Α-aminoalkyl Radicals Research Articles

Visible-Light-Mediated Nucleophilic Addition of an α-Aminoalkyl Radical to Isocyanate or Isothiocyanate

A visible-light photoredox synthesis of α-amino amide or α-amino thioamide from N,N-dimethylaniline derivatives and aryl isocyanate or aryl isothiocyanate was developed. Bis[2-(4,6-difluorophenyl)pyridinato-C(2),N](picolinato)iridium(III) (FIrpic) was found to be the effective catalyst among six catalysts screened. The reaction involves generation of α-aminoalkyl radicals from tertiary amines, followed by radical addition to the electron-deficient carbon of isocyanate and isothiocyanate.

Oxidation of Primary Amines to Oximes with Molecular Oxygen using 1,1-Diphenyl-2-picrylhydrazyl and WO3/Al2O3 as Catalysts

The oxidative transformation of primary amines to their corresponding oximes proceeds with high efficiency under molecular oxygen diluted with molecular nitrogen (O2/N2 = 7/93 v/v, 5 MPa) in the presence of the catalysts 1,1-diphenyl-2-picrylhydrazyl (DPPH) and tungusten oxide/alumina (WO3/Al2O3). The method is environmentally benign, because the reaction requires only molecular oxygen as the terminal oxidant and gives water as a side product. Various alicyclic amines and aliphatic amines can be converted to their corresponding oximes in excellent yields. It is noteworthy that the oxidative transformation of primary amines proceeds chemoselectively in the presence of other functional groups. The key step of the present oxidation is a fast electron transfer from the primary amine to DPPH followed by proton transfer to give the α-aminoalkyl radical intermediate, which undergoes reaction with molecular oxygen and hydrogen abstraction to give α-aminoalkyl hydroperoxide. Subsequent reaction of the peroxide with WO3/Al2O3 gives oximes. The aerobic oxidation of secondary amines gives the corresponding nitrones. Aerobic oxidative transformation of cyclohexylamines to cyclohexanone oximes is important as a method for industrial production of ε-caprolactam, a raw material for Nylon 6.

Electron and hydrogen self-exchange of free radicals of sterically hindered tertiary aliphatic amines investigated by photo-CIDNP

The photoreactions of diazabicyclo[2,2,2]octane (DABCO) and triisopropylamine (TIPA) with the sensitizers anthraquinone (AQ) and xanthone (XA) or benzophenone (BP) were investigated by time-resolved photo-CIDNP (photochemically induced dynamic nuclear polarization) experiments. By varying the radical-pair concentration, it was ensured that these measurements respond only to self-exchange reactions of the free amine-derived radicals (radical cations DH•+ or α-amino alkyl radicals D•) with the parent amine DH; the acid–base equilibrium between DH•+ and D• also plays no role. Although the sensitizer does not at all participate in the observed processes, it has a pronounced influence on the CIDNP kinetics because the reaction occurs through successive radical pairs. With AQ, the polarizations stem from the initially formed radical-ion pairs, and escaping DH•+ then undergoes electron self-exchange with DH. In the reaction sensitized with XA (or BP), the polarizations arise in a secondary pair of neutral radicals that is rapidly produced by in-cage proton transfer, and the CIDNP kinetics are due to hydrogen self-exchange between escaping D• and DH. For TIPA, the activation parameters of both self-exchange reactions were determined. Outer-sphere reorganization energies obtained with the Marcus theory gave very good agreement between experimental and calculated values of ∆G‡298.

Direct sp3 CH Amination of Nitrogen‐Containing Benzoheterocycles Mediated by Visible‐Light‐Photoredox Catalysts

Visible-light-mediated direct sp(3) C-H amination of benzocyclic amines via α-aminoalkyl radicals by using photoredox catalysts is described here. The obtained N,N-acetals were also successfully applied for carbon-carbon bond forming reactions with carbon nucleophiles. The procedure is suitable for a late-stage modification of C-H bonds to C-C bonds.

