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CHEM 221: Stereochemistry / Isomerism

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image by Sean MacEntee

Regioselective and Regiospecific
In regiochemistry, which is the study of the orientation of a reaction that deals with an asymmetrical reactant, two terms become very important. These terms are regioselectivity and regiospecificity of the reaction. Generally speaking, if a reaction takes place that produces two or more products and one of the products predominates, the reaction is said to be regioselective. On the other hand, if one of the products completely predominates (or nearly so), then the reaction is said to be regiospecific.

Chirality and Enantiomers
Chirality is the ability of a molecule or compound to exist in two nonsuperimposable forms that happen be mirror images of one another. One way in which we can demonstrate this is by using our right and left hand. Our hands are said to be chiral objects because they are mirror-images of one another and are nonsuperimposable. In a similar way, molecules are said to be chiral if they have a nonsuperimposable mirror image known as the enantiomer.

Optical Activity and Optically Active Molecules
Visible light is composed of regions of oscillating electric and magnetic fields that are perpendicular with respect to one another. Although light produced by the sun exists in its unpolarized form, we can polarize the light using a special device. This means that the polarizer device screens (or blocks) out all the electric and magnetic fields except the one that moves along one direction. This light is called plane polarized light. The interesting thing about plane polarized light is that chiral molecules have the ability to rotate the plane-polarized light some amount of degrees when the light travels through that molecule. A chiral molecule that rotates light is said to be optically active. If the molecule rotates the plane-polarized light in the clockwise direction, we call that rotation a dextrorotatory rotation. However, if the light rotates counterclockwise, we call that rotation levorotatory.

Racemic Mixtures
Recall that a chiral molecule is a molecule that contains two nonsuperimposible mirror-images of one another, each called an enantiomer. A racemic mixture is defined as a mixture of equal amounts of the two enantiomer forms of a given chiral molecule. One interesting aspect about a racemic mixture is that it is optically inactive, meaning it does not rotate plane polarized light. Actually to be more technical, it does rotate light but it rotates it in both directions by equal degrees and so the net rotation is zero.

Absolute Configuration
The absolute configuration gives us a way to differentiate between the two types of enantiomers of any chiral molecule. The first step in determining the absolute configuration is to determine where the stereogenic carbon is. The stereogenic carbon is the carbon that is attached to four different groups. Once you have determine the stereogenic carbon, you're next step is to assign the priority for the four different groups attached to the stereogenic carbon using the cahn-ingold-prelog system. If the top groups create an arrow that points counterclockwise, then the enantiomer has the S absolute configuration. On the other hand, if the arrow points clockwise, then the enantiomer has the R configuration.

Absolute Configuration Examples
In these several examples, our goal will be to determine the absolute configuration of the chiral molecule by locating the stereogenic carbon and using the Cahn-Ingold-Prelog priority system to prioritize the four different groups. The highest priority group is given a 1 while the lower priority group is given a 4.

Chemical Differences between Enantiomers
One common physical difference between any two enantiomers of a given chiral molecule is the ability to rotate plain polarized light. Remember, when one enantiomer rotates plane polarized light in one direction, the second enantiomer rotates plane polarized light in the opposing direction. Another important difference between any pair of enantiomers is that they interact differently with other chiral molecules.

Stereoisomers are isomers that have the same exact molecular formula and connectivity of atoms but their atoms are arranged differently in the three-dimensional space. Stereoisomers come in two categories: enantiomers and diastereomers. A diasteremoer is a stereoisomer that is not an enantiomer.

Meso Compounds
Simply put, meso compounds are molecules that contain stereogenic carbons (carbons attached to four different groups) and yet are overall achiral, which means that they do not rotate plane-polarized light and are optically inactive. Meso compounds are also superimposable.

Chiral Resolution
Chiral resolution is the process of separating the two different types of enantiomers found in a racemic mixture of some chiral molecule. This process involves reacting the racemic mixture with a different chiral molecule and thereby producing two different diastereomers. Since diastereomers differ from one another with respect to their physical properties, we can readily separate these two compounds using a process such as distillation.