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Journal of Molecular Catalysis A: Chemical 370 (2013) 56– 63
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Catalysis A: Chemical
j o ur nal ho me p age: www.elsev ier .com/ locate /molcata
n situ inhibitor (HCl) removal promoted heterogeneous Friedel–Crafts reactionf polystyrene microsphere with Lewis acids catalysts
iang Li, Rongyue Zhang, Juan Li, Xiaofeng Yan, Lianyan Wang, Fangling Gong ∗, Zhiguo Su,uanghui Ma ∗
ational Key Lab of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China
r t i c l e i n f o
rticle history:eceived 29 September 2012eceived in revised form 6 December 2012ccepted 6 December 2012
a b s t r a c t
Friedel–Crafts (FC) acylation is regarded as one of the key routes for graft substitution reaction. In thisstudy, by-product HCl formed in the FC reaction has a major drawback inhibitory effect on the Lewis acidcatalysts’ activity, and therefore reduces the FC reaction yield. With the need for more environmentallyand economically benign processes, in situ inhibitor removal approach can be applied as a new strategy on
vailable online 3 January 2013
eywords:Clolystyrene microspheresriedel–Crafts reaction
one pot heterogeneous FC acylation. The inhibitor can be taken away from the vicinity of the catalysts assoon as it is formed. The chlorine weight percentage after FC acylation on polystyrene (PSt) microspheresunder mild reaction conditions can be enhanced from 3.2% to 4.0% in acetone, from 2.9% to 3.6% inmethanol, and from 4.4% to 5.3% in chloroform, respectively. It is important to note that the key featureof this reaction is operational simplicity and high yield.
n situ inhibitor removal
. Introduction
Aryl carbonyl compounds have garnered extensive attentions synthetic targets, most notably in the chemical production ofonsteroidal anti-inflammatory drugs (NSAIDs). Common drugsuch as naproxen, ibuprofen, fluribiprofen, and dichlofenac all con-ain this moiety [1,2]. Friedel–Crafts (FC) acylation reactions haveerved as one of the key premier routes to these products. Inecent years, this methodology has become an emerging field andxpanded to include esters, amides, and lactones as carbonyl cou-ling partners [3–8].
However, the catalytic activity of Lewis acid in FC process isasily inhibited by products as the reaction goes on, together withteric hindrance effect, which leads to the FC reaction yield androductivity economically infeasible. Consequently much atten-ion has now been paid to eliminate the product inhibition on theewis acid catalysts in the liquid phase through the design of solidupported catalysts that can divide the catalysts and products inwo different phases [1,3,6]. These solid–liquid biphase systemsere carried out to prevent the products dissolved in the liquidhase from inhibiting the activity of solid supported Lewis acid
atalysts. For example, solid zeolites, clay or resin-supported Lewiscids were found to be quite promising for FC acylation reactionsf activated aromatic compounds [9–12].∗ Corresponding authors. Tel.: +86 010 82627072; fax: +86 010 82627072.E-mail addresses: [email protected] (F. Gong), [email protected]
G. Ma).
381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.ttp://dx.doi.org/10.1016/j.molcata.2012.12.009
© 2012 Elsevier B.V. All rights reserved.
Polystyrene (PSt) is a special type of important aromatic com-pound family, which are typically used in biomedical applicationsdue to their ability to facilitate procedures such as cell sortingand immune precipitation [13–19]. However, it is essential toenable the matrix surface to be more hydrophilic in order toavoid irreversible interactions or protein denaturation. Thus, sur-face hydrophilization of the PSt beads should be performed by usinghydrophilic polymer. The FC acylation or FC alkylation FC reactionis usually the first step for the functionalization of PSt micro-spheres, for example, bone graft substitution to the aromatic ring.However, since the conventional FC alkylation method uses highlycarcinogenic chloromethyl ether as chloromethylation reagent, thedevelopment of PSt functional substitution through FC acylationreaction has gained much attention [17–24]. In normal practice,the catalyst in FC reaction was Lewis acid such as metal halides(AlCl3), with an acylation agent in a liquid solvent [4,5]. Actually, astoichiometric excess of Lewis acid catalysts were used to providefavorable guarantee for the synthetic yield [6–8]. In FC acylationprocess of microspheres, the product acyl-PSt microspheres andthe Lewis acid catalysts were in the solid and liquid phase, respec-tively, thus, it is regarded that the products have little effect on thecatalytic activity.
