The purification of nicosulfuron from phenol-rich mother liquors is challenged by strong solute-impurity co-solvency, which hinders targeted impurity rejection and stable polymorph control. To address this, empirical solubility correlation (modified Apelblat equation), ternary thermodynamic modeling (NRTL), and molecular dynamics (MD) simulations were integrated with solid-liquid equilibrium and slurry purification studies. Solubility measurements and MD simulations revealed that phenol acts as a potent co-solvent by associating with the nicosulfuron urea bridge via strong hydrogen bonding. Comparative solvent-mediated slurry purifications were conducted to disrupt these interactions. Methanol functioned as a lattice filler, co-crystallizing with the solute to form a metastable hemi-solvate (Form S1) that entrapped residual phenol and transformed into the undesired Form IV during drying. Conversely, ethanol successfully decoupled impurity rejection from phase selection. Energy analysis revealed that ethanol displaced phenol from solute clusters in the liquid phase. Experimental results confirmed the thermodynamic dominance of the anhydrous phase under slurry conditions, inherently preventing impurity-trapping solvate formation. This thermodynamically driven phase-selection mechanism enabled the direct isolation of stable anhydrous Form Ia (>99% purity), establishing a robust strategy for impurity rejection and solid-form manipulation of sulfonylurea herbicides in highly non-ideal industrial systems.
- Open Access
- Article
Polymorphism and Purification Mechanism of Nicosulfuron
- Mingchen Zhang 1,2,
- Chao Tang 3,
- Yan Zhang 2,4,*,
- Guangji Zhang 2,4,
- Songlin Zheng 3,
- Wenbo Huang 5,
- Jingcai Cheng 2
Author Information
Received: 29 Jun 2026 | Revised: 31 Aug 2026 | Accepted: 15 Sep 2026 | Published: 23 Sep 2026
Abstract
Keywords
nicosulfuron | solubility | thermodynamics | crystallization | molecular dynamics
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