An environmentally friendly, photocontrollable and highly recyclable catalyst for use in a one-pot three-component Mannich reaction

Article abstract of DOI:10.1016/j.molcata.2016.05.006

An environmentally friendly, photocontrollable and highly recyclable catalyst (ZrOPPAZOSO₃H) has been synthesized by the immobilization of 4-[4-(6-phosphonic acid-hexanoxyl)phenylazo]benzenesulfonic acid onto zirconium phosphonate. This catalyst was characterized by Fourier transform infrared, scanning electron microscopy, X-ray powder diffraction, nitrogen adsorption-desorption and UV-vis analyses. The catalytic activity of ZrOPPAZOSO₃H was investigated towards the one-pot three-component Mannich-type reaction of benzaldehyde, aniline and cyclohexanone in water at room temperature, and gave excellent yields. Interestingly, the catalytic activity could be regulated by photoirradiation. Furthermore, upon completion of the reaction, the product could be readily separated by extraction, and the water phase reused in the next run. Lastly, the catalyst could be readily recovered by centrifugation and reused up to six times without any discernible impact on its activity.

Full text of DOI:10.1016/j.molcata.2016.05.006

Accepted Manuscript
Title: An environmentally friendly, photocontrollable and
highly recyclable catalyst for use in a one-pot
three-component Mannich reaction
Author: Qian Tang Hong-jiang Quan Song Liu Lan-tao Liu
Cheuk-fai Chow Cheng-bin Gong
PII:
S1381-1169(16)30177-7
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2016.05.006
MOLCAA 9881
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
21-3-2016
29-4-2016
10-5-2016
Please cite this article as: Qian Tang, Hong-jiang Quan, Song Liu, Lan-tao Liu, Cheuk-
fai Chow, Cheng-bin Gong, An environmentally friendly, photocontrollable and highly
recyclable catalyst for use in a one-pot three-component Mannich reaction, Journal of
Molecular Catalysis A: Chemical http://dx.doi.org/10.1016/j.molcata.2016.05.006
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An environmentally friendly, photocontrollable and highly
recyclable catalyst for use in a one-pot three-component
Mannich reaction
Qian Tanga, Hong-jiang Quana, Song Liua, Lan-tao Liu,a Cheuk-fai Chow,b,*
Cheng-bin Gonga,*
a The Key Laboratory of Applied Chemistry of Chongqing Municipality, College of
Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715,
China
*Corresponding author: Dr. C.B. Gong, gongcbtq@swu.edu.cn. Fax: 86 23 68254000,
Tel.: 86 23 68252360
b
Department of Science and Environmental Studies, The Hong Kong Institute of
Education, Hong Kong. cfchow@ied.edu.hk
1

Graphical Abstract
Highlights
 An azobenzene-containing catalyst supported on zirconium phosphonate was
synthesized
 The catalyst catalyzes one-pot three-component Mannich reaction in water
 The catalyzed Mannich reaction could be photo-controllable
 The catalyst could be recycled and recovered easily
Abstract: An environmentally friendly, photocontrollable and highly recyclable
catalyst (ZrOPPAZOSO3H) has been synthesized by the immobilization of
4-[4-(6-phosphonic acid-hexanoxyl)phenylazo]benzenesulfonic acid onto zirconium
phosphonate. This catalyst was characterized by Fourier transform infrared, scanning
electron microscopy, X-ray powder diffraction, nitrogen adsorption-desorption and
UV-Vis analyses. The catalytic activity of ZrOPPAZOSO3H was investigated towards
the one-pot three-component Mannich-type reaction of benzaldehyde, aniline and
2

cyclohexanone in water at room temperature, and gave excellent yields. Interestingly,
the catalytic activity could be regulated by photoirradiation. Furthermore, upon
completion of the reaction, the product could be readily separated by extraction, and
the water phase reused in the next run. Lastly, the catalyst could be readily recovered
by centrifugation and reused up to six times without any discernible impact on its
activity.
Keywords: Mannich reaction; Environmentally friendly catalyst; Photocontrollable;
Azobenzene; Zirconium phosphonate
1. Introduction
The Mannich reaction involves the reaction of two carbonyl compounds with an
amine to give a β-amino-carbonyl compound via a C–C bond-forming reaction in the
presence of a proper catalyst [1]. β-Amino-carbonyl compounds are important
intermediates in the synthesis of pharmaceutical agents and natural products [2], and
the Mannich reaction has therefore attracted considerable interest from numerous
research groups. A variety of different catalysts have been developed for the Mannich
reaction, including Bronsted acids [3-6], Lewis acids [7-18] and several other organic
or inorganic compounds [19-22]. However, most of these methods are conducted in
organic solvents [3-7,9-13,15-17,19-22] or organic solvent-water mixtures [14,18].
The development of novel catalysts capable of catalyzing the Mannich reaction of a
wide range of substrates in water is therefore highly desired and research in this area
has grown considerable, because of the economical and environmental benefits of
water. However, the use of water as a solvent has been limited because of the poor
3

