Sequence Rules for Specifying Configuration

Louis Pasteur (1822-1895) was born at Dole in the Jura region of France, the son of leather tanners. After receiving his doctorate from the Ecole Normale Superieure at age 25, his landmark discovery of tartaric acid enantiomers was made only 1 year later. Pasteur is best known for his studies in bacteriology and for his discovery of vaccines for anthrax and rabies. 

Pasteur made the surprising observation that two distinct kinds of crys tals precipitated. Furthermore, the two kinds of crystals were mirror images an were related in the same way that a right hand is related to a left hand. 

we would describe Pasteur s work by saying that he had discovered enantiomers. Enantiomers, also called optical isomers, have identical physical properties, such as melting point and boiling point, but differ in the direction in which their solutions rotate plane-polarized light. 

Test your knowledge of Key Ideas by using resources in ThomsonNOW or by answering end-of-chapter problems marked with A. 

Rule 1 Look at the four atoms directly attached to the chirality center, and assign priorities in order of decreasing atomic number. The atom with the highest atomic number is ranked first the atom with the lowest atomic number (usually hydrogen) is ranked fourth. 

Structural drawings provide a visual representation of stereochemistry, but a written method for indicating the three-dimensional arrangement, or configuration, of substituents at a chirality center is also needed. The method used employs a set of sequence rules to rank the four groups attached to the chirality center and then looks at the handedness with which those groups are attached. 

Called the Cahn-Ingold-Prelog rules after the chemists who proposed them, the sequence mles are as follows  

If a decision can t be reached by ranking the first atoms in the substituent, look at the second, third, or fourth atoms away from the chirality center until the first difference is found. A -CH2CH3 substituent and a -CH3 substituent are equivalent by mle 1 because both have carbon as the first atom. By mle 2, however, ethyl ranks higher than methyl because ethyl has a carbon as its highest second atom, while methyl has only hydrogen as its second atom. Look at the following pairs of examples to see how the rule works  

Multiple-bonded atoms are equivalent to the same number of single-bonded atoms. For example, an aldehyde substituent (—CH=0), which has a carbon atom doubly bonded to one oxygen, is equivalent to a substituent having a carbon atom singly bonded to two oxygens  

One additional point needs to be mentioned—the matter of absolute configuration. How do we know that the assignments of R and S configuration are correct in an absolute, rather than a relative, sense Since we can t see the molecules themselves, how do we know that the R configuration belongs to the levorotatory enantiomer of lactic acid This difficult question was finally solved in 1951, when an X-ray diffraction method for determining the absolute spatial arrangement of atoms in a molecule was found. Based on those results, we can say with certainty that the R,S conventions are correct. 

1 year later. Pasteur is best known for his studies in bacteriology and for his discovery of vaccines for anthrax and rabies. 

Rufe 2 If d deciiioij can t be leac heel by lankiri tlie brst atoois hi the substiliieuts, look at the second, third, or fourth atoms outward until a difference is found. 

Rule 3 Multiple-bonded atoms are equivalent to the same number of single-bonded atoms. Foi example  

Thomson Click Organic Interactive to assign absolute configurations using the Cahn Ingold-Preiog rules. 

Thomson Click Organic Interactive to manipulate three-dimensional models and assign RS designations. 

FIGURE 5.6 Drawings of sodium ammonium tartrate crystais taken from Pasteur s originai sketches. One of the crystais is right-handed and one is ieft-handed.  

FIGURE 5.8 Assigning configura- (a) tion to (a) (R)-(—)-lactic acid and (b) (S)-(+)-lactic acid. 

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