Ytterbium(III) chloride hydrate is used as an effective catalyst to prepare acetals by reacting with trimethyl orthoformate. It reacts with N-alkylsalicylideneimines to prepare yttrium(III) Schiff base complexes. It is widely used as NMR shift reagent, calcium ion probe and in DNA microarrays. Its anhydrous form acts as a Lewis acid and catalyzes the alkylation reactions such as aldol reaction and Pictet-Spengler reaction.

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