SOLVOLYTIC FORMATION OF 1,2-DICHLORO-3,4-EPOXYBUTANE FROM BUTADIENE MONOXIDE UNDER PHYSIOLOGICAL CONDITIONS

Butadiene monoxide, a presumed carcinogenic metabolite of butadiene, i s stable in water or phosphate buffer, but was found to rapidly disapp ear from the headspace of solutions (10(-6) to 10(-4) M) in phosphate- buffered saline incubated at 37 degrees C. The process was first order with respect to monoxide concentration, with an apparent rate constan t of 6.6 x 10(-4) sec(-1). Mass spectrometric examination of the major product formed indicated it to be 1,2-dichloro-3,4-epoxybutane, which was confirmed by synthesis. Formation of the dichloro epoxide was lin early dependent on chloride ion concentration of the medium, but indep endent of dissolved oxygen. The formation of the dichloro epoxide is e xplained by slow solvolytic formation of a chloronium ion from butadie ne monoxide, which is followed by attack of chloride ion to generate c hlorine and butadiene. The chlorine is then rapidly trapped by second molecule of butadiene monoxide. This was confirmed by competitive trap ping of generated chlorine by inclusion of crotyl alcohol in the incub ation. A similar pathway has recently been demonstrated for reversible formation of bromine from solvolytically generated bromonium ions. Th e facile formation of dichloroepoxybutane under physiological conditio ns may be of significance in the toxicity of butadiene.