Solubility of Paracetamol in Pure Solvents

TLDR

Paracetamol has very low solubility in nonpolar and chlorinated hydrocarbons, moderate solubility in medium‑polarity solvents such as DMF, DMSO, and diethylamine, higher solubility in alcohols that decreases with increasing carbon‑chain length, and the lowest solubility in water compared to other polar solvents. The authors measured paracetamol solubility in 26 solvents over a temperature range of –5 °C to +30 °C and calculated the ideal solubility and activity coefficients for the saturated solutions.

Abstract

The solubility of paracetamol (4-hydroxyacetanilide) in 26 solvents in the temperature range from −5 to +30 °C is reported. Paracetamol has a very low solubility in nonpolar and chlorinated hydrocarbons such as toluene and carbon tetrachloride whereas the solubility is very high in solvents of medium polarity such as N,N-dimethylformamide, dimethyl sulfoxide, and diethylamine. Paracetamol is soluble in alcohols, but the solubility decreases with an increase in the length of the carbon chain in the n-alcohol homologous series (methanol to 1-octanol). The solubility of paracetamol in water is much lower than in other polar solvents such as the alcohols. The ideal solubility of paracetamol is calculated, and the activity coefficient in the saturated solutions is estimated.