solubility of most organic reactants in water. For example, most of the reported
Mannich reactions conducted in water use silyl enol ethers as precursors [23] or have
to be performed in the presence of surfactants (such as sodium dodecyl sulfate) [24,25]
or ionic liquids [26,27]. Unfortunately, silyl enol ethers have to be prepared from the
corresponding carbonyl compounds and the Mannich reactions of these substrates
generally require an organic solvent. The use of surfactants or ionic liquids in these
reactions can lead to phase separation issues. Several researchers have reported the
use of water-soluble catalysts such as heteropoly acids and its salts [28,29]
Bi(OTf)3•4H2O [30], 5-sulfosalicylic acid [31], calix[n]arene quaternary ammonium
salts [32] and boron chelate complexes [33]. However, catalysts of this type can be
difficult to recover from the reaction mixture because of their good solubility.
Catalysts supported on a stable solid substrate are therefore highly desired because
they can be readily recycled [34,35].
To address these challenges, we developed a novel environmentally friendly,
recyclable and photocontrollable catalyst (ZrOPPAZOSO3H, Scheme 1) for a one-pot
three-component Mannich reaction in water by tethering a sulfonated azobenzene to
zirconium phosphate. It was envisaged that the sulfonic acid group in this catalyst
would serve as a catalytic moiety, as well as enhancing the aqueous solubility of the
catalyst. The recyclability of the catalyst could be realized by tethering the
azobenzene moiety to zirconium phosphate, which is a versatile material with a
layered structure. Azobenzene chromophores [36-40] are well-known photoresponsive
moieties, and the photoirradiation of these systems can induces trans/cis isomerization
4

processes, resulting in pronounced changes in their geometry, which can promote or
slow down specific reactions. The catalyst developed in this study demonstrated
photo-controllability, as well as being environmentally friendly and highly recyclable
for the one-pot three-component Mannich reaction of unmodified aldehydes, ketones
and amines in water. Indeed, photo-activated or photocontrollable catalysts for
Mannich reactions are rarely found in literature and the current system is interesting
for further exploring its potential applications in inhibition reactions.
2. Experimental details
2.1. Materials and methods
All of the chemicals used in the current study were purchased from Aladdin
Co. (Shanghai, China) and used without further purification.
Fourier transform infrared (FT-IR) spectra were recorded on a Perkin-Elmer
Model GX Spectrometer (Perkin-Elmer, Waltham, USA) as KBr pellets using
polystyrene as a standard. X-ray diffraction (XRD) patterns were recorded on a
LabX XRD-6100X-ray Diffractometer (SHIMADZU, City, Japan) with Cu-Kα
monochromated radiation (λ=1.5406 Å) at 36 kV and 20 mA. The
morphological characteristics of the ZrOPPAZOSO3H catalyst were determined
1
by scanning electron microscopy (SEM; S-4800, Hitachi, Tokyo, Japan). H
NMR and 13C NMR (300 MHz) spectra were recorded on a Bruker
AV-300NMR instrument (Bruker, USA) at ambient temperature using TMS as
an internal reference standard. Nitrogen adsorption-desorption analysis was
5

conducted at 77 K on an Autosorb-1 apparatus (Quantachrome, USA). The
specific surface areas and pore diameters were calculated using the BET and
BJH models, respectively. UV-Vis spectra were recorded with an UV-4802
spectrophotometer (UNICO Shanghai Instruments Co. Ltd, Shanghai, China)
using a CEL-S500 Xe lamp (Beijing Zhongjiao Jinyuan Keji Co., Ltd, Beijing,
China) as a light source. Wavelengths of 365 and 440 nm were selected using
365 and 440 nm filters, respectively.
2.2. Synthesis of ZrOPPAZOSO3H
The synthesis of ZrOPPAZOSO3H was completed over five steps (Scheme
2).
2.2.1. Synthesis of 4-[(4-Hydroxy)phenylazo]benzenesulfonic acid
4-[(4-Hydroxy)phenylazo]benzenesulfonic acid was synthesized according to a
modified version of previous methods reported by Ma, Kumar and Gong [41-43].
Briefly, sulfanilic acid (3.48 g, 20.0 mmol), sodium nitrite (1.52 g, 22.0 mmol) and
water (8.0 mL) were added to a 250 mL round-bottomed flask, and the resulting
mixture was cooled in an ice bath under stirring. An ice-cold mixture of water (8.0
mL) and conc. HCl (36%, 8.0 mL) was then added to the reaction flask in a dropwise
manner, and the resulting diazonium salt solution was stirred for 1 h at 0–5 °C. The
diazonium salt solution was added to an ice-cold mixture of phenol (2.48 g, 20.4
mmol) and aqueous NaOH solution (40 mL, 3.0 mol L–1) in a dropwise manner over
45 min. The resulting mixture was stirred at 0 °C for 2 h and then acidified to pH=3
with conc. HCl to give an orange precipitate, which was collected by filtration to give
6