ChemInform Abstract: Visible‐Light‐Mediated Addition of α‐Aminoalkyl Radicals Generated from α‐Silylamines to α,β‐Unsaturated Carbonyl Compounds

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Atmospheric Chemistry of 2-Aminoethanol (MEA): Reaction of the NH2•CHCH2OH Radical with O2

The alkanolamine 2-aminoethanol (NH(2)CH(2)CH(2)OH), otherwise known as monoethanolamine (MEA), is a widely used solvent for carbon capture, yet relatively little is known about its atmospheric chemistry. The hydroxyl radical initiated oxidation of MEA is thought to predominantly form the α-aminoalkyl radical NH(2)(•)CHCH(2)OH, which will subsequently react with O(2) in the atmosphere to produce a peroxyl radical. We have investigated the reaction of O(2) with the NH(2)(•)CHCH(2)OH radical using quantum chemical calculations and master equation kinetic modeling. This reaction is found to proceed predominantly via a chemically activated mechanism under tropospheric conditions to directly produce the imine 2-iminoethanol (NH═CHCH(2)OH) + HO(2)(•), with lesser amounts of the collisionally deactivated peroxyl radical NH(2)CH(O(2)(•))CH(2)OH. By largely bypassing a peroxyl radical intermediate, this process avoids ozone-promoting conversion of NO to NO(2) and makes the oxidation of MEA to 2-iminoethanol HO(x)-neutral overall. The imine product of MEA oxidation is proposed as an important intermediate in the formation of aerosols via uptake to water droplets and subsequent hydrolysis to ammonia and glycolaldehyde.

ChemInform Abstract: Visible‐Light‐Mediated Utilization of α‐Aminoalkyl Radicals: Addition to Electron‐Deficient Alkenes Using Photoredox Catalysts.

Synthetic use of α-aminoalkyl radicals formed by single electron oxidation of amines is quite limited. Here we demonstrate addition of α-aminoalkyl radicals to electron-deficient alkenes by visible-light-mediated electron transfer using transition metal polypyridyl complexes as photocatalysts, via a sequential redox pathway.

Reactivity of neonicotinoid insecticides with carbonate radicals

The reaction of three chloronicotinoid insecticides, namely Imidacloprid (IMD), Thiacloprid (THIA) and Acetamiprid (ACT), with carbonate radicals (CO3−) was investigated. The second order rate constants (4 ± 1) × 106, (2.8 ± 0.5) × 105, and (1.5 ± 1) × 105 M−1 s−1 were determined for IMD, THIA and ACT, respectively. The absorption spectra of the organic intermediates formed after CO3− attack to IMD is in line with those reported for α-aminoalkyl radicals. A reaction mechanism involving an initial charge transfer from the amidine nitrogen of the insecticides to CO3− is proposed and further supported by the identified reaction products. The pyridine moiety of the insecticides remains unaffected until nicotinic acid is formed. CO3− radical reactivity towards IMD, ACT, and THIA is low compared to that of HO• radicals, excited triplet states, and 1O2, and is therefore little effective in depleting neonicotinoid insecticides.

Visible-Light-Mediated Utilization of α-Aminoalkyl Radicals: Addition to Electron-Deficient Alkenes Using Photoredox Catalysts

Synthetic use of α-aminoalkyl radicals formed by single electron oxidation of amines is quite limited. Here we demonstrate addition of α-aminoalkyl radicals to electron-deficient alkenes by visible-light-mediated electron transfer using transition metal polypyridyl complexes as photocatalysts, via a sequential redox pathway.

Visible-light-mediated addition of α-aminoalkyl radicals generated from α-silylamines to α,β-unsaturated carbonyl compounds

Visible-light-mediated addition of α-aminoalkyl radicals generated from α-silylamines to α,β-unsaturated carbonyl compounds using a photoredox catalyst is developed. We also succeeded in the isolation of a silyl enol ether as a primary product of the photochemical reaction.

