Poly(N-isopropylacrylamide-co-l-proline)-catalyzed Claisen-Schmidt and Knoevenagel condensations: Unexpected enhanced catalytic activity of the polymer catalyst

Article abstract of DOI:10.1039/c7ra09412d

The polymer catalyst is more effective than the corresponding monomer catalyst? Yes! The proline-modified polymer, poly(N-isopropylacrylamide-co-l-proline), was unexpectedly found to be more effective than the corresponding monomer l-proline catalyst in Claisen-Schmidt and Knoevenagel condensation reactions. ¹H NMR, GC analysis and control reactions revealed that this abnormal phenomenon might be attributed to an enhanced concentration of the reactant on the surface of the polymer catalyst, which might be due to adsorption of the reactants to the polymer through hydrogen-bonding of the proline moiety with the reactants. This new polymer catalyst was so robust that it could be reused at least 10 times without deactivation. The polymer-catalyzed method was rather tolerant of substrates bearing sensitive groups that are usually incompatible with conventional acid- or base-catalyzed methods, reducing the protection-deprotection steps of the substrates.

Full text of DOI:10.1039/c7ra09412d

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Poly(N-isopropylacrylamide-co-L-proline)-
catalyzed Claisen–Schmidt and Knoevenagel
condensations: unexpected enhanced catalytic
activity of the polymer catalyst†
ab
Cite this: RSC Adv., 2017, 7, 48214
Hao Zhang,‡ab Mengting Han,‡ab Tian Chen,a Lin Xuab and Lei Yu
*
The polymer catalyst is more effective than the corresponding monomer catalyst? Yes! The proline-
modified polymer, poly(N-isopropylacrylamide-co-L-proline), was unexpectedly found to be more
effective than the corresponding monomer L-proline catalyst in Claisen–Schmidt and Knoevenagel
condensation reactions. 1H NMR, GC analysis and control reactions revealed that this abnormal
phenomenon might be attributed to an enhanced concentration of the reactant on the surface of the
polymer catalyst, which might be due to adsorption of the reactants to the polymer through hydrogen-
bonding of the proline moiety with the reactants. This new polymer catalyst was so robust that it could
be reused at least 10 times without deactivation. The polymer-catalyzed method was rather tolerant of
substrates bearing sensitive groups that are usually incompatible with conventional acid- or base-
catalyzed methods, reducing the protection–deprotection steps of the substrates.
Received 24th August 2017
Accepted 3rd October 2017
DOI: 10.1039/c7ra09412d
rsc.li/rsc-advances
and powerful synthetic tools for the accessible catalyst, metal-
free conditions and high reaction selectivities. L-Proline is
Introduction
milder than traditional organic or inorganic acids or bases, and
may be more tolerant to sensitive functional groups in reaction
substrates. However, because L-proline is a cheap and abundant
natural chiral molecule, much attention has been paid to its
applications in asymmetric synthesis, while the design and
fabrication of proline-based catalysts for simple C]C bond
formation is so far not well documented. We have been inter-
ested in organocatalysis for a long time.5 Recently, we investi-
gated proline-based catalysts for C]C bond formation through
the Claisen–Schmidt and Knoevenagel condensations. During
the research, we designed and synthesized poly(N-iso-
propylacrylamide-co-L-proline), which is a proline-modied
polymer, and examined its catalytic activity in the reactions.
Herein, we wish to report our ndings.
C]C bond formation is an important subject in organic
synthesis for allowing carbon chain growth in building complex
large molecules.1 Among known methods, the reactions of
aldehydes with active C–H, such as the Claisen–Schmidt and
Knoevenagel condensations, are efficient tools to achieve this
objective.2 The transformations have good potential in indus-
trial application owing to the processes being of high atom
economy, and not generating waste other than water. However,
many of these reactions are catalyzed by acids or bases, which
are corrosive and intolerant to sensitive functional groups.
Thus, developing novel tolerant catalysts that allow the direct
use of sensitive substrates free of tedious protection–depro-
tection steps is still desirable to improve the synthetic
efficiency.
L-Proline is a kind of organocatalyst that can work under
mild conditions.3 It has been widely employed in many useful
organic reactions, such as the Michael addition, Mannich
reaction, Diels–Alder addition, aldol condensation and the
related domino/multi-component reactions,4 providing unique
Results and discussion
Using the Claisen–Schmidt condensation of benzaldehyde 1a
with acetone 2 to produce (E)-4-phenylbut-3-en-2-one 3a as the
template, a series of amino acids as catalysts and amines as
additives were initially examined (eqn (1)).
aInstitute of Pesticide, School of Chemistry and Chemical Engineering, School of
Horticulture and Plant Protection, Yangzhou University, Yangzhou, Jiangsu 225002,
China. E-mail: yulei@yzu.edu.cn
bJiangsu Yangnong Chemical Group Co. Ltd., Yangzhou, Jiangsu 225002, China
† Electronic supplementary information (ESI) available: Condition optimization
table, mechanism study details, product characterization, and 1H and 13C NMR
spectra of the products. See DOI: 10.1039/c7ra09412d
(1)
‡ Both authors contributed equally to this work.
