1950

Conformational Analysis

Hermann Sachse (1862–1893), Ernst Mohr (1873–1926), Odd Hassel (1897–1981), Derek Harold Richard Barton (1918–1998)

One of the early triumphs of X-ray crystallography was the determination of the structure of diamond in 1918. As shown by German chemist Ernst Mohr, it turned out to be a three-dimensional network of tetrahedral carbon atoms (just the way van ’t Hoff had pictured them). The way that every atom in the lattice was bonded to its neighbors definitely explained diamond’s hard and inert nature—it’s as tied-down a structure as anyone could imagine.

If you trace out six-membered rings of carbons in the lattice, you get a characteristic one-end-up, one-end-down shape known to chemists as a “chair” conformation. (The six-membered ring with both ends pointing up is the “boat” conformer.) It was not widely appreciated that six-membered rings by themselves would behave the same way, although German chemist Hermann Sachse had tried to point this out in 1890. Norwegian physical chemist Odd Hassel showed, in 1943, that it was basically impossible for a single-bonded carbon ring like this to be flat: it had to have three-dimensional geometry.

Hassel went on to work out many of the details of six-membered ring conformations, which are extremely common structures across organic chemistry. Not all organic chemists were willing to believe that these structures were important under real reaction conditions, though, until 1950, when English organic chemist Sir Derek Harold Richard Barton explained many patterns of reactivity by showing how they influenced the products that could be formed. He drew many examples from steroid chemistry, which was being explored in detail and yielding results that could be explained only by paying close attention to the various ring geometries. Reagents have easier (or harder) paths in space to get to their reacting partners depending on what side of a flexible six-membered ring they approach from, for example.

Barton’s theories eventually won him great acclaim and, in 1969, a Nobel Prize. But he always referred to the 1950 publication explaining the link between molecular conformation and reactivity as his “lucky paper,” insisting that others could have figured out the same principles by closely studying the literature (and their own reactions!).

This three-dimensional model shows the conformation of a six-membered ring of carbon atoms.