Structure and conformation of the cortisone side chain

The results of a recent crystal structure analysis of the 4‐chloro‐derivative of cortisone have been used to describe the exact conformation of the C‐17 side chain in this molecule. The results of this analysis are compared with those obtained from molecular orbital calculations, and from optical rotatory dispersion, circular dichroism, infrared and nuclear magnetic resonance measurements. The C‐17 side chain shows no evidence of internal hydrogen bonding, either with the C‐17 or with the C‐21 hydroxyl groups, and it is shown that such hydrogen bonding is unfeasible, both in the crystal and in solution. Evidence regarding the preferred conformation of C‐17 acyl side chains in general, is also presented.