Aminoalkyl radicals

Thus, deprotonation of the aminium radical from a secondary or primary amine will at last form an amino radical instead of an aminoalkyl radical and a CH2CH2CN radical. This amino radical will then serve as one of the active species for the initiation of polymerization. 

Photoredox systems involving carbonyl compounds and amines are used in many applications. Carbonyl compounds employed include benzophenone and derivatives, a-diketones [e.g. benzil, cainphoroquinone (85),2W 291 9,10-phenanthrene quinone], and xanthone and coumarin derivatives. The amines are tertiary and must have a-hydrogens [e.g. N,A7-dimethylani 1 ine, Michler s ketone (86)]. The radicals formed are an a-aminoalkyl radical and a ketyl radical. 

The reaction between the photoexcited carbonyl compound and an amine occurs with substantially greater facility than that with most other hydrogen donors. The rate constants for triplet quenching by amines show little dependence on the amine a-C-H bond strength. However, the ability of the amine to release an electron is important.- - This is in keeping with a mechanism of radical generation which involves initial electron (or charge) transfer from the amine to the photoexcited carbonyl compound. Loss of a proton from the resultant complex (exciplex) results in an a-aminoalkyl radical which initiates polymerization. The... 

Table 12 C—N Rotational barriers (kcal mol ) of substituted aminoalkyl radicals HjNCHR."...

The a-aminoalkyl radical intermediates from electrochemical oxidation of amines show a strong tendency to lose a further electron and form an immonium ion. This process shows an anodic polarographic wave at negative electrode poten-... 

Polarographic half-wave potentials for a-aminoalkyl radical oxidation. 

Radical ion pairs also react by proton, atom, or group transfer. We illustrate proton transfer in reactions of aromatic hydrocarbons with tertiary amines. These reactions cause reduction or reductive coupling. In the reduction of naphthalene, the initial ET is followed by H" transfer from cation to anion, forming 67 paired with an aminoalkyl radical the pair combines to generate... 

In analogy to the a-deprotonation of tertiary amine radical cations (see above), amines bearing an a-trimethylsilyl group may undergo heterolytic cleavage of the C—Si bond upon ET, particularly in the presence of nucleophiles. The resulting aminoalkyl radical may couple, for example, to the enone radical anion (71 ) generating 142. " ... 

Carbon monoxide has been used to scavenge OH fonned from the ozonolysis of alkenes. The CO2 tints generated was detected by FTIR spectroscopy and the "OH yields for individual reactions were calculated.239 The significance of the OH-induced intramolecular transformation of glutathione thiyl radicals to a-aminoalkyl radicals has been discussed with respect to its biological implications.240 The kinetics and mechanism of the process indicated that it could be a significant pathway for the selfremoval of glutathione thiyl radicals in vivo. 

Das S, von Sonntag C (1986) Oxidation of trimethylamine by OH radicals in aqueous solution, as studied by pulse radiolysis, ESR and product analysis. The reactions of the alkylamine radical cation, the aminoalkyl radical and the protonated aminoalkyl radical. Z Naturforsch 41b 505-513 Dixon WT, Norman ROC, Buley AL (1964) Electron spin resonance studies of oxidation. Part II. Aliphatic acids and substituted acids. J Chem Soc 3625-3634 Draper HH, Squires EJ, Mahmoodi H, Wu J, Agarwal S, Hadley M (1993) A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials. Free Rad Biol Med 15 353-363... 

The reaction of OH with trimethylamine in aqueous solution leads to the formation of the alkylaminium radical cation [CH3N,+], aminoalkyl radicals [(ClI3)2NCII2 and protonated aminoalkyl radicals [(CH3)2N(H+)CH2-] which have markedly different properties (Das and von Sonntag 1986 for a theoretical study see Armstrong et al. 1992). The aminoalkyl radicals react rapidly with 02 thereby giving rise to 02- (Das et al. 1987). 

The formation of the reducing aminoalkyl radical formed in reaction (23) that had escaped detection in the earlier studies (Neta and Fessenden 1971) has now also been confirmed by EPR (Hug et al. 2000b). 

