An experimental and computational study of new spiro-barbituric acid pyrazoline scaffolds: restricted rotationvs.annular tautomerism

Abstract

A regioselective [3+2] cycloaddition (32CA) reaction to synthesize unsymmetric spiro-barbituric pyrazolines containing a chromone or phenolic pyrazole moiety was achieved, providing good to excellent yields.

A review of the synthetic strategies toward spirobarbiturate-fused 3- to 7-membered rings

“…DFT calculations of spirobarbiturate scaffolds containing a locked phenolic pyrazole moiety demonstrated the predominance of restricted rotation about a single C-C bond over annular tautomerism. 63 A highly regioselective approach for preparing 4-bromo-7,9dimethyl-1-aryl-2-oxa-3,7,9-triazaspiro[4.5]dec-3-ene-6,8,10-trione derivatives was developed; it involved a 1,3-dipolar cycloaddition reaction between barbiturate-based olefins and nitrile oxide 25 by treatment with K 2 CO 3 in THF at room temperature. The dibromoformaldoximes, which are valuable reagents to synthesize nitrogen-and oxygen-containing heterocyclic compounds and can install multiple stereogenic centers with high atom economy through 1,3-dipolar cycloaddition, were prepared by using glyoxylic acid and hydroxylamine hydrochloride followed by bromination (Scheme 24).…”

“…DFT calculations of spirobarbiturate scaffolds containing a locked phenolic pyrazole moiety demonstrated the predominance of restricted rotation about a single C–C bond over annular tautomerism. 63…”

An expedient metal-free cascade route to chromonyl diene scaffolds: thermodynamic vs. kinetic control

“…The acetic acid-mediated synthesis involving Knoevenagel condensation of 3-formylchromone with 1,3-dimethylbarbituric acid in water is known. 23 We found that the resulting multifunctional synthon 1b could in situ react with ylidenemalononitrile 2b, which have been used extensively as vinylogous donors in Michael reactions. 24 Indeed, the chromonyl triene product containing barbiturate moiety 3b was obtained in a 65% yield within 24 hours.…”