Highly active hybrid mesoporous silica-supported base organocatalysts for C–C bond formation

Article abstract of DOI:10.1016/j.cattod.2019.09.041

New base hybrid catalysts, based on silyl-derivatives of molecules carrying amino, diamino, pyrrolidine, pyrazolium and imidazolium functionalities have been successfully achieved through post synthetic grafting onto M41S-type support. Different character

Full text of DOI:10.1016/j.cattod.2019.09.041

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Highly Active Hybrid Mesoporous Silica-Supported Base
Organocatalysts for C-C Bond Formation
´
A. Erigoni, M.C. Hernandez-Soto, F. Rey, C. Segarra, U. D´ıaz
PII:
S0920-5861(19)30538-3
DOI:
https://doi.org/10.1016/j.cattod.2019.09.041
CATTOD 12494
Reference:
To appear in:
Catalysis Today
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Revised Date:
Accepted Date:
1 July 2019
3 September 2019
25 September 2019
´
Please cite this article as: Erigoni A, Hernandez-Soto MC, Rey F, Segarra C, D´ıaz U, Highly
Active Hybrid Mesoporous Silica-Supported Base Organocatalysts for C-C Bond Formation,
Catalysis Today (2019), doi: https://doi.org/10.1016/j.cattod.2019.09.041
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Highly Active Hybrid Mesoporous Silica-Supported
Base Organocatalysts for C-C Bond Formation
A. Erigonia, M.C. Hernández-Sotoa, F. Reya, C. Segarraa,* and U. Díaza,*
aInstituto de Tecnología Química, Universitat Politècnica de València-Consejo
Superior de Investigaciones Científicas, Avenida de los Naranjos s/n, E-46022
Valencia, Spain.
*Corresponding authors.
E-mail address: canseal@itq.upv.es (C. Segarra); udiaz@itq.upv.es (U. Díaz)
Graphical abstract
Highlights

Hybrids carrying amino, diamino, pyrrolidine, pyrazolium and imidazolium
functions.

Active catalysts for C-C bond forming reactions, Knoevenagel and Michael
processes.


Reactivity correlated with basicity and reaction mechanisms.
Possibility to combine structural functions to generate multisite catalysts.

Abstract: New base hybrid catalysts, based on silyl-derivatives of molecules
carrying amino, diamino, pyrrolidine, pyrazolium and imidazolium functionalities
have been successfully achieved through post synthetic grafting onto M41S-type
support. Different characterization techniques were implemented to study the
characteristics of the materials, such as elemental analysis, solid state MAS NMR
and FTIR spectroscopies, X-ray diffraction (XRD), thermogravimetric and
differential thermal analyses (TGA-DTA) and textural properties through N2
physisorption analysis. The catalytic activity and recyclability of these compounds
as base catalysts was demonstrated for C-C bond forming reactions such as
Knoevenagel condensations and Michael additions rationalizing the differences
observed as function of the reaction mechanisms. An enamine mechanism was
proposed for Knoevenagel condensations and an enolate mechanism for Michael
additions.
Keywords: Organic-Inorganic Hybrid Catalysts; Base sites; Mesoporous and
Microporous materials; C-C bond forming reactions.
1. Introduction
In the last years, the design of new hybrid organic-inorganic catalysts based on
organocatalysts incorporated into the framework of conventional inorganic supports
is becoming an area of growing interest due to their specific physical and chemical
properties. The use of these hybrid catalysts allows combining increased flexibility,
functionality and efficiency of soluble organic homogeneous catalysts, with the
thermal and mechanic stability of inorganic solids, leading to ‘green catalytic
processes’, with higher selectivity and conversion and easy catalyst recovery.[1-3]
Different routes can be followed to synthesise organic–inorganic hybrid catalysts
that include: adsorption of the organic species inside the pores of the inorganic host,
inclusion of the organic moieties within the pores of the support by a “ship in a
bottle” type procedure, one-pot synthesis of a composite material with the organic
fragments located into the walls of the pores by hydrolysis and condensation routes,
and post-synthetic grafting of the organic moieties onto the surface of the inorganic
support.[4-6]
Post-grafting of silica surfaces using functionalized organosilanes is one of the most
extensively used methods, primarily due to its versatility and to the avoidance of the
synthetic step related to the extraction of the surfactant from the pore channels,
typical of most synthesis carried out following one-pot approaches.[7-8]

