Fusion methods vs. Kofler-Mikro-Methoden

Abstract

The use of the hot stage microscope has received a tremendous impetus during the last dozen years almost entirely through the inspiration and efforts of the Ko/ler's. Their development of techniques and the application of these techniques to the identification and characterization of organic compounds is an outstanding contribution not only to microchemistry but to more general research methods in organic and physical chemistry.The study of fusible compounds, usually organic, as a function of temperature Under the microscope is called simply "Mikro-lV [ethoden" to designate the fields of interest of the Ko/ler's and their co-workers whereas the term "fusion methods" has been used in the United States to designate the same fields of interest. The title of this report should not in any way indicate anything other than good-natured rivalry between the two schools of thought. Rather the title was chosen to indicate that there are differences in technique and application worthy of closer study. By such a discussion an appreciation of the overall field of the applications of the microscope to the study of fusible compounds and their mixtures may be enhanced.Fusion methods were developed in the United Sta~es somewhat later than the"Mikro-Methoden" although apparently independently. Since these two schools of thought developed along different lines with different results it is interesting to make a systematic comparison. Both groups were familiar almost from the start with the publications of Otto Lehmann who, in his volume titled "Die Kristallanalyse" dated 18911, described many of these techniques including the mixed fusion (Kontaktmethode) for qualitative determination of the phase diagram (as a basis for the determination of identity or lack of identity of two compounds).

Cocrystals of Lamotrigine Based on Coformers Involving Carbonyl Group Discovered by Hot-Stage Microscopy and DSC Screening

“…The microscopic observation of thermally treated binary systems was initially described by Lehmann and later on refined by Kofler . This method, also commonly called contact method by McCrone, is nowadays widely used for fast cocrystal screens of binary system. On the basis of known melting points of the cocrystal components, the Kofler contact method provides information about the formation of new solid phases or eutectic mixtures formation.…”

2,4,7-Trinitrofluorenone as Reagent for Microscopic Fusion Analysis

“…As carried on by the Koflers in Germany, identification of an unknown compound depends upon the measurement of the refractive index of its melt and the eutectic temperatures with two reference compounds (1). Fusion studies in this country (2) have proceeded along different lines. Most of the work has been directed toward detailed descriptions of the fusion behavior of individual compounds which serve for identification, alone or supplemented by crystallographic data.…”

Identification of Synthetic Fibers by Micro Fusion Methods

“…The limitation and precautions for these methods have been studied (5). Nitration of organic compounds such as phenoldisulfonic acid (4), 2,4-xylenol (7), and 3,4-xylenol (3) in the presence of sulfuric acid has been used.…”

“…Micro fusion methods have heretofore been applied only to monomeric systems. The general technique was originally developed by the Koflers in Germany (3), and extended and promoted in this country mainly through the efforts of McCrone (5) and coworkers. The identification of an unknown is based upon the use of a hot stage and microscope for determining (a) the melting point of the compound, (6) the eutectic melting point of the compound with a reference compound, (c) the refractive index of the melt, and (d) characteristic behavior observed during the heating and cooling of the compound.…”