9α-Chloro-16α-methyl-3,11-dioxoandrosta-1,4,6-triene-17β-carboxylic acid pinacolone solvate: catemeric hydrogen bonding and pinacolone solvation in a steroidal diketo acid derived from a commercial glucocorticoid

Abstract

The title ketocarboxylic acid, synthesized from the anti‐inflammatory clocortolone pivalate, crystallizes as C21H23ClO4·C6H12O, with one molecule of steroid and one of 3,3‐dimethylbutanone per asymmetric unit. The carboxyl group is highly ordered and the steroid molecules form translational carboxyl‐to‐ketone hydrogen‐bonding catemers [O...O = 2.682 (3) Å and O—H...O = 158°] that utilize the 3‐ketone group, with one chain proceeding in the [110] direction and the other in the [10] direction. One close intermolecular C—H...O=C contact is present, which involves the solvent O atom, but neither it nor the Cl atom nor the 11‐ketone group play any role in the classical hydrogen bonding.

Singularities in Molecular Conformation

“…Our survey of the Cambridge Structural Database (Version 5.36) revealed 7 solvate crystals with 11 independent pinacolone molecules. In three crystals the τ angle is in the 0–5° range, in three structures between 5 and 15°, and in four structures in the range from 15 to over 30°. ,− In the cocrystal with deoxycholic acid angle τ is the highest, of 30.05°, which is considered essential for its photosensitizing effect . The conformation of pinacolone, apart from torsion angle O1C2–C3–C4 (τ.…”

“…In 3 crystals the τ angle is in the 0-5° range, in 3 structures between 5-15º, and in 4 structures in the range from 15 to over 30°. 3,[17][18][19][20][21][22] In the co-crystal with deoxycholic acid angle τ is the highest, of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 7 30.05°, which is considered essential for its photosensitizing effect. 3 The conformation of pinacolone, apart from torsion angle O1=C2-C3-C4 (τ.…”

“…The minimum of potential energy occurs at 14° ± n ·120°. Red dashes indicate the torsion angles of pinacolone molecules present in cocrystalline compounds. ,− The Δ E p barriers have been indicated and the inset (top) expands the schematic Δ E p to over one full rotation of the tert -butyl group.…”