Proline-based polymeric monoliths: synthesis, characterization, and applications as organocatalysts in aldol reaction

Article abstract of DOI:10.1002/pola.23845

Proline-based polymer monoliths were synthesized via green protocol using lipase-catalyzed esterlfication of methacrylic acid and 4-hydroxyproline. Prolinyl methacrylate thus prepared was polymerized in situ as crosslinked monolith. The monolith was chara

Full text of DOI:10.1002/pola.23845

Proline-Based Polymeric Monoliths: Synthesis, Characterization, and
Applications as Organocatalysts in Aldol Reaction
DIPTI GARG,1 J.-H. AHN,2 GHANSHYAM S. CHAUHAN1
1Department of Chemistry, Himachal Pradesh University, Shimla 171005, Himahcal Pradesh, India
2Department of Chemical and Biological Engineering and Engineering Research Institute, Gyeongsang National University,
900 Gajwa-dong, Jinju 660-701, Republic of Korea
Received 4 September 2009; accepted 21 November 2009
DOI: 10.1002/pola.23845
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: Proline-based polymer monoliths were synthesized via
green protocol using lipase-catalyzed esterification of methacrylic
acid and 4-hydroxyproline. Prolinyl methacrylate thus prepared
was polymerized in situ as crosslinked monolith. The monolith
was characterized by various techniques such as Fourier transform
infrared, 1H-NMR, 13C-NMR, scanning electron microscopy (SEM),
X-ray diffraction (XRD), and nitrogen analysis and used as catalyst
in aldol reactions. The swelling behavior of the monolith was also
studied as function of various external parameters like pH and
temperature. The monoliths synthesized with 1% crosslinker was
selected as candidate monolith for use as catalyst in aldol reaction,
which was studied as a function of time, temperature, substrate
structure, and amount of water:EtOH. The catalysts exhibited high
efficiency in the cross aldol reaction, especially with the aromatic
substrates having electron withdrawing substituent, and also
good activity retention was observed when recycleability was
C
V
studied up to five cycles. 2010 Wiley Periodicals, Inc. J Polym Sci
Part A: Polym Chem 48: 1007–1015, 2010
KEYWORDS: aldol reaction; 4-hydroxyproline; lipase; polymer
catalyst; polymer monolith
INTRODUCTION In catalysis, it is often visualized that a cata-
lyst should combine the merits of organocatalyst, biocatalyst,
and polymer catalyst. Biocatalysts have comparative advant-
age over a synthetic catalyst as the former can work at nor-
mal operating conditions, and there is no danger of leaching
of the toxic ligand/active part of the catalyst. But the appli-
cability of biocatalysts over a wide range of conditions and
separation from the reaction medium after the completion of
reaction are two major limitations. These limitations can be
overcome by their immobilization on solid supports that
results in an ease of separation, enhanced recyclability and
reusability.1 The asymmetric catalysts are highly selective
and efficient, and despite being very expensive, their
research and industrial output far outweigh those of biocata-
lysts.2 The polymer-supported or ‘‘polymer catalyst’’ apart
from the significant advantage of the ease of separation are
effective due to the high concentrations of active groups on
the polymer chains.3 In most of the polymer-supported cata-
lysts, the active part is an inorganic metal or a complex of
palladium, titanium, or ruthenium.4–8 These are cost prohibi-
tive, and the leaching of the active groups of catalyst is a
major limitation. It is thus desirable that the monomer/s
comprising a polymer catalyst have active groups as part of
the monomer itself.
the active part of the monomer. Proline is a model ‘‘bifunc-
tional catalyst’’ and is christened as a ‘‘simplest enzyme’’9
and ‘‘universal asymmetric catalyst’’10 and it is useful in the
synthesis of chiral organic molecules by asymmetric transfor-
mation.11 It is nontoxic, easily available, and cost effective,
and it is reactive in water at room temperature. It is bifunc-
tional as the secondary amino group and carboxylic acid
impart it the catalytic activity. Proline as catalyst allows the
preparation and screening of large libraries of catalysts.12 It
was used since 1970, yet the real thrust to its catalytic
potential came after the breakthrough works of List et al.13
and Sakthivel et al.14 The use of proline as such is effective
in high amount (30 mol%), and its separation from water
poses another problem, and at present, the use of non-sol-
vents like chloroform and diethyl ether have been reported
to separate it from the solution phase.15,16 Hence, it is im-
perative that to realize cost effectiveness and green benefits
of proline as catalyst, it was heterogenized by anchoring on
different solid supports.17–23 Consequently, the immobiliza-
tion of proline has become one of the most explored areas of
catalysis, especially in aldol reaction using water as medium.
The support reported for proline range from highly porous
and rigid inorganic supports24–28 to soluble polymers such
as polyethylene glycol (PEG).29,30 More recently, polystyrene
(PS) has been used as an efficient polymeric backbone with
and without second component to support proline and its
In view of the above, in this communication we report
monomer and monolithic hydrogel synthesis with proline as
Correspondence to: G. S. Chauhan (E-mail: ghanshyam_in2000@yahoo.com or ghanshyamschauhan@gmail.com)
C
V
Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 48, 1007–1015 (2010) 2010 Wiley Periodicals, Inc.
