Aldol condensation reaction molecular modeling

The presence on the furan ring of several substituents, each of which can give rise to rotational isomerism, increases the number of possible conformations. Furan-2,5-dicarbaldehyde represents a classic example. In principle four conformations are possible for this compound (59). Analysis of the electric dipole moments of furan-2,5-dicarbaldehyde in solvents of low dielectric permittivity enabled the relative populations of the conformers to be determined <89JST(196)227>. Experimental data suggest that the compound exists as a mixture of mixed ( ,Z)/(Z, )- and ( , )-conformers with ( ,Z) + (Z, ) = 0.68 and 0.96, ( , ) = 0.32 and 0.04, according to the solvent. Molecular orbital AMI-calculated enthalpies of all the conformers confirm the presence of the mixtures with populations of ( ,Z) -H (Z,E) = 0.38 and ( , ) = 0.60. Another conformational analysis of the same derivative, obtained by an experimental dipole moment determination combined with theoretical MNDO calculations <89H(29)657>, indicates the presence of a conformational equilibrium in which the ( ,Z)-conformation has the biggest contribution, and that the two aldehyde groups are not equivalent. Experimental confirmation has been performed for two model reactions monoprotection with MeOH/TsOH and aldolic condensation. 

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