Changing mechanisms in the beta-cyclodextrin-mediated hydrolysis of phenyl esters of perfluoroalkanoic acids

The rate of hydrolysis of esters CF(3)(CF(2))(n)COOPh (1 (n = 1), 2 (n = 2), and 3 (n = 6)) was measured at pH 6.00 and at pH higher than 9.00 in the presence of beta-cyclodextrin (beta-CD). For compounds 1 and 2 the reaction rate decreases as the beta-CD concentration increases, and they show saturation effects at all pH. It is suggested that the substrate forms an inclusion complex with cyclodextrin. Analysis of the rate data allows calculation of the association equilibrium constant, K(CD), the rate constant for the reaction of the included compound, k(c), and K(TS) which is the hypothetical association equilibrium constant for the transition state of the cyclodextrin-mediated reaction. The dependence of log K(CD) and log K(TS) with the number of atoms in the chain is different. We suggest that the reactions of 1 and 2 take place with the perfluorinated alkyl chain included in the cavity, whereas the transition state for the reaction of phenyl trifluoroacetate involves a complex with the aryl ring inside the cavity. At low pH the inhibition comes from the protection of the carbonyl group toward nucleophilic attack by water. In basic pH the reaction of HO(-) as an external nucleophile is also inhibited. The cyclodextrin-mediated reaction involves the ionized OH group at the rim of the cyclodextrin cavity with poor efficiency due to an unfavorable orientation of the substrate in the complex. On the other hand, the reaction of compound 3 is strongly accelerated by cyclodextrin because the association of the substrate with cyclodextrin competes with the monomer-aggregate equilibrium and at high enough cyclodextrin concentration the main species present in solution is the complex between 3 and cyclodextrin.     

Cyclodextrin nanosponges: a potential catalyst and catalyst support for synthesis of xanthenes

The nanoporous framework of a cyclodextrin nanosponge was used as catalyst for accelerating the one-pot, three-component reaction of dimedone, aldehyde, and phenols for synthesis of xanthene derivatives. Moreover, the nanocavities of cyclodextrin nanosponges were exploited for immobilization of heteropolyacids through the wet impregnation method. This catalyst exhibited superior catalytic performance compared to the bare cyclodextrin nanosponge. Despite the good catalytic activity, the leaching of the catalytic species did not allow efficient recovery and reusability. To circumvent this problem, the cyclodextrin nanosponge was amine-functionalized prior to heteropolyacid immobilization. The results proved that the amine functionalities had an effective role in preserving the catalytic species and improving the reusability through decreasing the leaching time. This catalyst was used for synthesis of a variety of xanthenes in aqueous media. The catalytic amount of catalyst afforded the desired product in excellent yields and with a relatively short reaction time. The results suggested cyclodextrin nanosponge-based catalysts as potential candidates for promoting chemical reactions.     

Cooperative perfunctionalization and partial labeling of 6-azido-6-deoxy-α-cyclodextrin through copper(I)-catalyzed azide-alkyne cycloaddition

In a microwave and ligand-assisted cyclodextrin click cluster synthesis, we observed the cooperative perfunctionalization in the click reaction of 6-azido-6-deoxy-α-cyclodextrin under our optimized reaction conditions. MALDI-MS data and partial fluorescein labeling via the one-pot/stepwise methods confirmed the occurrence of cooperative perfunctionalization: the fully triazole-functionalized cyclodextrin click cluster became the major product with limited alkyne equivalents. To the best of our knowledge, this work constitutes the first example of a ‘cooperative’ click reaction of an azido-cyclodextrin. This cooperative perfunctionalization of cyclodextrin click clusters offers useful synthetic insights into the partial reporter labeling strategy using azido-cyclodextrin.     

Synthesis of polyrotaxanes based on α-cyclodextrin and poly(ethylene oxide)

Inclusion complexes of poly(ethylene oxide) with α-cyclodextrin are the key compounds in the synthesis of polyrotaxanes. These complexes prepared in aqueous solutions contain free cyclodextrin, which cocrystallizes with the major reaction product. These complexes dissociate upon dissolution in DMF and DMSO to form cyclodextrin and pseudopolyrotaxanes with a low cyclodextrin content. Polyrotaxane was synthesized with the use of poly(ethylene oxide)-α,ω-bis-amine as a linear component. The end-groups of the polymer in the inclusion complex were modified by the reaction with 2,4-dinitrofluorobenzene. A procedure was developed for purification of a polyrotaxane with high cyclodextrin content. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1914–1918, August, 2005.     

