Pyrolytic syntheses of fused bridgehead nitrogen heterocycles

• Main Author: Stevenson, Elizabeth
• Published: University of Edinburgh 1999
• Subjects: 547.59
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662429

There are two distinct areas of work in this thesis, both involving pyrolytic syntheses of nitrogen heterocycles. The first area of work extends a previous synthesis of 1<I>H</I>-azepin-3(2<I>H</I>)-ones to examples with a fused ring in the 1,2-position. The synthetic strategy for such azepinones involved preparation of enaminals incorporating cyclic amines with different ring sizes, then condensation of the enaminals with Meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione). Flash Vacuum Pyrolysis (F.V.P.) of the Meldrum's acid derivative gave the fused azepinone with dicyclopentadienone formed by a competing reaction. As the size and nature of the nitrogen containing ring of the Meldrum's acid derivative was systematically altered, the amount of azepinone formed reached a maximum with six and seven membered rings. The crystal structure of two typical enaminals were elucidated. The electron impact mass spectra of enaminals had not been previously studied and showed an unusual (M-17) breakdown peak due to loss of OH from the molecular ion and deuterium labelling studies were carried out to determine the mechanism of this breakdown. The hydrogen atom of the OH lost, was found to come from the aliphatic position α-to the nitrogen atom of the enaminal. The second stage of the cascade mechanism involves concerted loss of an alcohol molecule from 2-(2-alkoxycarbonylphenyl)pyrrole followed by the electrocyclic ring closure of the resulting ketene intermediate. These two thermal processes were combined by using readily available 1-substituted pyrroles, giving <I>5H</I>-pyrrolo[2,1-<I>a</I>]isoindol-5-one in high yield. The chemical and physical properties of <I>5H</I>-pyrrolo[2,1-<I>a</I>]isoindol-5-one were studied. The pyrolysis strategy was extended to include a number of derivatives structurally related to the original precursor, and in all cases the expected cyclised products were obtained. When the corresponding 1-(2-hydroxymethylphenyl)pyrrole was pyrolysed at 925 °C, <I>5H</I>-pyrrolo[2,1-<I>a</I>] isoindole was only a minor product and benzofulvene and naphthalene were formed. The mechanism of formation of these hydrocarbons was studied by deuterium labelling.