Previous uncharted, we find that by-product HCl formed in FCacylation process does not evaporate immediately, otherwise, iseasily soluble in type of solvents used, which has a major drawback
inhibitory effect on the synthetic efficiency according to some novelmeasurements such as laser scanning confocalmicroscope (LSCM).To the best of our knowledge, our work to this field is the studyof inhibitor on heterogeneous FC acylation reaction catalyzed by
Q. Li et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 56– 63 57
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the methanol was used as solvent, there were 100 g methanol,10.08 g dried PSt microspheres, 25.2 g SnCl4, 27.5 g chloroacetylchloride in the pot. When the acetone was used as solvent, therewere 100 g methanol, 10.25 g dried PSt microspheres, 28.2 g SnCl4,
Sch
ewis acids, using in situ inhibitor removal strategy to enhance theatalysis process, which has virtually not been reported in the openiterature.
. Experimental
.1. Materials
Divinylbenzene (DVB, Dongda Chemical Engineering Groupo., China) was washed with 5 wt% aqueous sodium hydroxideolution and deionized water, and dried by anhydrous sodiumulfate. Sodium dodecyl sulfate (SDS, biochemical grade) wasurchased from Merck. Sodium sulfate (Na2SO4), sodium bicar-onate (NaHCO3), benzoyl peroxide (BPO, with 25 wt% moistureontent, reagent grade), heptane, tetrahydrofuran (THF), toluene,ethanol, acetone, 1,2-dichloroethane, 4-methyl-2-pentanol, N,N-
imethylformamide, hydroquinone, chloroacetyl chloride, anhy-rous aluminum chloride (AlCl3), anhydrous stannic chlorideSnCl4), anhydrous lithium chloride (LiCl) and other organic sol-ents were purchased from Beijing Chemical Reagents Company.auryl alcohol (LOH) was purchased from Tokyo Kasei Kogyoo. Ltd. Polyvinyl alcohol (PVA, degree of polymerization 1700,egree of hydrolysis 88.5%) was kindly provided by Kuraray (Japan).olystyrene (PSt) was prepared by membrane emulsion polymer-zation. All the reagents were of analytic grade unless otherwiseescribed.
.2. Preparation of porous polystyrene microspheres
The mixture of monomer and porogen dissolving BPO initiatornd lauryl alcohol as interface stabilizer were used as dispersedhase. An aqueous solution of PVA (stabilizer), SDS (surfactant),a2SO4 (electrolyte), and HQ (inhibitor) was used as continuoushase. The dispersed phase was pressed through the pores of thePG (Shirasu Porous Glass) membrane into the aqueous phaseontinuously by applying nitrogen gas pressure. The membraneor emulsification was purchased from SPG Technology. 3.1, 5.2,0.2-�m membranes were chosen in this study. The droplet sizerepared was about four to six times as large as the pore size of theembrane. In this context, we noted a potential connection to our
revious work demonstrating that the SPG membrane emulsifica-ion process provided emulsion products [13,14].
The obtained emulsion was transferred to a four-neck glasseparator flask equipped with a semicircular anchor-type blade,
condenser, and a nitrogen inlet nozzle. The emulsion was bub-led with nitrogen gas for 1 h. Then, the nozzle was lifted and theemperature was elevated to 80 ◦C gradually. Then polymerizationas carried out for 24 h under nitrogen atmosphere. The prepared
St microspheres were collected and washed with hot water andthanol for four times, extracted in a Soxhlet apparatus with ace-one, and then dried under vacuum.
.3. Heterogeneous FC reaction
Catalytic reactions were carried out in a four-neck glass flasktted with a cooling condenser and in water bath. The batch
.
experiments were equipped with mechanical stirring at 150 rpm.An organic solvent was added into the pot to swell the PSt micro-spheres fully for 24 h. The mass stoichiometric ratio (mL/g) betweensolvent and microsphere was 12.5:1. The mass stoichiometric ratio(mol/mol) of microsphere, Lewis acid catalyst (AlCl3, SnCl4, LiCl)and acylation agent was 1.0:1.1:1.2. 0.001–0.005 vvm (air vol-ume/culture volume/min) N2 was ventilated into the pot. Theacylation formula was showed as below (Scheme 1). The ben-zene rings of microspheres undergo acylation predominantly at thepara-position [4,15–17].
