Importance of chemical polymorphism in modern crop protection

Abstract

The development of agrochemical products faces many scientific challenges. After selection of an agrochemical candidate its properties will have to be optimized to guarantee best bioavailability and stability under many different conditions in various formulation types. These challenges are influenced by the solid-state properties of the active ingredient and this makes the selection of an optimized solid-state form of modern agrochemicals at early development stages very valuable. The increasing awareness of the solid state of agrochemicals is reflected in the importance of polymorphism patent applications, which may enhance the risk of litigations. This review aims to present strategies for the solid-form selection process of agrochemical development candidates. It introduces the different techniques for crystallization and analytics and demonstrates the influence of the solid state on different formulation types. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Keywords: chemical polymorphism; crystallization; fungicides; herbicides; insecticides; organic solid state; polymorphism screening; solid-state selection.

Figure 1

Statistical evaluation on polymorphism screenings done on agrochemical a.i. at Bayer: (a) ratio of monomorphism versus polymorphism; (b) number of polymorphs per a.i.

Figure 2

The organic solid state and its diversity, described as one‐component versus multicomponent system.

Figure 3

Chemical structure of fluopyram and needle‐like habit of fluopyram crystals at 100‐fold optical magnification.

Figure 4

X‐ray single‐crystal structure of bixafen butyrolactone solvate.

Figure 5

Simplified description of a solid‐state selection workflow.

Figure 6

Energy/temperature diagrams of monotropically and enantiotropically related crystalline forms I (mp I) and II (mp II).

Figure 7

Thermoanalytical data and single‐crystal X‐ray structures of crystalline forms I and II of tembotrione.

Figure 8

Cyclic DSC measurement of an early development a.i. candidate. First heating curve: (a) solid transition and (b) melting signal of the high melting form. Second heating curve: (c) glass transition of the amorphous phase, (d) recrystallization of the amorphous phase and (e) melting signal of the resulting lowest melting form. Third heating curve: (f) recrystallization out of the melting process of the lowest melting form and (g) melting signal of the resulting recrystallized form.

Figure 9

Thermomicroscopic observation of the polymorphic inversion of fluopicolide form III to form II and form I. Micrographs were taken by B. Mehl (Bayer Pharma, Material Science).

Figure 10

Comparison of ATR mid IR spectra of modification I (black) and III (magenta) of imidacloprid. The differences in comparison of the two spectra are marked.

Figure 11

Comparison of FT Raman spectra of Sencor SC (black) and modification II (magenta) of metribuzin. The spectra were recorded without any sample preparation.

Figure 12

Crystal packing motifs of modification I and II of prothioconazole.

Figure 13

Calculated morphologies of modification I and II of prothioconazole in comparison to its recrystallized sample.