Solvent and leaving g roup 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.

Article abstract of DOI:10.1016/S0040-4020(97)00486-9

Contrary to tile 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 die leaving group employed have been found to participate in the selectivity control. In DMSO, propensity to dialkylation increases strongly in die order I < Br << CI, 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).