Effect of cyclodextrin complexation in bromine addition to unsymmetrical olefins: evidence for participation of cyclodextrin hydroxyl groups

Multiple recognition by cyclodextrin in a bimolecular reaction, namely bromination of styrene, methyl cinnamate, phenylacetylene and allylbenzene, has been studied. Bromohydrin is obtained as a major product along with dibromide in the bromination of styrene and methyl cinnamate. The percentage of bromohydrin decreases as the cavity size increases. With phenylacetylene, bromophenylacetylene and phenacyl bromide are obtained in addition to the dibromides. In the bromination of cyclodextrin complexes of allylbenzene, the product distribution is the same as in solution bromination. The observed results demonstrate the efficiency of cyclodextrin in stabilizing the open carbocationic intermediate and thus provide chemical evidence for the participation of cyclodextrin hydroxyl groups.     

Environmentally friendly procedure for the aqueous oxidation of benzyl alcohols to aldehydes with dibromodimethylhydantoin (DBDMH) and cyclodextrin: Scope and mechanistic insights

Reported herein is an environmentally friendly procedure for the oxidation of benzyl alcohols to aldehydes using an inexpensive, commercially available reagent, 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), and a variety of cyclodextrin additives under fully aqueous solvent conditions. This reaction proceeds with moderate to good yields for a broad scope of benzyl alcohol substrates, with the cyclodextrin acting to enhance the desired reactivity and limit undesired aromatic bromination side products. The reported experiments provide substantial mechanistic insight that will drive further reaction optimization and have broad-reaching applications.     

环糊精衍生物在金属催化有机合成中的应用

综述了环糊精(包括α-环糊精,β-环糊精和γ-环糊精)衍生物在金属催化有机合成中的应用,主要包括其作为金属离子配体、金属纳米粒子稳定剂和反相相转移催化剂在氧化、水解、还原、偶联等金属催化反应中的应用.其中环糊精衍生物作为金属离子配体应用最广,由于环糊精部分与底物形成包结络合物,拉近了底物和具有催化活性的金属离子的距离,并固定了底物的反应部位,往往可以显著提高催化反应的反应速率,增强反应的区域选择性和对映选择性.     

Asymmetric Synthesis in the Presence of Cyclodextrins

Oxidative couplings of 2-naphthol, 6-bromo-2-naphthol and2-naphthylamine were achieved at room temperature in the presence of H₂O₂, horseradish peroxidase and a suitable cyclodextrin.2-Thionaphthol behaved differently, yielding the corresponding disulfide. Yields of binaphthyl derivatives were generally excellent, and a fairly good enantiomeric excess was observed. Under similar reaction conditions methyl 2-(6-methoxy-2-naphthyl) propanoate, when treated with esterase in the presence of cyclodextrin, yielded naproxen (a well-known anti-inflammatory drug) with a good enantiomeric excess. No reaction product was detected in the absence of cyclodextrin. Cyclodextrins do not act as simple transfer agents.     

Synthesis of Terpyridine Derivatives Containing β—Cyclodextrin

A novel β-cyclodextrin-based terpyridine derivatives has been prepared by the coupling of 4‘‘‘‘‘‘‘‘-(4“-bromomethyl phenyl)-2,2‘‘‘‘‘‘‘‘:6‘‘‘‘‘‘‘‘,2“-terpyridine with mono-6-hydroxy permethylated β-cyclodextrin.The cyclodextrin dimmer appending a 4‘‘‘‘‘‘‘‘-phenyl-2,2‘‘‘‘‘‘‘‘:6‘‘‘‘‘‘‘‘,2“-terpyridine spacer on the primary faces was synthesized by reaction of 4‘‘‘‘‘‘‘‘-phenyl-2,2‘‘‘‘‘‘‘‘:6‘‘‘‘‘‘‘‘,2“-terpyridine-6,6‘‘‘‘‘‘‘‘-dicarbonitrile with an excess of 6-deoxy-6-O-tosyl-β-cyclodextrin.     

