A thermodynamic, C-13 NMR, and O-17 NMR study of isomeric 4,7-dihydro-1,3-dioxepins and 4,5-dihydro-1,3-dioxepins

The relative thermodynamic stabilities of 4,7-dihydro-1,3-dioxepin (4,6-dio xacycloheptene, 1a) and 4,5-dihydro-1,3-dioxepin (3,5-dioxacycloheptene, 1b ), and of a number of their 2-substituted derivatives, have been determined by base-catalyzed chemical equilibration in DMSO solution. Without excepti on, the 4,5-dihydro isomer is the dominating species at thermodynamic equil ibrium The relative stability of the b form is promoted by the presence of a single alkyl group on C-2, whereas two alkyl groups on C-2 have an opposi te effect. In general, the thermodynamic parameters Delta H-m(theta) and De lta S-m(theta) of isomerization vary unexpectedly with the pattern of subst itution at C-2. These trends appear to be derived from significant substitu ent-induced conformational changes in the b isomer, as suggested by C-13 an d O-17 NMR chemical shift data.