Long range electrical field effects in solvolysis and ¹³C‐NMR shielding of androstanes with halogen, hydroxy and oxo substituents

Abstract

The solvolysis of 21 different 3‐ or 17‐androstanyl tosylates or chlorides with halogen, hydroxy or oxo substituents in 17‐ or 3‐position shows rate constant variations in hexafluoro isopropanol of up to 6·3 with regular differences for epimeric substituents. Similar variations ae seen over a distance of ∼10 Å in 13C‐NMR shifts at C‐17‐ones of androstan‐17‐ones with varied halogen substituents in C‐3, whereas the shielding observed at other distant carbon atoms excludes significant through bond effects. It is shown how, on the basis of suitable Coulomb‐type equations and of force field minimized geometries, both the stability variation of carbocationic transition states and the carbonyl group polarization are predictable by linear electric field effects, using the same parametrization.

The Use of Complexation Induced Proton NMR Chemical Shifts for Structural Analysis of Host-Guest Complexes in Solution

“…In this approach, however, experiment and calculation are mixed; the use of NOEs for this purpose is less problematic as it is commonly used only as a cut-off constraint, and in principle only depends on a single distance relationship. NMR shifts are always a mixture of several, more complex screening mechanisms; in view of sizeable long distance effects, which for example for LEF has been even observed with non-charged steroids over 8 , [15] NMR shifts lend themselves less for cut-off constraints than NOEs do.…”

Classical H-NMR shielding calculations with the program SHIFT and conformational analysis of three cyclophanes

“…in steroids with an X-Y distance >10Å) were correctly reproduced. 12 Anisotropy effects generated by single bonds with a diversity of published susceptibility values were found to be misleading 6,13 and are neglected.…”

Crystallographic searches for weak interactions – the limitations of data mining

“…Fluorine is used very often in view of its well known strong substituent effects (Smart, 2001), also on electrostatic potentials; it can in steroids, for example, lead to a twofold decrease of reaction rates at distances as large as 10 Å , or corresponding 13 C NMR shift changes by 0.25 p.p.m. (Schneider & Becker, 1989). That statistical analyses of the Protein Data Bank (PDB) exhibit more contacts with fluorine as acceptor is not really surprising (Taylor, 2017), as in contrast to databases such as the CSD, which include all kinds of synthetic derivatives, many…”