Nevertheless, an optimal grafting procedure must keep into account the possibility
of partial pores blockage and the undesired oligomerization of the silylated organic
precursors.[9-11] In the design of hybrid organic-inorganic catalysts, silica-based
materials are the most implemented supports, due to their highly reactive surface,
tunable pore size and relatively high thermal and mechanic stability.[12] Moreover,
weakly acidic silanols present of the surface of the support have been shown to play
an important role in both enhancing or inhibiting the catalytic activity of the pending
active sites, depending on the specific reaction.[13-16] Additionally, the range of
alkoxysilanes that can be grafted to the surface silanols allows for a highly tunable
series of organic moieties that can be tethered to the surface to catalyze the desired
reaction.[17-19]
Specifically, the synergistic effect of base active sites and acidic surface silanol
groups in promoting aldol condensation reactions have been thoroughly studied.[20-
22] Several authors reported that capping the silanols with methyl groups greatly
affected the activity of the hybrid catalysts.[23-24] On the other hand, the presence
of more strongly acidic active sites (i.e. carboxylic acids), together with the amine,
was shown to provide lower catalytic activity, probably due to the fact that stronger
acidity would make the proton transfer to the amine more likely to occur, ultimately
causing the deactivation of the base catalytic sites.[25] The influence of the length
of the linker is also a key factor in designing a such silica-supported base catalysts:
flexible linkers (C3 or longer) allows for the amine to get into close proximity of the
silanols, enabling their cooperation in catalysing the reaction.[26] Nevertheless, for
mesoporous hybrids with a pore diameter of about 2 nm, linkers that are longer than
C3 were reported to be detrimental for the catalytic activity.[27] Additionally, for
the aldol condensation, different researches postulated sequential activation of the
ketone (electrophile) to form the reactive enamine intermediate using a single
silanol, which then attacks the aldehyde.[28-30]
In this work, organic–inorganic hybrid materials based on silyl-derivatives with base
functionalities as amino, diamino and pyrrolidine molecules, pyrazolium and
imidazolium hydroxides have been successfully achieved through post synthetic
grafting on the surface of pure silica M41S-type support. Based on the consideration
mentioned above, a propyl chain was chosen as linker (both when using commercial
and non-commercial silyl-derivatives) as it was shown to be the optimal length for
amines grafted within pore channels with a diameter of about 2 nm. The synthesized
hybrids materials were extensively characterized and tested as base catalysts for the
Knoevenagel condensation of benzaldehyde with compounds containing activated
methylenic groups. From the catalytic results an imine/enamine mechanism was
proposed to follow the reaction and several catalyst recycles were performed to
evaluate catalyst deactivation and reusability. These catalysts were studied also in

the Michael addition of ethyl 2-oxocyclopentane 2-carboxylate and methyl vinyl
ketone and an enolate mechanism is proposed from the data in catalysis,
2. Experimental Section
2.1. Catalysts Preparation
2.1.1. Synthesis of MCM-41.
MCM-41
was
synthesized
according
to
a
previous
report.31
Cetyltrimethylammonium bromide (13.66 g, 7.6 mmol) was dissolved in distilled
water (91 mL) with an aqueous tetramethylammonium hydroxide solution (25 wt %,
23.66 g) in a 250 mL flask at 40 ºC. The mixture was stirred vigorously. Aerosil 200
(15 g) was added and the mixture was stirred for 1 h. The gel is then transferred into
a stainless steel autoclave and reacted under static condition at 135 °C for 24 h. The
resulting solid was filtered and washed several times with distilled water, and the
powder was dried at 100 °C in an oven overnight. The powder was calcined under a
flow of N2, ramped from room temperature to 540 °C at 3 °C/min and held at 540 °C
for 1 h. Subsequently, the powder was held at the same temperature under a flow of
air for 6h and finally the sample was cooled to room temperature for 2 more extra
hours (10 °C/min).
2.1.2. Synthesis of the silylated base precursors III, IV, V and VI.
III. 2-aminopyrrolidine (2.32 mmol, 200 mg) and 3-isocyanatopropyltriethoxysilane
(2.32 mmol, 564 mg) were placed in a Schlenck under N2 containing dry CH3CN
and the solution was stirred at -57 ºC for 6h. After this time, the solvent was removed
under reduced pressure and the resulting gel was washed with ether (Scheme 1a).
IV-VI. The corresponding amount of the azol compound (1.3 mmol, 110 mg for 1-
methylpyrazole and 1-methylimidazol and 128mg for 1,2-dimethylimidazol) and 3-
iodopropyltrimethoxysilane (1.3 mmol, 387 mg) were placed in a round bottomed
flask under N2 containing dry CH3CN and the solution was refluxed overnight. After
this time, the solvent was removed under reduced pressure and the resulting gel was
washed with ether (Scheme 1a).
2.1.3. Grafting of the silyl-derivatives on MCM-41.
1-3 (4 mol %): MCM-41 (2 g) was placed in a Schlenck under vacuum at 150 °C for
2 h. Dry toluene was added into the Schlenck and the mixture was stirred at RT for
1 h. After that, the corresponding amount of silyl base precursor (1.3 mmol, 295 mg
for APTES I, 297 mg for N-(2-Aminoethyl)-3-(trimethoxysilyl)propylamine II and
445 mg for III) was added and the resulting mixture was refluxed for 24 h. After this

