Chapter 21 Carboxylic Acid Derivatives Jo Blackburn Richland College, Dallas, TX Dallas County...
-
Upload
magnus-bates -
Category
Documents
-
view
223 -
download
1
Transcript of Chapter 21 Carboxylic Acid Derivatives Jo Blackburn Richland College, Dallas, TX Dallas County...
Chapter 21Carboxylic Acid Derivatives
Jo BlackburnRichland College, Dallas, TX
Dallas County Community College District2003,Prentice Hall
Organic Chemistry, 5th EditionL. G. Wade, Jr.
Chapter 21 2
Acid Derivatives
• All can be converted to the carboxylic acid by acidic or basic hydrolysis.
• Esters and amides common in nature.
=>
R C
O
X R C
O
O C
O
R' R C
O
O R R C
O
NH2 R C N
RCOX (RCO)2O RCOOR RCONH2 RCN
Chapter 21 3
Naming Esters
• Esters are named as alkyl carboxylates.
• Alkyl from the alcohol, carboxylate from the carboxylic acid precursor.
isobutyl acetate2-methylpropyl ethanoate
CH3CHCH2OCCH3
CH3 O
HCOCH2
O
benzyl formatebenzyl methanoate
=>
Chapter 21 4
Cyclic Esters
• Reaction of -OH and -COOH on same molecule produces a cyclic ester, lactone.
• To name, add word lactone to the IUPAC acid name or replace the -ic acid of common name with -olactone.
O
O
H3C
CH3
4-hydroxy-2-methylpentanoic acid lactone-methyl--valerolactone
=>
Chapter 21 5
Amides• Product of the reaction of a carboxylic
acid and ammonia or an amine.
• Not basic because the lone pair on nitrogen is delocalized by resonance.
HC
O
N
H
HH
C
O
N
H
H
_
+
Bond angles around Nare close to 120. =>
Chapter 21 6
Classes of Amides
• 1 amide has one C-N bond (two N-H).
• 2 amide or N-substituted amide has two C-N bonds (one N-H).
• 3 amide or N,N-disubstituted amide has three C-N bonds (no N-H).
=>
Chapter 21 7
Naming Amides
• For 1 amide, drop -ic or -oic acid from the carboxylic acid name, add -amide.
• For 2 and 3 amides, the alkyl groups bonded to nitrogen are named with N- to indicate their position.
CH3CHC N
O
CH2CH3
CH3
CH3
N-ethyl-N,2-dimethylpropanamideN-ethyl-N-methylisobutyramide
=>
Chapter 21 8
Cyclic Amides
• Reaction of -NH2 and -COOH on same molecule produces a cyclic amide, lactam.
• To name, add word lactam to the IUPAC acid name or replace the -ic acid of common name with -olactam.
N
O
CH3
H4-aminopentanoic acid lactam
-valerolactam
=>
Chapter 21 9
Nitriles• -CN can be hydrolyzed to carboxylic
acid, so nitriles are acid derivatives.
• Nitrogen is sp hybridized, lone pair tightly held, so not very basic. (pKb about 24).
=>
Chapter 21 10
Naming Nitriles
• For IUPAC names, add -nitrile to the alkane name.
• Common names come from the carboxylic acid. Replace -ic acid with -onitrile.
CH3CHCH2CH2CH2CN
Br
5-bromohexanenitrile-bromocapronitrile
C N
Cyclohexanecarbonitrile =>
Chapter 21 11
Acid Halides
• More reactive than acids; the halogen withdraws e- density from carbonyl.
• Named by replacing -ic acid with -yl halide.
C
O
Cl CH3CHCH2C
Br O
Br
benzoyl chloride
3-bromobutanoyl bromide-bromobutyryl bromide
=>
Chapter 21 12
Acid Anhydrides• Two molecules of acid combine with the
loss of water to form the anhydride.
• Anhydrides are more reactive than acids, but less reactive than acid chlorides.
• A carboxylate ion is the leaving group in nucleophilic acyl substitution reactions.
R C
O
O H RC
O
OH R C
O
O C
O
R
=>
Chapter 21 13
Naming Anhydrides• The word acid is replaced with anhydride.
• For a mixed anhydride, name both acids.
• Diacids may form anhydrides if a 5- or 6-membered ring is the product.
CH3 C
O
O C
O
CH3
ethanoic anhydrideacetic anhydride
O
O
O1,2-benzenedicarboxylic anhydride
phthalic anhydride =>
Chapter 21 14
Multifunctional Compounds
• The functional group with the highest priority determines the parent name.
• Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne.
C
CN
O
OCH2CH3 ethyl o-cyanobenzoate=>
Chapter 21 15
Boiling Points
Even 3 amides havestrong attractions.
=>
Chapter 21 16
Melting Points
• Amides have very high melting points.
