Ch 17- Carboxylic Acids and their derivatives

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

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

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

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

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

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.

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

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

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

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

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

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

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

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:

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

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:

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

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:

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

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

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