Amine Radical Cation Research Articles

A concept of an electron transfer stopped-flow method

A new concept of an electron transfer stopped-flow (ETSF) method is proposed. In the ETSF method, unstable cation radicals are formed via the electron transfer reactions with stable cation radicals whose oxidation potential is positive to that of unstable ones. Thus, by combining the electron transfer reactions with the stopped-flow operation, absorption spectroscopic measurements for short-lived cation radical become possible with a reduced dead time from the point of the generation of cation radicals to the point of the optical measurement, in particular, with a help of a rapid-scan spectrophotometer. By mixing an acetonitrile (AN) solution of tris(p-bromophenyl)amine cation radical (TBPA ⋅+) with an AN solution of methyldiphenylamine (MDPA) or diphenylamine (HDPA), the kinetic analyses could be carried out successfully for the dimerization reactions of MDPA ⋅+ and HDPA ⋅+ as well as the observations of their absorption spectra. It was found that fast reactions whose second order rate constants are around 10 7 M −1s −1 can be analyzed using the ETSF method.

Covalent Modification of a Glassy Carbon Surface by 4-Aminobenzoic Acid and Its Application in Fabrication of a Polyoxometalates-Consisting Monolayer and Multilayer Films

4-Aminobenzoic acid (4-ABA) was covalently grafted on a glassy carbon electrode (GCE) by amine cation radical formation in the electrooxidation process of the amino-containing compound. X-ray photoelectron spectroscopy measurement proves the presence of 4-carboxylphenylamine monolayer on the GCE. The redox responses of various electroactive probes were investigated on the 4-ABA-modified GCE. Electron transfer to Fe(CN)63- in solutions of various pHs was studied by both cyclic voltammetry and electrochemical impedance analysis on the modified electrode. Changes in the solution pH value result in the variation of the terminal group charge state, based on which surface pKa values are estimated. The 4-ABA-modified GCE was used as a suitable charged substrate to fabricate polyoxometalates-consisting (POM-consisting) monolayer and multilayer films through layer-by-layer assembly based on electrostatic attraction. Cyclic voltammetry shows the uniform growth of these three-dimensional multilayer films. Taking K10...

Time-resolved FT-EPR study of photoreduction of duroquinone by triethylamine in methanol

Using time resolved Fourier transform EPR spectroscopy the photoreduction of duroquinone by triethylamine in methanol solution was investigated. It is found that the spin-polarized (CIDEP) duroquinone triplet deactivates by electron transfer from triethylamine generating duroquinone radical anion and amine radical cation, and by hydrogen transfer from the solvent generating durosemiquinone radical and hydroxymethyl radical, respectively. All radicals are observed at different conditions and are spin-polarized by triplet mechanism and partially by ST0 radical pair mechanism. The time dependence of FT-EPR intensities of radical cation and radical anion on the amine concentration is investigated in the range of 1 to 100 mM triethylamine. The contribution of the triplet mechanism to the spin polarization of radicals changes with different triethylamine concentrations. The durosemiquinone radical is found to be transformed into duroquinone radical anion in the presence of triethylamine in the solution. CIDNP experiments indicate that the hydrogen back transfer between the durosemiquinone radical and hydroxymethyl radical pair has a significant influence on the time behaviour of duroquinone radical anion. The intensity of triethylamine radical cation is found to be decreased with the increase of triethylamine concentration, which is interpreted that the triethylamine radical cation is deprotonated by the amine. Based on the FT-EPR results, a new complete mechanism is proposed.

Monoamine oxidase-catalyzed oxidation of endo,endo-2-amino-6-[(Z)-2′-phenyl]ethenylbicyclo[2.2.1]heptane, a potential probe for a radical cation intermediate

An 11-step synthesis of endo,endo-2-amino-6-[(E)-2′-phenyl]ethenylbicyclo[2.2.1]heptane (6) and the corresponding (Z)-isomer (7) was carried out in an attempt to make a compound that could trap the purported amine radical cation intermediate during monoamine oxidase (MAO)-catalyzed oxidation of amines. The E-isomer was not a substrate for MAO, and the Z-isomer was a very poor substrate. No trapping product was observed. Possible explanations for the inability of these compounds to trap a potential radical cation intermediate are discussed.

