Kinetics and mechanism of the reaction of thionyl chloride with substituted acetophenone semicarbazones. The synthesis of 1,2,3-thiadiazoles

Abstract

The reaction of thionyl chloride with a series of para-substituted acetophenone semicarbazones, which gives 1,2,3-thiadiazoles, involved an electrophilic attack. The rates correlated with the substituent σ⁺ constants and gave a Hammett ρ value of –0.55. The reaction had a low activation energy and a high negative entropy in the solvents thionyl chloride and carbon tetrachloride (ΔE^‡ 9.46 kcal mol^–1; ΔH^‡, 8.8 kcal mol^–1; ΔS^‡–43.3 cal K^–1 mol^–1 for p-methylacetophenone semicarbazone in SOCl₂). The rates of reaction of the semicarbazones were the same as the rates of appearance of the cyclised products, and there were no long-lived intermediates. The stoicheiometry of the reaction involved equimolar proportions of SOCl₂ and of semicarbazone and the reaction was first-order in both reagents. Along with 4-aryl-1,2,3-thiadiazoles the final products were carbon dioxide, ammonium chloride, and hydrogen chloride. The mechanism proposed involves an ordered transition state with an approach of the electrophile above the plane of the hydrazone E-isomer via complexation with the conjugated π–n electron system. Tautomeric non-hydrazone forms of the semicarbazone are not involved in the rate-determining step.