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Structured hydroxyapatite composites as efficient

Cite this: Catal. Sci. Technol., 2021,
solid base catalysts for condensation reactions†
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11, 3428
Tharun Jose,a Jamal Ftounib and Pieter C. A. Bruijnincx *a

Herein, we report the use of structured hydroxyapatite composite (SHCs) as highly efficient and recyclable
solid base catalysts for various condensation reactions. Catalyst performance as function of catalyst
loading, reaction time and reaction temperature were studied in the solventless self-aldol condensation
reaction of butyraldehyde to 2-ethylhexenal under mild reaction conditions. SHC catalysts were found to
outperform benchmark solid base catalysts such as MgO, TiO2, calcium carbonate and hydroxyapatites.
Characterization of the synthesized SHC catalysts by a range of surface analysis, spectroscopic and
electron microscopy techniques, showed that a moderate acid/base ratio and high BET surface area to be
Received 19th January 2021, key to their high efficiency. Furthermore, recycling experiments showed the catalyst to be stable over
Accepted 7th April 2021
multiple runs. Moreover, the most active SHC catalyst was investigated in other prototypical condensation
DOI: 10.1039/d1cy00102g
reactions such as the Knoevenagel condensation, Claisen–Schmidt condensation and Henry reaction, again
showing excellent performance. These results highlight the versatility of these SHC materials and their
rsc.li/catalysis potential for industrial employment as solid base catalysts.

Introduction feedstock, offering the opportunity to produce longer carbon

chain products with high atom economy and with limited
Catalytic condensation reactions are an important tool to generation of (harmless) by-products.10 In particular, aldol
upgrade platform chemicals by C–C bond formation to give condensation reactions are being heavily studied in the
higher value products used for applications ranging from context of bio-oil upgrading, as they achieve oxygen removal
transportation fuels to fine or specialty chemicals.1,2 Some of from the aldehyde fraction of bio-oils, which can make up to
the prototypical condensation reactions include the aldol, 20 wt% of this feed, at no carbon loss. Similarly, such
Knoevenagel, Henry and Claisen–Schmidt condensations, condensation reactions are often central to the upgrading of
among others. For instance, butyraldehyde's self-aldol oxygenated biobased platform molecules.10,11
condensation product 2-ethylhexenal is used as an Liquid phase aldol condensation reactions are typically
intermediate for the synthesis of insecticides, plasticizers and base-catalyzed, either by soluble bases or by solid materials
other fine chemicals.3 Its derivative 2-ethylhexanoic acid is, such as alkali-metal containing zeolites,12 alkaline-earth
for example, used in cosmetics, pharmaceuticals, paints and metal oxides,13 and hydrotalcites.14–16 Solid base use can
coatings.4 Alternatively, the reduction of 2-ethylhexenal yields indeed provide considerable advantages in terms of
2-ethylhexanol, which finds application as or is used as sustainability when it comes to waste generation, catalyst
precursor to plasticizers, wetting agents, solvents, fragrances recovery, solvent use, etc.17,18 Challenges in solid base-
and lubricants5 and is produced at a volume of 2.5 mton per catalyzed conversions, on the other hand, include
year.6 Knoevenagel and Henry reactions in turn yield, for deactivation of the catalyst by poisoning, as well as catalyst
example, valuable chalcones and nitroarenes used in the instability issues, e.g. by leaching of the material into
production of pharmaceuticals, rubber, plastics, flavonoids solution.19 To address these challenges, the development of
and dyes.7–9 Recently, condensation reactions have become new solid base catalysts that show improved performance
even more significant as a tool to upgrade bio-derived and are, preferably, made from readily obtainable materials,
is therefore a subject of considerable interest.
In this context, hydroxyapatites (HAPs), naturally
a
Organic Chemistry and Catalysis, Debye Institute for Nanomaterials Science, occurring minerals with the general formula Ca10(PO4)6(OH)2,
Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
have shown to be excellent catalysts for Knoevenagel,
E-mail: p.c.a.bruijnincx@uu.nl
b
Omya International AG, Froschackerstrasse 6, CH-4622 Egerkingen, Switzerland
Claisen–Schmidt, Henry and aldol condensation
† Electronic supplementary information (ESI) available. See DOI: 10.1039/ reactions.11,20–28 HAP is the most stable calcium phosphate
d1cy00102g salt and the principal inorganic constituent of human bones

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and teeth.29,30 HAPs receive considerable attention as their

ability to form solid solutions, to accept many anionic and
cationic substituents, and to tune its acid/base properties
makes them highly versatile as heterogeneous catalysts for
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liquid-phase condensation reactions.20

HAPs are highly non-stoichiometric solids, with the Ca/P
ratio commonly being used as an index of non-stoichiometry
(the stoichiometric ratio being 1.67) as well as of their acid–
base properties.30,31 It is well known that HAPs are
predominantly acidic when Ca/P ∼1.50, show both acidic and
Open Access Article. Published on 12 April 2021. Downloaded on 11/19/2024 8:52:20 AM.

