Carboxylic Acids

1
Chapter 12

• Carboxylic Acids Derivatives

2
Carboxylic acids

• One of most common groups in nature
• oxidizing environment

3
Designations

• Carboxyl group
• Designations

4
Bonding

• Carbon is sp2 hybridized trigonal planar
• carbonyl has 1 s bond and 1 p bond

5
Derivatives of carboxylic acids

• Derivatives have replaced OH group with another
  group (leaving group)
• R can be carbon or hydrogen

6
Nomenclature of carboxylic acids

• Common names

7
Nomenclature of carboxylic acids - IUPAC

• Carboxyl group has priority.
• Find longest chain containing carboxyl group.
• Number chain to give the carboxyl group 1.
• Name parent as alkanoic acid

8
Nomenclature

• Carboxyl groups attached to ring
• name as cycloalkanecarboxylic acid
• Dicarboxylic acids
• name as alkanedioc acid

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Nomenclature of derivatives--salts

• Salts of carboxylic acids name metal and replace
  oic acid with oate

10
Nomenclature Esters

• General structure of esters

11
Naming esters

• Name esters as alkyl alkanoate
• name group on alcohol oxygen
• name acyl group - drop ic acid and replace with
  oate (just like salt)

12
Nomenclature

• Practice

13
Nomenclature of Acid Halides

• Name as alkanoyl halide
• replace oic acid with oyl halide
• if attached to ring, name as cycloalkanecarbonyl
  halide

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Nomenclature of Anhydrides

• For symmetrical anhydrides (two identical acyl
  groups), replace oic acid with oic anhydride)
• Practice
• For non-symmetrical anhydrides, name each acid
  group in alphabetical order

15
Nomenclature of Primary Amides

• For amides having two hydrogens, replace oic
  acid with amide
• Practice
• Nomenclature of secondary and tertiary amides,
  Chapter 14.

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Practice Naming

• Name the following

cyclohexyl 2-chlorobenzoate
(R)-5-hydroxy-2-methylheptanoic acid
propyl formate (propyl methanoate)
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Properties of Carboxylic Acids and Esters

• A. Boiling Point
• carboxylic acids have very high boiling points
• strong hydrogen bonding
• carboxylic acids can form dimers
• esters have lower boiling points since cant
  hydrogen bond (polar--so dipole/dipole
  interactions)

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Properties

• Solubility of carboxylic acids
• low molecular weight carboxylic acids (acids
  containing 1-4 carbons) are soluble in water
• can form hydrogen bonds with water
• can be hydrogen bond donor and hydrogen bond
  acceptor
• higher molecular weight carboxylic acids are not
  soluble, since too much hydrophobic carbon

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Properties

• Esters are less soluble than carboxylic acids
• can be hydrogen bond acceptors from water
  molecule but cant donate a hydrogen bond

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Odors of Acids and Esters

• Carboxylic acids stink (sharp, unpleasant odors)
• butanoic acid (rancid butter)
• hexanoic acid (goats)
• Esters have pleasant, fruity odors
• methyl butanoate -- apple
• pentyl ethanoate (pentyl acetate) -- banana
• ethyl methanoate (ethyl formate) -- rum
• used extensively in perfume industry

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Acidity of Carboxylic Acids

• Carboxylic acids are weak acids, but are much
  stronger than phenols and much, much stronger
  than alcohols

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Acidity

• Carboxylic acids are stronger acids than alcohols
  or phenols because conjugate base is stabilized
• Why is conjugate base stable?

stronger acid
weaker conjugate base
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Acidity

• Carboxylic acids are stronger acids than alcohols
  due to inductive effect
• electron-withdrawing groups increase acidity by
• withdrawing electron density and weakening the
  O-H bond
• stabilizing negative charge in conjugate base
• the greater the number of EWG, the stronger the
  acid

24
Acidity

• Proximity to carboxyl group affects acidity the
  closer the electron-withdrawing group is to the
  carboxyl group, the stronger the acid
• effect falls off quickly. If too far away, no
  effect on acidity.

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Acidity

• Salts of carboxylic acids
• formed by reaction of carboxylic acid with base
• changes solubility properties
• can be used to separate carboxylic acids from
  other organic compounds, which wont dissolve in
  aqueous sodium hydroxide or sodium bicarbonate

water-insoluble
water-soluble
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Synthesis of Carboxylic Acids

• Oxidation of primary alcohols (section 8.7)
• Oxidation of aldehydes with Tollens or Fehlings
  solution (section 10.4) (forms silver mirror or
  red precipitate)
• Oxidation of alkyl benzenes (section 5.9)

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New Syntheses of Carboxylic Acids--Grignard

• Grignard Reaction with CO2
• Grignard reagent acts as nucleophile and adds to
  carbonyl of carbon dioxide
• examples

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New Synthesis SN2 Reaction and Hydrolysis

• Reaction of primary or secondary halide with
  cyanide ion generates nitrile
• which can be hydrolyzed in acid to carboxylic
  acid
• example

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Synthesis

• Both Grignard and SN2 reactions make new
  Carbon-Carbon bonds
• Grignard and SN2 reaction produce carboxylic acid
  with ONE more carbon that starting material.

