You can familiarise yourselves with these terms using the following glossary for non-specialists:
Handedness (or chirality) is the same property describing molecules as describing hands: left and right. You can’t put a left glove on your right hand.
Racemisation is the process of converting a molecule of one handedness (left or right) to the opposite handedness, and it must involve some kind of breaking and putting back together. The result is a racemate, a mixture of equal amounts of molecules with left and right handedness.
Resolution is the process of separating molecules of one handedness from molecules of the other from a mixture of the two.
Stereochemistry is the branch of chemistry dealing with the 3D shape of molecules and their handedness.
Stereochemistry is even for today’s chemists a bit of a headache: organic chemists are familiar with the concepts of molecular chirality, but to a large extent unfamiliar with chirality on the macroscopic scale. Crystallisation scientists and crystallographers on the other hand are comfortable with the latter. It all began in 19th century France.
Ghislaine Vantomme and Jeanne Crassous recently published a good account on the intense activity in the field of stereochemistry that took place in that era. The report (free to read here) focuses on the work of Louis Pasteur in the area of molecular and crystal chirality, viewed from the perspective of the modern chemist.
But at the time it was all discussed in terms of crystalline properties and solution properties. No use of molecular structure. Pasteur uncovered racemisation and resolution 20 years before the tetrahedral structure of carbon was discovered. The story of his discovery is the kind of textbook novelty that gets me excited, but sadly few chemists remember.
I wanted to read Pasteur’s account for myself, so I went on a bit of a quest in search of the original publications. Fortunately, a list of them is available from the Pasteur foundation, together with links to the texts. The only problem is they are in French.
For this reason, I will only endeavour to discuss one of them: Transformation des acides tartriques en acide racémique – Découverte de l’acide tartrique inactif. Nouvelle méthode de séparation de l’acide racémique en acides tartriques droit et gauche C. R. T. 37 (1853) 162-166.
It is worth noting that Pasteur had been working in the area for 5 years, and his (or someone else’s) enthusiasm is obvious in this communication letter: L. Pasteur, dans une Lettre adressée à M. Biot, annonce qu’il est parvenu à transformer l’acide tartrique en acide racémique C. R. T. 36 (1853) 973, where the text is italicised.
So how does his article sound to the modern chemist? Let’s see. This is technical, so feel free to skip to number 8 on the list. If you’re a French-speaking chemist and disagree with my translation, please let me know in the comments. I’d like to know better!
- Chinconine tartrate (the L-(+) natural form) is gradually heated to convert to chinconicine (it looks to me like ring opening by hydride shift) tartrate. Prolonged heating at 170 °C results in the alkaloid decomposing (forming some tarry material called quinoidine), but more importantly results in some of the racemic tartrate being formed. Treating with calcium chloride in the workup allows for isolation of racemic calcium tartrate.
- The alkaloid salts are used as the free acid decomposes at such temperature. The transformation also works with a ‘tartrate ether’ which does not have another optically active component beside the tartrate.
- The racemic acid isolated has identical physical and chemical properties to an authentic sample, and furthermore can be separated into left and right tartaric acids (only later does he mention how he achieved this).
- It follows that the right tartaric acid was converted artificially into the left.
- The experiment was repeated with left tartaric acid to give racemic acid under the same conditions. The conclusion is immense: a collection of dissymetric molecules can be converted to their inverse solely under heating; and the racemic is a mixture of the two isomers.
- Another product was discovered in the tarry residue: inactive tartaric acid, what we now call meso. Pasteur extended the reaction time, and this time he kept the filtrate after removing the racemic calcium tartrate. After 24 h he had crystallised the inactive calcium tartrate.
- Pasteur concluded the meso was formed from the racemic, and like a good scientist, he heated the isolated racemic to prove he could form the meso without starting from optically active materials.
- The most exciting part: “le sel double de soude et d’ammoniaque. Les cristaux qui prennet naissance sont de deux sortes; je sépare manuellement ces cristaux d’après le caractère de leur forme hémiédrique : il n’y a rien là de général. Ce dédoublement s’offre ici comme un accident.”
In my translation: “the double sodium and ammonium salt. The crystals prepared are of two kinds; I separated them manually using the form of their hemihedral shape: this is nothing but particular. This resolution opportunity is an accident.”
- And then in the summary he drops another bomb discovery: resolution by crystallisation of diastereomeric salts: he preferentially crystallised left tartrate of cinchonine from the racemate solution.
This was an immense discovery. Pasteur was aware of it, but he was even more aware of how lucky he had been to stumble on just the right compound to provide him with the experimental results to power his logic work.
The lack of experimental detail is shocking by modern standards. In spite of this, the science is solid and many of the same experiments are the foundation for chemical enquiry. Science was an honourable gentlemen’s enterprise, and there was nothing wrong with that. What I loved, however, was how reasoning and emotion (yes, look at all the exclamation marks in the original) were well at home in his scientific writing. Emotion, when existent in today’s scientific writing, is often weak and artificial, and reasoning restrained and implied. And you certainly don’t see many ‘I’s.
As a final note, Vantomme and Crassous reference the discovery of the meso form (entry 6 on my list) to 1858. I don’t have access to this material, but according to my understanding this discovery was reported in 1853.
You are free to do your own digging if you would like, but the important message is this: there is no better reference than the original report. Try and find it!