time, the mixture was filtrated and washed with toluene, CH2Cl2 and ethanol and the
resulting solid was dried overnight at 100 °C (Scheme 1b).
4-6 (4 mol %): MCM-41 (2 g) was placed in a Schlenck under vacuumat 150 °C for
2 h. Dry CH3CN was added into the Schlenck together with the corresponding
amount of the silyl-derivative (1.3 mmol, 496 mg for IV and V and 515 mg for VI),
and the mixture was stirred at room temperature for 1 h. After that, trimethylamine
(1.3 mmol, 186 L) was added and the resulting mixture was refluxed for 24 h. Next,
the mixture was filtrated and washed with CH3CN and acetone and the resulting solid
was treated three times with a methanol solution of TMAOH (0.2 M) at room
temperature for 30 min to exchange the halogen for hydroxide groups. The final solid
was washed abundantly with distilled H2O and acetone and dried overnight at 100
ºC (Scheme 1b).
2.1.4. Syntheis of 1-HMDS.
1 (0.5 g) was placed in a Schlenck, outgassed at 150 °C for 2 h. Meanwhile, a solution
of hexamethyldisilazane (HMDS,1.25 mmol, 202 mg) in DMF (83.3 mmol, 6.1 mL)
was prepared under N2. After the outgassing, 1 was cooled at room temperature and
the HMDS solution was added in the Schlenck. The final composition of the mixture
was SiO2 : 0.15 HMDS : 10 DMF. The mixture was stirred at 120 °C for 2 h. The
samples was filtered, washed with CH2Cl2 and dried overnight at 100 °C.
2.2.Characterization Techniques.
XRD analysis was carried out with a Philips X’PERT diffractometer equipped with
a proportional detector and a secondary graphite monochromator. Data were
collected stepwise over the 2° ≤ 2θ ≤ 20° angular region, with steps of 0.02° 2θ, 20
s/step accumulation time, and Cu Kα (λ = 1.54178 Å) radiation. C, N, S, and H
contents were determined with a Carlo Erba 1106 elemental analyzer.
Thermogravimetric and differential thermal analyses (TGA-DTA) were conducted
in an air stream with a Mettler Toledo TGA/SDTA 851E analyzer. Nitrogen
adsorption isotherms were measured at −196 °C with a Micromeritics ASAP 2010
volumetric adsorption analyzer. Before the measurements, the samples were
outgassed for 12 h at 100 °C. The BET specific surface area [32]was calculated from
the nitrogen adsorption data in the relative pressure range from 0.04 to 0.2. The total
pore volume[33]was obtained from the amount of N2 adsorbed at a relative pressure
of about 0.99. External surface area and micropore volume were estimated using the
t-plot method in the t range from 3.5 to 5. The pore diameter and the pore size
distribution were calculated using the Barret−Joyner−Halenda (BJH)[34] method
on the adsorption branch of the nitrogen isotherms. Solid state MAS NMR spectra
were recorded at room temperature under magic angle spinning (MAS) in a Bruker
AV-400 spectrometer. The single pulse 29Si spectra were acquired at 79.5 MHz with
a 7 mm Bruker BL-7 probe, using pulses of 3.5 μs corresponding to a flip angle of

3/4 π radians and a recycle delay of 240 s. The 1H to 13C crosspolarization (CP)
spectra were acquired by using a 90° pulse for 1H of 5 μs, a contact time of 5 ms,
and a recycle of 3 ms. The 13C spectra were recorded with a 7 mm Bruker BL-7 probe
and at a sample spinning rate of 5 kHz. 13C and 29Si were referred to adamantine and
13
tetramethylsilane, respectively. Liquid state C NMR spectra were recorded at 75
MHz using a Bruker AMX300 instrument. Chemical shifts are quoted in ppm and
are referenced to the appropriate residual solvent peak.
2.3.Catalytic tests
2.3.1. Knoevenagel condensation.
The reaction was carried out in high pressure pyrex tubes with constant magnetic
stirring. A mixture of benzaldehyde (1.0 mmol, 106 mg) with ethyl cyanoacetate (1.0
mmol, 113 mg) or ethyl acetoacetate (1.0 mmol, 130 mg) or diethyl malonate (1.0
mmol, 160 mg), anisole (as internal standard,1 mmol) and base catalyst (10 mol %
or 2 mol % active site), was refluxed at 80 °C in 4 mL of acetonitrile for 24 h. The
reaction was monitored by NMR analysis using CDCl3 as deuterated solvent.
2.3.2. Michael addition.
In a glass microreactor (2 mL) with a magnetic stir bar, ethyl 2-oxocyclopentane 2-
carboxylate (1.0 mmol, 156 mg,), methyl vinyl ketone (1.0 mmol, 70 mg), 4-
chlorotoluene (as internal standard, 1 mmol, 126 mg,) and base catalyst (5 mol %
active site), was stirred at room temperature in 0.5 mL of CH3CN for 3 h. The
reaction was monitored by NMR analysis using d3-CD3CN as deuterated solvent.
3. Results and Discussion
3.1.Synthesis of the Hybrid Mesoporous Base Catalysts.
Firstly, the non-commercial silylated base precursors were synthesized starting from
cheap and readily available 1-methylpyrazole, 1-methylimidazol and 1,2-
dimethylimidazol through thermally induced condensation with 3-
iodopropyltrimethoxysilane giving IV, V and VI, respectively. In the case of III, the
condensation between 2-aminopyrrolidine and 3-isocyanatopropyltriethoxysilane
was carried out at -57 ºC in order to inhibit the reaction of the isocyanate with the
secondary amine in the N-heterocycle. The silylation processes were followed by
13
29
1
13
29
liquid (1H, C, Si) NMR (see Figure S1 for H NMR spectra, C and Si NMR
spectra are shown in Figure 2 and 3, respectively). In particular, the 1H NMR spectra
of the silylated base precursors IV, V and VI show the signals assigned to CH groups
of the azolium ring at higher chemical shifts compared to those of the corresponding
azol rings, due to the un-shielding effect given by the presence of the positive charge.

For III, the 13C NMR spectrum shows the characteristic signal corresponding to the
carbonyl urea group confirming the condensation of the cyano group. The silylated
base precursors were then grafted onto MCM-41 support, to give the hybrid base
catalysts 1-6 (Scheme 1b).
Scheme 1. a) Scheme of 3-triethoxysilylpropylamine (APTES) I and N-(2-Aminoethyl)-3-
(trimethoxysilyl)propylamine II and synthesis of the silylated base precursors III, IV, V and
VI. b) Synthetic steps implemented in the synthesis of the silica-supported base cataysts 1-
6. i) MCM-41, dry Toluene, 1h, RT; ii) silylated base precursor I, II or III, 24h, reflux; iii)
MCM-41, silylated base precursor IV, V or VI, dry CH3CN, 1h, RT, iv) TEA, reflux, 24h;
v) TMAOH, CH3OH, 30 min.
3.2.Characterization of the Hybrid Mesoporous Base Catalysts.

