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Chapter 21Carboxylic Acid Derivatives
(continued)
Jo BlackburnRichland College, Dallas, TX
Dallas County Community College District2006,Prentice Hall
Organic Chemistry, 6th EditionL. G. Wade, Jr.
Chapter 21 2
Hydrolysis of Acid Chlorides and Anhydrides
• Hydrolysis occurs quickly, even in moist air with no acid or base catalyst.
• Reagents must be protected from moisture.
=>
Chapter 21 3
Acid Hydrolysis of Esters
• Reverse of Fischer esterification.
• Reaches equilibrium.
• Use a large excess of water.
+CH3 C
O
OCH3 HOH CH3 C
O
OH + CH3OHH+
=>
Chapter 21 4
Saponification
• Base-catalyzed hydrolysis of ester.
• “Saponification” means “soap-making.”
• Soaps are made by heating NaOH with a fat (triester of glycerol) to produce the sodium salt of a fatty acid - a soap.
• One example of a soap is sodium stearate, Na+ -OOC(CH2)16CH3. =>
Chapter 21 6
Hydrolysis of Nitriles• Under mild conditions, nitriles hydrolyze
to an amide.
• Heating with aqueous acid or base will hydrolyze a nitrile to an acid.
=>
Chapter 21 7
Reduction to Alcohols
Lithium aluminum hydride reduces acids, acid chlorides, and esters to primary alcohols.
=>
Chapter 21 8
Reduction to Aldehydes
Acid chlorides will react with a weaker reducing agent to yield an aldehyde.
=>
Chapter 21 9
Reduction to Amines
• Lithium aluminum hydride reduces amides and nitriles to amines.
• Nitriles and 1 amides reduce to 1 amines.
• A 2 amide reduces to a 2 amine.
• A 3 amide reduces to a 3 amine.
=>
Chapter 21 10
Organometallic Reagents
Grignard reagents and organolithium reagents add twice to acid chlorides and esters to give alcohols after protonation.
=>
Chapter 21 11
Grignard Reagentsand Nitriles
A Grignard reagent or organolithium reagent attacks the cyano group to yield an imine which is hydrolyzed to a ketone.
=>
Chapter 21 12
Acid Chloride Synthesis
• Use thionyl chloride, SOCl2, or oxalyl chloride, (COCl)2.
• Other products are gases.
=>
Chapter 21 14
Acid Chloride Reactions (2)
3° alcohol
ketone
1° alcohol
aldehyde
acylbenzene =>
AlCl3
Chapter 21 15
Industrial Synthesis of Acetic Anhydride
• Four billion pounds/year produced.
• Use high heat (750°C) and triethyl phosphate catalyst to produce ketene.
CH3 C
O
OH(EtO)3P O
heat
CH
HC O
CH
HC O + CH3 C
O
OH CH3 C
O
O C
O
CH3
=>
Chapter 21 16
Lab Synthesisof Anhydrides
• React acid chloride with carboxylic acid or carboxylate ion.
C
O
Cl+ CH3 C
O
O_ C
O
O C
O
CH3
• Heat dicarboxylic acids to form cyclic anhydrides. C
O
OH
C
O
OHO
O
O=>
Chapter 21 18
Anhydride vs. Acid Chloride• Acetic anhydride is cheaper, gives a
better yield than acetyl chloride.
• Use acetic formic anhydride to produce formate esters and formamides.
• Use cyclic anhydrides to produce a difunctional molecule.
C
O
OCH2CH3
C
O
OHO
O
O
CH3CH2OH=>
Chapter 21 19
Synthesis of Esters
R C
O
OR'R C
O
OH + R'OHH+
+ HOH
acid
R C
O
OR'R C
O
Cl + R'OH + HCl
acid chloride
R C
O
OR'R C
O
O C
O
R + R'OHH+
+ RCOOH
acid anhydride
R C
O
OH CH2N2+ R C
O
OCH3 N2+methyl ester =>
Chapter 21 21
Lactones• Formation favored for five- and six-
membered rings.O
OCOOH
OH H+
H2O+
• For larger rings, remove water to shift equilibrium toward products
H+
H2O+O
O
OH
COOH
=>
Chapter 21 23
Synthesis of AmidesR C
O
OH + HOH+ R'NH2heat
R C
O
NHR'
acid
R C
O
O C
O
R + RCOOHR'2NH R C
O
NR'2+acid anhydride
R C
O
OR'' + R''OHR'NH2 R C
O
NHR'+ester
R C
O
NH2R C N + H2OH+ or OH-
nitrile =>
acid chlorideR'2NH2
+Cl-+R C
O
NR'2R'2NH+ 2R C
O
Cl
Chapter 21 25
Lactam Formation• Five- and six-membered rings can be
formed by heating - and -amino acids.
• Smaller or larger rings do not form readily. =>
Chapter 21 26
-Lactams
• Highly reactive, 4-membered ring.
• Found in antibiotics isolated from fungi.
Amide ester !!
=>
Chapter 21 28
Synthesis of Nitriles
R C
O
NH2 R C NPOCl3
1° amide
R C N +R X NaCN Na+X-
alkyl halide
+Ar N N+ CuCN Ar CN N2
diazonium salt
R C
O
R'HCNKCN
R C R'
HO CN
aldehyde or ketone
cyanohydrin =>
Chapter 21 30
ThioestersMore reactive than esters because:
-S-R is a better leaving group than -O-RResonance overlap is not as effective.
=>
Chapter 21 31
Carbonic Acid Esters
• CO2 in water contains some H2CO3.
• Diesters are stable.
• Synthesized from phosgene.
+C
O
ClCl CH3CH2OCOCH2CH3
O
2 CH3CH2OH
diethyl carbonate
=>
phosgene
Chapter 21 32
Urea and Urethanes
• Urea is the diamide of carbonic acid.
• Urethanes are esters of a monoamide of carbonic acid.
+C
O
ClCl C
O
NH2H2N2 NH3urea
N C O
H2ONH C OH
O
a carbamic acid
ROHNH C OR
O
a urethane =>