Effect of substituents on the formation of isomeric isoxazolo heterocycles: rationalization by semi-empirical PM3 molecular orbital calculations

Abstract

The different behavior of 4-amino-vs 4-hydroxypyridinones 7 and 8, respectively, towards hydroxylamine is rationalized with the aid of semi-empirical PM3 molecular orbital calculations including solvent effects. Four different mechanisms leading to either isoxazolo [4,3-c]pyridinones 9 or isoxazolo[4,5-c]pyridinones 10 are considered. Based on computed activation energies reaction of hydroxylamine via its oxygen atom as nucleophile is highly disfavored. For compound 7 a b-carbon addition of NH 2 OH at C-4 of the pyridinone accompanied by amine exchange and ring closure to 9 is by far the most feasible pathway. In contrast to 7, according to both NMR spectroscopy and molecular orbital [semi-empirical PM3 and hybrid density functional/Hartree-Fock (B3LYP/6-31G*)] calculations, 8 exists as a mixture of tautomers 8A (ca 20%) and (Z)-8B (ca 80%). Both tautomers of 8 are predicted to react with hydroxylamine at the hydroxyethylidene carbon atom [(Z)-8B] or acyl functionality (8A) to give hydroxyaminoethylidene compound 38 (oxime 23). Subsequent cyclization of either of these intermediates leads to compound 10.

Biotransformation of the triketone herbicide mesotrione by a Bacillus strain. Metabolite profiling using liquid chromatography/electrospray ionization quadrupole time‐of‐flight mass spectrometry

“…[23][24][25] The ringchain tautomerism (cyclized or open) is modulated by substituent effects. In the presence of a keto function, the open form is stabilized by a strong intramolecular (internal) hydrogen bond.…”

Reactions of Aldehydes and Ketones and Their Derivatives

“…Treatment of (E)-cinnamaldehyde (70) with an equivalent of phenyllithium in THF yields the enol (71), as expected. However, a number of other products are formed with an excess, including dihydrochalcone (72), the result of a tandem addition β-alkylation.…”

“…Semiempirical calculations have been used to tease out four different mechanisms for the reactions, as well as the effects of tautomeric equilibria in the reactants 70. …”

Synthesis of 4-Dialkylamino-6-Trifluoromethyl-5,6-dihydro-2-pyridinones via Cyclization of Enamines with α-Chloro-β,β,β-trifluoroethylisocyanates

“…A proof of the conjugation in 'push-pull' alkene's fragment of acylimines 6 and 7 is NMR data (Figure 3). Considerably broaden signals in 19 F NMR spectra testify to the fact that conformational interconversion is decreased. Thus, in benzene solution at 20 °C: d F = -69 with Dn 1/2 = 120 Hz and d F = -68 with Dn 1/2 = 180 Hz for 6 and 7, respectively, were observed.…”

“…It should be noted that 5,6-dihydro-2-pyridinones synthesized incorporate latent 1,3-CCC-bielectrophilic fragment and are very promising building blocks for further synthesis of more complicated condensed trifluoromethyl heterocyclic compounds fused to dihydropyridone ring. 19 All procedures with hydrolytically sensitive a-chloroethylisocyanates and trifluoromethylacylimines were carried out in atmosphere of anhyd Ar. All solvents were purified and dried by standard methods.…”