1. Ch 17- Carboxylic Acids and their derivatives

2. Introduction The Carboxyl group
One of the most widely occurring groups in chemistry and biochemistry
It is the parent group of a large family of related compounds called acyl compounds or carboxylic acid derivatives
Examples

3. Nomenclature Carboxylic Acids IUPAC nomenclature
Drop –e
Add –oic acid
The carboxyl carbon is assigned #1
Examples
Common Names:

4. Esters
To name an ester, you name the group attached to the oxygen as an alkyl group first then name the rest as the acid, dropping the –ic acid and adding –ate
Examples

5. Nomenclature Carboxylic Anhydrides IUPAC
Drop the acid from the name of the carboxylic acid and then add the word anhydride

6. Nomenclature Acyl Chlorides IUPAC
Drop the –ic acid, then add –yl chloride

7. Nomenclature Amides IUPAC Drop the –ic acid, then add –amide
Alkyl groups on the nitrogen atom of amides are named as substituents, and N- is used as the locant.

8. Nomenclature Nitriles IUPAC
Acyclic nitriles are named by adding the suffix –nitrile to the name of the corresponding hydrocarbon.
The Carbon of the nitrile is assigned the #1

9. Properties Polar Carboxylic Acid can form strong hydrogen bonds
Results in high boiling points
Appreciable water solubility

10. Synthesis of Carboxylic Acids
1) oxidation of Alkenes
2) oxidation of Aldehydes and primary alcohols
3) Oxidation of alkyl benzenes
4) Oxidation of a benzene ring

11. Synthesis of Carboxylic Acids
5) Oxidation of methyl ketones (haloform reaction)
6) Hydrolysis of cyanohydrins and other nitriles
7) Carbonation of Grignard reagents

12. Reactions of Carboxylic Acids
1) Nucleophilic Addition- Elimination at the Acyl Carbon
In the past, we have seen the nucleophilic addition to the carbonyl carbon
When the carbon is a carboxyl carbon, one of a carboxylic acid or a derivative, the addition is followed by an elimination and the return of the carbonyl group

13. Reactions of Carboxylic Acids
These two reactions have the same initial step
The initial step involves nucleophilic addition at the carbonyl carbon
With both groups of compounds, this initial attack is facilitated by the same factors:
The relative steric openness of the carbonyl carbon atom
The ability of the carbonyl oxygen atom to accommodate an electron pair of the C-O double bond

14. Reactions of Carboxylic Acids
After that initial step, the reactions differ.
The aldehyde/ketone usually accept a proton to form a stable addition product
In contrast, the acyl compound usually eliminates a leaving group to regenerate the Carbon-Oxygen double bond
This leads to a substitution product instead of an addition product

15. Reactions of Carboxylic Acids
Acyl compounds react as they do because they all have good, or reasonably good, leaving groups attached to the carbonyl carbon
An acid chloride, for example, can eliminate a chloride ion which is a very weak, stable base, thus a good leaving group.
Examples:

16. Reactions of Carboxylic Acids
Aldehydes and ketones do not perform this elimination because they would have to eliminate a hydride (H-) or alkanide (R-) species.
Both are very reactive and not good leaving groups

17. Order of Reactivity of Acyl Compounds
Series:
In general, the carboxylic acid derivatives can be synthesized from one another through this addition-elimination reaction
However, we must keep in mind the reactivity series
Less reactive acyl compounds can be synthesized from more reactive ones, but the reverse is usually very difficult and requires special reagents
Examples:

18. Synthesis of Esters
Fisher Esterifications- an acid-catalyzed condensation reaction between an alcohol and a carboxylic acid
Examples:
Mechanism:
Note: Oxygen in ester comes from alcohol

19. Reactions of Esters Base Promoted Hydrolysis of Esters: Saponification
Esters are made by acid-catalyzed hydrolysis of Carboxylic acids
They can be converted back to the carboxylic acid through a base catalyzed mechanism called saponification
Example:
Mechanism:

20. Lactones Lactones- a cyclic ester
They can be made from carboxylic acids with a hydroxyl group at the gamma or delta position
The reaction is acid catalyzed:
Lactones are hydrolyzed in aqueous base just like other esters back to the carboxylic acid

21. Decarboxylations of Carboxylic Acids
Decarboxylation- a reaction in which a carboxylic acid loses CO2
Example:
These reactions are not easy to perform and usually require special groups to be present to occur
One example is carboxylic acid with a ketone at the beta position

22. Decarboxylations of Carboxylic Acids
There are two reasons for the ease of this reaction:
1) The reaction can proceed through a six membered cyclic transition state to form an enol which tautomerises to the ketone
2) When the carboxylate anion decarboxylates, it forms a resonance-stabilized enolate anion