Titanocene dichloride and poly(o-aminophenol) as a new heterogeneous cooperative catalysis system for three-component Mannich reaction

Article abstract of DOI:10.1039/c5cy00793c

A new heterogeneous cooperative catalysis system featuring the synergistic effect of an organometallic Lewis acid and a Bronsted acid supporter was developed. The catalysis system successfully catalyzed the direct Mannich reaction of both aromatic and aliphatic ketones in excellent yields. The catalyst can be recycled at least five times and the yield of the Mannich product remains over 90%.

Full text of DOI:10.1039/c5cy00793c

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Titanocene dichloride and polyIJo-aminophenol) as
a new heterogeneous cooperative catalysis system
for three-component Mannich reaction†
Cite this: Catal. Sci. Technol., 2015,
5, 4346
Received 29th May 2015,
Accepted 14th July 2015
*
Xuyang Zhu, Chun Chen, Binxun Yu, Ya Wu, Guofang Zhang, Weiqiang Zhang and
*
Ziwei Gao
DOI: 10.1039/c5cy00793c
www.rsc.org/catalysis
A new heterogeneous cooperative catalysis system featuring the
synergistic effect of an organometallic Lewis acid and a Brønsted
acid supporter was developed. The catalysis system successfully
catalyzed the direct Mannich reaction of both aromatic and
aliphatic ketones in excellent yields. The catalyst can be recycled
at least five times and the yield of the Mannich product remains
over 90%.
complex metal ions.7 Moreover, coordination between PANI
and different metal can be adjusted by introducing different
substituents into the phenyl ring. PolyIJo-aminophenol)
(POAP) is an interesting member of the class of substituted
PANIs.8 The hydroxyl group in the phenyl ring can coordinate
to the titanocene center of titanocene dichloride.
Herein, we disclosed a heterogeneous binary acid system
featuring an air-stable organometallic precusor, titanocene
dichloride, and POAP as a cooperative Brønsted acid sup-
porter, which allowed for mild and highly efficient Mannich
reactions of both aryl and alkyl ketones with excellent yields.
To the best of our knowledge, this is the first time that a
heterogeneous organometallic binary catalyst with coopera-
tive dual activation is observed in C–C bond forming
reactions.
Nowadays, a lot of interest and efforts have been devoted to
the use of the early transition metal, titanium, because of its
abundant and cheap characteristics.1 Titanocenes which have
stable C–M bonds in water and air are more stable than other
traditional titanium salts.2 As the simplest titanocene, the
application of titanocene dichloride as a Lewis acid catalyst to
directly generate new carbon–carbon bonds is still limited,
presumably because the Lewis acidity of the titanocene center
is too weak.3 However, we found that the Lewis acidity of
titanocene dichloride can be deliberately adjusted by
exploiting the oxo-ligands to exhibit satisfactory catalytic
activities in a homogeneous system.4
From an economic point of view, heterogeneous catalysts
provide an attractive alternative to the corresponding homo-
geneous catalysts which are hampered by poor catalyst stabil-
ity or difficult catalyst recovery.5 In heterogeneous systems,
polymer-supported metal complexes are gaining importance
as efficient heterogeneous catalysts for a variety of organic
transformations.6 Among the polymers, polyaniline (PANI) is
found to be one of the most promising support materials
because of its distinctive characteristics such as facile prepar-
ative protocols from a cheap starting material (aniline), high
environmental stability, and non-solubility in most organic
solvents. Meanwhile, the protonated secondary or tertiary
imine functionalities endow PANI with strong affinity for
To test our proposal, functional polyanilines expected to
be efficient structures of cooperative Brønsted acid sup-
porters to Cp2TiCl2 were investigated. By using benzaldehyde,
aniline and acetophenone as model substrates, we tested the
three-component Mannich reaction at 25 °C with 10 mol%
Cp2TiCl2 and 10 mg of the polymer (Table 1).
Pleasingly, POAP preferably activates Cp2TiCl2 to provide
the desired Mannich product. After stirring for six hours,
condensation afforded the product in 97% yield (Table 1,
entry 2). When POAP was replaced with PANI, which has no
hydroxyl group in the phenyl ring, the yield decreased obvi-
ously (Table 1, entry 3). The 67% yield of the product was
obtained in the reaction using poly(o-methoxyaniline)
(POMA) as the supporter, because coordination of the oxygen
atom on the methoxy group to Cp2TiCl2 is difficult to achieve
(Table 1, entry 4). The results suggested that the phenol
group is crucial to induce direct Mannich reaction. The weak
Brønsted acidity of the phenol group could be suitable for
adjusting the Lewis acidity of the titanocene in situ. As the
doping agent, camphorsulfonic acid (CSA) was used for the
preparation of POAP. To test the catalytic activity of CSA, it
was adopted as an additive in the Cp2TiCl2-catalyzed
Mannich reaction, but the yield of the ketone product was
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education,
School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an
710062, PR China. E-mail: zwgao@snnu.edu.cn; Fax: +86 29 81530821
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c5cy00793c
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Table 1 The effect of substituted polyanilines and their analogues on
Cp2TiCl2-catalyzed Mannich reactiona
Entry
Catalyst
Yieldb (%)
1
2
3
4
5
6
7c
Cp2TiCl2
20
97
58
67
49
37
96
Cp2TiCl2 + POAP
Cp2TiCl2 + PANI
Cp2TiCl2 + POMA
Cp2TiCl2 + CSA
POAP
Fig. 2 XRD analysis of (a) Cp2TiCl2, (b) POAP-supported Cp2TiCl2 and
(c) POAP.
