2-(Perfluoroalkyl)ethanols by thermal alkylation of ambidentate lactams with 2-(perfluoroalkyl)-1-iodoalkanes, in the presence of added water. A change in mechanism and stoichiometry of the reaction. Isolation of a water adduct of the lactim ether intermediate

Article abstract of DOI:10.1021/jo960831g

Thermal alkylation of amides by an alkyl halide gives alcohols and esters, and the intriguing behavior of ambidentate lactams in this reaction with 2-(perfluoroalkyl)-1-iodoethanes and lactam 2 is summarized in Scheme 1.2-(Perfluoroalkyl)ethanols (3) are the principal alkylation product, and there is obtained a range of coproducts in varying amounts. A lactim ether salt (6·HI) is the first reaction intermediate in a sequence of reactions. For δ-valerolactam (8) or ε-caprolactam (11), conversion to 3 falls precipitously and R(F)CH=CH₂ (4) becomes a major product. However, when water is introduced, alkylation rate of 2 by iodoalkane 1 increases, the conversion to 3 and 4 decreases, and a new lactim ether salt, 7.HI (the water adduct of 6·HI), is formed. Conversion to 3 is suppressed because coproduct 2 is weakly basic and the equilibrium lies on the side of the basic amine salt (7·HI). The mass spectrum of 2-hydroxy-2-[[(2-(perfluorohexyl)ethyl]oxy]pyrrolidine (7) includes the parent ion and a fragment (m/z = 131) of the intact pyrrolidine ring with an attached hydroxy group. Basic hydrolysis of product mixtures containing 7·HI in a protic solvent gives a high yield of 3 and 2. The higher lactams, 8 or 11, with 1 and water give the lactam salts efficiently; yield of 4 is low and yield of 3, by subsequent reaction with base, is high. With water present, the reaction rates of 8 and 1 are greater than for 2 and 1; water increases both the alkylation step and the water displacement step. Improved homogeneity of reaction mixtures and a specific solvent effect in which water stabilizes the bipolar transition state may be responsible for improved rates and yields.