basic characteristics when the Ca/P ratio is between 1.50 and

1.67 and are predominantly basic when the ratio is ≥1.67. Fig. 1 SEM images of the SHC solid samples.
Carbonate-rich apatites are more basic and typically
synthesized by co-precipitation of sodium carbonates, or by
means of addition of atmospheric CO2 as CO32− anions, an additional amount of octa-calcium phosphate. The CC
which in turn compensate the charge of excess calcium and HAP percentages in SHC-3, SHC-4 and SHC-5 range from
cations in the apatite solids. The use of calcium carbonate 11–15 and 79–85%, respectively. SHC-1 and SHC-2 are more
(CC) as a source of calcium for carbonate-rich HAP synthesis CC rich at 50% and 79%, respectively. Thermal gravimetric
has advantages over the normally employed sources, such as analysis (TGA-DSC) of the SHC samples (Fig. S1†) showed
calcium nitrate, phosphate, chloride or acetate.11,20,31–33 The them to be thermally stable up to 600 °C. The SHC solids all
drawbacks of these non-CC calcium salts are their relatively have a similar morphology. The SEM images (Fig. 1) showed
high costs and the waste originating from associated that the surface of the SHCs is characterized by lamellar HAP
counterions and laborious washing steps. Indeed, CC- surrounded by agglomerated fine CC particulates. It was
derived, carbonate-rich HAP materials thus constitute a class previously shown by FIB-SEM analysis that the structure of
of natural and abundant materials that can be exploited for the particles consists of a CC core surrounded by a HAP
their enhanced basicity, given that their Ca/P ratio is larger shell.38
than 1.67.34–36 In addition to the catalyst precursors used, Table 1 displays the bulk (from ICP-OES) and surface
the choice of synthesis route, also to a large extent, (from XPS) compositions of all SHC catalysts and the Ca/P
determines catalyst properties as well as the ease of material ratio, which, as noted above, is indicative of the acid/base
synthesis scale-up. For example, HAP synthesis is often properties of the materials.20,31 The data shows that all the
carried out via sol–gel procedures, making its production in catalysts have a Ca/P ratio higher than 1.67, suggesting them
industrial amounts challenging. Alternatively, a method has to be predominantly basic (vide infra). Activation is
been disclosed to synthesize CC-based, carbonate-rich HAP mandatory for most of the solid base catalysts prior to
minerals,37 by etching CC and reprecipitating carbonated reaction, as basic sites may be blocked by CO2 and H2O,
HAP materials as structured hydroxyapatite composites resulting in poor activity.19,39 Hence, all catalysts were
(SHCs) by externally supplying CO2 in the form of carbonic subjected to thermal activation at 200 °C for 4 h. The
acid, in the presence of phosphate ions. This procedure nitrogen physisorption measurements in Table 2 show that
allows considerable variation of the CC content in the final the thermal activation procedure did not affect the surface
material. This synthesis approach thus offers advantages over areas or pore volumes. The samples showed a considerable
alternative routes and the acid/base properties of the difference in surface area, ranging from 21.0 to 156.2 m2 g−1.
materials were anticipated to be promising for condensation For comparison, the BET surface area and total pore volume
catalysis. We report the use of these SHC materials as solid of commercially available solids such as MgO, TiO2, CaCO3
base catalysts, first exploring their performance in the self- and HAPs are also included, high (HAP-H) and low (HAP-L)
aldol condensation of butyraldehyde and later expanding the surface area examples for the latter. The nitrogen adsorption/
scope to other condensation reactions. Detailed desorption isotherm plots for the SHC catalysts are presented
characterization data is presented, as well as the in the ESI† (Fig. S2). The thermal treatment also did not alter
development of a regeneration protocol to allow SHC reuse. the phase composition of the materials of any of the samples,
as evidenced by the XRD data displayed in Fig. 2. Moreover,
Results and discussion the characteristic, sharp (104) diffraction peak of CC at 34° is
decreasing as HAP content increases from SHC-1 to SHC-5;
Five SHC materials were used in this study, varying in phase on the contrary an increase in the characteristic, strong (211)
composition and surface area. The mineral compositions of reflection of HAP at 37° is seen.
the as-synthesized SHC materials were determined by The catalysts were first tested for the self-aldol
Rietveld refinement of the powder X-ray diffraction (XRD) condensation reaction using butyraldehyde as the benchmark
patterns (Fig. 2 and Table S1, ESI†). The materials consist substrate, under various experimental conditions. Initial
mainly of CC and HAP components, with SHC-5 containing screening conditions consisted of 130 °C for a reaction time

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Fig. 2 XRD structures of SHC catalysts. (a) Before thermal activation and (b) after thermal activation at 200 °C for 4 h.

