Advances in organic synthesis using polymer-supported reagents and scavengers under microwave irradiation

Summary Microwave-assisted and polymer-supported organic syntheses have emerged independently as versatile tools for rapid generation of organic molecules. Chemists are increasingly looking for a combination of both techniques for efficient organic synthesis. This review covers the recent literature on organic synthesis using microwave heating in conjunction with polymer-supported reagents and scavengers.     

Solid-supported reagents and catalysts for the preparation of large ring compounds

Parallel combinatorial synthesis in solution using immobilized reagents, catalysts, and scavengers has emerged as a powerful technique for the preparation of diverse libraries of compounds. This technique has only recently been applied to the synthesis of large-ring compounds. In this comprehensive review several strategies are presented and discussed, including Pd-catalyzed allylic alkylation, Stille-coupling, macrolactonization and macrolactamization using solid supported reagents and catalysts. In several cases site isolation has allowed operation of these macrocyclization reactions in concentrated solution (pseudo-dilution effect).     

High-loading polyglycerol supported reagents for Mitsunobu- and acylation-reactions and other useful polyglycerol derivatives

Summary In this paper we present soluble dendritic polyglycerol (PG) supported reagents PG-DEAD, PG-PPh₃, and PG-DCC as well as scavengers PG-carbonate, PG-carbazate, and PG-amine, which all have been synthesized in high overall conversions and yields using simple purification techniques. The supported reagents have been used simultaneously in Mitsunobu and acylation reactions. All polymeric reagents and scavengers can be removed by simple precipitation/filtration protocols to give chromatography-free products of high purity. In the course of the syntheses of the polymeric reagents three intermediates turned out to be precious polyglycerol derivatives: a mixed carbonate as an electrophilic derivative, polyglyceryl carbazate as a scavenger for carbonyl compounds, as well as polyglycerylamines as amino analogues of polyglycerol.     

Polymer resin library and the discovery of highly efficient polymer supported reagents and scavengers

Summary This paper is focused on the preparation of a library of highly efficient, tailor made, macroporous resins as supports for reagents and scavengers. From this library a macroporous resin, prepared with 40% cross-linking and with a porogen level of 300% in toluene gave a material superior to those presently available, and was shown to be highly efficient in the preparation of novel highly reactive polymer supported reagents, including scavengers and oxidants.     

Enhancement of sonochemical degradation of phenol using hydrogen atom scavengers

Sonochemical degradation of phenol was found to be enhanced in the presence of the volatile hydrogen atom scavengers CCl4 and perfluorohexane. The non-volatile hydrogen atom scavenger iodate did not enhance phenol degradation. The first order rate constant for aqueous phenol degradation in separate experiments using different sonochemical probes increased in the presence of 150 microM CCl4 from 0.014 to 0.031 min(-1) (probe 1) and from 0.022 to 0.061 min(-1) (probe 2). In the presence of <1.5 microM C6H14, the first order rate constant increased from 0.014 to 0.032 min(-1) (probe 1). Hydroquinone was the major observed reaction intermediate both in the presence and absence of hydrogen atom scavengers. Hydroquinone yields were substantially higher in the presence of hydrogen atom scavengers, suggesting that hydroxyl radical pathways for phenol degradation were enhanced by the hydrogen atom scavengers. These additives may be useful in improving pollutant degradation efficiency or improving synthetic processes that rely on hydroxyl radical as a key intermediate.     

Using pulsed wave ultrasound to evaluate the suitability of hydroxyl radical scavengers in sonochemical systems

Hydroxyl radical (OH) scavengers are commonly used in sonochemistry to probe the site and nature of reaction in aqueous cavitational systems. Using pulsed wave (PW) ultrasound with comparative sonochemistry we evaluated the performance of OH scavengers (i.e., formic acid, carbonic acid, terephthalic acid/terephthalate, iodide, methanesulfonate, benzenesulfonate, and acetic acid/acetate) in a sonochemical system to determine which OH scavengers react only in bulk solution and which OH scavengers interact with cavitation bubbles. The ability of each scavenger to interact with cavitation bubbles was assessed by comparing the pulse enhancement (PE) of 10 μM of a probe compound, carbamazepine (CBZ), in the presence and absence of a scavenger. Based on PE results, acetic acid/acetate appears to scavenge OH in bulk solution, and not interact with cavitation bubbles. Methanesulfonate acts as reaction promoter, increasing rather than inhibiting the degradation of CBZ. For formic acid, carbonic acid, terephthalic acid/terephthalate, benzenesulfonate, and iodide, the PE was significantly decreased compared to in the absence of the scavenger. These scavengers not only quench OH in bulk solution but also affect the cavity interface. The robustness of acetic acid/acetate as a bulk OH scavenger was validated for pH values between 3.5 and 8.9 and acetic acid/acetate concentrations from 0.5 to 0.1 M.     

