Binary co-crystal

Finally, some examples of 3-D motifs in halogen-based binary co-crystals include tetrabromoadamantane hexamethylenetetramine [85], 1,4-di-iodotetrafluoroben-zene hexamethylenetetramine [51] and iodoformihexamethylenetetramine [86]. 

Finally, carbamazepine tetracarboxylic acid-adamantane [115] represents one of the few examples of clearly defined and predictable 3-D motif observed in a hydrogen-bond-based binary co-crystal. 

The most widely used synthons for the directed assembly of binary co-crystals have contained a carboxylic acid in combination with a suitable N-containing heterocycle. For example, there are currently three co-crystals in the CSD with pyrazine [126], seven with phenazine[127], sixteen with 4,4 -bipyridine [128], one with pyrimidine [129], and nine co-crystals with either azapyrine, quinoline, phenantroline [130] and a benzoic acid-based counterpart. In every case, the expected/intended carboxylic acid - -N(heterocycle), O-H- -N, hydrogen bond is present. For slightly more complex heterocycles (i.e. with added substituents capable of hydrogen bonding) the results are still very consistent 11 of 12 carbox-... 

Beyond Binary Co-crystals The Need for Supramolecular Reagents... 

For example, both polarization induced 1-0 and COOH-COOH interactions were exploited to generate a ID extended network in a binary co-crystal of 1,4-dinitrobenzene and 4-iodo-cinnamic acid. The corresponding crystal structure of the binary solid displayed the presence of both COOH-COOH and I-NO2 interactions resulting in ID extended chain (Fig. 4.11) [63]. 

Fig. 2 Main intermolecular interactions in the 1 2 binary co-crystal of 2 and 2,6-difluorobenzoic acid...

Fig. 9 Primary hydrogen bonds in a binary co-crystal of (Z)-4-(cyano(hydroxyimino)methyl) benzoic acid and ditopic hydrogen-bond acceptor...

Binary molecular co-crystals of 2,5-bis(3-pyridyl)-l,3,4-oxadiazole and 2,5-bis-(4-pyridyl)-l,3,4-oxadiazole with benzene-1,3,5-tricarboxylic and benzene-1,2,4,5-tetracarboxylic acids were studied by X-ray and thermogravimetric analysis of mass loss <2005MI1247>. Dipole moments were used to study the flexoelectric effect in guest-host mixtures of 2,5-(4-pentylbenzene)-l,3,4-oxadiazole with commercial liquid crystal hosts <2005CM6354>. The luminescence properties of many other copolymers were also investigated (see Section 5.06.12.3). 

A potential difficulty for the design of binary systems is maintaining the independence of the two supramolecular functionalities. In the case of the 8 12 co-crystal, two possible arrangements may be envisaged since both molecules possess the appropriate oxalamide functionality to generate a-networks. The... 

This section will provide some practical approaches to the design of binary and ternary supermolecules and co-crystals by outlining supramolecular synthetic strategies based upon modular hydrogen-bond driven approaches. 

At this point we are essentially left with two families of compounds binary charge-transfer complexes and hydrogen-bonded or halogen-bonded co-crystals. This section will focus almost exclusively upon representatives from the latter categories [67]. The terms binary/ternary supermolecule indicates a discrete species with predictable and desirable connectivity, constructed from two /three different molecular species and assembled via directional non-covalent forces [68-78]. 

Phosphine oxide-based olefination reactions continue to be widely used in synthesis, for example, in those leading to vitamin D3 and its derivatives. An alternative method for the conversion of diastereomerically pure menthyl phosphinates to optically active phosphine oxides has been reported. Structural studies on a variety of phosphine oxide binary and ternary co-crystallization compounds have been carried out and the first complex involving the binary PO ligand has been prepared. 

Aakeroy and co-workers and Nangia and co-workers were successful in the exploitation of Etter s hydrogen bonding hierarchy rule to design binary and ternary complexes of nicotinamide (2) and iso-nicotinamide (3) with carboxylic acids and phenols [14]. Synthon I was retained in iso-nicotinamide co-crystals with succinic acid and 3-hydroxybenzoic acid (Figure 7.6) [14d]. In these structures the carboxylic acid interacts, as a strong proton donor, with a strong proton acceptor such as pyridine. 

Data on the electronic stmcture of Co and Co alloys may be found in [1.92]. Phase diagrams, crystal stmc-tures, and thermod)uiamic data of binary Co alloys may be found in [1.93]. 

Figure 4.38 (a) Phase diagram and (b) DSC curves (or a binary system with a co-crystallization point [55]... 

When preparing co-amorphous binary mixtures, the possibiUty of a co-crystal formation should be kept to mind. The saccharin example in Sect. 21.2.2 highlights the possibility of formation of an amorphous solid dispersion while attempting the preparation of a co-crystal using a small molecular weight excipient. One could easily think that the opposite, i.e., formation of a co-crystal upon attempting to prepare an... 

Figure 8.13 (a) Molecular diagrams of co-crystal components diphenylamine and benzophenone, (b) wireframe representation of a single hydrogen-bonded assembly in the co-crystal of benzophenone and diphenylamine and (c) sketch of the binary phase diagram for the mixture of diphenylamine and benzophenone. Point A (red) corresponds to the melting point of the submerged eutectic and path from A to B (blue) corresponds to the crystallization of the co-crystal from the intermediate eutectic phase. 

Melting point analysis and binary phase diagrams are well suited for the characterization of neat salt and co-crystal forms however, neat forms comprise only part of the solid form landscape of a given salt or co-crystal. 

Raman and IR spectroscopy have both been used extensively in the characterization of salts and co-crystals to identify functional groups corresponding to the individual components, to characterize proton transfer in the solid state and to confirm the presence of new binary phases based on unique IR/Raman fingerprints. Confirmation of the latter is achieved simply through comparison with the pure component spectra, as shown for an indomethacin-saccharin co-crystal in Figure 10.5. In this case, not only were the Raman carbonyl... 

Figure 12.1 Gibbs free energy functions (left column) and phase diagrams (right column) for binary systems with different thermodynamic properties of the co-crystal former B. The free energy functions are plotted for the separate liquid phases of A and B ((A)iiq + (B)iiq) as the reference state (AG = 0). Relative to this, the 1 1 mixture of liquid A and B ((A + B)iiq) is stabilized by 2Rrin(0.5) as a result of the mixing entropy. The melting points of A and AB are fixed and indicated by open circles, whereas the variable melting point of B is indicated by a solid circle. The liquidus curves in the phase diagrams are calculated based on the assumption of ideal behavior (Equations (12.1) to (12.3)).

The presence of a solvent in the crystallization process alleviates these problems, mainly by lowering the activation energy barrier for the rearrangement of the solute molecules into a new crystalline structure. Thus, the solvent has the classical function of a catalyst and will only affect the kinetics but not the thermodynamics of the transformation. This is valid as long as the solvent does not become part of the crystal structure, that is, is not forming a solvate with the solute. With respect to co-crystals this signifies that the existence of a thermodynamically stable binary compound is not a function of the solvent. 

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