of 22 h under solvent-free conditions at 3 mol% catalyst perform better. The results thus show that the high HAP
loading, conditions typically described in literature (see Table content materials (SHC-3, SHC-4 and SHC-5) gave the highest
S2† for an overview of literature results).40–46 The results, yield.
presented in Table 3, show that no conversion was obtained The reaction parameters (reaction time, catalyst loading
in the absence of a catalyst after 2 or 6 h and a 6% yield of and reaction temperature) were optimized using the most
the desired product at 8% conversion after 22 h (entry 1). active catalyst (SHC-3) under solvent-free conditions. As the
Entries 2 to 6 are commercially available solid base catalysts selectivity for the 2-ethylhexenal product was found to be
such as MgO, TiO2, CaCO3 and HAP, and are included for high throughout (>97%), butyraldehyde conversion will be
benchmarking. Among the benchmark solids, HAP-H showed used to describe catalyst performance. Variation of reaction
the best catalytic activity up to 6 h, whereas for 22 h MgO time showed that after 4 h butyraldehyde conversion is
and HAP-H showed similar performance, both having higher almost complete, showing only a very small gain after that
surface area compared to the rest of the commercial solids. (Fig. S3†). Catalyst loading was varied from 0.5 to 3 mol%,
Compared to these conventional solid base catalysts, SHC-3, resulting in a butyraldehyde conversion increase from 11 to
SHC-4 and SHC-5 (entries 9–11) exhibited excellent catalytic 96% (Fig. S4†). Generally, catalyst loadings of around 10
activity. While most SHC catalysts reached full conversion mol% or higher are described for the self-aldol condensation
after 22 h, the results after 6 h showed the activity to increase reactions (Table S2†).40,45–48 Typically, base catalysts are
in the order SHC-1 < SHC-2 < SHC-4 < SHC-5 < SHC-3. sensitive to atmospheric CO2 and moisture, and deactivation
Overall, under the selected reaction conditions, the desired of basic sites occurs to a greater extent compared to acid
product (2-ethylhexenal) is obtained in good yield and catalysts.19,39 Moreover, the condensation reaction generates
excellent selectivity throughout. As SHCs contain both CC
and HAP phases, a physical mixture of CC and HAP-L
Table 2 Nitrogen physisorption data for the SHC catalysts and
catalysts (entry 12), in the same proportion as SHC-3, was benchmark solid base materials
also tested; this combination proved to be the least active,
underperforming even in comparison with the individual BET surface area Total pore volume
(m2 g−1) (cm3 g−1)
components (entry 4 and 5). A comparison of the best
Entry Catalyst Beforea Afterb Beforea Afterb
performing SHC material (SHC-3) and HAP-H at the same
wt% of added catalyst (Table S3†) again showed the former to 1 SHC-1 21.0 19.3 0.03 0.13
2 SHC-2 56.7 58.1 0.10 0.41
3 SHC-3 156.2 160.3 0.30 0.87
Table 1 Bulk and surface composition of the SHC catalysts 4 SHC-4 86.7 85.5 0.19 0.18
5 SHC-5 105.5 106.7 0.67 0.65
ICP-OES XPS 6 MgO n.d. 239.5 n.d. 0.24
Ca P Ca/P Ca P Ca/P 7 TiO2 n.d. 7.4 n.d. 0.03
Catalyst (at%) (at%) (at. ratio) (at%) (at%) (at. ratio) 8 CaCO3 n.d. 6.6 n.d. 0.05
9 HAP-Lc 9.4 n.d. n.d. n.d.
SHC-1 87.9 12.1 7.3 14.2 6.7 2.1 10 HAP-Hc 100 n.d. n.d. n.d.
SHC-2 79.7 20.3 3.9 13.0 6.7 1.9
SHC-3 83.3 16.7 4.9 14.4 7.8 1.9 a
Before thermal activation. b After thermal activation at 200 °C for 4
SHC-4 79.7 20.3 3.9 14.1 6.7 2.1 h. c Publicly available information on commercial samples; n.d.-not
SHC-5 70.2 29.9 2.3 14.5 8.1 1.8 determined.

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Table 3 Screening of self-aldol condensation reaction of butyraldehyde into 2-ethylhexenal using various catalysts
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Time (h)
2 6 22
Entry Catalyst X (%) Y (%) X (%) Y (%) X (%) Y (%)
1 — 0 0 0 0 8 6
2 MgO 0 0 30 29 71 70
3 TiO2 0 0 9 9 50 47
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4 CaCO3 2 2 40 39 60 59
5 HAP-L 7 7 41 39 62 60
6 HAP-H 10 10 53 53 70 68
7 SHC-1 0 0 28 28 50 48
8 SHC-2 9 9 29 29 57 55
9 SHC-3 73 72 100 99 n.d. n.d.
10 SHC-4 18 18 70 69 88 85
11 SHC-5 58 57 91 89 100 98
12 CaCO3 + HAP-L 3 3 10 10 43 43

Reaction conditions: temperature = 130 °C; catalyst loading = 3 mol%; X = conversion, Y = yield; HAP-L = hydroxyapatite with lower surface area
(9.4 m2 g−1); HAP-H = hydroxyapatite with higher surface area (100 m2 g−1); entry 12, catalyst loading – CaCO3 = 0.5 mol%, HAP-L = 2.5 mol%;
n.d. = not determined; conversion and yield were determined by 1H NMR (CDCl3) using mesitylene as an internal standard.

water that can further tamper the basic active sites and activity (Table 3). The BET surface area of the SHC catalysts
require higher catalyst loadings to obtain good catalytic (Table 2) did correlate with catalytic activity (SHC-3 > SHC-5
activity.1 The SHC catalysts, however, already showed > SHC-4 > SHC-2 > SHC-1), i.e. the catalytic activity
excellent results at low loading of 3 mol%. The dependence increases along with the catalysts BET surface area. Similarly,
of butyraldehyde conversion on the reaction temperature was the pore volume also followed the similar trend as of BET
also investigated (Fig. S5†). Expectedly, at lower reaction surface area, except for SHC-4. SHC-4 (0.18 cm3 g−1) showed a
temperatures, the aldol addition products dominate, while at lower pore volume compared to SHC-2 (0.42 cm3 g−1),
temperatures above 100 °C, typically only the unsaturated whereas BET surface area, as well as surface Ca/P ratio (from
condensation products are detected. At temperatures above XPS) for SHC-4, was found to be higher compared to the
200 °C, further condensation to the trimer products could SHC-2 catalyst. In addition, SHC-4 contains more acidic and
also be observed.28 With the dimer 2-ethylhexenal being the basic sites than SHC-2, as discussed in the next section. In
desired product, we screened by varying the temperature general, the crystallinity, BET surface area and catalytic
range from 80 to 130 °C. Excellent activity with a selectivity of activity all negatively correlate with an increasing carbonate
>99% for the dimer product was obtained at 130 °C. content for the SHC materials, in agreement with literature.31
As presented in Table 1, XPS data showed that all the SHC The acid–base properties of the SHC solid catalysts and
catalysts have a Ca/P ratio higher than 1.67 and would act as the commercially available HAPs were studied with NH3 and
base catalysts, but this ratio did not correlate with catalytic CO2 TPD (Table 4). Detailed distribution of acidic/basic sites

Table 4 Number of acidic and basic sites as determined by NH3 and CO2-TPD, respectively

ICP-OES CO2-TPD NH3-TPD

−1
Entry Catalyst Ca/P atomic ratio Total number of basic sites (mmol g ) Total number of acidic sites (mmol g−1) Ref.
1 SHC-1 7.13 0.05 0.03 This work
2 SHC-2 3.93 0.08 0.09
3 SHC-3 4.95 0.33 0.19
4 SHC-4 3.88 0.15 0.13
5 SHC-5 2.34 0.08 0.12
6 HAP-L 1.85 0.06 0.02
7 HAP-H 1.89 0.13 0.11
8 Hap 1.69 0.10 0.76 31
9 Hap-CO3 1.70 0.13 0.65 31
10 HapE-NaCO3 2.39 0.10 0.14 31
11 Ca-HA 1.67 0.02 0.09 28

Hap = stoichiometric hydroxyapatite; Hap-CO3 = carbonated hydroxyapatite; HapE-NaCO3 = sodium-containing carbonate-rich hydroxyapatite;
Ca-HA = hydroxyapatite; ref. = references.