The 1,2 migration of NH 3 in protonated β-aminoalkyl radicals

The enthalpy barriers for 1,2-migration of NH 3 in protonated β-aminoalkyl radicals, β-distonic isomers of primary amine radical cations, were determined with composite ab initio quantum chemical methods of the Gaussian and CBS families. The rearrangements are close to thermoneutral for small, protonated β-aminoalkyl radicals, and the barriers range from 60 to 100 kJ mol −1, depending on the degree of substitution. The transition state resembles an NH 3 molecule symmetrically coordinated to an alkene radical cation. The heats of formation of the protonated C 2–C 4 β-aminoalkyl radicals are lower than those of the corresponding amine radical cations by 20–40 kJ mol −1. The geometry and conformations of primary amine radical cations and their distonic isomers are briefly discussed.

Studies of the Anodic Oxidation of 1,4-Diazabicyclo

The title compound (1) was studied at platinum and gold electrodes in acetonitrile. A reversible oxidation peak occurs at +0.30 V vs the standard potential for ferrocenium ion/ferrocene. This process is followed by a second irreversible anodic peak that is due to the oxidation of the initially formed radical cation to the dication. The principal ultimate product of the first oxidation, the conjugate acid of 1, is also oxidized over the range of potentials corresponding to the second anodic peak. The rate of disappearance of the radical cation of 1 has been determined by cyclic voltammetry. The results are best interpreted in terms of parallel pseudo-first-order decay (k(1) = 0.6 s(-)(1)) and second-order reactions. The first of these second-order reactions is either proton transfer from the radical cation to neutral 1 or hydrogen atom abstraction by the radical cation from neutral 1, reactions that give the same products (k(2) = 100 M(-)(1) s(-)(1)) and are kinetically indistinguishable. The other second-order reaction is the hydrogen-atom-transfer disproportionation of the radical cation giving the conjugate acid of 1 and the immonium ion (k(3) = 100 M(-)(1) s(-)(1)). Both second-order processes must be included to account for the results. The present results are thought to be the first experimental evidence for the occurrence of hydrogen-atom-transfer disproportionation of amine radical cations.

The reactions of ozone with tertiary amines including the complexing agents nitrilotriacetic acid (NTA) and ethylenediaminetetraacetic acid (EDTA) in aqueous solution

Using the stopped-flow technique, the rate constants of the reaction of ozone with a number of amines have been determined. While the protonated amines do not react with ozone, the free amines react with rate constants of around 106 dm3 mol−1 s−1 in the case of tertiary and secondary amines, while primary amines react more slowly. Mono-protonated EDTA reacts only with k=1.6×105 and mono-protonated 1,4-diazabicyclo[2.2.2]octane (DABCO) with k = 3.5 × 103 dm3 mol−1 s−1. In aqueous solution, tertiary amines react with ozone mainly by forming the aminoxide and singlet dioxygen [O2(1Δg)] and to a lesser extent the secondary amine and the corresponding aldehyde, a reaction which can be partially suppressed by tert-butyl alcohol. These data suggest that O-transfer [aminoxide plus O2(1Δg)] is in competition with an electron transfer which leads to the amine radical cation and an ozonide radical. In water, the latter gives rise to ˙OH which further reacts with the amine (and ozone). The amine radical cation deprotonates at a neighbouring carbon. The resulting radical adds dioxygen. Subsequent elimination of O2˙− and hydrolysis of the Schiff-base thus formed leads to the secondary amine and the corresponding aldehyde. In its reaction with ozone, O2˙− yields further ˙OH. Their reaction with the amines leads to the same intermediate as the free-radical pathway of ozone does, i.e. induces a chain reaction. This is interfered with by tert-butyl alcohol at the OH-radical stage. When complexed to Fe(III), EDTA reacts only very slowly with ozone (k = 330 dm3 mol−1 s−1). This explains why EDTA is not readily removed by ozonation in drinking-water processing.

Electron Transfer from Aromatic Amines to Excited Coumarin Dyes: Fluorescence Quenching and Picosecond Transient Absorption Studies

Electron transfer (ET) from aniline, N-alkylanilines, N,N-dialkylanilines, and o-phenylenediamine to a number of excited (S1) 4-CF3-coumarin dyes having differently substituted 7-amino groups have been investigated in acetonitrile solutions using steady-state (SS) and time-resolved (TR) fluorescence quenching measurements. Direct evidence for the ET reactions in the present systems have been obtained by characterizing the amine cation radicals using picosecond transient absorption measurements in the visible region. The experimentally determined bimolecular quenching constants (kq) are seen to correlate nicely with the free energy changes (ΔG°) for the ET reactions, within the framework of the Marcus ET theory. The total reorganization energy (λ) estimated from such correlation indicates that the solvent reorganization (λs) plays the major role in governing the ET dynamics in the present systems. A comparison of the present results under diffusive conditions with those reported earlier under nondiffusive conditions indicates that the ET dynamics in the latter cases are much faster than in the former. The results are discussed considering a structural difference between the encounter complexes formed under diffusive and nondiffusive conditions.

