Solvent and leaving group effects on the mono- vs. dialkylation of alkali salts of diethyl malonate with 1,2-bis-, 1,2,4,5-tetrakis- and 1,2,3,4,5,6-hexakis(halomethyl)benzenes. A new insight into selectivity control of malonester synthesis.

Contrary to the widely held opinion that protic (''acidic'') solvents favor monoalkylation whereas aprotic (''inert'') solvents support dialkylation of diethyl malonate carbanion, exactly opposite results have been obtained in the reaction of the dibromide 7, tetrabromide 4 and hexabromide 1 in ethanol and dimethyl sulfoxide, the former solvent preferring strongly dialkylation (cyclization) and the latter monoalkylation. Investigation in a broader spectrum of solvents demonstrated that hydrogen bonding as well as ion-pairing may play an important role in the selectivity control, both strongly supporting dialkylation. When a separation of ion-pairs is induced with 18-crown-6, monoalkylation prevails in the reaction. The solvent and the leaving group employed have been found to participate in the selectivity control. In DMSO, propensity to dialkylation increases strongly in the order I < Br << Cl, again in discord with earlier predictions. Rationale for the novel findings is provided on the basis of kinetic analysis of the overall reaction and is expressed by the limiting equations (5) and (7). (C) 1997 Elsevier Science Ltd.