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is presented in the Table S4.† The SHC catalysts that showed

good catalytic activity (SHC-3, SHC-4 and SHC-5), exhibited a
good share of both basic and acidic sites. For SHC-2 and
SHC-5, the number of acidic sites was found to be slightly
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higher compared to the number of basic sites, even though

the Ca/P ratios of these catalysts were higher than 1.67.
Similar results have been previously reported for the HAP
catalysts, as shown in Table 4, entries 8–11.28,31 Fig. 3 shows
the CO2 desorption profiles, indicative of the nature of the
basic sites, for the most active catalysts (SHC-3, SHC-4 and
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SHC-5) and Fig. S6† for SHC-1 and SHC-2. It is known that a
combination of moderate acidic and basic sites is beneficial
Fig. 4 NH3-TPD curves for the SHC solids. Moderate acidic sites =
for catalytic activity for aldol condensation reactions.11,28 The 150–400 °C.
results here are in line with this, with e.g. the least active
SHC-1 material possessing only weak basic sites (Fig. S6†).
The most active catalysts (SHC-3 and SHC-5) mainly have
basic sites of moderate strength (temperature of desorption anticipated, vital to impart good catalytic activity in this aldol
between 150–400 °C) and fewer weaker ones (<150 °C). SHC- condensation reaction.
4, in contrast, has more weak basic sites than moderate ones. Catalyst recycling or reusability is evidently important
In line with this, the probability for basic site from economic and environmental points of view.49,50
accommodation increases with pore volume,19 and SHC-4 is Deactivation may even be more of a concern for solid base
at the lower end of the pore volume range with 0.18 cm3 g−1. catalysts compared to solid acid catalysts particularly in
As noted above, some acidity is also important for the self- liquid phase reactions at elevated temperatures with polar
aldol condensation reaction, e.g., to aid the dehydration step. substrates.39 To validate the potential for reuse of the SHC
Acidity measurements with NH3-TPD were comparable to the solid catalysts, recycling experiments were performed with
CO2-TPD results, with SHC-3 giving the highest number of SHC-3. After each run, the catalyst was recuperated, washed
acidic sites. The acidity of all the SHC catalysts was found to thoroughly with solvent, dried, weighed and subsequently
be in the moderate range (150–400 °C), as shown in Fig. 4. applied in an ensuing run. As a slight amount of material is
That striking the right balance in strength and ratio of inevitably lost during such a protocol, the substrate amount
basic and acid sites is more important than only strong was adjusted to keep the catalyst loading at 3 mol% in each
basicity, is illustrated by the fact that while MgO has both reuse (Table 5). In general, no physical change to the catalyst,
more and stronger basic sites than SHC-3, it is less active in nor dissolution of the material into solution were noticed.
the condensation reaction (Table 3 and Fig. S7†). Commercial Entries 1 and 2 show the first recycle experiments with SHC-
hydroxyapatite (HAP-H), on the other hand, has a
comparable, but basic sites are distributed as a border line
between weaker and moderate region than the active SHC Table 5 Recycle studies of the SHC catalysts

catalysts (Fig. S8† and Table 4), resulting in a lower activity Yield (%)
Washing
(compare to SHC-3, SHC-4 and SHC-5) (Table 3). For HAP-L, Entry Catalyst solvent Run no. 4h 22 h
all basic sites are of weak strength (Fig. S8†). In summary,
1 SHC-3 Ether 1 (fresh) 88 n.d.
the presence of moderate acidic and basic sites is, as 2 11 55
3 7 58
4 13 57
2 MeOH 1 (fresh) 89 n.d.
2 21
3 SHC-4 Ether 1 (fresh) 42 n.d.
2 36 74
3 35 73
4 35 73
4 SHC-4 MeOH 1 (fresh) 42 n.d.
2 33
3 39
4 39
5 SHC-3 MeOH 1 (fresh) 90
2 25
3 64
4 66

Reaction conditions: aldehyde = butyraldehyde; temperature = 130

Fig. 3 CO2-TPD curves for the SHC solids. Weak basic sites ≤150 °C, °C; catalyst loading = 3 mol%; results from NMR; IS = mesitylene;
moderate basic sites = 150–400 °C. MeOH = methanol; n.d. = not determined.

