Cooling rate “window” in the crystallization of metacetamol form II

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.