Copper(0)‐mediated living radical polymerization of acrylonitrile: SET‐LRP or AGET‐ATRP

Cu(0)‐mediated living radical polymerization was first extended to acrylonitrile (AN) to synthesize polyacrylonitrile with a high molecular weight and a low polydispersity index. This was achieved by using Cu(0)/hexamethylated tris(2‐aminoethyl)amine (Me₆‐TREN) as the catalyst, 2‐bromopropionitrile as the initiator, and dimethyl sulfoxide (DMSO) as the solvent. The reaction was performed under mild reaction conditions at ambient temperature and thus biradical termination reaction was low. The rapid and extensive disproportionation of Cu(I)Br/Me₆‐TREN in DMSO/AN supports a mechanism consistent with a single electron transfer‐living radical polymerization (SET‐LRP) rather than activators generated by electron transfer atom transfer radical polymerization (AGET ATRP). ¹H NMR analysis and chain extension experiment confirm the high chain‐end functionality of the resultant polymer. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Tin-free radical alkoxyamine addition and isomerization reactions by using the persistent radical effect: variation of the alkoxyamine structure

Various C-centered radicals can efficiently be generated through thermal C-O-bond homolysis of alkoxyamines. This method is used to perform environmentally benign radical cyclization and intermolecular addition reactions. These alkoxyamine isomerizations and intermolecular carboaminoxylations are mediated by the persistent radical effect (PRE). In the paper, the effect of the variation of the alkoxyamine structure--in particular steric effects in the nitroxide moiety--on the outcome of the PRE mediated radical reactions will be discussed. Fourteen different nitroxides were used in the studies. It will be shown that reaction times can be shortened about 100 times upon careful tuning of the alkoxyamine structure. Activation energies for the C-O-bond homolysis of the various alkoxyamines are provided. The kinetic data are used to explain the reaction outcome of the PRE-mediated processes.     

Low temperature TEMPO‐mediated styrene polymerization in miniemulsion

The 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO)‐mediated stable free radical polymerization of styrene in miniemulsion at 100 °C is demonstrated. Although this temperature is 20–35 °C lower than typical temperatures used for TEMPO‐mediated polymerizations, reasonable reaction rates were achieved by the addition of ascorbic acid or a free radical initiator. More importantly, the living character of the chains was preserved; the degree of polymer “livingness” was comparable to polymerizations conducted at 135 °C. Polydispersities were broader than that observed in well‐controlled systems, ranging from ～1.4–1.6, and consistent with expectations for systems having a low activation rate. The results are significant for two reasons. They will facilitate TEMPO‐mediated minemulsion polymerizations in nonpressurized (or minimally pressurized) reactors, and they reveal the potential to expand the traditional temperature range of TEMPO and possibly other nitroxides in bulk, solution, and miniemulsion. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 232–242, 2006     

The Role of a Metallocene Additive in Radically Initiated Polymerization when Solving Direct and Inverse Kinetic Problems

Polymerization of methyl methacrylate, initiated by benzoyl peroxide in the presence of titanocene dichloride, is considered from the point of view of formal kinetics. Based on the kinetic scheme of the process (which includes the reactions of classical radical polymerization, the reaction of benzoyl peroxide with titanocene dichloride, the reactions of the controlled radical polymerization of organometallic mediated radical polymerization (OMRP) and atom transfer radical polymerization (ATRP), the reaction of the formation of a coordinating active site and the coordinating chain propagation on a mathematical model of the kinetics of the process is created. This model also makes it possible to calculate the molecular-mass characteristics of poly(methyl methacrylate). As a result of the solution of the inverse kinetic problem at a temperature of 343 K, the values of the reaction rate constants of the kinetic scheme are found under which the discrepancy between the calculated models and experimental data is minimal. Using the developed model of the kinetics of the process, a numerical experiment is performed (i.e., a direct kinetic problem is solved). This problem revealed the following regularities of the process. (1) An increase in the initial concentration of titanocene dichloride at a constant initial concentration of benzoyl peroxide leads to an increase in the rate of consumption of benzoyl peroxide but not to an increase in the initial rate of the process compared to classical radical polymerization. (2) With an increase in the initial concentration of titanocene dichloride, the lifetime of the macroradicals at the initial stage of the process is reduced, and hence the molecular weight of the resulting polymethyl methacrylate is less than that of the polymethyl methacrylate obtained in the absence of titanocene dichloride, and it will increase during the process of approaching the final values. (3) During the polymerization of methyl methacrylate, initiated by benzoyl peroxide in the presence of titanocene dichloride, a smoothing gel effect (as in the case of the polymerization of methyl methacrylate initiated by benzoyl peroxide in the presence of ferrocene) does not occur since titanocene dichloride forms stable complexes with methyl methacrylate and, consequently, it participates in reactions consuming macroradicals to a lesser degree than ferrocene.     

