title: Polymorphism in paracetamol: evidence of additional forms IV and V at high pressure.
abstract: The structural phase stability of N-(4-hydroxyphenyl) acetamide (paracetamol) has been studied at ambient temperature up to 23 GPa using Raman spectroscopy. Spectral changes have provided further evidence for a highly kinetically driven Form I → II transition that occurs as a mixed phase from 4.8 to 6.5 GPa, and might complete as early as 7 GPa. Upon further compression to 8.1 GPa, a drastic shift in spectral signature was observed providing the first evidence for a previously undiscovered Form IV of paracetamol. Additional shifts in mode intensities were observed near 11 GPa indicating a potential restructuring of the hydrogen bonding network and/or structural modification to a potentially new Form V. Phase boundaries at 7 and 8 GPa were confirmed under hydrostatic conditions using Raman spectroscopy. Spectral changes indicate that the transition Form IV → V occurs near 11 GPa. Multiple ab initio harmonic frequency calculations at different levels of theory were performed with a B3LYP/6-31G** being used to provide a more robust mode assignment to our experimentally obtained Raman modes. High pressure X-ray diffraction (XRD) was performed up to 21 GPa, which provided further evidence for a highly kinetically driven Form I → II transition in agreement with our Raman measurements. In addition, the XRD provided further evidence for the existence of Form IV near 8 GPa and Form V near 11 GPa with Form V persisting up to 21 GPa.
authors.affiliation: Department of Physics and ‡Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Smith
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Bishop
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Montgomery
authors.forename: Tracy P
authors.initials: TP
authors.lastname: Hamilton
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Vohra
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D006860:Hydrogen Bonding; D007700:Kinetics; D015394:Molecular Structure; D011312:Pressure; D013059:Spectrum Analysis, Raman; D013696:Temperature; D014732:Vibration
chemical_list: D000082:Acetaminophen