Carboxylic Acids

1
Carboxylic Acids

• nomenclature

2
Carboxylic Acids

• nomenclature

3
Carboxylic Acid Derivatives

• Removal of the OH from the carboxylic acid
• acyl group

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Carboxylic Acid Derivatives

• further........

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Carboxylic Acid Derivatives

• therefore....

Acid Chlorides
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Carboxylic Acid Derivatives
Acid Anhydrides
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Carboxylic Acid Derivatives Salts Esters

• When naming, the acid section is always named
  last (it has the highest priority), and the
  suffix is changed
• from -ic to ate

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Carboxylic Acid Derivatives Amides

• Substitute -oic or -ic for amide

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• For substituted amides....

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Carboxylic Acid Derivatives Imides

• Imides Amides derived from dicarboxylic acids

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Carboxylic Acid Derivatives Nitriles

• nitriles are carboxylic acid derivatives as they
  can be hydrolysed to amides and subsequently,
  acids

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Carboxylic Acid Derivatives Physical Properties

• Carboxylic acids are generally water soluble
• salts are more soluble (ionic)
• strongly hydrogen bonded, exist as dimers(even
  in the gas phase)

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Carboxylic Acid Derivatives Acidity

• Note Inductive effect electron withdrawing
  groups increase acidity. e.g. F-CH2-COOH pka
  2.59
• (F withdraws electron density from carboxylic
  acid group enables H to be removed more
  easily.
• Throughbond effect i.e. the further away, the
  less influence
• electron donating groups decrease acidity.

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Synthesis of Carboxylic Acids (Review)

• a) Oxidation Reactions
• i) Primary alcohols and aldehydes
• ii) Oxidative Cleavage of Alkenes (see 1st year
  notes)

O
eg Jones Reagent Tollens Reagent (AgNO3,
NH4OH)
carboxylic acids
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Synthesis of Carboxylic Acids

• iii) Synthesis of benzoic acids
• oxidation of any alkyl benzene

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Synthesis of Carboxylic Acids

• b) Hydrolysis Reactions
• i) hydrolysis of nitriles
• ii) hydrolysis of other acid derivatives (eg
  esters, acid chlorides etc etc etc)

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Synthesis of Carboxylic Acids

• c) Carboxylation of Grignard Reagents

addition of CO2 to Grignard reagents
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Synthesis of Carboxylic Acids

• carboxylation reactions (continued)
• mechanism...
• can also use organolithium species(replacing
  Grignard reagent)
• NOTE addition of one extra carbon to original
  molecule

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Reactions of Carboxylic Acids

• Summary

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Reactions of Carboxylic Acids

• a) ?-substitution
• Bromination The Hell-Volhard-Zelinski
  Reaction
• via nucleophilic substitution of Br-, forming the
  acid bromide

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Reactions of Carboxylic Acids

• b) Decarboxylation
• heavy metal with a halogen

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Reactions of Carboxylic Acids

• c) Deprotonation
• carboxylic acids are usually sufficiently acidic
  for NaOH to deprotonate
• d) Reduction
• use LiAlH4 (i.e NOT NaBH4 sodium borohydride)

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Reactions of Carboxylic Acids

• reduction (continued)
• borane reacts faster with carboxylic acids
  (relative to nitro groups) and therefore
  selectivity is achieved
• LiAlH4 would also reduce nitro group

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Reactions of Carboxylic Acids

• e) nucleophilic Acyl Substitution
• these derivatives are usually prepared from the
  acid chloride (rather than the acid) as the acid
  chlorides are more reactive

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Reactions of Carboxylic Acids
the chloro is a good leaving group ? molecule
susceptible to nucleophilic attack

• acid chlorides.....
• can use PCl3 or oxalyl chloride (Cl-CO-CO-Cl)
  instead of thionyl chloride.

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Mechanism of Nucleophilic Acyl Subsitution

• 1st step is the rate determining step

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Mechanism of Nucleophilic Acyl Subsitution

• example

tetrahedral intermediate
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Nucleophilic Acyl Subsitution Reactivity

• Steric factors the more sterically hindered,
  the less reactive
• Electronic Factors more strongly favour
  polarized derivatives (more
  reactive)electronegative halogen polarizes
  the carbon more strongly than the alkoxy or amino
  group.

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Preparation of Acid Anhydrides

• 1) Dehydration of the Acid
• water must be removed (to avoid hydrolysis)
• limited use

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Preparation of Acid Anhydrides

• 2) Nucleophilic Acyl Substitution
• acyl chloride carboxylate anion
• Note suitable for synthesis of unsymmetrical
  anhydrides

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Preparation of Esters

• 1) Direct reaction of carboxylic acids and
  alcohols
• acid catalysed (increases the acidity of the
  carboxylic acid)
• all steps are reversible ? need to drive
  reaction to the right i.e. remove water or add
  excess water
• hydrolysis of esters with water (acid
  catalysed) is the reverse reaction

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Preparation of Esters Mechanism

• Same mechanism applies for hydrolysis of esters,
  simply in reverse.

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Preparation of Esters

• 2) Reaction of acid chlorides with
  alcohols
• Mechanism is nucleophilic acyl substitution
  (i.e. the same as previously)
• Most general and versatile reaction
• note preparation of alcohol derivatives
  practical formation of esters!

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Preparation of Esters

• 3) Reaction of anhydrides with alcohols

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Preparation of Esters

• 4) Transesterification
• heat and catalyst (either acid or base)
  required
• need to push equilibrium towards desired
  products

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Lactones

• Lactones are cyclic esters
• 5- or 6- membered rings are highly favoured

a ?-lactone
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Amides
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Peptides and Proteins Amides

• amino acids connected by a seris of amide bonds
• links are called peptides
• macromolecules of this type are proteins

amide or peptide bond
amide bond can be hydrolysed under acidic or
basic conditions digestion
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Reactions of Amides

• Reduction
• LiAlH4 will reduce the carbonyl bond

95
20 amide
20 amine
80
a lactam (cyclic amide)
cyclic amine
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Hydrolysis Reactions

• Reaction with water as nucleophile
• Acid chlorides and anhydrides
• react quickly with water producing the
  corresponding carboxylic acid (they are often
  water soluble)

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Hydrolysis Reactions

• Esters hydrolysis requires heat and a
  catalyst
• a) acid catalysed ester hydrolysis
• equilibrium ? use a large excess of water
• mechanism is the reverse of acid catalysed
  esterification
• b) Saponification base catalysed ester
  hydrolysis
• hydrolysis of an animal fat, glycerol (3 x acid
  esterified with long chain alcoholsfatty acids)
  yields soaps

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Mechanism of Saponification
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Hydrolysis of Amides and Nitriles

• heat and strong acid or base required
• (similar mechanism to that on previous slide)