After the acylation reaction finished, the grafting PSt micro-spheres were collected and treated with cold hydrochloric acid(3%, w/v) to remove the catalyst. After filtering, the microsphereswere washed with THF to remove residual solvent from the solidPSt, washed again with distilled water until free of chloride ions inthe cleaning solution, and dried at 60 ◦C under vacuum. In situ HClremoval process, solid sodium bicarbonate was used to capture themineral acid (sodium bicarbonate/PSt = 1:1 mol/mol).
2.4. Preparation of HCl at different titers in solvent
When H2SO4 in dropping funnel was dropped slowly into thesolid NaCl in 200 mL four-neck glass flask, HCl was produced anddissolved in the solvent. Different solvent systems dissolved HClat saturated solubility at different temperature. The solvent dis-solved HCl at saturation concentration was mixed with the samefresh solvent via stoichiometric ratio to prepare HCl at differentconcentration (Fig. 1).
2.5. HCl effect on catalytic reactions
Aqueous organic solvents containing different concentrations ofHCl were added individually to the catalytic reaction system. When
Fig. 1. HCl at saturation concentration was obtained in various solvents. 1. Sulfuricacid in dropping funnel. 2. Sodium chloride in four-neck flask. 3. HCl in different sol-vent. 4. Electro thermal water bath.5 Electronic balance. 6. Residual gas absorptionapparatus.
58 Q. Li et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 56– 63
s befo
3umTcm
2
2
oedv
2
o(
2
wsUt
2
w
Fig. 2. SEM micrographs of prepared acyl-PSt microsphere
0.7 g chloroacetyl chloride in the pot. When the chloroform wassed as solvent, there were 100 g chloroform, 5.36 g dried PSticrospheres, 13.4 g SnCl4, 14.6 g chloroacetyl chloride in the pot.
he reaction time was controlled at 5 h, and the temperature washosen as 50 ◦C. Chlorine weight percentage after FC acylation waseasured to study the HCl inhibitory effect.
.6. Characterization
.6.1. Measurement of size distribution of microspheresThe droplet diameters before and after polymerization were
bserved with an XSZ-H3 optical microscope (Coic, China). Diam-ters of about 400 droplets were counted to calculate the averageiameter and the size distribution, which was expressed by a CValue.
.6.2. Observation of surface feature of microspheresThe morphology and porous features of microspheres were
bserved by JSM-6700F (JEOL, Japan) scanning electron microscopySEM).
.6.3. Measurement of surface area and pore size of microspheresSpecific surface area and pore size distribution of microspheres
ere characterized by BET nitrogen adsorption/desorption mea-urements with a Quantasorb apparatus (Quantachrome Corp.,
SA) at 60 ◦C. Samples were degassed under vacuum for 24 h prioro data collection.
.6.4. FT/IR spectra measurement of PSt and modified PStThe JASCO FT/IR 660 plus infrared spectrometer (JASCO, Japan)
as used for Fourier transform infrared (FT/IR) analyses.
re (1(a) and 1(b)) and after (2(a) and 2(b)) washing steps.
2.6.5. Zeta potentials and conductivity measurementsZeta potentials and conductivity of organic solvents and HCl-
dissolved organic solvents were obtained in room temperatureusing Zetasizer Nano ZS (Malvern Instruments Ltd., UK) equippedwith pH, conductivity probes.
2.6.6. Laser scanning confocalmicroscope (LSCM) measurementFluorescein isothiocyanate isomer I (FITC)-labeling acylated
PSt microspheres adsorption experiments were conducted ina 4 ◦C incubator, 200 rpm. After 24 h adsorption, the micro-spheres were separated from the FITC solution by centrifugationand washed with pH 8.0, 0.05 M PBS buffer five times toremove residual FITC molecules completely. After being placedon a slide glass and being covered with cover glass, themicrospheres were observed with a TCS SP2 laser scanning con-focalmicroscope (LSCM) (Leica, Germany) to visualize the FCacylation efficiency of FITC-labeling chloroacetyl chloride ontoPSt microspheres. Chloroacetyl PSt microspheres can be markedby FITC, while unmodified PSt microspheres cannot. The sam-ples were detected at 488 nm of excitation wavelengths, andthe fluorescent images at 520–550 nm wavelengths were thentaken.