The silica-supported base catalysts were characterized by X-ray diffraction (Figure.
1). The diffractograms of all the samples exhibits the (100) reflection peak at low
diffraction angles (2θ = 2.3−2.6°) and the (110) and (200) reflections at 2θ =
3.8−4.8°, indicating the preservation of the 2D hexagonal structure of the MCM-41
throughout the grafting procedure and the exchange in basic pH.[35,36] Focusing on
the (100) peak, a slight difference in its position can be observed in the samples. This
is partly due to the different size of the pending moieties, which affects the mean
pore diameter to a different extent and therefore cause a displacement of the peak
proportional to the size of the pending moieties. Nevertheless, a full understanding
of these features should keep into account the bending of the organic moieties and
their interaction with the surface of the support.
Figure 1. Powder XRD diffraction patterns of the bare MCM-41 silica and the silica-
supported base catalysts 1-6.
The presence of the silylated base precursors in the synthesized hybrid materials was
determined by means of elemental analysis. The C, H, N contents and the calculated
percentage in weight of the organic moieties present in the silica-supported base
materials are summarized in Table 1. The organic content of the hybrid materials
increases according to the molecular weight of the silylated base precursor. Thus,
the highest organic content corresponds to catalyst 3 (10.4 %), where the molecular
weight of the organic moiety III is 333.5 g/mol. Accordingly, the smallest organic

content corresponds to catalyst 1 (4.4 %), where the molecular weight of the organic
moiety I is 221.37 g/mol. Lastly, the organic content for catalyst 4 and 5 is practically
the same (8.3 and 8.6, respectively), being the molecular weight of both organic
moieties IV and V is 362.38 g/mol. The amount of N allowed for the determination
of the quantity of active sites per gram. Minor differences in the active base sites
loading were observed between the six catalysts (Table 1).
Table 1. Organic content in the mesoporous hybrid materials estimated by elemental
analysis.
Catalysts
Cat. 1
Cat. 2
Cat. 3
Cat. 4
Cat. 5
Cat. 6
N%
1.1
2.4
2.5
1.9
2.0
2.0
C%
3.3
5.8
7.9
6.3
6.6
7.3
Organic content (EA)%
Active sites (mmol/g)a
4.4
8.2
10.4
8.3
8.6
9.3
0.786
0.857
0.595
0.678
0.714
0.714
aActive sites = N% / 14 / 100 / nN. nN = number of nitrogen atoms present in the sylil-derivative compound.
Thermogravimetric analysis was performed in order to gain insights about the
thermal stability of organic units introduced in the hybrid materials. The weight loss
(TGA) and its respective derivative curves (DTA) for the silylated base catalysts 1-
6 are shown in Figure S2. In all cases, a first weight loss due to the removal of
physisorbed water is observed at around 90–150 ºC. The decomposition of the
organic moieties occurs in the range between 200–400 ºC for all samples. In all the
hybrids, a progressive weight loss at temperatures above 500 °C was detected due to
dehydroxylation phenomena, i.e. condensation of external silanol groups with the
release of water molecules and formation of strained siloxane bridges.
To study the integrity of the organic moieties in the final solid catalysts and
specifically the covalent insertion of the silylated base precursor into the structure of
13
the MCM-41 support, solid state MAS NMR spectroscopy was implemented. C
CP/MAS NMR spectra of all the hybrid base materials were recorded and compared
to the spectra recorded on the silyl-derivatives prior grafting (liquid NMR) (Figure
13
2a-f). In all cases, the C spectra of the hybrids present the typical signals of the
silylated-derivatives confirming the integrity of the organic moieties after the
synthesis process. Specifically, the 13C peaks due to the propyl chains appear in the
range 0–70 ppm for 1-6, while the peaks corresponding to the rest of the carbon
atoms of catalyst 2 and 3 appear in the same range, with the exception of the
characteristic C=O signal of catalyst 3 that is visible at 160 ppm. For catalysts 4, 5
and 6 the signal due to the methyl group NCH3 appears at a range of 33–36 ppm.

The rest of aromatic signals corresponding to the azol rings are visible at the expected
range between 107–142 ppm (see the inset in Figure 2 for the labels of C atoms).
Figure 2. 13C CP/MAS NMR spectra of the hybrid base catalyst and the silyl-derivatives
counterparts: (a) catalyst 1 and silyl-derivative I, (b) catalyst 2 and silyl-derivative II, (c)
catalyst 3 and silyl-derivative III, (d) catalyst 4 and silyl-derivative IV, (e) catalyst 5 and silyl-
derivative V and (f) catalyst 6 and silyl-derivative VI. *Solvent residual peak.
29Si MAS NMR spectra of the hybrids mesoporous base materials 1-6 (Figure 3a-f)
exhibit bands from -50 to -80 ppm assigned to T-type silicon species corresponding
to silicon atoms directly bounded to carbon atoms, confirming that the grafting of
silylated-derivatives occurs through alkoxy terminal groups of the silylated moieties
which react with external silanol groups present onto the inorganic surface support.
29
Comparison of Si NMR spectra of the hybrids with the silylated base precursors
(see the inset of Figure 3) confirms also the incorporation of the organic molecules
into the framework of non-ordered mesoporous silica. Silylated-derivatives I, II, V
and VI exhibit a peak centred at around – 43 ppm which, after the grafting, is shifted
in the range -50 to -80 ppm, supporting the covalent incorporation of the silylated
organic species into the silica framework. Additionally, the presence of the support
gives rise to Q-type signals related to bulk and surface silicon atoms. Specifically,
three peaks at -92, -100 and -110 ppm are present, due to Q2 (Si(OH)2(OSi)2), Q3
(Si(OH)(OSi)3) and Q4 (Si(OSi)4) silicon units, respectively.[37] The integration of
29
T and Q peaks in the Si BD/MAS NMR spectra was performed to calculate the
T/(Q + T) ratio and to evaluate the number of functionalized silicon atoms in the