POAP-supported Cp2TiCl2
a
Benzaldehyde, 1.0 mmol; aniline, 1.1 mmol; acetophenone, 1.5
mmol; Cp2TiCl2, 0.10 mmol; polymer, 10 mg or CSA, 0.10 mmol; 25
b
c
°C; 6 h. Isolated yields. Benzaldehyde, 1.0 mmol; aniline, 1.1
mmol; acetophenone, 1.5 mmol; heterogeneous catalyst, 35 mg; 25
°C; 6 h.
Fig. 3 shows the FTIR spectra of POAP and POAP-
supported Cp2TiCl2. In curve (b), the bands at 3100, 1441,
1027 and 820 cm−1 are characteristic of C–H vibrations of the
cyclopentadienyl group.9 Compared to that in curve (a), the
intensity of the band at 3453 cm−1 (the stretching vibration
of the hydroxyl group) became much weaker and the band at
1188 cm−1 (the characteristic bending vibration of the
hydroxyl group of phenol) in curve (b) disappeared, implying
that a reaction between Cp2TiCl2 and POAP occurred and the
O–H bond was cleaved to form a new Ti–O bond, which was
supported by the appearance of the band at 756 cm−1. The
band at 756 cm−1 is usually assigned to the characteristic
Ti–O stretching vibration.10 Moreover, the bands of the ben-
zene ring of POAP shift to lower wavenumbers. The disap-
pearance of the characteristic O–H vibration at 1188 cm−1
and the appearance of Ti–O vibration at 756 cm−1 clearly indi-
cate a strong interaction between Cp2TiCl2 and POAP.
The coordination of Cp2TiCl2 to POAP is further supported
by the XPS spectrum (Fig. 4(b)). The photoelectron peaks at
457.3 and 463.1 eV are the characteristic doublets of Ti 2p
core-level spectra of titanocene and TiO, respectively.11 All
elements including C, N, O, Ti and Cl are found in the XPS
spectrum of the prepared composite (Fig. 4(a)), which further
confirms that the prepared catalyst is generated from the
reaction of POAP and Cp2TiCl2. From analysis of the content,
the content of chlorine is almost identical to that of titanium
in the catalyst, which indirectly proves that one chlorine
atom of each Cp2TiCl2 remains after coordination of Cp2TiCl2
to POAP.
only 49% (Table 1, entry 5). As control reactions, only using
Cp2TiCl2 or POAP as individual catalysts afforded the product
in 20% and 37% yields, respectively (Table 1, entries 1 and
6). Among the polyanilines above, POAP is therefore the best
cooperative Brønsted acid supporter for Cp2TiCl2-catalyzed
direct Mannich reaction.
Inspired by the preliminary results, POAP-supported
Cp2TiCl2 was prepared to determine the possible catalytic
species of the catalysis system. Cp2TiCl2 and POAP were
mixed in CH2Cl2 with aniline at 25 °C. After stirring for 24 h,
the heterogeneous catalyst was obtained by washing, filtering
and drying. To our pleasure, POAP-supported Cp2TiCl2 as the
catalyst afforded the desired product in 96% yield (Table 1,
entry 7). The catalytic active species were characterized by
SEM, XRD, FTIR and XPS.
The SEM images (Fig. 1) show that very tiny Cp2TiCl2 par-
ticles are supported on the POAP surface. It can be seen that
the XRD pattern (Fig. 2) of POAP-supported Cp2TiCl2 has
peaks at 2θ = 15.2°, 16.1° and 20.0°, which indicate that the
interaction between Cp2TiCl2 and POAP affords a new sub-
stance. Moreover, the peaks at 2θ = 13.7° and 15.7°, which
are the characteristic peaks of Cp2TiCl2 and POAP, respec-
tively (Fig. 2(a) and (c)), indicate that partial structures of
Cp2TiCl2 and POAP remain.
Fig. 1 SEM images of (a, b) POAP and (c, d) POAP-supported Cp2TiCl2.
Fig. 3 FTIR spectra of (a) POAP and (b) POAP-supported Cp2TiCl2.
