HERON reactions

Aldehyde 54 and the hydroxamic acids 55 were generated together in an acid-catalysed elimination reaction (Scheme 7 pathway (ii)). A crossover experiment indicated that esters are formed in a concerted rearrangement concomitant with the likely formation of the hydroxynitrene 57 (Scheme 7 pathway (iii)) while there is no evidence to date for the formation of hydroxynitrene, joint solvolysis of equimolar quantities of /V-acetoxy-/V-butoxy-/>-chlorobenzamide 26e and N- acetoxy-/V-benzyloxybenzamide 27a afforded significant quantities of butyl p-chlorobenzo-ate (36%) and benzyl benzoate (54%) as the only esters. This is an example of a HERON reaction, which has been identified in these laboratories as a characteristic rearrangement of bisheteroatom-substituted amides.32,33,42 43 155 158 Since ester formation was shown to prevail in neutral or low acid concentrations, it could involve the conjugate anion of the hydroxamic acid (vide infra).158... 

Studies at different acid strengths indicated that pathways (i) and (ii) (Scheme 7) were favoured over the non-acid-catalysed HERON reaction pathway (iii) at higher acid concentrations. 

Reactions with aromatic amines - the HERON reaction... 

Fig. 18 B3LYP/6-31G -derived energetics, ground and transition state properties for the HERON reaction of iV-methoxy-N-dimethylaminoformamide to 1,1-dimethyldiazene and methyl formate.

Kinetic studies. HERON reactions of 7V-acyloxy-/V-alkoxyamides, which can be conveniently followed by NMR in <74-methanol by monitoring the disappearance of the mutagen or aniline and formation of ester and tetrazene, conform to classical bimolecular kinetics being first order in both mutagen and TV-methyl-aniline.41 43,46,105 Arrhenius parameters and bimolecular rate constants (308 K) for a range of /V- a cy 1 o x y - TV- a 1 k o x y a m i de s 25-30 are collated in Table 5. 

These authors also reported that /V-acyloxy-/V-alkoxyamides did not undergo methanolysis under the same conditions but treatment of /V-acctoxy-/V-ethoxybenz-amide 25a in more forcing conditions with NaOMe in DME afforded a mixture of ethyl and methylbenzoate, 97 and 98 (Scheme 20). They attributed the formation of the former to a HERON reaction and methyl benzoate to the direct attack of methoxide at the amide carbonyl. 

It is seems plausible that the HERON reaction to give ethyl benzoate 97 involves the anion of /V-ethoxybenzohydroxamic acid 99, formed by methoxide reaction at... 

Formation of ester 108 could involve dimerisation of alkoxyamidyls 102 and thermal rearrangement of the hydrazines 107 to esters and nitrogen according to Scheme 12, although a HERON reaction (Scheme 21, pathway (iii)) cannot be discounted under these conditions (vide infra). Anhydrides 101 are almost certainly formed by a HERON reaction (Scheme 21, pathway (ii)). 

HERON reactions either directly, or of products of solvolysis or Sn2 displacement... 

HERON reactions of, 75-76, lit reaction of azide with, 85/ structure, 44, 45/ 46/ 47 Frei intrazeolite photooxygenation, 253/ 255, 258, 261, see also Wagnerova Class II intrazeolite photooxygenation... 

Heteroatom rearrangements on nitrogen (HERON) reaction, 67, 70-74, 83, 94 bonding in, 72... 

Nuclear magnetic resonance spectroscopy for /V-acyloxy-/V-alkoxyamides 13C NMR spectroscopy, 56-58 15N NMR spectroscopy, 58-59 dynamic 1H NMR spectroscopy, 59 Nucleophilic substitution (SN2) reactions, /V-acyloxy-/V-alkoxyamidcs, 70-90 alcoholysis reactions, 89-90 with aromatic amines, HERON reactions, 70-74... 

Thermal decomposition reactions, of IV-acyloxy-lV-alkoxyamides, 90-96 free radical decomposition, 91-93 HERON reactions, 93-96 Thiazine dyes, 233... 

The reaction of azide with A-chlorohydroxamic esters has proved to be an excellent source of highly hindered esters . The rearrangement of 82 to 83 (Scheme 16), apart from being highly favourable energetically, is characterized by an early transition state with little disruption to the carbonyl. In these HERON reactions, the N—C 0) bond... 

This was the first-discovered HERON reaction but such reactions appear to be common to most A-heteroatom-snbstituted hydroxamic esters and will be described in detail in Section Vl.C, which deals more fully with the reactions of A-aminohydroxamic esters. 

There is one report of competitive nucleophilic attack at the amide carbonyl in an Ai-acyloxy-A-aUtoxyamide. Shtamburg and coworkers have reported that MeONa reacted with Ai-acetoxy-A-ethoxybenzamide (159) in DME giving methyl and ethyl benzoate (160 and 161) (Scheme 26) . They attributed the formation of methyl benzoate to the direct attack of methoxide ion at the amide carbonyl rather than at nitrogen. The formation of 161 was attributed to a HERON reaction. Though not mentioned by the authors, it seems likely that under these aprotic conditions, 162 could also have been formed by methoxide attack at the acetate carbonyl leading to an anion-induced HERON reaction, by analogy with the reaction of Ai-acyloxy-Ai-alkoxyamides and aqueous hydroxide discussed above (Section IV.C.3.c)... 

HERON reactions of iV-acyloxy-iV-alkoxyamides in non-polar media would be expected to favour migration of acyloxyl groups since anomeric effects are strongest in this direction (Figure 15, Section IV.B.l). 

In the presence of the hydrogen donor tri-Af-butyltin hydride, only hydroxamic ester 195 is formed and the reaction is presumed to involve N—O bond homolysis to give the resonance-stabilized Af-alkoxyamidyl radicals (198), which in the presence of BusSnH are reduced to hydroxamic ester according to Scheme 30. In the absence of BusSnH hydride, formation of esters probably involves alkoxyamidyl dimerization to hydrazines (199) as intermediates (see Section Vl.C, Scheme 34), although HERON reactions of 194 with production of methoxynitrene cannot be discounted. Mesityl radicals, formed by the... 

Density fnnctional calculations on 215b-d at the B3P86 level have been carried ont as part of a detailed study of the HERON reaction of hydrazines (see Section VI.C). These afforded symmetrical gauche structures l(EE) as lowest energy conformers N—N (1.37 A), N—C(0) (1.38 A) and N—O (1.40 A) bond lengths were similar to those from HF/6-31G calculations. ... 

Theoretical treatment of the HERON reaction of N-alkoxy-N-aminoamides... 

FIGURE 26. B3LYP/6-31G transition state for the HERON reaction of //-formyloxy-At-(At, At -dimethylamino)formamide (214) to 1,1-dimethyldiazene (220) and methyl formate (173)... 

However, subsequent studies provided unequivocal evidence for consecutive three-centre rearrangements, the first step of which is a normal HERON reaction. Independent studies of decomposition of unsymmetrical hydrazines (227a and 227b) produced esters... 

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