hybrids (Table 2). The Sifunc/Sitot ratio evidences that the percentage of grafting
achieved in this catalysts is the range 1.9-4.7 mol% respect to total silica.
Figure 3. 29Si BD/MAS NMR spectra of the hybrid base catalyst and the silyl-derivatives
counterparts: (a) catalyst 1 and silyl-derivative I, (b) catalyst 2 and silyl-derivative II, (c)
catalyst 3, (d) catalyst 4, (e) catalyst 5 and silyl-derivative V and (f) catalyst 6 and silyl-
derivative VI.
Table 2. Functionalized silicon atoms in the mesoporous hybrid materials.
Catalysts
Cat. 1
Cat. 2
Cat. 3
Cat. 4
Cat. 5
Cat. 6
Sifunc/Sitot (NMR)
0.047
0.023
0.019
0.023
0.020
0.042
FTIR spectra were recorded on the base hybrids, after outgassing at 120 °C for 2 h
(Figure 4). Focusing on the high frequency region of the spectra, a signal at 3740
cm-1 is observed in all six catalysts and bestowed to the stretching modes of isolated
silanols. A broad signal centred between 3700 and 3500 cm-1 is ascribed to the

stretching modes of hydroxyl groups in interaction with each other through H-bond.
Additionally, in the ionic hybrids (spectra 4-6), a component of this composite band
stands out at about 3650 cm-1 which is bestowed to the stretching modes of the
hydroxyl anions present as counter ion. Spectra 1 and 2 show two signals centred at
about 3370 and 3310 cm-1 related to the asymmetric and symmetric stretching modes
of the N-H bond, respectively. In the same region of the spectrum of catalyst 3, a
composed signal is observed between 3500 and 3260 cm-1, due to the presence of N-
H stretching modes in the urea group (about 3440 cm-1) and in the pyrrolidine ring
(asymmetric at 3365 cm-1; symmetric at 3300 cm-1). Spectra of hybrid 4-6 show
composite signals between 3200 and 3000 cm-1, bestowed to the alkene C-H
stretching modes, in the azo-cycles. In the region comprised between 3000-2840 cm-
1, signals related to the alkane C-H stretching modes are observed in all six
spectra.[38]
Due to the similar chemical structure, the low frequency region of the spectra
recorded on catalyst 1 and 2 show resembling features: a peak centered at 1590 cm-
1
due to the primary amine N-H bending modes is observed in both spectra;
moreover, a week signals at 1460 cm-1 is seen and ascribed to the scissor vibration
modes of the CH2 groups present in the propyl chain. In the spectrum of catalyst 3,
two intense and partially overlapped bands are visible at 1635 and 1605 cm-1. The
first one is bestowed to the stretching modes of the carbonyl C-O bonds in the urea
group (Amide I band), whereas the second one is related to the amide II band, i.e. a
motion combining N-H bending and C-N stretching of the amide group.
Additionally, a band at 1535 cm-1 is observed and tentatively ascribed to the N-H
bending modes in the pyrrolidine ring. In the region between 1490 and 1370 cm-1
signals related to R-C-H bending modes of species (where R is either a nitrogen or a
carbon atom) are observed. Due to the lack of spectroscopic data reported in the
literature and to the complex nature of the pyrazolium ion, no specific assignation of
the signal present in the low frequency region of spectrum 4 was possible.[38]
The low frequency region of the spectra recorded on the imidazolium-derivative
catalysts (5 and 6) show similar spectroscopic features. Firstly, a signal related to a
motion combining C4-C5 and C-N stretching is present at 1570 cm-1 (spectrum 5)
and 1585 cm-1 (spectrum 6); Moreover, a signal centred at about 1480 cm-1 is
bestowed to the CH3(N1) scissoring modes. The spectrum of hybrid 6 also show a
typical band related to the N1-C2-N3 stretching + CH3(C2) rocking modes centred at
about 1535 cm-1.[39]

Figure 4. FTIR spectra of catalysts 1-6 after outgassing at 120 °C
3.3.Textural Properties.
The textural properties of the hybrid materials 1-6 studied by means of N2
physisorption analysis at 77 K are reported in Table 3 and compared to a pure MCM-
41. In all cases, the isotherms show a type IV behavior, with a hysteresis loop, typical
of mesoporous materials (Figure 5). The N2 uptake is consistent with MCM-41-type
materials. In particular, all the hybrids mesoporous catalysts show an isotherm with
the inflexion point between p/p0 0.2–0.3 while the inflexion point of the silica is
observed at higher p/p0 value, meaning that the pore diameter is slightly larger than
for the hybrids materials. By analysing the isotherms by the Brunauer-Emmett-Teller
(BET) method, specific surface areas (SSA) in the range between 844–1159 m2/g
were observed. The pore volume of the hybrids and of the purely inorganic support
were calculated by means of the Barrett-Joyner-Halenda (BJH) method (Table 3).
Upon grafting, the BJH pore volume drops from 0.8 to 0.4-0.5 cm3/g, due to the
presence of the pending organic moieties, which partially block the free porous
volume.

