New Way of Mono-BOC Protection of Diamines

poster · 16 years ago
by József Szegezdi, László Kovács (ChemAxon, InFarmatik)
Calculator Plugins (logP logD pKa etc...)
The calculated pKa values could serve good interpretation for the selective reaction of different diamines in acidic medium. Summarizing the basic requirement for mono protection is 5 difference between the pKa values of the two amino groups. The lower is the pKa of the free amine of the mono-Boc species the higher is the yield of the mono-boc product. Isolated diamines can be reacted according to the following rule: in acidic medium the lower in neutral medium the greater pKa valued nitrogen can be protected with acceptable selectivity. Alkyl chain longer than 3 carbons reduces the favorable neighborhood effect. Over 8 pKa difference value the amines can be reacted selectively in chemical reactions. There are certain problems which this model overlooks:
    1. Stability of the protected amines vs. pH and temperature 2. Stability of the heterocyclic systems vs. pH and temperature
The bulky Boc O is very sensitive to the steric hindrance, which is confirmed by regioselectivity of the Boc-protection and the sensitivity of the reaction velocity to the steric hindrance. Advancing Library Design and Organic Synthesis, La Jolla, California, February 24-27, 2003 Download