Merging supramolecular catalysis and aminocatalysis: Amino-appended β-cyclodextrins (ACDs) as efficient and recyclable supramolecular catalysts for the synthesis of tetraketones

Article abstract of DOI:10.1039/c6ra01002d

Well-designed amino-appended β-cyclodextrins (ACDs) with an amino side chain of different lengths at the primary face of β-CD were synthesized and employed in the catalytic synthesis of a series of tetraketones as supramolecular catalysts in water for the first time. Yields of 58-97% were obtained with up to 30 examples of substrate. The catalyst could be recycled easily, while a 92% yield and 84% rate of catalyst recovery could be achieved after 8 cycles of catalyst recycling. Moreover, a catalytic mechanism merging supramolecular catalysis and aminocatalysis could be proposed through detailed 1D and 2D NMR, ESI-MS and Job plot analyses. This protocol retained the promising characteristics of ambient temperature, green medium, simple operation, broad substrate scope, excellent yields, superb catalyst recycling performance and unique catalytic mechanism.

Full text of DOI:10.1039/c6ra01002d

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PAPER
Merging supramolecular catalysis and
aminocatalysis: amino-appended b-cyclodextrins
(ACDs) as efficient and recyclable supramolecular
catalysts for the synthesis of tetraketones†
Cite this: RSC Adv., 2016, 6, 22034
*
Yufeng Ren, Bo Yang and Xiali Liao
Well-designed amino-appended b-cyclodextrins (ACDs) with an amino side chain of different lengths at the
primary face of b-CD were synthesized and employed in the catalytic synthesis of a series of tetraketones as
supramolecular catalysts in water for the first time. Yields of 58–97% were obtained with up to 30 examples
of substrate. The catalyst could be recycled easily, while a 92% yield and 84% rate of catalyst recovery could
be achieved after 8 cycles of catalyst recycling. Moreover, a catalytic mechanism merging supramolecular
catalysis and aminocatalysis could be proposed through detailed 1D and 2D NMR, ESI-MS and Job plot
analyses. This protocol retained the promising characteristics of ambient temperature, green medium,
simple operation, broad substrate scope, excellent yields, superb catalyst recycling performance and
unique catalytic mechanism.
Received 12th January 2016
Accepted 16th February 2016
DOI: 10.1039/c6ra01002d
www.rsc.org/advances
Due to the biological and chemical importances of tetraketones,
synthesis of such molecules has provoked more and more interests
Introduction
of chemists. Varies of synthetic methods were reported involving
Tetraketones are organic multifunctional molecules with four
carbonyl groups. Since the rst synthesis of tetraketones reported
by Merling in 1894,1 they have exhibited important biological
activities such as tyrosinase inhibition,2 lipoxygenase inhibition3,4
and antioxidant activities.3–5 In addition to that, tetraketones have
been frequently used as important precursors for the synthesis
of biologically important heterocyclic compounds such
as xanthenediones6 and acridinediones (Scheme 1).7–10
Scheme 1 Tetraketone and its derivatives.
Faculty of Life Science and Technology, Kunming University of Science and Technology,
Kunming, 650500, China. E-mail: xlliao@yahoo.com
† Electronic supplementary information (ESI) available: Spectral data of catalysts
and products. See DOI: 10.1039/c6ra01002d
Fig. 1 The structure of ACDs.
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pyridine,2 TEAB,3 In(OTf),3,5 metal hydroxides,11,12 L-proline,13 and aminocatalysis by construction of amino-appended b-CD
molecular iodine,14 HClO4–SiO2,15 nickel nanoparticles,16 choline (ACD) catalysts.
chloride17 and nano SiO2Cl (ref. 18) as catalysts or without any
Recently, b-CD catalysts modied with amino groups were
catalyst.19 Nevertheless, more efficient and environmentally benign employed in catalytic reactions such as oxidation,47 addi-
approaches to tetraketones are still in demand.