Cationic-modified cyclodextrin nanosphere/anionic polymer as flocculation/sorption systems

Simultaneous removal of dissolved and colloidal substances has been a challenging task. The cationic-modified beta-cyclodextrin nanospheres synthesized in this work, in conjunction with a water-soluble polyacrylamide-based anionic polymer, potentially provide a novel approach to address the problem. The cyclodextrin was rendered cationic using (2,3-epoxypropyl)trimethylammonium chloride as a reagent. The cationicity of the modified cyclodextrin and the reaction between cyclodextrin and the reagent were characterized by electrophoresis measurement, polyelectrolyte titration, and NMR. As a dual-component flocculation system, the cationic cyclodextrin/anionic polymer significantly induced clay flocculation, lowering the relative turbidity of the clay suspension over a wide pH range. Meanwhile, as a nanospherical absorbent, the modified cyclodextrins exhibited strong affinity toward aromatic compounds via inclusion complex formation in the hydrophobic cavities, which was monitored by UV spectroscopy. These systems facilitated the simultaneous removal of dissolved and colloidal substances, which was unachievable previously. In addition, the interaction between anionic polymers and the clay particles pretreated with cationic cyclodextrin was investigated in order to reveal the flocculation mechanism.     

Denitrosation of N-Nitrososulfonamide as Chemical Probe for Determination of Binding Constants to Cyclodextrins

The influence of β-CD concentration on the acid hydrolysis of N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) has been studied in the presence and absence of different alcohol concentrations. The rate of the denitrosation reaction in bulk water decrease as the β-CD concentration increases due to MNTS complexation in the CD cavity and the reaction taking place exclusively outside the cyclodextrin. Changes in this inhibition due to the presence of β-CD allow us to obtain the binding constants of different alcohols to the cyclodextrin. These binding constants are in very good agreement with those determined in the bibliography by other methods.     

Synthesis and Polymerization of Carbamate-Linked Cyclodextrin Methacrylate Monomers

Abstract

A one-step synthesis for cyclodextrin methacrylate monomers was examined starting from α-, β- and γ-cyclodextrin. The reaction of 2-isocyanatoethyl methacrylate as well as allylisocyanate with the corresponding cyclodextrin gave the monofunctionalized carbamate-linked cyclodextrin methacrylates 2, 6 and 9 and allylcarbamates 11 and 14 in moderate yields. By NMR spectroscopic means, it could be proven that in all cases only the primary 6-hydroxyl groups of the cyclodextrins reacted with the isocyanate group. For the synthesis of a β-cyclodextrin monoallyl compound, a substitution reaction of purchasable 6-O-monotoluenesulfonyl-β-cyclodextrin with allylamine gave 6-N-allylamino-6-deoxy-β-cyclodextrin 18 in high yield. The reaction of 2-isocyanatoethyl methacrylate with α-cyclodextrin to the 6-O-carbamoyl-2-methylpropenoylethyl-α-cyclodextrin (2) was optimized so that the monomer 2 could be prepared on a larger scale without chromatographic separation. The aqueous radical homopolymerization of 2 with the peroxodisulfate/bisulfite redox initiator gave the water soluble cyclodextrin polymer 19 in good yield. Its molecular weight was determined by gel permeation chromatography to be M_n = 101,800 corresponding to an average degree of polymerization P_n = 90.     

β‐Cyclodextrin‐catalyzed decomposition of Caro's acid

The kinetics and mechanism of decomposition of peroxomonosulphate (PMS) in aqueous sodium hydroxide medium in the presence β‐cyclodextrin has been investigated. The rate of decomposition of PMS is considerably enhanced by the added β‐cyclodextrin. The reaction follows first order kinetics with respect to [PMS]. The experimental results suggest the formation of β‐cyclodextrin peroxy anion by the interaction between SO₅^2?, and β‐cyclodextrin anion (BCDO^?). β‐Cyclodextrin peroxy anion subsequently reacts with PMS to give O₂, SO₄^2? and β‐cyclodextrin anion. The rate constant for the β‐cyclodextrin‐catalyzed decomposition of SO₅^2? (BCD + SO₅^2?) is of the same order of magnitude as that of the reaction HSO₅^2? + SO₅^2? products. © 2002 Wiley Periodic mals, Inc. Int J Chem Kinet 34: 508–513, 2002     

Reversal of regioselectivity and enhancement of rates of nitrile oxide cycloadditions through transient attachment of dipolarophiles to cyclodextrins

