Hydrolysis of Medium-Ring Phosphates. Mechanism of Rate Acceleration by an Amino Group

Article abstract of DOI:10.1021/jo00348a029

A series of 2-oxo-2-(p-nitrophenoxy)-1,3-dioxa-2-phosphacyclooctane derivatives (1-5) having either a nitrogen or a sulfur atom placed transannularly in the ring were synthesized, and their rates of hydrolysis were examined.The pH-rate profile shows that while 1 undergoes hydrolysis over a wide pH range, others are hydrolyzed at a significant rate only in basic medium, thus implicating the amino function for rate enhancement.By comparison with rates obtained with 2 and 3 and the quarternary derivative 4, a mechanism involving rate-determining proton transfer from nitrogen to phosphoryl oxygen has been proposed for the hydrolysis of 1 at an acidic pH.The enhancement in the rate of spontaneous hydrolysis of the same compound, however, is explained by a combination of intramolecular general-base and nucleophilic catalysis.