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3, highlighting a drastic drop-in catalytic activity in the fresh run, the catalyst was subjected to a thermal activation
second run, giving only an 11% yield after 4 h. Extending the at 200 °C for 4 h, whereas for runs 3 and 4 the thermal
reaction time to 22 h led to an increase in yield to around activation was performed at 200 °C overnight. For both
55%, a level that was maintained also upon subsequent catalysts, a small drop-in activity was still seen in the 2nd
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recycling. These results thus demonstrate the catalyst to still run; whereas an improvement in the catalytic performance
be active under these recycling conditions, but much less so was observed in runs 3 and 4. Analysis of the spent and
than the fresh catalyst. XRD analysis (Fig. S9†), for entry 1, regenerated materials by FT-IR (Fig. S12†) again points at the
showed that the structure remained intact after the first formation of carbonaceous materials as primary cause for
recycle. Similarly, SEM images (Fig. S10†) did not show any catalyst deactivation. For both SHC-3 and SHC-4, IR spectra
visual change in SHC-3's morphology. Encouragingly, ICP of the catalysts recovered after first run showed more
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analysis of the reaction mixture of entry 1 (Table S5†), after carbonaceous materials, as indicated by bands seen between
separating the catalyst by filtration, showed no leaching of 3000–2800 cm−1, which can be attributed to aldehyde C–H
Ca or P (entry 3, Table S5†); elemental analysis however, did and/or C–H alkyl stretching vibrations; additionally, the
show an increase in carbon content (entry 2, Table S5†), spectra of the SHC-3 catalyst also showed a broad OH peak
suggesting carbonaceous material deposition to cause the around 3400 cm−1.54,55 As previously stated, prior to the 2nd
drop in catalytic activity by blockage of active sites.39,51–53 run, the recovered catalysts were subjected to thermal
Changing the catalyst washing solvent from diethyl ether to activation at 200 °C for only 4 h, whereas for runs 3 and 4,
more polar methanol resulted in an improved catalytic the thermal activation was done overnight. The resulting
activity upon reuse (entry 2, Table 5), but did not yet lead to improvement seen in activity for runs 3 and 4, coincided with
full restoration of activity. As carbon deposition may likely the disappearance of the peaks around 3000 and 3400 cm−1,
also be a function of total basicity/acidity, this was expected after the 4th run. The results thus show that the catalyst
to be less of an issue for some of the other SHC materials, activity can be close to completely regained by proper
thus providing a payoff between (initial) activity and stability. thermal reactivation and selection of catalyst washing
Indeed, upon switching to SHC-4 (entry 3, Table 5), we noted solvent. Overall, SHC-4 catalyst showed better recyclability,
that activity could be close to fully maintained upon recycling even though its catalytic activity was on the lower end,
up to four times. Again, as for SHC-4 XRD analysis showed compared to the SHC-3 catalyst. The difference in pore
that crystallinity was preserved (Fig. S11†). That SHC-3 volume (0.87 vs. 0.18 cm3 g−1 for SHC-3 and SHC-4,
showed a more dramatic loss in activity than SHC-4 respectively), while initially unfavorable for activity, could
correlates with the larger loss of BET surface area and basic then have the upside of allowing less coke to be
sites (CO2-TPD) of the former (Table S6†), in line with accommodated.
deactivation by carbon deposition. The applicability of the SHC materials was finally tested in
Further improvement of the catalyst regeneration protocol other condensation reactions, using SHC-3 in prototypical
involved reversal of active site blockage by CO2 or H2O.19,39,52 Knoevenagel, Claisen–Schmidt and Henry reactions. The
Indeed, thermal reactivation after washing further improved reaction conditions were optimized similarly to the self-aldol
recyclability. Table 5, entries 4 and 5, illustrates the recycling condensation reactions and the results are displayed in
experiments for both SHC-4 (entry 4) and SHC-3 (entry 5) Table 6. Entry 1 shows the results of the Knoevenagel
where after each cycle the catalyst has been subjected to a condensation reaction between benzaldehyde and
thermal reactivation and washing using methanol as the malononitrile to produce 2-benzilidenemalononitrile, a
solvent. For both catalysts (entries 4 and 5), after the first versatile chemical building block. Compared to the self-aldol

Table 6 Other condensation reactions

Time (h)

T 2 6 22 44
Entry Reactions Product (°C) X (%) Y (%) X (%) Y (%) X (%) Y (%) X (%) Y (%)
1 Knoevenagel condensation 70 40 38 87 83 100 95 n.d.
130 67 67 93 92 100 96

2 Claisen–Schmidt condensation 130 19 17 39 35 75 74 98 97

3 Henry reaction 130 14 9 29 27 69 68 96 95

Reaction conditions: catalyst loading = 3 mol%; catalyst: SHC-3; T = temperature; X = conversion, Y = yield; entry 1, substrate 1 = benzaldehyde,
substrate 2 = malononitrile; entry 2, substrate 1 = benzaldehyde, substrate 2 = acetophenone; entry 3, substrate 1 = benzaldehyde, substrate 2 =
nitromethane; substrate ratio: 1 : 2; n.d. = not determined; conversion and yield were determined by 1H NMR (CDCl3) using mesitylene as an
internal standard.

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condensation reaction, the Knoevenagel reaction worked well Experimental

at lower reaction temperatures too. SHC-3 also proved to be
active, albeit more moderately, in chalcone synthesis through Unless otherwise noted, all commercial reagents were used
the Claisen–Schmidt condensation reaction of benzaldehyde as received without further purification. Butyraldehyde
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and acetophenone (entry 2). Finally, the Henry reaction (≥99.5%), malononitrile (≥99%), nitromethane (≥99%),
between benzaldehyde and nitromethane gave β-nitrostyrene mesitylene (98%), HAP-L nanopowder (<200 nm, particle
as the main product. The Henry reaction is well-known for size, ≥97%), HAP-H (5 μm, particle size) and TiO2
the reversible nature of the nitroaldol addition product and nanopowder (<100 nm particle size, 99.5%) were purchased
after 2 h of reaction, both the nitroaldol product (2-nitro-1- from Sigma-Aldrich. Benzaldehyde (98+%), acetophenone
phenylethanol) and the condensation product (β-nitrostyrene) (98%), CC (98+%) and MgO (98%) were obtained from Acros
Open Access Article. Published on 12 April 2021. Downloaded on 11/19/2024 8:52:20 AM.

were detected with yields of 33% and 67%, respectively. organics.

