Reaction mechanisms nitrenium ions

More recently Hand et al. (ref. 9) have studied the decomposition reaction of N-chloro-a-amino acid anions in neutral aqueous solution, where the main reaction products are carbon dioxide, chloride ion and imines (which hydrolyze rapidly to amine and carbonyl products). They found that the reaction rate constant of decarboxylation was independent of pH, so they ruled out a proton assisted decarboxylation mechanism, and the one proposed consists of a concerted decarboxylation. For N-bromoamino acids decomposition in the pH interval 9-11 a similar concerted mechanism was proposed by Antelo et al. (ref. 10), where the formation of a nitrenium ion (ref. 11) can be ruled out because it is not consistent with the experimental results. Antelo et al. have also established that when the decomposition reaction takes place at pH < 9, the disproportionation reaction of the N-Br-amino acid becomes important, and the decomposition goes through the N,N-dibromoamino acid. This reaction is also important for N-chloroamino compounds but at more acidic pH values, because the disproportionation reaction... 

Among the evidence for this mechanism are the facts that other products are obtained when the reaction is run in the presence of competing nucleophiles, for example, p-ethoxyaniline when ethanol is present, and that when the para position is blocked, compounds similar to 23 are isolated. In the case of 2,6-dimethylphe-nylhydroxylamine, the intermediate nitrenium ion 22 was trapped, and its lifetime in solution was measured. The reaction of 22 with water was found to be diffusion controlled. ... 

In the presence of alcohols, the corresponding ethers are formed and added nucleophiles such as chloride ion40 or azide ion41 lead to the chloro- and azido-amine products, respectively. Rate constants are independent of the concentration of added nucleophile. Labelled 180 from the solvent is incorporated in the product42. All the evidence points to a reaction mechanism where water is lost from the O-protonated reactant to give a nitrenium ion-iminium ion intermediate which is rapidly trapped by a nucleophile (H2O in this case) to give the final product. This is shown in Scheme 7. Protonation at N- is likely to be more extensive, but there is no pathway to products from the N-protonated intermediate. 

McEwan and co-worker" examined the acid-catalyzed decomposition of unsymmetrical benzhydryl azides 18 and some related species (Fig. 13.11). The aryl migration step showed very little discrimination between aryl rings with electron-donating and those with electron-withdrawing substituents. This low selectivity was judged to be more consistent with formation of a discrete nitrenium ion intermediate (19). These workers reasoned that a concerted migration would exhibit higher selectivity toward donor-substituted arenes, because in that mechanism the electrons from the arene would participate in the reaction. 

These results lead to a general mechanism for the reaction nitrenium ions with aromatic compounds (Fig. 13.71). Initial encounter leads to a 7i-complex (141). The latter is converted into isomeric a complexes (142-144) which, in turn, either tau-tomerize to give stable adducts (145-147) or else dissociate to give radicals. The relative rates of these processes depend on the reactivities of the nitrenium ion and the arene. With less reactive nitrenium ions the 7i-complex is relatively long lived. With more reactive nitrenium ions the n complex forms in a low steady-state... 

In Bamberger s time the chemistry of arylnitrenes was unknown so he did not know of the characteristic reactions that could be used to preclude their intermediacy. The formulation of the mechanism in terms of a nitrenium ion is due to Heller, Hughes, and Ingold who showed in 1951 that the reaction rate is proportional to the concentration of protonated hydroxylamine, reaching a constant value in sufficiently acidic solutions. They also discovered that the reaction rate is independent of [CP] in HCl solutions even under conditions in which 5b and 6b are major products. Other workers showed through hydrolysis in 0-H20 that 4 is produced in an interm olecular process, and that no is incorporated into 3 during the reaction. ... 

Okamoto and co-workers noted that N-phenylhydroxylamine gave predominately diphenylamine on treatment with benzene in TFA but mostly 4-aminobiphenyl and 2-aminobiphenyl in the stronger acid trifluoromethane-sulfonic acid (TFSA). Similar results were obtained if benzene was replaced by toluene or anisole. The authors suggested that the reaction in TFA proceeded through O-protonated hydroxylamine either via a direct Sn2 displacement on N by the aromatic nucleophile or via attack of the aromatic compound on the N of a nitrenium ion. In TFSA they favored a mechanism in which the diprotonated hydroxylamine lost water to generate an iminium-benzenium dication (11, Scheme 5), a protonated nitrenium ion. " This... 

Phenyl azide was also found to react with alkenes in TFA (Scheme 11). The reaction was assumed to go via an aziridinium ion generated from attack of the alkene on the nitrenium ion because of the overall /rans-addition to the alkene noted in product 29. An alternative Sn2 mechanism was disfavored because phenyl azide decomposes at 21 °C in 50 vol% cyclohexene/TFA with an almost identical first-order rate constant as in 50vol% benzene/TFA even though cyclohexene is a considerably stronger nucleophile than benzene. ... 

The mechanism of Scheme 34 quantitatively explains the yields of rearrangement, solvent-derived and N3-derived products of hydrolysis of hydroxylamine or hydroxamic acid esters that yield selective nitrenium ions (log 5 One of the characteristics of these hydrolysis reactions is the... 

Mechanism A proposes initial attack by N-7 of d-G on the nitrenium ion to generate the N-7 adduct 110, followed by an intramolecular rearrangement to form the cationic C-8 intermediate 111. The evidence for the mechanism includes the precedent of other electrophiles, including carbocations, that usually react at N-7 of d-G," and the reported isolation of 113 (Scheme 50) and its reduction with NaBH4 into 114." Novak and co-workers were not able to isolate an adduct similar to 113 from the reaction of 76n and 76o... 

The reactions of the selective nitrenium ions 75h and 75o with glutathione (GSH) in H2O exhibit different characteristics from those described above. Scheme 53 illustrates the products and reaction mechanism deduced for the reaction of 75o with GSH." Product yield data taken at varying pH showed that the reactive form of GSH was its conjugate base GS . The rate constant... 

Reactions of nitrenium ions with lifetimes in aqueous solution ns. It is clear from the work presented to date that these species react predominately by ion-pair or preassociation mechanisms, but the detailed processes are far from clear. The possible transition to a true bimolecular substitution mechanism (Sn2) has also not been systematically investigated. 

---