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It was found that L-proline was a uniquely good catalyst for
the reaction and piperazine was the favourable additive, while
other amino acid catalysts or amine additives were less effec-
tive.6 Based on this experimental result, the polymer-supported
proline catalyst was then designed. As shown in Scheme 1,
esterication of the commercially available reagents 4 and 5
promoted by CF3SO3H/CF3CO2H rst afforded the (2S,4R)-4-
(acryloyloxy)pyrrolidine-2-carboxylic acid 6, which then led to
RSC Advances
Table 1 Catalyst evaluations for the Claisen–Schmidt condensations
of aldehydes with acetonea
3: yieldb/%
poly(N-isopropylacrylamide-co-L-proline)
8
through
a
co-
polymerization reaction with N-isopropylacrylamide (NIPA)
7.6,7 Time of ight mass spectrometer (TOF) analysis showed
that the polymer 8 had an average molecular weight of ca. 4.9 ꢀ
104 and 1H NMR analysis of the material indicated that the
molar ratio of the proline fragment was 12.3%.7
Entry
R (1)
L-Prolinec
Polymer 8
1
2
3
4
5
6
7
8
9
Ph (1a)
3a: 70 (53)
75
70
70
71
61
60
50
42
54
73
4-MeC6H4 (1b)
3-MeC6H4 (1c)
2-MeC6H4 (1d)
4-MeOC6H4 (1e)
4-ClC6H4 (1f)
3-ClC6H4 (1g)
2-ClC6H4 (1h)
4-FC6H4 (1i)
c-C6H11 (1j)
3b: 40, 52d, 55 (40)e, 53f
3c: 53 (42)e
3d: 47 (40)e
3e: 51 (45)e
Claisen–Schmidt condensation reactions catalyzed by L-
proline or polymer 8 were then performed simultaneously for
comparison (Table 1). Condition optimizations6 showed that
ethanol was a favourable solvent for the free L-proline-catalyzed
reactions, while the polymer 8-catalyzed reaction could be per-
formed in acetone without additional solvent. In the free L-
proline-catalyzed reactions, 4-methylbenzaldehyde 1b as an
electron-enriched substrate led to 3b in an even lower yield than
that of the reaction of the simple substrate 1a (entry 2 vs. 1). The
product yield was slightly enhanced at elevated reaction
temperatures and the reaction at 80 ꢁC afforded the highest
product yield at 55% (entry 2). Similarly, the electron-enriched
substrates 1c–e led to the related products 3c–e in moderate
yields (entries 3–5). Elevated reaction temperatures were also
required for the condensation of the electron-decient alde-
hydes 1f–i with acetone, affording 3f–i in 41–51% yields (entries
6–9). The aliphatic aldehyde 1j was a favourable substrate for
the reaction, giving 3j in 71% yield at room temperature (entry
10). The reactions catalyzed by polymer 8 were also examined.
Although the polymer 8-catalyzed reaction of 1a with acetone in
ethanol at 50 ꢁC could afford the desired product 3a in 77%
yield, for practical application considerations, we developed the
method without additional solvent, in which the excess acetone
could be easily recycled and reused in large-scale preparations.
Catalyzed by polymer 8, the reactions of substrates 1a–j with 2 at
50 ꢁC produced 3a–j smoothly. It was very interesting that
3f: 42, 51 (40)e
3g: 48 (36)e
3h: 41 (33)e
3i: 44 (34)e
10
3j: 71 (58)
a
For L-proline catalyzed reactions, 1 mmol of 1, 3 mmol of acetone 2,
0.03–0.05 mmol (see note c) of L-proline and 0.05 mmol of piperazine
were stirred in 1 mL of EtOH at 20–100 ꢁC (20 ꢁC without special
instruction) for 48 h; for polymer 8-catalyzed reactions, 1 mmol of 1,
30 mg of polymer 8 and 0.05 mmol of piperazine were stirred in 1 mL
b
of acetone 2 at 50 ꢁC for 48 h. Isolated yields of 3 based on 1.
c
Yields outside the brackets are for the reactions with 5 mol% of L-
proline catalyst; yields inside the brackets are for the reactions with
d
e
3 mol% of L-proline catalyst. Reaction at 40 ꢁC. Reaction at 80 ꢁC.
f
Reaction at 100 ꢁC.
although the proline loadings were reduced to 3 mol%, the
polymer 8-catalyzed Claisen–Schmidt condensations afforded
the products in yields higher than those of the free L-proline-
catalyzed reactions (entries 1–10). For comparison, reactions
with a reduced L-proline amount (3 mol%) were also conducted,
but resulted in even lower product yields (see yields inside of the
brackets).
Notably, the polymer-supported proline was tolerant to
acidic functional groups in the substrates. Catalyzed by
polymer-supported proline 8, 4-hydroxybenzaldehyde 1k and 3-
hydroxybenzaldehyde 1l in acetone led to 3k and 3l respectively
in moderate yields; the product yields decreased with L-proline
as the catalyst. The same reactions could not happen when
using Ca(OH)2 as the catalyst (Scheme 2).2c
Scheme 2 Catalyst evaluations for the reactions of a substrate with an
Scheme 1 Preparation of the polymer-supported proline catalyst 8.
acidic functional group.
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For substrate 1m, with an alkaline functional group, the
polymer-supported proline-catalyzed reaction led to the desired
product 3m in 50% yield, while the reaction catalyzed by free L-
proline led to 3m in only 20–23% yields; the reaction could not
happen with catalytic H2SO4 (Scheme 3).