With dehydration being irreversible, the selectivity to the SHCs were obtained from Omya International. The core–
latter further increased with reaction time to 92% and shell SHC materials consist of a CC core and a shell a
>99% after 6 h and 22 h, respectively, with conversions of lamellar HAP surrounded by agglomerated fine CC
29 and 69%. particulates. The samples are produced by etching CC
particles and reprecipitating modified surface structure with
Conclusions in situ or externally supplied CO2 in the form of carbonic
acid. To facilitate the in situ production of CO2, acids such as
SHC materials, consisting of a combination of CC and HAP phosphoric acid can be used, resulting in a mixed mineral
phase and made from readily available minerals, were found morphology. Variations in the etching process produce a
to be excellent solid base catalysts for the self-aldol range of morphologies with recrystallized surfaces, consisting
condensation of butyraldehyde. A high HAP content proved of incorporated hydroxyapatite (HAP) in the case of
beneficial for catalysis with the materials containing ca. 15% phosphoric acid.
CC and 85% HAP, respectively, performing best. As evident XRD patterns were recorded using a Bruker D2 Phaser
from the control experiments, careful synthesis and close powder X-ray diffractometer using a Co radiation source, Co
interaction between the HAP and CC phases seems key to Kα = 1.789 Å. Measurements were carried out between 10–70°
provide the best catalytic activity for SHC catalysts, as the 2θ using a scan speed of 0.5 s per step. TGA was conducted
physical mixtures of HAP and CC or individual components using Mettler Toledo TGA/DSC 3+. The samples were heated
proved much less effective. Investigation of various reaction from 25 up to 600 °C with a ramp of 25 °C and a 10 min hold
parameters indicated that the butyraldehyde conversion at 105 °C and 500 °C, with an air flow of 80 ml min−1. XPS
reached its maximum when the reaction was carried out with experiments were carried out in a Kratos AXIS Ultra DLD
3 mol% of catalyst loading, at 130 °C for 4 h. Catalytic activity spectrometer using a monochromatic Al Kα radiation (hυ =
increased with BET surface area, as well as with 1486.6 eV) operating at 225 W (15 mA, 15 kV). Instrument
mesoporosity. Striking a balance in the amount, nature and base pressure was 5 × 10−10 Torr. SEM images were recorded
ratio of acidic and basic sites is crucial for catalytic on two different instruments, (a) for general characterization:
performance in the self-aldol condensation reaction; all a Sigma VP field emission scanning electron microscope
active SHC catalysts combine a higher number of moderate (Carl Zeiss AG, Germany) and a variable pressure secondary
acidic and basic sites with some weak acidic and basic sites. electron detector (VPSE) and/or secondary electron detector
Upon proper regeneration by washing and thermal (SE) with a chamber pressure of about 50 Pa, (b) for recycle
reactivation, the SHC catalysts proved to be recyclable. experiments: the surface images were taken with a
Furthermore, the SHC catalysts also performed well in other ThermoScientific phenom Pro X microscope operated at 10
condensation reactions such as the Knoevenagel kV acceleration voltage. The Ca and P contents of the SHC
condensation, Claisen–Schmidt condensation and Henry solids were analysed via ICP-OES technique using a Perkin
reactions. Elmer Avio 500 device. The textural properties of the SHC
In general, compared to widely employed solid base solids were analysed by recording an N2 physisorption
catalysts such as MgO and HAP, SHC catalysts performed isotherms with a Micromeritics Tristar 3000 setup. The
better in the self-aldol condensation reaction of samples were outgassed prior to performing the
butyraldehyde. The SHC materials are industrially available, measurement overnight at 300 °C under a N2 flow. Surface
porous, and stable structures made from naturally abundant areas were determined using the Brunauer–Emmett–Teller
and non-toxic precursors and have now been shown to (BET) theory. The carbon content of the SHC catalysts was
perform well as solid base catalysts for condensation obtained from EA and it was carried out using a Fisons
reactions. As such, these highly active solid base catalysts, of NA1500 NCS analyser. Infrared spectra were recorded using a
which the acid–base and morphological properties can be Perkin Elmer Spectrum Two FT-IR spectrometer.
carefully tuned, provide a promising new addition to the Temperature programmed desorption of ammonia (NH3-
existing portfolio of industrially employed solid base TPD) measurements were performed using a Micromeritics
catalysts. ASAP2920 apparatus. 0.1 g of sample was dried in situ under

3434 | Catal. Sci. Technol., 2021, 11, 3428–3436 This journal is © The Royal Society of Chemistry 2021
 View Article Online

Catalysis Science & Technology Paper

an He flow with a temperature ramp of 5 °C min−1 up to 400 Claisen–Schmidt condensation reaction,

°C. Subsequently, the sample was cooled to 100 °C; at this benzylideneacetophenone (chalcone): 1H NMR (CDCl3, 100
point, NH3 pulses of 25.3 cm3 min−1 were applied. The MHz) δ = 7.40–7.67 (m, 9H), 7.82 (d, J = 15.7 Hz, 1 H), 8.03
sample was then heated to 600 °C with a ramp of 5 °C min−1 (dd, J = 8.4, 1.4 Hz, 2 H) ppm. 13C NMR (400 MHz, CDCl3); δ
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to induce desorption of NH3. A procedure similar to the one = 122.26, 128.44, 128.59, 128.65, 128.77, 130.65, 132.91,
described for NH3-TPD was employed for temperature 134.58, 137.26, 145.03, 198.24.
programmed desorption of CO2 (CO2-TPD), the main Henry reaction, 2-nitrovinylbenzene (β-nitrostyrene): 1H
difference being the lower temperature (50 vs. 100 °C) at NMR (CDCl3, 400 MHz) δ 7.41–7.51 (m, 3H), 7.54–7.57 (m,
which CO2 pulses are fed to the sample. For calculating the 2H), 7.59 (d, J = 13.7 Hz, 1H), 8.01 (d, J = 13.7 Hz, 1H) ppm.
number of acidic or basic sites, it was assumed that only one 13
C NMR (100 MHz, CDCl3); δ = 129.10, 129.39, 130.08,
Open Access Article. Published on 12 April 2021. Downloaded on 11/19/2024 8:52:20 AM.

