Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 328

Brief Organic Chemistry

Summer 2004

Lecture Notes: 29 June

© R. Paselk 2004


Chemistry of Aldehydes and Ketones, cont.

Keto-Enol Tautomerization

Tautomers are constitutional isomersdiffering only in the positions fo hydrogen and a double bond relative to O, N, or S in a molecule.

Basically we can say that tautomers occur because of resonance stabilization of a carbocation on an α-carbon (a carbon adjacent to a carbonyl carbon) of a carbonyl group:

As a result of this stabilization we see an equilibrium between the keto and enol (en = double bond, ol = alcohol) forms of aldehydes and ketones:

Generally the keto form will predominate, and most enols quickly tautomerize to ketones with a negative free energy. Thus for acetone:

K = [enol]/[ketone] = [1-propene-2-ol]/[acetone] = (6 x 10-9)/1 = 6 x 10-9, asssuming 6 x 10-7 percent of acetone exists as the enol form,

and ΔG = -RT ln (6 x 10-9) = 47 kJ/ml

So acetone is favored by -47 kJ/mol!

Racemization: Tautomerization can lead to racemization of compounds with a chiral α-carbon. This occurs as the two chiral forms equilibrate via the achiral enediol intermediate:


Ketone Oxidation

Ketones can also oxidize via an enol intermediate. The important industrial synthesis of adipic acid, a precursor of nylon is shown below:


Catalytic Reduction (Hydration)

Both aldehydes and ketones can be reduced to alcohol via catalytic hydrogenation. However, this process is of limited utility since other groups, such as double bonds, may be reduced as well:


Metallic Hydride Reduction

Aldehydes and ketones can be reduced by another, more controlled strategy in which the carbonyl carbon is attacked by hydride ion. The two common hydride reagents, sodium borohydride and lithium aluminum hydride, are shown withthe hydride ion below:

Both reagents provide up to four hydride ions, which act as strong nucleophiles:

This process is often shown as a single reaction, with methanol and water numbered above and below the arrow.

Note tha the metal hydride reagent provides the hydrogen attached to the carbonyl carbon, as one would expect from a nucleophilic attack, while the second, alcoholic, hydrogen comes from water:

Lithium aluminum hydride reacts violently with water, methanol (MeOH) and other protic solvents to release hydrogen gas and hydroxides, sometimes explosively.


Grignard Reagents

Alkyl halides will react with elemental magnesium (magnesium metal) in ether to give organometallic compounds known as Grignard Reagents.

Where R = 1° - 3° alkyl or aryl. Note that the Mg inserts itself between the carbon and the halide! As an example:

Remember that magnesium is in the second group on the Periodic table, the alkaline earth metals, therefore it tends to give up two electrons very readily. Thus the Mg-C bond is quite polar, with the electrons residing closer to the carbon. The carbon thus becomes a nucleophile!

Let's look at how they can be used to synthesis alkanes from alkyl halides as an example:

Note that this is often written as a single equation with the two steps acknowledged with numbers:


The reaction of an aldehyde with a Grignard reagent gives a secondary alcohol, while ketones give tertiary alcohols:

If the stating material is formaldehyde, H2CO, then a primary alcohol results.

Synthesis from Grignard reagents is limited by the making of the Grignard itself. Thus Grignard reagents cannot be made from compounds having nucleophilic functional groups such as : -OH, -NH2, -SH, -COOH, -NO2, -CHO, -COR, -CN, OR -CONH2. In these compounds either the compound reacts with itself when attempting to prepare the Grignard, or the acidic protons react with the Grignard as it forms.

Notice that the formation of alcohols with Grignard reagents is an irreversible process. Once the reaction has occurred the added group is no longer capable of forming a good leaving group! Once again we see that C-C bonds are hard to break, and making them takes special conditions in the reactants.



Carboxylic Acids and their Derivatives


Carboxylic acids (-COOH): In IUPAC simple open chain carboxylic acids are named -oic acid. The carboxyl carbon is always numbered as C1. Notice that carboxyl groups take precedence over all other functional groups, so if there is a carboxyl group present its a carboxylic acid. Chains with carboxyl groups on both ends will be -dioic acids. Examples:


5-Chloro-4-(2-hydroxybutyl)-7-oxooctanoic acid


4-Bromooctanedioic acid

For rings with an attached -COOH a different system is used by IUPAC, and the compounds are named -carboxylic acid. Examples


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Last modified 29 June 2004