The mutual interaction of substituents in the aromatic ring is one of the fundamentals of organic chemistry. Acetyl and methoxy substituted benzenes are abundant in value added lignin valorisation products. Using the transpiration method, the absolute vapor pressures of methoxy-acetophenones were measured and used to calculate the standard molar enthalpies of vaporisation. The new thermodynamic results and those available in the literature were evaluated in this work using structure–property correlations. The gas-phase standard molar enthalpies formation of methoxy-acetophenones were estimated using a high-level quantum chemical method G4. The pair-wise interactions of acetyl and methoxy substituents were derived in the frame of a “centerpiece” group-contribution approach. It was shown that in the case of agglomeration of up to three substituents in the benzene ring, no additional interactions are generally required for a reliable prediction of the thermodynamic properties of value-added compounds from lignin utilization processes.