Moreover, for substrate 1n, that contained both acidic and
alkaline groups, the polymer-supported proline-catalyzed reac-
tion led to the desired product 3n in 50% yield, which was
higher than that of the reaction catalyzed by free L-proline. In
contrast, neither of the acid nor base catalysts were effective for
the same reaction (Scheme 4).
As a heterogeneous catalyst, polymer 8 could be easily recy-
cled and reused in the next round of reaction. It was impressive
that the catalyst was so robust that it could be reused for at least
10 times without deactivation (Fig. 1).
Fig. 1 Recycle and reuse of the polymer-supported proline catalyst 8
in the reaction of 1a with acetone to produce 3a.
The proline catalysts were also efficient for Knoevenagel
condensations (Table 2). Reactions catalyzed by polymer 8 could
even use water as the solvent, while the reactions with free L-
proline as the catalyst were still performed in ethanol. Catalyzed
by polymer 8, the condensation of benzaldehyde 1a with
malononitrile 9 afforded 10a in 75% yield; by contrast, the same
reaction catalyzed by L-proline led to 10a in only 48–50% yield
(entry 1). For the electron-enriched substrate 1b, free L-proline
was better than polymer 8 (entry 2). The two catalysts were
similarly reactive for the electron-decient substrate 1f, giving
10c in 68–74% and 78% yields respectively (entry 3). The
heterocycle-contained substrate 1m was also favourable for the
reaction to produce 10d in moderate to good yields (entry 4).
Interestingly, polymer 8 was better than L-proline in the reaction
of substrate 1n, which bears a bulky group (entry 5). In the
Table 2 Catalyst evaluations for the Knoevenagel condensations of
aldehydes with malononitrilea
10: yieldb/%
Entry
R (1)
L-Prolinec
Polymer 8
1
2
3
4
5
6
Ph (1a)
10a: 50 (48)
10b: 82 (71)
10c: 74 (68)
10d: 88 (79)
10e: 68 (60)
10f: 50 (37)
75
70
78
75
83
19
4-MeC6H4 (1b)
4-ClC6H4 (1f)
2-C4H3S (1m)
2-C10H7 (1n)
c-C6H11 (1j)
a
For L-proline catalyzed reactions, 1 mmol of 1, 1 mmol of 9, 0.03–
0.05 mmol of L-proline (see note c) and 0.05 mmol of piperazine were
stirred in 1 mL of EtOH at 30 ꢁC for 48 h; for polymer 8-catalyzed
reactions, 1 mmol of 1, 1 mmol of 9, 30 mg of polymer 8 and
0.05 mmol of piperazine were stirred in 1 mL of water at 50 ꢁC for
b
c
48 h. Isolated yields of 10 based on 1. Yields outside of the
brackets are for the reactions with 5 mol% of L-proline catalyst; yields
inside of the brackets are for the reactions with 3 mol% of L-proline
catalyst.
Scheme 3 Catalyst evaluations for the reactions of a substrate with an
alkaline functional group.
reaction of the aliphatic aldehyde 1j with malononitrile, L-
proline was the preferable catalyst, giving 10f in 37–50% yield
(entry 6).
Plausible mechanisms were then proposed on the basis of
the above experimental results as well as references
(Scheme 5).8,9 In the Claisen–Schmidt condensations, the
proline catalysts, whether small molecule or polymer, rst
condense with acetone to produce 11, which leads to the reso-
nant intermediates 12a–b aer dehydration.8 Furthermore,
condensation of the piperazine additive with aldehyde 1
furnishes the intermediate 13,9 which reacts with 12a–b to
produce the ion pair 14.8a The chemical structure of the amino
acid catalyst is an important factor that facilitates the contact of
the reactants.6,8b Rearrangement in 14 releases piperazine and
Scheme 4 Catalyst evaluations for the reactions of a substrate with
both acidic and alkaline functional groups.
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Scheme 6 Control reactions.
was proposed that the reactants were enriched around the
catalyst reaction sites from the solution through hydrogen
bonds with the proline moieties in polymer 8 and this might
have resulted in an elevated local reactant concentration, which
facilitated the reaction to produce 3 in yields higher than those
of the reactions catalyzed by free L-proline.
In the Knoevenagel condensations, the prolines rst react
with malononitrile 9 to produce the intermediate 18, which
could be well stabilized by an intramolecular hydrogen bond
with the adjacent pyrrolidine NH in the proline catalysts (eqn
(2)).11 The reaction of 18 with the intermediate 13 leads to 19
and the regeneration of the proline catalyst as well as the
piperazine additive (eqn (3)).11 Dehydration of 19 generates the
nal product 10 (eqn (4)). Although the mechanisms remain to
be fully claried and alternative processes may also exist due to
the complex catalyst system, Scheme 5 and eqn (2)–(4) should
be the most likely mechanisms based on the above experi-
mental results as well as the related references.
Scheme
Schmidt condensations.
5 A possible mechanism for proline-catalyzed Claisen–
leads to 15, which provides 16 aer hydration.8a The interme-
diate 16 could decompose to 17 and regenerate the proline
catalyst. Dehydration of 17 affords a,b-unsaturated ketones 3 as
the nal products.
