Reversed-phase TLC study of the lipophilicity of some 3-hydroxy-1,2-benzisoxazoles substituted in the benzene ring

Summary

The relative lipophilicity, R _M0 , and specific hydrophobic surface area of eleven 3-hydroxy-1,2-benzoisoxazoles substituted in the benzene ring (two isomeric fluoro, three isomeric chloro, three isomeric bromo and dibromo derivatives, and a nitro derivative) have been studied by reversed-phase thin layer chromatography (RP-TLC) on silica gel RP-C18 plates with methanol-water mixtures as mobile phases. Linear correlation between the volume fraction of methanol and R _M values over a limited range was established with high correlation coefficients ( r > 0.99). Lipophilicity R _M0 was compared with computed partition coefficients IAlogP, AlogP _s, clogP, milogP, logP _KOWIN, and xlogP. The best correlation ( r > 0.9) was found between R _M0 and logP _KOWIN and xlogP values. Principal-components analysis (PCA) was also used to compare R _M0 values with computed partition coefficients. The chromatographic behaviour of 3-hydroxy-1,2-benzisoxazoles was compared with that of their bioisosteric analogues 1,2-benzisothiazolonoles. Experimental R _M0 values for both groups of compounds were in accordance with the equation R _M0 = aR _M0 + b ( r > 0.9).