2.6.7. Measurement of acylation yieldThe microspheres were firstly dried at 105 ◦C for 2 h. 0.1 g
dried microspheres, 1.5 g potassium nitrate 2 g sodium hydrox-ide were measured and put into a Ni-pot. The mixture wasburned out. The chlorine element contained in the sample was
washed fully and transformed into chloride ions with deion-ized water. Subsequently, the traditional Volhard method wasadopted to analyze the chlorine content (wt%). The chlorineweight percentage measured was used to show the FC acylationyield.
Q. Li et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 56– 63 59
4000 350 0 300 0 250 0 200 0 150 0 100 0 50 020
30
40
50
60
70
80
90
100T
(%)
-1
PSt
Acyl- PSt
670 cm-1
F
3
3
cbaccFastacP
3
lAmstutma
TS
s
-10
-5
0
5
65
4
32
1
6
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1
HCl-satu rate d chlo roform
Chlo roform
HCl-satu rate d meth anol
HCl-satu rate d a ceto ne
Meth anolZeta
po
ten
tial
(m
V)
Aceto ne
less than 5 g/100 g methanol, 5 g/100 g acetone and 5 g/1000 g chlo-roform, respectively. As the increase of HCl concentrations, thechlorine weight percentage decreased and finally maintained at acertain degree. The reason of low FC reaction yield was still under
0.0002
0.0004
0.0006
0.0008
HCl-satu rate d c hlo roform
chlorofr om
HCl-satu rate d a ceto ne
Co
nd
ucti
vit
y(m
S/c
m)
Aceto ne
cm
ig. 3. FT/IR spectra of PSt microspheres before (black) and after (red) acylation.
. Results and discussion
.1. Preparation of PSt microspheres
Uniformly sized crosslinked PSt microspheres with high spe-ific surface areas and narrow size distribution were synthesizedy membrane emulsification technique as starting materials forcylation. The span value of PSt microspheres was 0.688 with arosslinking degree of 20%. The average diameter, pore size and spe-ific surface area were 29.2 �m, 14.3 nm and 502 m2/g. Meanwhile,C catalysts, liquid acylation agents and inorganic salts can easilyccumulate on the surface of PSt microspheres (Fig. 2a). Thus, atrict washing step was needed for the further modification or syn-hesis processes (Fig. 2b). FT/IR analysis showed a band at 670 cm−1
scribed to the stretching vibration absorption of –C Cl bond inhloroacyl group, which confirmed that solid-phase acylation onSt microspheres actually occurred (Fig. 3).
.2. Inhibitor of the PSt FC acylation processes
HCl was a conventional mineral acid by-product of the FC acy-ation processes catalyzed by many metal halides Lewis acids.ccording to measurement, we found HCl was quite soluble inany aspects of common acylation solvents used in reaction
ystem. Table 1 showed the solubility of HCl was substan-ially different in different solvents at different temperatures
nder normal pressure. When methanol was used as the acyla-ion solvent, the saturated HCl can reach nearly 100.2 g/100.0 gethanol. The solubility of HCl in solvent followed the orders methanol > ethanol > acetone > n-butanol > glycerol > n-hexane >
able 1olubility of HCl in different FC acylation solvents.
Solvent Solubility (g/100 g solvent) Relative polaritya
0 ◦C 25 ◦C
Waterb Miscible Miscible 1.0Methanol 100.2 61.6 0.762Ethanol 71.3 50.5 0.654Acetonec 57.9 42.5 0.355n-Butanol 50.2 38.5 0.586Glycerol 33.5 26.1 0.812n-Hexane 1.2 0.8 0.009Chloroform 0.9 0.4 0.259
a The values for relative polarity were normalized from measurements of solventhifts of absorption spectra [25].
b Water cannot be used as the FC acylation solvent in this study.c Acetone turning red.