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Synthesis

• Convert starting material to product
• count carbons same number--transformation
• oxidation reaction -- Jones reagent

31
Synthesis

• Convert starting material to product
• adding a carbon Grignard or SN2
• since tertiary halide, cant do SN2, must be
  Grignard

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Nucleophilic Acyl Substitution

• Addition reactions of aldehydes and ketones
• Carboxylic acid derivates (not carboxylic acids)
  undergo addition-elimination reactions to
  regenerate carbonyl

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Nucleophilic Acyl Substitution Reactions

• Addition-elimination reactions
• addition of nucleophile to carbonyl and
  generation of tetrahedral intermediate (usually
  slow step in reaction)
• leaving group leaves to regenerate carbonyl
• net result is substitution of one group (the
  nucleophile) for another group (the leaving
  group)
• Not like SN2, since not one step
• Energy diagram (on board)

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Reactivity of carboxylic acid derivatives

• Better the leaving group, the faster the
  reaction
• Leaving group weaker the base, the better the
  leaving group, the faster the reaction
• order of reactivity acid halides gt anhydrides gt
  esters gt amides

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Reactivity

• More reactive derivative can be converted into
  less reactive derivative
• acid halide can be converted into anhydride or
  ester or amide
• anhydride can be converted to ester or amide
• ester can be converted into amide
• amide cant be converted into anything
• carboxylic acids can be converted into any other
  derivative

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Conversion of Carboxylic Acids

• Converting carboxylic acid to acid halide--SOCl2
• Acid chlorides react with nucleophiles to produce
  other derivatives

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Examples

• Converting acids to acid chlorides
• Converting acid chlorides to other derivatives

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Conversion of Anhydrides to other derivatives

• Anhydrides not as reactive as acid halides, but
  more reactive than esters or amides

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Examples

• Conversion of anhydrides to esters
• Conversion of anhydrides to amides

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Reduction of Carboxylic Acids and Derivatives

• LAH reduces carboxylic acids, esters and acid
  halides to alcohols
• nucleophilic attack on carbonyl by hydride ion

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Reduction of acid chlorides

• Acid chlorides can be reduced to aldehydes with
  tri(tert-butoxy)hydride
• milder reducing agent will react with acid
  halides, but not aldehyde
• recall that LAH reduces acid chlorides all the
  way to alcohol

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Practice

• Give the product

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Synthesis of Esters

• Two methods
• 1st method 2-step method convert carboxylic
  acid to acid chloride and then react with
  alcohol
• example

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Synthesis of Esters

• Fisher esterification
• condensation reaction of acid alcohol --gt ester
• equilibrium reaction
• Le Chateliers principle
• remove water
• use large excess of acid or alcohol

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Mechanism of Fisher esterification

• Labeling studies show that oxygen from the
  alcohol forms the new s bond to the carbonyl
• mechanism involves nucleophilic attack of the
  alcohol on the carbonyl of the acid

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Mechanism of Fisher esterification

• Step 1 protonation of carboxyl oxygen
• Step 2 attack of the nucleophile on the
  protonated carbonyl

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Mechanism

• Step 3 loss of proton from oxygen of the
  original alcohol and transfer of proton to oxygen
  of the acid
• Step 4loss of water

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Mechanism

• Step 5 loss of proton to generate ester
• Hydrolysis of esters to form carboxylic acids and
  alcohols
• mechanism is just the reverse of the Fisher
  esterification!

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Hydrolysis of Ester

• Mechanism
• Identify the products of hydrolysis

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Hydrolysis and Saponification of Esters

• Hydrolysis
• acid-catalyzed
• produces carboxylic acid and alcohol
• equilibrium reaction
• Saponification
• in base
• produces salt of carboxylic acid and alcoho
• SOAP

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Products of hydrolysis

• Give the products of hydrolysis
• find ester functional group

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Claissen Condensation of Esters

• Reaction produces b-ketoesters

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Claissen condensation of esters

• Esters with a-hydrogens are acidic (pKa 25)
• a-hydrogen can be deprotonated with strong base
  (alkoxides) to form resonance-stabilized
  carbanion
• reaction similar to aldol reaction, except form
  b-ketoesters instead of b-hydoxyaldehydes.

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Mechanism of Claissen Condensation

• Step 1 deprotonation of a-hydrogen and
  generation of resonance-stabilized carbanion
• Step 2 attack by the carbanion on the carbonyl
  carbon of another ester to form a tetrahedral
  intermediate

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Mechanism

• Step 3 elimination of leaving group from
  tetrahedral intermediate

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Crossed Claissen Condensations

• If two different esters, both with a-hydrogens,
  get mixture of products.
• Crossed Claissen One ester should be without
  a-hydrogens

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Biochemical Condensations

• Biological aldol condensation
• reaction of oxaloacetic acid and coenzyme A

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Biochemical Claissen Condensations

• Diabetes not enough oxaloacetic acid to react
  with all of the acetyl coenzyme A, acetyl
  coenzyme A reacts with itself
• hydrolysis