Thermochemistry of drugs: experimental and theoretical study of analgesics

Acetanilides are broadly used in the pharmaceutical industry. Thermochemical data on vapor pressures, solid-gas, liquid-gas, and solid-liquid phase transitions, as well as on enthalpies of formation of substituted acetanilides have been collected and evaluated with help of additional experimental measurements. Absolute vapor pressures of meta- and para-substituted acetanilides were studied by using transpiration method. Significant disagreement of available literature data on isomeric hydroxyacetanilides was detected and resolved. A quick estimation scheme of vaporization enthalpies of substituted acetanilides at 298.15K was developed based on structure-property relationships. Quantum-chemical methods were applied for calculation of theoretical gas-phase enthalpies of formation of substituted acetanilides. Theoretical values together with results from structure-property analysis allowed for validation of the experimental crystalline state enthalpies of formation and prediction of these values based on quantum-chemical calculations.