The reactions of nitrile oxides with monosubstituted dipolarophiles, such as propiolamide, typically afford proportionally 80 % or more of the 3,5-disubstituted cycloadducts. By contrast, the reactions of 6(A)-deoxy-6(A)-propynamido-beta-cyclodextrin with 4-tert-butylbenzonitrile oxide and 4-phenylbenzonitrile oxide afford >90 % and approximately 85 % of the corresponding 3,4-disubstituted isoxazoles, respectively. As well as reversing the regioselectivity, the cyclodextrin increases the rates of these cycloadditions. The extent of the acceleration is up to more than three orders of magnitude for the production of the cycloadduct preferred by the cyclodextrin, but even the rate of reaction to give the less favored regioisomer is increased. With 6(A)-deoxy-6(A)-propynamido-beta-cyclodextrin, the cycloadducts are not easily separated from the cyclodextrin, as the amide bond is not readily cleaved. In comparison, the regioselectivity of the cycloadditions of 4-tert-butylbenzonitrile oxide with acrylic acid, methacrylic acid, and crotonic acid is also altered by formation of the corresponding cyclodextrin esters, by factors of 500, >10, and >100, respectively. The rates of cycloaddition are also increased by up to 475 times, and in these cases the products of cycloaddition are readily released from the cyclodextrin through ester hydrolysis. Incorporating these processes into a reaction cycle, acylation of beta-cyclodextrin with p-nitrophenyl acrylate and subsequent treatment first with 4-tert-butylbenzonitrile oxide and then with base, the latter to catalyze ester hydrolysis and regenerate the beta-cyclodextrin, affords proportionally fivefold more of the 3,4-disubstituted isoxazoline than is produced directly from acrylic acid.     

Convenient preparation and effective separation of the C-2 and C-3 tosylates of α-cyclodextrin

Secondary tosylates of α-cyclodextrin were conveniently prepared by the reaction of the cyclodextrin with tosyl chloride in alkaline water where pH of the mixture should be allowed to decrease as the proceeding of reaction, and were effectively separated by reversed-phase column chromatography.     

A Cyclodextrin Molecular Reactor for the Regioselective Synthesis of 1,5-disubstituted-1,2,3-triazoles

6^A-Deoxy-6^A-propynamido-β-cyclodextrin reacts with 4-tert-butylphenyl azide in aqueous solution, to form the 5-(aminocarbonyl)-substituted triazole in preference to the 4-(aminocarbonyl)-substituted analogue, in a ratio of 25:1. The cyclodextrin moiety templates the reaction through the formation of a host-guest complex of the dipole with the dipolarophile, controlling the regioselectivity of cycloaddition. In a control reaction under similar conditions, with propiolamide instead of the cyclodextrin derivative, 5- and 4-(aminocarbonyl)-1-(4-tert-butylphenyl)-1,2,3-triazole were formed in a ratio of 1:4. As well as reversing the regioselectivity, the cyclodextrin substituent increases the rate of cycloaddition, by at least two orders of magnitude for the reaction to give the 5-substituted cycloadduct. Even the rate of formation of the 4-substituted cycloadduct is increased by a factor of two. Less marked effects are observed with phenyl azide and 4-tert-butylbenzyl azide as dipoles.     

Preparation of a permethylated β‐cyclodextrin chiral stationary phase by one‐pot hydrosilylation and immobilization at the C2 position for chiral high‐performance liquid chromatography

A novel cyclodextrin intermediate, mono‐2^A‐allylcarbamido‐2^A‐deoxy‐permethylated β‐cyclodextrin, was synthesized by reacting allylamine and newly prepared mono‐2^A‐azido‐2^A‐deoxy‐permethylated β‐cyclodextrin by the Staudinger reaction and anchored onto porous silica beads by a one‐pot hydrosilylation and immobilization procedure to afford a novel chiral stationary phase. This stationary phase acts as a new member of the previous chiral stationary phase series immobilized on the cyclodextrin C2 position. This stationary phase depicted enantiomeric separation abilities toward a series of bicyclic and tricyclic racemates under reversed‐phase conditions. The resolutions for hesperetin and naringenin achieved on the current phase reached 3.91 and 1.11, respectively, much higher than the previous permethylated β‐cyclodextrin with the linkage at the C6 position.     

