Hydrogen bonding is one of the most important interactions encountered in the gas,liquid and solid states. It plays a key role in mediating many chemical,physical and biochemical processes [1, 2, 3]. It is a bond between an electron-deficient hydrogen and a region of high electron density [4,5],typically between a hydrogen atom attached to either O or N and another electronegative atom such as F,N or O. Recently,hydrogen-bond- mediated catalytic processes have been studied extensively and several outstanding reviews have been published [6, 7, 8].
b-cyclodextrin (b-CD) is a cyclic oligosaccharide consisting of seven D-glucopyranose units linked by α-(1-4) glycosidic bonds to form a torus-shape with an inner hydrophobic and outer hydrophilic structure. It can efficiently accommodate a wide variety of compounds in the cavity to form inclusion complexes in solution or in the solid state [9,10]. The selective association of target molecules by b-CD is extremely similar to the molecular recognition of a substrate by an enzyme. b-CD has been used to catalyze a number of chemical reactions via. non-covalent bonding,and has demonstrated enzyme-like specificity and selectivity [11, 12, 13]. Recent reports have indicated that the presence of hydrogen bonds between b-CD and the substrate results in a significant improvement in the reaction selectivity [14, 15, 16]. However,b-CD is not a good model for enzyme catalysis because b-CD has limited catalytic activity due to the weak intermolecular interactions between b-CDand the substrate. If the catalytic site could have the synergistic effects of more functional groups,recognition should be m ore precise,and more like what is seen in enzyme recognition [17, 18, 19]. But to the best of our knowledge,b-CD derivatives based on the synergistic effects of multiple hydrogen bonds have not been applied to organic reactions,despite some reports on the acceleration of reaction rates and obvious enhancements in selectivity [20, 21, 22].
In the present study,b-cyclodextrin-functionalized cellulose polymer (b-CDCP) has been developed to investigate the production of natural benzaldehyde under mild conditions by the synergistic effects of additional weak interactions e.g. hydrogen-bonding between the polymer and the substrate (Scheme 1). Various physical chemistry techniques have been used to characterize the structure of the polymer. Density functional theory (DFT),a useful technique to define the host-guest interactions and the catalytic mechanism,has been employed to investigate the nature of the inclusion process on the reaction. Additionally,a plausible oxidation mechanism has been proposed based on XPS,FTIR and other experimental results.
b-CDCP was synthesized by reacting b-CD with epichlorohydrin cross-linked cellulose in a NaOH solution according to a procedure reported earlier with some modifications [23]. 2 g of cellulose was dispersed in 30 mL of 25% NaOH solution. 7 mL of epichlorohydrin was then added dropwise to the mixture. The mixture was further stirred at 40 °C for 4 h. Subsequently,the intermediate was filtered,washed by acetone and water to remove epichlorohydrin thoroughly,and then centrifuged and rinsed with water to remove any residual NaOH and any water-soluble impurities until the pH of the supernatant approached neutral. The intermediate was dried under vacuum at 40 °C for 12 h to obtain epichlorohydrin modified cellulose (CE).
2 g CE dispersed in 30 mL NaOH solution (25%) was mixed with 0.7 g of b-CD,and the mixture was stirred at 40 °C for 6 h. The solid product was separated by centrifugation and washed until neutral with distilled water. Finally,it was dried at 60 °C for 24 h under vacuum. The amount of b-CD immobilized on the cellulose was determined to be 0.146 mmol/g by the previously reported method [24].
b-CDCP was completely dispersed in 25 mL deionized water. An equimolar amount of cinnamaldehyde was then added. The solution was stirred at 25 °C and 250 r/min for 1 h,and then centrifuged. The resultant solid was washed with distilled water to remove any residual substrate,and dried at 50 °C for 12 h under vacuum. The product was stored in a desiccator before use.
FTIR spectra (400-4000 cm−1) were recorded on a Bruker TENSOR 37 FT-IR spectrometer. XPS spectra were measured on a Vacuum Generator ESCALAB 250 spectrometer with an Al Kα monochromatic X-ray source and a hemispherical analyzer. A fixed analyzer pass energy of 150 eV was used for the survey scans,and high-resolution scans of core-level regions were recorded using a 20 eV pass energy. All core-level spectra were referenced to the C1s neutral carbon peak at 284.5 eV and obtained at a takeoff at 90° to the sample surface.