-15
Fig. 4. (a) Effect of HCl on the Zeta (�) potential of acylation solvents.
chloroform. Several polar solvents resulted in high HCl solubility.Thus, the polarity of solvent was one of key factors affecting theinhibitor concentration.
The chlorine weight percentage after FC acylation on PStmicrospheres varied dramatically at different initial inhibitoryconcentrations of HCl. Varied organic solvents were used as theswelling and mixing reagents. Fig. 6a showed the inhibitory effecton the chlorine weight percentage when the titers of HCl were
0.0000
0.00
0.02
0.04
0.06
0.08
13.2
13.4
13.6
13.8
14.0
14.2
14.4
14.6
14.8
15.0
HCl-satu rate d meth ano l
Co
nd
uct
ivit
y(m
S/c
m)
Meth anol
Fig. 5. Effect of HCl on the conductivity of acylation solvents.
60 Q. Li et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 56– 63
0 5 10 15 200
1
2
3
4
5
Ch
lori
ne
wei
gh
t p
erce
nta
ge
(%)
Initial HC l conce ntratio ns ( g/1 00g meth anol)
(a)
0
1
2
3
4
5 (b)Meth anol syst em
contr olled b atch
Ch
lori
ne w
eig
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perc
en
tag
e (
%)
in situ HCl re mova l
0 5 10 15 200
1
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3
4
5 (a)
Ch
lori
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weig
ht
per
cen
tag
e (%
)
Initial HC l conce ntratio ns (g/1 00g a ceto ne)
0
1
2
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5 (b)
contr olled b atch
Ch
lori
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weig
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per
cen
tag
e (%
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in situ HCl remova l
Aceto ne s yst em
0 5 10 15 200
1
2
3
4
5 (a)
Ch
lori
ne
weig
ht
per
cen
tag
e (%
)
Initial HC l c once ntratio ns (g/1 000g c hlo roform)
0
1
2
3
4
5
6
(b)Chlo roform s yst em
contr olled b atch
Ch
lori
ne
wei
gh
t p
erce
nta
ge
(%)
in situ HCl re mova l
F solveF
wbfrosmrs
crb�fc
ig. 6. (a) HCl inhibition on the PSt Friedel–Crafts acylation processes in differentriedel–Crafts acylation processes in different solvents.
orldwide research. A function of Lewis acid catalysts was to sta-ilize the transient carbocations and maintain a proper chiral formor reaction. Mineral acids can challenge with Lewis acids to inter-upt the enantioselective reactions, which decreased the activityf Lewis acid catalyst. Especially, when acetone was used as theolvent, the colorless acetone turned extremely red after dissolvedultivalent metal cations from Lewis acids catalysts. The possible
eason was that the Al3+/Sn4+/Li+–acetone complexes possessed aignificantly large red shift [26,27].
Zeta (�) potential is a measure of the electrical potential thatauses interparticle repulsion. The � potential is correlated with theheological properties of dispersions [28], and this correlation can
e used in the formulation of modified microspheres. Fig. 4 showspotential changed dramatically when HCl dissolved in the dif-erent solvents. In detail, the pure solvents acetone, methanol andhloroform had a � potential of −14.2 mV, +4.96 mV and +2.12 mV,
nts: � methanol, © acetone, ♦ chloroform; (b) In situ HCl removal enhanced PSt
respectively. However, HCl-saturated acetone, methanol and chlo-roform had a � potential of +0.13 mV, −3.56 mV and +3.02 mV,respectively. These values were not surprising, considering that themineral acid (HCl) had a disturbance on the solution environmentand therefore reduced the FC catalysis efficiency. Moreover, HClhad the different effect on the acylation solvents, for example, the� potential of chloroform was less affected than the other solvents.