Table 3. Textural properties of the hybrid base catalysts 1-6
Catalysts
SSABET
(m2 g–1)
973
1159
1005
998
Pore volume
(cm3 g–1)
0.47
Cat. 1
Cat. 2
Cat. 3
0.55
0.43
0.45
Cat. 4
Cat. 5
Cat. 6
MCM-41
1023
1038
1064
0.46
0.44
0.81
Figure 5. N2 adsorption isotherms of the hybrid base catalysts 1-6.
3.4.Catalytic Activity.
In order to investigate and compare their reactivity as base catalysts, hybrids 1-6
were tested in the condensation of carbonyl compounds with active methylenic
substrates, in reactions such as Knoevenagel condensation and Michael addition.
These reactions are a key tool in organic synthesis for C-C bond formation and for
the synthesis of substituted alkene products which are of great interest to produce
important intermediates and final products for perfumes, pharmaceutical, dyes and
polymers,[40-44] due to their properties as enzyme inhibitors, antitumor, anti-
inflammatory, and antibacterial agents.[45-48]

3.4.1. Knoevenagel condensation.
This reaction can be catalyzed by strong and weak bases, depending on the level of
activation of the reactant containing methylenic activated groups which makes it an
adequate reaction for comparing catalysts with different basicity. The kinetics of the
Knoevenagel reaction is generally considered to be a first order reaction with respect
to each reactant and the catalysts.[49-52] Thus, we compared the catalytic
performance of hybrid base catalysts 1-6 in the Knoevenagel condensation between
benzaldehyde and substrates with different pKa values (with distinct activated
methylenic groups), such as ethyl cyanoacetate (pKa ≈ 9), ethyl acetoacetate (pKa ≈
11) and diethyl malonate (pKa ≈ 13) (Scheme 2). Additionally, a catalytic test of one
of the ionic catalysts prior the exchange of I- for OH- (catalyst 6, entry 6-I) was
carried out. Lastly, in order to investigate the effect of the surface silanols on the
activity of the catalysts, the surface of 1 was passivated with hexamethyldisilazane
(HMDS) and the resulting catalyst (1-HMDS) was tested.
Scheme 2. Scheme of the Knoevenagel reaction of benzaldehyde and ethyl cyanoacetate,
ethyl acetoacetate and diethyl malonate.
Firstly, the Knoevenagel condensation between benzaldehyde and ethyl
cyanoacetate using the hybrid base catalysts with an active site loading of 10 mol%
showed a high activity for the neutral base catalysts 1-3 and ionic base catalysts 4-6.
Quantitative yields of the final product A were achieved with 100% selectivity after
30 min (Table 3, entry 1-6, and Figure 6).

Table 3. Knoevenagel condensation of benzaldehyde and ethyl cyanoacetate, ethyl
acetoacetate and diethyl malonate.
Entry
Catalysts
Yield (%)
Yield (%)
Yield (%)
Aa
93
90
95
91
89
91
21
20
19
1
Bd
65
63
46
0
Cd
45
22
18
0
1
2
3
4
5
6
7
8
9
Cat. 1
Cat. 2
Cat. 3
Cat. 4
Cat. 5
0
0
-
-
-
-
0
0
-
-
-
-
Cat. 6
Cat. 1-HMDS
MCM-41b
Cat. 6-I c
None
10
aReaction conditions: benzaldehyde (1 mmol), ethyl cyanoacetate (1 mmol), ethyl
acetoacetate (1 mmol), diethyl malonate (1 mmol) and CH3CN (4 ml) at 80 ºC for
0.5 h with 10 mol % of base sites. b200 mg of MCM-41, 24 h. c2 h, d24h.
Figure 6. Catalytic activity of the hybrid base catalysts in the Knoevenagel condensation of
benzaldehyde with ethyl cyanoacetate (10 mol % catalyst loading).
The same reaction was carried out using catalyst 1-HMDS. The values show that the
catalytic activity decreases giving only a 21% yield after 30 min and longer reaction
times of 24 hours are required to obtain quantitative yields, emphasizing the vital
role the weakly acidic silanols play in reaction (Table 3, entry 7; Figure 6).[29-30]
Moreover, when the reaction was carried out only with MCM-41 a 20% yield was
obtained after 24 h, showing that the weakly acidic silanols were able to catalyse the
Knoevenagel condensation without the cooperation of the base active site (Table 3,
entry 8). Catalyst 6-I was also tested in the Knoevenagel condensation of

ethylcyanoacetate with benzaldehyde. The results show that catalyst 6-I was not able
to catalyse the reaction effectively and after 2 hours only a 19% yield is achieved
(same activity of the pure silica MCM-41), demonstrating the importance of the
hydroxide group to carry out the reaction (Table 3, entry 9, Figure 6). A blank
experiment without any hybrid base catalyst was also performed (Table 3, entry 10),
and the data show that the reaction does not occur in the absence of the catalysts.
The Knoevenagel condensation between benzaldehyde and the other two active
methylenic substrates with higher pKa, ethyl acetoacetate and diethyl malonate, to
obtain products B and C, respectively, using the hybrid base catalysts with a catalyst
loading of 10 mol % showed a moderate activity of the neutral base catalysts 1-3
(Table 3, entry 1-3, Figure S3, Figure S4). The data showed that in both reactions
the best catalysts was 1 and the substrate ethyl acetoacetate (pKa ≈ 11) was activated
more easily than the substrate diethyl malonate (pKa ≈ 13) giving a 65% yield of the
final product B and a 45% yield of final product C after 24 hours, respectively (Table
3, entry 1, Figure S3, Figure S4). On the contrary, when using the ionic base catalysts
4-6 the results show that the reaction does not occur at all (Table 3, entry 4-6). This
observation is consistent with an imine or enamine mechanism of the Knoevenagel
condensation using a primary or secondary amine base catalyst, respectively.[53]
The proposed reaction imine mechanism promoted by surface silanol groups is given
in Scheme 3, using as example catalyst 1 and ethyl cyanoacetate as starting substrate.
The catalytic cycle began with the formation of a hydrogen bond between the free
silanol group and the oxygen of the carbonyl group of benzaldehyde. Next, the free
electron pair of the amine attacked the activated carbonyl group of benzaldehyde,
and a carbinolamine was formed through a proton-transfer. This carbinolamine
dehydrated, yielding an imine intermediate. The activated methylene get
deprotonated by the base to give a stabilized enolate, which then attacked the imine
group and generated a new carbon-carbon bond. A rearrangement then ensued that
releases the amine base, regenerating the catalyst, and yielding the final olefin
product. When the silanol groups were end-capped with trimethylsilyl groups, the
initial activation by hydrogen-bonding was absent which resulted in a lower catalytic
activity (Table 3, entry 7; Figure 6). This explained why, when using the hydroxide
base catalysts 4-6, which did not have a primary or a secondary amine group that can
be converted into an imine or enamine via aldehyde activation, these were not able
to catalyse the reaction between aldehyde and the less active methylenic substrates.

