Cooling rate “window” in the crystallization of metacetamol form II
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Melting and crystallization of metacetamol (C8H9NO2, N-(3-hydroxyphenyl)acetamide, structural isomer of paracetamol) were measured using DSC cycling heating–cooling between room temperature and 165 °C with constant heating rate of 6 °C min−1 and variable cooling rate ranging from 3 to 24 °C min−1. The selection of the cooling rate allows us to control the crystallization of metacetamol into one of its two polymorphs, I or II. Pure form II of metacetamol (recently discovered) is crystallized after the cooling rate of 6 °C min−1. Increase or decrease in the cooling rate suppresses the crystallization of the form II and produces the form I with remnant amorphous phase and a small impurity of the form II. The melting points and enthalpies of fusion are 420 K and 26.0 ± 1.3 kJ mol−1 for the form I and 399 K and 21.3 ± 1.1 kJ mol−1 for the form II, respectively.
KeywordsCooling rate DSC Metacetamol Polymorphism
The experiments were supported by a Year Abroad Program of the School of Chemistry, University of Edinburgh (LMcG), Russian Ministry of Education and Science, project 1828 and a project No И-37 of the Siberian Branch of Russian Academy of Sciences (DR). Denis Rychkov and Lindsay McGregor thank professors Elena Boldyreva and Colin R. Pulham for supervision. VAD acknowledges that his work was supported by state Assignment Project No. 0330-2016-004.
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