LXXXIV.—Freezing point curves for some binary mixtures of organic substances, chiefly phenols and amines

Abstract

If there is a summit, the composition of the mixture, which freezes at this maximum temperature, gives the formula of the compound produced. When the two constituent substauces form more than one compound, there is a branch of the composite curve corresponding with each, and when solidification commences in a mixture the composition of which lies within the limits of such a branch, the solid that separates is the compound to which this particular branch belongs. These types of composite freezing point curves have been experimentally realised for binary systems of various kinds. Thus, curves like that in Fig. ' 1 have been obtained for mixtures of inorganic salts

Making Co-CrystalsThe Utility of Ternary Phase Diagrams

“…Multicomponent solid phases of active pharmaceutical ingredients (APIs) have become increasingly important in the drug-development process, primarily because they offer an alternative to the physical properties of neat API solid phases. , Co-crystals are a subset of these and are defined as crystalline materials in which two or more components are neutral molecules and solids at room temperature. , Previously referred to as binary compounds or complexes, co-crystals were first identified in the 19th century by melt crystallization. − Currently, solution crystallization is the preferred method for co-crystal formation, particularly to obtain single crystals for structure analysis. , However, its apparent failure in a number of cases , has led to the use of solid-state grinding and more recently, so-called “solvent drop” grinding techniques as alternatives to solution crystallization. − These latter, empirical process developments are not well-understood and their success has lent an air of mystery to the preparative methodology of co-crystal formation. Thus, for example, Shan et al reported on the preparation of a number of co-crystals of cyclohexan-1,3 cis ,5 cis -tricarboxylic acid by grinding and attempted to rationalize their results by invoking the concept of kinetic enhancements due to orientational and conformational freedom at interfaces, molecular collisions, and formation of tiny seed crystals resulting from solvent addition.…”

“…3,4 Previously referred to as binary compounds or complexes, cocrystals were first identified in the 19th century by melt crystallization. [5][6][7] Currently, solution crystallization is the preferred method for co-crystal formation, particularly to obtain single crystals for structure analysis. 8,9 However, its apparent failure in a number of cases 10,11 has led to the use of solid-state grinding and more recently, so-called "solvent drop" grinding techniques as alternatives to solution crystallization.…”

Novel Application of an In Situ Raman Technique for a Co-Crystal Ternary Phase Diagram Determination

“…14 Melt crystallization was applied to achieve co-crystals/double salts for the last two centuries. 15,16 At present, solution crystallization 17 and solvent drop grinding 18 techniques were developed for co-crystal formation; however, the former is the favored pathway. 19 A potential drawback of the solution crystallization method is precipitating out a single constituent phase due to the diversification of process conditions, such as operation temperatures, ratios, and/or additional sequence of raw materials.…”

Structure of the 2:1 complex of phenol and urea

“…Introduction. Phase equilibrium studies of the phenolurea system by thermal analysis reveal the existence of a compound having 2:1 stoichiometry (Philip, 1903;Puschin & Konig, 1928;Palobekov & Bergman, 1966). Evidence has been adduced from IR spectra for the participation of all of the N and O atoms in hydrogen bonding (Chesnokov & Bokhovkin, 1966).…”