Chapter 18 - Functional Derivatives of Carboxylic Acids

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• 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)%%

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