Enantiomer Classification

[Theophrastus]

Quite recently, I've been reading through a (impudent and screwy) biochemistry text, and was surprised that in contrast to the D and L method, used to classify enantiomers, based on how they react to polarized light, some mysterious R and S method is currently being used alternatively. Sadly, the text provides no reference to this second system. What is the R and S method based upon? And what do R and S even stand for (in relation to isomers of course, as in relation to myself, they would stand for restless and something else, which ought not be said (think along the lines of vulgar language, for a general idea)) ? Some answers would be most appreciated. Once again I ask that if anyone knows the name of a good introductory text by biochemistry I would be most gracious. (Theo goes off to make some silane gas in the lab to burn his already dilapidated text in)

[GDG]

The d and l nomenclature defines optical isomers by the direction in which they rotate polarized light. R and S is what chemists use to define the actual structure of a molecule that has an asymmetric center.

 

Suppose you have a molecule of 2-chlorobutane:

 

CH3-C(H)(Cl)-CH2-CH3

 

That second carbon atom is asymmetric (chiral) because it has 4 different substituents. To figure out whether this molecule is R or S, first figure out which substituent has the lowest atomic number (H in this case). Mentally orient the molecule so you are looking at the chiral carbon, with the C-H bond facing directly away from you. Because carbon with 4 sp3 bonds adopts a tetrahedral configuration, you will see (mentally) the central carbon atom and the other three substituents arranged around it in a triangle. In this case, you'll have as substituents CH3, Cl, and CH2CH3.

 

Next, assign priority to each of the substituents based on the atomic number of the atom that is actually attached to the central chiral carbon atom. Clearly, chlorine get top priority in our example. For the methyl and ethyl groups, both have a carbon atom bound to the central chiral carbon, so to decide priority between them you look at which atom has a higher priority substituent of its own. In our example, the methyl group has only Hs, while the ethyl group has 2 Hs and a CH3: the carbon in that terminal CH3 give ethyl priority.

 

Finally, look back at your molecule and follow the substituents around in order of priority, highest to lowest (Cl, ethyl, methyl). If following the substituents takes you clockwise, the asymmetric carbon is called "R": if counter-clockwise, it is "S".

 

If the molecule has any other chiral carbon atoms, repeat for each one. It is not uncommon to see a chemical name preceeded by ®®(S)(R/S)®, showing the stereochemistry at each of several chiral centers. "R/S" of course means that you have a mixture of both isomers.

 

Of course, whether the molecule is R or S does not tell you whether it is d or l. As to what R and S stand for, I assume they derive from the Latin for right and left.

[Kaeroll]

Nice guide, GDG. Rep +

 

The rules for R/S are known as the Cahn-Ingold-Prelog rules and are used habitually by chemists. Much nicer than the empirically derived D/L system. The R/S tags derive from the Latin rectus and sinister, meaning right and left. The first years I tutor found it helpful to remember that S is anticlockwise, as you draw the letter S in an anticlockwise direction. More detail on the CIP rules can be found in pretty much any undergrad chemistry text; if your library has a copy of Clayden, Greeves, Warren and Wothers' organic text it's usually quite thorough on such things.

 

As for an introductory biochemistry text I'm not too sure, but if you're taking biochem courses, Berg (et al) is quite accessible albeit a little challenging.

[Fuzzwood]

Or, very simple: the R from right

[UC]

I like pretty pictures, how about you?

 

On the left I have a typical drawing of 2-chlorobutane, which says nothing about it's chirality. I've labelled it as racemic, which means a 1:1 mix of the enantiomers. Many reactions produce racemates of enatiomeric products, but especially with pharmaceuticals (where only one enantiomer is biologically active), finding reactions that produce more of one than the other or only one of the two is important.

 

Then, I've added the implicit hydrogens in, showing how all the carbons have a tetrahedral arrangement of bonds around them. The straight lines are in the plane of the screen while the solid lines project out toward you and the dashed lines project back. With this configuration visible, you can see the two non-superimposable forms of 2-chlorobutane.

 

I then inverted everything (basically, looking at it from the other side) on the right enantiomer so that the hydrogen was pointing back into the page, as it already was on the left. Then I simplified the drawings, but maintained the relative positions of the the three substituents and labelled them according to priority. As you can see, motion around the stereocenter from highest to lowest priority defines the enantiomer.

 

Of course, the lowest priority substituent doesn't have to be hydrogen. For 1-bromo-1-chloro-1-fluoroethane, the lowest priority substituent would be a methyl group, which would be treated the same way as hydrogen was above. For iodobromochlorofluoromethane, fluorine would be lowest priority, etc.

Edited May 24, 2009 by UC

[UC]

Also, see here for some information on the priority system: http://en.wikipedia.org/wiki/Cahn%E2%80%93Ingold%E2%80%93Prelog_priority_rules

[Theophrastus]

Thanks for all the links, and the clear, and wonderfully elaborate explanations; I'm really at a loss for words (I have laringitis ) However, looking back, and attaining a bit of work on chirality, I realised another question, that I should have asked: Let's say we have the molecule 2, 4 chlorohexane, instead of simply 2 chlorobutane. Here you would have 2 stereocenters, in place of one. In such an event, in listing the R and S, I would assume that, the listings would be done numerically; first the second carbon, then the fourth. Is this assumption correct?

[GDG]

Yep. It is common to see designations such as 2S,4R-2,4-dichlorohexane.

[Jeju]

I believe u're satisfied with all contributions. Find a text on STEREO CHEMISTRY to broaden your knowledge more on this topic.