A Spectacular Example of the Importance of Rotational Barriers: The Ionization of Meldrum's Acid

Article abstract of DOI:10.1021/ja00237a028

The free energy of ionization of Meldrum's acid (I) is 11.68 kcal/mol more spontaneous than that of its acyclic analogue, dimethyl malonate.This energy difference must represent one of the largest stereoelectronic effects in the literature of organic chemistry and demands careful elucidation.This paper probes the problem by comparing the effects of various structural contributions to the carbon acidity of Meldrum's acid.The most dramatic effect results from increasing the size of the bislactone ring system.There is a rapid decrease in acidity between the 6-membered and 10-membered ring until the 13-membered ring has the same pK_a as dimethyl malonate.The obvious conclusion from the assembled results is that the difference between the acidities Meldrum's acid and the larger ring bislactones or diesters lies in the barrier to rotation around the ester bonds.Over half of the 11.68-kcal/mol effect may be explained empirically through the 3-4-kcal/mol stabilization of the Z conformation of esters relative to the E conformation.Another 3 kcal/mol may be assigned to the cyclization effect seen also in the β-diketone series.