On the choice of optimal conformation in linear free-energy relationships. Reactivity of 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids with diphenyldiazomethane
Abstract
Rate constants for the esterification of eleven 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids
with diphenyldiazomethane in ethanol at 30 C were determined, and correlated with substituent constants
using classical Hammett and related methods. Statistically valid results for the para-substituted
compounds were obtained by the Swain–Lupton approach. The compounds studied had significant conformational
mobility due to seven rotatable bonds in their backbone. Going beyond the classical Hammett
approach, we established a relatively fast procedure to find the optimal conformations that can
be used in linear free-energy relationships, combining molecular dynamics with semiempirical calculations,
and calculations using a higher level of theory (DFT and MP2). Fair correlations were observed with
frontier orbitals, allowing inclusion of ortho-substituted derivatives and clarifying artifact-like data, as
perceived by the Hammett-type approach.
Keywords:
Conformational space / Rate constants / Linear free-energy relationships / Frontier orbitalsSource:
Tetrahedron Letters, 2012, 53, 5, 553-556Publisher:
- Amsterdam : Elsevier
Projects:
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-172035)
- High-Performance Computing Infrastructure for South East Europe's Research Communities (EU-261499)
DOI: 10.1016/j.tetlet.2011.11.097
ISSN: 00404039