When the amino group is fully deprotonated, the rate of the H-transfer is 1.5 x 10s s4, but also around pH 7 the reaction is still fast, at the ms timescale (for a quantum mechanical study see Rauk et al. 2001). Upon the decay of the amnioal-kyl radicals formed in reaction (35) ammonia as formed in a yield that points to disproportionation as the major process (Zhao et al. 1997). The fact that the ami-noalkyl radical is the thermodynamically favored species does not mean that the repair of DNA radicals by GSH (Chap. 12.11) is not due to its action as a thiol. As with many other examples described in this book, the much faster kinetics that lead to a metastable intermediate (here the formation of the thiyl radical) rather than the thermodynamics as determined by the most stable species (here the aminoalkyl radical) determine the pathway the the reaction. In fact, the C-H BDE of the peptide linkage is lower than the S-H BDE and repair of DNA radicals by peptides, e.g., proteins would be thermodynamically favored over a repair by thiols but this reaction is retarded kinetically (Reid et al. 2003a,b). 

Zhao R, Lind J,Merenyi G, EriksonTE(1997) Significance of the intramolecular transformation of glutathione thiyl radicals to a-aminoalkyl radicals. Thermochemical and biological implications. J Chem Soc Perkin Trans 2 569-574... 

Aminium radical cations and aminoalkyl radicals have substantially different spin density distributions and, therefore, substantially different hyperfine coupling (hfc) patterns. Aminium radical cations have appreciable proton hfcs only in the position adjacent to the nitrogen center whereas the neutral aminoalkyl radicals have sizable hfcs in both the a- and (3-positions. CIDNP effects induced in these species are expected to reflect these differences. 

Fig. 12a—e. H CIDNP spectra of diethylvinylamine observed during the reaction of (a) anthraquinone with triethylamine, (b) benzoquinone with triethylamine in acetone-d6, (c) benzoquinone with triethylamine in acetonitrile-d3. Traces (d) and (e) show theoretical spectra calculated for the exclusive involvement of the aminoalkyl radical and of the aminium radical ion, respectively. The change from emission (trace a) to enhanced absorption (trace c) for the doublets near 6.0 ppm indicates an increasing involvement of the aminium radical ion [178]... 

Tertiary amines have also been employed in electron transfer reactions with a variety of different acceptors, including enones, aromatic hydrocarbons, cyanoaro-matics, and stilbene derivatives. These reactions also provide convincing evidence for the intermediacy of aminoalkyl radicals. For example, the photoinduced electron transfer reactions of aromatic hydrocarbons, viz. naphthalene, with tertiary amines result in the reduction of the hydrocarbon as well as reductive coupling [183, 184]. Vinyl-dialkylamines can be envisaged as the complementary dehydrogenation products their formation was confirmed by CIDNP experiments [185]. 

Das and co-workers have described the generation of a-aminoalkyl radicals from cyclic secondary amines using anthraquinone-photocatalysis [95JCS(P1)1797]. The conjugate addition of the a-aminoalkyl radical to enoates has been examined. The cyclized compound is obtained directly from the reaction. The chemical yield of 149 is low and it is accompanied by 148, a product arising from nucleophilic addition of the amine to the crotonate. 

The use of amides as source of carbamoyl and a-aminoalkyl radicals has also been widely employed since the 1970s [11]. Fenton-type systems utilizing tert-butyl hydroperoxide or hydrogen peroxide in the presence of Fe(II) salts and the S2Os2 / Ag+ system have been applied in the functionalization of aromatic bases with amides (Equation 14.7). 

Another approach involves the use of an electron-poor olefin acting both as an absorbing electron acceptor and as a radical trap. In this case, a PET reaction between a cyclohexenone derivative and a silylated amine led to a radical ion pair. Desilylation of the silyl amine radical cation intermediate in polar protic solvent (e.g., MeOH) and subsequent aminoalkyl radical attack onto the enone radical anion yielded the alkylated cyclohexanones [23]. 

Other methods for the preparation of selenium-containing molecules for radical reactions have been used as well. In Scheme 8 the radical cyclization of compound 44 to the tetrahydrofuran derivative 45 is shown as a crucial step in natural product syntheses. Mixed acetal can also be used for the generation of radicals. 1-Alkoxy and 1-aminoalkyl radicals can be generated from 0,Se- and N,Se-acetals in a direct way. The corresponding 0,Hal- or N,Hal-mixed acetals are instable and this approach is rarely used. But the selenium-containing mixed acetals can be isolated and purified and are excellent radical precursors.241 For example, acetals such as 139 can be converted into the mixed 0,Se-aeetals by reaction with diisobutylaluminum phenyl selenide. The mixed acetal 140 is then used under radical reaction conditions for the efficient formation of new carbon-carbon bonds (Scheme 36).242... 

The 1,2-migration of amino groups in /3-aminoalkyl radicals such as 24 has also been of interest because of the involvement of these species in the enzyme-catalyzed elimination of ammonia from 1,2-amino alcohols.47-50 These studies have also been reviewed recently by Radom et al45... 

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