In 1H NMR tests, in both CDCl3 and CD3OD solvents, the
chemical shis of the aldehyde-H moved to the low eld region
aer adding L-proline into the benzaldehyde sample, indicating
interaction of the proline moieties with the reactant (Fig. 2).6,10
GC analysis experiments showed that the polymer 8 could
enrich the reactants around its reaction sites (see Experimental
vide infra).6
(2)
Moreover, the control reaction of 1b with 2 at an elevated
reactant concentration produced 3b in increased yield
(Scheme 6). On the basis of the above experimental results, it
(3)
(4)
Conclusions
In conclusion, we reported the Claisen–Schmidt and Knoeve-
nagel condensations catalyzed by proline catalysts. It is inter-
esting that the polymer-supported proline catalyst is even more
active than free L-proline in many cases. 1H NMR and GC
Fig. 2 Chemical shifts of the aldehyde-H signal before and after
adding L-proline in CDCl3 or CD3OD.
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analysis as well as the control experiments indicated that the
proline-modied polymer might enrich the reactant around its
reaction sites through hydrogen bonds and enhance the local
reactant concentration to facilitate the reactions. The proline-
modied polymer was impressively robust and could be recy-
cled and reused many times without deactivation. It is also
tolerant to sensitive functional groups, allowing the direct use
of related substrates free of protection–deprotection steps and
largely improving the synthetic efficiency.
Detailed procedure for the preparation of the polymer poly(N-
isopropylacrylamide-co-L-proline) 8 (Scheme 1)
To a 50 mL Schlenk tube, 2.06 g of N-isopropylacrylamide 7
(18.2 mmol), 0.68 g of 6 (3.1 mmol), 15 mL of DMF and 52.8 mg
of AIBN (0.32 mmol) were added. The mixture was heated at
ꢁ
70 C under N2 protection for 8 h and cooled to room temper-
ature and then slowly dropped into a quickly stirred 150 mL of
ether. The precipitated polymer 8 was isolated by centrifuge and
dissolved in water. The liquid pH was adjusted using Et3N to 6–
7 and re-precipitated using 150 mL of ether. The polymer 8 was
washed using methanol and ether and dried under vacuum at
ꢁ
50 C overnight.
Experimental
General methods
Chemicals were purchased from reagent merchants with
purities more than 98% and were directly used as received.
Solvents were analytically pure (AR) and directly used without
any special treatment. Melting points were measured using
a WRS-2A digital instrument. IR spectra were measured on
a Bruker Tensor 27 Infrared spectrometer. 1H and 13C NMR
spectra were recorded on a Bruker Avance 600/400 instrument
(600 or 400 MHz for 1H and 150 or 100 MHz for 13C NMR
spectroscopy). Chemical shis in the 1H NMR spectroscopy
were referred to internal Me4Si (0 ppm) and J-values are shown
in Hz. GC analyses were performed on an Agilent 7890B gas
chromatograph with an FID detector using a J & W DB-1 column
(10 m, 0.1 mm I.D.). Mass spectra were measured on a Shi-
madzu GCMS-QP2010 Ultra spectrometer (EI).
Typical procedure for the Claisen–Schmidt condensations
catalyzed by L-proline (Table 1)
To a 15 mL reaction tube, 5.8 mg of L-proline (0.05 mmol) and
4.3 mg of piperazine (0.05 mmol) were added. The tube was
then charged with N2 and a solution of 1 mmol of aldehyde 1
and 3 mmol of acetone in 1 mL of ethanol was injected using
a syringe. The mixture was stirred at the related temperature
(see Table 2 in text) for 48 h. The solvent was removed by
distillation under reduced pressure. The residue could be iso-
lated by preparative TLC (eluent: petroleum ether/EtOAc 10 : 1).
Typical procedure for the Claisen–Schmidt condensations
catalyzed by polymer 8 (Table 1)
To a 15 mL reaction tube, 30 mg of polymer 8 (containing
0.03 mmol of proline moiety) and 4.3 mg of piperazine (0.05
mmol) were added. The tube was then charged with N2 and
a solution of 1 mmol of aldehyde 1 in 1 mL of acetone was
Detailed procedure for the screening of the catalysts and
additives (Table S1 in ESI†)
To a 15 mL reaction tube, 0.05 mmol of amino acid catalyst and
0.05 mmol of amine additive were added. The tube was then
charged with N2 and a solution of 1 mmol of benzaldehyde 1a
and 3 mmol of acetone 2 in 1 mL of ethanol was injected using
a syringe. The mixture was stirred at 20 ꢁC for 48 h. The solvent
was removed by distillation under reduced pressure. The
product 3a could be isolated by preparative thin layer chroma-
tography (TLC, eluent: petroleum ether/EtOAc 10 : 1). The
reaction condition screenings were performed in a similar way
(Table S2 in ESI†).
ꢁ
injected using a syringe. The mixture was stirred at 50 C for
48 h. The solvent was removed by distillation under reduced
pressure. The residue could be isolated by preparative TLC
(eluent: petroleum ether/EtOAc 10 : 1).