A Multifunctional Microfluidic Platform for High-Throughput Experimentation of Electroorganic Chemistry

Electroorganic synthesis is a promising tool to design sustainable transformations and discover new reactivities. However, the added setup complexity caused by electrodes in the system impedes efficient screening of reaction conditions. Herein, we present a microfluidic platform that enables automated high-throughput experimentation (HTE) for electroorganic synthesis at a 15-microliter scale. Two HTE modules are demonstrated: 1) the rapid electrochemical reaction condition screening for a radical–radical cross-coupling reaction on micro-fabricated interdigitated electrodes, and 2) measurements of kinetics for mediated anodic oxidations using the microliter-scale cyclic voltammetry. The presented modular approach could be deployed for a range of other electroorganic chemistry applications beyond the demonstrated functionalities.     

Transition Metal Free Cycloamination of Prenyl Carbamates and Ureas Promoted by Aryldiazonium Salts

Upon treatment with aryldiazonium salts, prenyl carbamates and ureas undergo redox‐neutral azocycloamination. In general, N‐aryl O‐prenyl carbamates cyclize in a photocatalytic reaction with visible light and an organic dye. With electron‐deficient diazonium salts, electronic matching with an electron‐rich N‐aryl substituent results in a reaction proceeding in the ground state, without either light or photocatalyst. Cyclic voltammetry suggests that this radical reaction is initiated by hydrogen‐atom abstraction mediated by an aryl radical, followed by a radical addition cascade and proton‐coupled hole propagation. The reaction proceeds at room temperature in short reaction times, and a range of functional groups is tolerated.     

Deactivation reactions in the modeled 2,2,6,6‐tetramethyl‐1‐piperidinyloxy‐mediated free‐radical polymerization of styrene: A comparative study with the 2,2,6,6‐tetramethyl‐1‐piperidinyloxy/acrylonitrile system

The competitiveness of the combination and disproportionation reactions between a 1‐phenylpropyl radical, standing for a growing polystyryl macroradical, and a 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) radical in the nitroxide‐mediated free‐radical polymerization of styrene was quantitatively evaluated by the study of the transition geometry and the potential energy profiles for the competing reactions with the use of quantum‐mechanical calculations at the density functional theory (DFT) UB3‐LYP/6‐311+G(3df, 2p)//(unrestricted) Austin Model 1 level of theory. The search for transition geometries resulted in six and two transition structures for the radical combination and disproportionation reactions, respectively. The former transition structures, mainly differing in the out‐of‐plane angle of the N? O bond in the transition structure TEMPO molecule, were correlated with the activation energy, which was determined to be in the range of 8.4–19.4 kcal mol^?1 from a single‐point calculation at the DFT UB3‐LYP/6‐311+G(3df, 2p)//unrestricted Austin Model 1 level. The calculated activation energy for the disproportionation reaction was less favorable by a value of more than 30 kcal mol^?1 in comparison with that for the combination reaction. The approximate barrier difference for the TEMPO addition and disproportionation reaction was slightly smaller for the styrene polymerization system than for the acrylonitrile polymerization system, thus indicating that a β‐proton abstraction through a TEMPO radical from the polymer backbone could diminish control over the radical polymerization of styrene with the nitroxide even more than in the latter system. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 232–241, 2007     

