N.O-bond heterolysis

The influence of / ara-substituents on the benzamide and benzyloxyl side chains upon the pre-equilibrium protonation step is likely to be negligible considering their remoteness from the site of protonation and their electronic influence must rather impact upon the rate determining N-O bond heterolysis step. Para-substituents on the leaving group should impact upon both the protonation and bond heterolysis steps. 

Product analyses showed that for all five esters, the OH - and buffer-dependent components generated the corresponding hydroxamic acids. The pH-independent reaction also led to the hydroxamic acid product for 39c and 39f, but 39a and 39e generated products that appeared to be derived from N—O bond heterolysis in the pH region dominated by (pH < 8). ... 

The magnitude of the rate constants were such that 46e exhibited a U-shaped pH-rate profile with a broad pH-independent region from pH 3.5 to 7.0 in which /Cobs Reaction products isolated within this pH range were consistent with those previously observed for 46a-d, and CU and 1 had effects on product distribution and identity similar to those discussed above for 46a-d. It was concluded that the pH-independent reaction involved N—O bond heterolysis to yield nitrenium ion intermediates as in Scheme 24. ... 

A-Benzyloxy-)8-lactam 70 in the presence of Rh2(AcO)4 was found to undergo ring closure to provide the carbapenam 71. The initially generated carbenoid may first interact with a nitrogen electron lone pair to give ylide 72. Proton abstraction from the benzylic position by this ylide, followed by N — O bond heterolysis, yields the cyclized product and benzaldehyde (90TL1807 91JOC2688). 

The chiral phosphoric acid (123)-catalyzed highly enantioselective a-hydroxylation of j8-dicarbonyl compounds (138) and (139) to give (141) or (142) through a tandem aminoxylation/N-O bond heterolysis sequence using nitroso compounds, such as (140), as the oxygen source, has been described by Zhong et al. (Scheme 37). ... 

Thus A-acyloxy-iV-alkoxyamides undergo acid-catalysed solvolysis forming A-acyloxy-A-alkoxynitrenium ions. However, the rate of uncatalysed reaction was negligible under the same conditions. Anomeric weakening of the N-O bond in the neutral species is insufficient to promote heterolysis. However, protonation of the acyloxyl group, renders this substituent at nitrogen more electronegative (Fig. 14a)... 

Saczewski and Debowski reported the l,4-diaza-3-oxa-Cope rearrangement of N-cyanate anilides (equation 52). Prototropic rearomatization of 176 and internal nucleophilic addition afford the corresponding benzimidazolinone 177, usually in moderate yields (32-78%). A concerted [3,3]-sigmatropic rearrangement is proposed based on the absence of para rearrangement product that usually results from homolysis or heterolysis of the N—O bond followed by recombination of the two radicals or ions. 

The first term of the rate law requires acid-catalyzed decomposition of the conjugated acid of the ester. This term predominates only under strongly acidic conditions. It has not been investigated in detail, but the major product of the acid catalyzed reaction is the corresponding hydroxylamine. The second term predominates under neutral to mildly acidic conditions. This term is consistent with uncatalyzed heterolysis of the N—O bond of the neutral ester to generate a heteroaryinitrenium ion. " The rate law is more complicated than that for reactive esters of carbocyclic hydroxylamines or hydroxamic acids that show pH-independent decomposition over a wide pH range. The kinetic behavior of the heterocyclic esters is caused by protonation of a pyridyl or imidazolyl N under mildly acidic conditions. The protonated substrates are not subject to spontaneous uncatalyzed decomposition, so decreases under acidic conditions until acid-catalyzed... 

The full paper concerning the reaction of acyl chlorides (benzoyl and toluene-p-sulphonyl chlorides) with the steroidal nitrone derivative (23) of conanine has been published. Additional information concerning the mechanism of these reactions is given. Thus, it was shown that the formation of the a -benzyloxyimine (24) needs acidic conditions which favour the heterolysis of the N—O bond (Scheme 2). At room temperature, under Schotten-Baumann conditions, the epimeric compounds (25) were obtained from (23) with benzoyl chloride. Compound (25) gave (24) on refluxing in neutral solvent or by treatment with acid, whereas (24) was obtained directly from (23) when treated with a benzene solution of benzoyl chloride in the presence of aqueous sulphuric acid. 