Reactivities of mixed organozinc and mixed organocopper reagents. Part 7. Comparison of the transfer rate of the same group in allylation of mixed and homo diorganozinc reagents

A detailed direct kinetic study has been carried out to compare the reaction rate of transferable group, Ph in mixed phenylzinc reagents, RPhZn (R = n‐alkyl) and in homo diphenylzinc reagent, Ph₂Zn in their reactions with allyl bromide in THF at 25–(?15) °C. Empirical rata law and activation parameters are consistent with a second‐order substitution reaction. The allylation rate of transferable group Ph in RPhZn (R = n‐alkyl) has been found higher than the rate of Ph group in Ph₂Zn. A mechanism which accommodates the kinetic data and higher allylation rate of transferable group Ph in RPhZn than that in Ph₂Zn is given. Copyright © 2013 John Wiley & Sons, Ltd.     

Effective scavenging at cryotemperatures: further increasing the dose tolerance of protein crystals

The rate of radiation damage to macromolecular crystals at both room temperature and 100 K has previously been shown to be reduced by the use of certain radical scavengers. Here the effects of sodium nitrate, an electron scavenger, are investigated at 100 K. For sodium nitrate at a concentration of 0.5 M in chicken egg‐white lysozyme crystals, the dose tolerance is increased by a factor of two as judged from the global damage parameters, and no specific structural damage to the disulfide bonds is seen until the dose is greatly in excess (more than a factor of five) of the value at which damage appears in electron density maps derived from a scavenger‐free crystal. In the electron density maps, ordered nitrate ions adjacent to the disulfide bonds are seen to lose an O atom, and appear to protect the disulfide bonds. In addition, results reinforcing previous reports on the effectiveness of ascorbate are presented. The mechanisms of action of both scavengers in the crystalline environment are elucidated.     

Polyborylated reagents for modern organic synthesis

Diverse kinds of gem- and vic-diborylated compounds are now readily available thanks to advances in gem-diborylation of lithium carbenoids as well as vic-diborylation of carbon-carbon multiple bonds with diboron compounds. These diborylated reagents lead to invention of polyborylated reagents and many novel and useful synthetic methods for supreme stereocontrol. This review summarizes preparative methods and synthetic reactions of di- and polyborylated reagents with the emphasis on multiple bond formation.     

High‐pressure effects on the Diels–Alder reaction in room temperature ionic liquids

The effect of pressure on the Diels–Alder reaction was examined in room temperature ionic liquids, followed by high‐pressure FT‐IR spectroscopy using pressures up to 150 MPa. Pressure enhances the kinetic sensitivity of the reaction. The kinetic effect of fluorophobic interactions was examined using ionic liquids with fluorous cations. Ionic liquids in combination with ZnI₂ as a Lewis acid catalyst were also studied under high pressure. Copyright © 2007 John Wiley & Sons, Ltd.     

Room‐temperature scavengers for macromolecular crystallography: increased lifetimes and modified dose dependence of the intensity decay

The advent of highly intense wiggler and undulator beamlines has reintroduced the problem of X‐ray radiation damage in protein crystals even at cryogenic temperatures (100 K). Although cryocrystallography can be utilized for the majority of protein crystals, certain macromolecular crystals (e.g. of viruses) suffer large increases in mosaicity upon flash cooling and data are still collected at room temperature (293 K). An alternative mechanism to cryocooling for prolonging crystal lifetime is the use of radioprotectants. These compounds are able to scavenge the free radical species formed upon X‐ray irradiation which are thought to be responsible for part of the observed damage. Three putative radioprotectants, ascorbate, 1,4‐benzoquinone and 2,2,6,6‐tetramethyl‐4‐piperidone (TEMP), were tested for their ability to prolong lysozyme crystal lifetimes at 293 K. Plots of relative summed intensity against dose were used as a metric to assess radioprotectant ability: ascorbate and 1,4‐benzoquinone appear to be effective, whereas studies on TEMP were inconclusive. Ascorbate, which scavenges OH radicals (k_OH = 8 × 10⁹ M^?1 s^?1) and electrons with a lower rate constant (k_e‐(aq) = 3.0 × 10⁸ M^?1 s^?1), doubled the crystal dose tolerance, whereas 1,4‐benzoquinone, which also scavenges both OH radicals (k_OH = 1.2 × 10⁹ M^?1 s^?1) and electrons (k_e‐(aq) = 1.2 × 10¹⁰ M^?1 s^?1), offered a ninefold increase in dose tolerance at the dose rates used. Pivotally, these preliminary results on a limited number of samples show that the two scavengers also induced a striking change in the dose dependence of the intensity decay from a first‐order to a zeroth‐order process.     