氨基修饰β-环糊精衍生物水相仿生催化不对称Michael加成反应

在不对称 Michael加成反应中,有机小分子如伯胺、吡咯烷类衍生物、(硫)脲类、手性方酰胺、联萘类、奎宁类、手性膦、离子液体和肽类等是目前使用的主要催化剂,如果能避免或少量使用有机溶剂,则更符合“绿色化学”的环境友好发展方向.β-环糊精的内腔疏水,而外部亲水,可以类似酶分子结合有机反应物,在水相体系进行催化反应.当β-环糊精分子上连接催化部位或结合部位时,能产生更优异的包结底物和诱导对映选择性的能力.目前基于β-环糊精衍生物构筑人工类酶催化剂用于不对称 Michael加成反应的报道较少.本文通过亲核取代反应将氨基类有机小分子与单(6-O-p-甲苯磺酰基)-β-环糊精结合,得到9个氨基修饰β-环糊精衍生物CD-1–CD-9(收率在24.2%–64.9%,分子结构通过1H NMR,13C NMR和 ESI-MS表征确认),并用于室温水相体系不对称Michael加成的仿生催化反应,以期获得较好的催化反应活性和对映选择性.通过设计不同β-环糊精衍生物的修饰基团结构、改变反应介质pH值和反应底物结构,分析了Michael加成反应体系产物产率和对映选择性的变化,采用2D-1H ROESY NMR、紫外吸收光谱、红外光谱和和量子化学计算,分析了β-环糊精衍生物和反应底物分子的包结状态,探究了反应过程机理.结果显示,在该水相体系中进行的不对称Michael加成反应产物产率和对映体过量值(ee值)受修饰基团结构、反应介质pH值和底物结构影响较大.当反应介质pH值低于6.0时,由于氨基分子被质子化而失去催化活性;当 pH值为7.5时,获得中等水平的对映选择性,通过量子化学在 ONIOM (B3LYP/6-31G(d)：PM3)水平上的优化计算发现,底物分子与β-环糊精衍生物的包结可以出现两种形式：当底物分子的活性部位接近β-环糊精衍生物小口端的修饰基团时,产生分子内催化,诱导反应产生较好的对映选择性;当底物分子的活性部位远离β-环糊精衍生物小口端的修饰基团时,产生分子间催化,几乎没有对映选择性,而这两种情况同时存在.当底物分子以较大的空间位阻与β-环糊精疏水性空腔结合时,产生较好的对映选择性,邻位取代的2-硝基-β-硝基苯乙烯比对位取代的4-硝基-β-硝基苯乙烯 ee值更高,通过量子化学优化计算证实空间位阻效应.应用2-金刚烷酮与β-环糊精衍生物空腔形成竞争性的包结反应实验,产物产率和ee值都下降,说明β-环糊精衍生物的疏水性空腔是产生不对称诱导和催化活性不可或缺的部分,底物分子与β-环糊精衍生物的包结过程通过2D-1H ROESY NMR和紫外吸收图谱获得确认.其中L-2-氨甲基吡咯烷修饰β-环糊精 CD-1表现出较好的反应对映选择性,在溶剂(pH =7.5,0.5 mol/L CH3COONa-HCl)2 mL,环己酮2 mmol,2-硝基-β-硝基苯乙烯0.2 mmol,CD-1用量0.04 mmol,25°C反应96.0 h的条件下,环己酮与2-硝基-β-硝基苯乙烯 Michael加成产物的 ee值达71%,产率为47%.该反应过程在β-环糊精衍生物的疏水性空腔内进行,修饰基团L-2-氨甲基吡咯烷与环己酮形成烯胺的催化反应.     

Preparation of cyclodextrin membrane and its selective permeation

Smooth and stable cyclodextrin membranes are successfully prepared from the oriented-cyclodextrin-polymers, by drying layers of the polymers. The polymers are obtained by the reaction of the crystal of -cyclodextrin-water inclusion complex with hexamethylene diisocyanate as cross-linking agent in anisole. The cyclodextrin membranes exhibit selective permeation of various materials in water.     

A family of single‐isomer,dicationic cyclodextrin chiral selectors for capillary electrophoresis: Mono‐6A‐ammonium‐6C‐butylimidazolium‐β‐cyclodextrin chlorides

The first member of the single‐isomer, dicationic cyclodextrin (CD) family, 6^A‐ammonium‐6^C‐butylimidazolium‐β‐cyclodextrin chlorides (AMBIMCD), has been synthesized, analytically characterized, and used to separate a variety of acidic enantiomers and amino acids by CE. Starting from mono‐6^A‐azido‐β‐cyclodextrin, the cationic imidazolium and ammonium moieties were subsequently introduced onto primary ring of β‐cyclodextrin via nucleophilic addition and Staudinger reaction. The analytically pure AC regio‐isomer CD was further obtained via column chromatography. This dicationic CD exhibited excellent enantioselectivities for selected analytes at concentration as low as 0.5 mM, which were even better than those of its mono‐imidazolium or ammonium‐substitued counterpart CDs at 10 equivalent concentrations. The effective mobilities of all studied analytes were found to decrease with the concentration of AMBIMCD. Inclusion complexation in combination with eletrostatic interactions seemed to account for the enhanced chiral discrimination process.