Highly regioselective access to 7-substituted 1,4,7,10-tetraazacyclododecane-1-carbaldehyde derivatives: synthetic aspects and NMR elucidation of the structures. X-Ray crystal structures of 7-triphenylmethyl-1,4,7,10-tetraazacyclododecane-1-carbaldehyde and 7-triphenylmethyloctahydro-5H,9bH-2a,4a,7,9a-tetraazacycloocta [cd] pentalene

Abstract

7-Substituted 1,4,7,10-tetraazacyclododecane-1-carbaldehydes have been prepared through the ring opening of orthoamide protected intermediates which, in turn, were obtained by reaction of mono N-substituted 1,4,7,10-tetraazacyclododecane derivatives with dimethylformamide diethyl acetal. Orthoamide ring opening occurs under mild reaction conditions and is highly regiospecific. A number of mono- and bi-dimensional NMR experiments have been performed to assign unambiguously the structure of the opened compounds. The regiochemistry of such compounds has also been confirmed by elucidation of the solid-state structure of 7-triphenylmethyl-1,4,7,10-tetraazacyclododecane-1-carbaldehyde by X-ray crystallography. The crystal structure of 7-triphenylmethyloctahydro-5H,9bH-2a,4a,7,9a-tetraazacycloocta[cd]pentalene has also been determined.