the crude product. The crude material was then purified by recrystallization from
ethanol to give 4.02 g of pure 4-[(4-hydroxy)phenylazo]benzene sulfonic acid as an
1
orange solid. Yield: 71.9 %. H NMR (300 MHz, DMSO-d6) δ (ppm): 10.4 (s, 1H),
7.83 (d, 2H), 7.76 (s, 4H), 6.96 (d, 2H).
2.2.2. Synthesis of 4-[4-(6-diethylphosphonohexanoxyl)-phenylazo] benzenesulfonic
acid
Diethyl (6-bromo-hexanyl)phosphonate was synthesized according to a method
reported by Cernetic [44] with some minor modifications. Briefly, 1,6-dibromohexane
(10.0 g, 32 mmol) was heated at reflux under nitrogen and treated with
triethylphosphite (1.4 mL, 8 mmol), which was added in dropwise manner. The
resulting mixture was stirred for 12 h at 148 °C and then cooled to room temperature.
The crude product was purified by column chromatography over silica gel eluting
with ethyl acetate/petroleum ether (1:10, v/v) to give 1.63 g of diethyl
1
(6-bromohexanyl)-phosphonate as a colorless liquid. Yield: 66.0%. H NMR (300
MHz, CDCl3) δ (ppm): 4.11 (m, 4H), 3.42 (t, 2H), 1.78 (m, 8H), 1.46–1.26
(unresolved
coupling,
combined
integral,
8H).
was
4-[4-(6-Diethylphosphonohexanoxyl)-phenylazo]benzene-sulfonic
acid
synthesized according to a literature procedure reported by Cernetic and Tamura
[44,45]. 4-(4-Hydroxyphenylazo)benzenesulfonic acid (2.50 g, 9.00 mmol),
potassium carbonate (3.72 mg, 26.95 mmol) and acetone (60 mL) were added to a 100
mL round-bottomed flask, and the resulting mixture was stirred for 1 h at room
temperature. KI (0.15 g, 0.90 mmol) and diethyl (6-bromohexanyl)phosphonate (3.25
7

g, 10.78 mmol) were then added to the flask, and the resultant mixture was heated at
reflux with stirring for 48 h. The mixture was cooled to room temperature and filtered
to remove the inorganic salts. The filtrate was evaporated to dryness under vacuum to
give the crude product as a solid. The crude was purified by recrystallization from
ethanol to give 3.30 g of pure 4-[4-(6-diethylphosphonohexanoxyl-phenylazo]-
1
benzenesulfonic acid as an orange solid. Yield: 73.6%. H NMR (300 MHz,
DMSO-d6) δ (ppm): 7.90 (d, 2H), 7.79 (d, 4H), 7.13 (d, 2H), 4.08 (t, 2H), 3.96 (m,
4H), 1.68-1.75 (m, 4H), 1.43–1.52 (m, 6H), 1.23 (s, 6H); 13C NMR (75 MHz,
DMSO-d6) δ (ppm): 162.05, 152.21, 150.77, 146.61, 127.14, 125.10, 122.16, 115.56,
68.43, 61.25, 29.93, 28.81, 25.41, 24.47, 22.48, 16.75.
2.2.3. Synthesis of 4-[4-(6-phosphonic acid-hexanoxyl)phenylazo] benzenesulfonic
acid (PAAZOSO3H)
PAAZOSO3H was synthesized using methods from the literature with some
modifications [44,46,47]. Trimethylsilylbromide (2.12 mL, 16.05 mmol) was added in
a dropwise manner to a solution of 4-[4-(6-diethylphosphonohexanoxyl)
phenylazo]benzenesulfonic acid (2.0 g, 4.01 mmol) in anhydrous CH2Cl2 (20 mL),
and the resulting mixture was stirred under N2 for 6 h at room temperature. The
CH2Cl2 and excess trimethylsilylbromide were subsequently removed under reduced
pressure to give a residue, which was hydrolyzed with water (20 mL) under N2 over a
period of 2 h to give a brown precipitate. The precipitate was collected by filtration
and dried under vacuum for 24 h at 50 °C to give 1.49 g of PAAZOSO3H as a brown
1
solid. Yield: 83.8 %. H NMR (300 MHz, DMSO-d6) δ (ppm): 7.90 (d, 2H), 7.79 (d,
8

