SOME APPROACHES TO THE SYNTHESIS OF FLUORINATED ALCOHOLS AND ESTERS. III. SYNTHESIS OF 2-(F-ALKYL)ETHANOLS FROM 2-(F-ALKYL)-1-IODOETHANES AND AMIDES

Article abstract of DOI:10.1016/S0022-1139(00)80531-X

1-iodo-2-(F-alkyl)ethanes, R_FCH2CH2I, when heated with a large excess of N-methylformamide (NMF) give in high yield, mixtures of predominately R_FCH2CH2OH, some formate ester and a little R_FCH=CH2.In a study of this process, significant variables were examined, including solvent, reactant ratio, effect of water, and alternative amide reactants.The coproduct from NMF is the amidine salt, (1+)*I(1-).By contrast, R_FCH2CH2I with N,N-dimethylformamide (DMF) and water (one or two mols) gives chiefly the formate ester; the coproduct is Me2NH2(1+)*I(1-).A mechanistic scheme is proposed: in the first step, an alkyl imidate salt, e.g., F>(1+)*I(1-) is formed by O-alkylation of NMF; reaction of the imidate with more NMF gives a tetrahedral intermediate that breaks down rapidly to R_FCH2CH2OH, and HC(=NHMe)NMeCHO(1+)*I(1-).The formate ester is derived from the alcohol and this N-formyl acylating agent, in a subsequent step.Analogously, the alkyl imidate salt from DMF and R_FCH2CH2I reacts with water as nucleophile (but not with DMF) to give a tetrahedral intermediate that cleaves under stereoelectronic control to formate ester and amine salt, but not to alcohol.Quantitative isolation of amine salt and amidine salt, and observed rates of reaction give solid support to this proposed mechanism.