Hydroxy-1-aminoindans and derivatives: preparation, stability, and reactivity.
The chemical stability and reactivity of hydroxy-1-aminoindans and their N-propargyl derivatives are strongly affected by the position of the OH group and its orientation relative to that of the amino moiety. Thus, the 4- and 6-OH regioisomers were found to be stable, while the 5-OH analogues were found to be inherently unstable as the free bases. The latter, having a para orientation between the OH and the amino moieties, could be isolated only as their hydrochloride salts. 7-Hydroxy-1-aminoindans and 7-hydroxy-1-propargylaminoindans represent an intermediate case; while sufficiently stable even as free bases, they exhibit, under certain experimental conditions, unexpected reactivity. The instability of the 5- and 7-hydroxy-aminoindans is attributed to their facile conversion to the corresponding, reactive quinone methide (QM) intermediates. The o-QM obtained from 7-hydroxy-aminoindans was successfully trapped with ethyl vinyl ether via a Diels-Alder reaction to give tricyclic acetals 32a,b.
Herzig
Yaacov
Y
Global Innovative Research and Development, Teva Pharmaceutical Industries Limited, Netanya 42504, Israel.
Lerman
Lena
L
Goldenberg
Willy
W
Lerner
David
D
Gottlieb
Hugo E
HE
Nudelman
Abraham
A
D007189:Indans / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011355:Prodrugs / Q000737:chemistry
D007189:Indans; D011355:Prodrugs