PROLINE-BASED POLYMERIC MONOLITHS, GARG, AHN, AND CHAUHAN
1007

JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
derivatives in the enantioselective direct aldol reaction.31–35
To enhance the activity of the hydrophobic backbone, it has
been grafted on to TentaGel36 or PEG-PS aminated resins im-
mobilized with proline tripeptides (D-Pro-Tyr-Phe) for use in
aldol reactions in a triphasic solvent media (water/acetone/
tetrahydrofuran (THF), 1/1/1)6.37 Proline-catalyzed asymmet-
ric aldol reaction has also been carried out successfully with
supports like ionic liquids,38–42 polyelectrolyte system43 with
efficient catalyst recovery. Moreover, dendritic polymers cata-
lysts with anchored proline have been reported to affect high
yield and enantioselectivity.44–48 Proline has also been modi-
fied to different proline-based polymers for studies and appli-
cations other than polymer catalysts. These polymers include
poly-(proline),49 acryloyl-L-proline esters,50–57 poly(acryloyl-L-
proline methyl ester/styrene),58 proline-substituted acrylam-
ide (AAm),59 and copolymers as poly(ester-carbonate)60 or
block copolymers and derived from proline derivatives.61–63
MBAAm and APS (1% of the initial weight of MAAc). The re-
sultant solution was taken into ampoules of 20 length with a
diameter of 0.50 under vacuum suction. The ampoules were
sealed and placed in chemical reactor at 70 ꢀC for 60 min.
The monolith, thus formed, was repeatedly treated with dis-
tilled water with stirring, and dried at 40 ꢀC in an air oven.
Such repeated stirring and drying cycles were carried till a
constant weight was obtained, and there after the resultant
monolith was cut in small discs of uniform dimensions. Fol-
lowing the same procedure, poly(MAAc) and poly(PrMA)
were also prepared for use as reference.
Characterization of Different Polymers and Monoliths
Fourier transform infrared (FTIR) spectra were recorded in
KBr pellets on Nicollet 5700 Spectrophotometer. Nuclear
magnetic resonance (NMR) spectra were recorded on INOVA
400 MHz; all the spectra were confirmed by comparing the
digitized line spectra with the estimated shifts by computer
software, viz. ChemNMR Pro (ChemDraw Ultra). SEMs were
recorded on Jeol JSM-6100 scanning electron microscope,
nitrogen analysis of the monoliths (before and after use) was
carried on Carlo Erba EA-1108, and XRD recorded D8
Advance, 120 Bruker AXS using Cu Ka radiation (3 kW). The
swelling studies was carried in triplicate by using 0.1 g of
the disc cut from the monoliths from 10 to 1440 min, 20–
60 ꢀC and at pH 4.0, 7.0, and 9.2 by an earlier reported
procedure.65
Most of these studies are related to the copolymerization of
proline or its anchoring/immobilization on a inorganic or
polymeric backbone support by covalent attachement or
derivatization of its carboxylate group, or the grafting onto
hydrophobic backbone like PS. Although the former process
results in the loss of its natural benefits as catalyst, the latter
restricts its applications in water despite offering benefits of
easy separation. We have not encountered any report on the
synthesis of a monomer with proline or its derivatives to
yield a polymer monolith through biocatalytic route and use
of the resultant monolith as organocatalyst. In view of the
above, in this communication we report synthesis, characteri-
zation and use of the new polymeric monoliths for catalysis
of aldol reaction in water as reaction medium.
Application in Aldol Reaction
Monolith discs (30 mol%), benzaldehyde (9.42 mM), and ac-
etaldehyde (9.42 mM) were taken in H2O:EtOH (6:4, 10 mL).
The reaction mixture was stirred in chemical reactor for 18
h at 20 ꢀC; thereafter the monolith was filtered, washed
thoroughly with water and ethanol, and dried under vacuum
for further use. From the filtrate, the solvent and excess of
aldehyde/ketone were removed under the reduced pressure
at room temperature. The resulting residue was taken in
ethyl acetate (30 mL) and stirred with 10% NaHCO3 solution
(10 mL). The organic layer was separated, washed with
brine, dried over anhydrous Na2SO4, and concentrated under
reduced pressure. The crude oil was extracted from petro-
leum ether. Each reaction was carried out by setting reaction
in triplicate along with a corresponding control reaction. For
the optimization of the reaction conditions, the reaction was
assayed at different time intervals (6, 12, 18, 24, and 30 h)
EXPERIMENTAL
Materials
AAm, lipase, N,N-methylenebisacrylamide (N,N-MBAAm), p-
methoxybenzaldehyde and N,N,N,N-tetramethylethylene dia-
mine (Sisco, Mumbai, India), acetaldehyde, benzaldehyde, do-
decyl methacrylate (DMA; Merck, Mumbai), p-chlorobenzal-
dehyde, p-nitrobenzaldehyde, methacrylic acid (MAAc) and
4-hydroxyproline (HiMedia, Mumbai, India), ammonium per-
sulphate (APS) (Qualigens Fine Chemicals, Mumbai), molecu-
lar sieves-4 Å, 1.5 mm (IDP, Hyderabad, India), and tris(hy-
droxymethyl)-aminomethane (tris-buffer, S.D. Fine, Mumbai,
India) were used as received but for n-hexane that was dis-
tilled before use.
