1999) 10219–10220.
[29] M. Shi, Y.M. Xu, Catalytic Y.M, Asymmetric Baylis-Hillman reaction of imines with
methyl vinyl ketone and methyl acrylate, Angew. Chem. Int. Ed. 41 (2002)
4507–4510.
[30] S. Saaby, M. Bella, K.A. Jørgensen, Asymmetric construction of quaternary stereo-
centers by direct organocatalytic amination of α-substituted α-cyanoacetates and β-
dicarbonyl compounds, J. Am. Chem. Soc. 126 (2004) 8120–8121.
[31] Y. Du, X. Han, X. Lu, Alkaloids-catalysed regio- and enantioselective allylic nu-
cleophilic substitution of tert-butyl carbonate of the Morita-Baylis-Hillman pro-
ducts, Tetrahedron Lett. 45 (2004) 4967–4971.
[32] Gy. Szőllősi, L. Kovács, V. Kozma, V.J. Kolcsár, Asymmetric Michael addition cat-
alysed by a cinchona alkaloid derivative non-covalently immobilized on layered
inorganic supports, Reac. Kinet. Mech. Cat. 121 (2017) 293–306.
[33] R.T. Baker, S. Kobayashi, W. Leitner, Divide et impera – multiphase, green solvent
and immobilization strategies for molecular catalysis, Adv. Synth. Catal. 348 (2006)
1337–1340.
[58] B.R. Venugopal, C. Shivakumara, M. Rajamathi, Effect of various factors influencing
the delamination behavior of surfactant intercalated layered double hydroxides, J.
Colloid Interface Sci. 294 (2006) 234–239.
[59] N. Iyi, K. Fujii, K. Okamoto, T. Sasaki, Factors influencing the hydration of layered
double hydroxides (LDHs) and the appearance of an intermediate second staging
phase, Appl. Clay Sci. 35 (2007) 218–227.
[34] I.M. Mándity, S.B. Ötvös, Gy. Szőllősi, F. Fülöp, Harnessing the versatility of con-
tinuous‐flow processes: Selective and efficient reactions, Chem. Rec. 16 (2016)
1018–1033.
[60] D. Tichit, B. Coq, Catalysis by hydrotalcites and related materials, Cattech 7 (2003)
[35] G. Xie, D. Feng, X. Ma, 9-Amino (9-deoxy) epi-cinchona alkaloid-tethered alumi-
nium phosphonate architectures for heterogeneous cooperative catalysis: asym-
metric aldol and double-Michael cascade reaction, Mol. Catal. 434 (2017) 86–95.
[36] C. Li, Chiral synthesis on catalysts immobilized in microporous and mesoporous
materials, Catal. Rev. 46 (2004) 419–492.
206–217.
[61] M. Mokhtar, T.S. Saleh, S.N. Basahel, Mg-Al hydrotalcites as efficient catalysts for
aza-Michael addition reaction: a green protocol, J. Mol. Catal. A 353 (2012)
122–131.
[62] Z.P. Xu, P.S. Braterman, High affinity of dodecylbenzene sulfonate for layered
double hydroxide and resulting morphological changes, J. Mater. Chem. 13 (2003)
268–273.
[37] C. Yu, J. He, Synergic catalytic effects in confined spaces, Chem. Commun. 48
(2012) 4933–4940.
[38] A.V. Malkov, M. Figlus, G. Cooke, S.T. Caldwell, G. Rabani, M.R. Prestly,
P. Kočovský, Organocatalysts immobilised onto gold nanoparticles: application in
the asymmetric reduction of imines with trichlorosilane, Org. Biomol. Chem. 7
(2009) 1878–1883.
[39] L. Zhong, J. Xiao, C. Li, An unexpected inversion of enantioselectivity in direct
asymmetric aldol reactions on a unique L-proline/γ-Al2O3 catalyst, J. Catal. 243
(2006) 422–445.
[63] Q. Tao, J. Yuan, R.L. Frost, H. He, P. Yuan, J. Zhu, Effect of surfactant concentration
on the stacking modes of organo-silylated layered double hydroxides, Appl. Clay
Sci. 45 (2009) 262–269.
[64] N. Nagai, H. Hashimoto, FT-IR-ATR study of depth profile of SiO2 ultrathin films,
Appl. Surf. Sci. 172 (2001) 307–311.
[65] J.T. Kloprogge, D. Wharton, L. Hickey, R.L. Frost, Infrared and Raman study of
2−
−
interlayer anions CO32−, NO3−, SO4
and ClO4 in Mg/Al-hydrotalcite, Am.
[40] F.G. Finelli, L.S. Miranda, R.O. de Souza, Expanding the toolbox of asymmetric
organocatalysis by continuous-flow process, Chem. Commun. 51 (2015)
3708–3722.
[41] J. Lu, P.H. Toy, Organic polymer supports for synthesis and for reagent and catalyst
immobilization, Chem. Rev. 109 (2009) 815–838.
Miner. 87 (2002) 623–629.
[66] V. Rives, S. Kannan, Layered double hydroxides with the hydrotalcite-type structure
containing Cu2+, Ni2+ and Al3+, J. Mater. Chem. 10 (2000) 489–495.
[67] L.J. Fina, Depth profiling of polymer surfaces with FT-IR spectroscopy, Appl.
