Fluoroalkene chemistry: Part 1. Highly-toxic fluorobutenes and their mode of toxicity: reactions of perfluoroisobutene and polyfluorinated cyclobutenes with thiols

The reactions of four highly-toxic fluorobutenes – perfluoroisobutene (PFIB), 1-hydropentafluorocyclobutene (1-H), hexafluorocyclobutene (HFCB) and 3-chloropentafluorocyclobutene (3-Cl)—with propanethiol, 2,6-dimethoxybenzenethiol and N-acetylcysteine isopropyl ester were studied. PFIB and HFCB reacted with two molar equivalents of the aliphatic thiols, but with only one molar equivalent of the aromatic thiol (presumably due to steric hindrance) and resembled phosgene in their reactivity. The fluorocyclobutenes 1-H and 3-Cl reacted with one and up to three molar equivalents of the aliphatic thiols, respectively, but with only one molar equivalent of the aromatic thiol. The products of allyl and vinyl substitution were isolated and characterised as fully as possible. The inhalation toxicities of the fluorocyclobutenes to rodents correlated with the number of easily-displaceable fluorine substituents, supporting the contention that toxicity is due to reaction with biological thiols in the lung.