What Is Melting Points

Most organic compounds have melting points below 200 ºC. Some decompose before melting, a few sublime, but a majority undergo repeated melting and crystallization without any change in molecular structure. When a pure crystalline compound is heated, or a liquid cooled, the change in sample temperature with time is roughly uniform. However, if the solid melts, or the liquid freezes, a discontinuity occurs and the temperature of the sample remains constant until the phase change is complete. This behavior is shown in the diagram on the right, with the green segment representing the solid phase, light blue the liquid, and red the temperature invariant liquid/solid equilibrium. For a given compound, this temperature represents its melting point (or freezing point), and is a reproducible constant as long as the external pressure does not change. The length of the horizontal portion depends on the size of the sample, since a quantity of heat proportional to the heat of fusion must be added (or removed) before the phase change is complete. Now it is well known that the freezing point of a solvent is lowered by a dissolved solute, e.g. brine compared with water. If two crystalline compounds (A & B) are thoroughly mixed, the melting point of that mixture is normally depressed and broadened, relative to the characteristic sharp melting point of each pure component. This provides a useful means for establishing the identity or non-identity of two or more compounds, since the melting points of numerous solid organic compounds are documented and commonly used as a test of purity. The phase diagram on the right shows the melting point behavior of mixtures ranging from pure A on the left to pure B on the right. A small amount of compound B in a sample of compound A lowers (and broadens) its melting point; and the same is true for a sample of B containing a little A. The lowest mixture melting point, e, is called the eutectic point. For example, if A is cinnamic acid, m.p. 137 ºC, and B is benzoic acid, m.p. 122 ºC, the eutectic point is 82 ºC. Below the temperature of the isothermal line ced, the mixture is entirely solid, consisting of aconglomerate of solid A and solid B. Above this temperature the mixture is either a liquid or a liquid solid mixture, the composition of which varies. In some rare cases of nonpolar compounds of similar size and crystal structure, a true solid solution of one in the other, rather than a conglomerate, is formed. Melting or freezing takes place over a broad temperature range and there is no true eutectic point.

An interesting but less common mixed system involves molecular components that form a tight complex or molecular compound, capable of existing as a discrete species in equilibrium with a liquid of the same composition. Such a species usually has a sharp congruent melting point and produces a phase diagram having the appearance of two adjacent eutectic diagrams. An example of such a system is shown on the right, the molecular compound being represented as A:B or C. One such mixture consists of α-naphthol, m.p. 94 ºC, and p-toluidine, m.p. 43 ºC. The A:B complex has a melting point of 54 ºC, and the phase diagram displays two eutectic points, the first at 50 ºC, the second at 30 ºC. Molecular complexes of this kind commonly have a 50:50 stoichiometry, as shown, but other integral ratios are known. In addition to the potential complications noted above, the simple process of taking a melting point may also be influenced by changes in crystal structure, either before or after an initial melt. The existence of more than one crystal form for a given compound is called polymorphism.

                                                    Polymorphism

Polymorphs of a compound are different crystal forms in which the lattice arrangement of molecules are dissimilar. These distinct solids usually have different melting points, solubilities, densities and optical properties. Many polymorphic compounds have flexible molecules that may assume different conformations, and X-ray examination of these solids shows that their crystal lattices impose certain conformational constraints. When melted or in solution, different polymorphic crystals of this kind produce the same rapidly equilibrating mixture of molecular species. Polymorphism is similar to, but distinct from, hydrated or solvated crystalline forms. It has been estimated that over 50% of known organic compounds may be capable of polymorphism.

The ribofuranose tetraacetate, shown at the upper left below, was the source of an early puzzle involving polymorphism. The compound was first prepared in England in 1946, and had a melting point of 58 ºC. Several years later the same material, having the same melting point, was prepared independently in Germany and the United States. The American chemists then found that the melting points of their early preparations had risen to 85 ºC. Eventually, it became apparent that any laboratory into which the higher melting form had been introduced was no longer able to make the lower melting form. Microscopic seeds of the stable polymorph in the environment inevitably directed crystallization to that end. X-ray diffraction data showed the lower melting polymorph to be monoclinic, space group P2. The higher melting form was orthorhombic, space group P2₁2₁2₁.
Polymorphism has proven to be a critical factor in pharmaceuticals, solid state pigments and polymer manufacture. Some examples are described below.

		Acetaminophen is a common analgesic (e.g. Tylenol). It is usually obtained as monoclinic prisms (upper picture) on crystallization from water. A less stable orthorhombic polymorph, having better physical properties for pressing into tablets, is shown beneath the first. Quinacridone is an important pigment used in paints and inks. It has a rigid flat molecular structure, and in dilute solution has a light yellow color. Three polymorphs have been identified. Intermolecular hydrogen bonds are an important feature in all off these. The crystal colors range from bright red to violet. The anti-ulcer drug ranitidine (Zantac) was first patented by Glaxo-Wellcome in 1978. Seven years later a second polymorph of ranitidine was patented by the same company. This extended the licensing coverage until 2002, and efforts to market a generic form were thwarted, because it was not possible to prepare the first polymorph uncontaminated by the second. The relatively simple aryl thiophene, designated EL1, was prepared and studied by chemists at the Eli Lilly Company. It displayed six polymorphic crystal forms, pictures of which are shown on the left. Polymorphs of EL1 Example Color/Shape Crystal Form Melting Point I yellow prisms monoclinic P21/n[14] 110 ºC II reddish plates monoclinic P21/n[14] 113 ºC III orange needles monoclinic P21/c[14] 115 ºC IV yellow needles triclinic P1[2] rearranges to VI V orange plates orthorhombic Pbca[61] rearranges to I VI red prisms triclinic P1[2] 106 ºC

A common example of changes in polymorphism is shown by chocolate that has suffered heating and/or long storage. Over time, or when it resets after softening, it may have white patches on it, no longer melts in your mouth, and doesn't taste as good as it should. This is because chocolate has more than six polymorphs, and only one is ideal as a confection. It is created under carefully-controlled factory conditions. Improper storage or transport conditions cause chocolate to transform into other polymorphs.
Chocolate is in essence cocoa mass and sugar particles suspended in a cocoa butter matrix. Cocoa butter is a mixture of triglycerides in which stearoyl, oleoyl and palmitoyl groups predominate. It is the polymorphs of this matrix that influence the quality of chocolate. Low melting polymorphs feel too sticky or thick in the mouth. Form V, the best tasting polymorph of cocoa butter, has a melting point of 34 to 36 ºC, slightly less than the interior of the human body, which is one reason it melts in the mouth. Unfortunately, the higher melting form VI is more stable and is produced over time.

Polymorphs of Chocolate

Polymorph	Melting Point	Comments
I	17.4 ºC	Produced by rapid cooling of a melt.
II	23.4 ºC	Produced by cooling the melt at 2 ºC/min.
III	26 ºC	Produced by transformation of form II at 5-10 ºC.
IV	27 ºC	Produced by transformation of form III by storing at 16-21 ºC.
V	34 ºC	Produced by tempering (cooling then reheating slightly while mixing).
VI	36-37 ºC	Produced from V after spending 4 months at room temperature.