William R. Ashcroft

Indole β-nucleophilic substitution. Part 5. Synthesis of the four isomeric 5H-pyrido [x,y-b] carbazole-5,11-diones and benzo analogues

The four isomeric 6H-pyrido[x′,y′:5,6]oxepino[3,2-b] indol-5(12H)-ones were transformed by alkali and air into the title pyridocarbazolequinones. A mechanism is proposed for these transformations.

The relative stabilities of 6-membered cyclic allylamine/enamine systems

Abstract Evidence on the relative stabilities of acyclic allylamine/enamine systems and methods for the isomerisation of the former into the latter are reviewed. Previous evidence on the related question of the thermodynamic stabilities of 3-piperideines/2-piperideines is presented. The view that 6-membered cyclic allylamines are thermodynamically preferred over their enamine isomers is refuted by demonstrating the base-catalysed equilibrative isomerisations of several 1-alkyl-4-acyl-1,2,5,6-tetrahydropyridines into their 1-alkyl-4-acyl-1,4,5,6-tetrahydropyridine isomers. It is shown that the conjugated CO group in these examples is unnecessary to effect isomerisation: for example even in the simplest possible situation, 1-methyl-1,2,5,6-tetrahydropyridine can be isomerised into 1-methyl-1,4,5,6-tetrahydropyridine, though a stronger base is necessary.

Efficient syntheses of ‘ellipticine quinone’ and the other three isomeric 5H-pyrido[x,y-b]carbazole-5,11(6H)-diones

6H-Pyrido[x′,y′ : 5,6]oxepino[3,2-b]indol-5-(12H)-ones (3) are efficiently converted by hot alcoholic base in air into the corresponding 5H-pyrido[x,y-b]-carbazole-5,11(6H)-diones (5).

Indole β-nucleophilic substitution. Part 3. Synthesis of four isomeric pyrido[x′,y′:5,6]oxepino[3,2-b]indolones

Condensations of 2-lithio-1-phenylsulphonylindole with the four pyridine analogues of phthalide gave 1-phenylsulphonylindol-2-yl o-hydroxymethylpyridyl ketones, from which on treatment with base were obtained the title compounds, by a process of intramolecular Indole β-nucleophilic substitution. This new aspect of Indole chemistry is discussed in the context of other related processes.

Cyclic allylamine–enamine systems. Part 7. A theoretical study of the relative energies of isomeric cyclic allylamine–enamine systems

The relative energies of a series of isomeric cyclic allylamine–enamine systems have been calculated by MINDO/3 and ab initio MO methods including complete geometry optimisation. The MINDO/3 results are shown to be reliable by comparison with experiment and with the ab initio results. Thus, for a particular pair of N-methyltetrahydropyridine-4-carbaldehyde isomers (12) and (13), both ab initio and MINDO/3 methods give similar optimised geometries and predict the enamine to be more stable than the allylamine by 1.5 and 1.3 kJ mo–1 respectively. This energy difference is predicted to be increased by up to 3 kJ mol–1 in water.

Synthesis of the pyridine analogues of phthalide

Routes for the preparation of the four isomeric pyridine analogues of phthalide are described starting from the readily available pyridine 2,3- and 3,4-diacids, or derivatives, and making use of the differential reactivity of substituents at pyridine 2-versus 3- and 3-versus 4-positions.