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Chemistry 2131:
Organic Chemistry for the Life Sciences (3)

Reactions of Carboxylic Acids

• an extension of the property of carboxylic acid acidity is that they react with strong bases such as NaOH or KOH to give water soluble salts
• as mentioned last day, there is an effect on solubility. The presence of the full charge (even though it is shared by both oxygen atoms) increased the polarity and hence water solubility of the molecules. For instance, where benzoic acid is only slightly soluble in water, sodium benzoate has a solubility of 60 g/100 ml.
• carboxylic acids can also react with ammonia to give ammonium salts
• to name the salts of carboxylic acids, the cation is named first as usual then the carboxylate is named

2. Fischer Esterification:

• most of the chemistry of carboxyl groups that we will look at will come when we look at the carboxylic acid derivatives, but shades of things to come, is the Fischer esterification reaction.
• an ester is functional group which contains a carboxyl group but the hydroxyl H is replaced with an alkyl group
• esters are often prepared by the reaction of carboxylic acids with alcohols under acidic conditions
• these reactions are reversible (as you will appreciate better in a couple of days). So, the position of the equilibrium determines how far to completion the reaction proceeds
• let's look at the mechanism. It is acid catalysed. The first step is the protonation of the carbonyl carbon on the carboxyl group. This makes the carbonyl carbon more electron deficient making it more susceptible to nucleophilic attack
• a lone pair on the alcohol oxygen attacks the carbonyl carbon pushing the electrons back up onto the carbonyl oxygen. This generates a new oxonium ion.
• the oxonium ion is deprotonated by water. Thus, a tetrahedral carbonyl addition intermediate is generated
• this is the point where this reaction looks a little different. One of the hydroxyl groups becomes protonated from a hydronium ion.
• in the final step, water removes a proton from the other hydroxyl, the electrons come down to form a pi bond and the water group is pushed off.
• the product is an ester
• the reaction is fully reversible. A good exercise would be to figure out the reverse reaction

3. Decarboxylation of Beta-keto Acids:

• another reaction of carboxylic acids which had important implications for biology is the decarboxylation of beta-keto acids
• first of all, what is a beta-keto acid? This is a little tricky. The carbon immediately adjacent to the carboxyl carbon is called the alpha carbon. The one next to it is the beta carbon. So, a beta keto acid is a carboxylic acid that has a keto group (a carbonyl) on the number 3 carbon.
• these are the only carboxylic acids that decarboxylate under moderate conditions (mild heat or enzyme catalysis)
• let's look at 3-oxobutanoic acid. The mechanism involves a cyclic six-membered transition state. If you draw the carboxylic acid acid with the C-OH bond up and the C=O to the right, the CH₂ group to theleft, and the carbonyl group up, then you can more easily appreciate how this works.
• the carbonyl oxygen picks the proton off of the hydroxyl oxygen, the electrons from the O-H bond come down to form a new pi bond. The C-C bond breaks and makes a new C=C. This gives us an enol.
• the enol tautomerizes into a ketone.

4. Structure and Nomenclature of Carboxylic Acid Derivatives:

• derivatives of carboxylic acids all have a carbonyl group with an electronegative atom attached to it. In a carboxylic acid itself this electronegative atom is the oxygen of a hydroxyl group.
• the first group we'll look at is the acid halides. These molecules all have a carbonyl group attached to a halide atom, usually a chloride group.
• they are named by dropping th "ic acid" from the carboxylic acid and replacing it with "-yl halide". For example ethanoyl chloride, benzoyl chloride...
• next there are the carboxylic acid anhydrides. The functional group is an oxygen atom with 2 acyl groups attached to it. It is as though you put to carboxylic acids together and got rid of water.
• these can be either symmetrical anhydrides (both sides the same) or asymmetrical (two different R groups).
• to name anhydrides, one names the carboxylic acid, drops the word acid, and replaces it with anhydride. If only one acid is named, it is assumed to be symmetrical. Example acetic anhydride, benzoic anhydride.
• interestingly you can get cyclic anhydrides
• next there are the esters. You already know what these are, the hydroxyl group is replaced with a -OR group.
• to nae these you name the alkyl group first, then the carboxylate. For example isopropyl benzoate, ethyl ethanoate
• cyclic esters are possible. These are called lactones. To name them, the "ic acid" is dropped and replaced with "-olactone". For example, 4-butanolactone. Note that the carbonyl carbon is number 1, the 4 carbon in this case had the hydroxyl group
• finally we have the amides. This consists of a carbonyl carbon bonded to an -NH₂ group.
• these are named by dropping the "oic acid" ending and replacing it with "-amide". For example, benzamide.
• if the nitrogen has one or more alkyl groups on it, the group is named and its position is indicated with an N-. For example, N-methylethanamide, or N,N-dimethylmethanamide.
• cyclic amides are also possible, and are called lactams. They are named exactly as lactones, replacing the ending lactone with lactam.