Investigation of Polymorphism in 2-Amino-4,5-dimethylthiophene-3-carbonitrile
Abstract
Crystallization screens on 2-amino-4,5-dimethylthiophene-3-carbonitrile revealed the existence of three concomitant polymorphs (trimorphs) that were obtained under identical crystallization conditions. Forms I and II adopt a block-like morphology, while Form III crystallizes as plates. These trimorphs were characterized via single crystal X-ray diffraction (SCXRD), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) techniques. This was followed by a detailed examination of the supramolecular architecture and the associated intermolecular interactions in all of the crystalline forms of this compound. The crystal structure highlights the pivotal role of strong N–H···N hydrogen bonds alongside weak C–H···π/S/N interactions in directing the molecular packing and contributing to the observed polymorphism. The Hirshfeld surfaces and two-dimensional fingerprint plots provide a quantitative picture of the interaction type and distribution of these intermolecular interactions. Moreover, the lattice energy calculations revealed comparable stabilities among the three forms, wherein Form II exhibits the highest lattice energy, indicating greater thermodynamic stability in comparison to the other forms. The comparative analysis highlights the role of specific intermolecular interactions in governing the packing and stability of these polymorphs. Furthermore, the subtle role of these interactions is responsible for the altered modes of crystal packing, thereby justifying the occurrence of polymorphism in this molecule.
Fields of Study & Subjects
Crystallography and molecular interactions
Crystal structures of chemical compounds
X-ray Diffraction in Crystallography
Publication details
- Journal / source
- Crystal Growth & Design
- Publisher
- American Chemical Society (ACS)
- Volume
- 26
- Issue
- 4
- Pages
- 1477–1486
- Publication date
- 9 February 2026
- Language
- EN