tion,48–51 selective protection of amines,52 cross-couplings53,54
Cyclodextrins (CDs) are a family of oligosaccharides which and synthesis of heterocyclic compounds.55–57 However, the
are usually composed of 6, 7 or 8 D-glucose monomers linked by types of amino-containing groups appended to b-CD remain
a-1,4-glycosidic bonds, referred to as a-, b- and g-CD respec- very limited to date, which has severely hampered their appli-
tively.20,21 In terms of their virtues of aqueous solubilities, low cations. Thus newly designed ACDs are in urgent need and are
toxicities and biodegradability, CDs are widely utilized in of great challenge. Considering the potential unique reaction
chemical, food, cosmetics and pharmaceutical elds.22–25 CDs mode inside the CD cavity accompanied by possible self-
have hydrophilic outer shell and hydrophobic inner cavity, inclusion between CD and amino side chains of appropriate
which could encapsulate guest molecules to form host–guest lengths58 and its impact on catalytic performance, ACDs (Fig. 1)
inclusion complexes. Water insoluble drug molecules could with amino side chains of different lengths were designed and
improve their physicochemical properties such as water solu- synthesized and their performances on catalytic synthesis of
bility, stability, bioavailability and even targeted drug delivery tetraketones were evaluated.
performance by formation of inclusion complexes with
CDs.26–33 In the eld of organic synthesis, CDs also play
a remarkable role as supramolecular catalysts in various cata-
lytic transformations such as oxidation, reduction, hydrolysis
and condensation, etc.34–41 Among CD catalysts, b-CD is the
Results and discussion
The ACDs were prepared by concise procedures as shown in
Scheme 2. Mono-6-(4-tolunesulfonyl)-6-deoxy-b-CD (TsCD) was
rst synthesized using 4-tolunesulfonyl chloride (TsCl) in an
aqueous solution of sodium hydroxide. Catalyst a0 was ob-
tained via a two-step sequence of azide replacement and then
Staudinger reduction from TsCD. On the other hand, catalysts
a1–a3 were prepared by nucleophilic substitution on TsCD with
specic amino compounds.
most popular one due to its readiest availability. However,
catalytic reactions using native b-CD have been severely limited
by its relatively low water solubility and functional homoge-
neity. Chemical modication of b-CD has emerged as an
effective approach to addressing this issue. Inspired by the
powerful organocatalysis with amines in recent decades,42–46 we
designed to combine the power of supramolecular catalysis
Scheme 2 Preparation of ACDs.
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The obtained ACDs were subsequently thrown in the catalytic likely to react with 4-nitrobenzaldehyde by condensation inside
synthesis of tetraketones. The optimization of reaction condi- the cavity of a3.
tions was performed with benzaldehyde and dimedone in water
In order to further explore the possible interacting mode of
at room temperature (Table 1). b-CD could give the highest yield catalyst a3 with substrates, the ROESY of the reaction mixture of
(73%) among a-, b- and g-CD with a 5 mol% catalyst loading a3/4-nitrobenzaldehyde/dimedone was recorded in D2O (Fig. 2).
(entries 2–4), equaling to that without no catalysts (entry 1). It showed appreciable correlation of aromatic protons (Ho, Hm)
Moderate yields were obtained when alkali metal salts (entries of 4-nitrobenzaldehyde with inner protons (H-3, H-5) of a3,
5–7) or ammonium phase-transfer catalysts (entries 8 & 9) were namely, Hm correlated with both H-3 and H-5, while Ho only
used, while natural amino acids gave only low to moderate correlated with H-3 (Fig. 2(A)). Considering that H-3 is located at
yields (entries 10–12). When ACDs were employed in this reac- the side of the secondary face of a3, this suggested the probably
tion, yields were promoted signicantly, up to 81%, 80%, 90% spatial layout of 4-nitrobenzaldehyde in the cavity of a3 with the
and 92% with catalysts a0–a3, respectively (entries 13–16). carbonyl group near to the secondary face of a3. Besides, there
Neither increasing nor decreasing the catalyst loading of a3 (to were signicant correlations between the ethylene protons (H-
2% or 10%) did bring benet to the yield (entries 17 & 18). en) of the amino side chain of a3 with H-3 and H-5 (Fig. 2(B)),
However, it rose to 96% when reducing the reaction time from 5 which were consistent with that of native a3 (see ESI†). This
h to 1 h (entry 19), and fell down to 79% when further indicated that the amino side chain inserted inside the cavity of
decreasing to 0.5 h (entry 20). Noticeably, the reaction temper- a3 during the reaction.
ature was found to play a crucial role on this reaction for the
Furthermore, electrospray ionization mass spectrometry
yield declined sharply as cooled to 0 ꢀC (entry 21), which could (ESI-MS) analysis of a3/4-nitrobenzaldehyde complex was used
be attributed to the decreased water solubility of a3 at such a low
temperature. On the contrary, moderate to good yields could be
obtained at higher temperatures (entries 22 & 23). Signicant
solvent effects were also observed while it gave 40% and 92%
yields in ethanol and DMF respectively (entries 24 & 25), as DMF
was normally a superior solvent like water for ACDs.
