Solvent Selection in the Detritylation Reaction for the Solid-Phase Synthesis of Oligonucleotides

Abstract This study examined the choice of solvent in the detritylation reaction for solid-phase oligonucleotide synthesis. In addition to being chemically inert under detritylation conditions, such a solvent should not bind with acid used in this reaction. These considerations explained the only two choices of solvent currently used in the detritylation reaction: dichloromethane and toluene. Other solvents, such as ethyl acetate, acetonitrile, THF, and nitromethane are shown by NMR spectroscopy to bind with trichloroacetic acid. Therefore, these are undesirable solvents for the detritylation reaction, confirmed by solid-phase synthesis experiments.