molecule of NH3 or CO2 can adsorb on a single site. Detailed 130.15, 132.11, 137.69, 139.03.
procedure in ESI† (E1).
The aldol condensation of butyraldehyde was performed Conflicts of interest
in a batch reaction system, under vigorous magnetic stirring
and a nitrogen atmosphere. Prior to the reaction, all the SHC T. J., J. F. and P. C. A. B. are listed as inventors on a patent
solids were thermally activated at 200 °C for 4 h. In a typical application filed by Omya International related to the results
experiment, a 50 mL two-necked flask connected to a reflux described in the manuscript.
condenser was filled with 55.6 mmol of butyraldehyde, 3
mol% SHC (mol% = catalyst loading (mmol)/butyraldehyde Acknowledgements
(mmol) × 100) of catalyst (SHC solids) and mesitylene as the The authors thank Dr. Craig DePorter, Dr. Daniel E. Gerard,
internal standard. After passing the N2 through the Dr. Nicole Russ and Sarah Gysin, from Omya International,
headspace of the reaction system and setting a constant, for their support. Omya International is kindly acknowledged
vigorous stirring rate, the reaction mixture was heated up to for financial support.
the required temperature (80–130 °C). The progress of the
reaction was monitored by taking samples from the reaction Notes and references
media at different intervals of time (2–22 h). For the recycling
experiments, the used catalyst was filtered, washed 1 S. Fakirov, Prog. Polym. Sci., 2019, 89, 1–18.
thoroughly with a solvent (ether or methanol), dried at 200 2 A. Dhakshinamoorthy, M. Opanasenko, J. Čejka and H.
°C, weighed and then applied in a subsequent run. The Garcia, Adv. Synth. Catal., 2013, 355, 247–268.
conversion and yield were determined by 1H NMR (CDCl3). 3 S. K. Sharma and R. V. Jasra, Ind. Eng. Chem. Res., 2011, 50,
The 1H spectra (400 MHz) and 13C spectra (100 MHz) were 2815–2821.
recorded on an Agilent MRF400 or a Varian AS400 4 R. Raju and K. Prasad, Tetrahedron, 2012, 68, 1341–1349.
spectrometer at 25 °C. The chemical shifts are reported in 5 R. D. Ashford, Ashford's Dictionary of industrial chemicals,
the standard δ notation of parts per million, referenced to Wavelength, Saltash, 2011.
residual peak of the solvent, as determined relative to TMS (δ 6 G. J. Kelly, F. King and M. Kett, Green Chem., 2002, 4,
= 0 ppm). 392–399.
All the other condensation reactions were carried out 7 A. Miller, W. Keener, M. Watwood and F. Roberto, Appl.
similarly to the aldol condensation reaction. For the Microbiol. Biotechnol., 2002, 58, 183–188.
Knoevenagel condensation reaction, the substrates employed 8 E. Rohrmann, R. G. Jones and H. A. Shonle, J. Am. Chem.
were benzaldehyde and malononitrile, similarly for the Soc., 1944, 66, 1856–1857.
Claisen–Schmidt condensation reaction, benzaldehyde and 9 K. Ramawat and J. M. Mérillon, Natural Products:
acetophenone were used and the substrates, benzaldehyde Phytochemistry, Botany and Metabolism of Alkaloids, Phenolics
and nitromethane for the Henry reaction. In all cases the and Terpenes, 2013.
substrate ratio is maintained 1 (benzaldehyde) : 2 and the 10 L. Wu, T. Moteki, A. A. Gokhale, D. W. Flaherty and F. D.
catalyst loading of 3 mol% was used, and temperatures of Toste, Chem, 2016, 1, 32–58.
130 °C was employed except for Knoevenagel condensation, 11 E. G. Rodrigues, T. C. Keller, S. Mitchell and J. Pérez-
where a lower reaction temperature (70 °C) was also used. Ramírez, Green Chem., 2014, 16, 4870–4874.
Aldol condensation reaction, 2-ethyl-2-hexenal: 1H NMR 12 M. J. Climent, A. Corma, H. Garcia and J. Primo, J. Catal.,
(CDCl3, 400 MHz) δ = 0.98 (m, 6H), 1.56 (m, 2H), 2.36 (m, 4H), 1991, 130, 138–146.
6.43 (t, J = 7.5 Hz 1H), 9.36 (s, 1H). 13C NMR (100 MHz, CDCl3); 13 A. M. Frey, J. Yang, C. Feche, N. Essayem, D. R. Stellwagen,
δ = 13.47, 14.02, 17.40, 22.10, 30.82, 145.53, 154.77, 195.26. F. Figueras, K. P. de Jong and J. H. Bitter, J. Catal.,
Knoevenagel condensation reaction, 2-benzylidene- 2013, 305, 1–6.
malononitrile: 1H NMR (400 MHz, CDCl3) δ (ppm): 7.55 (t, J = 14 W. Bing, L. Zheng, S. He, D. Rao, M. Xu, L. Zheng, B. Wang,
7.6 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.78 (s, 1H), 7.91 (d, J = Y. Wang and M. Wei, ACS Catal., 2018, 8, 656–664.
7.3 Hz, 2H), 13C NMR (100 MHz, CDCl3); δ = 82.86, 112.48, 15 O. Kikhtyanin, D. Kadlec, R. Velvarská and D. Kubička,
113.51, 129.60, 130.70, 134.54, 159.88. ChemCatChem, 2018, 10, 1464–1475.

This journal is © The Royal Society of Chemistry 2021 Catal. Sci. Technol., 2021, 11, 3428–3436 | 3435
 View Article Online

Paper Catalysis Science & Technology

16 W. Bing, H. Wang, L. Zheng, D. Rao, Y. Yang, L. Zheng, B. 35 C. Verwilghen, M. Chkir, S. Rio, A. Nzihou, P. Sharrock and
Wang, Y. Wang and M. Wei, Green Chem., 2018, 20, G. Depelsenaire, Mater. Sci. Eng., C, 2009, 29, 771–773.
3071–3080. 36 D. M. Roy and S. K. Linnehan, Nature, 1974, 247, 220–222.
17 H. Hattori, Chem. Rev., 1995, 95, 537–558. 37 J. Ftouni, T. Jose and P. C. A. Bruijnincx, CH Pat.,
This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.

