Aminium deprotonation

As with arene-amine radical ion pairs, the ion pairs formed between ketones and amines can also suffer a-deprotona-tion. When triplet benzophenone is intercepted by amino acids, the aminium cation radical can be detected at acidic pH, but only the radical formed by aminium deprotonation is detectable in base (178). In the interaction of thioxanthone with trialky lamines, the triplet quenching rate constant correlates with amine oxidation potential, implicating rate determining radical ion pair formation which can also be observed spectroscopically. That the efficiency of electron exchange controls the overall reaction efficiency is consistent with the absence of an appreciable isotope effect when t-butylamine is used as an electron donor (179). 

Goez M and Sartorius I 1993 Photo-CIDNP investigation of the deprotonation of aminium cations J. Am. Chem. Soc. 115 11 123-33... 

This aminium radical salt in aqueous solution in the form of solvated radical salt is very stable and will not polymerize acrylonitrile even with CeHsCOONa to form the corresponding benzoate. Therefore, we believe that in the nucleophilic displacement, there must be some intermediate step, such as intimate ion pair and cyclic transition state, which will then proceed the deprotonation to form the active aminium radical ion [14], as shown in Scheme 1. The presence of the above aminomethyl radical has also been verified [15] through ultraviolet (UV) analysis of this polymer formed such as PAN or PMMA with the characteristic band as the end group. 

Formation of an intimate ion pair of OH " and aminium radical cation was also proposed for the intermediate step before deprotonation. The presence of the above radical was verified through UV analysis of the polymer formed with the characteristic band on the end group. Through chromatographic analysis of the TBH-DMT reaction products, H2O was detected as the above mechanism proposes after deprotonation. 

The process for initiating radical formation in aromatic amine-vinyl monomer systems have been studied by Feng et al. [80-86] who proposed the formation of an aminium radical as the active state of an exciplex as intimate ion-pair and then a cyclic transition state which then would undergo a proton transfer process of deprotonation leading to the formation of active radical species for initiation as follows ... 

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. 

The end group of the polymers, photoinitiated with aromatic amine with or without the presence of carbonyl compound BP, has been detected with absorption spectrophotometry and fluororescence spectrophotometry [90]. The spectra showed the presence of tertiary amino end group in the polymers initiated with secondary amine such as NMA and the presence of secondary amino end group in the polymers initiated with primary amine such as aniline. These results show that the amino radicals, formed through the deprotonation of the aminium radical in the active state of the exciplex from the primary or secondary aromatic amine molecule, are responsible for the initiation of the polymerization. 

Product 34 predominates in the polar aprotic solvent (acetonitrile), while in the polar protic solvent (methanol) products 35 are formed preferentially. The different products are caused by the relative rate of deprotonation against desilylation of the aminium radical, that is in turn governed by the action of enone anion radical in acetonitrile as opposed to that of nucleophilic attack by methanol. In an aprotic, less silophilic solvent (acetonitrile), where the enone anion radical should be a strong base, the proton transfer is favoured and leads to the formation of product 34. In aprotic solvents or when a lithium cation is present, the enone anion radical basicity is reduced by hydrogen bonding or coordination by lithium cation, and the major product is the desilylated 35 (Scheme 4). 

A similar pattern of reactivity has been observed by Burrows and coworkers for the reaction between A -acetyllysine methyl ester (Lys) and dG. This reaction was studied in order to gain an understanding of structural aspects of DNA-protein cross-links (DPCs). These cross-links are regarded as a common lesion of oxidative damage to cells, but remain, from a chemical point, a poorly understood DNA lesion. As pointed out by Burrows, oxidation of protein-DNA complexes should occur preferentially at the primary amines since these sites have a lower oxidation potential (1.1 V vs. NHE, pH 10) than G. While protonation of the primary amine inhibits the oxidative process, transient deprotonation of a lysine residue would give rise to a lysine aminyl radical (or aminium radical cation). Using... 

In summary, these results constitute strong evidence for the two-step reaction sequence. They require that the deprotonation of the aminium radical cation be competitive on the CIDNP timescale i.e. surprisingly fast since it involves a carbon acid. The results delineate the fate of the amine derived intermediates with particular clarity, since they are observed directly for amine derived products. The conclusions based on the above CIDNP results were confirmed by time resolved optical spectroscopy in a variety of systems [179-182]. However, in essentially all these systems the reaction progress is monitored by following the complementary spectra of the acceptor derived radical intermediates, such as ketyl, semiquinone, stilbene, or thioindigo radical anions. 

The one-electron oxidation of a secondary amine results in the formation of a secondary aminium ion which on deprotonation gives an aminyl radical (Scheme 1). The nature of the final products derived from these intermediates dqiends very much on the structure of the substrate and the reaction conditions. If the amine has a hydrogen atom on the a-carbon atom the major products usually result from deprotonation at this a-position. With aromatic secondary amines, products can result from coupling of the delocalized radicals at a ring carbon atom. The formal dimerization of aminyl radicals shown in Scheme 21 is therefore not often a useful method of preparation of hydrazines. Nickel peroxide has been used to oxidize diphenylamine to tetraphenylhydrazine in moderate yield, and other secondary arylamines also give... 

For example, addition of 2 equivalents of a nonnucleophilic base, 2,6-di-tert-butylpyridine, to the reaction system almost totally suppressed the reaction (Table 9). This proposes that acid catalyzed enolization is important for the a-Umpolung. In support of mechanism 1 the yields of the a-methoxylated products increased with decreasing oxidation strength of the oxidant (Table 10), since endergonic oxidation of the ketone 70 is slowed down (Fig. 2). On the other hand, in the presence of stronger aminium salts the ketone tautomer is oxidized which however does not lead to deprotonation in the benzylic position... 