4H), 7.13 (d, 2H), 4.08 (t, 2H), 1.77 (s, 2H), 1.46 (m, 6H), 1.31 (s, 2H); 13C NMR (75
MHz, DMSO-d6) δ (ppm): 162.07, 152.22, 150.78, 146.62, 127.39, 125.10, 122.16,
115.56, 68.42, 35.51, 30.22, 28.88, 25.56, 23.17.
2.2.4. Synthesis of inorganic-organic hybrid zirconium phosphonate ZrOPPAZOSO3H
The ZrOPPAZOSO3H catalyst was prepared by the direct precipitation method
[48-50]. Briefly, a mixture of PAAZOSO3H (0.30 g, 0.68 mmol), NaH2PO4•2H2O
(0.22 g, 1.41 mmol), conc. HCl (36%, 2.0 mL) and DMSO (20.0 mL) was stirred at
room temperature until all of the solids completely dissolved. The solution was then
treated with 4.0 mL of an aqueous ZrOCl2•8H2O solution (0.67 g, 2.09 mmol) in a
dropwise manner under stirring, and the resulting mixture was aged at 65 °C for 6 h.
The mixture was then cooled to room temperature and filtered to give a solid, which
was washed with H2O until the washings became neutral (pH=7). The washed solid
was then dried under vacuum at 50 °C for 24 h to afford 0.93 g of ZrOPPAZOSO3H
as a red-brown solid.
For
comparison,
we
also
prepared
organic
4-[4-6-zirconium
phosphate-hexanoxyl]phenylazo] benzenesulfonic acid (ZrOPAZOSO3H) and
inorganic zirconium phosphonate. ZrOPAZOSO3H was prepared by the direct
precipitation method according to literature procedures [48-50]. Briefly, a mixture of
PAAZOSO3H (0.50 g, 1.13 mmol), conc. HCl (36%, 2.0 mL) and DMSO (20 mL)
was stirred at room temperature until all of the solids completely dissolved. The
solution was then treated with 4.0 mL of an aqueous ZrOCl2•8H2O solution (0.40 g,
1.24 mmol) in a dropwise manner under stirring, and the resulting mixture was aged
9

at 65 °C for 6 h. The mixture was cooled to room temperature and filtered to give a
solid, which was washed with H2O until the washings became neutral (pH=7). The
washed solid was then dried under vacuum at 50 °C for 24 h to afford 0.63 g of
ZrOPAZOSO3H as a brown solid. Inorganic zirconium phosphonate was prepared
according to previous reports [48-50].
2.3. Spectroscopic characterization and photoisomerization studies
Spectroscopic characterization and photoisomerization experiments for
PAAZOSO3H, ZrOPPAZOSO3H and ZrOPAZOSO3H were conducted in DMSO
using a 1.0 cm path length quartz cuvette at room temperature in all cases.
Suspensions of ZrOPPAZOSO3H and ZrOPAZOSO3H were maintained with
magnetic stirrers and irradiated at 365 nm, followed by 440 nm. The kinetic properties
of the photoisomerization (trans→cis) reactions were analysed using kinetic Eq. (1),
as follows [37]:
A0  A
ln
 kt
(1)
A  A
t
where A0, At and A∞ are the absorbance wavelengths at 365 and 440 nm of the
azobenzene chromophores at times 0, t and the photostationary state, respectively, and
k is the rate constant of the photoisomerization process.
2.4. Mannich reaction
All of the Mannich reactions were performed in a 3.0 mL quartz cell (1.0 cm optical
path length) equipped with a magnetic stirrer. Typically, ZrOPPAZOSO3H (18.9 wt%
with respect to benzaldehyde), benzaldehyde (53.0 mg, 0.5 mmol), aniline (46.5 mg,
0.5 mmol), cyclohexanone (53.9 mg, 0.55 mmol) and H2O (3.0 mL) were charged
10

into the quartz cell, and the resulting mixture was irradiated at 365 nm under stirring
for 5 h at room temperature. The progress of the reaction was monitored by thin layer
chromatography. The desired product formed as a white precipitate over time and was
extracted from the reaction mixture with ethyl acetate (3×5.0 mL). The combined
organic extracts were evaporated to dryness under vacuum to give the Mannich
reaction product as colorless crystals. The catalyst remained in the water phase.
Typical procedure for the recycling and recovery of the catalyst
2.5. Recycling of the ZrOPPAZOSO3H catalyst
The water phase containing the ZrOPPAZOSO3H catalyst was readily recycled
following the extraction of the product with ethyl acetate. Most notably, the water
phase could be used directly in a subsequent run following the addition of fresh
reactants.
2.6. Recovery of the ZrOPPAZOSO3H catalyst
The catalyst was readily recovered by centrifugation following by filtration upon
completion of the recycling runs.
3. Results and discussion
FT-IR spectra of PAAZOSO3H, ZrOPPAZOSO3H and ZrOPAZOSO3H are shown
in Fig. 1. The strong and broad absorption bands centered around 3440 cm−1 in the
spectra of PAAZOSO3H, ZrOPPAZOSO3H and ZrOPAZOSO3H were attributed to O–
H stretching vibrations. The absorption bands at 2936 and 2862 cm–1 were attributed
to the C–H stretching vibrations. The sharp absorption bands at 1601 and 1501 cm–1
11

