10G. Carboxylic Anhydrides, Esters + Amides

Question 1

Carboxylic Anhydrides, Esters + Amides

Answer 1

• three more classes of carboxylic derivatives
• anhydrides are so reactive that they are rarely found in nature
• esters + amides are widespread in biology

Question 2

Anhydride

Answer 2

• a compound containing two carbonyl groups bonded to an oxygen atom

^O=C - O - C^=O

• to name anhydrides, ‘anhydride’ replaces ‘acid’ in the name of the carboxylic acid from which it is derived

Question 3

Ester

Answer 3

• a compound containing a carbonyl group bonded to an -OR group

^O=C - O - C

• names of esters are derived from the names of the parent carboxylic acids
• the alkyl group bonded to the oxygen is named first, followed by the name of the acid with -ate replacing -ic acid
• cyclic esters are known as lactones
• the most common method for the preparation of esters is fischer esterification

Question 4

Amides

Answer 4

• a compound containing a carbonyl group bonded to a nitrogen

^O=C - N

• amides are classified as primary (1^o), secondary (2^o) or tertiary (3^o) depending on the number of carbon groups bonded to the nitrogen
• when naming amides, -amide replaces -oic acid or -ic acid of the parent acid
• if the nitrogen atom of the amide is bonded to an alkyl or aryl group, the group is named + its location on nitrogen is indicated by N-
• two alkyl groups are indicated by N, N-di-
• cyclic amides are known as lactams
• a four membered lactam is essential to the functioning of the penicillin + cephalosporin antibiotics
• amides can be prepared in two ways
• one way is to treat a carboxylic acid with an amine + remove an -OH from the acid + an -H from the amione. This acid-base reaction forms an ammonium salt, which splits out water if heated to a high enough temperature, leaving the amide
• the more common way to prepare amides is to treat an anhydride with an amine

Question 5

Reactions

Answer 5

the most common reaction of each of the three functional groups is with compounds that contain either an -OH group, such as water or an alcohol, or an H-N group, such as ammonia or a primary or secondary amine

• the oxygen or nitrogen atom will add to the carbon of the carboxyl group + the hydrogen atom will add to the carbonyl oxygen to give a tetrahedral carbonyl addition intermediate. The intermediate then collapses to regenerate the carbonyl group + produce either a new carboxyl derivative or a carboxylic acid

Question 6

Hydrolisis Reactions

Answer 6

• a chemical decomposition involving the breaking of a bond + the addition of the elements of water
• carboxylic anhydrides, especially low molecular weight ones, react readily with water to produce two carboxylic acids. One of the C-O bonds breaks + -OH is added to the carbon + -H is added to the oxygen
• all esters are hydrolized very slowly even when in boiling water. However, when the ester is heated an aqueous acid or base, the reaction is much quicker
• hydrolisis of esters in aqueous acid is the reverse of fischer esterification
• the excess of water drives the equilibrium to produce the carboxylic acid + alcohol
• hydrolisis of an ester can also be carried out using a hot aqueous base such as NaOH(aq). This reaction is known as ‘saponification’
• there are two major differences between hydrolisis of esters in aqueous acid + aqueous base
• firstly, for hydrolisis of an ester in aqueous acid, the acid is required in only catalytic amounts. For hydrolisis in aqueous base, the base is required in stoichiometric amounts - one mole of base per mole of ester - because the base is a reactant, not just a catalyst
• secondly, hydrolisis of an ester in aqueous acid is reversible. Hydrolisis in aqueous base is irreversible because the carboxylate anion does not react with water or hydroxide ion
• amides require more vigorous conditions for hydrolisis in both acid + base
• hydrolisis of amides in hot aqueous acid produces a carboxylic acid + an ammonium ion
• the products of amide hydrolisis in aqueous base are a carboxylic acid salt + ammonia or an amine
• in each reaction, complete hydrolisis of the amide requires one mole of base or acid per mole of amide

Question 7

Reactions with Alcohols

Answer 7

• anhydrides react with alcohols + phenols to produce one mole of ester + one mole of carboxylic acid
• the reaction of an alcohol with an anhydride is a useful method for the synthesis of esters
• esters react with alcohols in an acid catalyzed equilibrium reaction known as ‘tranesterification’
• amides do not react with alcohols

Question 8

Reactions with Ammonia + Amines

Answer 8

• anhydrides react with ammonia + primary + secondary amines to form amides
• esters react with ammonia + primary + secondary amines to also form amides
• because carboxylic acids are easily converted to esters by fischer esterification + amides can be prepared readily from esters, this provides a simple path for converting carboxylic acids to amides
• amides do not react with ammonia or amines