Scheme 3. Proposed enamine catalytic reaction cycle of the Knoevenagel reaction of
benzaldehyde and ethyl cyanoacetate, catalyzed by catalyst 1-3, as an example only catalyst
1 is represented.
Due to the high activity of the hybrid base catalysts in the Knoevenagel condensation
between benzaldehyde and ethyl cyanoacetate to obtain product A (Scheme 2), the
catalyst loading of the catalyst 1-6 was decreased from 10 mol % to 2 mol % to
obtain information about the kinetics of the reaction. Quantitative yields of final
product A are achieved at around 4 h in the case of neutral base catalyst 1-3, whereas
ionic base catalysts 4-6 needed longer reaction times to accomplish full yield (Table
4, entry 1-3 and 4-6, Figure 7). As expected, these results followed the catalytic
trends shown using 10 % mol of catalyst loading (Table 3, Figure 7). Turnover
frequencies calculated after 15 min reaction showed that hybrid base catalyst 1
presented the highest TOF, with a value comparable to those of mesoporous hybrid
materials,
containing
proton
sponges
(derived
of
1,8-
bis(dimethylamino)naphthalene (DMAN) compounds).[54] Similarly, initial rates
and kinetic constants reported in Table 4 demonstrated that catalytic performance of
hybrid base catalysts, specifically catalyst 1, was comparable with that exhibited by
known mesoporous hybrid catalysts, containing base proton sponges (DMAN
compounds) into the framework.[54] This comparison confirmed the validity of
hybrid base catalysts (catalyst 1) to be used as active base catalysts for C-C bond
formation reactions as Knoevenagel condensation.

Table 4. Knoevenagel condensation of benzaldehyde and ethyl cyanoacetate.
Entry
Catalysts
Time
(h)
Yield Aa
(%)
TONb
TOFc
(h−1)
r0
k
(mol·L−1·h−1)
(h−1)
1
2
3
4
5
6
Cat. 1
Cat. 2
Cat. 3
Cat. 4
Cat. 5
Cat. 6
4
4
4
24
24
24
95
93
91
97
95
93
48
47
46
49
48
47
96
60
56
30
36
46
0.49
0.31
0.29
0.16
0.19
0.24
1.97
1.24
1.15
0.62
0.74
0.97
aReaction conditions: benzaldehyde (1 mmol), ethyl cyanoacetate (1 mmol) and CH3CN (4 ml) at 80 ºC with 2 mol
% of base sites. bTON calculated at final conversion. cTOF calculated at 15 min.
Figure 7. Catalytic activity of the hybrid base catalysts in the Knoevenagel condensation of
benzaldehyde with ethyl cyanoacetate (2 mol % catalyst loading).
Catalyst deactivation and reusability were studied in the Knoevenagel condensation
between benzaldehyde and ethyl cyanoacetate, using the three most active catalyst
1-3 with 10 mol % of catalyst loading during four successive uses and after 4 h of
reaction (Figure 8). After each experiment, the catalysts were filtered with CH3CN,
washed with acetone, dried at 100 °C, and reused. The yields were similar for the
first three catalytic runs, confirming that the hybrid catalysts were recyclable and
only a slight loss in activity was observable after four consecutive catalytic uses.
XRD diffraction and elemental analysis of the three used hybrid base catalysts 1-3
were carried out to access the stability and integrity of the inorganic framework after
four catalytic cycles. The XRD patterns (Figure S5) show that the first (100)

diffraction band characteristic of MCM-41 structure was still present after four
consecutive catalytic performances, confirming that the mesoporous MCM-41
morphology was preserved. Moreover, the elemental analysis performed on the three
used catalyst 1-3, revealed that no leaching occurred from 1 to 3 runs whereas after
the fourth run an evident loss in the N content was observed, in line with the decrease
observed in the yield (Table S1). Additionally, to verify the heterogeneous character
of the hybrid base catalysts, a leaching test was performed in the Knoevenagel
condensation between benzaldehyde and ethyl cyanoacetate using the three most
active catalyst, i.e. 1-3, with 10 mol % of catalyst loading. Thus, when reaction time
was 5 min, solid catalysts were filtered from the reaction mixture and the reaction
was continued in absence of solid catalyst. After 2 h, a negligible 1% yield increase
of the final product was observed (Table S2), proving that no leaching occurs at the
condition at which the reaction is carried out.
Figure 8. Recycling tests of Knoevenagel condensation between benzaldehyde and ethyl
cyanoacetate (2 mol % catalyst loading). The yield (%) is reported after 4 h of reaction.
3.4.2. Michael addition
For the reaction of Michael addition, ethyl 2-oxocyclopentane 2-carboxylate
(EtOCC) and methyl vinyl ketone (MVK) were chosen as the donor and the acceptor
substrate, respectively (Scheme 4). In all the cases, products coming from side
reactions such as rearrangements, dimerizations or other condensations were not
observed, and high selectivity to the 1,4-adduct can be achieved. This excellent
selectivity must be attributed to the well-defined strong basicity of the ionic base
catalysts catalyst 4-6, due to the hydroxide group.

