Structural systematics and conformational analyses
of a 3x3 isomer grid of fluoro-N-(pyridyl)benzamides:
physicochemical correlations, polymorphism and isomorphous relationships
Mocilac, PavleORCID: 0000-0002-0789-9528, Donnelly, Katie and Gallagher, John F.ORCID: 0000-0003-4130-4556
(2012)
Structural systematics and conformational analyses
of a 3x3 isomer grid of fluoro-N-(pyridyl)benzamides:
physicochemical correlations, polymorphism and isomorphous relationships.
Acta Crystallographica. Section B: Structural Science, 68
.
pp. 189-203.
ISSN 0108-7681
An isomer grid of nine fluoro-N-(pyridyl)benzamides (Fxx)
(x = para-/meta-/ortho-) has been examined to correlate
structural relationships between the experimental crystal
structure and ab initio calculations, based on the effect of
fluorine (Fx) and pyridine N-atom (x) substitution patterns on molecular conformation. Eight isomers form N—H...N
hydrogen bonds, and only one (Fom) aggregates via
intermolecular N—H...O=C interactions exclusively. The
Fpm and Fom isomers both crystallize as two polymorphs with
Fpm_O (N—H...O=C chains, P-syn) and Fpm_N (N—
H...N chains, P-anti) both in P21/n (Z0 = 1) differing by their meta-N atom locations (P-syn, P-anti; Npyridine referenced to N—H), whereas the disordered Fom_O is mostly P-syn (Z` = 6) compared with Fom_F (P-anti) (Z` = 1). In the Fxo triad
twisted dimers form cyclic R22(8) rings via N—H...N interactions. Computational modelling and conformational preferences of the isomer grid demonstrate that the solid-state conformations generally conform with the most stable
calculated conformations except for the Fxm triad, while
calculations of the Fox triad predict the intramolecular N—
H...F interaction established by spectroscopic and crystallographic data. Comparisons of Fxx with related isomer grids reveal a high degree of similarity in solid-state aggregation and physicochemical properties, while correlation of the melting point behaviour indicates the significance of the substituent position on melting point behaviour rather than the nature of the substituent.