ꢀ
at different temperatures (20–40 C). Moreover, the effect of
solvent concentration was also determined by varying the
concentration of H2O:EtOH. The reaction mixture was ana-
lyzed directly by withdrawing aliquot with from time to
time, which was analyzed by high performance liquid chro-
matography (HPLC), and the percent conversion was calcu-
lated on the basis of the benzaldehyde consumed. The reac-
tion was quenched by freezing the reaction mixture. The
solid catalyst was filtered, washed thoroughly with water
and ethanol, and dried under vacuum to study reusability of
the catalyst, which was studied by reusing the used catalyst
as such or by stirring with ethyl acetate for 1 h prior to the
next reusability cycle. The optimized conditions thus
obtained were further used in different cross-aldol reactions.
Synthesis of Monomers and Polymer Monoliths
Lipase was immobilized in situ on a hydrogel comprising of
28 mM AAm and 3.5 mM DMA that was prepared by an ear-
lier reported procedure.64 Two hundred milligram of the im-
mobilized lipase was used to catalyze reaction of MAAc with
4-hydroxyproline using a molar ratio of 1: 1.25 in 10.0 mL
of n-hexane and 300 mg of molecular sieves. The reactions
were carried in Meꢀttler
b Autochem chemical reactor
(Autochem, US) at 50 C for 12 h with constant stirring. The
immobilized lipase was separated by filtration from the reac-
tion mixture and to the resultant filtrate containing prolinyl
methacrylate was added 10.0 mL distilled water and N,N-
1008
INTERSCIENCE.WILEY.COM/JOURNAL/JPOLA

ARTICLE
SCHEME 1 Process and mechanism of the immobilized lipase-catalyzed monomer synthesis.
Quantification and Characterization of Products
tor). The sample was analyzed using (65% v/v) acetonitrile
in water as mobile phase at flow rate of 1.0 mL minꢂ1 at
ambient temperature. The absorbance was recorded at 210
nm. The injection volume was 0.5 lL. All the standard curves
(0.1–1.0 mM) were prepared under similar conditions. The
spectra were recorded over the range of 4500–500 cmꢂ1 by
All the compounds synthesized using polymer catalysts were
quantified by using HPLC (HPLC was performed using Perkin
Elmer series 200 Ic pump equipped Inertsil ODS-3, 4.6 ꢁ
150 mm, 5 mm in particle size, GL Sciences, Japan, and
Applied Biosystems 785 Å programmable absorbance detec-
PROLINE-BASED POLYMERIC MONOLITHS, GARG, AHN, AND CHAUHAN
1009

JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
1H-NMR spectrum of poly(MAAc) [Fig. 4(a)] presented as
reference shows signals at 1.62 d and 2.27 d corresponding
to the methylene protons, whereas in 1H-NMR spectrum of
poly(PrMA) signals appears at 2.4 d corresponding to the
protons of –NH, and –CH2 positioned adjacent to –COOH
groups in the pyrrolidine ring. The signal at 2.45 d corre-
sponds to methylene proton situated a to –NH, a quartet at
3.4 d corresponds to –CH group a to polymer chain linkage,
and a triplet at 4.3 d corresponds to –CH placed a to –COOH
of the pyrrolidine ring [Fig. 4(b)]. 13C-NMR spectrum of poly
(PrMA) has two peaks at 179 ppm and 174 ppm due to the
presence of two –C¼O groups, the peak at 70 ppm relates to
the carbon positioned a to –C¼O and b to –NH, at 60 ppm
corresponds to carbon a to –NH and –COOH, at 53 ppm
corresponds to carbon placed between –NH and –CO, and
the signals at 37 ppm and 34 ppm correspond to carbon b
to –COOH and methylene of the polymer chain, respectively
(not presented). The contrast of this spectrum with the ref-
erence polymer studied provides evidence of the formation
of poly(PrMA).
FIGURE 1 XRD of poly(PrMA-cl-N,N-MBAAm).
means of OMNIC software. Optical rotations were obtained
by research polarimeter (SIPCON, SP-01A) in ethanol. IR
spectra of the products were recorded as described earlier.