1 mmol of cinnamaldehyde was dissolved in 25 mL of deionized water at 70 °C in a 100 mL three-necked flask equipped with a reflux condenser and electromagnetic stirrer. 1 g of b-CDCP was then added and the mixture was stirred for 30 min. 2 mmol of NaHCO3 dissolved in 4 mL of 30% H2O2 was slowly added dropwise. The mixture was stirred at 70 °C for 3 h,and then extracted with ethyl acetate and centrifuged. The organic phase was analyzed by GC-MS with naphthalene as an internal standard. The data were reproducible to within 5%.
Cinnamaldehyde (1 mmol) was dissolved in 100 mL of deionized water in a 100 mL three-necked flask equipped with a reflux condenser and magnetic stirrer,before 0.5 g of b-CDCP was added. The mixtures were heated to reaction temperature (30,40,50 or 60 °C) and stirred for 30 min. Then,2 mL of 30% H2O2 and 1.5 mmol of NaHCO3 were added rapidly and the oxidation reaction occurred. 0.5 mL of the reaction mixture was sampled at 20-min intervals. Each sample was diluted to 100 mL with deionized water and its absorbance at 290 nm was measured to quantify the amount of cinnamaldehyde.
Molecular dynamic (MD) simulations were performed with Material Studio version 4.3 (Accelrys,Boston,USA). A COMPASS force field was employed in all MD simulations according to previous reports [25]. The structure of b-CD with cinnamaldehyde or benzaldehyde was first energy optimized,and then subjected to an inclusion molecule. The models were constructed at a fixed 1:1 molar ratio of cinnamaldehyde or benzaldehyde to b-CD in β-CDCP. The binding energy (BE) can be expressed as:
BE = EC - EG - EH (1)
where EC,EG,and EH were the total energy of inclusion complex,guests,and host,respectively. β-CDCP was used as the host,and cinnamaldehyde or benzaldehyde was selected as the model guest. The total energy of EC,EG,and EH can be expressed as:
EC = Eb + En+ EvdW + EE (2)
where Eb is the valence energy,En is the non-bond energy,EvdW is the van der Waals interaction energy,and EE is the electrostatic energy.
The amorphous structure of the host-guest inclusion complex was generated under periodic boundary conditions. The lengths of the cell were over 2.0 nm × 2.0 nm for the inclusion complexes with 500 molecules of water in the system. The density of β-CD,cinnamaldehyde,and benzaldehyde in the systems was maintained in Synthia units at 1.27,1.05,and 1.04 g/cm3 at 25 °C. Of the configurations,only the lowest energy one,as calculated by molecular mechanics,was chosen to be the initial configuration. 5000 steps of energy minimization were executed with Smart algorithm to remove unfavorable interactions in the initial configuration. A 100-ps molecular dynamic simulation was performed using normal pressure and temperature conditions with a time step of 1 fs in the range of 0-37 °C. A cut-off distance of 0.85 nm and a buffer of 0.05 nm were adopted to minimize calculations of non-bonding interactions. Electrostatic charges in the model were calculated by the charge equilibration method. The duration of the equilibration dynamics was 100 ps. Models of inclusion complex were then subjected to molecular dynamics at least 1000 ps. The hydrogen calculation was performed by hydrogen build following this geometric parameter: the hydrogen-acceptor distance < 0.3 nm and the donor-hydrogen-acceptor angle > 90.0° [20].
The binding energy (BE) in water-explicit system can be calculated as follows:
BE(sol) = EC(sol) - EG(sol) - EH(sol) (3)
where EC(sol),EG(sol),and EH(sol) were the total energy of inclusion complex,guests,and host in water system,respectively.
The FTIR spectra of cellulose,β-CDand β-CDCP are shown in Fig. 1(a). The IR spectrum of β-CDCP is similar to that of β-CD,indicating the β-CD in β-CDCP has not changed shape. The characteristic peak of the -OH stretching vibration at 3446 cm−1 for β-CDCP is stronger than that of cellulose. The increase of intensity could be attributed to the presence of more -OH groups in β-CDCP. The C-O-C band at 1030 cm−1 is observed in β-CDCP,whereas no band which can be assigned to the epoxy ring is observed at 1260 cm−1. This result strongly suggests that the epoxy ring of epichlorohydrin molecule has been opened in the hydrolysis reaction to form the polymer framework. In addition,the peak at 890 cm−1 is a characteristic band of a-(1,4) glucopyranose in β-CD [26],which provides some evidence that β-CD has been immobilized successfully on the cellulose through cross-linking with epichlorohydrin. XPS also provides some quantitative information on the surface composition of cellulose before and after modification. The C1s and O1s bands of β-CDCP,cellulose and β-CD are shown in Fig. 1(b). The results clearly indicate that β-CDCP has a higher surface C/O ratio (1.7) than cellulose (0.8).
