Stabilization of a Metastable Polymorph of 4-Methyl-2-nitroacetanilide by Isomorphic Additives

4-Methyl-2-nitroacetanilide ( 1 ) crystallizes in white ( 1 W), amber ( 1 A), and yellow ( 1 Y) modifications. The isomorphic molecules 4-chloro-2-nitroacetanilide ( 2 ) and 2-nitro-4-trifluoromethylacetanilide ( 3 ) were synthesized, and their effects on the crystallization of 1 were studied. The percentages of an additive incorporated into the 1 W, 1 A, and 1 Y crystal lattices were determined by HPLC. Compound 2 is incorporated as a solid solution in 1 A up to levels of 30% (w/w), whereas the incorporation efficiency of 3 is much lower at the same doping level. From these results it can be assumed that 2 causes less disruption to the host lattices than does 3 . At the same doping level of an additive, 1 A incorporates the additive at a greater level than 1 W or 1 Y. As the incorporation level of an additive increases, both the solution and solid-state transformation rate from 1 A to either 1 W or 1 Y decreases. Structural comparison of the 1 W, 1 A, and 1 Y crystal lattices indicates that the additives may be least disruptive to the 1 A lattice, therefore explaining the greater incorporation efficiency of an additive in 1 A.