The monoliths behaved as hydrogel and the maximum %
swelling was observed in the case of polymers having 1%
crosslinker, thus, exhibiting an increase in the degree and
intensity of crosslinking at the higher crosslinker concen-
trations. Under the swelling conditions studied, all the
hydrogels exhibited enhanced swelling with an increase in
temperature, but these deswell above 50 ꢀC (figures not
RESULTS AND DISCUSSION
Monomer Synthesis
Immobilized lipase had a high protein binding efficiency
(81%) and exhibited enzyme activity of 5.61 U/mL. It was
used to synthesize monomer, PrMA, as illustrated in Scheme
1. The esterification reaction involving acylation and deacyla-
tion on the active site of lipase are also illustrated.66,67 The
optical rotation of the proline itself or poly(PrMA) in water
was found to be ([a]D ¼ ꢂ2.01, c ¼ 0.1).
Characterization of Polymers
% N was found in the monomers PrMA, and in its network
was found to be 9.95 and 4.26. The monomer formation is
supported by the lower amount of N in the monomers than
the precursor 4-trans hydroxyproline. XRDs exhibit high
crystallinity with sharp peaks in the regions of ꢃ20–ꢃ40
theta with important peaks at 1.133 at 21.84 and 2.081 at
38.2 theta for poly(PrMA-cl-N,N-MBAAm) (Fig. 1). SEMs of
the monolith show outgrowths on the surface of the net-
works that is attributed to the aggregation of the pendant
prolinyl groups. Evidently, the surface morphology of the
intensely crosslinked polymers exhibits small pore size [Fig.
2(a) and (b)]. Appearance of the characteristic peaks of 4-
hydroxyproline in the FTIR spectrum of poly(PrMA) suggests
the formation of monomers and their polymers [Fig. 3(a,b)].
The spectrum of the monolith has two characteristic bands,
that is, 1641 and 1593 cmꢂ1 associated with COOꢂ absorb-
ance and þNH2 deformations of proline. Absence of peak at
1730 cmꢂ1 rules out the possibility of the presence of the
unionized proline.68 The dipolar nature of the prolinyl moi-
ety is supported by the appearance of two strong bands at
883 and 920 cmꢂ1, due to þNH2 and ꢂCOOꢂ. Distinct
changes in the intensity or shifting in the peaks of the char-
acteristic peaks was also observed in the spectra of the
monoliths when compared with that of PrMA.
FIGURE 2 SEMs of poly(PrMA-cl-N,N-MBAAm) at two different
conditions.
1010
INTERSCIENCE.WILEY.COM/JOURNAL/JPOLA

ARTICLE
reaction systems.69 Aldol condensation is a reversible and
exothermic reaction; the maximum yields are generally
obtained at 5–25 ꢀC.70 From the histogram, it was inferred
that the concentration of solvent had profound effect71–76 on
the reaction kinetics (Fig. 6). The solvent composition at 6:4
(H2O: EtOH) increased % conversion from 24% to 62%. The
high % conversion of catalyst in water is attributed to the
good swelling properties of the polymeric monolith in water
thereby opening up the catalytic sites and increasing the
accessibility and contact of reactants with the catalyst.77 The
total absence of water or EtOH (H2O:EtOH ¼ 10:0 or 0:10)
in both the extremes reduced the extent of reaction, which is
in conformity with that reported in literature.69 The role of
water as reaction medium helps in increasing the total cata-
lyst concentration within the catalytic cycle due to suppres-
sion of spectator species. In the absence of water, irreversi-
ble deactivation due to formation of oxazolidinone derived
from proline and aldehyde.78 These results indicate that ac-
etaldehyde can react with a reactive electrophilic aldehyde
even in the presence of a large excess of water, and this can
be understood with the hydrogel nature of the catalyst.
However, because of the lower polarity of the substrate
and reagent, the optimum catalytic activity was observed in
the aqueous EtOH. The composition of solvent system
(H2O:EtOH) at 6:4 resulted in the maximum % conversion as
at this concentration there is no interaction between constit-
uent molecules as it behaves ideally,79 whereas with the
reverse composition (H2O:EtOH ¼ 4:6), there was drastic
FIGURE 3 FTIR of (a) poly(MAAc) and (b) 4-hydroxyproline and
(c) poly(MAAc-cl-N,N-MBAAm).
presented). On change of pH, higher swelling was observed
in the alkaline medium (pH 9.2) than in acidic medium (pH
4.0). The data generated from the swelling studies demon-
strated that the swelling capacity of the proline-based poly-
mers was higher than the reference crosslinked poly(MAAc).
The increase of the ionic units along the main chain of
hydrogel leads to an increase in the repulsive forces among
similar ionic groups resulting in the loosening of the net-
work chains, and thus, favouring the higher or increased
water uptake.
Applications as Organocatlayst: Effect of Time,
Temperature and Solvent Composition in Aldol Reaction,
and Selection of Catalyst
On the basis of the swelling behavior, the monoliths synthe-
sized with 1% crosslinker were used as catalysts to examine
their catalytic activity in the reaction of benzaldehyde with
acetaldehyde. % Conversion was determined from the con-
sumption of benzaldehyde during the advancement of reac-
tion with HPLC. The maximum % conversion (63) was
obtained at 18 h, 20 ꢀC, in H2O: EtOH (6:4) solvent with 30
mol% catalyst loading. The progress of reaction was initially
fast up to 18 h, and later it became independent of time
(Fig. 5). Thus, from ꢀthe reaction profile the optimum reaction
time of 18 h at 20 C was obtained. The contact of the cata-
lyst and the substrates increased with time. This is far lower
than the reported contact time (48–72 h) for this type of
FIGURE 4 1H-NMR (from top) poly(MAAc) and poly(PrMA).