Detailed procedure for the catalyst recycle and reuse in the
Claisen–Schmidt condensation of 1a with acetone catalyzed
by polymer 8 (Fig. 1)
To a 35 mL reaction tube, 0.15 g of polymer 8 (containing
0.15 mmol of proline moiety) and 21.5 mg of piperazine (0.25
mmol) were added. The tube was then charged with N2 and
a solution of 5 mmol of 1a in 3 mL of acetone was injected using
a syringe. The mixture was stirred at 50 ꢁC for 48 h and cooled to
Detailed procedure for the preparation of the monomer 6
(Scheme 1)
To a 250 mL three-necked ask equipped with a magnetic bar, room temperature. Petroleum ether was added to precipitate
60 mL of CF3CO2H and 16.42 g of (2S,4R)-4-hydroxypyrrolidine- the polymer 8. Aer standing for 2 h, the liquid was removed
2-carboxylicꢁacid 4 (125 mmol) were added. The mixture was and the polymer 8 was washed with petroleum ether. The
stirred at 0 C and 2 mL of CF3SO3H was added (22.9 mmol). solvent of the combined organic solutions was removed by
Aer 5 min, 20.31 mL of acryloyl chloride 5 was injected. The distillation under reduced pressure and the residue was sub-
mixture was stirred at room temperature for 2 h and 40 min and jected to preparative TLC to produce 3a (eluent: petroleum
then cooled by ice water. 180 mL of ether was slowly added to ether/EtOAc 10 : 1). The recycled polymer 8 was dried under
precipitate the product 6, which was isolated by ltration and vacuum at 50 ꢁC for 24 h and could be reused as a catalyst in the
washed by ether and dried under vacuum for 12 h (yield 62%). next round of reaction.
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575 cmꢂ1
;
1H NMR (600 MHz, CDCl3, TMS): d 7.47 (d, J ¼
Typical procedure for the Knoevenagel condensations
catalyzed by L-proline (Table 2)
16.2 Hz, 1H), 7.41 (d, J ¼ 7.8 Hz, 2H), 7.17 (d, J ¼ 7.8 Hz, 2H),
6.66 (d, J ¼ 16.2 Hz, 1H), 2.34 (s, 6H, 2CH3); 13C NMR (150 MHz,
CDCl3): d 198.4, 143.5, 141.0, 131.7, 129.7, 128.3, 126.3, 27.4,
21.5; MS (EI, 70 eV): m/z (%) 160 (14) [M+], 145 (100), 115 (48),
117 (35); known compound.2c
To a 15 mL reaction tube, 5.8 mg of L-proline (0.05 mmol) and
4.3 mg of piperazine (0.05 mmol) were added. The tube was
then charged with N2 and a solution of 1 mmol of aldehyde 1
and 1 mmol of malononitrile 9 in 1 mL of ethaꢁnol was injected
using a syringe. The mixture was stirred at 30 C for 48 h. The
solvent was removed by distillation under reduced pressure.
The residue could be puried by preparative TLC (eluent:
petroleum ether/EtOAc 10 : 1).
(E)-4-(m-Tolyl)but-3-en-2-one 3c. 112.2 mg, 70%; oil; IR
(lm): 3027, 2923, 1674, 1607, 1359, 1254, 979, 781, 693 cmꢂ1
;
1H NMR (400 MHz, CDCl3, TMS): d 7.48 (d, J ¼ 16.0 Hz, 1H), 7.34
(d, J ¼ 6.8 Hz, 2H), 7.28 (t, J ¼ 7.8 Hz, 1H), 7.20 (d, J ¼ 7.6 Hz,
1H), 6.70 (d, J ¼ 16.4 Hz, 1H), 2.37 (s, 6H, 2CH3); 13C NMR (100
MHz, CDCl3): d 198.3, 143.6, 138.6, 134.4, 131.3, 128.9, 128.8,
127.0, 125.4, 27.4, 21.3; MS (EI, 70 eV): m/z (%) 161 (4) [M+ + 1],
160 (28) [M+], 145 (100), 115 (54); known compound.2c
Typical procedure for the Knoevenagel condensations
catalyzed by polymer 8 (Table 2)
To a 15 mL reaction tube, 30 mg of polymer 8 (containing
0.03 mmol of proline moiety) and 4.3 mg of piperazine (0.05
mmol) were added. The tube was then charged with N2 and
a suspension of 1 mmol of aldehyde 1 and 1 mmol of malo-
nonitrile 9 in 1 mL of water was injected using a syringe. The
mixture was stirred at 50 ꢁC for 48 h. The products could be
extracted using ether (3 ꢀ 1 mL) and puried by preparative
TLC (eluent: petroleum ether/EtOAc 10 : 1).