For the enhancement of heterogeneous FC reaction with Lewisacids catalysts, the conductivity should stay approximately con-stant. However, HCl had an important effect on the conductivityof acylation solvents. Fig. 5 shows conductivity changed dramat-ically when HCl dissolved in the different solvents. The pure
solvents acetone, methanol and chloroform had a conductiv-ity of 6.95 × 10−4 mS/cm, 0.0612 mS/cm and 2.04 × 10−4 mS/cm,respectively. However, HCl-saturated acetone, methanol and chlo-roform had a conductivity of 3.01 × 10−4 mS/cm, 14.0 mS/cm and
Q. Li et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 56– 63 61
chloro
3oiit
3
scgba
watrfrbib
vct0miHcs
tmPcwmo
3
a
Fig. 7. LSCM of FC acylation on microsphere, a, HCl inhibition process in
.77 × 10−4 mS/cm, respectively. Moreover, HCl had a huge effectn the conductivity of methanol, which resulted in a 228-foldncrease of conductivity. The soluble H+ can be adsorbed to thentermediate of the FC acylation process (Scheme 1), thus, affecthe FC catalysis efficiency and finally reduced the catalysis yield.
.3. In situ inhibitor removal enhanced PSt FC acylation
Present industrial practice requires a stoichiometric amount ofoluble Lewis acids (e.g., AlCl3) or strong mineral acids (e.g., HF) asatalysts [3–5]. Although a number of economically infeasible andreen Lewis acid catalysts had been found to facilitate FC acylation,y-product mineral acids dissolved in solvent inhibited acylationfter accumulation to a certain concentrations.
In this study, solid neutralization agent sodium bicarbonateas chose for in situ mineral acid removal, which was an efficient
pproach to remove the inhibitory by-product from the vicinity ofhe catalysts as soon as it is formed. As shown in Fig. 6b, the chlo-ine weight percentage was improved from 3.2% to 4.0% in acetone,rom 2.9% to 3.6% in methanol, and from 4.4% to 5.3% in chloroform,espectively. In situ mineral acid removal can avoid direct contactetween by-product and Lewis acids in liquid environment, and
ncrease the yield by overcoming the inhibitory or toxic effects ofy-product.
Mineral acid can be neutralized by sodium bicarbonate, and con-ersed to carbon dioxide gas and solid sodium chloride. Sodiumhloride was insoluble in organic solvents used. For example,he solubility of sodium chloride at normal temperature was.05 g/g ethanol. The major roles of acylation solvents were PSticrospheres swelling, Lewis acids dissolving and reagents mix-
ng [15,17,19]. As HCl had a relatively low solubility in chloroform,Cl showed little effect on the � potential and conductivity of inhloroform system, and the 4.4% chlorine content in chloroformystem was obtained without in situ HCl removal (Fig. 6b).
Laser scanning confocal microscope (LSCM) was used to studyhe HCl inhibition effect for the first time. As shown in figure below,
uch less fluorescence was detected from the surface of acylatedSt micropsheres under HCl inhibition (Fig. 7a), while great fluores-ent acylated PSt micropsheres were observed with a high chlorineeight percentage after FC acylation with in situ HCl removal treat-ent (Fig. 7b). This comparative study provided a straight insight
n the HCl inhibition effect on FC acylation on PSt microspheres.
.4. Factors affected PSt FC acylation processes
After initial optimization, we investigated other factors thatffected PSt FC acylation processes.
form b, in situ HCl removal enhanced acylation processes in chloroform.
As the acylation reaction can easily occurred on the swellingPSt microspheres, smaller microsphere diameters contributed torelatively higher specific surface area and inner critical pathway,which improved the acylation yield (Fig. 8a).
Insufficient solvent (15 mL) cannot swell PSt microspheres suf-ficiently. But the additional crosslinking reaction easily occurredin less solvent volume [17]. If the volume of the solvent continu-ously increased, the concentrations of the chloroacylation reagentbecame lower, resulting in a declining of the chlorine content(Fig. 8b).
Although the acidity of the three Lewis acid catalysts followsthe order: AlCl3 > SnCl4 > LiCl, under the same reaction conditionsSnCl4 enabled the highest yield reaction. These Lewis acids can dis-solve in many organic solvents totally. AlCl3 had strong ability toaccept electron from the benzene ring of PSt microspheres, whichcaused fragmentation of the microspheres and affected the modi-fication processes [17–20]. SnCl4 was a suitable Lewis acid catalystfor the FC acylation of PSt microspheres (Fig. 8c). Initially, as a plentyof hydrogen atoms in benzene ring of microspheres was availablefor substitution reaction, the yield increased. As time went by, thecontent of the chloroacyl group on PSt microspheres may decrease,since some additional crosslinking occurred [4,17].