Activation of aliphatic C–H bonds by tetracyanobenzene photosensitization. A time-resolved and steady-state investigation

The photochemistry of 1,2,4,5-tetracyanobenzene (TCB) in acetonitrile in the presence of representative aliphatic donors (cyclohexane, 1,4-dioxane and triethylamine) has been investigated by femtosecond (fs) and nanoseconds (ns) flash photolysis as well as steady state irradiation in order to define the kinetic frame for the activation of aliphatic C–H bonds. Unlike in the case of aromatics, no ground state complex (except possibly in the case of triethylamine) or exciplex is formed. The lowest excited singlet is quenched and forms the free radical ions. The efficiency of the process, measured by the yield of TCB˙− (0.84 with cyclohexane, 0.15 with 1,4-dioxane, 0.37 with triethylamine) depends on the rate of return electron transfer, low for a high exothermicity. The chemical reaction following the electron transfer step depends on the properties of the radical cation. Thus, with cyclohexane deprotonation is slow and does not occur measurably on a microsecond scale, while on a longer time scale, the formation of alkyl radicals competes with back electron transfer between the free ions. The deprotonation of amine radical cations is faster and the resulting α-aminoalkyl radicals reduce a further molecule of TCB, causing the accumulation of the radical anion which is indefinitely stable in the absence of oxygen.

ChemInform Abstract: EPR Studies on the Photofragmentation of 2,2-Dialkyl-2- alkylaminoacetophenones

Free radical reactions induced by photolysis of 2,2-dialkyl-2-alkylaminoacetophenone photocuring agents have been studied by continuous wave (CW) and time-resolved EPR spectroscopy. In all solvents α-cleavage from the triplet state is the major process. In hydrogen donor solvents it is accompanied by photoreduction followed by a rapid amine elimination from the ketyl radical inter-mediate. The benzoyl and α-aminoalkyl radicals resulting from α-cleavage readily add to acrylonitrile whereas radicals formed by photoreduction do not.

ChemInform Abstract: Thiazolidine Derivatives: A New Source of α-Aminoalkyl Radicals for Carbon-Carbon Bond Formation in Synthesis.

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Photoinduced Size-Controlled Generation of Silver Nanoparticles Coated with Carboxylate-Derivatized Thioxanthones

We report a new strategy for a rapid photoinduced synthesis of monodisperse ligand-coated silver nanoparticles. Such nanoparticles are produced through a very fast reduction of Ag+ by α-aminoalkyl radicals which are first generated from hydrogen abstraction toward an aliphatic amine by the excited triplet state of the 2-substituted thioxanthone series (TX−O−CH2−COO− and TX−S−CH2−COO−). The quantum yield of this prior reaction is tuned by the substituent effect on thioxanthones and leads to a kinetic control of the conversion of Ag+ to Ag(0). Combined with the capping role of a carboxylate function linked to the chromophores, a size regulation of the growing nanoparticles is both promoted and optimized because of a concomitant kinetics adjustment between the photoreduction process and the subsequent functionalization of the nanoparticles. We demonstrate that the optimal adjustment is then obtained with TX−S−CH2−COO−.

Synthetic use of the primary kinetic isotope effect in hydrogen atom transfer: generation of α-aminoalkyl radicals

The extent to which deuterium can act as a protecting group to prevent unwanted 1,5-hydrogen atom transfer to aryl and vinyl radical intermediates was examined in the context of the generation of α-aminoalkyl radicals in a pyrrolidine ring. Intra- and intermolecular radical trapping following hydrogen atom transfer provides an illustration of the use of the primary kinetic isotope effect in directing the outcome of synthetic C-C bond-forming processes.

Photophysical Properties and Two-Photon Polymerization Ability of a Nitroalkoxystilbene Derivative

The photophysical behavior of the trans-4-propoxy 4′-nitrostilbene (PNS) as well as its one- and two-photon polymerization properties are reported. A detailed solvatochromic analysis of the steady-state and time-resolved fluorescence indicates that the locally excited state of PNS (LE) undergoes multiple deactivation pathways which are sequentially triggered by the solvent polarity. In low polar solvent, an efficient intersystem crossing (ISC) identified as a S1→Tn process leads to the population of the lowest triple state from which the trans−cis photoisomerization is mainly proceeding. From ns-laser flash photolysis measurements, it also appears that the T1 state which exhibits a nπ* character can efficiently abstract a hydrogen from aliphatic amines and subsequently produces α-aminoalkyl radicals, highly reactive species for the photoinitiation of free-radical polymerization. As a consequence, PNS constitutes a good photoinitiating system. However, the further increase of the solvent polarity opens a new relaxation pathway which populates a highly polar TICT level to the detriment of ISC and trans−cis photoisomerization. A strong increase of the fluorescence quantum yield with a concomitant decrease of the trans−cis photoisomerization one is then observed. At the high end of the solvent-polarity scale, an adding non-radiative deactivation process associated with the twisting of the nitro group leads to a noticeable decrease of the fluorescence process. The photoinduced charge transfer process which largely impacts the photophysical feature of such a D−π−A system also promotes the two-photon absorption properties of PNS. The chromophore exhibits a sizable two-photon absorption spectrum in the 700−900 nm region with δ of about 180 ± 15 GM at 750 nm. In conjunction with its photoinitiating properties, the two-photon polymerization ability of PNS was finally demonstrated. A systematic comparison with a 2,7 diaminofluorene derivative used as reference for two-photon polymerization confirms the substantial improvement of the two-photon polymerization efficiency.

