Hydrolytic stabilization of protected p-hydroxybenzyl halides designed as latent quinone methide precursors
by Dyer, Robert Gordon; Turnbull, Kenneth D.
The hydrolysis rates of a series of protected p-hydroxybenzyl halides designed to generate a p-quinone methide through 1,6-elimination following photolytic deprotection have been investigated in order to optimize hydrolytic stability. A number of p-hydroxybenzyl halides containing an ether-or carbonate-linked photolabile hydroxy protecting group and a fluoride, chloride, or bromide benzylic leaving group have been synthesized. The hydrolysis rates of these derivatives in different water/acetonitrile mixtures and temperatures have been determined. The hydrolysis half-life of the benzyl bromide with the p-hydroxy protected as the carbonate-linked alpha-methylnitroveratryl (18c) is more than 750 times that of the ether-linked analogue (16c). These studies afford a Hammett sigma(p)(+) of +0.28 for the carbonate-linked derivatives compared to a sigma(p)(+) of -0.39 for the ether-linked derivatives. The theoretical hydrolysis half-life of the most stable benzyl fluoride in 100% water was sufficiently long so as to preclude extrapolation, while the chloride was approximately 50 h, and even the bromide was estimated to be nearly 5 h.
- Journal of Organic Chemistry
- Start Page
- 0022-3263; 1520-6904