Stereoelectronic Effects of Substituent Groups in the Solid State. Crystal Chemistry of Some Cubanecarboxylic and Phenylpropiolic Acids

Abstract

A series of 4-substituted cubanecarboxylic acids and phenylpropiolic acids have been studied with the aim of elucidating steric and electronic factors exerted by the 4-substituent in the formation of the dimer, or alternatively, the rare syn-anti catemer patterns in their respective crystal structures. It is shown that catemer formation depends critically on the ability of a proximal C-H group to form a supportive C-H‚‚‚O bond. In turn, this means that the C-H group must be sufficiently activated toward hydrogen bond formation. Such activation is inherent to the cubyl group but must be present additionally from a suitable electron withdrawing group in the phenylpropiolic acids. In any event, while C-H activation is necessary for catemer formation it is not sufficient. The substituent group that is present in the 4-position must also be sufficiently bulky so as to form a close packed array that is compatible with the catemer geometry. These trends are justified by the crystal structures of the 12 acids in the two families wherein the 4-substituent group is H, F, Cl, Br, I, and CH 3 . Our results indicate that electronic and steric effects of functional groups may be distinguished in the solid state, in that the formation of either a dimer or catemer may be rationalized on the basis of these effects.

Not Your Usual Bioisostere: Solid State Study of 3D Interactions in Cubanes

“…The first section is the methyl esters as outlined in Figure , all of which feature a methyl ester in the 1‐position of the cubane scaffold. When looking at 1‐(methoxycarbonyl) cubane ( 18 ) there is a short contact between O 1 and the cubane hydrogen atoms which is compounded by a short contact between O 2 and the methyl hydrogen atoms (Figure A) . These connections result in a linear network between the cubane molecules directed by the ester group.…”

“…Both the 4‐fluoro ( 19 ) and 4‐chloro derivatives ( 20 ) form tight networks where the esters can interact face‐to‐face. However, due to the size difference, fluorine interacts in a bifurcated fashion with the nearest hydrogen to the halogen substitute (Figure S19), whereas chlorine interacts with the hydrogens closest to the ester moiety (Figure B) . Both the 4‐bromo ( 21 ) and the 4‐iodo ( 22 ) compound show a more staggered and wider packing pattern.…”

“…A further study investigated how the C−H bond of cubane is activated toward hydrogen bond formation and its ability to support a framework with stabilizing C−H⋅⋅⋅O bonds . Initially, the authors chose to work with primary cubane carboxamides to observe the formation of N−H⋅⋅⋅O hydrogen bonds .…”

Nonconjugated Hydrocarbons as Rigid‐Linear Motifs: Isosteres for Material Sciences and Bioorganic and Medicinal Chemistry

“…Following this work, an additional study was carried out that further showed how the C−H bond of cubane is activated toward hydrogen‐bond formation and its ability to support a crystallographic framework with stabilizing C−H⋅⋅⋅O bonds . This was demonstrated in an alternative way with a series of primary cubane carboxamides, which investigated the N−H⋅⋅⋅O hydrogen bonds in amides .…”

Visualization of Hyperconjugation and Subsequent Structural Distortions through 3D Printing of Crystal Structures

“…This can be attributed to fact that the bond lengths and angles in the models represent the average values – a seriously flawed over generalization that struggling students or non-chemists would likely not be able to correct, leading to wrong conclusions or product designs. Moreover, simple well established effects, like inductive effects or resonance, cannot be captured in any of these models yet there is a repository of crystal structure data evidence (derived from experimental single-crystal X-ray diffraction data) that show the consequences of these electronic effects on molecular structure [5–8]. While 3D images from crystal structures can be readily produced from unambiguous single-crystal X-ray diffraction data, the visualization of these images is limited to a 2D computer screen.…”