**1. Introduction**

Polymorphism and cocrystallization are tools to add or enhance desirable properties of crystalline products [1–3]. The developments in this field in recent years have enabled more carefully tunable properties [4]. The tunability of the properties of (co)crystalline systems is of much importance, especially in the fields of pharmacy and medicine [5–7]. By introducing various coformers, factors like solubility, stability, bioavailability, or tolerability of active pharmaceutical ingredients can be influenced [8–10]. A better understanding of the driving force behind the genesis of molecular aggregation processes in the solid state can therefore be helpful to increase the e fficiency of the synthesis of such crystalline products. Steed et al. have explained that asymmetry of crystalline structures can be exploited to purposefully produce medically relevant cocrystals [11]. While binary cocrystals have been focused on more commonly, less attention has been imposed on higher multicomponent systems like ternary [12], or even quaternary and quintenary [13] structures. In contrast to a well thought out stepwise multistage organic synthesis, a typical approach of a multicomponent crystal design starts with a retrosynthetic analysis of the target molecule followed by a one-pot reaction of all components in solution or solid state. To develop sophisticated and reliable protocols for multicomponent crystal syntheses, the complex modular assembly processes must be investigated by analysis of a hierarchy of intermolecular interactions and the molecular environment of involved components on each aggregation step [14].

In recent years, the group of Desiraju proposed that di ffering structural environments in the (n − 1)-multicomponent systems could lead to a state in which the incorporation of a new coformer would be more favourable for the overall structure [13]. Furthermore, Nangia and Bolla have confirmed that when using geometrically similar (in regards to size, planarity, etc.) heterosynthons,

the formation of multicomponent crystals could simply be predicted by the strongest hydrogen bond former interactions, showing the importance of the kinetic e ffect [15]. Results presented by Aakeröy and Gunawardana also lay an emphasis on the geometric environment of (n − 1)-crystal systems as crucial for the formation of higher component products [16].

Hence, in this contribution, in contrast to a one-pot synthesis, the controlled stepwise syntheses of a selected crystalline ternary multicomponent system is presented. The mechanism of the formation of multicomponent cocrystals could be figured out based on the analysis of molecular arrangemen<sup>t</sup> in solid state of the selected components. The binary cocrystals as well as the final resulting ternary multicomponent system were characterized by X-ray analysis.

For this, 2-methylresorcinol (MRS) formation capabilities in conjunction with the N-bases tetramethylpyrazine (TMP) and 1,2-bis(4-pyridyl)ethane (BPE) (Scheme 1) were investigated, using neat, drop-, or liquid-assisted grinding techniques. Additionally, sequential and one-pot reactions were performed. The obtained crystalline products were characterized using Powder X-ray Di ffraction (PXRD) and single crystal structure analysis.

**Scheme 1.** Selected compounds.
