Electrocyclic aromatic substitution by the diazo-group. Part 3. Studies on substituent directive effects and on the mechanism of benzo-1,2-diazepine formation by the cyclisation of 1-aryl-3-diazoalkenes

Abstract

The 1,7-cyclisation of diazo-compounds of type (4) which have an unsymmetrically placed substituent X gives both benzodiazepine isomers (6) and (8). The majority of substituents studied (X = R, OR, Cl) exert a directing effect which favours the formation of the less thermodynamically stable isomer (6) while only t-butyl and trifluoromethyl favour the formation of the para-isomer (8). A mechanistic study of the cyclisations of (6; X = Me and H) using ²H-labelled substrates has shown that the electrocyclisation step is reversible (Scheme 1; k_–1≠ 0). However for other substituents (X = OR, CF₃, Cl)k_–2(o)≠ 0 and the ortho-isomers undergo slow thermal isomerisation at 80 °C to give the more stable para-isomers (8). The observed directing effects of the substituents X are exerted via their effects on k₁, k_–1, and k₂ and although it is not possible to separate these effects for the majority of the substituents it was shown from the labelling study that the k₂/k_–1 ratio for the ortho-intermediate (5; X = Me) was markedly higher than that for the para-intermediate (7; X = Me).