Structural Characterization of the Regioisomers of Di(hydroxydibutyl)ether by GC-EI MS and theoretical calculations

Di(hydroxybutyl) ether (DHBE), a liver protecting drug, is composed of a mixture of three regioisomers: 4-(3-hydroxybutoxy)-2-butanol (1), 3-(4-hydroxy-2-butoxy)-1-butanol (2), and 3-(3-hydroxybutoxy)-1-butanol (3). Unequivocal differentiation of each regioisomer of DHBE was rapidly obtained without isolation of the single components, using GC-MS with electron ionization (EI). Themass spectrum of 1 showed a rearrangement ion at m/z 118, characteristic of the 3-hydroxybutyl chain, deriving from loss of acetaldehyde from the molecular ion, whereas 2 and 3 were characterized by the ion at m/z 117, expected from aα-cleavage of the 4-hydroxy-2-butyl chain. The species at m/z 118, in turn, loses a water molecule via a mechanism involving both alcohol hydrogens, as shown by deuterium exchange experiments. Both this finding and theoretical calculations support amechanism in which the loss of acetaldehyde in 1 occurs via a cyclic intermediate, stabilized by a strong hydrogen bond between the alcohol oxygen bearing the charge and the other alcohol oxygen, and involves initial hydrogen transfer from the former to the latter. The EI spectrum of 2, having two4-hydroxy-2-butyl chains, showed the fragmentations expected fromclassical fragmentation rules of aliphatic ethers and alcohols, whereas the EI spectrum of 3, bearing one 4-hydroxy-2-butyl and one 3-hydroxybutyl chain, showed essentially the characteristic fragments of both chains. Copyright © 2009 John Wiley & Sons, Ltd.