Acid halides, acid anhydrides, esters, amides, and nitriles are the most significant carboxylic acid derivatives.

• An acyl group is linked to a halogen, commonly Cl, in acid halides.

• Acid halides are called by substituting the parent acid's -ic acid with -yl halide.

• Two acyl groups are linked to an O atom in an acid anhydride.

Acid anhydrides are called by substituting the term anhydride for the word acid in the parent acid.

• The name of the alkyl or aryl group linked to the O atom comes first, followed by the name of the parent acid in which -ic acid is substituted by -ate.

• Lactones are cyclic esters that include the acyl carbon and the O atom.

An acyl group is linked to a N atom in amides.

• If the N atom has one or two groups attached to it, the groups are called after the designator N-, and the parent acid's -ic acid is substituted by -amide.

Lactams are cyclic amides with an acyl carbon and a N atom in the ring.

• The N atom in amides is sp2 hybridized as a result of a third important resonance contributing structure that forms a double bond between the acyl C and N atoms.

The acyl C!N bond has a partial double bond nature and a significant rotation barrier.

• The C atom of the amide acyl is less electrophilic than the C atoms of the other carboxylic acid derivatives.

• The N atom of amide is not basic.

• Nitriles: refer to having a cyano group bonded to carbon. Nitriles are named by replacing -oic acid of the parent acid with -onitrile

Imides are distinguished from amides by the presence of two acyl groups connected to the same N atom.

• Imides are significantly more acidic than amides due to the delocalization of the negative charge of the N-deprotonated anion over both carbonyls.

• Imides (pKa 8–10) dissolve in aqueous NaOH by forming water-soluble sodium salts, as shown in the image attached.

Because the imide anion is stabilized by delocalization of the negative charge onto the two carbonyl oxygens, imides are more acidic than amides.

Sulfonamide Acidity (as shown in the image attached) Sulfonamides (pKa 9–10) create water-soluble salts when dissolved in aqueous NaOH.

• The sulfonamide anion is stabilized by negative charge delocalization onto the two O atoms.

• Nucleophilic acyl substitution is a common reaction in carboxylic acid derivatives.

• A strong nucleophile adds straight to the electrophilic acyl carbon, causing the C bond to break "O p bond is formed, resulting in a tetrahedral carbonyl addition intermediate.

Acid can catalyze the reaction with weaker nucleophiles, in which case the acyl O atom is protonated first.

• The tetrahedral intermediate collapses due to the loss of a leaving group and the reformation of the C "The op bond.

Anions that are more stable are better anionic leaving groups.

• The ability to leave the group grows in the following order: H2N2, RO2, O' R!C!O2, Cl2.

• The order of stability conferred by resonance is acid chloride, acid anhydride, ester, and amide.

• The reactivity of carboxylic acid derivatives increases in the following order: amide, ester, acid anhydride, acid chloride.

Acid chlorides and acid anhydrides readily react with water to form carboxylic acid and HCl, or two molecules of carboxylic acid, respectively.

• The reaction is catalyzed by acid, although it will take place even if no acid is introduced since the acid created in the reaction catalyzes the process.

The hydrolysis of esters and amides requires acid or base, although acid halides and acid anhydrides need not.

An acid's job is to improve the electrophilicity of the carbonyl and protonate the leaving group to assist its exit.

• – HO2 is a powerful enough nucleophile to attack the ester or amide carbonyl directly.

• In order for the reaction to be stoichiometric, rather than catalytic, one HO2 molecule is required.

• In the presence of an acid catalyst, esters react with water to form a carboxylic acid and alcohol.

• The mechanism is same.

Esters and HCl are formed when acid chlorides combine with alcohols.

• This reaction is similar to the synthesis of sulfonic esters, which was explained in Section 10.5D.

• When the ester is acid-sensitive, a base such as a tertiary amine is utilized to neutralize the HCl as it forms.

Esters combine with alcohols in an acid-catalyzed reaction termed transesterification, an equilibrium process in which one ester!

• Amides are insufficiently reactive to react with alcohols.

• Acid chlorides react with two equivalents of ammonia and one equivalent each of 1° and 2° amines to generate an amide and one equivalent of ammonium chloride.

Acid anhydrides react with two equivalents of ammonia and one equivalent of 1° and 2° amines to generate an amide and one equivalent of an ammonium carboxylate salt; esters react slowly with ammonia and one equivalent of 1° and 2° amines to form an amide and an alcohol.

The basic rule is that any less reactive carboxylic acid derivative may be created by combining any more reactive carboxylic acid derivative with the suitable oxygen or nitrogen nucleophile.

• Any of the other carboxylic acid derivatives may be made using acid chlorides.

• Because acid chlorides may be generated from carboxylic acids using SOCl2 and any carboxylic acid derivatives can be hydrolyzed, any of the carboxylic acid derivatives can be interconverted.

The processes depicted in the chapter are combinations of the four phases listed below:

• Putting on a proton (Adding a proton) – Removing a proton (Take a proton away)

• A nucleophile attacks a sp2 carbon, resulting in a tetrahedral addition intermediate. (Form a new bond between a nucleophile and an electrophile)