Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 328

Brief Organic Chemistry

Summer 2004

Lecture Notes: 6 July

© R. Paselk 2004
 
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Carboxylic Acids, cont.

Decarboxylation: Most carboxylic acids will decarboxylate at high temperatures, but not readily - they are really quite stable:

R-COOH Æ R-H + OCO

On the other hand, β-keto (2-oxo) acids decarboxylate very readily due to the added stability of the α-carbanion leaving group. we also see a specific geometrical enhancement due to the readily available six-membered ring intermediate shown below in the decarboxylation of 3-oxobutanoic acid (a metabolyte made in response to fasitng, diabetes, etc.) to make acetone:

Selective Reduction: Carboxylic acids may be reduced selectively catalytically and with Hydrides. Note that the products differ in each case.

Synthesis of Acid Anhydrides from Carboxylic Acids: Acid anhydrides are not readily prepared from the acids (rather, they are unstable, and tend to hydrolyze to the acids). Only acetic acid is available commercially. This synthesis can be accomplished by mixing the acid with a very powerful dehydrating agent such as phosphorus pentoxide (P2O5)

Synthesis of Amides from Acids: Amide synthesis from acids is difficult because the amine in the reaction will titrate the acid to the ionized form, which is now resistant to attack since it is now negatively charged. However, in biological systems such reactions are quite common, made possible by the incredible catalytic power of enzymes.

 

Carboxylic Acid Derivatives

Nomenclature

Acid Halides (-RCOX): Name as acids, but replace -ic acid with -yl halide, or -carboxylic acid with -carbonyl halide. Examples

Acid Anhydrides (RCOOCOR): Name as acids, but replace acid with anhydride. Examples

Amides (RCONH2): Amides containing -NH2 are named by replacing the -oic or -ic acid with -amide, whereas -carboxylic acid is replaced with -carboxamide. In ternal cyclic amides are called lactams. Examples

With N substituted amides the attachment to the nitrogen must be indicated. Thus CH3CONHCH3 is named N-Methylacetamide and CH3CONH(CH2CH3)2 is N,N-Diethylacetamide.

Esters (RCOOR'): IUPAC names esters by first naming the alkyl group on the oxygen followed by the carboxylic acid, but named as a salt (-ic becomes -ate). Internal cyclic esters are called lactones. Examples

 

Chemistry of the Carboxylic Acid Derivatives

Let's look at the relative reactivity of the various acid derivatives towards nucleophilic substitution:

Acid Chlorides > Acid Anhydrides > Esters > Amides.

In each case the carboxyl group is the same, so the differing reactivities must be due to differences in the leaving groups. The weakest base, that is the most stable basic ion, will be the best leaving group, in this case chloride ion, the conjugate base of a strong acid.

Note that each can be used to make all of the derivatives below it in the list.

Acid Chlorides (most reactions also apply to other Acid Halides): We saw in the last lecture that acid chlorides can be synthesized from acids by use of the strong nucleophilic reagent, thionyl chloride (SOCl2 - why does this reagent work? Note that two of the products, sulfur dioxide and hydrogen chloride are gases, which will drive the reaction to completion as they evolve.).

Most of the chemistry of acid halides occurs by nucleophilic acyl substitution reactions:

Hydrolysis (carboxylic acid synthesis): Water acts as a nucleophile to make acids:

Acid Anhydride Synthesis: Acid salts react with acid chlorides as nucleophiles to give acid anhydrides:

Alcoholysis (ester synthesis): Alcohols react with acid chlorides as nucleophiles to give esters:

Ester synthesis is usually carried out in the presence of an amine base which reacts with the HCl produced, preventing side reactions.

Aminolysis (amide synthesis): Amines react with acid chlorides as nucleophiles to give amides:

Note that an excess of amine equal to the amount of amide to be synthesized must added due to its reaction with the HCl produced in the reaction.

Acid Anhydrides: The synthesis of acid anhydrides from acid chlorides was covered previously. Acid anhydride chemistry is similar to that of acid chlorides: they can be used to make esters, acids, and amides. They are somewhat less reactive than acid chlorides, so the reactions go slower.

Although acetic anhydride is widely used to make esters and amides, the fact that only "half" of the molecule is used (the other half is the leaving group) dictates that acid chlorides are used in most other synthesis:

Ester Synthesis: Alcohols react with acid anhydrides as nucleophiles to give esters:

Amide Synthesis: Amines react with acid anhydrides as nucleophiles to give amides:


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Last modified 6 July 2004