Issue 22, 2016

4-Aminoquinaldine monohydrate polymorphism: prediction and impurity aided discovery of a difficult to access stable form

Abstract

Crystal structure prediction studies indicated the existence of an unknown high density monohydrate structure (Hy1B°) as the global energy minimum for 4-aminoquinaldine (4-AQ). We thus performed an interdisciplinary experimental and computational study elucidating the crystal structures, solid form inter-relationships, and kinetic and thermodynamic stabilities of the stable anhydrate (AH I°), the kinetic monohydrate (Hy1A) and this novel monohydrate polymorph (Hy1B°) of 4-AQ. The crystal structure of Hy1B° was determined by combining laboratory powder X-ray diffraction data and ab initio calculations. Dehydration studies with differential scanning calorimetry and solubility measurements confirmed the result of the lattice energy calculations, which identified Hy1B° as the thermodynamically most stable hydrate form. At 25 °C the equilibrium of the 4-AQ hydrate/anhydrate system was observed at an aw (water activity) of 0.14. The finding of Hy1B° was complicated by the fact that the metastable but kinetically stable Hy1A shows a higher nucleation and growth rate. The presence of an impurity in an available 4-AQ sample facilitated the nucleation of Hy1B°, whose crystallisation is favored under hydrothermal conditions. The value of combining experimental with theoretical studies in hydrate screening and characterisation, as well as the reasons for hydrate formation in 4-AQ, are discussed.

Graphical abstract: 4-Aminoquinaldine monohydrate polymorphism: prediction and impurity aided discovery of a difficult to access stable form

Supplementary files

Article information

Article type
Paper
Submitted
02 set 2015
Accepted
09 out 2015
First published
15 out 2015

CrystEngComm, 2016,18, 4053-4067

4-Aminoquinaldine monohydrate polymorphism: prediction and impurity aided discovery of a difficult to access stable form

D. E. Braun, H. Oberacher, K. Arnhard, M. Orlova and U. J. Griesser, CrystEngComm, 2016, 18, 4053 DOI: 10.1039/C5CE01758K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements