Reactivity of lactones and GHB formation.
The behavior of lactones in their hydrolysis reactions is a good indicator of their reactivity as electrophilic molecules. The hydrolysis of four- to six-membered lactones was investigated in neutral (water) and slightly acid media and in water/dioxane media. The following conclusions were drawn: (i) The reactivity of beta-propiolactone in neutral water is more than four times greater than that of beta-butyrolactone, due to the flow of charge caused by the latter's methyl substituent. Reactivity is enthalpy-controlled. (ii) The reactivity of beta-lactones diminishes in water/dioxane media when the percentage of dioxane increases. The increase in the dioxane percentage relaxing the intermolecular hydrogen bonds in the ordered structure of the water reduces DeltaH# and simultaneously increases the -DeltaS# value. (iii) An inverse solvent kinetic isotope effect in the acid-catalyzed hydrolysis of gamma-butyrolactone and delta-valerolactone was observed, this being indicative of acyl cleavage. (iv) The DeltaH# and DeltaS# values permit discrimination between alkyl and acyl cleavage. (v) A correlation was found between the chemical reactivity of lactones and their carcinogenic activity. (vi) The results suggest that orally ingested gamma-butyrolactone remains largely in its nonhydrolyzed form in the stomach before passing into the blood. (vii) The concentration equilibrium constant of GHB formation at human body temperature is Keq (37 degrees C)=0.40. (viii) Study of GHB formation shows that, contrary to earlier results, this is an endothermic process, with DeltarH=3.6 kJ mol(-1).
Pérez-Prior
M Teresa
MT
Departamento de Química Física, Universidad de Salamanca, E-37008 Salamanca, Spain.
Manso
José A
JA
del Pilar García-Santos
M
M
Calle
Emilio
E
Casado
Julio
J
D000818:Animals; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity; D007783:Lactones / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D012978:Sodium Oxybate / Q000737:chemistry*
D002273:Carcinogens; D007783:Lactones; D012978:Sodium Oxybate