Organic Chemistry Fifth Edition

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Chem 234 Organic Chemistry II Professor Duncan
J. Wardrop
Spring 2004
University of Illinois at Chicago
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19.13Reactions of Carboxylic AcidsA Review and
a Preview
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Reactions of Carboxylic Acids

• Acidity (Sections 19.4-19.9)
• Reduction with LiAlH4 (Section 15.3)
• Esterification (Section 15.8)
• Reaction with Thionyl Chloride (Section 12.7)

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Acidity of Carboxylic Acids
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Reactions of Carboxylic Acids
New reactions in this chapter

• ??Halogenation
• Decarboxylation
• But first we revisit acid-catalyzed
  esterificationto examine its mechanism.

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19.14Mechanism of Acid-Catalyzed Esterification
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Fischer Esterification - A Reversible Process
Acidic Dehydration
Acid Alcohol
Ester Water
Acidic Hydrolysis
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Mechanism of Fischer Esterification

• The mechanism involves two stages
• 1) formation of tetrahedral intermediate (3
  steps)
• 2) dissociation of tetrahedral intermediate
  (3 steps)

tetrahedral intermediate in esterification of
benzoic acid with methanol
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Stage One Formation of Tetrahedral Intermediate

• methanol adds to the carbonyl group of the
  carboxylic acid
• the tetrahedral intermediate is analogous to a
  hemiacetal

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Stage Two Collapse of Tetrahedral Intermediate to
Ester

• this stage corresponds to an acid-catalyzed
  dehydration

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Mechanism of formationoftetrahedral intermediate
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Step 1
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Step 1

• carbonyl oxygen is protonated because cation
  produced is stabilized by electron delocalization
  (resonance)

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Step 2

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Step 3
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Tetrahedral intermediatetoester stage
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Step 4
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Step 5
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Step 5
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Step 6
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Key Features of Mechanism

• Activation of carbonyl group by protonation of
  carbonyl oxygen
• Nucleophilic addition of alcohol to carbonyl
  groupforms tetrahedral intermediate
• Elimination of water from tetrahedral
  intermediate restores carbonyl group

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Review of Fischer Esterification
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Industrial Use of Fischer Esterification Polyester
- Dacron
http//www.dupont.com/fiberfill/dacron-main.html
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A Waste of Good Chemistry
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19.15Intramolecular Ester FormationLactones
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Lactones - Cyclic Esters

• Lactones are cyclic esters
• Formed by intramolecular esterification in
  acompound that contains a hydroxyl group anda
  carboxylic acid function

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Many Natural Products Contain Lactone Rings
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Other Lactone Natural Products
Orlistat inhibits dietary fat absorption by 30
(3 x 120 mg)
XENICAL (orlistat) is a lipase inhibitor for
obesity management that acts by inhibiting the
absorption of dietary fats.
http//www.rocheusa.com/products/xenical/pi.html
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Lactones are Formed From w-Hydroxy Carboxylic
Acids via Esterification


H2O
4-hydroxybutanoic acid
4-butanolide

• IUPAC nomenclature replace the -oic acid ending
  of the carboxylic acid by -olide
• identify the oxygenated carbon by number

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Lactonization via Esterification


H2O
4-hydroxybutanoic acid
4-butanolide
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Lactone Nomenclature

?
?
?
?
?
?
?
?-butyrolactone
?-valerolactone

• Ring size is designated by Greek letter
  corresponding to oxygenated carbon
• A ? lactone has a five-membered ring
• A ? lactone has a six-membered ring

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w-Hydroxy Carboxylic Acids Readily Undergo
Lactonization

• Reactions designed to give hydroxy acids often
  yield the corresponding lactone, especially if
  theresulting ring is 5- or 6-membered.

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Example
5-hexanolide (78)
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19.16?-Halogenation of Carboxylic AcidsThe
Hell-Volhard-Zelinsky Reaction
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a-Halogenation of Carboxylic Acids


X2
HX

• analogous to ?-halogenation of aldehydes and
  ketones
• key question Is enol content of carboxylic
  acids high enough to permit reaction to occur
  at reasonable rate? (Answer is NO)

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But...
P or PX3


X2
HX

• reaction works well if a small amount
  ofphosphorus or a phosphorus trihalide is added
  tothe reaction mixture
• this combination is called the Hell-Volhard-Zelin
  sky reaction

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Example of H.V.Z. Reaction

Br2
PCl3
benzene80C
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Example of H.V.Z. Reaction
Br2
P
(77)

• Value ?-Halogen can be replaced by
  nucleophilic substitution

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Why is the H.V.Z. Reaction Valuable?
Br2
P
(77)
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Synthesis of a-Amino Acids via H.V.Z. Reaction
Br2
(CH3)2CHCH2COH
PCl3
(88)
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19.17Decarboxylation of Malonic Acidand Related
Compounds
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Decarboxylation of Carboxylic Acids
Simple carboxylic acids do not decarboxylatereadi
ly.

RH
CO2
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Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other.

• This compound is the enol form of acetic acid.

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Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other.
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Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other.
Groups other than H may be present.

R
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1,3-Dicarboxylic Acids Undergo Decarboxylation
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Decarboxylation of Substituted Malonic Acids
One carboxyl group assists the loss of the other.

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Decarboxylation of Substituted Malonic Acids
One carboxyl group assists the loss of the other.
Groups other than OH may be present.
R
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Mechanism of Decarboxylation
This kind of compoundis called a ?-keto acid.
?
?

• Decarboxylation of a ?-keto acid gives a ketone.

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Decarboxylation of b-Keto Carboxylic Acids
25C

CO2
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Information Suggested Problems
Suggested Problems 19.24-19.34 ------------------
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fice Hour Thursday, 3.30 P.M., SES
4446 ---------------------------------------------
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