18 Y. Ono, J. Catal., 2003, 216, 406–415. 20199667.5-1109, 2020.

19 L.-B. Sun, X.-Q. Liu and H.-C. Zhou, Chem. Soc. Rev., 38 M. Farzan, R. Roth, G. Québatte, J. Schoelkopf, J. Huwyler
2015, 44, 5092–5147. and M. Puchkov, Pharmaceutics, 2019, 11, 32.
20 A. Fihri, C. Len, R. S. Varma and A. Solhy, Coord. Chem. Rev., 39 I. Sádaba, M. López Granados, A. Riisager and E. Taarning,
2017, 347, 48–76. Green Chem., 2015, 17, 4133–4145.
21 A. Smahi, A. Solhy, H. El Badaoui, A. Amoukal, A. Tikad, M. 40 X. Zhang, H. An, H. Zhang, X. Zhao and Y. Wang, Ind. Eng.
Maizi and S. D. Sebti, Appl. Catal., A, 2003, 250, 151–159. Chem. Res., 2014, 53, 16707–16714.
Open Access Article. Published on 12 April 2021. Downloaded on 11/19/2024 8:52:20 AM.

22 S. D. Sebti, R. Tahir, R. Nazih, A. Saber and S. D. Boulaajaj, 41 H. A. Patel, S. K. Sharma and R. V. Jasra, J. Mol. Catal. A:
Appl. Catal., A, 2002, 228, 155–159. Chem., 2008, 286, 31–40.
23 N. Elazarifi, A. Ezzamarty, J. Leglise, L.-C. D. Ménorval and 42 T. Jose, N. Sudheesh and R. S. Shukla, J. Mol. Catal. A:
C. Moreau, Appl. Catal., A, 2004, 267, 235–240. Chem., 2010, 333, 158–166.
24 S. Sebti, A. Solhy, R. Tahir and A. Smahi, Appl. Catal., A, 43 D. Sun, S. Moriya, Y. Yamada and S. Sato, Appl. Catal., A,
2002, 235, 273–281. 2016, 524, 8–16.
25 A. Solhy, R. Tahir, S. Sebti, R. Skouta, M. Bousmina, M. 44 D. Liang, G. Li, Y. Liu, J. Wu and X. Zhang, Catal. Commun.,
Zahouily and M. Larzek, Appl. Catal., A, 2010, 374, 189–193. 2016, 81, 33–36.
26 N. Neelakandeswari, G. Sangami, P. Emayavaramban, R. 45 X. Xu, H. Meng, Y. Lu and C. Li, RSC Adv., 2018, 8,
Karvembu, N. Dharmaraj and H. Y. Kim, Tetrahedron Lett., 30610–30615.
2012, 53, 2980–2984. 46 Z. Wang, P. Fongarland, G. Lu and N. Essayem, J. Catal.,
27 Z. D. Young, S. Hanspal and R. J. Davis, ACS Catal., 2016, 6, 2014, 318, 108–118.
3193–3202. 47 Y. Watanabe, K. Sawada and M. Hayashi, Green Chem.,
28 A. M. Hernández-Giménez, J. Ruiz-Martínez, B. Puértolas, J. 2010, 12, 384–386.
Pérez-Ramírez, P. C. A. Bruijnincx and B. M. Weckhuysen, 48 A. Corma, V. Fornés, R. M. Martín-Aranda and F. Rey,
Top. Catal., 2017, 60, 1522–1536. J. Catal., 1992, 134, 58–65.
29 T. J. Webster, E. A. Massa-Schlueter, J. L. Smith and E. B. 49 M. Marafi and A. Stanislaus, Resour., Conserv. Recycl.,
Slamovich, Biomaterials, 2004, 25, 2111–2121. 2008, 52, 859–873.
30 S. Kannan, J. H. G. Rocha and J. M. F. Ferreira, J. Mater. 50 J. H. Clark, T. J. Farmer, L. Herrero-Davila and J. Sherwood,
Chem., 2006, 16, 286–291. Green Chem., 2016, 18, 3914–3934.
31 L. Silvester, J.-F. Lamonier, R.-N. Vannier, C. Lamonier, M. 51 M. Guisnet and P. Magnoux, Appl. Catal., A, 2001, 212, 83–96.
Capron, A.-S. Mamede, F. Pourpoint, A. Gervasini and F. 52 C. Sievers, Y. Noda, L. Qi, E. M. Albuquerque, R. M. Rioux
Dumeignil, J. Mater. Chem. A, 2014, 2, 11073–11090. and S. L. Scott, ACS Catal., 2016, 6, 8286–8307.
32 T. Hara, S. Kanai, K. Mori, T. Mizugaki, K. Ebitani, K. 53 O. Kikhtyanin, V. Kelbichová, D. Vitvarová, M. Kubů and D.
Jitsukawa and K. Kaneda, J. Org. Chem., 2006, 71, 7455–7462. Kubička, Catal. Today, 2014, 227, 154–162.
33 D. A. Nowicki, J. M. S. Skakle and I. R. Gibson, J. Mater. 54 J. Shangguan, C.-H. Li, M.-Q. Miao and Z. Yang, New Carbon
Chem. A, 2018, 6, 5367–5377. Mater., 2008, 23, 37–43.
34 D. Pham Minh, N. D. Tran, A. Nzihou and P. Sharrock, Ind. 55 S. Zeng, S. Liu, Y. Qi, L. Cui, Q. Dai and C. Bai, RSC Adv.,
Eng. Chem. Res., 2013, 52, 1439–1447. 2018, 8, 11462–11468.

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