LECTURE NOTES # 5

I. Aldehydes and ketones - review the chemical reactions of these two families since they behave similarly and undergo many of the same reactions.

1. Review nucleophilic addition reactions. As the name implies, a nucleophilic addition reaction involves the addition of a nucleophile to the carbonyl group. Some possibilities are: hydroxide ion; hydride ion; carbon anions; water; ammonia; and alcohols. The general mechanism of nucleophilic addition is the nucleophile forms a new bond to the carbonyl-group carbon, the carbon-oxygen double bond breaks, and a proton bonds to the oxygen. An electron pair from the nucleophile attacks the electrophilic carbonyl carbon, pushing an electron pair from the carbon-oxygen double bond out onto oxygen. The carbonyl carbon rehybridizes from SP² to SP³. Protonation of the anion resulting from nucleophilic attack yields the neutral alcohol addition product. Review base- and acid-catalyzed hydration reactions, noting the initial point of attack of base and acid are different.

Ammonia and primary amines add to aldehydes and ketones to yield imines, which contain the carbonyl carbon double bonded to nitrogen rather than to oxygen. Imines are formed by the nucleophilic addition to the carbonyl group by the nucleophilic amine, followed by the loss of water from the amino alcohol addition product. Later we will see that the imine can be converted to an amino acid.

2. Review the general mechanism of a carbonyl condensation reaction. One carbonyl component with an alpha-hydrogen atom on the alpha-carbon, the carbon bonded to the carbonyl carbon, is converted by base into its enolate ion. This enolate ion acts as a nucleophilic donor and adds to the electrophilic carbonyl group of the acceptor component. Protonation of the tetrahedral alkoxide ion intermediate gives the neutral condensation product and regenerates the base. This type of reaction is important in many biological condensation reactions, recall the formation of citric acid to begin the Krebs Cycle in cellular respiration and the biosynthesis of steroids, fats, and other lipids.

II. ISOMERS

1. Constitutional - different connections and free rotation of single bonds.

(1) structural - several types such as skeletal, functional group, and positional.

(2) conformational - free rotation of single bonds, ethane and cycloalkanes.

2. Configurational - different geometry, cannot be interconverted without bond breakage.

(3) geometric isomers - cis/trans, carbon to carbon double bond.

(4) enantiomers - sometimes termed optical or stereo-isomers, occur in pairs as D or (+) and L or (-), + and - refer to direction of rotation of plane polarized light, D and L refer to specific arrangement using glyceraldehyde as the model molecule, these two forms are not superimposable on their mirror image, require the presence of one or more chiral carbon atoms; chiral carbons have four different substituent groups bonded to them. Write the structural formula for D- and L-glyceraldehyde and learn them.

(5) meso compounds - have 2 or > chiral carbons, but show mirror images, with a plane of symmetry, an example is meso-tartaric acid, which contains two chiral carbons each with a hydrogen, hydroxyl, and carboxyl functional group. Write out the structure and note the plane of symmetry. Also note that these molecules are different from enantiomers, and extend the concept of D- and L-forms.

(6) diastereomers - have non-mirror images, contain 2 or > chiral carbons, somewhat like the relationship between hand and foot, rather than right and left hand. Note that these molecules also extend the concept of D- and L-forms.

(7) anomers - based on ring closure via hemiacetal or hemiketal formation, ring closure forms a new chiral carbon and the two resulting forms are termed alpha and beta. By definition alpha shows the hydroxyl on C₁ down or trans to C₆ and beta shows the hydroxyl up or cis to the same carbon. Note this is an intramolecular reaction between the functional groups of alcohol and aldehyde, to produce an ether of the heterocyclic type i.e. a pyran ring. Write out the structure of beta-D-glucose, and be sure that you can show the formation of these two anomers. Note that these molecules also extend the concept of D- and L-forms.

3. Use this outline as a guide to organizing your study of the importance of the shape of molecules. These concepts and terms will be applied to many biological molecules, and it is of interest to note that all cells use D-sugars rather than L-sugars or a mixture; all cells use L-amino acids rather than D-amino acids or a mixture; all cells use phosphatides, among the lipids, in the L-form rather than the D-form or a mixture. What is the advantage, to cells, of using only one form of a molecule that is able to exist in two forms? Remember the term racemic mixture, which contains equal amounts of an enantiomeric pair, indicates that from a chemical point of view both forms are equally possible.