Beckmann rearrangement. O-4-Pentenyl oximes are activated by NB S to undergo N-0 bond heterolysis and thence Beckmann rearrangement. 

Photolysis of benzene solutions of l-methoxycarbonyl-2-naphthylmethyl 2,6-di-methyl substituted phenyl ethers induces C-O cleavage with formation of 2,4-cyclohexadienone intermediates which are subsequently photo-rearranged into meta substituted phenols. In methanol, 9-anthrylmethoxy-pyrid-2-one or l-pyrenylmethoxypyrid-2-one undergo photoheterolysis to give the C-O heterolysis products l-hydroxypyrid-2-one and the arylmethyl methyl ether, together with 2-pyridone, aryl-substituted methanol and aryl aldehyde derived from homolysis of the N-O bond. Evidence shows that an intramolecular exciplex plays a crucial role in C-O bond heterolysis. 

Both N-N and N-C bond fission occurs on irradiation of the hydrazone derivatives (191). The photodegradation of the phenylhydrazone and the hydrazone of benzil have also been described. a-Ketoiminyl radicals are formed on irradiation of oximino ketones at low temperature. A study of the photochemical decomposition of sulfamic esters and their use as initiators of cross-linking of a melamine resin have been described. The bispyridinyl radical (192) is formed by one electron reduction of the corresponding pyridinium salts. The irradiation of this biradical at 77 K results in C-N bond fission with the formation of benzene-1,3-diyl. The predominant products from the irradiation (X,> 340 nm) of (193) in methanol were identified as A -hydroxy-2-pyridone and (194) from the fission of the C-O bond. Other products were 2-pyridone, (195) and (196) that arise from O-N bond fission. The reaction is to some extent substituent dependent and a detailed analysis of the reaction systems has identified an intramolecular exciplex as the key intermediate in the C-O bond heterolysis. 

Figure 22. Proposed mechanism in which facilitated N,0-bond heterolysis arises from the O-acylation of an arylhydroxylamine compound bound at the active site of a-KGD.

H—F. In the crudest approximation, one may say that the orbitals of C, N, O, and F are all approximately the same size and therefore the interaction matrix element hab will be approximately the same size for any A- pair. The dominant factor determining the heterolysis energy therefore is the difference in orbital energies in the denominator, and one has directly the prediction (Figure 4.2) that ease of heterolytic cleavage for C—X is in the order C > N > > F. The C—C bond is least likely to dissociate heterolytically and the C—F bond the most likely. In an absolute sense, of course, heterolytic cleavage is not a likely process for any of these bonds in the absence of other factors, as discussed below. 

The rate of the reaction is increased by electron-releasing substituents in the benzene ring (in contrast to the mild enhancement by electron-withdrawing substituents in the pyrolysis of 1,2-diphenylacetates, (Section 2.9) and by electron-withdrawing substituents in the alkyl function, R (226). These facts are consistent with a cyclic mechanism in which N-O heterolysis is more advanced than C-H heterolysis or O-H bond formation in the transition state. The alpha isomers are more reactive than the beta isomers, but study of the latter is complicated as in the presence of traces of acid they are isomerised to the alpha form. 

Bordwell et al., 1988, 1989) and Amett (Amett et al., 1990a,b, 1992 Venimadhavan et al., 1992) have employed thermodynamic cycles consisting of heterolysis of a molecule and redox processes of the resulting ions to evaluate homolytic dissociation energies of C—H, C—C, C—N, C—O and C—S bonds in solution. In a similar way, knowledge of the A//het(R-R ) values allows determination of the heat of homolysis of carbon-carbon bonds [A/fhomo(R"R )] using (27). The results are summarized in Table 4. 

The examples mentioned above are characterized by heterolysis of C—O, C—N, or C—P bonds. Finally, a solvent-dependent Lewis acid/base reaction between carbo-cations and carbanions, produced by heterolysis of a weak C—C bond, is presented cf. also Section 2.6). 

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