3-amino-1-phenoxybutan-2-ols and 1-amino-3-phenoxybutan-2-ols as potentially active beta-adrenergic antagonists

To study the relationship between side-chain methylation and selective beta-receptor antagonism, eight aminophenoxybutanols were prepared, comprised of two series containing four compounds each: (A) 3-amino-1-phenoxybutan-2-ols(I), and (B) l-amino-3-phenoxybutan-2-ols(II). Synthesis was achieved by treating two isomeric phenols (4,4-dimethylphenol or 4-ethylphenol) with 3-bromo-1,2-epoxybutane, catalyzed with BF[subscript 3]-etherate, which resulted in a mixture of 3-bromo-1-phenoxy- and 1-bromo-3-phenoxybutan-2-ols. Subsequent refluxing with i-propyl- or t-butylamine afforded I and II. The mixture thus formed was separated by column chromatography and found to consist of approximately 30% I and 70% II. The structure of II was unexpected; it was assumed that a 3-amino-2-phenoxybutan-l-ol (the "abnormal" product) would prevail. PMR, CMR and mass spectral data were employed for structure elucidation.