Nickel-catalyzed cross-coupling of bromophenols with Grignard reagents in the solid phase synthesis

Polymer-bound substituted bromophenols were found to readily undergo a Ni(0)-catalyzed cross-coupling reaction with Grignard reagents to give a variety of substituted phenols and hydroquinones, after cleavage from the support, in moderate to high yields. The requisite bromophenol derivatives, which were prepared from the corrresponding phenols and hydroquinone using BTMA Br₃ or TBA Br₃, were attached to the solid support by the Mitsunobu reaction.     

On the hydroperoxyl radical scavenging activity of two Edaravone derivatives: mechanism and kinetics

The free radical scavenging activity of two Edaravone (EDA) derivatives (C1 and D1) has been studied in aqueous and lipid solutions using the Density Functional Theory. Different mechanisms of reaction have been considered, as well as the acid/base equilibrium in aqueous solution. The studied compounds were found to be rather poor ^?OOH scavengers in non‐polar environments, but better than the parent molecule, EDA, which suggests that the peroxyl scavenging activity of this kind of compounds in lipid media could be increased via structural modifications. In aqueous solution, at physiological pH, D1 is predicted to be a better peroxyl scavenger than C1, and slightly better than its parent molecule, EDA. Their excellent activity, under such conditions, is attributed to the electron transfer from their anionic forms. D1 was found to be among the best peroxyl scavengers known so far, with a rate constant for its reaction with ^?OOH near the diffusion limit regime (2.3 × 10⁸ M^?1s^?1). Copyright © 2013 John Wiley & Sons, Ltd.     

Kinetic equations for exactly solvable models of geminate reactions in the presence of scavengers

The kinetic equations for an exactly solvable scavenger problem were presented in the form of the equation of general kinetic theory. Presenting the memory function as the sum of Markovian and non-Markovian parts yielded a binary approximation corresponding to low scavenger concentrations. It was demonstrated that the bulk channel of the formation of product D can be separated into two subchannels: the reaction of a scavenger C with the reactant B that left a geminate pair AB for the bulk solution (bulk subchannel) and with the reactant B that retains a spatial correlation with the reactant A (geminate subchannel). Note that the geminate subchannel of the D-channel and the geminate subchannel of the formation of product P are of three-particle nature, and, therefore, their rates cannot be expressed through the relative mobilities of the reactants in pairs BC and AB. The obtained equations of general kinetic theory were transformed so as to impart them the regular form of the rate equations accepted in chemistry, with a bulk reaction rate constant and nonuniform terms (sources) associated with the initial spatial correlations between the reactants. Nevertheless, these equations differ substantially from those reported in the literature.     

Enhancement of ultrasonically initiated emulsion polymerization rate using aliphatic alcohols as hydroxyl radical scavengers

Ultrasonically initiated emulsion polymerization of styrene was carried out in the presence of aliphatic alcohols, e.g. methanol, ethanol, n-pronanol and n-butanol, as volatile hydroxyl radical scavengers. With the addition of methanol, the polymerization rate of styrene increased, while the molecular weight and the average particle size of the produced polystyrene decreased because more radicals were produced in the presence of methanol. This is true also for the other polymerization system using other aliphatic alcohols, such as ethanol, n-pronanol and n-butanol, suggesting that the alcohols enter into cavitation bubbles and further react with hydroxyl radicals (*OH) from the sonolysis of water to produce hydroxyalkyl radicals, so as to reduce the recombination of *H and *OH radicals, therefore more radicals will be present in the systems for initiating polymerization. Obviously, it is an effective way to enhance ultrasonically initiated emulsion polymerization rate of styrene by adding volatile hydroxyl radical scavenger.     

