GENERAL BASE CATALYSIS OF THIOSEMICARBAZONE FORMATION

Thiosemicarbazone formation from p-chlorobenzaldehyde exhibits a change in rate-determining step at about pH 4, similar to that in semicarbazone formation, with rate-determining amine attack below and rate-determining dehydration above this pH. The attack step is subject to general acid catalysis by carboxylic acids with a Brφnsted coefficient α = 0.15. It is also subject to base catalysis. The dehydration step provides the first reported example of general base catalysis of this class of reaction. A number of bases of different structure and charge type follow a Brφnsted line of slope 0.71. The reverse reaction is formulated as an attack of hydroxide ion on the free imine which is subject to general acid catalysis. The solvent deuterium isotope effects, kH/kD, are 3.2 and 2.6 for catalysis by triethylenediamine and 3-quinuclidinol, respectively, whereas kOH-/kOD- is 1.05. The dehydration step is subject to general acid catalysis by phosphate and dimethylmalonate monoanions, as well as by the solvated proton. The isotope effect, kkH/kD/kD, on the ionization constants as acids of both thiosemicarbazide(pKakH/kD′ = 12.81) and p-chlorobenzaldehyde thiosemicarbazone (pKakH/kD′ = 11.20) is 4.0 ± 0.1. © 1969, American Chemical Society. All rights reserved.