3-Fluoro-1-hydroxypropan-2-one (fluorohydroxyacetone) and some esters. Syntheses and effects in BDF1 mice

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Abstract
1-(Benzoyloxy), 1-(4-nitrobenzoyloxy) and 1-(3,5-dinitrobenzoyloxy) derivatives of 3-fluoro-, 3-chloro- and 3-bromopropan-2-one were prepared by oxidation of the 1-benzoyloxy-3-halopropan-2-ols in turn prepared from the appropriate benzoyl chloride and 3-halo-1,2-propanediols. 1-Benzoyloxy-3-fluoropropan-2-one was allowed to react with acidic trimethyl orthoformate to yield 1-benzoyloxy-2,2-dimethoxy-3-fluoropropane which on basic hydrolysis afforded 2,2-dimethoxy-3-fluoropropan-1-ol (fluorohydroxyacetone dimethyl ketal). This was deketalized with aqueous HCl to afford 3-fluoro-1-hydroxypropan-2-one (fluorohydroxyacetone). By reacting 1-chloro-3-fluoropropan-2-one and 1,3-dichloropropan-2-one with potassium acetate, 1-acetoxy-3-fluoropropan-2-one and 1-acetoxy-3-chloropropan-2-one (fluoro- and chlorohydroxyacetone acetate, respectively) were obtained. Sodium benzoate and 1-chloropropan-2-one produced 1-benzoyloxypropan-2-one. Structure-activity relationships are discussed which relate chemical structure, alkylating ability, toxicity and antitumor effects. Comparative toxicities in mice showed decreasing toxicity, on a molar basis, in the 1-benzoyloxy-3-halopropan-2-one series of bromo > fluoro > chloro. Ketones were much more toxic than the corresponding alcohols. In general the phosphate and benzoyloxy derivatives are more toxic than acetoxy compounds, with nitro-substituted benzoyloxy derivatives being much less toxic.

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