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- Publisher
- de Gruyter
- Copyright
- Copyright © 2012 by the
- ISSN
- 2084-7246
- eISSN
- 2084-7246
- DOI
- 10.2478/supcat-2012-0003
- Publisher site
- See Article on Publisher Site
Abstract
Hydrogen/deuterium (H/D) exchange at the -H of -carbonyl esters has been used as a useful probe to demonstrate the kinetic aspects of cucurbit[7]uril-catalyzed processes. The rate constants for H/D exchange of ethyl acetoacetate (1), methyl acetoacetate (2) and dimethyl malonate (3) have been determined in the absence and presence of cucurbit[7] uril by 1H NMR spectroscopy. H/D exchange at the -H of -carbonyl esters is inhibited by cucurbit[7]uril in D2O, where the inhibitory factor order methyl acetoacetate > ethyl acetoacetate > dimethyl malonate, is in good agreement with the order of their binding constants. In the previous research, the models are oftentimes restricted to positively charged substrate. We now extend this research to neutral substrates, hence demonstrating further the versatile applications of cucurbiturils in the field of supramolecular catalysis. Keywords -carbonyl ester · Cucurbituril · Supramolecular catalysis · Host-guest complex · Inhibitory factor Received 11 September 2012 Accepted 28 October 2012 Xiulei Xu1, Yao Wang1, Li Liu2* Dalian University of Technology, Dalian 116024, China Dalian Institute of Chemical Physics, CAS, Dalian 116023, China © Versita Sp. z o.o. 1. Introduction Cucurbit[n]urils (CB[n], n = 5-10) are cyclic oligomers of glycoluril with an interior hydrophobic cavity and polar carbonyl groups surrounding the two identical portals [1-5]. They can accommodate cationic and neutral guests through iondipole interactions, hydrophobic effect or hydrogen bonds. Consequently, chemical reactivity of the guests could be altered due to the complexation, resulting in rate change, selectivity change and even new products. Mock firstly reported that 1,3-dipolar cycloaddition reaction could be accelerated by a factor of 5.5×104 under the influence of CB[6] [6,7]. More recently, applications of CB[n] as catalyst were investigated in a variety of reactions [8-11], such as hydrolysis [12], solvolysis [13], desilylation [14], thiol-disulfide interchange [15], oxidation [16] and photoreactions [17-22]. -Carbonyl esters are important chemicals widely used in organic synthesis [23-25]. The -H of -carbonyl esters are acidic due to the electron-withdrawing effects of the two neighboring carbonyl groups [26], and the carbanion thereby formed can undergo nucleophilic substitution. Ohwada reported that the acidity of the -H of carbonyl compounds can be represented in terms of the electron-accepting orbital levels of the unoccupied reactive hybrid orbital of the C-H moiety [27]. The C-H acidity in the -carbonyl esters, which renders the protons susceptible to deuterium exchange, is a useful probe for characterizing kinetic aspects of CB-catalyzed processes. In this paper, H/D exchange at the -H of the -carbonyl esters (1-3) has been studied in the absence and presence of CB[7] in D2O at room temperature (Figure 1). The H/D exchange reactions can be monitored by 1H NMR spectroscopy and the rate constants acquired. 2. Experimental Procedure Cucurbit[7]uril was synthesized using a published procedure [3] and characterized by NMR (see Supplementary Material). Ethyl acetoacetate (1), methyl acetoacetate (2) and dimethyl malonate (3) were purified by distillation prior to use. All the 1H NMR spectra were recorded on an Avance III 500 MHz NMR spectrometer. 3. Results and Discussion Ethyl acetoacetate (1) was chosen as the model to study the effect of CB[7] on the H/D exchange reaction. Firstly 1H NMR Figure 1. Compounds described in the text. * E-mail: lliu@dicp.ac.cn titration experiments were performed in D2O to investigate the host-guest interaction of 1 with CB[7]. Experimentally, this was accomplished by gradually increasing the mole ratio of CB[7] with a constant concentration of 1 at room temperature. Upon addition of CB[7], the resonance signals of 1 moving upfield indicate their positioning within the cavity of CB[7]. The spectra in Figure 2 also show fast exchange on the NMR time scale with only one set of guest peaks being observed. The resonance signals are consistently shifted upfield until saturation is reached (see Figure 3). Fitting of these data to a 1:1 binding isotherm yields a binding constant of 