Rosser, Adam Andrew

Glover, Stephen

Fellows, Christopher

2019-02-11

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<p>Anomeric amides, amides bearing two electronegative atoms at nitrogen, constitute a new class of amides with reduced resonance and pyramidal nitrogens. <i>N-Alkoxy-N</i>aminoamides are known to undergo thermal rearrangements by the HERON (heteroatom rearrangements on nitrogen) reaction. Thermal instability in several other species including <i>N-acyloxy-N</i>-alkoxyamides and <i>N,N</i>-dialkoxyamides, had been noted. Consequently, the thermal decomposition of <i>N-acetoxy-N</i>-(4-substitutedbenzyloxy)benzamides were examined by GC-MS, ¹H NMR and ¹³C NMR. It was found that they decompose at 90 °C in [D8]-toluene by competing homolytic and HERON reaction pathways. Homolysis of the anomerically weakened N–OAc bond ultimately leads to <i>(5H)</i>-1,4,2-dioxazole species, while the HERON reaction by acyloxyl migration leads to anhydrides and reactive alkoxynitrene intermediates, which undergo subsequent intra- and intermolecular reactions under reaction conditions. The thermal decompositions of acyclic <i>N,N</i>-dialkoxyamides were shown to decompose exclusively by homolysis of an N–OR bond to form N-alkoxyamidyl radicals and alkoxyl radicals, generating a range of products. On the other hand, alicyclic <i>N,N</i>-dialkoxyamides, such as <i>N</i>-butoxy-δ-valerolactam, were observed to be unstable, undergoing HERON reactions at room temperature.</p> <p>Limited synthetic pathways for <i>N,N</i>-dialkoxyamides had been reported. A new, convenient synthesis using hypervalent iodine reagents, PIFA and PIDA, was developed and used to synthesise a range of acyclic and cyclic <i>N,N</i>-dialkoxyamides. Spectroscopic data for all synthesised species are in line with X-ray diffraction and computed structures of acyclic species, demonstrating highly pyramidal amide nitrogens (χN ≈ 55°) and appreciable loss of amide character. </p> <p>A new, widely applicable computational method to estimate resonance energy in a range of amides has been developed. This transamidation (TA) method, which employs readily computed ground-state energies and isodesmic equations, measures the resonance energy and amidicity of a range of anomeric amide systems relative to <i>N,N</i>-dimethylacetamide and demonstrated the loss of stabilising amide resonance energy in the N,Nbisheteroatom-substituted species. Amidicities of anomeric amides determined by the TA method agree with results produced using the independent COSNAR (carbonyl substitution nitrogen atom replacement) method. Both methods show a reduction in amidicity as the electron-withdrawing strength of <i>N</i>-substituents increases. Parsing computationally modelled HERON reactions with these results, the activation barriers were partitioned into a rearrangement component, describing the physical rearrangement, and a resonance energy component, describing the residual amide resonance, which must be overcome. Further, it was demonstrated that as a driving force for the HERON reaction, reduction in amide resonance, though significant in certain anomeric amides with strongly electron-withdrawing substituents, is subordinate to a strong anomeric interaction. </p> <p>To complete the series of investigations into properties of anomeric amides, <i>N</i>-alkylthiylsubstituted anomeric amides, an unusual and unexplored class, were investigated computationally. Modelling of SNO, SNN, and SNCl systems suggest that these amides would bear similar characteristics to other anomeric amides: anomeric interactions, longer N–C(O) bonds, and pyramidalisation of the amide nitrogen in line with electronwithdrawing capabilities of the <i>N</i>-substituents. Modelled HERON reactions for these amides had high activation barriers, similar to HERON-active ONOAc systems, but, like acyclic ONO systems, the lack of a strong anomeric interaction would realistically prohibit the HERON reaction. </p>

https://hdl.handle.net/1959.11/57361

University of New England

Theoretical Properties and Heron Reactions of Anomeric Amides

Thesis Doctoral

Publication