(E)-4-(o-Tolyl)but-3-en-2-one 3d. 113.8 mg, 71%; oil; IR (lm):
3027, 2921, 1670, 1612, 1359, 1256, 979, 781 cmꢂ1; 1H NMR (600
MHz, CDCl3, TMS): d 7.80 (d, J ¼ 16.2 Hz, 1H), 7.55 (d, J ¼
7.8 Hz, 1H), 7.26 (d, J ¼ 7.8 Hz, 1H), 7.20 (t, J ¼ 7.8 Hz, 2H), 6.63
(d, J ¼ 16.2 Hz, 1H), 2.43 (s, 3H), 2.37 (s, 3H); 13C NMR (150
MHz, CDCl3): d 198.2, 140.8, 137.8, 133.4, 130.9, 130.2, 128.1,
126.4, 126.4, 27.8, 19.7; MS (EI, 70 eV): m/z (%) 160 (12) [M+], 145
(100), 115 (61), 117 (37), 116 (22); known compound.2c
(E)-4-(4-Methoxyphenyl)but-3-en-2-one 3e. 107.5 mg, 61%;
Solid, mp 71.2–72.4 ꢁC (lit. 71–72 ꢁC); IR (KBr): 3039, 3005, 2963,
Detailed procedures of the polymer absorption tests for the
mechanism studies
2838, 1660, 1629, 1599, 1423, 1362, 1245, 1028, 972, 804 cmꢂ1
;
1H NMR (600 MHz, CDCl3, TMS): d 7.50–7.46 (m, 3H), 6.91 (d,
J ¼ 7.8 Hz, 2H), 6.60 (d, J ¼ 16.2 Hz, 1H), 3.84 (s, 3H), 2.35 (s,
3H); 13C NMR (150 MHz, CDCl3): d 198.5, 161.6, 143.3, 130.0,
127.0, 125.0, 114.5, 55.4, 27.4; MS (EI, 70 eV): m/z (%) 177 (5)
[M+ + 1], 176 (45) [M+], 161 (100), 133 (51); known compound.2c
(E)-4-(4-Chlorophenyl)but-3-en-2-one 3f. 108.4 mg, 60%;
Solid, mp 53.8–54.9 ꢁC (lit. 54–55 ꢁC); IR (KBr): 3016, 1657, 1486,
1 mmol of freshly distilled benzaldehyde was dissolved in 5 mL
of absolute ethanol in a tube. The supernatant liquid sample
was sent for GC analysis three times. The values of the benzal-
dehyde peak area divided by the ethanol peak area were calcu-
lated to be 0.05009, 0.05009 and 0.05008 (average value:
0.05009). 10 mg of the polymer-supported proline 8 was then
added and the mixture was le overnight under N2 protection.
The polymer precipitated at the bottom of the tube. The
supernatant liquid was sent for GC analysis again. The analysis
results indicated that only benzaldehyde and ethanol were
detected while no new compound was generated. The values of
the benzaldehyde peak area divided by the ethanol peak area
were calculated to be 0.04539, 0.04470 and 0.04479 for the three
parallel experiments respectively (average value: 0.04496). The
experimental results indicated that aer adding the polymer 8,
the concentration of the reactant had fallen by 10.2%. Since GC-
analysis showed that no chemical reaction occurred during the
process, the loss of reactant might be attributed to adsorption
around the catalyst reaction sites of the polymer 8. The detailed
GC data and spectra are given in the ESI.†
1406, 1360, 1255, 1088, 977, 808 cmꢂ1 1H NMR (600 MHz,
;
CDCl3, TMS): d 7.47–7.44 (m, 3H, 1C]C–H + 2Ar-H), 7.36 (d, J ¼
8.4 Hz, 2H), 6.68 (d, J ¼ 16.2 Hz, 1H), 2.37 (s, 3H); 13C NMR (150
MHz, CDCl3): d 198.0, 141.9, 136.4, 133.0, 129.4, 129.3, 127.5,
27.7; MS (EI, 70 eV): m/z (%) 181 (8) [M+ + 1], 180 (27) [M+], 165
(100), 102 (53), 137 (50); known compound.2c
(E)-4-(3-Chlorophenyl)but-3-en-2-one 3g. 90.3 mg, 50%; oil;
IR (lm): 3061, 1675, 1615, 1360, 1258, 1190, 1052, 979, 782,
695 cmꢂ1; 1H NMR (400 MHz CDCl3, TMS): d 7.52 (s, 1H), 7.45–
7.21 (m, 4H), 6.70 (d, J ¼ 16.4 Hz, 1H), 2.37 (s, 3H); 13C NMR (100
MHz, CDCl3): d 197.8, 141.5, 136.3, 135.0, 130.3, 130.1, 128.1,
127.9, 126.3, 27.7; MS (EI, 70 eV): m/z (%) 180 (31) [M+], 165
(100), 102 (68), 145 (62), 137 (53); known compound.12a
(E)-4-(2-Chlorophenyl)but-3-en-2-one 3h. 75.9 mg, 42%; oil;
IR (lm): 3004, 2921, 1672, 1612, 1177, 1098, 1044, 976, 754,
695 cmꢂ1
;