N-Alkyl-N-cyclopropylanilines as mechanistic probes in the nitrosation of N,N-dialkyl aromatic amines.

A group of N-cyclopropyl-N-alkylanilines has been synthesized, and their reaction with nitrous acid in aqueous acetic acid at 0 degrees C was examined. All compounds reacted rapidly to produce the corresponding N-alkyl-N-nitrosoaniline by specific cleavage of the cyclopropyl group from the nitrogen. The transformations were unaffected by the nature of the alkyl substituent (Me, Et, (i)()Pr, Bn). The reaction of 4-chloro-N-2-phenylcyclopropyl-N-methylaniline with nitrous acid gave 4-chloro-N-methyl-N-nitrosoaniline (76%), cinnamaldehyde (55%), 3-phenyl-5-hydroxyisoxazoline (26%), and 5-(N-4-chlorophenylmethylamino)-3-phenylisoxazoline (8%). Both the selective cleavage of the cyclopropyl group from the aromatic amine nitrogen and nature of the products derived from the cyclopropane ring support a mechanism involving the formation of an amine radical cation. This step is followed by rapid cyclopropyl ring opening to produce an iminium ion with a C-centered radical which either combines with NO or is oxidized.

Regio- and Diastereoselective Synthesis of α-Cyanoamines by Anodic Oxidation of 6-Membered α-Silylamines

The electrochemical cyanation of N-benzyl-substituted cyclic six-membered α-silylamines including tetrahydroquinoline and piperidine derivatives was studied. The results of these investigations demonstrate that α-silylamines are valuable precursors for the preparation of the corresponding α-cyanoamines. The TMS group α to the N atom not only governs the chemoselectivity of the iminium formation through a preferential desilylation reaction under the experimental conditions (i.e., amine cation radical desilylation versus deprotonation), it also lowers the oxidation potential of tertiary amines compared to their non-TMS counterparts. Both the stereoselectivity and regioselectivity of the cyanide addition were investigated with 3-methylpiperidine as the model compound. The formation of a single cisdiastereoisomer in which the 2-cyano group is axial and the 5-methyl group is equatorial, indicates that the addition of the cyanide anion onto the iminium species is under stereoelectronic control. In addition, the redox reaction involving the intermediate nitrogen-centered cation radical and the cyanide anions played no role, because the α-silyl radical has such a short lifetime.

Regio- and Diastereoselective Synthesis of α-Cyanoamines by Anodic Oxidation of 6-Membered α-Silylamines

The electrochemical cyanation of N-benzyl-substituted cyclic six-membered α-silylamines including tetrahydroquinoline and piperidine derivatives was studied. The results of these investigations demonstrate that α-silylamines are valuable precursors for the preparation of the corresponding α-cyanoamines. The TMS group α to the N atom not only governs the chemoselectivity of the iminium formation through a preferential desilylation reaction under the experimental conditions (i.e., amine cation radical desilylation versus deprotonation), it also lowers the oxidation potential of tertiary amines compared to their non-TMS counterparts. Both the stereoselectivity and regioselectivity of the cyanide addition were investigated with 3-methylpiperidine as the model compound. The formation of a single cisdiastereoisomer in which the 2-cyano group is axial and the 5-methyl group is equatorial, indicates that the addition of the cyanide anion onto the iminium species is under stereoelectronic control. In addition, the redox reaction involving the intermediate nitrogen-centered cation radical and the cyanide anions played no role, because the α-silyl radical has such a short lifetime.

Triarylaminium Salt Induced Oxidative Cyclizations of Tertiary Amines. Convenient Access to 2-Substituted Pyrrolidinium Salts

Although they are common intermediates, the application of aliphatic tertiary aminium radical cations to organic synthesis has so far been restricted to α-deprotonation and related reactions. We report the very convenient oxidative generation and facile 5-exo cyclization of tertiary amimium radical cations to distonic 2-substituted pyrrolidinium radical cations. These can be further oxidized to 1,3-dications and trapped by nucleophiles as water, alcohols, or chloride ion. Preliminary mechanistic issues and implications will be presented.