PROLINE-BASED POLYMERIC MONOLITHS, GARG, AHN, AND CHAUHAN
1011

JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE 5 Effect of time on the cross-aldol reaction of benzal-
dehyde with acetaldehyde by proline-based catalysts (tempera-
ture ¼ 20 ꢀC, catalyst loading ¼ 30 mol %, without solvent).
FIGURE 6 Effect of solvent composition on the cross-aldol
reaction of benzaldehyde with acetaldehyde (time ¼ 18 h, tem-
perature ¼ 20 ꢀC, catalyst loading ¼ 30 mol %).
decrease in the % conversion as with an increase in the con-
centration of EtOH there was a decrease of water-solute
interaction energy which leads to an increase in the water-
water aggregation or an increase of hydrophobic interactions
of ethyl groups of EtOH. This hinders the action of the OH
groups of interfacial water molecules which play a key role
in catalyzing reactions via the formation of hydrogen
bonds.80
The key intermediate in the direct intermolecular asymmet-
ric aldol reaction is an enamine formation between proline
catalyst and the corresponding donor substrate. In the pro-
posed mechanism, enamine attacks the carbonyl group of
the aromatic aldehyde acceptor forming a highly organized
tricyclic hydrogen bonded framework resembling a metal-
free Zimmermann-Traxler type transition state. Therefore, as
reported by Barbas and coworkers,14 a base and an acidic
proton, both are required for the effective catalysis to occur
as hydrogen bonding is an essential feature of the transition
state. Moreover, it is also speculated that the ester in the
polymeric catalysts makes N-H more acidic due to its elec-
tron-withdrawing property (Scheme 3). This results in the
formation of a stronger hydrogen bond in the transition
state.81 Therefore, the presence of an ester group as in the
present case induced a positive effect on the performance of
the polymeric catalyst. The reusability of the polymer
A generalized aldol reaction is shown in Scheme 2. Benzalde-
hyde and some portion of the acetaldehyde formed an or-
ganic phase. The remaining acetaldehyde was dissolved in
the aqueous phase, where it reacted with the hydrophilic
polymeric proline, most of which in water is present in the
zwitterionic form. As acetaldehyde dissolves in both the
aqueous and organic phases, it extracts proline from water
to the organic phase. A noteworthy advantage of the present
reaction is the realization of an organic solvent-free system.
SCHEME 2 Model aldol reaction.
1012
INTERSCIENCE.WILEY.COM/JOURNAL/JPOLA

ARTICLE
SCHEME 3 Proposed mechanism of aldol reaction.
catalysts was studied. The efficacy of the catalysts remained
good up to a few cycles and the % conversion decreased in
a linear fashion with an increase in the number of cycles.
The successive decrease in the catalytic activity could be
construed as loss of the active (proline) component from the
polymer by hydrolysis. However, the latter was discounted
from the nature of the reaction system which is of nonhydro-
lyzing nature. The nitrogen analysis of the ‘‘as prepared’’
monolith and that used in five repeated cycles did not show
an appreciable variation in the % N contents. The other pos-
sibility was that some residual product got adsorbed on the
polymer monolith surface as the prolinyl part and the net-
work created by crosslinking contribute to such adsorption
process. In repeat experiments, the stirring of the used
monolith with ethyl acetate was subjected for longer dura-
tion (24 h) than studied earlier (1 h) to ensure complete cat-
alyst regeneration. The result was an improvement in the
sustainability of the catalytic activity (Fig. 7). The observed
retention of the catalytic activity after five cycles is reasona-
ble as also reported elsewhere.33
Cross Aldol Reaction
A wide range of aromatic aldehydes was used as substrate in
the cross-aldol reaction and for ketone-aldehyde cross-aldol
reaction under optimum conditions to give aldol adduct. The
% conversion was determined by monitoring the reaction
FIGURE 7 Reusability cycles of the polymer catalyst in cross-
aldol reaction of p-substituted benzaldehyde with acetaldehyde
(time ¼ 18 h, temperature ¼ 20 ꢀC, catalyst loading ¼ 30 mol %,
H2O:EtOH ¼ 6:4).
FIGURE 8 Effect of various substituents on aldehyde cross-
aldol reaction of p-substituted benzaldehyde with acetaldehyde
(time ¼ 18 h, temperature ¼ 20 ꢀC, catalyst loading ¼ 30 mol %,
H2O:EtOH ¼ 6:4).
