Mechanism of Methoxide Ion Substitution in the Z and E Isomers of O-Methylbenzohydroximoyl Halides

Article abstract of DOI:10.1021/jo030299e

Kinetics and stereochemical studies have been carried out on the reactions of the Z and E isomers of O-methylbenzohydroximoyl halides [1Z and 1E, ArC(X)= NOCH₃] with sodium methoxide in 9:1 DMSO-methanol. The reactions of methoxide ion with hydroximoyl fluorides (X = F) are stereospecific. The reaction with 1Z (X = F) gives only the Z substitution product (1Z, X = OCH ₃). The reaction of methoxide ion with 1E (X = F) is less selective, giving ca. 85% E substitution product. The Hammett ρ-values for the Z and E isomers (X = F) are +2.94 and +3.30, respectively. The element effects for 1Z (Ar = C₆H₅) are 2.21 (X = Br):1.00 (X = Cl):79.7 (X = F). The 1E element effects are (Ar = C₆H₅) 1.00 (X = Cl):8.3 (X = F) and (Ar = 4-CH₃OC₆H₄) 1.97 (X = Br):1.00 (X = Cl):12.1 (X = F). The entropies of activation for these reactions are negative (for example, ΔS? = - 15 eu for 1Z and ΔS? = - 14 eu for 1E, Ar = 4-CH₃OC₆H ₄, X = F). These experimental observations are consistent with a mechanism proceeding through a tetrahedral intermediate. Ab initio calculations were carried out to help explain the stereospecificity of these reactions. These calculations indicate that the tetrahedral intermediate from the Z isomer undergoes rapid elimination to the Z substitution product before stereomutation can take place. These calculations also show that the lowest barrier for rotation around the carbon-nitrogen single bond in the tetrahedral intermediate derived from 1E leads to an intermediate that eliminates fluoride ion to give E product.