Download Ch 17- Carboxylic Acids and their derivatives

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