On the mechanism of reaction of radicals with tirapazamine

Ketyl radicals produced by photolysis of ketones or di-tert-butyl peroxide (DTBP) in alcohol solvents react rapidly with tirapazamine (TPZ). The acetone ketyl radical (ACOH) reacts with TPZ with an absolute second-order rate constant of (9.7 +/- 0.4) x 108 M-1 s-1. The reaction kinetics can be followed by monitoring the bleaching of TPZ absorption at 475 nm or the formation of a reaction product which absorbs at 320 and 410 nm. The ACOD radical reacts with TPZ in 2-propanol-OD with an absolute rate constant of (6.7 +/- 0.5) x 108 M-1 s-1, corresponding to a kinetic isotope effect (KIE) of 1.4. Deuteration of the radical on carbon (ACOH-d6) retards the reaction of the radical with TPZ even further (absolute rate constant = (4.8 +/- 0.04) x 108 M-1 s-1). This result corresponds to a KIE of 2.0. Radicals derived from dioxane and diisopropyl ether by flash photolysis of DTBP in ethereal solvent react with TPZ more slowly than do ketyl radicals. It is concluded that ketyl radicals react, in part, with TPZ in organic solvents by transfer of a hydrogen atom from the OH and CH3 groups of the ketyl radical to the oxygen atom at the N4 position of TPZ to form acetone or acetone enol and a radical derivative of TPZ (TPZH). The latter species absorbs at 320 and 405 nm, has a lifetime of hundreds of microseconds in alcohol solvents, and decays by disproportionation to form TPZ and a reduced heterocycle. The reduced heterocycle eventually forms a desoxytirapazamine by a polar mechanism. The results are supported by density functional theory calculations. It is proposed that dioxanyl radical will also react, in part, with TPZ by transfer of a hydrogen atom from the carbon adjacent to the radical center to the oxygen atom at the N4 position of TPZ. This produces the enol ether and the previously mentioned TPZH radical. It is further posited that ether radicals react a bit more slowly than ketyl radicals because they lack the second mode of hydrogen transfer (from the OH group) that is present in the ACOH radical. Our data are permissive of the possibility that ether radicals add to TPZ at a rate that is competitive with beta-hydrogen atom transfer.     

QUINONES AS MEDIATORS OF ELECTRON TRANSFER FROM MEMBRANE-BOUND CHLOROPHYLL TO CYTOCHROME c IN THE AQUEOUS PHASE IN LIPID BILAYER VESICLES: SYNERGISTIC ENHANCEMENT OF CYTOCHROME c REDUCTION BY LIPOPHILIC/ HYDROPHILIC QUINONE PAIRS

Laser flash photolysis has been used to determine the kinetics of cytochrome c reduction by chlorophyll triplet state in negatively-charged lipid bilayer vesicles, as mediated by quinones. Large synergistic enhancements in the yield of reduced cytochrome were obtained using a pair of quinones, one of which was lipophilic (e.g. benzoquinone, 2,6-di-f-butylbenzoquinone) and the other of which was hydrophilic (e.g. l,2-naphthoquinone-4-sulfonate). The mechanism was shown to involve initial quenching of the triplet by the membrane-associated quinone to form chlorophyll cation radical and quinone anion radical. An interquinone electron transfer process followed this reaction, which occurred at the membrane-water interface, and greatly facilitated electron transport from within the bilayer to the aqueous phase. This process formed the basis of the synergistic effect. Cytochrome c reduction occurred in the water phase by reaction with the anion radical of the hydrophilic quinone. Finally, the reduced cytochrome was reoxidized by a slow reaction with chlorophyll cation radical. Under the most favorable conditions, we estimate that the quantum yield of conversion of triplet quenching events to reduction of cytochrome approached unity. The lifetime of the reduced protein and oxidized chlorophyll could be as long as 140 ms, under the best conditions. This system has properties which are thus quite favorable for solar energy conversion in a biomimetic process.     

Controlled hydrogenation of P(VDF-co-CTFE) to prepare P(VDF-co-TrFE-co-CTFE) in the presence of CuX (X = Cl, Br) complexes

An environmentally friendly and controllable P(VDF-co-CTFE) hydrogenation route involving the transition-metal complex mediated radical chain transfer reaction is successfully developed to synthesize P(VDF-co-CTFE-co-TrFE). The typical transition metal catalysts of ATRP reaction could be applied in this process.     

The Persistent Radical Effect in Organic Synthesis

Radical–radical couplings are mostly nearly diffusion‐controlled processes. Therefore, the selective cross‐coupling of two different radicals is challenging and not a synthetically valuable transformation. However, if the radicals have different lifetimes and if they are generated at equal rates, cross‐coupling will become the dominant process. This high cross‐selectivity is based on a kinetic phenomenon called the persistent radical effect (PRE). In this Review, an explanation of the PRE supported by simulations of simple model systems is provided. Radical stabilities are discussed within the context of their lifetimes, and various examples of PRE‐mediated radical–radical couplings in synthesis are summarized. It is shown that the PRE is not restricted to the coupling of a persistent with a transient radical. If one coupling partner is longer‐lived than the other transient radical, the PRE operates and high cross‐selectivity is achieved. This important point expands the scope of PRE‐mediated radical chemistry. The Review is divided into two parts, namely 1) the coupling of persistent or longer‐lived organic radicals and 2) “radical–metal crossover reactions”; here, metal‐centered radical species and more generally longer‐lived transition‐metal complexes that are able to react with radicals are discussed—a field that has flourished recently.     