Table 1 The optimization of reaction conditionsa
The best catalytic potency of catalyst a3 in water could be
supported by the evidence that it had superior water solubility
of up to 656.9 mg mLꢁ1, which was also the best among ACDs
(see ESI†).
With the optimized conditions in hand, the substrate scope
was explored (Table 2). Reaction of dimedone with substituted
benzaldehydes with either electro-donating or withdrawing
groups all gave excellent yields of expected products (85–95%,
entries 2–15), as well as naphthaldehyde and heterocyclic
aromatic aldehydes (92–96%, entries 16–18). Two benzenedi-
carboxaldehydes were also screened and both gave high yields
(entries 19 & 20). Aliphatic aldehydes including acyclic and
cyclic ones were also found to be expedient substrates for this
reaction (92–97%, entries 21–27). Besides, 7-uoroisatin as an
aldehyde analogue gave moderate yield (entry 28). Moreover,
reactions of benzaldehyde with 1,3-cyclohexanedione or
4-hydroxy-6-methyl-2H-pyran-2-one gave very good yields
(entries 29 & 30) as well.
Entry
Catalyst (mol%)
Time (h)
Temp (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
8
None
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
1
0.5
1
1
1
1
1
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
0
73
43
73
41
53
60
63
72
76
75
22
58
81
80
90
92
89
90
96
79
18
94
81
40
92
a-CD (5)
b-CD (5)
g-CD (5)
NaCl (5)
NaBr (5)
KBr (5)
TBACc (5)
TEAId (5)
L-Proline (5)
L-Cysteine (5)
L-Aspartic acid (5)
a0 (5)
a1 (5)
a2 (5)
a3 (5)
a3 (2)
a3 (10)
a3 (5)
a3 (5)
a3 (5)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24e
25f
The reaction mechanism was then extensively studied by
spectroscopic analyses. The formation of inclusion complexes
1
of ACDs with substrates was demonstrated by H NMR spectra
of a3, a3/4-nitrobenzaldehyde complex and freeze-dried reac-
tion mixture of a3/4-nitrobenzaldehyde/dimedone in D2O
(Table 3). It was observed that downeld shis of H-3 (0.011
ppm) and H-5 (0.004 ppm) protons of a3/4-nitrobenzaldehyde
complex (B) occurred compared to that of a3 (A), which indi-
cated the formation of inclusion complex of 4-nitro-
benzaldehyde with a3. Further study on the 1H NMR spectra of
the freeze-dried reaction mixture of a3/4-nitrobenzaldehyde/
dimedone (C) revealed that there were signicant upeld
shis of H-3 (0.057 ppm), H-5 (0.088) and H-6 (0.034 ppm)
compared to that of a3 (A). This indicated that dimedone was
a3 (5)
a3 (5)
a3 (5)
a3 (5)
55
80
r.t.
r.t.
a
General reaction conditions: benzaldehyde (1 mmol), dimedone
b
c
(2.10 mmol), and water (5 mL) at r.t. Isolated yield. TBAC ¼
d
tetrabutylammonium chloride. TEAI ¼ tetraethylammonium iodide.
e
Ethanol as the solvent. f N,N-Dimethylformide (DMF) as the solvent.
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Table 2 Substrate scopea
Mp (ꢀC)
Obs.
Entry
Aldehyde
1,3-Diketone
Time (h)
Product
Yieldb (%)
Lit.
