Gas-phase reaction of heterocycles over solid-supported molybdenum trioxide

Abstract

Flash vacuum pyrolysis over molybdenum trioxide supported on pumice stone has been evaluated as a synthetic method in heterocyclic chemistry. The method is effective in dehydrogenation of partly saturated heterocycles such as tetrahydroquinoline and tetrahydroisoquinoline to form the corresponding aromatic compounds in high yield. For other simple heterocycles there is fragmentation rather than dehydrogenation. A series of 2-oxazolines were found to fragment cleanly to give the corresponding nitrile and aldehyde in what appears to be a new thermal reaction of this ring system and this proceeded also in the absence of MoO₃. For oxazolines bearing an ester group at position 4 a different process led to unstable 4-methyleneoxazolidin-5-ones.

Application of the method to Hantzsch dihydropyridines gave a range of outcomes. Very ready dehydrogenation to the pyridines was followed at higher temperatures by stepwise loss of the two ester groups leading eventually to the 2,6-disubstituted pyridine in high yield. When there were phenyl groups present at the 2- and 6-positions, additional cyclisation led to indeno-fused pyridinones whose structure was confirmed by X-ray diffraction in one case. Based on this result, the corresponding Hantzsch esters with 2-, 3- and 4-pyridyl in place of phenyl at positions 2 and 6 were prepared and their FVP was examined in detail. In none of the cases was the analogous cyclisation observed but the method provided useful syntheses of the corresponding terpyridyls as well as terpyridyl mono and diesters and the corresponding carboxylic acids.

Based upon the observation that tetrahydropyran-4-one and tetrahydrothiapyran-4-one gave cyclopentenone upon FVP over supported MoO₃, the method was evaluated for bringing about Nazarov cyclisation of suitably substituted tetrahydropyran-4-ones, or the corresponding dienones and this proved to be successful in some cases although in others fragmentation was observed instead.

Date of Award	29 Jul 2020
Original language	English
Awarding Institution	University of St Andrews
Supervisor	R Alan Aitken (Supervisor)