Sila–pharmaca. Part 32. Crystal and molecular structures of the (R)-enantiomer and the racemate of the antimuscarinic agent (cyclohexyl)phenyl[2-(pyrrolidin-1-yl)ethyl]silanol (sila–procyclidine)

Abstract

The crystal structures of the (R)-enantiomer (2b) and the racemate (1b) of (cyclohexyl)phenyl[2-(pyrrolidin-1-yl)ethyl]silanol (sila–procyclidine) have been determined X-ray structural analysis. The absolute configuration of (2b) was established. (2b) crystallizes in the orthorhombic space group P2₁2₁2₁, with a= 15.221(1), b= 17.967(1), c= 6.463(1)Å, and Z= 4. (1b) crystallizes in the monoclinic space group P2₁/c, with a= 6.441(1), b= 17.182(7), c= 16.707(4)Å, β= 103.86(2)°, and Z= 4. The structures were refined to respective R factors of 0.044 and 0.058. The molecular conformation of sila–procyclidine is identical in the two different structures. Intermolecular O–H ⋯ N hydrogen bonding is observed in both crystal lattices. In (1b)(R)- and (S)-configurated molecules form centrosymmetric dimers, in (2b) the (R)-configurated molecules are linked into infinite chains parallel to the c axis. The (R)-configurated sila–procyclidine (2b) has higher affinity for ileal and atrial muscarinic receptors of the guinea pig than the (S)-configurated enantiomer (3b).