The radical reactions of imine radicals produced from the metal salts oxidation of 2-amino-1,4-benzoquinones

The metal salts mediated oxidative free radical reaction of 2-amino-1,4-benzoquinones is described. Imine radicals can be generated by the oxidation of 2-amino-1,4-benzoquinones with Mn(III) and Ag(II). The dimeric products 4 and 14 were formed via the intermolecular radical coupling reaction of the corresponding radical intermediates 5 and 15. In the presence of styrene, twistane 17 was afforded from 2-phenylamino-1,4-benzoquinone 1 via a radical annulation reaction of imine radical 5.     

Enantioselective Radical‐Polar Crossover Reactions of Indanonecarboxamides with Alkenes

Highly efficient asymmetric intermolecular radical‐polar crossover reactions were realized by combining a chiral N,N′‐dioxide/Ni^II complex catalyst with Ag₂O under mild reaction conditions. Various terminal alkenes and indanonecarboxamides/esters underwent radical addition/cyclization reactions to afford spiro‐iminolactones and spirolactones with good to excellent yields (up to 99 %) and enantioselectivities (up to 97 % ee). Furthermore, a range of different radical‐mediated oxidation/elimination or epoxide ring‐opening products were obtained under mild reaction conditions. The Lewis acid catalysts exhibited excellent performance and precluded the strong background reaction.     

Copper-promoted enantioselective Reformatsky-type reaction with ketones

Controlled living polymerization of a broad range of monomers is a radical process known as ATRP (atom transfer radical polymerization) and is mediated by a variety of metals. A complex of copper has been found to be the most efficient catalyst, with a copper(I)/copper(II) catalytic cycle. The radical, enantioselective catalytic Reformatsky reaction mediated by Me₂Zn can be efficiently promoted by copper(I) complexes avoiding the use of other promoters such as air and oxidant, giving more reproducible and affordable conditions. The CuCN-mediated enantioselective addition of ethyliodoacetate to functionalized ketones is described in this paper.     

Conversion of C5 into C6 cyclic species through the formation of C7 intermediates

We have recently proposed that the addition of C2H2 to the cyclopentadienyl radical can lead to the rapid formation of the cycloheptatrienyl radical and, in succession, of the indenyl radical. These reactions represent an interesting and unexplored route for the enlargement of gas-phase cyclic species. In this work we report ab initio calculations we performed with the aim of investigating in detail the gas-phase reactivity of cycloheptatrienyl and indenyl radicals. We found that the reaction of the cycloheptatrienyl radical with atomic hydrogen can lead to its fast conversion into the more stable benzyl radical. This reaction pathway involves the intermediate formation of heptatriene, norcaradiene, and toluene. Successively we investigated whether this reaction mechanism can be extended to polycyclic aromatic hydrocarbons (PAHs). For this purpose we studied the reaction of C2H2 with the indenyl radical, which can be considered as a superior homologue of the cyclopentadienyl radical. This reaction proceeds through a pathway similar to that proposed for C5H5 but with a reaction rate about an order of magnitude smaller. The present calculations extend thus the previously proposed C5-C7-C9 mechanism to bicyclic PAH and suggest a fast route for the conversion of C5 into C6 cyclic radicals, mediated by the formation of C7 cyclic species.     

A mechanistic study of the 2-thienylmethyl + HO2 radical recombination reaction

Radical recombination reactions are important in the combustion of fuel oils. Shale oil contains alkylated heteroaromatic species, the simplest example of which is the 2-thienylmethyl radical. The ab initio potential energy surface for the reaction of the 2-thienylmethyl radical with the HO(2) radical has been examined. Seventeen product channels corresponding to either addition/elimination or direct hydrogen abstraction have been characterized for the first time. Direct hydrogen abstract from HO(2) proceeds via a weakly bound van der Waals complex, which leads to 2-methylthiophene, 2-methylene-2,3-dihydrothiophene, or 2-methylene-2,5-dihydrothiophene depending upon the 2-thienylmethyl radical reaction site. The addition pathway for the two radical reactants is barrierless with the formation of three adducts, as distinguished by HO(2) reaction at three different sites on the 2-thienylmethyl radical. The addition is exothermic by 37-55 kcal mol(-1) relative to the entrance channel, and these excess energies are available to promote further decomposition or rearrangement of the adducts, leading to nascent products such as H, OH, H(2)O, and CH(2)O. The reaction surfaces are characterized by relatively low barriers (most lower than 10 kcal mol(-1)). Upon the basis of a careful analysis of the overall barrier heights and reaction exothermicities, the formations of O(2), OH, and H(2)O are likely to be important pathways in the radical recombination reactions of 2-thienylmethyl + HO(2).     