Trisubstituted Nitrogen Oxidations and Aminium Radical Cation Deprotonations... 

Deprotonation at the a-carbon of aminium radicals produced in SET reactions... 

The results of these studies were compared with those obtained earlier for the stilbene amine photoaddition [7, 11] and amine-enone photoelectron-transfer-catalyzed cyclizations (Table 7). The effects of a-substituents on the a-CH deprotonation rates of aminium radicals measured in the stilbene-amine photoaddition... 

The competition between fragmentation of the C-C bond and deprotonation (Scheme 11) of the aminium radical has been extensively probed by Whitten and others [132-139]. Cleavage of the C-C bond can occur to produce either carboca-tions (Eq. 11) or radicals (Eq. 12). 

The photoreduction of 9,10-anthraquinone-1,5-disulfonate by 2,2,6,6-tetramethyl piperidine in aqueous media has been studied in the nanosecond and microsecond time domains by use of time-resolved optical and ESR measurements [171]. Electron transfer from the amine to the excited state of the anthraquinone derivative occurs with a rate constant of 5.7 x 10 m s . The aminyl radicals formed via deprotonation of the aminium radicals are long-lived (ca 0.5 ms), because the steric hindrance of these radicals slows down recombination reactions. The aminyl radicals formed in these systems have been characterized by ESR. 

One-electron transfer from the substrate amino group to flavin (FI) results in the formation of the aminium radical and the flavin radical anion (FC) (Scheme 15). Deprotonation of the aminium radical to yield an a-aminoalkyl radical followed by a second electron transfer to the flavin radical anion will result in the formation of the reduced flavin and iminium ion. Alternatively the iminium ion can be formed by path d in Scheme 15 this involves formation of a covalent adduct which can... 

As discussed earUer, the aminium radical formed in this process can either undergo deprotonation and subsequent electron transfer (path a, Scheme 15) or lose a hydrogen atom (path c, Scheme 15). To differentiate between these processes... 

Studies using isotopic labeling as well as mechanism based on inactivation such as 4-alkyldihydropyridines and cycloalkylamines have supported the view that the first step involves an electron-transfer process (path a. Scheme 23) [18, 184-186, 211]. Deprotonation of the resultant aminium radical would yield the a-aminoalkyl radical. The formation of the dealkylated amine and carbonyl derivative has been proposed to occur via a second electron transfer to the enzyme and a nonenzymatic hydrolysis of the imine formed. In the P-450 catalyzed reaction, however this process is proposed to occur via a radical recombination process to yield a carbinolamine (99) which then decomposes to the dealkylated amine and the corresponding carbonyl derivative. Evidence for this was obtained by the incorporation of label from 02, into the carbonyl derivative [212-214]. 

Synthesis of oxazabicycloalkanes and related products was achieved by a one pot electron-proton-electron (EPE) transfer mediated reactions of the amine moiety [317]. Here the iminium cation is formed from the second electron oxidation of the a-aminoalkyl radical, generated via the a-deprotonation of the planar aminium radical owing to their low ionization potential. The iminium cation thus formed can... 

Okazaki O, Guengerich FP. Evidence for specific base catalysis in M-dealkylation reactions catalyzed by cytochrome P450 and chloroperoxidase. Differences in rates of deprotonation of aminium radicals as an explanation for high kinetic hydrogen isotope effects observed with peroxidases. / Biol Chem 1993 268 1546-52. 

Watanabe et al. (134) and Miwa et al. (135) have suggested a single-electron transfer mechanism for the enzymic N-demethylation reaction based on the small kinetic isotope effect, since the deprotonation of the a-hydrogen of the aminium radicals prepared by several means is known to proceed with smaller values (134, 135). The oxidation of cyclopropylamine by P-450 has been shown to afford products believed to be derived from the aminium radical intermediate... 

Hydrogen abstractions in ketone/amine and quinone/amine systems continue to attract the attention of CIDNP spectroscopists [94] despite the facts that the application of CIDNP to these reactions dates back to 1974 [95] and that the basic mechanism — electron transfer from the amine DH followed by deprotonation of the resulting aminium cation DH + to give an a-aminoalkyl radical D" has already been cleared up in those early investigations [46]. CIDNP spectroscopy is very well suited to probe the microscopic details of such reactions that involve more than one radical intermediate. Polarizations can arise in both DH + and D, but the spin density distributions of these two radicals differ strongly. Hence, the polar-... 

Figure 14. Dependence on AG°n.cage of the deprotonation pathway (see Chart IX) of the aminium cation derived from triethylamine. The ratio 2IJIf of polarizations of the olefinic a and j8 protons of diethylvinylamine (cf. Fig. 13) is shown as function of AG°, cage a value of about — 1 indicates complete in-cage deprotonation, a value of about +9 exclusive deprotonation outside the cage. (Top) Variation of AG ., . by variation of the sensitizer. (Bottom) By variation of the solvent. The solid lines are a global best fit to both data sets. The labels (see [94e]) at the curves denote sensitizer and solvent, respectively. [Reproduced from ref. [94e] with permission. Copyright 1994 VCH Verlagsgesellschaft Weinheim.]...

Tertiary amines have been reported to undergo addition to singlet trans-stilbene product selectivity appears to be determined by the orientation of deprotonation of the aminium radical intermediate by the stilbene radical anion. Intramolecular addition has been observed in 5-2-(r-methylalkyl)-aniline (220) on irradiation in methanol to give the 25,3/ -2,3-dimethylindoline... 

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