Experiments were conducted to optimize the extraction equilibrium of reactive systems (water + heterocyclic carboxylic acid + Alamine 300/diluent) at T = 298.2 K and P = 101.3 kPa. The uptake capacity of the commercial composite solvent Alamine 300/diluent approximates the order: 2‐furoic acid ≥ alpha‐oxo‐2‐furanacetic acid > tetrahydro‐2‐furoic acid, and n‐heptane < 1,2‐dichloroethane < 1‐heptanol ≤ 2‐heptanone. Four differentiable models featuring the effects of separation ratio R and synergistic enhancement SE factors are stringently tested to identify global optimization ranges by derivative variation method as follows: 0.2 < R < 0.8 and 4 < SE < 7 for 1‐heptanol and 2‐heptanone, 1.2 < R < 3.5 and 4 < SE < 6.5 for 1,2‐dichloroethane, 2 < R < 80 and 4 < SE < 80 for n‐heptane, and Alamine 300 concentration 0.12–0.18 mol dm−3. Consecutively, the optimum mass transfer stages of a countercurrent extraction are calculated by Kremser–Souders–Brown equation. The equilibrium properties are estimated precisely according to linear solvation energy relation with substantial improvement linear solvation energy relation with substantial improvement (LSER‐si), solvation probability relation solvation probability relation (SPR) and Chemodel‐modified yielding mean relative errors of 7.0%, 0.08% and 20.4%, respectively.