Scheme 4. Scheme of the Michael addition of ethyl 2-oxocyclopentane 2-carboxylate and
methyl vinyl ketone.
Firstly, the reaction between ethyl 2-oxocyclopentane 2-carboxylate (EtOCC) and
methyl vinyl ketone (MVK) was carried using all the hybrid base catalysts 1-6 with
5 mol % of catalyst loading at room temperature for 3 h (Scheme 4). For neutral base
catalysts 1-3 low yields of the final product D were achieved (Table 5, entry 1-3,
Figure 9). Surprisingly, when using the ionic catalysts 4-6 the yields increased up to
moderate values in the range of 56-69% yield (Table 5, entry 4-6), evidencing that
the hydroxide basicity was crucial to achieve high performances in Michael
additions. These three azolium base catalysts presented the positive charge
delocalized on the ring conferring more base character to the hydroxide groups of
the catalysts in the order 4 < 5 < 6. Pyrazolium base catalyst 4 delocalized the
positive charge less effectively than imidazolium base catalyst 5 and 6, besides
dimethyl imidazolium base catalyst 6 presented a electrodonating methyl group that
may stabilize the positive charge, conferring more base character to the catalyst than
the imidazolium base catalyst 5. Moreover, these last results compared well with
those obtained for solid base catalysts having a hydroxide group.[55] However, the
Brönsted basicity of these groups was somewhat lower than when they are
unsupported.[55]
Finally, the same reaction was carried out using catalyst 1-HMDS not having free
silanols to prevent acid-base cooperative catalysis. The values show that the catalytic
activity decreases achieving only a 14% yield after 4 h, confirming that the weakly
acidic silanols also play an important role in in Michael additions (Table 5, entry 7).
For Michael additions an enolate mechanism was proposed where the ionic base
catalysts are the best candidates to catalyse this reaction due to the stronger basicity
conferred by the hydroxide groups.[56] The proposed reaction enolate mechanism is
shown in Scheme 4, using as example catalyst 3. The catalytic cycle began with the
deprotonation of the methylenic active substrate (EtOCC) by the hydroxide group
that lead to the enolate ion. Next, this nucleophile reacted with the electrophilic
alkene (MVK) to form a new carbon-carbon bond. Proton abstraction from the
protonated base by the enolate achieved the final Michael addition product.

Table 5. Michael addition of ethyl 2-oxocyclopentane 2-carboxylate and methyl vinyl ketone
Entry
Catalysts
Yield (%)a
TONb
Time (1 h) (4 h)
1
2
3
4
5
6
7
12
8
5
32
37
48
7
19
9
8
56
63
69
14
4
2
2
11
13
14
3
1
2
3
5
6
7
1-HMDS
aReaction conditions: ethyl 2-oxocyclopentane 2-carboxylate (1 mmol),
methyl vinyl ketone (1 mmol) and CH3CN (0.5 ml) at 25 ºC with 5 mol %
of base sites. bTON calculated at final conversion.
Scheme 4. Proposed enolate catalytic reaction cycle of Michael addition between ethyl 2-
oxocyclopentane 2-carboxylate (EtOCC) and methyl vinyl ketone (MVK), catalyzed by
catalyst 4-6, as an example only catalyst 4 is represented.
4. Conclusions
Hybrid mesoporous base materials, synthesized by means of post-grafting
procedures and containing neutral (amine, diamine, pyrrolidine) or ionic
(pyrazolium, imidazoliun) base sites, have been successfully synthesised and
evaluated in different catalytic transformations. The characterisation of the hybrids
has revealed that the organic bases were preserved inside the mesoporous silica
network, providing strong base properties to the hybrid materials. These hybrid

catalysts were tested in the Knoevenagel condensation and Michael addition,
respectively. In particular, for Knoevenagel condensation, the neutral base catalysts
showed higher catalytic activity with respect to the other ionic hybrids. This superior
activity could be justified by the imine and enamine mechanism of the reaction that
was favoured with the presence of primary and secondary amine, respectively.
Additionally, the presence of silanols groups in the framework of the support would
perform a cooperative electrophilic activation. On the other hand, for Michael
addition, the ionic base catalysts were more efficient than the neutral base catalysts,
suggesting that an enolate mechanism was taking place and it was favoured when
hydroxide groups were present as base sites. The achieved results show that the
synthesis method to generate active hybrid materials opens the possibility of
combining these base sites with other acid and/or redox structural functions to
generate multisite catalysts for carrying out cascade type or one-pot multistep
catalytic processes.
Acknowledgments:
The authors are grateful for financial support from the Spanish Government by
MAT2017-82288-C2-1-P and Severo Ochoa Excellence Program SEV-2016-0683.
The authors thank the MULTY2HYCAT (EU-Horizon 2020 funded project under
grant agreement no.720783). A. E. acknowledges “La Caixa” foundation for PhD
scholarship.
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