Oxidation of cinnamaldehyde to benzaldehyde was carried out at 70 °C as shown in Scheme 1. The performance of different catalysts is summarized in Table 1. In order to allow comparison of catalytic effectiveness in terms of productivity per mass of catalyst,one separate specific activity was calculated for each catalyst,with respect to the dry mass of the catalyst as follows [27]:
Specific activity = [substrate] (μmol) x Yield (%)/catalyst (g) x Time (min) (4)
From Table 1,β-CDCP gave higher benzaldehyde yield and specific activity than b-CD,and the results greatly decreased in the absence of catalyst. In addition,similar results were obtained with cellulose and CE as the catalyst,indicating that their contribution to the benzaldehyde yield was very low. Therefore,the high yield of benzaldehyde was not due to the presence of cellulose or CE. These studies suggest that the weak interactions involved in the inclusion of substrate in the β-CD are important for the selective oxidation of cinnamaldehyde. However,the synergistic effects based on the weak interactions between β-CD and the functional group of cellulose played a crucial role in the high efficiency of the oxidation of cinnamaldehyde.
The effect of the β-CDCP loading on the oxidation of cinnamaldehyde to benzaldehyde was also investigated by varying the catalyst amount from 0 to 1.5 g,as shown in Fig. 2.
The conversion of cinnamaldehyde and yield of benzaldehydeincreased as the catalyst amount increased,coupled with a slight enhancement in selectivity for benzaldehyde. Maximal conversion (ca. 95%) was obtained with 1.0 g of catalyst. This oxidation reaction gave a 71% yield of benzaldehyde. After this,excessive β-CDCP leads to unwanted side reactions and decrease the yield of benzaldehyde.
The effect of reaction temperature on the oxidation of cinnamaldehyde was investigated,as shown in Fig. 3.
The results indicated that increasing the temperature improved the conversion of cinnamaldehyde and yield of benzaldehyde significantly,suggesting the reaction was highly sensitive to the temperature. 95% cinnamaldehyde conversion and 71% benzaldehyde yield were obtained at 70 °C. However,when the temperature exceeded 70 °C,the yield decreased due to decomposition of H2O2. Lower temperatures are also preferred to reduce the decomposition of benzaldehyde [14]. Thus the optimal temperature for the oxidation of cinnamaldehyde to benzaldehyde was 70 °C.
H2O2 is an environmentally-friendly oxidant since water is the sole byproduct [28,29]. The amount of H2O2 used in the system also influenced the oxidation of cinnamaldehyde. As shown in Table 2,the conversion increased with increasing amounts of H2O2. 95% conversion of cinnamaldehyde and 71% yield of benzaldehyde were obtained with 4 mL of H2O2. Further increase of H2O2 amount did not improve the conversion.
H2O2 is a rather weak oxidant in the absence of an activator. According to previously published results [28,30],the bicarbonate-H2O2 system is a simple and efficient method for the activation of H2O2. The effect of the NaHCO3 amount on the oxidation of cinnamaldehyde was investigated and the results are presented in Fig. 4. The NaHCO3 amount played an important role in the oxidation of cinnamaldehyde. In the absence of NaHCO3,the conversion of cinnamaldehyde and yield of benzaldehyde were only 7% and 4%,respectively. When the NaHCO3 amount reached 2 mmol,95% conversion of cinnamaldehyde and 71% yield of benzaldehyde were obtained.The activation was considered to start with a combination of H2O2 and bicarbonate in an equilibrium process to produce peroxymonocarbonate (Eq. (5)).
HCO3- + H2O2- = HCO4- + H2O (5)
Peroxymonocarbonate is an active oxidant,with structure HOOCO2-,which efficiently promotes the epoxidation of cinnamaldehyde,and further oxidation to benzaldehyde,which will be discussed later.
The oxidation rate of cinnamaldehyde in the presence of β-CDCP is shown in Fig. 5 (a). A linear relationship between ln(C0/Ct) and time was observed,indicating the reaction follow pseudo-first-order kinetics:
ln (C0/Ct) = kt (6)
Here,C0,Ct,t,and k are the initial cinnamaldehyde concentration,cinnamaldehyde concentration at t,reaction time,and the apparent reaction rate (min−1),respectively. The slope of ln (C0/Ct) vs t was used to calculate k.
The rate constant k was calculated from Fig. 5 (a). It was found to increase from 0.00687 to 0.0357 min−1 when the temperature was increased from 30 to 60 °C.
Fitting results of the first-order kinetic model indicated the oxidation of cinnamaldehyde to benzaldehyde,in the absence of β-CDCP,and followed a pseudo-first-order kinetic model (Fig. 5 (b)). The rate constant increased from 0.00403 to 0.0286 min−1 as the temperature was increased from 30 to 60 °C.