were assigned to C=C stretching vibrations. A sharp absorption band was observed at
1034 cm–1 in the spectra of ZrOPPAZOSO3H and ZrOPAZOSO3H, which was
attributed to the stretching vibrations of the P–O–Zr bonds. Notably, the intensity of
this peak was much stronger in the ZrOPPAZOSO3H spectrum than it was for
ZrOPAZOSO3H, thereby proving the structural formation of ZrOPPAZOSO3H and
ZrOPAZOSO3H [51].
Fig. 2 shows the XRD patterns of zirconium phosphonate, ZrOPAZOSO3H and
ZrOPPAZOSO3H. The characteristic diffraction peak of zirconium phosphonate at
2θ=8.0° was consistent with the formation of a layered structure with an interlayer
distance of 1.1 nm. Weak diffraction peaks were observed for ZrOPAZOSO3H and
ZrOPPAZOSO3H at 2θ=8.0°, which demonstrated that these materials had layered
structures. The broad diffraction peaks around 2θ=21° were indicative of the
amorphous nature of ZrOPAZOSO3H and ZrOPPAZOSO3H. ZrOPPAZOSO3H gave a
diffraction peak around 2θ=33°, which was consistent with the formation of some
crystalline material [52].
Fig. 3 shows SEM images of ZrOPAZOSO3H (Fig. 3A) and ZrOPPAZOSO3H
(Fig. 3B). A comparison of the SEM images of these two materials revealed that
ZrOPPAZOSO3H was composed of smaller and looser particles with a more
flake-like morphology (Fig. 3B), with the length of each flake being about 200 nm.
Fig. 4 shows the UV-Vis spectra and spectral changes for DMSO solutions of
PAAZOSO3H, ZrOPAZOSO3H and ZrOPPAZOSO3H following alternate periods of
irradiation at 365 and 440 nm. Fig. 4A shows the UV-Vis spectra and spectral changes
12

of a DMSO solution of the azobenzene monomer PAAZOSO3H upon its irradiation at
365 nm. UV irradiation at 365 nm induced a trans→cis photoisomerization reaction,
resulting in a decrease in the absorbance at 358 nm. Subsequent irradiation at 440 nm
reversed this process and returned the solution back to its original state (Fig. 4B),
demonstrating that these photoinduced isomerization processes are completely
reversible. ZrOPAZOSO3H and ZrOPPAZOSO3H showed similar reversible
photoisomerization phenomenon (Fig. 4C–F), thereby illustrating that the azobenzene
chromophores tethered to zirconium phosphonate maintained reversible
photoisomerization properties. However, the rate constants (k) of ZrOPAZOSO3H and
ZrOPPAZOSO3H were smaller than that of PAAZOSO3H (Table 1). The rate
constants decreased according to the order kPAZOSO3H>kZrOPAZOSO3H>kZrOPPAZOSO3H. This
order was attributed to the growing rigidity of the environment, which would hinder
the reorientation of the azobenzene chromophores.
Fig. 5(A and B) show the nitrogen adsorption–desorption isotherms of
ZrOPAZOSO3H and ZrOPPAZOSO3H and their corresponding pore size distributions.
The textural parameters of ZrOPAZOSO3H and ZrOPPAZOSO3H were calculated
using the BJH method at 77 K. The adsorption isotherms of ZrOPAZOSO3H and
ZrOPPAZOSO3H were both typical Type IV isotherms. The pore size distribution of
ZrOPAZOSO3H gave three narrow peaks at 1.18, 1.67 and 2.32 nm, as well as a broad
peak between 3.72 and 4.80 nm, which had a maximum at 4.20 nm. The pore size
distribution of ZrOPPAZOSO3H gave three narrow peaks at 1.09, 1.38 and 1.72 nm,
as well as two broad peaks in the range of 2.42–2.88 and 3.81–5.54 nm, with
13

maximum values at 2.19 and 4.50 nm, respectively. These results demonstrated that
the pores of ZrOPAZOSO3H and ZrOPPAZOSO3H were between micro and
mesoporous. The surface areas and total pore volumes of ZrOPAZOSO3H and
ZrOPPAZOSO3H were determined to be 10.02 m2 g–1 and 0.0252 cm3 g–1, and 47.74
m2 g–1 and 0.1429 cm3 g–1, respectively. The pore size, surface area and total pore
volume properties of ZrOPPAZOSO3H were larger than those of ZrOPAZOSO3H.
These differences were attributed to the addition of inorganic NaH2PO4•2H2O, which
would have promoted the formation of some crystalline material.
The catalytic properties of ZrOPPAZOSO3H were evaluated using the one-pot
three-component Mannich reaction of benzaldehyde, aniline and cyclohexanone at
room temperature as a model reaction (Scheme 3). The experimental conditions for
this transformation, including the solvent, amount of catalyst, reaction time and molar
ratio of reactants, were fully optimized (Table 2).
Excellent yields were obtained in MeOH (97.2%), EtOH (98.0%) and H2O (94.5%)
(Table 2, entries 1–5). Water was selected as the best solvent for further investigation
because it is environment-friendly. Furthermore, preliminary results revealed that
polar solvents were beneficial for this reaction.
Optimization experiments revealed that yield increased as the amount of catalyst
increased (Table 2, entries 6–11), with an 18.9 wt% loading of the ZrOPPAZOSO3H
catalyst with respect to benzaldehyde giving the highest yield (94.5%). To illustrate
the efficiency of the catalyst, we conducted the same reaction in the absence of
ZrOPPAZOSO3H (Table 2, entry 6). This reaction failed to afford any of the desired
14