PROLINE-BASED POLYMERIC MONOLITHS, GARG, AHN, AND CHAUHAN
1013

JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
5 Kaur, S.; Singh, G.; Gupta, V. K. J Polym Sci Part A: Polym
with HPLC. A series of p-substituted benzaldehyde reacted
with acetaldehyde under optimal conditions to give aldol
adduct with high degree of % conversion (Fig. 8). The induc-
tive nature of the substituent strongly affected the conver-
sion rate of the reaction. Significantly, a considerable conver-
sion, that is, 93% was also achieved with p-Cl as a
substituent. Remarkably higher % conversion, up to 99%,
was achieved with p-nitrobenzaldehyde. The strong electron
withdrawing effect on the electron-deficient aromatic alde-
hyde, along with the ester group present on the catalysts,
further increased the strength of hydrogen bond in the tran-
sition state. As discussed in the mechanism, the hydrogen
bond formation is the essential feature in the transition
state, which improved the performance of the catalyst.
Chem 2008, 46, 7299–7309.
6 Svoboda, J.; Sedlacek, J.; Zednik, J.; Dvorakova, G.; Trhli-
kova, O.; Redrov, D.; Balcar, H.; Vohlidal, J. J Polym Sci Part A:
Polym Chem 2008, 46, 2776–2787.
7 Islam, S. M.; Tuhina, K.; Mubarak, M.; Mondal, P. J Mol Catal
A: Chem 2009, 297, 18–25.
8 Sivudu, K. S.; Reddy, N. M.; Prasad, M. N.; Raju, K. M.;
Mohan, Y. M.; Yadav, J. S.; Sabitha, G.; Shailaja, D. J Mol Catal
A: Chem 2008, 295, 10–17.
9 Movassaghi, M.; Jacobsen, E. N. Science 2002, 298,
1904–1905.
10 Tang, Z.; Yang, Z. H.; Chen, X. H.; Cun, L. F.; Mi, A. Q.;
Jiang, Y. Z.; Gong, L. Z. J Am Chem Soc 2005, 127, 9285–9289.
In the ketone-aldehyde aldol reaction, a range of p-substi-
tuted benzaldehyde was made to react with distilled acetone
following the general procedure as cited earlier. Appreciably,
a high % conversion was obtained with p-chlorobenzalde-
hyde (89%), p-nitrobenzaldehyde (86%), and p-methoxyben-
zaldehyde (85%). Similar electronic effects on the % conver-
sion are also reported in literature for p-chlorobenzaldehyde,
p-cyanobenzaldehyde, and p-nitrobenzaldehyde for the modi-
fied proline-catalyzed cross aldol reactions though % conver-
sion was low.81 However, the % conversion with benzalde-
hyde (as the substrate) was found to be low. Notably, the %
conversion between 12 and 55% was achieved with a more
complex ketone, 2-acetylfuran. From the last two reactions, it
follows that extent and purposes of the reaction are depend-
ent on the structural effects of the substrates.
11 Paraskar, A. S. Synlett 2003, 582–583.
12 Copeland, G. T.; Miller, S. J. J Am Chem Soc 1999, 121,
4306–4307.
13 List, B.; Lerner, R. A.; Barbas, C. F., III. J Am Chem Soc
2000, 122, 2395–2396.
14 Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III. J Am Chem
Soc 2001, 123, 5260–5267.
15 Hamaya, J.; Suzuki, T.; Hoshi, T.; Shimizu, K.-I.; Kitayama,
Y.; Hagiwara, H. Synlett 2003, 873–875.
16 Luo, S. H.; Li, J. Y.; Xu, H.; Zhang, L.; Cheng, J. P. Org Lett
2007, 9, 3675–3678.
17 Calderon, F.; Fernandez, R.; Sanchez, F.; Fernandez-Mayora-
las, A. Adv Synth Catal 2005, 347, 1395–1403.
18 Dambruoso, P.; Massi, A.; Dondoni, A. Org Lett 2005, 7,
CONCLUSIONS
4657–4660.
Prolinyl methacrylate (monomer) was synthesized by bioca-
talytic route using esterification reaction for the covalent
attachment of 4-hydroxyproline to MAAc using immobilized
lipase. The monomer was polymerized to polymer monoliths,
and the latter were used as heterogeneous polymer catalysts
in the aldol reaction that was studied in three forms viz. sim-
ple aldol, cross aldol, and ketone-aldehyde reaction. The high
efficiency of the catalysts and selectivity for aromatic alde-
hydes was observed as high % conversion (even up to 99%),
was achieved with p-chloro and p-nitro substituted benzalde-
hydes. The results exhibit high reproducibility of results, and
the catalyst efficiency was retained at reasonably high levels
when studied up to five cycles.
19 Luo, S.; Li, J.; Zhang, L.; Xu, H.; Cheng, J.-P. Chem Eur J
2008, 14, 1273–1281.
20 Luo, S.; Zheng, X.; Cheng, J.-P. Chem Commun 2008, 44,
5719–5721.
21 Varela, M. C.; Dixon, S. M.; Lam, K. S.; Schore, N. E. Tetra-
hedron 2008, 64, 10087–10090.