Amount of catalyst was one of key factors affecting the acy-lation processes [21]. As the increase of catalyst amounts, thechlorine weight percentage increased. When the stoichiometricratio (mol/mol) between SnCl4 and PSt was more than 1.1, thechlorine weight percentage did not changed (Fig. 8d).
Fig. 8e showed when the ratio of acylation reagent/PSt(mol/mol) was less than 1.2:1, the chlorine weight percent-age increased together with increase of acylation reagent. If thestoichiometric ratio was more than 1.2:1, the chlorine weight per-centage did not increase. As the acylation reaction occurred, sterichindrance of the PSt linkage network affected the molecular inter-action which resulted the maximum reaction yield.
Fig. 8f showed the effect of temperature on the yield. Chiral,functional Lewis-acid catalysts stabilized the transient carboca-tions and were able to mediate enantioselective reactions underthe proper temperature [10–12]. High temperature can acceler-ate the formation of carbocations so as to improve the FC reaction[9].
After one batch reaction, the acyl-PSt microspheres werecleaned and dried. We hoped to increase the chlorine weight per-centage. Thus, the acyl-PSt microspheres were put into the reaction
pot again under the same acylation condition. The fed-batch strat-egy was typically used in catalyst-industrial processes to overcomeproduct/by-product inhibition with a high yield or productivityin the reactor. However, the fed-batch strategy cannot improve
62 Q. Li et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 56– 63
0 2 4 6 8 100
1
2
3
4
5 50 μm
30 μm
15 μm
Ch
lori
ne
wei
gh
t p
erce
nta
ge
(%)
Time (h)
PSt dia meter effec t
(a)
0 2 4 6 8 100
1
2
3
4
5
(b)
15 mL
25 mL
35 mL
Ch
lori
ne w
eig
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perc
en
tag
e (
%)
Time (h)
Solv ent volu me eff ect
0 2 4 6 8 100
1
2
3
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5
(c)
AlCl3
SnCl4
LiCl
Ch
lori
ne
wei
gh
t p
erce
nta
ge
(%)
Time (h)
Lewis-acid s effect
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.60
1
2
3
4
5
(d)
Catal yst a mou nt eff ect
Ch
lori
ne w
eig
ht
perc
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e (
%)
Cat/PS t (mol)
0.0 0.4 0.8 1.2 1.60
1
2
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(e)Ch
lori
ne
wei
gh
t p
erce
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(%)
Chlo roace tyl chlo rid e/PSt (mol)
Acylation reage nt effec t
0 2 4 6 8 10 120
1
2
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5
(f)
37 oC
25 oC
0 oC
Ch
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wei
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erce
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Time (h)
Tempe ratu re eff ect
0 5 10 15 20 25 300
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(g)
Batc h 3Batc h 2
Ch
lori
ne
wei
gh
t p
erce
nta
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(%)
Time (h)
Batc h 1
Fed -batc h re action eff ect
Fig. 8. PSt Friedel–Crafts acylation processes affected by factors including (a) PSt diameter, (b) solvent volume, (c) Lewis-acids and reaction time, (d) catalyst amount, (e)acylation reagent, (f) reaction temperature and (g) fed-batch reaction.
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Q. Li et al. / Journal of Molecular
hlorine weight percentage in this study. One batch reaction wasnough for the FC acylation (Fig. 8g).
. Conclusions
In summary, mineral acid can inhibit Lewis acids catalysts ineterogeneous FC reaction system. In situ inhibitor removal is a suc-essful strategy to improve the heterogeneous acylation efficiencynder mild reaction conditions, which render the process econom-
cally attractive. Short reaction times, easy work-up, high yields,nd easy performing of the process are other obvious advantagesf the present method.
cknowledgments
Financial support by the National Science Foundation of ChinaNo. 21206175, 20820102036 and No. 51103158) and by the Beijingatural Science Foundation (Preparation of polystyrene particlesith diverse physical properties and evaluation of the effect on
ellular response) were gratefully acknowledged.
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