material. These results indicated that the presence of ZrOPPAZOSO3H was critical to
the success of this reaction. The same reaction was also carried out using zirconium
phosphate as a catalyst to rule out the possibility that the catalysis was caused by the
zirconium phosphate support (Table 2, entry 12). This reaction gave a much lower
yield (8.6%) of the Mannich product. Using organic ZrOPAZOSO3H as the catalyst
(Table 2, entry 13), we obtained a yield of 67.9%. These results therefore demonstrate
that the inorganic-organic hybrid zirconium phosphate catalyst gave the best results in
terms of the yield of the desired product.
The yield also increased as the reaction time increased and reached a maximum
after 5 h (Table 2, entries 1, 14–18). The highest yield was obtained with a molar ratio
of benzaldehyde:aniline:cyclohexanone=1.0:1.0:1.1 (Table 2, entries 1, 19–24).
Notably, the activity of the ZrOPPAZOSO3H catalyst could be photocontrolled
(Fig. 6). For example, yields of 60.6, 94.5, 50.7 and 36.6% were obtained under the
same conditions for experiments conducted at ambient conditions (namely, under
natural light), under irradiation at 365 and 440 nm, and in the dark, respectively.
Similar trends were also observed when ZrOPAZOSO3H, PAAZOSO3H, and
4-hydroxyl-[4-(6-phosphonic acid-hexanoxyl)phenylazobenzene (PAAZOOH, ESI,
Fig. S1) were used as the catalyst. The reason for this trend can be explained as
follows. At ambient conditions, azobenzene chromophores exist in both trans and cis
form, and moderate yield was obtained (ESI, Fig. S2). Irradiation at 365 nm would
induce the trans→cis isomerization of the substrate (Scheme 1), thereby bringing the
sulfonic acid farther away from the zirconium phosphate and promoting the reaction.
15

Most of the azobenzene chromophores would exist in their trans form upon
irradiation at 440 nm, moving the sulfonic acid closer to the zirconium phosphate, the
interaction between sulfonic acid and hydroxyl groups of zirconium phosphate would
probably result in a reduction in the rate of the reaction. The lowest yield was
obtained in the dark because of the near-complete conversion of the cis form to the
trans form [53]. Therefore, photocontrolled catalyzed Mannich reaction was realized.
When zirconium phosphate and benzene sulfonic acid (BSA) without photosensitive
azobenzene were used as the catalyst, slightly higher yield was obtained under UV or
visible light irradiation compared to the case in the dark. This was probably caused by
the slightly elevated temperature (about 8°C) upon photoirradiation. Compared with
the Mannich reaction results using PAAZOSO3H and BSA as the catalysts, lower
yields were obtained when PAAZOOH was used as the catalyst. This illustrated that
sulfonic acid plays important role in the catalysed Mannich reaction.
It is noteworthy that the catalyst could be readily recycled and recovered
following the reaction. Upon completion of the catalyzed Mannich reaction, the solid
product was easily separated from the reaction system by extraction with ethyl acetate.
The remaining aqueous solution could be used directly in the next reaction run by
simply adding the required reactants. The recovery of the catalyst was also easy. After
completion of the reaction and the subsequent isolation of the product, the catalyst in
the aqueous phase was simply obtained by centrifugation for future use (ESI, Fig. S3).
It’s clearly that the supported ZrOPPAZOSO3H and ZrOPAZOSO3H can be easily
recovered from aqueous solvent. However, the non-supported materials
16

(PAAZOSO3H, PAAZOOH, and BSA) cannot be recovered from the aqueous solvent
by simple centrifugation. As shown in Fig. 7, the catalyst continued to afford an
excellent yield (91.8%) after six runs, which represents a better performance than
several previously reported catalysts [26,35,54].
The scope of this newly developed ZrOPPAZOSO3H-catalyzed Mannich reaction
was evaluated using a wide range of substituted benzaldehydes and aniline under the
optimized conditions. As shown in Table 3, the reaction proceeded smoothly with
aromatic aldehydes bearing an electron-donating group (e.g., OCH3 or CH3) at their
4-position. Anilines bearing an electron-withdrawing group (e.g., CN, NO2 or Cl) at
their 4-position also reacted smoothly. Moderate yields (56-78%) were obtained,
which were lower than the results using non-substituted reactants. The possible reason
for this could be ascribed to their bad solubility in water. Significant increase in yield
was obtained if a small fraction of ethanol was added into this reaction system.
4. Conclusions
In this study, we have described our initial efforts towards the development
of a novel environmentally friendly, photo-controllable and recyclable catalyst
for the three-component Mannich reaction of benzaldehyde, aniline and
cyclohexanone in water. The catalyst developed in this study is based on the
combination of sulfonic acid with an azobenzene chromophore and zirconium
phosphonate. This new catalyst photo-controllably catalyzed the one-pot,
three-component Mannich reaction of aldehydes, amines and ketones in water.
17

Furthermore, this catalyst can be readily recycled and reused. The
environmentally friendly, photocontrollable and recyclable properties of this
catalyst could make it possible to use this system in other acid-catalyzed
organic reactions.
Acknowledgements
This work was funded by a grant from the Chong Qing Science and Technology
Commission (CQ CSTC 2013jcyjA50026) and a grant from the Research Grants
Council of Hong Kong SAR, China (ECS no. 800312).
18

