Homolytic Amination

This oxidation [Eq. (7)] is favored by the easier oxidability of the cyclohexadienyl radical and by the experimental conditions used in these cases, in which there is always a very low concentration of N-chloroamine and a relatively high concentration of metal salt. 

Generally, when the electrophilic chlorination is not a serious competitive process, the reaction is in fact carried out in the presence of a very low concentration of metal salt, which has a very low solubility in the reaction medium, and high concentration of N-chloroamine. 

To be acceptable, the mechanism of the homolytic amination must explain the two main macroscopic phenomena in apparent discrepancy the very high positional and substrate selectivity with most of the aromatic substrates, and the low positional selectivity with alkylbenzenes. 

AH the structural factors which favor an electron-transfer by stabilizing the polcir form [8) decrease the activation energy and determine the very high sensitivity of the polar effects of the amination reaction. 

The same exceptional sensitivity to poleu factors was also observed with amino radicals in the addition to olefinic systems n.29) (no addition takes place, for example, with acrylic monomers). 

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Heteroaromatics very reactive toward electrophilic species, such as furan and pyrrole, are not suitable for homolytic aminations owing to their low stability under the reaction conditions. Thiophene, however, can be aminated, leading to 2-dialkylamino derivatives. ... 

Attack at the 2-position has been effected with stabilized radicals such as benzyl and triphenylmethyl. Substitution has also been observed with alkylthio, phenylethynyl and thienyl radicals since the latter two are very reactive, substitution occurs at both positions 2 and 3 (73US295). Thiophene can also be homolytically aminated with amino cation-radicals, leading to 2-dialkylamino derivatives (74AHC(16)123>. 

The homolytic amination by N-chloroamines is of great synthetic interest, with a selectivity and versatility comparable to those of the most selective electrophilic substitutions. The overall stoichiometry is shown by Eq. (1)... 

Table 4. Homolytic amination of polycyclic aromatic compounds...

Table 5. Orientation in the homolytic amination of halobenzenes 2 ) and methyl cinamate 2D by N-chlorodimethylamine...

All the previous results show that the homolytic amination is not distinguishable from a highly selective electrophilic reaction, with regard to orientation and reactivity. In contrast, the results of Table 6 show that alkylbenzenes are the... 

Table 6. Homolytic amination of benzene and alkyl benzenes...

The partial rate factors and the isomer distribution in the amination by di-methylamino radical cation of toluene, isopropylbenzene, -butylbenzene, biphenyl and naphtalene are reported in Table 7. These partial rate factors are far the highest ever observed in homolytic substitutions so that the general character of the homolytic amination allows a more relevant analogy to be drawn with the electrophilic substitutions than with the homol5rtic arylation, the only homol5rtic substitution for which numerous and accurate quantitative data exist in homo-cyclic aromatic series. 

On the basis of the mechanistic conclusion reached for the homolytic amination of alkylbenzenes, a new explanation was suggested for the much-discussed Baker-Nathan and inductive order in electrophilic substitutions of alkylbenzenes. 

A common aspect characterizing both the homolytic amination and the substitution of protonated hetero-aromatic bases by nucleophilic free radicals is the presence of a nitrogen atom with a positive charge. This presence determines strong polar effects whether it characterizes the radical (R2NH) or the aromatic... 

Table 2. Homolytic amination of aromatic compounds with protonated iV-chloroamines...

Table 3. Homolytic amination of olefinic compounds with protonated N Olefinic substrate N-Chloroamine Initiator Time (min) Adduct...

Following the radical pathway" the next step is a homolytical cleavage of the N-R bond. The rearrangement to yield the tertiary amine 3 then proceeds via an intermediate radical-pair 4a. The order of migration is propargyl > allyl > benzyl > alkyl ... 

In contrast to the acid, sodium nitrite should not in general be added in excess. Firstly, as far as the ratio of amine to nitrite is concerned, diazotization is practically a quantitative reaction. In consequence, it provides the most important method for determining aromatic amines by titration. Secondly, an excess of nitrous acid exerts a very unfavorable influence on the stability of diazo solutions, as was shown by Gies and Pfeil (1952). Mechanistically the reactions between aromatic diazonium and nitrite ions were investigated more recently by Opgenorth and Rtichardt (1974). They showed that the primary and major reaction is the formation of aryl radicals from the intermediate arenediazonitrite (Ar —N2 —NO2). Details will be discussed in the context of homolytic dediazoniations (Secs. 8.6 and 10.6). 

There are amines such as A-methylnitroamine, that are too weakly nucleophilic to be able to form covalent adducts with arenediazonium ions. The products of the latter appear to be those of salts ArNJ N(N02)CH3, as found by Baranchik et al. (1957). Amides also appear not to be sufficiently nucleophilic, but thioamides are, as is shown by the reaction of A-phenylthiourea in the presence of NaOH (Scheme 13-12 Nesynov et al., 1970). First a (probably homolytic) phenylation-de-diazoniation takes place, followed by A-coupling. Selenourea also reacts a mixture of products is formed, which indicates a reaction of the same type as with thiourea (Nesynov and Aldokhina, 1976). 

The same group recently disclosed a related free radical process, namely an efficient one-pot sequence comprising a homolytic aromatic substitution followed by an ionic Homer-Wadsworth-Emmons olefination, for the production of a small library of a,/3-unsaturated oxindoles (Scheme 6.164) [311]. Suitable TEMPO-derived alkoxy-amine precursors were exposed to microwave irradiation in N,N-dimethylformam-ide for 2 min to generate an oxindole intermediate via a radical reaction pathway (intramolecular homolytic aromatic substitution). After the addition of potassium tert-butoxide base (1.2 equivalents) and a suitable aromatic aldehyde (10-20 equivalents), the mixture was further exposed to microwave irradiation at 180 °C for 6 min to provide the a,jS-unsaturated oxindoles in moderate to high overall yields. A number of related oxindoles were also prepared via the same one-pot radical/ionic pathway (Scheme 6.164). 

Hence, the copper surface catalyzes the following reactions (a) decomposition of hydroperoxide to free radicals, (b) generation of free radicals by dioxygen, (c) reaction of hydroperoxide with amine, and (d) heterogeneous reaction of dioxygen with amine with free radical formation. All these reactions occur homolytically [13]. The products of amines oxidation additionally retard the oxidation of hydrocarbons after induction period. The kinetic characteristics of these reactions (T-6, T = 398 K, [13]) are presented below. 

The LFP studies of the reaction of the A-methyl-A-4-biphenylylnitrenium ion with a series of arenes showed that no detectable intermediate formed in these reactions. The rate constants of these reactions correlated neither with the oxidation potentials of the traps (as would be expected were the initial step electron transfer) nor with the basicity of these traps (a proxy for their susceptibility toward direct formation of the sigma complex). Instead, a good correlation of these rate constants was found with the ability of the traps to form n complexes with picric acid (Fig. 13.68). On this basis, it was concluded the initial step in these reactions was the rapid formation of a ti complex (140) between the nitrenium ion (138) and the arene (139). This was followed by a-complex formation and tautomerization to give adducts, or a relatively slow homolytic dissociation to give (ultimately) the parent amine. 

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