Polymorphism and Desmotropy in Heterocyclic Crystal Structures

Abstract

There is some confusion about concepts such as polymorphism, tautomerism, tautomeric polymorphism, and desmotropy. This perspective review tries to clarify them by defining their boundaries. Most examples are from heterocyclic compounds and differentiate between NH/OH tautomers (fast prototropy) and CH ones (slow prototropy). In the case of “tautomeric polymorphism” and “desmotropy” it is strongly recommended to use desmotropy. The different possibilities of crystallization of tautomers are examined in the conclusion.

Halogen‐Bond Effects on the Thermo‐ and Photochromic Behaviour of Anil‐Based Molecular Co‐crystals

“…Indeed, chemical shifts strongly depend on the position of both double bonds and protons. Several examples of SSNMR spectroscopy and diffraction investigations of tautomeric and desmotrophic systems, such as pyrazoles and pyrazolinones, are reported in the literature . Recently, the tautomeric state of Pigment Yellow 138 was investigated by solid‐state 1D and 2D multinuclear NMR spectroscopy experiments, and direct evidence of the presence of the NH tautomer was provided by 1 H– 14 N HMQC SSNMR spectroscopy at very fast MAS.…”

“…Several examples of SSNMR spectroscopy and diffraction investigations of tautomeric and desmotrophic systems, such as pyrazoles andp yrazolinones, [35][36][37][38] are reportedi nt he literature. [39] Recently,t he tautomeric state of Pigment Yellow 138 was investigated by solid-state 1D and 2D multinuclear NMR spectroscopy experiments,a nd direct evidenceo ft he presence of the NH tautomer was provided by 1 H-14 NH MQC SSNMR spectroscopya t very fast MAS. 2-Thiobarbituric acid is ar epresentative case because both polymorphism and tautomeric polymorphism have been found and studied by X-ray crystallography,a sw ell as by 1 H, 13 Ca nd 15 NC PMASN MR spectroscopy.…”

Structural and Theoretical Study of Salts of the [B9H14]− Ion: Isolation of Multiple Isomers and Implications for Energy Storage

“…The isolation of the {2×μH, 3×endo} form in the solid state is unprecedented in the literature and raises the question as to the possible role of the counterion in its stabilization. The crystallization of separate tautomers is itself a well‐known phenomenon for classes of molecules such as azoles, but appears unreported for borane crystal structures. In the case of 2 , the conformational flexibility of [C 4 mpyrr] + appears to allow it to separately stabilize both isomers.…”

A theoretical NMR study of polymorphism in crystal structures of azoles and benzazoles

“…Polymorphism refers to the ability of a compound in the solid state to exist in two or more spatial arrangements, namely, polymorphs, keeping unaltered its molecular connectivity. [1][2][3] Tautomerism is a related term that involves the rapid interconversion between two isomers trough an electrofuge group (being called prototropy if the group is a proton). These concepts are especially relevant in medicinal chemistry, reinforcing or blocking the activity of some drugs.…”