References
[1] S. Mukherjee, J.W. Yang, S. Hoffmann, B. List, Chem. Rev. 107 (2007)
5471–5569.
[2] M. Arend, B. Westermann, N. Risch, Angew. Chem. Int. Edit. 37 (1998)
1044–1070.
[3] R. Muller, H. Goesmann, H. Waldmann, Angew. Chem. Int. Edit. 38 (1999)
184–187.
[4] M. Sickert, F. Abels, M. Lang, J. Sieler, C. Birkemeyer, C. Schneider,
Chem-Eur. J. 16 (2010) 2806–2818.
[5] M.A. Bigdeli, F. Nemati, G.H. Mahdavinia, Tetrahedron Lett. 48 (2007)
6801–6804.
[6] H. Wu, Y. Shen, L.Y. Fan, Y. Wan, P. Zhang, C.F. Chen, W.X. Wang,
Tetrahedron 63 (2007) 2404–2408.
[7] Y. Li, M.H. Xu, Org. Lett. 14 (2012) 2062–2065.
[8] Y. Wu, C. Chen, G. Jia, X.Y. Zhu, H.M. Sun, G.F. Zhang, W.Q. Zhang, Z.W.
Gao, Chem-Eur. J. 20 (2014) 8530–8535.
[9] X.F. Xu, P.Y. Zavalij, M.P. Doyle, Angew. Chem. Int. Edit. 51 (2012) 9829–
9833.
[10] B. Karimi, E. Jafari, D. Enders, Chem-Eur. J. 19 (2013) 10142–10145.
[11] T. Arai, A. Mishiro, E. Matsumura, A. Awata, M. Shirasugi, Chem-Eur. J. 18
(2012) 11219–11222.
19

[12] W.G. Shou, Y.Y. Yang, Y.G. Wang, Tetrahedron Lett. 47 (2006) 1845–
1847.
[13] Y.Y. Yang, W.G. Shou, Y.G. Wang, Tetrahedron 62 (2006) 10079–10086.
[14] B.C. Ranu, S. Samanta, S.K. Guchhait, Tetrahedron 58 (2002) 983–988.
[15] R. Wang, B.G. Li, T.K. Huang, L. Shi, X.X. Lu, Tetrahedron Lett. 48 (2007)
2071–2073.
[16] Z. Li, X.L. Ma, J. Liu, X. Feng, G.Q. Tian, A.G. Zhu, J. Mol. Catal. A-Chem.
272 (2007) 132–135.
[17] Y. Yamashita, M. Ueno, Y. Kuriyama, S. Kobayashi, Adv. Synth. Catal. 344
(
2002) 929–931.
[18] S. Kobayashi, T. Hamada, K. Manabe, J. Am. Chem. Soc. 124 (2002) 5640–
5641.
[19] K. Nagata, Y. Kuga, A. Higashi, A. Kinoshita, T. Kanemitsu, M. Miyazaki,
T. Itoh, J. Org. Chem. 78 (2013) 7131–7136.
[20] E. Gomez-Bengoa, M. Maestro, A. Mielgo, I. Otazo, C. Palomo, I. Velilla,
Chem-Eur. J. 16 (2010) 5333–5342.
[21] A.T. Khan, T. Parvin, L.H. Choudhury, Eur. J. Org. Chem. 2008 (2008) 834–
839.
[22] L. Mengozzi, A. Gualandi, P.G. Cozzi, Chem. Sci. 5 (2014) 3915–3921.
[23] E. Veverkova, L. Liptakova, M. Veverka, R. Sebesta,
Tetrahedron-Asymmetr. 24 (2013) 548–552.
[24] K. Manabe, S. Kobayashi, Org. Lett. 1 (1999) 1965–1967.
20

[25] T. Chang, L.Q. He, L. Bian, H.Y. Han, M.X. Yuan, X.R. Gao, RSC Adv. 4
(2014) 727–731.
[26] L.Q. He, S.J. Qin, T. Chang, Y.Z. Sun, J.Q. Zhao, Int. J. Mol. Sci. 15 (2014)
8656–8666.
[27] Y.M. Ren, J.J. Shao, Z.C. Wu, R.C. Yang, Z. Zhang, T.X. Tao, Synthetic
Commun. 44 (2014) 2529–2534.
[28] G. Li, R. L. Long, S.L. Yang, L.P. Zhang, Kinet. Catal. 52 (2011) 559–563.
[29] Y.H. Hui, W. Shi, S.L. Xie, C.C. Wang, Z.F. Xie, Chinese J. Org. Chem. 34
(2014) 1212–1217.
[30] T. Ollevier, E. Nadeau, A.A. Guay-Begin, Tetrahedron Lett. 47 (2006) 8351–
8354.
[31] C. Chen, X.Y. Zhu, Y. Wu, H.M. Sun, G.F. Zhang, W.Q. Zhang, Z.W. Gao,
J. Mol. Catal. A-Chem. 395 (2014) 124–127.
[32] S. Sayin, M. Yilmaz, RSC Adv. 4 (2014) 2219–2225.
[33] C. Mukhopadhyay, A. Datta, R.J. Butcher, Tetrahedron Lett. 50 (2009)
4246–4250.
[34] E. Rafiee, S. Eavani, Green Chem. 13 (2011) 2116–2122.
[35] D. Zareyee, H. Alizadeh, RSC Adv. 4 (2014) 37941–37946.
[36] G.S. Kumar, D.C. Neckers, Chem. Rev. 89 (1989) 1915–1925.
[37] Q. Tang, X.Z. Meng, H.B. Jiang, T.Y. Zhou, C.B. Gong, X.K. Fu, S.Q. Shi, J.
Mater. Chem. 20 (2010) 9133–9139.
21

