unfavorable 1,3-diaxial interactions of cyclohexane. Consequently its twist-boat conformation is populated; in the corresponding tetramethyl structure, 3,3,6,6-tetramethyl-1,2,4,5-tetrathiane, the twist-boat conformation dominates. Historical background In 1890, , a 28-year-old assistant in Berlin, published instructions for folding a piece of paper to represent two forms of cyclohexane he called symmetrical and asymmetrical (what we would now call chair and boat). He clearly understood that these forms had two positions for the hydrogen atoms (again, to use modern terminology, axial and equatorial), that two chairs would probably interconvert, and even how certain substituents might favor one of the chair forms (). Because he expressed all this in mathematical language, few chemists of the time understood his arguments. He had several attempts at publishing these ideas, but none succeeded in capturing the imagination of chemists. His death in 1893 at the age of 31 meant his ideas sank into obscurity. It was only in 1918 that , based on the molecular structure of diamond that had recently been solved using the then very new technique of X-ray crystallography, was able to successfully argue that Sachse's chair was the pivotal motif. Derek Barton and Odd Hassel shared the 1969 Nobel Prize in Chemistry for work on the conformations of cyclohexane and various other molecules. Practical applications Cyclohexane is the most stable of the cycloalkanes, due to the stability of adapting to its chair conformer. This conformer stability allows cyclohexane to be used as a standard in lab analyses. More specifically, cyclohexane is used as a standard for pharmaceutical reference in solvent analysis of pharmaceutical compounds and raw materials. This specific standard signifies that cyclohexane is used in quality analysis of food and beverages, pharmaceutical release testing, and pharmaceutical method development; these various methods test for purity, biosafety, and bioavailability of products. The stability of the chair conformer of cyclohexane gives the cycloalkane a versatile and important application when regarding the safety and properties of pharmaceuticals. References Further reading Colin A. Russell, 1975, "The Origins of Conformational Analysis," in Van 't Hoff–Le Bel Centennial, O. B. Ramsay, Ed. (ACS Symposium Series 12), Washington, D.C.: American Chemical Society, pp. 159–178. William Reusch, 2010, "Ring Conformations" and "Substituted Cyclohexane Compounds," in Virtual Textbook of Organic Chemistry, East Lansing, MI, USA:Michigan State University, see and , accessed 20 June 2015. External links Java applets of all conformations from the University of Nijmegen Stereochemistry de:Konformation#Konformationen bei cyclischen Molekülen it:Cicloesano#Conformazione