According to the Arrhenius equation:
k = Ae-Ea/RT (7)
Eq. (7) could be rearranged as Eq. (8):
ln k = ln A - Ea/RT (8)
Arrhenius plots of ln k and 1/T are shown in Fig. 6. The plots are linear and the activation energy Ea in the presence and absence of β-CDCP were calculated to be 42.55 and 50.87 kJ/mol,respectively. It is obvious that β-CDCP decreases the energy barrier of the oxidation.
Unlike free β-CD,the β-CDCP catalyst could be easily recovered from the reaction solution and reused. To examine its reusability,it was recovered by centrifugation after each batch. The obtained precipitate was washed with ethanol and deionized water. After drying,the catalyst was reused for the next run. As shown in Fig. 7,the results indicate that the conversion and selectivity of the reused catalyst remain nearly constant for four cycles.
FTIR measurements can provide useful information about hydrogen bonds and the formation of inclusion complexes [31].
The IR spectra of β-CDCP,the inclusion complex,and cinnamaldehyde are shown in Fig. 8. The spectrum of the inclusion complex (2) is similar to that of b-CDCP (1),indicating that the structure of the inclusion complex and b-CDCP are similar. The stretching absorption of C-H of the benzene ring at 3030 cm−1 and the absorption peak intensity of the C-H in aldehyde group (-CHO) at 2820 and 2750 cm−1 disappeared in the IR spectrum of the inclusion complex. For cinnamaldehyde,the C-O stretching absorption at 1688 cm−1 shifted to 1668 cm−1 in inclusion complex. This could be attributed to cinnamaldehyde occupying the cavity of b-CD in b-CDCP. Furthermore,the C-O-H absorption in the inclusion complex at 1335 and 1250 cm−1 was much stronger than that in b-CDCP. These indicate the formation of hydrogen bonds between the hydroxyl groups of b-CD in b-CDCP and the carbonyl groups of cinnamaldehyde. Based on the discussion above,it is reasonable to conclude that a host-guest inclusion complex has been formed [32].
XPS is useful for the analysis of specific interactions within the β-CDCP/cinnamaldehyde inclusion complex [33]. XPS spectra of C1s and O1s in β-CDCP before and after cinnamaldehyde inclusion are shown in Fig. 9. The carbon signals shown in Fig. 9 (a) gave three different binding energies at 284.8,286.6 and 287.9 eV,which are attributed to C-C (or C-H),C-O,and C =O (or O-C-O) in the stem chain,respectively [34,35]. Similarly,Fig. 9 (c) shows the O 1s spectrum with two peaks at 532.8 and 533.7 eV which are assigned to O-H and O=C,respectively [35,36]. Comparing the binding energy of each element in β-CDCP and the β-CDCP/cinnamaldehyde inclusion complex,the C1s binding energy of C=O in the inclusion complex decreased from 287.9 to 282.2 eV (Fig. 9 (b)),and O 1s binding energy of O-C in the inclusion complex decreased from 533.5 to 533.2 eV (Fig. 9 (d)). Moreover,two peaks at 287.2 and 531.6 eV were detected,which were assigned to the C1s of C-H×××O and the O 1s of the H-O×××O group in the inclusion complex,respectively. All these results provide additional evidence of the interaction between the surface C-OH group of the β-CDCP and C=O group of cinnamaldehyde via a hydrogen bond.
To investigate the binding interaction between equimolar amounts of cinnamaldehyde or benzaldehydewith β-CDCP,the optimized structure at the energy minimum for the β-CDCP guest complexes are shown in Fig. 10. The number of hydrogen bonds,the type,bond length (r),and bond angle (A) as calculated by the Forcite program package are shown in Table 3.
