Conformational and intramolecular hydrogen bonding effects on post-emergence and pre-emergence selectivities of herbicidal pyrrole dicarboxylates

Dimethyl 2‐methyl‐5‐(chloropyridin‐2‐yl)pyrrole‐3,4‐dicarboxylates in which the chlorine atom is substituted at different positions of the pyridine ring have widely varying biological properties. The 3‐chloro analog (I) is a post‐emergence and pre‐emergence herbicide, the 4‐ and 5‐chloro analogs (II, III) are post‐emergence herbicides but not pre‐emergence, and the 6‐chloro analog (IV) is inactive. Computer graphic and molecular mechanics analyses of their molecular conformations showed that the 4‐ and 5‐chloro analogs adopt a coplanar, intramolecularly hydrogen bonded conformation whereas the 3‐chloro analog does not. High‐level quantum mechanical calculations of the conformational preferences of related model systems were in agreement with these results. Based on this, II and III were predicted to have higher octanol/water partition coefficients relative to I, leading to higher soil binding and weaker xylem transport, hence their observed weaker pre‐emergence activities. Experimental measurements of octanol/water partition coefficients, soil binding, and infrared hydrogen bonding studies verified these predictions. Molecular modeling techniques are usually used for designing compounds to fit enzyme active sites and designing putative receptor models. This study demonstrates the usefulness of these techniques for dealing with transport problems.