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

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Abstract

4-Methyl-2-nitroacetanilide (1) crystallizes in white (1W), amber (1A), and yellow (1Y) 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 1W, 1A, and 1Y crystal lattices were determined by HPLC. Compound 2 is incorporated as a solid solution in 1A 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, 1A incorporates the additive at a greater level than 1W or 1Y. As the incorporation level of an additive increases, both the solution and solid-state transformation rate from 1A to either 1W or 1Y decreases. Structural comparison of the 1W, 1A, and 1Y crystal lattices indicates that the additives may be least disruptive to the 1A lattice, therefore explaining the greater incorporation efficiency of an additive in 1A.

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