The regioselectivity of nucleophilic addition of azoles to unsymmetric
al fumarates yielding the corresponding (+/-)-2-azol-1-ylsuccinates ha
s been studied, The major regioisomer has been identified as the one o
btained from the attack of the azole to the more congestive side of th
e double bond. These results have been interpreted in terms of HOMO-LU
MO interactions using semiempirical AM1 molecular orbital calculations
, Addition of amines as alternative heteronucleophiles has been also e
xplored to confirm the regioselectivity. Neutral hydrolysis of the two
n-butyl ethyl (+/-)-2-imidazol-1-ylsuccinate regioisomers 8a and 8b h
as shown that this hydrolysis takes place faster than with the corresp
onding symmetrical di-n-butyl (+/-)-2-imidazol-1-ylsuccinate, and the
apparent rate of hydrolysis is independent of the size of the alcohol
moiety.