Thermochemistry of paracetamol

Combustion calorimetry, Calvet-drop sublimation calorimetry, and the Knudsen effusion method were used to determine the standard (p ^o = 0.1 MPa) molar enthalpies of formation of monoclinic (form I) and gaseous paracetamol, at T = 298.15 K: Updelta_textf H_textm^texto ( textC ₈ textH ₉ textO ₂ textN,text cr I ) = - ( 4 10.4 ±1. 3)text kJ  textmol ^{- 1} Updelta_{text{f}} H_{text{m}}^{text{o}} left( {{text{C}}_{ 8} {text{H}}_{ 9} {text{O}}_{ 2} {text{N}},{text{ cr I}}} right) = - ( 4 10.4 pm 1. 3){text{ kJ}};{text{mol}}^{ - 1} and Updelta_textf H_textm^texto ( textC ₈ textH ₉ textO ₂ textN,text g ) = - ( 2 80.5 ±1. 9)text kJ  textmol ^{- 1} . Updelta_{text{f}} H_{text{m}}^{text{o}} left( {{text{C}}_{ 8} {text{H}}_{ 9} {text{O}}_{ 2} {text{N}},{text{ g}}} right) = - ( 2 80.5 pm 1. 9){text{ kJ}};{text{mol}}^{ - 1} . From the obtained Updelta_textf H_textm^texto ( textC ₈ textH ₉ textO ₂ textN,text cr I ) Updelta_{text{f}} H_{text{m}}^{text{o}} left( {{text{C}}_{ 8} {text{H}}_{ 9} {text{O}}_{ 2} {text{N}},{text{ cr I}}} right) value and published data, it was also possible to derive the standard molar enthalpies of formation of the two other known polymorphs of paracetamol (forms II and III), at 298.15 K: Updelta_textf H_textm^texto ( textC ₈ textH ₉ textO ₂ textN,text crII ) = - ( 40 8.4 ±1. 3)text kJ  textmol ^{- 1} Updelta_{text{f}} H_{text{m}}^{text{o}} left( {{text{C}}_{ 8} {text{H}}_{ 9} {text{O}}_{ 2} {text{N}},{text{ crII}}} right) = - ( 40 8.4 pm 1. 3){text{ kJ}};{text{mol}}^{ - 1} and Updelta_textf H_textm^texto ( textC ₈ textH ₉ textO ₂ textN,text crIII ) = - ( 40 7.4 ±1. 3)text kJ  textmol ^{- 1} . Updelta_{text{f}} H_{text{m}}^{text{o}} left( {{text{C}}_{ 8} {text{H}}_{ 9} {text{O}}_{ 2} {text{N}},{text{ crIII}}} right) = - ( 40 7.4 pm 1. 3){text{ kJ}};{text{mol}}^{ - 1} . The proposed Updelta_textf H_textm^texto ( textC ₈ textH ₉ textO ₂ textN,text g ) Updelta_{text{f}} H_{text{m}}^{text{o}} left( {{text{C}}_{ 8} {text{H}}_{ 9} {text{O}}_{ 2} {text{N}},{text{ g}}} right) value, together with the experimental enthalpies of formation of acetophenone and 4′-hydroxyacetophenone, taken from the literature, and a re-evaluated enthalpy of formation of acetanilide, Updelta_textf H_textm^texto ( textC ₈ textH ₉ textON,text g ) = - ( 10 9. 2 ± 2. 2)text kJ  textmol ^{- 1} , Updelta_{text{f}} H_{text{m}}^{text{o}} left( {{text{C}}_{ 8} {text{H}}_{ 9} {text{ON}},{text{ g}}} right) = - ( 10 9. 2,pm,2. 2){text{ kJ}};{text{mol}}^{ - 1} , were used to assess the predictions of the B3LYP/cc-pVTZ and CBS-QB3 methods for the enthalpy of a isodesmic and isogyric reaction involving those species. This test supported the reliability of the theoretical methods, and indicated a good thermodynamic consistency between the Updelta_textf H_textm^texto Updelta_{text{f}} H_{text{m}}^{text{o}} (C₈H₉O₂N, g) value obtained in this study and the remaining experimental data used in the Updelta_textr H_textm^texto Updelta_{text{r}} H_{text{m}}^{text{o}} calculation. It also led to the conclusion that the presently recommended enthalpy of formation of gaseous acetanilide in Cox and Pilcher and Pedley’s compilations should be corrected by ~20 kJ mol⁻¹.