1
2
3
4
5
6
7
8
C6H5CHO (1a)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
1
1
5
5
2
2
2
2
2
2
1
2
1
1
1
1
1
1
5
5
1
1
5
1
1
1
1
5
2
2
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
3t
3u
3v
3w
3x
3y
3z
3aa
3bb
3cc
3dd
96
90
95
91
93
91
93
96
94
87
94
85
96
93
95
96
93
92
97
90
95
92
94
97
96
94
95
58
96
90
205–207
135–136
243
196–197
143
204 (ref. 16)
132–133 (ref. 62)
248–250 (ref. 3)
187–189 (ref. 59)
138 (ref. 62)
186–189 (ref. 18)
146–148 (ref. 5)
189–191 (ref. 15)
196–197 (ref. 60)
146–148 (ref. 18)
190–192 (ref. 18)
—
4-Me-C6H4CHO (1b)
3-OH-C6H4CHO (1c)
4-OH-C6H4CHO (1d)
4-OMe-C6H4CHO (1e)
3,4-(OMe)2-C6H3CHO (1f)
2,5-(OMe)2-C6H3CHO (1g)
3,4,5-(OMe)3-C6H2CHO (1h)
3-OMe-4-OH-C6H3CHO (1i)
4-Cl-C6H5CHO (1j)
183
154–156
195–196
206–209
147–148
193–195
194
191–193
202–205
195
9
10
11
12
13
14
15
16
17
18
19c
20c
21
22
23
24
25
26
27
28
29
30
4-F-C6H4CHO (1k)
3,4-Cl2-C6H3CHO (1l)
2-NO2-C6H4CHO (1m)
3-NO2-C6H4CHO (1n)
4-NO2-C6H4CHO (1o)
2-Naphthaldehyde (1p)
3-Pyridinecarboxaldehyde (1q)
2-Thenaldehyde (1r)
Terephthalaldehyde (1s)
Isophthalaldehyde (1t)
HCHO (1u)
CH3CHO (1v)
HCOCO2Et (1w)
Butyraldehyde (1x)
Isobutyraldehyde (1y)
3-Methyl butanal (1z)
Cyclohexanaldehyde (1aa)
7-Fluoroisatin (1bb)
C6H5CHO (1a)
188–190 (ref. 3)
197–198 (ref. 59)
190 (ref. 16)
—
218
98
—
160–162
322–323
303–305
188–190
185–186
100–101
120–122
153
170–171
185–186
308
213–215
174–175
156–157 (ref. 61)
—
—
192–193 (ref. 60)
182–184 (ref. 60)
—
130 (ref. 16)
153–154 (ref. 3)
—
—
—
207–208 (ref. 19)
167–169 (ref. 19)
C6H5CHO (1a)
a
b
General reaction conditions: aldehyde (1 mmol), diketone (2.10 mmol), a3 (0.05 mmol) in water (5 mL) at room temperature. Isolated yields.
Dimedone: 4.20 mmol.
c
to elucidate the host–guest interactions between a3 and 4-
In addition, the inclusion mode of inclusion complexation of
nitrobenzaldehyde. A quasi-molecular ion of 1396.5350 (m/z) a3/4-nitrobenzaldehyde was studied by Job's method.63,64
was detected, which referred to the dehydration condensation Within the concentration scope, the Job plot showed
product between a3 and 4-nitrobenzaldehyde (calcd: m/z ¼ a maximum at a molar fraction of 0.5 (Fig. 4), which
1396.5360 for [M + H]+) (Fig. 3).
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1
Table 3 H NMR spectra (500 MHz, in D2O at 25 ꢀC) of (A) a3, (B) a3/4-
nitrobenzaldehyde complex, and (C) freeze-dried reaction mixture of
a3/4-nitrobenzaldehyde/dimedone
Fig. 3 ESI-MS of a3/4-nitrobenzaldehyde complex.
Though more evidences were still needed to verify them, they
were surely ascribed to both non-covalent and covalent inter-
actions between the host and guest, which merged supramo-
lecular catalysis and aminocatalysis in this reaction.
d (ppm)
Possible reaction mechanism for the a3-catalyzed synthesis
of tetraketones was proposed based on the above information
(Scheme 3). It could be initiated by the formation of iminium
intermediate (1) from the dehydration condensation of 4-
nitrobenzaldehyde with a3 inside the cavity of a3, followed by
the nucleophilic addition of a dimedone. The resultant adduct
subsequently underwent a deamination reaction to form the a,
b-unsaturated diketone (2) by a H-transfer, towards which
a Michael addition was carried out by another dimedone to
furnish the tetraketone.
Protons
A
B
C
H-3 of a3
H-5 of a3
H-6 of a3
3.740
3.655
3.681
3.751
3.659
3.732
3.683
3.567
3.647
indicated a 1 : 1 inclusion stoichiometry between a3 and 4-
nitrobenzaldehyde.
Thus the inclusion mode of a3/4-nitrobenzaldehyde could be
demonstrated as patterns of 1 : 1 or 2 : 2 (Fig. 5(A) and (B)).