[38] Q. Tang, Y.T. Nie, C.B. Gong, C.F. Chow, J.D. Peng, M.H.W. Lam, J. Mater.
Chem. 22 (2012) 19812–19820.
[39] Z.Y. Li, H.J. Quan, C.B. Gong, Y.Z. Yang, Q. Tang, Y.B. Wei, X.B. Ma,
M.H.W. Lam, Food Chem. 172 (2015) 56–62.
[40] H.D. Liu, A.X. Zheng, C.B. Gong, X.B. Ma, M.H.W. Lam, C.F. Chow, Q.
Tang, RSC Adv. 5 (2015) 62539–62542.
[41] H.C. Ma, J.B. Fei, Y. Cui, J. Zhao, A.H. Wang, J.B. Li, Chem. Commun. 49
(2013) 9956–9958.
[42] A. Kumar, R.R. Ujjwal, A. Mittal, A. Bansal, U. Ojha, ACS Appl. Mater.
Inter. 6 (2014) 1855–1865.
[43] C.B. Gong, K.L. Wong, M.H.W. Lam, Chem. Mater. 20 (2008) 1353–1358.
[44] N. Cernetic, O. Acton, T. Weidner, D.O. Hutchins, J.E. Baio, H. Ma, A.K.Y.
Jen, Org. Electron. 13 (2012) 3226–3233.
[45] Y. Tamura, L. Sheng, S. Nakazawa, T. Higashihara, M. Ueda, J. Polym. Sci.
Pol. Chem. 50 (2012) 4334–4340.
[46] V. Besse, L. Le Pluart, W.D. Cook, T.N. Pham, P.J. Madec, J. Polym. Sci.
Pol. Chem. 51 (2013) 149–157.
[47] G. Arrachart, I. Karatchevtseva, A. Heinemann, D.J. Cassidy, G. Triani, J.
Mater. Chem. 21 (2011) 13040–13046.
[48] Y. Du, D.D. Feng, J.W. Wan, X.B. Ma, Appl. Catal. A-Gen 479 (2014) 49–
58.
22

[49] R. Wang, J.W. Wan, X.B. Ma, X. Xu, L. Liu, Dalton Trans. 42 (2013) 6513–
6522.
[50] X.Z. Lin, Z.Y. Yuan, RSC Adv. 4 (2014) 32443–32450.
[51] Y.J. Jia, Y.J. Zhang, R.W. Wang, J.J. Yi, X. Feng, Q.H. Xu, Ind. Eng. Chem.
Res. 51 (2012) 12266–12273.
[52] a) R.Q. Zeng, X.K. Fu, Y. Sui, X.B. Yang, M.D. Sun, J.R. Chen, J.
Organomet. Chem. 693 (2008) 2666–2672. b) X.B. Yang, X.K. Fu, Y. Huang,
R.Q. Zeng, Chem. Pap. 65 (2011) 829–834.
[53] S. Samanta, A.A. Beharry, O. Sadovski, T.M. McCormick, A. Babalhavaeji,
V. Tropepe, G.A. Woolley, J. Am. Chem. Soc. 135 (2013) 9777–9784.
[54] X. Zheng, Y.B. Qian, Y.M. Wang, Eur. J. Org. Chem. 2010 (2010) 515–522.
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Figure Captions
Fig. 1. FT-IR spectra of PAAZOSO3H, ZrOPPAZOSO3H, and ZrOPAZOSO3H.
Fig. 2. High-angle XRD patterns of zirconium phosphonate, ZrOPAZOSO3H and
ZrOPPAZOSO3H.
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Fig. 3. SEM images of ZrOPAZOSO3H (A) and ZrOPPAZOSO3H (B).
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Fig. 4. UV-Vis spectra and spectral changes for a solution of PAAZOSO3H in DMSO
(1.0 × 10–5 mol L–1) upon irradiation at 365 nm (A) and 440 nm (B). UV-Vis spectra
and spectral changes for a solution of ZrOPAZOSO3H in DMSO (0.2 mg mL–1) upon
irradiation at 365 nm (C) and 440 nm (D). UV-Vis spectra and spectral changes for a
solution of ZrOPPAZOSO3H in DMSO (0.2 mg mL–1) upon irradiation at 365 nm (E)
and 440 nm (F).
26

27

28

Fig. 5. Nitrogen adsorption-desorption isotherms of ZrOPAZOSO3H (A) and
ZrOPPAZOSO3H (B) at 77 K. Insets: the corresponding pore size distributions
calculated using the BJH method.
29