• Melting points increase with increasing number of N-H bonds.
H C
O
NCH3
CH3CH3 C
O
NH
CH3
CH3CH2 C
O
N
H
H
m.p. -61C m.p. 28C m.p. 79C
=>
Chapter 21 17
Solubility• Acid chlorides and anhydrides are too
reactive to be used with water or alcohol.
• Esters, 3 amides, and nitriles are good polar aprotic solvents.
• Solvents commonly used in organic reactions:Ethyl acetateDimethylformamide (DMF)Acetonitrile
=>
Chapter 21 18
IR Spectroscopy
=> =>
Chapter 21 19
1H NMR Spectroscopy
=>
Chapter 21 20
13C NMR Spectroscopy
=>
Chapter 21 21
Interconversion ofAcid Derivatives
• Nucleophile adds to the carbonyl to form a tetrahedral intermediate.
• Leaving group leaves and C=O regenerates.
C
O
R YNuc_
C
O
R Y
Nuc
_
C
O
R Nuc+ Y
_
=>
Chapter 21 22
ReactivityReactivity decreases as leaving group
becomes more basic.
=>
Chapter 21 23
Interconversion of Derivatives
More reactive derivatives can be converted to less reactive derivatives.
=>
Chapter 21 24
Acid Chloride to Anhydride
• Acid or carboxylate ion attacks the C=O.
• Tetrahedral intermediate forms.
• Chloride ion leaves, C=O is restored, H+ is abstracted. =>
+ HClC
O
R OC
O
R'
_
C
O
R Cl
OH C
OR'
C
O
R ClR' C
O
O H+
- H+
Chapter 21 25
Acid Chloride to Ester
• Alcohol attacks the C=O.
• Tetrahedral intermediate forms.
• Chloride ion leaves, C=O is restored, H+
is abstracted. =>
+ HClC
O
R OR'
_
C
O
R Cl
OH R'
C
O
R Cl+
- H+
R' O H
Chapter 21 26
Acid Chloride to Amide• Ammonia yields a 1 amide
• A 1 amine yields a 2 amide
• A 2 amine yields a 3 amide
C
O
R NR'2
_
C
O
R Cl
NH R'2
C
O
R Cl+
R'2 N H
R'2 N HR'2NH2
+ Cl
-
+
=>
Chapter 21 27
Anhydride to Ester
• Alcohol attacks one C=O of anhydride.• Tetrahedral intermediate forms.• Carboxylate ion leaves, C=O is
restored, H+ is abstracted. =>
_
C
O
R OR'C
O
R OC
O
RR' O H+
C
O
R O
OH R'
C
O
R
_
O C
O
R +
Chapter 21 28
Anhydride to Amide
• Ammonia yields a 1 amide
• A 1 amine yields a 2 amide
• A 2 amine yields a 3 amide
_
C
O
R NR'2
C
O
R OC
O
RR'2 N H+
C
O
R O
NH R'2
C
O
R
_
O C
O
R +
=>
Chapter 21 29
Ester to Amide• Nucleophile must be NH3 or 1 amine.
• Prolonged heating required.
C
O
R NHR'
_
C
O
R OCH3
NH R'
H
C
O
R OCH3+
R' NH2 +OCH3
_
Surprise!
=>
Chapter 21 30
Leaving Groups
A strong base is not usually a leaving group unless it’s in an exothermic step.
=>
Chapter 21 31
Transesterification
• One alkoxy group can be replaced by another with acid or base catalyst.
• Use large excess of preferred alcohol.
C
O
OCH2CH3
+ CH3OHH
+ or
-OCH3
C
O
OCH3
CH3CH2OH+
=>
Chapter 21 32
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.
+CH3 C
O
Cl HOH CH3 C
O
OH + HCl
=>
Chapter 21 33
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 34
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 35
Hydrolysis of Amides
Prolonged heating in 6 M HCl or 40% aqueous NaOH is required.
+CH3 C
O
NHCH3-OH CH3 C
O
O-
+ CH3NH2H2O
+CH3 C
O
NHCH3 HCl CH3 C
O
OH + CH3NH3+Cl-
H2O
=>
Chapter 21 36
Hydrolysis of Nitriles
• Under mild conditions, nitriles hydrolyze to an amide.
• Heating with aqueous acid or base will hydrolyze a nitrile to an acid.
+ H2O
C N -OH
C
O
NH2 -OHheat
C
O
O-
+ NH3
=>
Chapter 21 37
Reduction to Alcohols
Lithium aluminum hydride reduces acids, acid chlorides, and esters to primary alcohols.
=>
CH3CH2OH+
CH2OH
H2O2)
1) LiAlH4
C
O
OCH2CH3
Chapter 21 38
Reduction to Aldehydes
Acid chlorides will react with a weaker reducing agent to yield an aldehyde.