Mathematical Simulation of Low-Frequency Mechanical Action on Bimolecular Reaction Kinetics in a Structured Liquid

A mathematical model of the physicochemical processes that occur under low-frequency mechanical action on bimolecular reaction kinetics with consideration for the association of reagents is presented. As a result of the mathematical simulation, special features of the kinetics and stability of the reaction modes were established. It was shown that, in a structured liquid, a formally simple reaction occurs as a complex process with the appearance of bistability regimes, the formation of a temporal dissipative structure, and the complex structure of intermediate concentration oscillations. The possibility of controlling transitions from stable to unstable reaction conditions and vice versa under changes in the external action amplitude was demonstrated.     

红外光谱分析技术在浮选过程中的应用研究进展

随着浮选研究的深入发展,以捕收剂为核心的浮选药剂作用机理的研究逐渐成为研究焦点。红外光谱以速度快、成本低、无损等特点成为浮选药剂作用机理研究最为重要的手段之一。首先从文献报道数量和比例说明红外光谱在该研究中的重要地位,并总结了常见浮选药剂的红外光谱特征,最后分别阐述了红外光谱在捕收剂、抑制剂、活化剂等浮选药剂作用机理中的应用研究进展。归纳出红外光谱用于判定捕收剂在矿物表面作用三种机制的判据： 如果捕收剂作用后的矿物表面有新的吸收峰,则捕收剂在矿物表面发生了化学反应;如果仅有吸收峰的位置发生移动,并超过测试设备本身误差范围的移动量,则捕收剂在矿物表面形成的是化学吸附;排除上述产生的新红外特征吸收峰和红外特征峰的移动,且通过反复水洗即可清除表面沾染的捕收剂分子,则捕收剂在矿物表面发生的是物理吸附。并指出红外光谱在浮选过程中的应用研究存在的两大问题,一是将捕收剂与矿物表面的化学反应和化学吸附机理混淆;二是忽视红外光谱仪器吸收峰位移2～4 cm-1背景误差。展望未来红外光谱在浮选过程中的应用研究应该着眼于多种药剂混合用药在矿物表面作用机理的研究,该领域内红外光谱的定量分析研究及红外光谱吸收峰位移的背景误差分析等三方面。     

Combination of microwave reactions with fluorous separations in the palladium-catalyzed synthesis of aryl sulfides

Coupling of microwave reactions with fluorous separations can dramatically increase the efficiency of high-speed synthesis. Described in this paper is a fluorous synthesis of aryl sulfides by palladium-catalyzed cross-coupling of aryl perfluoroalkylsulfonates (C8F17O2SOAr) with thiols (RSH) under microwave irradiation. Fluorous solid-phase extractions (F-SPE) are employed for the purification of reaction mixtures. No fluorous solvents are involved in reaction and separation processes. The fluorous synthesis is further extended to the multi-step synthesis of substituted hydantoin and amide scaffolds.     

Peculiarities of diffusion-controlled recombination kinetics at long time and/or for great initial reagent concentrations

The earlier developed generalized theory of bimolecular reactions between reagents (defects) in solids and liquids, based on a more complete than the standard one decoupling of the hierarchy of equations for many-point densities, is used for detailed calculations of theA+BAB reaction kinetics at long time (great reaction depth). The effects of great initial concentrations and relative diffusion coefficients upon the reaction kinetics are also studied. The earlier predicted lowering of the reaction rate due to a dynamical aggregation of similar (non-interacting) reagents is confirmed. The greater the initial reagent concentration and if one kind of reagents (A's orB's) are immobile, the more pronounced is the aggregation effect.One of the authors (E. K.) is greatly indebted to the Institute of Physics of Charles University for warm hospitality during his visit in autumn 1983 and Dr. L. Skála for the help in computer calculations at the early stage of this work.     

The free radical scavenging activity of lespedezacoumestan toward ˙OH radical: A quantum chemical and computational kinetics study

The free radical activity of lespedezacoumestan was investigated toward hydroxyl (˙OH) radical in polar and nonpolar media using density functional theory. Four reaction mechanisms including radical adduct formation, hydrogen atom transfer, sequential single electron‐proton transfer (SET‐PT), and sequential proton loss electron transfer were considered. The rate constants and branching ratio for all possible sites of reaction were calculated and reported for the first time. According to the obtained results, lespedezacoumestan reacts faster with ˙OH radical in aqueous solution than in nonpolar media. Also, lespedezacoumestan is an excellent ˙OH radical scavenger regardless of the environment polarity.