The recycling performance of catalyst a3 was evaluated with
benzaldehyde, dimedone and a3 in water as a model reaction
Fig. 2 ROESY of reaction mixture of a3/4-nitrobenzaldehyde/dimedone in D2O at 25 ꢀC.
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(Scheme 4). Almost pure product tetraketone could be obtained
by ltration aer the completion of the reaction, followed by
washing the lter cake with water. The ltrate containing
catalyst a3 could be reused directly aer removal of tetraketone
without any extraction of a3 from it, without signicant loss of
yield even aer 8 cycles (Fig. 6). Moreover, the catalyst could be
easily recovered with a rate up to 84% aer 8 cycles from the
ltrate by washing with some ethyl acetate followed by evapo-
ration of the aqueous phase in vacuo.
Moreover, the synthetic application of this protocol was
demonstrated by the gram-scale preparation of xanthendione
and acridinedione from tetraketone (Scheme 5). Xanthenedione
4a could be obtained by reuxing in acetic acid with 89% yield
while acridinedione 4b was synthesized in aqueous ammonium
acetate solution with 85% yield.
Fig. 4 Job plot for the a3/4-nitrobenzaldehyde inclusion system at
l ¼ 267.5 nm ([a3] + [4-nitrobenzaldehyde] ¼ 8.0 ꢂ 10ꢁ5 M) in
aqueous Na2CO3–NaHCO3 buffer (pH ¼ 10.5).
Conclusions
In summary, an efficient one-pot synthesis of tetraketones was
established by supramolecular catalysis with amino-appended b-
cyclodextrins in water for the rst time in this work. Yields of 58–
97% could be obtained with up to 30 examples of substrate. The
catalyst could be recycled easily without signicant loss of effi-
cacy and with high recovery rate aer 8 cycles. Moreover, the
reaction mechanism was elucidated extensively by spectroscopic
analyses, which indicated a catalytic mode of collaboration of
supramolecular catalysis and aminocatalysis. This protocol
retained excellences of simple operations, environmentally
benign conditions, a broad substrate scope, high yields, superb
catalyst recycling performance and unique catalytic mechanism.
Experimental
General
Fig. 5 Possible inclusion mode of a3/4-nitrobenzaldehyde.
Melting points (mp, uncorrected) were determined on an RY-1
instrument (Shanghai, China). IR spectra were recorded on
Scheme 3 Possible mechanism for a3-catalyzed synthesis of tetraketones.
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Scheme 4 Process of catalyst (a3) recycling.
(Bruker, Germany). Other reagents were all of chemical purity
and were used as received.
Typical synthetic procedure of ACDs: synthesis of a3
Mono-6-(4-tolunesulfonyl)-6-deoxy-b-CD (TsCD, 3.0 g) was dis-
solved with stirring in triethylenediamine (TEA, 20 mL) under
nitrogen atmosphere with the evolution of heat the solution (it
ꢀ
reached approximately 80 C) for 12 h. Aer the completion of
reaction, the solution was cooled to room temperature and was
added dropwise into acetone (400 mL). White precipitate was
collected by suction ltration, which could be further puried
by precipitation for 2–3 times (TLC monitored). Pure a3 was
obtained as pale yellow powder (2.5 g, 85%). Mp: 283 ꢀC
(decomp.); 1H NMR (400 MHz, D2O) d 2.85–2.61 (m, 12H,
ethylene of triethylenetetramine), 3.89–3.38 (m, H-2, 3, 4, 5, 6 of
CD), 5.08 (s, 7H, H-1 of CD). HRMS (ESI) m/z: calcd for
Fig. 6 Yields of catalyst (a3) recycling.
C
48H87N4O34 [M + H]+: 1263.5196, found [M + H]+: 1263.5194.
General procedure for the preparation of tetraketones
Aldehyde (1 mmol) suspended in water (5 mL) was stirred for 1
min, followed by the addition of a3 (0.05 mol). Aer stirring
constantly for 10 minutes, diketone (2.1 mmol) was added in
one portion. Aer the completion of reaction (monitored by
TLC), the resulted mixture was ltered by suction and the lter
cake was washed with cool water to obtain a fairly pure product,
which could be further puried by recrystallization from
ethanol.
Scheme 5 Gram-scale synthetic applications of tetraketone 3a.