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electron-donating or electron-withdrawing substituents
(Table 2). The reaction outcome was not significantly affected
by the substituent effect. Ketones with methoxy substituents
produced excellent results when benzaldehyde with the
electron-donating methoxy group and aniline with the
electron-withdrawing chlorine group were used (Table 2,
entries 9 and 10). To our pleasure, the sterically hindered
effect had no significant inhibitory effect on this method and
the yields of the desired products were still more than 85%
(Table 2, entries 3–5 and 7–10).
Fig. 4 XPS analysis of POAP-supported Cp2TiCl2: (a) full survey spec-
Moreover, the heterogeneous binary acid system also
showed satisfactory yields for the direct three-component
Mannich reactions with aliphatic ketones (Table 3). Using
3-pentanone as the substrate furnished the products in 75%
to 80% yields (Table 3, entries 1–3). Reaction of 2-pentanone
with o-chlorobenzaldehyde and aniline (Table 3, entry 5)
resulted in up to 90% yield. Notably, reaction of acetone with
benzaldehyde and aniline afforded the desired product in
86% yield (Table 3, entry 8), which was higher than those for
many other reported catalysts.12 The yield of benzaldehyde
with the electron-donating methoxy group was lower than
that with the electron-withdrawing nitro group for acetone
(Table 3, entries 9–10).
From an economic point of view, the stability and
sustained activity of the catalyst are of major importance.
Thus, the recovery and reusability of the catalyst were investi-
gated in the Mannich reaction of benzaldehyde, aniline and
acetophenone (Fig. 5). After the reaction, the catalyst was
readily recycled by washing with THF, filtration and drying.
To our delight, the catalytic activity of the catalyst had little
change after five catalytic cycles. This result suggests the high
chemical stability of the heterogeneous catalyst.
trum and (b) expanded spectrum of Ti 2p.
Table 2 The heterogeneous binary acid catalyst-catalyzed direct three-
component Mannich reactionsa
Entry
R1
R2
R3
Yieldb (%)
1
H
H
H
97
95
86
87
92
94
86
84
94
95
2
H
H
H
p-Cl
o-Cl
m-CH3
H
H
H
H
p-Cl
p-Cl
H
H
H
H
H
H
3c
4c
5c
6c
7c
8c
9c
10c
o-OCH3
p-NO2
m-OCH3
H
m-OCH3
m-OCH3
p-OCH3
H
o-OCH3
a
Aldehyde, 1.0 mmol; aniline, 1.1 mmol; ketone, 1.5 mmol;
b
Cp2TiCl2, 0.10 mmol; POAP, 10 mg; 25 °C; 6 h. Isolated yields.
c
Aldehyde, 1.0 mmol; aniline, 1.1 mmol; ketone, 1.5 mmol;
Cp2TiCl2, 0.10 mmol; POAP, 10 mg; 50 °C; 6 h.
A proposed cooperative catalytic cycle is outlined in Fig. 6.
Titanocene dichloride I is activated by POAP and transformed
into heterogeneous catalyst II. The incoming ketone is
deprotonated, in which the enolate is accelerated as the car-
bonyl coordinates to oxophile Ti. Then, the imine is activated
by protonation with a Brønsted acid.13 The key step of the
With the optimized conditions in hand, the scope and
limitation of the new catalysis system were evaluated with a
range of aromatic aldehydes, amines and ketones having
Table 3 Mannich reactions of aliphatic ketones catalyzed by the heterogeneous catalysta
Entry
R1
R2
R3
R4
Yieldb (%)
syn : antid
1
2
3
4
5
6
7
o-Cl
H
H
H
o-Cl
H
H
CH3
CH3
CH3
C2H5
C2H5
C2H5
C2H5
H
CH3
CH3
CH3
H
H
H
H
H
H
H
75
80
76
77
90
85
67
86
72
67
37 : 63
44 : 56
36 : 64
None
None
None
None
None
None
None
m-Cl
m-CH3
H
H
m-CH3
o-OCH3
H
H
H
H
H
8c
9c
10c
m-NO2
o-OCH3
H
H
a
b
c
Aldehyde, 1.0 mmol; aniline, 1.1 mmol; ketone, 1.5 mmol; Cp2TiCl2, 0.10 mmol; POAP, 10 mg; 50 °C; 6 h. Isolated yields. Aldehyde, 1.0
mmol; aniline, 1.1 mmol; ketone, 27.0 mmol; Cp2TiCl2, 0.10 mmol; POAP, 10 mg; 25 °C; 6 h. d Determined by 1H NMR.
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Lewis acid and a Brønsted acid supporter was developed. The
catalyst successfully catalyzed the three-component Mannich
reactions of both aromatic and aliphatic ketones in excellent
yields. After recycling for five times, the catalytic efficiency of
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Acknowledgements
This work was supported by the 111 Project (B14041) and the
National Natural Science Foundation of China (21271124,
21302118, 21371112 and 21171112).
This journal is © The Royal Society of Chemistry 2015
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