A Molecular Orbital Study on the Hole Transport Property of Organic Amine Compounds

Reorganization energy (λ1) in the ionization process of organic amines and that (λ2) of the electron attaching process of amine cation radicals are evaluated with AM1, ab initio MO, and DFT methods, where dimethylaniline, methyldiphenylamine, and triphenylamine are adopted as a model of a hole transport material. The total λ value (=λ1 + λ2) decreases in the order dimethylaniline > methyldiphenylamine > triphenylamine, which agrees well with an increasing order of experimentally reported hole transport mobility of diamines that are dimers of above-mentioned amines, N,N‘-tetraphenyl-[1,1‘-biphenyl]-4,4‘-diamine < N,N‘-dimethyl-N,N‘-diphenyl-[1,1‘-biphenyl]-diamine < N,N‘-tetramethyl-[1,1‘-biphenyl]-4,4‘-diamine. This relation is reasonably explained with Marcus theory, since the λ value is directly related to the activation energy of hole transfer from one amine cation radical to a neighboring neutral amine, according to Marcus theory. The geometry changes in the ionization process are inspected to find a ...

Ligand-Accelerated Catalysis of the Ullmann Condensation: Application to Hole Conducting Triarylamines

Ligand-Accelerated Catalysis of the Ullmann Condensation: Application to Hole Conducting Triarylamines

Transformation of sterically hindered amines (HALS) to nitroxyl radicals: What are the actual stabilizers?

By means of pulse radiolysis and laser flash photolysis data, in this paper detailed information is given about transient elementary reactions which are involved in the transformation of sterically hindered amines (2,2,6,6-tetramethyl-substituted piperidines, HALS compounds) into nitroxyl radicals. Hence, ionization of the amines proceeds (i) by electron transfer to parent cations in butyl chloride solution, (ii) by oxidation with one-electron oxidants such as e.g. sulfate radical anion, and (iii) by sensitized electron transfer to carbonyl triplets. By direct time-resolved observation of all intermediates, the amine radical cations were found to react in a sequence via aminyl and aminylperoxy radicals, finally forming nitroxyl radicals. Nitroxyl radicals themselves are persistent, but efficiently scavenge alkyl, alkoxy and alkylperoxy radicals. The results of the liquid state model experiments suggest the conclusion that the HALS compounds primarily have to be transformed into nitroxyl radicals and the latter ones are the actual stabilizers.

Syntheses of amino nitrones. Potential intramolecular traps for radical intermediates in monoamine oxidase-catalyzed reactions

Monoamine oxidase (MAO) is a flavin-dependent enzyme that catalyzes the oxidative deamination of a variety of amine neurotransmitters and toxic amines. Although there have been several studies that support the intermediacy of an amine radical cation and an α-radical during enzyme catalysis, there is no direct, i.e. EPR, evidence for these species as they are formed. Amino nitrones have been designed which, upon radical formation would produce an intermediate that is a resonance structure of the corresponding nitroxyl radical, which should be observable by EPR spectroscopy. Syntheses of seven different amino nitrones, three acyclic, and four cyclic analogues were attempted. The protected amino nitrones were stable, but all three of the acyclic amino nitrones were unstable. One of the cyclic analogues was very stable ( 39), one was stable only in organic solvents ( 40), one was stable only in aqueous medium below pH 6.5 ( 41), and the other ( 42) was stable for just a short time at room temperature, decomposing to a stable free radical. None of these analogues produced a MAO-catalyzed radical, yet 41 is a poor substrate ( K m = 0.2 mM; k cat = 0.034 min −1) and 39 is a mixed inhibitor ( K i = 26.5 mM). Although this approach does not appear to be applicable to amino nitrones, it should be a valuable approach for other enzymes where radical intermediates are suspected and nonamine nitrones can be utilized.

Cyclizations in the homolytic reactions of unsaturated nitriles withtert-butylmercury halides in the presence of proton donors

Cyclizations are observed in the homolytic reactions of t-BuHgI with CH2CHCH2YCH2CN [Y = CH2, O, CMe2, C(CO2Et)2, NCH2CN] and CH2CHCH2CH2YCH2CN [Y = CH2, O, C(CO2Et)2] in Me2SO in the presence of hydriodic acid. Only with Y = C(CO2Et)2 does the adduct radical, t-BuCH2ĊHCH2YCH2CN, undergo facile 5-exo cyclization in the absence of a proton donor. The other 5-exo and all 6-exo cyclizations require substrate protonation to yield t-BuCH2ĊH(CH2)nYCH2CNH+ (n = 1, 2), which cyclizes readily to the iminium radical cation followed by electron transfer with I− or t-BuHgI2− to form the imine as a precursor to the cyclopentanone or cyclohexanone upon hydrolysis. For CH2CHCH2C(CO2Et)2CH2CN the formation of the cyclopentanone is dramatically promoted by NH4I in the dark in the absence of any other acid. In this case, where cyclization of the adduct radical occurs readily without substrate activation, protonation of the cyclized iminyl radical allows the electron transfer with I− or t-BuHgI2− to occur with regeneration of t-Buċ. A similar effect is observed with CH2CHCH2C(CO2Et)2CH2N3 where only a slow reaction is observed upon photolysis with t-BuHgI in the absence of NH4I, although apparently cyclization of t-BuCH2ĊHCH2C(CO2Et)2CH2N3 (with loss of N2) occurs readily. In the presence of NH4I the cyclized aminyl radical can be protonated and the resulting amine radical cation readily reduced by I− or t-BuHgI2− to continue a chain process. With the thioesters CH2CHCH2YCH2C(O)SPh [Y = O, CH2, CMe2, C(CO2Et)2], significant cyclization upon photolysis with t-BuHgX occurred only for Y = C(CO2Et)2. © 1998 John Wiley & Sons, Ltd.