In-situ fabrication of polyacrylate–silver nanocomposite through photoinduced tandem reactions involving eosin dye

A silver–acrylate nanocomposite was prepared using a novel one-pot strategy involving eosin dye as visible sensitizer and an amine derivative as radicals' source. The mechanism highlighted by steady state photolysis and time-resolved absorption spectroscopy lies on the initial formation of a strong ion-pair complex between eosin and Ag +. Upon visible irradiation, the excited triplet state of the metal complex efficiently abstracts a hydrogen atom from the amine and produces an α-aminoalkyl radical. In acrylate monomer matrix, such a strong reactive species initiates a free radical photopolymerization and also provides the reduction of the silver cation. Through this ‘in-situ’ fabrication method, the kinetics formation of the nanocomposite and its detailed structural analysis are characterized by UV–visible, real-time FTIR absorption spectroscopy and by transmission electron microscopy.

An annelated thioxanthone as a new Type II initiator

5-Thia-naphthacen-12-one (TX-Np) was synthesized as a potential photoinitiator for radical polymerization. Polymerization studies revealed that TX-Np acts as a photoinitiator for radical polymerization of acrylic type monomers in the presence of N-methyldiethanolamine (MDEA). The phosphorescence spectrum measured at 77 K in ethanol showed an emission band at λ max = 505 nm corresponding to the approximate triplet energy of ca. 237 kJ/mol. The phosphorescence lifetime was found to be 197 ms corresponding to a π–π* nature of the lowest triplet state. The quantum yield for fluorescence emission ( ϕ f) in benzene was found to be 0.045. Spectroscopic and polymerization studies revealed that photoinitiation occurs through the α-aminoalkyl radical, similar to thioxanthone-based photoinitiators. Since MDEA is required for TX-Np to act as an initiator for acrylate polymerization, it is suggested that the TX-Np reacts with MDEA to give α-aminoalkyl radicals which initiate polymerization.

Photochemically induced radical addition of tertiary amines to C=C and C=O double bonds: A green chemistry contribution to organic synthesis

Abstract Photochemically induced electron transfer considerably enriches the redox chemistry of organic molecules. This primary step has been used to produce α-amino alkyl radicals that can be added to various double bonds. The addition to olefinic and carbonyl bonds is discussed. Homogeneous and heterogeneous photocatalysis methods with various electron-transfer sensitizers are described.

Divergent Synthetic Strategy Leading to Structurally Diverse Pyrrolidines and Piperidines from Common γ-Aminoalkyl Butenolide and Aldehyde Precursors

Condensation between aldehydes and the secondary amino function of 5-(aminoalkyl)furan-2(5H)-ones, obtained by the silyloxyfuran dienolate addition to imine-type derivatives, produces either aminoalkylbenzotriazoles or 1,2,3,4-tetrahydropyridines. The former can be reduced with SmI2 to generate alpha-aminoalkyl radicals that are trapped by the alpha,beta-unsaturated lactone moiety yielding substituted pyrrolidines diastereoselectively, while catalytic hydrogenation of the latter affords isomeric piperidine analogues. Alternatively, SmI2-promoted reduction of tetrahydropyridines in the presence of acid also leads to intermediate alpha-aminoalkyl radicals that participate in inter- or intramolecular olefin addition reactions. Further manipulation of the lactone functionality in various ways gives access to a number of interesting derivatives based upon either a pyrrolidine or a piperidine structural motif. As a result, a high degree of structural diversity is obtained in a few steps starting from a common set of simple materials.