The aim of this study was to investigate correlation between acid–base and catalytic properties of metal phosphate molecular sieves, such as silicoaluminophosphate molecular sieves SAPO-34 and Fe-substituted nickel phosphate Fe-VSB-5, in the reaction of propylene oxide with methanol. This reaction proceeds in two different ways, depending upon the nature of the samples, and gives rise to either primary and/or secondary alkyl ether of propylene glycol. The results indicate that acid–base properties of Fe-VSB-5 and SAPO-34 materials depend on the Fe and Si content, respectively. The increase in Fe content leads to an increase in basicity of VSB-5, while the increase in Si content favors the increase in acidity of SAPO-34. The strength and amount of Brönsted acid sites of Fe-VSB-5 and SAPO-34 are key factors to control their catalytic activity, while the strength and amounts of Lewis-acid sites and base sites are key factors to control the isomer selectivity.