Cyclizations in the homolytic reactions of unsaturated nitriles with tert‐butylmercury halides in the presence of proton donors

Cyclizations are observed in the homolytic reactions of t-BuHgI with CH2CHCH2YCH2CN [Y = CH2, O, CMe2, C(CO2Et)2, NCH2CN] and CH2CHCH2CH2YCH2CN [Y = CH2, O, C(CO2Et)2] in Me2SO in the presence of hydriodic acid. Only with Y = C(CO2Et)2 does the adduct radical, t-BuCH2ĊHCH2YCH2CN, undergo facile 5-exo cyclization in the absence of a proton donor. The other 5-exo and all 6-exo cyclizations require substrate protonation to yield t-BuCH2ĊH(CH2)nYCH2CNH+ (n = 1, 2), which cyclizes readily to the iminium radical cation followed by electron transfer with I− or t-BuHgI2− to form the imine as a precursor to the cyclopentanone or cyclohexanone upon hydrolysis. For CH2CHCH2C(CO2Et)2CH2CN the formation of the cyclopentanone is dramatically promoted by NH4I in the dark in the absence of any other acid. In this case, where cyclization of the adduct radical occurs readily without substrate activation, protonation of the cyclized iminyl radical allows the electron transfer with I− or t-BuHgI2− to occur with regeneration of t-Buċ. A similar effect is observed with CH2CHCH2C(CO2Et)2CH2N3 where only a slow reaction is observed upon photolysis with t-BuHgI in the absence of NH4I, although apparently cyclization of t-BuCH2ĊHCH2C(CO2Et)2CH2N3 (with loss of N2) occurs readily. In the presence of NH4I the cyclized aminyl radical can be protonated and the resulting amine radical cation readily reduced by I− or t-BuHgI2− to continue a chain process. With the thioesters CH2CHCH2YCH2C(O)SPh [Y = O, CH2, CMe2, C(CO2Et)2], significant cyclization upon photolysis with t-BuHgX occurred only for Y = C(CO2Et)2. © 1998 John Wiley & Sons, Ltd.

A New Strategy for the Design of Monoamine Oxidase Inactivators. Exploratory Studies with Tertiary Allylic and Propargylic Amino Alcohols

A new strategy for the design of monoamine oxidase (MAO) inhibitors is proposed. The strategy is based on the premise that tertiary-amine containing MAO-inactivators which operate by alkylation of active site nucleophiles are activated in situ by single electron transfer (SET) to the MAO-flavin cofactor to form aminium cation radicals which undergo secondary fragmentation reactions to produce reactive electrophiles. The purpose of the current work was to assess the feasibility and applicability of this proposal for the design of new families of MAO-inactivators. Based on the documented retro-aldol type fragmentation reactivity of β-amino-alcohol cation radicals, tertiary β-allylic and -propargylic β-amino-alcohols were expected to serve as precursors of conjugated ketones in SET-promoted processes. Evidence supporting this hypothesis was gained from studies of model SET-photoreactions of members of this amino-alcohol family with 3-methyllumiflavin (3MLF). The efficient production of 4a- and 4a,5-flavin ad...

Evidence for Radical Cations in Linked Mechanisms of N,N-Dialkyl Aromatic Amine Nitration and Nitrosative Dealkylation

N,N-Dialkyl aromatic amines react rapidly with nitrous acid to competitively produce a nitrosamine and a nitro compound. The mechanism of nitro compound formation involves a reaction of an amine radical cation with NO2, while the nitrosamine is produced by two competing pathways, one of which involves N-α-CH deprotonation of a radical cation with subsequent oxidative generation of an imminium ion, and the other of which occurs through NOH elimination of a nitrosammonium ion (R3N−NO+). All three pathways are linked through the reversible homolysis of R3N−NO+ to NO and a radical cation.