22 Yan, J.; Wang, L. Synthesis 2008, 2065–2072.
23 Lital, T.-S.; Tzofit, K.; Moshe, P. Eur J Org Chem 2009,
992–996.
24 Akagawa, K.; Sakamoto, S.; Kudo, K. Tetrahedron Lett 2007,
48, 985–987.
25 Doyaguez, E. G.; Calderon, F.; Sanchez, F.; Fernandez-May-
oralas, A. J Org Chem 2007, 72, 9353–9356.
26 Xu, L.-W.; Ju, Y.-D.; Li, L.; Qiu, H.-Y.; Jiang, J.-X.; Lai, G.-Q.
REFERENCES AND NOTES
Tetrahedron Lett 2008, 49, 7037–7041.
1 Chauhan, G. S.; Mahajan, S.; Siddiqui, M. K.; Gupta, R. J
27 Jincan, Y.; Lei, W. Chirality 2009, 21, 413–420.
Appl Polym Sci 2004, 92, 3135–3143.
28 Benaglia, M.; Celentano, G.; Cozzi, F. Adv Synth Catal 2001,
2 Rouhi, A. M. C&EN 2004, 82, 47–62.
343, 171–173.
3 Clapham, B.; Cho, C.-W.; Janda, K. D. J Org Chem 2001, 66,
29 Gu, L. Q.; Wu, Y. Y.; Zhang, Y. Z.; Zhao, G. J. Mol Catal A:
868–873.
Chem 2007, 263, 186–194.
4 Kumari, K. A.; Sreekumar, K. J Appl Polym Sci 1996, 59,
30 Font, D.; Jimeno, C.; Perica`s, M. A. Org Lett 2006, 8,
2039–2048.
4653–4655.
1014
INTERSCIENCE.WILEY.COM/JOURNAL/JPOLA

ARTICLE
31 Giacalone, F.; Gruttadauria, M.; Marculescu, A. M.; Noto, R.
57 Putnam, D.; Langer, R. Macromolecules 1999, 32,
Tetrahedron Lett 2007, 48, 255–259.
3658–3662.
32 Gruttadauria, M.; Giacalone, F.; Marculescu, A. M.; Meo, P.
58 Miyajima, M.; Yoshida, M.; Sato, H.; Omichi, H.; Katakai, R.;
L.; Riela, S.; Noto, R. Eur J Org Chem 2007, 4688–4698.
Higuchi, W. I. Eur Polym J 1994, 30, 827–831.
33 Liu, Y.-X.; Sun, Y.-N.; Tan, H.-H.; Liu, W.; Tao, J.-C. Tetrahe-
59 Sanda, F.; Kamatani, J.; Handa, H.; Endo, T. Macromole-
dron: Asymmetry 2007, 18, 2649–2656.
cules 1999, 32, 2490–2494.
34 Gruttadauria, M.; Giacalone, F.; Marculescu, A. M.; Noto, R.
60 Lee, R. S.; Yang, J.-M.; Lin, T.-F. J Polym Sci Part A: Polym
Adv Synth Catal 2008, 350, 1397–1405.
Chem 2004, 42, 2303–2312.
61 Lee, R.-S.; Yang, J.-M. J Polym Sci Part A: Polym Chem
35 Akagawa, K.; Sakamoto, S.; Kudo, K. Tetrahedron Lett 2005,
2005, 43, 1708–1717.
46, 8185–8187.
62 Lee, R.-S.; Lin, Z.-K.; Yang, J.-M. J Polym Sci Part A: Polym
36 Chai, L. T.; Wang, Q. R.; Tao, F. G. J Mol Catal A: Chem
Chem 2006, 44, 4268–4284.
2007, 276, 137–142.
63 Mori, H.; Kato, I.; Endo, T. Macromolecules 2009, 42,
37 Andreae, M. R. M.; Davis, A. P. Tetrahedron: Asymmetry
4985–4992.
2005, 16, 2487–2492.
64 Chauhan, G. S.; Chauhan, S.; Kumar, Y.; Thakur, U. S.; Kan-
38 Miao, W.; Chan, T. H. Adv Synth Catal 2006, 348, 1711–
war, S. S.; Kaushal, R. J Appl Polym Sci 2007, 105, 3006–3016.
1718.
65 Chauhan, G. S.; Chauhan, S. J Appl Polym Sci 2008, 109,
39 Cordova, A. Tetrahedron Lett 2004, 45, 3949–3952.
47–55.
40 Gruttadauria, M.; Riela, S.; Lo Meo, P.; D’Anna, F.; Noto, R.
66 Kuo, T. M.; Gardner, H. W. Lipid Biotechnology; Marcel Dek-
Tetrahedron Lett 2004, 45, 6113–6116.
ker: New York, 2002; pp 365–367.