Spectrosc. Rev. 29 (1994) 309–365.
[42] J.D. Revell, D. Gantenbein, P. Krattinger, H. Wennemers, Solid‐supported and pe-
gylated H–Pro–Pro–Asp–NHR as catalysts for asymmetric aldol reactions,
Biopolymers 84 (2006) 105–113.
[68] H. Xu, Dielectric properties and ferroelectric behavior of poly(vinylidene fluor-
ide‐trifluoroethylene) 50/50 copolymer ultrathin films, J. Appl. Polym. Sci. Symp.
80 (2001) 2259–2266.
[43] A. Stein, B.J. Melde, R.C. Schroden, Hybrid inorganic-organic mesoporous silicates
– nanoscopic reactors coming of age, Adv. Mater. 12 (2000) 1403–1419.
[44] A. Zamboulis, N. Moitra, J.J. Moreau, X. Cattoen, M.W.C. Man, Hybrid materials:
versatile matrices for supporting homogeneous catalysts, J. Mater. Chem. 20 (2010)
9322–9338.
[45] V. Srivastava, K. Gaubert, M. Pucheault, M. Vaultier, Organic-inorganic hybrid
materials for enantioselective organocatalysis, ChemCatChem 1 (2009) 94–98.
[46] Gy. Szőllősi, D. Gombkötő, A.Zs. Mogyorós, F. Fülöp, Surface‐improved asymmetric
Michael addition catalysed by amino acids adsorbed on Laponite, Adv. Synth. Catal.
360 (2018) 1992–2004.
[47] S. Vijaikumar, A. Dhakshinamoorthy, K. Pitchumani, l-Proline anchored hydro-
talcite clays: an efficient catalyst for asymmetric Michael addition, Appl. Catal. A
Gen. 340 (2008) 25–32.
[48] Z. An, W. Zhang, H. Shi, J. He, An effective heterogeneous L-proline catalyst for the
asymmetric aldol reaction using anionic clays as intercalated support, J. Catal. 241
(2006) 319–327.
[69] Y. Suetsugu, I. Shimoya, J. Tanaka, Configuration of carbonate ions in apatite
structure determined by polarized infrared spectroscopy, J. Am. Ceram. Soc. 81
(1998) 746–748.
[70] A. Nakano, M. Ushiyama, Y. Iwabuchi, S. Hatakeyama, Synthesis of an en-
antiocomplementary catalyst of β‐isocupreidine (β‐ICD) from quinine, Adv. Synth.
Catal. 347 (2005) 1790–1796.
[71] M.J. Hernandez-Moreno, M.A. Ulibarri, J.L. Rendon, C.J. Serna, IR characteristics of
hydrotalcite-like compounds, Phys. Chem. Miner. 12 (1985) 34–38.
[72] V.R. Constantino, T.J. Pinnavaia, T.J, Basic properties of Mg21-+x Alx3+ layered double
hydroxides intercalated by carbonate, hydroxide, chloride, and sulfate anions,
Inorg. Chem. 34 (1995) 883–892.
[73] Q. Tao, H. He, R.L. Frost, P. Yuan, J. Zhu, Nanomaterials based upon silylated
layered double hydroxides, Appl. Surf. Sci. 255 (2009) 4334–4340.
[74] Y. Xu, D. Su, H. Feng, X. Yan, N. Liu, Y. Sun, Continuous sol-gel derived SiOC/HfO2
fibers with high strength, RSC Adv. 5 (2015) 35026–35032.
[75] G.M. Renlund, S. Prochazka, R.H. Doremus, Silicon oxycarbide glasses: part II.
Structure and properties, J. Mater. Res. 6 (1991) 2716–2734.
[76] N. Iyi, T. Matsumoto, Y. Kaneko, K. Kitamura, Deintercalation of carbonate ions
from a hydrotalcite-like compound: enhanced decarbonation using acid–salt mixed
solution, Chem. Mater. 16 (2004) 2926–2932.
[49] M. Sipiczki, D.F. Srankó, Gy. Szőllősi, Á. Kukovecz, Z. Kónya, P. Sipos, I. Pálinkó,
Preparation, characterisation and some reactions of organocatalysts immobilised
between the layers of a CaFe-layered double hydroxide, Top. Catal. 55 (2012)
858–864.
[50] L.W. Zhao, Shi H.M, J.Z. Wang, J. He, Nanosheet‐enhanced asymmetric induction of
chiral α‐amino acids in catalytic aldol reaction, Chem. Eur. J. 18 (2012)
15323–15329.
[77] A. Urakawa, D.M. Meier, H. Rüegger, A. Baiker, Conformational behavior of
cinchonidine revisited: a combined theoretical and experimental study, J. Phys.
Chem. A 112 (2008) 7250–7255.
[51] L. Zhang, S. Luo, J.P. Cheng, Non-covalent immobilization of asymmetric organo-
[78] S. Kristyán, Origin of proposed mechanistic models in heterogeneous catalytic en-
antioselective hydrogenation of pyruvates comes from the conformation properties
of internal rotation of cinchona alkaloids, J. Phys. Chem. C 113 (2009)
21700–21712.
catalysts, Catal. Sci. Technol. 1 (2011) 507–516.
[52] D.G. Evans, R.C.T. Slade, Structural aspects of layered double hydroxides, Struct.
Bond. 119 (2006) 1–87.
7