Schmidt reaction and beckmann rearrangement in the series of 3-azabicyclo[3.3.1]nonan-9-one derivatives

Abstract

SHORT COMMUNICATIONSWhile developing our studies [1] on the reactivity of 3-azabicyclo[3.3.1]nonan-9-one derivatives, which are fairly accessible compounds [2], in the present work we used these ketones as substrates in the Schmidt reaction [3], and the corresponding oximes, in the Beckmann rearrangement [4]. N-Arylmethyl-3-azabicyclo[3.3.1]nonan-9-ones I-III reacted with sodium azide in the presence of concentrated sulfuric acid at -5 to 0°C, following the Schmidt reaction pattern [5], to form new bicyclic compounds IV-VI (Scheme 1). azabicyclo[3.3.2]decan-9-one which was isolated as trifluoroacetate VIII (Scheme 3).

Intramolecular Schmidt reaction of tert-butyl 3-(3-azidopropyl)-4-oxopiperidine-1-carboxylate as a synthetic route to saturated fused aza heterocycles

“…Subsequently, analogous intramolecular cyclizations of various cyclic and aromatic azido ketones were studied, and fused polycyclic N-substituted lactams [6,7] and N-aryl-substituted lactams [8] were thus obtained. Apart from trifluoroacetic acid, titanium(IV) chloride, trifluoromethanesulfonic acid, and boron trifluoride-diethyl ether complex were used as catalysts.In continuation of our studies on the Schmidt reaction in the series of nitrogen-containing heterocyclic ketones [9], in the present work we made an attempt to accomplish intramolecular version of this reaction, as reported for analogous carbocyclic azido ketones [6]. For this purpose, we have synthesized azido ester V by alkylation of dimethylhydrazone III with 1-chloro-3-iodopropane [10] and subsequent nucleophilic substitution of the chlorine atom in IV by azido group on heating with sodium azide in DMSO (Scheme 2).…”

“…In continuation of our studies on the Schmidt reaction in the series of nitrogen-containing heterocyclic ketones [9], in the present work we made an attempt to accomplish intramolecular version of this reaction, as reported for analogous carbocyclic azido ketones [6]. For this purpose, we have synthesized azido ester V by alkylation of dimethylhydrazone III with 1-chloro-3-iodopropane [10] and subsequent nucleophilic substitution of the chlorine atom in IV by azido group on heating with sodium azide in DMSO (Scheme 2).…”

“…Treatment of azide V with trifluoroacetic acid induced intramolecular Schmidt reaction leading to the formation of a new heterocyclic system. The product,4,7,8,9,4]diazepine-2-carboxylate (VI) was isolated in 24% yield after chromatographic purification.The discovered reaction attracts interest from the practical viewpoint, taking into account that it leads to fused diazepine derivatives which are known as pharmacologically important heterocyclic systems. Examples are zolazepam [11] (anticonvulsant and anesthetic agent), anxiolytic ripazepam [12,13], and antidepressant zometapine [14].…”

“…Treatment of azide V with trifluoroacetic acid induced intramolecular Schmidt reaction leading to the formation of a new heterocyclic system. The product,4,7,8,9,4]diazepine-2-carboxylate (VI) was isolated in 24% yield after chromatographic purification.…”