As shown in Fig. 10,the hydrophobic moieties of cinnamaldehyde and benzaldehydemolecules are enclosed within β-CD. The hydrophilic parts of the cinnamaldehyde and benzaldehydemolecules are exposed to an aqueous environment and associate with water molecules. The optimized geometries in Table 3 revealed that the shortest distance between the O atom of carbonyl in cinnamaldehyde and the H atom of the hydroxyl group was 0.2104 nm,and the shortest distance between oxygen atom of carbonyl in benzaldehyde and hydrogen atom of the hydroxyl group was 0.2393 nm. These O-H×××O bond angles were 125.3° and 114.4°,respectively. The results indicated that the hydrogen bond interactions played a crucial role in the cinnamaldehyde/b-CDCP and benzaldehyde/b-CDCP complexes. The existence of a hydrogen bond effectively promotes substrate specificity of β-CDCP,significantly improving the s electivity towards benzaldehyde. As previously reported [37],the more negative the binding energy is,the more thermodynamically favorable the inclusion complex. From Table 4,the negative binding energy change clearly demonstrates that b-CDCP can form stable complexes with cinnamaldehyde and benzaldehyde,which was confirmed by calculations. The binding energy of b-CDCP/cinnamaldehyde (vacuum) (−63.32 kJ/mol) was more negative than b-CDCP/benzaldehyde (vacuum) (−32.24 kJ/mol) as calculated by the Forcite method. The binding energy for the inclusion complex of cinnamaldehyde/ b-CDCP (vacuum) was −31.08 kJ/mol lower than that of benzaldehyde/b-CDCP (vacuum). This relationship was also seen when the binding energy was calculated in water. It further confirms that the complex of b-CDCP/cinnamaldehyde is much more stable than that of b-CDCP/benzaldehyde.
The recently reported results also indicate the difference between the two binding energy of cinnamaldehyde and benzaldehyde with β-CDCP is the basis for the selective separation of different substrates via β-CD inclusion [31,37]. The binding energy for the complex of β-CDCP/cinnamaldehyde (−60.49 kJ/mol) in water was much lower than that of the β-CDCP/ benzaldehyde (−28.45 kJ/mol). Therefore,cinnamaldehyde is preferred in the hydrophobic cavity,while the benzaldehyde product tends to escape from the cavities of β-CD. Based on the DFT results,substrate specificity and mass transfer of β-CDCD significantly improves the catalytic activity and selectivity.
Based on above results,a reaction mechanism has been proposed for the oxidation of cinnamaldehyde catalyzed by NaHCO3-H2O2 in the presence of β-CDCP. For the mechanism,a basic assumption is that the essential functional sites are in the β-CD cavities. First,β-CD in the β-CDCP and cinnamaldehyde form an inclusion complex via intermolecular hydrogen bonding through a O-H×××O bond at the second rim of β-CD (Scheme 2). The host-guest interaction between cinnamaldehyde and parent β-CD has been verified by 1H NMR and ROESY as previously reported [14]. Nucleophilic attack by a hydroxide ion from the hydrolysis of NaHCO3 on the substrate gives benzaldehyde as a minor product. The result is in accordance with a previous report [14]. Second,H2O2 and bicarbonate combine in an equilibrium process to produce peroxymonocarbonate HOOCO2- [24, 25]. It is an active oxidant and efficiently promotes the epoxidation of cinnamaldehyde. Other non-covalent intermolecular interactions between β-CD and cinnamaldehyde also promote the nucleophilic oxidation. Large amounts of cinnamaldehyde are converted to the epoxide,and then it is further oxidized to benzaldehyde by peroxymonocarbonate. Finally,the catalyst is returned to its initi al state. It should be mentioned that alkaline hydrolysis is slow,and only 8% yield of the product is derived from this route in the present catalytic system.
In view of the efficient oxidation of cinnamaldehyde,oxidation of cinnamaldehyde derivatives has been also investigated and the results are listed in Table 4.
β-CD in the β-CDCP has been shown to form a host-guest complex with a substrate. This complexation depends on the size,shape and hydrophobicity of the guest molecule. In the present research,the oxidation of cinnamaldehyde derivatives could be carried out smoothly. However,2-nitro-,4-methoxy-,and 2-hydroxy-cinnamaldehydes were more reactive than α-methyl-cinnamaldehyde,indicating that the functional groups significantly affected the reaction. Conversely,the existence of an electron donating group lowered the reaction rate,demonstrating that the space required by the guest molecules is more important for efficient conversion than electronic effects in the present catalytic systems.
β-cyclodextrin-functionalized cellulose was successfully synthesized and utilized as a highly efficient heterogeneous catalyst for the synthesis of benzaldehyde. Compared with free β-CD,the use of cellulose as a supporting material can significantly improve the catalytic performance of immobilized β-CD. These investigations have revealed that the synergistic effect of the weak interactions between the polymer-supported b-CD and the substrate,e.g. hydrogen bonding,lead to higher activity and selectivity. It was also found that reaction parameters play important roles in determining the catalytic performance of the catalysts. In addition,these heterogeneous catalysts demonstrated excellent reusability in the oxidation of cinnamaldehyde and cinnamaldehyde derivatives. The oxidation process is clean,safe,and reproducible under mild reaction conditions.
2014, Vol. 35 Issue (4): 590-598
PDF (708KB)
2014, Vol. 35 Issue (4): 590-598
PDF (708KB)