Implications of Thermodynamic Control: Dynamic Equilibrium Under Ball Mill Grinding Conditions

Abstract

We report a powerful example of subtle dynamic equilibrium control under milling conditions using the base catalysed solid state disulfide exchange reaction between two homodimers (bis-2-nitrophenyldisulfide and bis-4-nitrophenyldisulfide) to produce the heterodimer (4-nitrophenyl-2nitrophenyl-disulfide). Under ball mill neat grinding conditions, the equilibrium is reproducibly represented by homodimers and Form A of the heterodimer in a molar ratio of 1 to 4. The heterodimer crystallizes in two different polymorphic forms, Form A and Form B, which can be interconverted by changing the milling conditions between neat grinding and liquid assisted grinding with a number of solvents. Because such milling equilibria are reversible and dynamic in nature, we interpret these end points as existing in local thermodynamic wells. Moreover, homodimer bis-2-nitrophenyldisulfide also shows two polymorphs, Form I and Form II, depending on the milling conditions, further complicating the picture. Because of the nanocrystalline nature of these solid forms, we suggest that surface effects are responsible for the switch in polymorph stabilities in the milling jar.

The origin of delayed polymorphism in molecular crystals under mechanochemical conditions

“…The first stage of material activation is achieved by reducing crystal size and hence increasing the influence of excess surface energy on structure stability, Figure 4a. 23 Consistent with previous reports on mechanochemical polymorphism, 23,32,35 both Form I and Form II were found to have characteristic crystal sizes (Scherrer size), thus indicating that comminution may be an origin for the onset of polymorphism. However, while the crystal size of Form I clearly decreased (from > 100 nm to ca.…”

“…Increasing evidence suggests that the crystal size obtained at mechanochemical equilibrium plays a dominating role on the crystallographic structure that results. 22,23,32 However, this concept does not yet account for the striking and often exceptionally long induction periods observed during mechanochemical reactions. 12,33,34 Scheme 1: Schematic representation of the system under study.…”

Quantitative reversible one pot interconversion of three crystalline polymorphs by ball mill grinding

“…We believe instead that the contaminant acts as a template for the nucleation of the different polymorphs. Importantly, as no base catalyst was used in these experiments, 14,25,26,28–32 no covalent bonds are expected to be broken during the turnover cycles displayed in Fig. 1.…”

“…Our model disulfide compound, 2-nitrophenyl-4-chlorophenyl-disulfide, here called 1-2 , has been investigated by our team for various purposes together with a few related phenyl-disulfide compounds with different functional groups on the phenyl ring. 2,14,25–32 The number “ 1 ” refers to the 2-nitrophenyl- part, and (2-nitrophenyl) 2 -disulfide is thus called 1-1 ; while the number “ 2 ” corresponds to the 4-chlorophenyl- part, and (4-chlorophenyl) 2 -disulfide is thus called 2-2 . Form B is the bulk thermodynamic polymorph of 1-2 under ambient temperature and pressure, and can be easily recrystallized from a range of solvents (see ESI† Section 3.5 for details).…”

Time‐Resolved In Situ Monitoring of Mechanochemical Reactions

“…[24] Once mechanical treatment is stopped, this excess energy is allowed to relax, although the relaxed state may still be "activated" with respect to the nascent state. [13] processes that lead to this steady state, [12,17,26] as well as its nature, [7,27] hold the key to better understand the driving forces behind mechanically driven solid-state transformations. These goals can only be achieved by following mechanochemical transformations through time-resolved in situ (TRIS) methods.…”