Chapter 18 - Functional Derivatives of Carboxylic Acids

  • 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)%%