Preparation of xanthenedione (4a)
Tetraketone 3a (2 g, 5.4 mmol) was added into acetic acid (20
mL) and was reuxed for 2 h. The reaction mixture was then
evaporated under reduced pressure and was poured into
crushed ice. The solid obtained by ltration was crystallized
from EtOH–H2O (8 : 2, v/v) to get pure 4a (1.69 g, 89%). Mp: 205
a Bio-Rad FTS-40 FT-IR spectrometer (Bio-Rad, USA). NMR
spectra were measured on a Bruker Avance DRX-500 or DRX-400
spectrometer (Bruker, Germany) at 298 K. HRESI-MS data were
recorded on a Bruker MicrOTOF Q-II mass spectrometer
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ꢀC; IR (KBr, cmꢁ1) 3061, 3031 (]C–H), 2956, 2874 (C–H), 1666
(C]O), 1460 (C]C); 1H NMR (500 MHz, CDCl3) d 7.30 (m, 2H,
Ar–H), 7.23 (t, J ¼ 7.6 Hz, 2H, Ar–H), 7.11 (t, J ¼ 7.3 Hz, 1H, Ar–
H), 4.77 (s, 1H), 2.48 (s, 4H, 2 ꢂ CH2), 2.22 (q, J ¼ 16.3 Hz, 4H, 2
ꢂ CH2), 1.12 (s, 6H, 2 ꢂ CH3), 1.01 (s, 6H, 2 ꢂ CH3); HRMS (ESI)
m/z: calcd for C23H26O3 [M + H]+: 351.1960, found [M + H]+:
351.1954.
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Preparation of acridinedione (4b)
A mixture of tetraketone 3a (2 g, 5.4 mmol) and ammonium
acetate (1.8 g, 24.0 mmol) in H2O (20 mL) was reuxed for 6 h.
Then the reaction mixture was cooled and was poured into
crushed ice. The solid obtained by ltration was puried by
recrystallisation from EtOH–H2O (8 : 2) to yield pure 4b (1.61 g,
85%). Mp: 279 ꢀC; IR (KBr) cmꢁ1 3283, 3210 (NH), 3064 (]C–H),
2959, 2874 (C–H), 1636 (C]O), 1480 (C]C); 1H NMR (500 MHz,
CDCl3) d 7.87 (s, 1H, NH), 7.35 (d, J ¼ 7.7 Hz, 2H, Ar–H), 7.20 (t, J
¼ 7.5 Hz, 2H, Ar–H), 7.08 (t, J ¼ 7.3 Hz, 1H), 5.11 (s, 1H), 2.23 (m,
8H, 4 ꢂ CH2), 1.08 (s, 6H, 2 ꢂ CH3), 0.96 (s, 6H, 2 ꢂ CH3);
HRMS (ESI) m/z: calcd for C23H27NO2 [M + Na]+: 372.1939, found
[M + Na]+: 372.1934.
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Preparation of a3/4-nitrobenzaldehyde complex
Catalyst a3 (0.1 mmol) was added in water (5 mL) and stirred
constantly to form a clear solution with the evolution of heat
(temperature of solution reached approximately 50 ꢀC). Then
a methanol solution of 4-nitrobenzaldehyde (0.1 mmol in 0.3
mL of methanol) was added dropwise followed by cooling to
room temperature with stirring. The mixture was subsequently
placed at 5 ꢀC for 12 h. It was ltered to remove any insolubles.
Dry powder obtained by rotary evaporation of the ltrate could
be subjected to spectroscopic analyses.
Recycling of catalyst a3
Aldehyde (1 mmol) suspended in water (5 mL) was stirred for 1
min, followed by the addition of a3 (0.05 mol). The mixture was
stirred constantly for 10 minutes, and then diketone (2.1 mmol)
was added in one portion. Aer the completion of reaction
(monitored by TLC), the resultant mixture was ltered by
suction and the lter cake was washed with the least amount of
water to obtain an almost pure product, which could be further
puried by rinsing with more water (about 50 mL) or by
recrystallization from ethanol. On the other hand, the next set
of substrates was directly added in the previously obtained
ltrate containing catalyst a3 and the mixture was allowed to
react to completion. Aer 8 cycles, the resultant ltrate was
washed with ethyl acetate (2 mL) followed by evaporation of the
aqueous phase in vacuo to retrieve the catalyst a3 (84%).
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Acknowledgements
The authors are grateful to the National Natural Science Foun-
dation of China (21362016) and Analysis & Testing Foundation
of Kunming University of Science and Technology (20150714)
for nancial supports.
This journal is © The Royal Society of Chemistry 2016
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