Structural characterization and comparative analysis of polymorphic forms of psilocin (4-hy-droxy-N,N-di-methyl-tryptamine).

Psilocin, the primary metabolite of the psychedelic compound psilocybin, crystallizes in two anhydrous polymorphic forms (I and II). Form I, first reported in 1974, was redetermined to modern standards, and its variable-temperature unit-cell parameters were measured. Form II, described for the first time, crystallizes in space group P21/n and exhibits a different molecular conformation: the N,N-dimethylethylene substituent is gauche, allowing the molecule to form a strong intramolecular O–H⋯N hydrogen bond. In Form II, molecules also form one-dimensional strands via N–H⋯O hydrogen bonds, and the structure shows whole-molecule disorder with an occupancy ratio of 0.689:0.311. Form I lacks intramolecular hydrogen bonds and instead forms a layered structure through intermolecular N–H⋯O and O–H⋯N hydrogen bonds.

Study at a glance

Abstract

The title compound, C12H16N2O, is a hy-droxy-substituted mono-amine alkaloid, and the primary metabolite of the naturally occurring psychedelic compound psilocybin. Crystalline forms of psilocin are known, but their characterization by single-crystal structure analysis is limited. Herein, two anhydrous polymorphic forms (I and II) of psilocin are described. The crystal structure of polymorphic Form I, in space group P21/c, was first reported in 1974. Along with the redeterm-ination to modern standards and unambiguous location of the acidic H atom and variable-temperature single-crystal unit-cell determinations for Form I, the Form II polymorph of the title compound, which crystallizes in the monoclinic space group P21/n, is described for the first time. The psilocin mol-ecules are present in both forms in their phenol-amine tautomeric forms (not resolved in the 1974 report). The mol-ecules in Forms I and II, however, feature different conformations of their N,N-dimethyl ethyl-ene substituent, with the N-C-C-C link in Form I being trans and in Form II being gauche, allowing the latter to bend back to the hydroxyl group of the same mol-ecule, leading to the formation of a strong intra-molecular O-H⋯N hydrogen bond between the hydroxyl moiety and ethyl-amino-nitro-gen group. In the extended structure of Form II, the mol-ecules form one-dimensional strands through N-H⋯O hydrogen bonds from the indole group to the oxygen atom of the hydroxyl moiety of an adjacent mol-ecule. Form II exhibits whole-mol-ecule disorder due to a pseudo-mirror operation, with an occupancy ratio of 0.689 (5):0.311 (5) for the two components. In contrast, Form I does not feature intra-molecular hydrogen bonds but forms a layered structure through inter-molecular N-H⋯O and O-H⋯N hydrogen bonds.