A ¹³C nuclear magnetic resonance study of the reversible substituent migration in several 2-acyl and 2-silyl derivatives of tropolone. Troponoid-IV

Abstract

. Can. J. Chem. 60, 231 (1982). The energy barrier for the reversible substituent migration was determined for a number of 2-acyl and 2-silyl derivatives of tropolone. The energy barrier is found to be dependent on the nature of the migrating group. Asymmetric monosubstitution on the ring shifts the equilibrium in favor of one dynamic isomer. In the two cases studied (3-bromotropolone and 3-bromotropoione acetate) it is found that the equilibrium is shifted towards the isomer bearing the bromine atom at the 7-position. Chem. 60, 231 (1982). Nous avons mesure la barriere energetique pour le processus de migration reversible du substituent en position 2 de quelques derives acyles et silyles de la tropolone. La nature du groupe migrateur modifie I'energie d'activation autant dans le cas des derives acyles que dans le cas des derives silyles. La presence d'une substitution asymetrique sur le cycle deplace I'equilibre vers un seul isomere dynamique. Dans les deux cas etudies (bromo-3-tropolone et acetate de bromo-3-tropolone) nous avons montre que I'equilibre favorise I'isomere portant I'atome de brome a la position 7.Parallel to other studies on the pharmaceutical activity of tropone and tropolone derivatives (I), we have recently reported on the additivity of substituent effects on I3C nmr chemical shifts for a number of 2-methoxytropone derivatives 1 and have shown that I3C nrnr is quite useful to distinguish between various isomers in the Zmethoxytropone family (2). A more challenging task involves the identification of the dynamic isomer favored by nonsymmetric tropolones and tropolone derivatives for which the 2-substituent is capable of rapid migration at room temperature of the type illustrated by 2a * 2b. It is well known that tropolone acetate undergoes rapid intramolecular acetyl migration at room temperature (4a S 4b) for which AG* is 10.8 kcal/mol (3a). The nonaveraging spectrum can be recorded below -60°C for which the correct line assignment was published in a previous paper in this series (36). A similar exchange process has been observed in substituted tropolone acetates such as 3,7-dibenzyltropolone acetate for which AG* was found to be 8 kcallmol (4).While investigating rearrangements of trialkylsilyl groups bonded to electronegative elements, Reich and Murcia (5) noted that the room temperature I3C nmr spectrum of 2-(2-butyldimethylsi1oxy)tropone contains only 4 lines, indicating a fast exchange of the trialkylsilyl group between the two oxygen atoms on the tropolone ring (5a = 56).In addition, they reported line broadening at about -70°C. but the slow exchange spectrum was not observed. Nevertheless, the authors estimated that AG* for the silyl group migration is about 8.2 kcall mol. A similar observation was reported by Hobson and co-workers (6) who prepared the trimethylsilyl ethers of tropolone (6) and 3-bromotropolone (7) and studied their IH nmr spectra down to -95°C. No significant change was observed for solutions of both trimethylsilyl ethers in toluene-d,, thus indicating a significantly...

A microwave study of hydrogen-transfer-triggered methyl-group rotation in 5-methyltropolone

“…The first step was to brominate tropolone in methanol at −10°C by dropwise addition of Br 2 following the methodology in Ref. 8. Upon warming to room temperature, a mixture of 3,7-dibromo and 3,5,7-tribromotropolone precipitated from the solution.…”

“…Upon warming to room temperature, a mixture of 3,7-dibromo and 3,5,7-tribromotropolone precipitated from the solution. 8 Recrystallization of this mixed precipitate from methanol gave 3,7-dibromotropolone ͑yield: 31%͒. Next, the Mannich reaction was utilized to place a morpholinomethyl group in the 5-position of the 3,7-dibromotropolone 9 ͑yield: 89%͒.…”