Cycloaddition reactions of imidazolium and phthalazinium dicyanomethanide 1,3-dipoles: synthesis, mechanism and the effect of water

The cycloaddition reactions of imidazolium-3-dicyanomethanide 1,3-dipoles with electron poor alkene and alkyne dipolarophiles were explored. The reactions of these azolium 1,3-dipoles with alkyne dipolarophiles generated unstable initial cycloadducts that rearranged in situ to yield ring expanded products. The imidazo[2,3-a]pyridine products were formed as loss of aromaticity in the initial fused cycloadduct drove the subsequent ring expansion rearrangement. Single regioisomers were produced when unsymmetrical dipolarophiles were used in the reactions. An imidazo[2,3-a]pyridine product was also generated when the 1-methyl-imidazolium-3-dicyanomethanide 1,3-dipole was reacted with the electron poor alkene N-phenylmaleimide. However, imidazolium-3-dicyanomethanide 1,3-dipoles reacted with maleic anhydride to form novel ylide products. These Michael Addition reactions generated unstable intermediates that underwent in situ 1,2-rearrangment to form the new spirally twisted imidazolium ylide compounds. The reaction of 1-phenyl-1,2,4-triazolium-4-dicyanomethanide 1,3-dipole with DMAD produced a stable initial cycloadduct that could be isolated under cold conditions. The initial cycloadduct easily underwent ring expansion rearrangement in solution at room temperature to form a 1,2,4-triazolo[4,5-a]pyridine product. Tracking the rearrangement by NMR spectroscopy revealed the presence of an intermediate that could be seen to develop and decline as the initial cycloadduct converted into the ring expanded product. The cycloaddition reaction of the phthalazinium dicyanomethanide 1,3-dipole with benzylidene acetone dipolarophiles was also examined in both acetonitrile and water. New 1,2-substituted tetrahydropyrrolo[2,1-a]phthalazine derivatives were synthesized. The reactions produced two products, both with the aryl substituent on the C-2 position. The major product in each case had the aryl substituent in the endo-position. The kinetics of the cycloaddition reactions of phthalazinium dicyanomethanide 1,3-dipole with benzylidene acetone dipolarophiles was also explored. Large rate accelerations were observed when the reactions were completed in aqueous acetonitrile rather than pure acetonitrile. Experimentally and theoretically derived Hammett plots ruled out increased polarity of the cycloaddition transition state as the cause of rate accelerations observed in the presence of water. The accelerations are most likely due to special hydrogen bonding effects. Cycloaddition reactions involving solid phthalazinium dicyanomethanide 1,3-dipole and the solid dipolarophiles p-chlorobenzylidene acetone and N-phenylmaleimide were completed using pure water as the reaction solvent. The p-chlorobenzylidene acetone dipolarophile required liquefaction to allow the “on water” cycloaddition to proceed. Liquefaction of N-phenylmaleimide was not required as the dipolarophile had sufficient solubility in water to generate an oil layer. Solid-solid reactions have therefore been shown to be possible using the “on water” methodology.

Funder

IRCSET

Rights

Attribution-NonCommercial-NoDerivs 3.0 Ireland

cbn

Collections

University of Galway Theses (PhD Theses)