41 Gruttadauria, M.; Riela, S.; Aprile, C.; Lo Meo, P.; D’Anna,
67 Jaeger, K.-E.; Ransac, S.; Dijkstra, B. W.; Colson, C.; Van
F.; Noto, R. Adv Synth Catal 2006, 348, 82–92.
Heuvel, M.; Misset, O. FEMS, Microbiol Rev 1994, 15, 29–63.
42 Li, P. H.; Wang, L.; Wang, M.; Zhang, Y. C. Eur J Org Chem
68 Bellamy, L. J. The Infra-Red Spectra of Complex Molecules;
2008, 1157–1160.
John Wiley and Sons: New York, 1966; p 234.
43 Kucherenko, A. S.; Struchkova, M. I.; Zlotin, S. G. Eur J Org
69 Hayashi, Y.; Aratake, S.; Itoh, T.; Okano, T.; Sumiya, T.;
Chem 2006, 2000–2004.
Shoji, M. Chem Commun 2007, 9, 957–959.
44 Bellis, E.; Kokotos, G. J Mol Catal A: Chem 2005, 241,
70 Nielsen, A. T.; Houlihan, W. J. The Aldol Condensation in
Organic Reactions; Adams, R., Blatt, A. H., Boekelheide, V.,
Cairns, T. L., Cram, D. J., House, H. O., Eds.; John Wiley &
Sons: New York, 1968; p 16.
166–174.
45 Kehat, T.; Portnoy, M. Chem Commun 2007, 2823–2825.
46 Goren, K.; Kehat, T.; Portnoy, M. Adv Synth Catal 2009, 351,
59–65.
71 Nyberg, A. I.; Usanp, A.; Pihko, P. M. Synlett 2004,
1891–1896.
47 Sanclimens, G.; Crespo, L.; Giralt, E.; Albericio, F.; Royo, M.
J Org Chem 2005, 70, 6274–6281.
72 Pihko, P. M.; Laurikainen, K. M.; Usano, A.; Nyberg, A. I.;
Kaavi, J. A. Tetrahedron 2006, 62, 317–328.
48 Wu, Y. Y.; Zhang, Y. Z.; Yu, M. L.; Zhao, G.; Wang, S. W.
Org Lett 2006, 8, 4417–4420.
73 Hayashi, Y.; Sumiya, T.; Takahashi, J.; Gotoh, H.; Urushima,
T.; Shoji, M.; Angew Chem Int Ed 2006, 45, 958–961.
49 Jung, J.-C.; Kim, H. D.; Ree, T.; Jhon, M. S. J Polym Sci Part
A: Polym Chem 1993, 31, 3377–3385.
74 Hayashi, Y.; Aratake, S.; Okano, T.; Takahashi, J.; Sumiya,
T.; Shoji, M. Angew Chem Int Ed 2006, 45, 5527–5529.
50 Hiroki, A.; Maekawa, Y.; Yoshida, M.; Kubota, K.; Katakai, R.
Polymer 2001, 42, 1863–1867.
75 Mase, N.; Nakai, Y.; Ohara, N.; Yoda, H.; Takabe, K.; Tanaka,
F.; Barbas, C. F., III. J Am Chem Soc 2006, 128, 734–735.
51 Hiroki, A.; Maekawa, Y.; Katakai, R.; Yamashita, T.; Muroya,
Y.; Katsumura, Y.; Yoshida, M. Macromolecules 2006, 39,
4132–4137.
76 Jiang, Z.; Liang, Z.; Wu, X.; Lu, Y. Chem Commun 2006,
2801–2803.
52 Mori, H.; Matsuyama, M.; Sutoh, K.; Endo, T. Macromole-
77 Zotova, N.; Franzke, A.; Armstrong, A.; Blackmond, D. G. J
cules 2006, 39, 4351–4360.
Am Chem Soc 2007, 129, 15100–15101.
78 Gruttadauria, M.; Giacalone, F.; Marculescu, A. M.; Salvo, A.
53 Mori, H.; Matsuyama, M.; Endo, T. Macromol Chem Phys
M. P.; Noto, R. ARKIVOC 2009, 5–15.
2008, 209, 2100–2112.
79 Atamas N. A.; Atamas A. A. World Acad Sc Eng Technol
54 Mori, H.; Iwaya, H.; Endo, T. Macromol Chem Phys 2007,
2009, 55, 1–4.
208, 1908–1918.
80 Gruttadauria, M.; Giacalone, F.; Notoa, R. Adv Synth Catal
55 Skey, J.; O’Reilly, R. K. J Polym Sci Part A: Polym Chem
2009, 351, 33–57.
2008, 46, 3690–3702.
81 Tang, Z.; Yang, Z. H.; Chen, X. H.; Cun, L. F.; Mi, A. Q.;
56 Mori, H.; Kato, I.; Matsuyama, M.; Endo, T. Macromolecules
Jiang, Y. Z.; Gong, L. Z. J Am Chem Soc 2005, 127, 9285–9289.
2008, 41, 5604–5615.
PROLINE-BASED POLYMERIC MONOLITHS, GARG, AHN, AND CHAUHAN
1015