644 M-1 for CB[7]·1 complex at 25°C [28]. The H/D exchange reactions of 1 in the absence and presence of CB[7] in D2O at room temperature have been monitored by 1 H NMR spectroscopy. In the presence of lower equiv. of CB[7], only a fraction of the guests are bound to CB[7], therefore the rate constant represents a combination of H/D exchange on free guest and CB[7]-bound guest. In this work, the rate constants of CB[7]-bound guest were determined in the presence of 4 equiv. of CB[7] under which condition upfield shifts remain stable (see Figure 3 and Supplementary Material) indicating all of the guests are approximately bound. The H/D exchange reactions of -H in 1 in the absence and presence of 4 equiv. of CB[7] were found to follow first-order kinetics. The rate constants were calculated accordingly by linear-regression analysis of reaction progress lnX (X = I0/It, where I is the integration of -H proton resonance, using -OCH2CH3 as non-exchanging reference) against time (see Figure 4). The resulting data in Table 1 demonstrate that the inhibitory factor is 1.7 for 1 at pD = 3.9. As the result from ethyl acetoacetate (1) revealed the inhibitory effect of CB[7] on H/D exchange of -H, we further continued with different structures of -carbonyl esters (2-3) to study the relationship between substrate structures and inhibitory effect of CB[7]. Upfield shifts in 1H NMR signals upon addition of CB[7] suggested the complexation of methyl acetoacetate (2) and dimethyl malonate (3) with CB[7]. In both examples, fast exchange was observed on the NMR time scale (see Figure 5). Fitting of the 1H NMR titration data to a 1:1 binding isotherm Figure 2. 1H NMR spectra of 1 (5 mM) in D2O with 0, 0.51, 1.43, 3.52, 5.03 equiv. of CB[7] from bottom up. CB[7] protons and HOD are labelled as · and , respectively. Figure 3. 1H NMR chemical shift of CH3CO of 1 (5 mM) as a function of the equiv. of CB[7]. Table 1. Rate constants for H/D exchange of 1, 2 and 3 in the absence and presence of CB[7] at pD = 3.9. Substrate 1 1 2 2 3 3 CB[7] 0 4 equiv. 0 4 equiv. 0 4 equiv. kex, s-1 2.27 × 10-4 1.34 × 10-4 2.03 × 10-4 7.77 × 10-5 3.95 × 10 -6 a 1.7 2.6 1.3 2.93 × 10-6 Figure 4. Plots of lnX against time for the -proton deuterium exchange of 1 (5 mM) in D2O with 0 () and 4 () equiv. of CB[7] at pD = 3.9. Inhibitory factor = kex(free)/kex(bound) X. Xu et al. yields binding constants of 881 M-1 for the CB[7]·2 complex, and 145 M-1 for the CB[7]·3 complex at 25°C [28]. The first-order rate constants for H/D exchange of the -H in 2-3 in the absence and presence of 4 equiv. of CB[7] were calculated from the plots of reaction progress lnX (X = I0/It, where I is the integration of -H proton resonance, using CH3CO- as non-exchanging reference for 2, CH3O- for 3) versus time (see Supplementary Material). The results in Table 1 show that the structural variations of -carbonyl esters influence the inhibitory degree of CB[7] on H/D exchange rates. The inhibitory factors were determined to be 2.6 for 2 and 1.3 for 3 at pD = 3.9. 4. Conclusions In summary, it appears that CB[7] can inhibit H/D exchange at the -H of -carbonyl esters. The relationship between substrate structure and inhibitory factor was established after careful determination of the rate constants of the free guest and bound guest; the inhibitory factor was found to vary with different structures of -carbonyl esters in the order: methyl acetoacetate > ethyl acetoacetate > dimethyl malonate, which is in good agreement with the order of the binding constants. Previous research by Wang et al. has investigated H/D exchange of the bis(imidazolium) dication [29], where the model was restricted to a positively charged substrate. We now extend this model to neutral substrates, hence demonstrating further the versatile applications of cucurbiturils in the field of supramolecular catalysis. Acknowledgements This project was supported by a grant from Advanced Programs for the Returned Overseas Chinese Scholars, Ministry of Human Resources and Social Security, and the National Natural Science Foundation of China (No. 21003123). Figure 5. (a) 1H NMR spectra of 2 (5 mM) in D2O with 0, 0.59, 2.09, 3.34, 5.30 equiv. of CB[7] from bottom up; (b) 1H NMR spectra of 3 (5 mM) in D2O with 0, 0.53, 1.73, 4.69, 5.10 equiv. of CB[7] from bottom up. CB[7] protons and HOD are labelled as and , respectively.
Journal
Supramolecular Catalysis – de Gruyter
Published: Nov 14, 2012