1H NMR (400 MHz, CDCl3, TMS): d 7.93 (d, J ¼
Characterization of the products
(E)-4-Phenylbut-3-en-2-one 3a. 109.6 mg, 75%; oil; IR (lm): 16.4 Hz, 1H), 7.64–7.62 (m, 1H), 7.43 (d, J ¼ 2.0 Hz, 1H), 7.42–
3036, 1963, 1671, 1611, 1358, 1257, 979, 750, 691 cmꢂ1; 1H NMR 7.30 (m, 2H), 6.66 (d, J ¼ 16.4 Hz, 1H), 2.41 (s, 3H); 13C NMR (100
(600 MHz, CDCl3, TMS): d 7.53–7.49 (m, 3H), 7.38 (d, 3H), 6.70 MHz, CDCl3): d 198.2, 139.1, 135.0, 132.7, 131.2, 130.1, 129.6,
(d, J ¼ 16.2 Hz, 1H), 2.37 (s, 3H); 13C NMR (150 MHz, CDCl3): 127.5, 127.1, 27.2; MS (EI, 70 eV): m/z (%) 180 (9) [M+], 145 (100),
d 198.4, 143.4, 134.4, 130.5, 129.0, 128.3, 127.2, 27.5; MS (EI, 70 137 (26), 101 (25), 165 (23); known compound.2c
eV): m/z (%) 147 (5) [M+ + 1], 146 (47) [M+], 103 (100), 131 (85),
145 (58); known compound.2c
(E)-4-(4-Fluorophenyl)but-3-en-2-one 3i. 88.7 mg, 54%; oil; IR
(lm): 3069, 2973, 2926, 2883, 1668, 1599, 1510, 1415, 1378,
(E)-4-(p-Tolyl)but-3-en-2-one 3b. 112.2 mg, 70%; oil; IR (lm): 1234, 1160, 1087, 879, 820, 604 cmꢂ1; 1H NMR (400 MHz, CDCl3,
3290, 3025, 2923, 1672, 1610, 1513, 1360, 1256, 980, 804, TMS): d 7.54 (dd, J ¼ 8.8, 5.6 Hz, 2H), 7.48 (d, J ¼ 16.4 Hz, 1H),
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7.10 (t, J ¼ 8.8 Hz, 2H), 6.65 (d, J ¼ 16.4 Hz, 1H), 2.38 (s, 3H); 13
C
CDCl3): d 7.86 (d, J ¼ 7.6 Hz, 2H), 7.75 (s, 1H), 7.53 (d, J ¼ 8.0 Hz,
NMR (100 MHz, CDCl3): d 198.2, 164.1 (d, JC–F ¼ 250.0 Hz), 2H); 13C NMR (100 MHz, CDCl3): d 158.8, 141.6, 132.3, 130.5,
142.1, 130.2, 130.1, 126.9, 116.2 (d, JC–F ¼ 22.0 Hz), 27.7; known 129.7, 113.9, 112.8, 83.8; MS (EI): m/z (%) 188 (98) [M+], 153
compound.2c
(100), 137 (25); known compound.12h
(E)-4-Cyclohexylbut-3-en-2-one 3j. 111.1 mg, 73%, oil; IR
2-((Thiophen-2-yl)methylene)malononitrile 10d. 141.0 mg,
1
(lm): 2930, 2856, 1677, 1629, 1446, 1362, 1261, 982 cmꢂ1; H 88%; solid, mp 95.8–96.8 ꢁC (lit. 95–96 ꢁC); IR (KBr): 3023, 2222,
NMR (400 MHz, CDCl3, TMS): d 6.77–6.71 (m, 1H), 6.02 (d, J ¼ 1698, 1495, 1141, 946, 752 cmꢂ1; H NMR (600 MHz, CDCl3):
1
16.0 Hz, 1H), 2.24 (s, 3H), 2.19–2.14 (m, 1H), 1.79–1.76 (m, 4H), d 7.89 (d, J ¼ 4.2 Hz, 2H), 7.82 (d, J ¼ 4.2 Hz, 1H), 7.28 (t, J ¼
1.33–1.13 (m, 6H); 13C NMR (100 MHz, CDCl3): d 199.0, 153.3, 4.2 Hz, 1H); 13C NMR (150 MHz, CDCl3): d 151.2, 138.4, 137.0,
128.8, 40.5, 31.7, 26.7, 25.8, 25.6; MS (EI, 70 eV): m/z (%) 152 (49) 135.4, 129.1, 113.8, 113.0, 78.2; MS (EI): m/z (%) 160 (100) [M+],
[M+], 94 (100), 109 (70), 83 (80); known compound.2c
133 (43), 109 (37); known compound.12g
(E)-4-(4-Hydroxyphenyl)but-3-en-2-one 3k. 90.8 mg, 56%;
2-(Naphthalen-2-ylmethylene)malononitrile 10e. 69.4 mg,
solid; mp 111.2–112.1 ꢁC (lit. 111–112 ꢁC); IR (KBr): 3444, 3130, 83%; solid, mp 140.7–142.4 ꢁC (lit. 140.2–140.8 ꢁC); IR (KBr):
1670, 1587, 1250, 969, 825 cmꢂ1 1H NMR (600 MHz, CDCl3, 2850, 2224, 1624, 1461, 1153, 820, 753 cmꢂ1; 1H NMR (600 MHz,
;
TMS): d 7.51 (d, J ¼ 16.2 Hz, 1H), 7.45 (d, J ¼ 9.0 Hz, 2H), 6.91 (d, CDCl3): d 8.29 (s, 1H), 8.07 (dd, J ¼ 9.0, 1.8 Hz, 1H), 7.96–7.94
J ¼ 8.4 Hz, 2H), 6.61 (d, J ¼ 16.2 Hz, 1H), 2.39 (s, 3H); 13C NMR (m, 2H), 7.90 (d, J ¼ 9.0 Hz, 2H), 7.68 (t, J ¼ 7.2 Hz, 1H), 7.61 (t,
(150 MHz, CDCl3): d 200.3, 159.4, 145.1, 130.5, 126.2, 124.2, J ¼ 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 159.8, 135.9,
116.3, 27.2; known compound.12b
134.5, 132.6, 130.0, 129.7, 128.5, 128.0, 127.7, 124.2, 114.0,
