TY  - JOUR
A1  - Sawatzky, Edgar
A1  - Drakopoulos, Antonios
A1  - Rölz, Martin
A1  - Sotriffer, Christoph
A1  - Engels, Bernd
A1  - Decker, Michael
T1  - Experimental and theoretical investigations into the stability of cyclic aminals
JF  - Beilstein Journal of Organic Chemistry
N2  - Background: Cyclic aminals are core features of natural products, drug molecules and important synthetic intermediates. Despite their relevance, systematic investigations into their stability towards hydrolysis depending on the pH value are lacking.

Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and density functional theory (DFT) based studies were applied to support and explain the results obtained. Rapid decomposition is observed in acidic aqueous media for all cyclic aminals which occurs as a reversible reaction. Electronic effects do not seem relevant with regard to stability, but the magnitude of the conformational energy of the ring system and pK a values of the N-3 nitrogen atom.

Conclusion: Cyclic aminals are stable compounds when not exposed to acidic media and their stability is mainly dependent on the conformational energy of the ring system. Therefore, for the preparation and work-up of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account.
KW  - quantum mechanics
KW  - hydrolysis
KW  - kinetics
KW  - molecular mechanics
KW  - natural products
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160976
VL  - 12
ER  -