Isomerization of Bicyclic Hydrazine Monoesters to N-Amino-2-pyridone Esters, Precursors to Bicyclic "Isosydnones"

Abstract

DONALD MACKAY and LICHIN L. WONG. Can. J. Chem. 53,1973Chem. 53, (1975. Selective aqueous alkaline hydrolysis of the diazetidine diesters 4 gives the basic monoesters 1 which isomerize quantitatively in trifluoroacetic acid or by refluxing with sodium methoxide in dioxane to the N-aminopyridone esters 2. The bridged pyridazine ester 5a can also be selectively hydrolyzed to the presumed intermediate 10, hydrolysis being accompanied by immediate isomerization to 2a. A common mechanistic pattern is proposed for these isomerizations.Heating of 2 causes loss of alcohol to give the mesoionic "isosydnone" 3, a fairly stable ring system slowly opened by ethanol to 2b and by concentrated alkali to the N-aminopyridone 16a. Oxidation of 16a with lead tetraacetate gives the pyridone 18a.DONALD MACKAY et LICHIN L. WONG. Can. J. Chem. 53,1973Chem. 53, (1975. L'hydrolyse alkaline aqueuse selective des diesters de diazetidine 4 conduit au monoester basique 1 qui s'isomerise quantitativernent en ester de N-aminopyridone 2 lorsqu'on le traite par de l'acide trifluoroacetique ou par reflux en presence de methylate de sodium dans le dioxanne. L'ester cyclise de pyridazine 5a peut aussi Ctre hydrolyse sklectivement pour conduire a I'intermkdiaire presume 10; I'hydrolyse est accompagnke par une isomtrisation immediate en 2a. On suggere que ces isomerisations precedent par un mecanisme commun.Le chauffage de 2 conduit a une perte d'alcool fournissant "l'isosydnone" mesoionique 3, un systeme cyclique relativement stable, ouvert lentement par l'ethanol pour conduire a 2b et par les bases concentrees pour conduire a la N-aminopyridone 16a. L'oxydation de 16a par le tetraaktate de plomb conduit a la pyridone 18a. [Traduit par le journal]We have recently reported that an excess of trifluoroacetic acid (TFA) isomerizes the basic diazetidine ester l a to the aminopyridone ester 2a which cyclizes with loss of methanol to the mesoionic structure 3 (1).We now wish to describe some aspects of the chemistry of these ring systems and in particular to show that the esters 2 can be obtained under other quite different reaction conditions, again involving deep seated skeletal rearrangements.The diesters 4, the precursors to 1, were readily available in quantity as the end products of the thermal isomerization of the adducts 5 of azo esters with 2,5-dimethyl-3,4-diphenylcyclopentadienone (2). Though they are very stable to heat we have already shown that 4a is labile to acid, TFA causing demethylation and rearrangement to 6 (3). We were interested in trying to prepare the parent nitrogen unsubstituted 1,2-diazetidine 7, since examples of such diazetidines are unknown.Under varying conditions of alkaline hydrolysis it was found that one ester group in 4a was always easily removed. The product l a was unstable to prolonged exposure to the hydrolysis conditions especially at high temperature or with high alkali concentration but when it was allowed to react completely'the major end product was not the expected 7, but the dimer of the cyclone 2,5-dimeth...

1,2-Diphenyl-3,5-dimethyl-4-oxo-6,7-diazabicyclo[3.2.0]hept-2-ene, a nitrogen unsubstituted diazetidine with an unusually unreactive nitrogen

“…As the present work will show, the protection afforded the environment round IV, leads to greatly diminished reactivity at it or its s u b~t i t u e n t s .~ An example of this effect already described is the alkaline hydrolysis of 3a and b which occurred easily at N, to give the basic esters 100 and b, but not at all at N, (9). Under more vigorous conditions the diazetidine ring was destroyed, giving the cyclone (with acid quite different reactions were observed both with 3a (lo) and with 10a (9)).…”

Cationic and mesoionic 1,3‐thiazolo‐[3,2‐c]quinazoline derivatives

“…A variety of monocyclic mesoionic compounds are known [9], but derivatives containing fused mesoionic rings are less common, especially those with the second ring heteroaromatic [10]. The author has now attempted to synthesize some of fused-ring mesoionic systems based on 4(3H)-quinzolinethiones.…”