Do Photolyases Need To Provide Considerable Activation Energy for the Splitting of Cyclobutane Pyrimidine Dimer Radical Anions?

cis-syn Cyclobutane pyrimidine dimers, major UV-induced DNA lesions, are efficiently repaired by DNA photolyases. The key step of the repair reaction is a light-driven electron transfer from the FADH(-) cofactor to the dimer; the resulting radical anion splits spontaneously. Whether the splitting reaction requires considerable activation energy is still under dispute. Recent reports show that the splitting reaction of a dimer radical anion has a significant activation barrier (0.45 eV), and so photolyases have to provide considerable energy. However, these results contradict observations that cis-syn dimer radical anions split into monomers at -196 degrees C, and that the full process of DNA photoreactivation was fast (1.5-2 ns). To investigate the activation energies of dimer radical anions, three model compounds 1-3 were prepared. These include a covalently linked cyclobutane thymine dimer and a tryptophan residue (1) or a flavin unit (3), and the covalently linked uracil dimer and tryptophan (2). Their properties of photosensitised splitting of the dimer units by tryptophan or flavin unit were investigated over a large temperature range, -196 to 70 degrees C. The activation energies were obtained from the temperature dependency of splitting reactions for 1 and 2, 1.9 kJ mol(-1) and 0.9 kJ mol(-1) for the thymine and uracil dimer radical anions, respectively. These values are much lower than that obtained for E. coli photolyase (0.45 eV), and are surmountable at -196 degrees C. The activation energies provide support for previous observations that repair efficiencies for uracil dimers are higher than thymine dimers, both in enzymatic and model systems. The mechanisms of highly efficient enzymatic DNA repair are discussed.     

AIBN/SmCl3/乳酸体系催化甲基丙烯酸甲酯的反向原子转移自由基聚合

利用稀土金属化合物三氯化钐(SmCl3)和二氯化钐(SmCl2)之间的单电子转移反应,以AIBN/SmCl3/乳酸作为反向原子转移自由基聚合(ReverseATRP)的催化体系,成功地实现了甲基丙烯酸甲酯(MMA)的反向ATRP,并考察了温度、溶剂和组分比对聚合反应的影响.MMA在该体系中的聚合反应是一级反应,所得PMMA的分子量与单体转化率成正比,聚合物的分子量分布较窄(Mw/Mn<1.5),具有活性聚合的特征.     

Sulfinate‐Salt‐Mediated Radical Relay Cyclization of Cyclic Ethers with 2‐Alkynylbenzonitriles toward 3‐Alkylated 1‐Indenones

A new sulfinate salt‐mediated radical relay for the completion of C(sp³)?H bond indenylation of cyclic ethers with readily available 2‐alkynylbenzonitriles by combining silver/tert‐butyl peroxide (TBHP) was established, providing a wide range of 3‐alkylated 1‐indenones with generally good yields. Interestingly, the current reaction system can tolerate an S‐centered radical and a C‐centered radical in one pot, in which the S‐centered radical promotes the formation of the C‐centered radical to induce a radical cascade without disturbing the reaction process. A reaction mechanism is also proposed based on control experiments.     

Electron Transfer Reactions of Radical Anions with TEMPO: A Versatile Route for Transformation of Living Anionic Polymerization into Stable Radical‐Mediated Polymerization

Summary: The possibility of transforming a living anionic polymerization into a stable radical‐mediated radical polymerization (SFRP) was demonstrated. For this purpose, 2,2,6,6‐tetramethylpiperidine‐N‐oxyl (TEMPO) alcoholate, formed by a one‐electron redox reaction between potassium naphthalene and TEMPO, was used to initiate the living anionic polymerization of ethylene oxide (EO). Poly(ethylene oxide) obtained in this way possessed TEMPO terminal units and was subsequently used as an initiator for the SFRP of styrene to give block copolymers.

A one‐electron redox reaction gives rise to TEMPO alcoholate, which is able to initiate the living anionic polymerization of ethylene oxide (EO).