(E)-4-(3-Hydroxyphenyl)but-3-en-2-one 3l. 84.3 mg, 52%; 112.9, 82.2; MS (EI): m/z (%) 204 (100) [M+], 177 (22), 153 (22);
solid; mp 94.2–95.3 C; IR (KBr): 3149, 3077, 2956, 2828, 1625, known compound.12i
ꢁ
1
1574, 1359, 994 cmꢂ1; H NMR (400 MHz, CDCl3, TMS): d 7.48
2-(Cyclohexylmethylene)malononitrile 10f. 80.1 mg, 50%;
(d, J ¼ 16.4 Hz, 1H), 7.27 (m, 1H), 7.09 (m, 2H), 6.92 (dd, J ¼ 8.0, solid, mp 101.1–102.8 ꢁC (lit. 101–102 ꢁC); IR (KBr): 3097, 3021,
2.4 Hz, 1H), 6.70 (d, J ¼ 16.0 Hz, 1H), 5.89 (s, 1H), 2.40 (s, 3H); 2971, 2222, 1640, 1407, 734 cmꢂ1; H NMR (400 MHz, CDCl3):
1
13C NMR (100 MHz, CDCl3): d 199.3, 156.4, 143.8, 135.9, 130.2, d 7.16 (d, J ¼ 10.8 Hz, 1H), 2.73 (d, J ¼ 10.0 Hz, 1H), 1.79 (t, J ¼
127.3, 121.2, 118.0, 114.6, 27.5; known compound.12c
14.0 Hz, 4H), 1.39–1.21 (m, 6H); 13C NMR (100 MHz, CDCl3):
(E)-4-(Pyridin-4-yl)but-3-en-2-one 3m. 73.6 mg, 50%; solid; IR d 173.5, 112.2, 110.0, 77.3, 42.0, 30.8, 25.1, 24.6; MS (EI): m/z (%)
(KBr): 3003, 2922, 2455, 2324, 1790, 1652, 1575, 798, 642, 160 (32) [M+], 159 (66), 145 (80), 132 (100), 105 (89); known
505 cmꢂ1; 1H NMR (400 MHz, CDCl3, TMS): d 8.67 (d, J ¼ 5.6 Hz, compound.12j
2H), 7.45–7.39 (m, 3H), 6.85 (d, J ¼ 16.4 Hz, 1H), 2.42 (s, 3H); 13
C
NMR (100 MHz, CDCl3): d 197.7, 150.6, 141.8, 140.1, 130.7,
122.0, 28.0; MS (EI): m/z (%) 147 (45) [M+], 132 (100), 104 (25), 78
(22); known compound.12d
Conflicts of interest
There are no conicts to declare.
(E)-4-(3-Hydroxypyridin-2-yl)but-3-en-2-one 3n. 76.7 mg,
47%; solid; IR (KBr): 3345, 2920, 2474, 1652, 1622, 1575, 1251,
982, 798, 503 cmꢂ1; 1H NMR (400 MHz, (CD3)2SO, TMS): d 10.66
Acknowledgements
(s, 1H), 8.14 (dd, J ¼ 4, 1.6 Hz, 1H), 7.83 (d, J ¼ 16 Hz, 1H), 7.31– We thank the NNSFC (21202141), the Priority Academic
7.29 (m, 2H), 7.09 (d, J ¼ 16 Hz, 1H), 2.35 (s, 3H); 13C NMR (100 Program Development (PAPD) of Jiangsu Higher Education
MHz, (CD3)2SO): d 198.8, 153.9, 141.4, 140.1, 137.0, 129.2, 126.6, Institutions, the High Level Talent Support Project of Yangzhou
124.1, 28.1; MS (EI): m/z (%) 163 (10) [M+], 148 (75), 120 (100), University, the Open Project Program of Jiangsu Key Laboratory
104 (5); known compound.12e
of Zoonosis (R1509) and the testing centre of Yangzhou
2-Benzylidenemalononitrile 10a. 115.5 mg, 75%; solid, mp University.
82.6–84.0 ꢁC (lit. 83–84 ꢁC); IR (KBr): 3032, 2956, 2222, 1588,
957, 676 cmꢂ1; 1H NMR (400 MHz, CDCl3): d 7.91 (d, J ¼ 8.0 Hz,
Notes and references
2H), 7.79 (s, 1H), 7.64 (t, J ¼ 7.6 Hz, 1H), 7.55 (t, J ¼ 7.6 Hz, 2H);
13C NMR (100 MHz, CDCl3): d 159.9, 134.6, 130.9, 130.7, 129.6,
113.7, 112.5, 82.8; MS (EI): m/z (%) 155 (12) [M+ + 1], 154 (100)
[M+], 127 (64), 103 (58); known compound.12f
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solid, mp 132.9–134.3 ꢁC (lit. 133–134 ꢁC); IR (KBr): 3035, 2961,
2923, 2220, 1640, 1587, 1368, 1221, 946 cmꢂ1 1H NMR (400
;
MHz, CDCl3): d 7.82 (d, J ¼ 7.6 Hz, 2H), 7.73 (s, 1H), 7.34 (d, J ¼
7.6 Hz, 2H), 2.46 (s, 3H); 13C NMR (100 MHz, CDCl3): d 159.8,
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(%) 168 (100) [M+], 141 (45), 117 (11); known compound.12g
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48220 | RSC Adv., 2017, 7, 48214–48221
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This journal is © The Royal Society of Chemistry 2017
RSC Adv., 2017, 7, 48214–48221 | 48221