Reactivity of Lactones and GHB Formation

Abstract

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).

Quantitative NMR Approach to Optimize the Formation of Chemical Building Blocks from Abundant Carbohydrates

“…Overall, we find the formation of the 3-deoxy and 3,4-dideoxy dehydration products (1-6)t ob eo nly weaklys ensitivet oward temperature variation between 120 and 180 8C. [25] Ta bulated yields of the variable-temperature experiments are collected in the Supporting Information (Table S2). [13] The product ratios of cyclic g-lactonec ompound 6 and open-chain 3-deoxy compounds 4 and 5 are temperature-dependent( Figure 4).…”

Ring‐opening of γ‐valerolactone with amino compounds

“…Both chemicals have been studied as intermediates to methylfuran, pentanediol, or alkanes,1, 6 and to precursors for the synthesis of biodegradable polymers 7. GVL, in particular, has been studied as a potential source for the manufacture of biodegradable polyesters8 through controlled ring‐opening polymerization 8–11. However, in contrast to δ‐valerolactone and ε‐caprolactone, GVL has a very low reactivity due to its low ring strain and direct polymerization resulting in relatively low molecular weight products 12–14…”

A Kinetic Approach to the Alkylating Potential of Carcinogenic Lactones

“…To gain quantitative knowledge about the effect of the hydrolysis of lactones on their alkylating capacity, both competing reactionsshydrolysis and alkylationswere studied in parallel. Previous work on the hydrolysis of lactones had been carried out in neutral and acid media (8).…”