=>
CH3CHCH2C
CH3 O
HLiAl(t-BuO)3HCH3CHCH2C
CH3 O
Cl
Chapter 21 39
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.
CH3 C
O
NHCH3 CH3 CH2 NHCH3LiAlH41)
2) H2O
=>
Chapter 21 40
Organometallic Reagents
Grignard reagents and organolithium reagents add twice to acid chlorides and esters to give alcohols after protonation.
C
O
OCH2CH3 CH3MgBr
ether
C
OH
CH3CH3
2 H3O+
=>
Chapter 21 41
Grignard Reagentsand Nitriles
A Grignard reagent or organolithium reagent attacks the cyano group to yield an imine which is hydrolyzed to a ketone.
C NCH3MgBr
etherH3O
+C N
H3C MgBrC O
H3C
=>
Chapter 21 42
Acid Chloride Synthesis
• Use thionyl chloride, SOCl2, or oxalyl chloride, (COCl)2.
• Other products are gases.
C
O
OH SOCl2C
O
Cl+ +SO2 HCl
=>
Chapter 21 43
Acid Chloride Reactions (1)
H2O
R'OH
R'NH2
R'COOH
R C
O
Cl
R C
O
OH + HCl
R C
O
OR'
R C
O
NHR'
R C
O
O C
O
R' + HCl
+ HCl
+ HCl
acid
ester
amide
acid anhydride =>
Chapter 21 44
Acid Chloride Reactions (2)
R C
O
H
R CH2OH
R C
O
R'
R C
OH
R'
R'
R C
O
Cl
H2O(2)
(1) 2 R'MgX
R'2CuLi
(1)
(2) H2O
LiAlH4
Li( BuO)3AlHt-
Z
AlCl3
C
O
RZ
3° alcohol
ketone
1° alcohol
aldehyde
acylbenzene =>
Chapter 21 45
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 46
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 47
Anhydride Reactions
R C
O
O C
O
R
R C
O
OH + RCOOH
R C
O
OR'
R C
O
NHR' + RCOOH
+ RCOOH
AlCl3
H2O
R'OH, H+
R'NH2
ZC
O
RZ
acid
ester
amide
=>acylbenzene
Chapter 21 48
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.
+ CH3 C
O
OHCH3 C
O
O C
O
H R NH2 H C
O
NHR +
• Use cyclic anhydrides to produce a difunctional molecule.
C
O
OCH2CH3
C
O
OHO
O
O
CH3CH2OH=>
Chapter 21 49
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 50
Reactions of Esters
R C
O
OR'
R C
O
OH + R'OH
R C
O
OR''
R C
O
NHR'' + R'OH
+ R'OH
R CH2OH
R C
OH
R''
R''H2O(2)
(1) 2 R''MgX
(1)
(2) H2O
LiAlH4
H2O
R''OH,
R''NH2
H+ or -OR''
acid
ester
amide
1° alcohol
3° alcohol
=>
Chapter 21 51
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 52
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 53
Reactions of Amides
R C
O
OH + R'NH2
R C
O
NHR'
R CH2NHR'(1)
(2) H2O
LiAlH4
H2OH+ or -OH
Br-, OH-
R NH2 + CO2
POCl3
(or P2O5)R C N
acid and amine
amine
1° amine
=>
nitrile
Chapter 21 54
Lactam Formation
• Five- and six-membered rings can be formed by heating - and -amino acids.
NH
OCOOH
NH2 heat+ H2O
• Smaller or larger rings do not form readily. =>
Chapter 21 55
-Lactams
• Highly reactive, 4-membered ring.
• Found in antibiotics isolated from fungi.
Amide ester !!
=>
Chapter 21 56
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 57
Reactions of Nitriles
R C
O
NH2
R CH2NH2(1)
(2)LiAlH4
H2OH+ or -OH
R C N
H+ or -OH
H2O R C
O
OH
H2O
R'MgXR C
N
R'
MgXH3O
+
R C
O
R'ketone
=>
amide acid
1° amine
Chapter 21 58
ThioestersMore reactive than esters because:
-S-R is a better leaving group than -O-RResonance overlap is not as effective.
=>
Chapter 21 59
Carbonic Acid Esters
• CO2 in water contains some H2CO3.
• Diesters are stable.
• Synthesized from phosgene.
+C
O
ClCl CH3CH2OCOCH2CH3
O
2 CH3CH2OH
diethyl carbonate
=>
Chapter 21 60
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 =>
Chapter 21 61
Polymers
• Polycarbonates are long-chain esters of carbonic acid.
• Polyurethanes are formed when a diol reacts with a diisocyanate.
N C ONCO
CH3
HOCH2CH2OH
NH CHN
CH3
C
O
OCH2CH2O
O
n
=>
Chapter 21 62
End of Chapter 21