carboxylic acid derivatives - w3.ualg.ptw3.ualg.pt/~abrigas/qoii0708a14_acidded.pdf · chapter 21,...
TRANSCRIPT
1
Carboxylic Acid Derivatives
Chapter 21 2
• Adapted from:
Organic Chemistry, 6th Edition;
Chapter 21, Carboxylic Acid Derivatives
L. G. Wade, Jr.
2
Chapter 21 3
Acid Derivatives
• All can be converted to the carboxylic
acid by acidic or basic hydrolysis.
• Esters and amides common in nature.
=>
Chapter 21 4
3
Chapter 21 5
Naming Esters
• Esters are named as alkyl carboxylates.
• Alkyl from the alcohol, carboxylate from
the carboxylic acid precursor.
CH3CH2 OH HO C
O
CH3
H+
+ + H2OCH3CH2 O C
O
CH3
ethanol
ethyl alcohol
ethanoic acid
acetic acid
ethyl ethanoate
ethyl acetate
=>
Chapter 21 6
Name These
CH3CHCH2OCCH3
CH3 O
HCOCH2
O
isobutyl acetate2-methylpropyl ethanoate
benzyl formatebenzyl methanoate
=>
4
Chapter 21 7
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
α-methyl-γ-valerolactone
=>
Chapter 21 8
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.
H
C
O
N
H
H
H
C
O
N
H
H
_
+
Bond angles around N
are close to 120°. =>
5
Chapter 21 9
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 10
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-dimethylpropanamide
N-ethyl-N-methylisobutyramide
=>
6
Chapter 21 11
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
γ-valerolactam
=>
Chapter 21 12
Nitriles
• -C≡N 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).
=>
7
Chapter 21 13
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 14
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
β-bromobutyryl bromide=>
8
Chapter 21 15
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 16
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 anhydride
acetic anhydride
O
O
O1,2-benzenedicarboxylic anhydride
phthalic anhydride =>
9
Chapter 21 17
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
OCH2CH3ethyl o-cyanobenzoate
=>
Chapter 21 18
Boiling Points
Even 3° amides havestrong attractions.
=>
10
Chapter 21 19
Melting Points
• Amides have very high melting points.
• Melting points increase with increasing
number of N-H bonds.
m.p. -61°C m.p. 28°C m.p. 79°C
=>
Chapter 21 20
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 acetate
�Dimethylformamide (DMF)
�Acetonitrile=>
11
Chapter 21 21
IR Spectroscopy
=>
Chapter 21 22
1H NMR Spectroscopy
=>
12
Chapter 21 23
13C NMR Spectroscopy
=>
Chapter 21 24
Interconversion ofAcid Derivatives
• Nucleophile adds to the carbonyl to form a
tetrahedral intermediate.
• Leaving group leaves and C=O regenerates.
=>
13
Chapter 21 25
ReactivityReactivity decreases as leaving group
becomes more basic.
=>
Chapter 21 26
14
Chapter 21 27
Interconversion of Derivatives
More reactive
derivatives can be
converted to less
reactive
derivatives.
=>
Chapter 21 28
15
Chapter 21 29
Chapter 21 30
16
Chapter 21 31
Chapter 21 32
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
O
R'
C
O
R ClR' C
O
O H
+
- H+
17
Chapter 21 33
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 34
Acid Chloride to Amide
• Ammonia yields a 1° amide
• A 1° amine yields a 2° amide
• A 2° amine yields a 3° amide
=>
18
Chapter 21 35
Anhydride to Ester
• Alcohol attacks one C=O of anhydride.
• Tetrahedral intermediate forms.
• Carboxylate ion leaves, C=O is restored, H+ is abstracted.
=>
Chapter 21 36
Anhydride to Amide
• Ammonia yields a 1° amide
• A 1° amine yields a 2° amide
• A 2° amine yields a 3° amide
=>
19
Chapter 21 37
Ester to Amide
• Nucleophile must be NH3 or 1° amine.
• Prolonged heating required.
Surprise!
=>
Chapter 21 38
Leaving Groups
A strong base is not usually a leaving
group unless it’s in an exothermic step.
=>
20
Chapter 21 39
Transesterification
• One alkoxy group can be replaced by
another with acid or base catalyst.
• Use large excess of preferred alcohol.
Chapter 21 40
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.
=>
21
Chapter 21 41
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 + CH3OH
H+
=>
Chapter 21 42
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.
=>
22
Chapter 21 43
Hydrolysis of Amides
Prolonged heating in 6 M HCl or 40%
aqueous NaOH is required.
=>
Chapter 21 44
Hydrolysis of Nitriles
• Under mild conditions, nitriles hydrolyze
to an amide.
• Heating with aqueous acid or base will hydrolyze a nitrile to an acid.
=>
23
Chapter 21 45
Reduction to Alcohols
Lithium aluminum hydride reduces acids,
acid chlorides, and esters to primary
alcohols.
=>
Chapter 21 46
Reduction to Aldehydes
Acid chlorides will react with a weaker
reducing agent to yield an aldehyde.
=>
24
Chapter 21 47
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 48
Organometallic Reagents
Grignard reagents and organolithium
reagents add twice to acid chlorides and
esters to give alcohols after protonation.
=>
25
Chapter 21 49
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 50
Acid Chloride Synthesis
• Use thionyl chloride, SOCl2, or oxalyl
chloride, (COCl)2.
• Other products are gases.
=>
26
Chapter 21 51
Acid Chloride Reactions (1)
acid
ester
amide
acid anhydride=>
Chapter 21 52
Acid Chloride Reactions (2)
3°alcohol
ketone
1°alcohol
aldehyde
acylbenzene=>
AlCl3
27
Chapter 21 53
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 54
Lab Synthesis
of 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
OH
O
O
O=>
28
Chapter 21 55
Anhydride Reactions
acid
ester
amide
=>
acylbenzene
AlCl3
Chapter 21 56
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
OH
O
O
O
CH3CH2OH=>
29
Chapter 21 57
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 58
Reactions of Esters
acid
ester
amide
1°alcohol
3°alcohol=>
30
Chapter 21 59
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 60
Polyesters
• Dacron® thread
• Mylar® tape
• Glyptal resin
• PET bottles
=>
31
Chapter 21 61
Synthesis of Amides
R C
O
OH + HOH+ R'NH2
heatR 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 62
Reactions of Amides
acid and amine
amine
1°amine
=>
nitrile
32
Chapter 21 63
Lactam Formation• Five- and six-membered rings can be
formed by heating γ- and δ-amino acids.
• Smaller or larger rings do not form readily.
=>
Chapter 21 64
β-Lactams
• Highly reactive, 4-membered ring.
• Found in antibiotics isolated from fungi.
Amide → ester !!
=>
33
Chapter 21 65
Polyamides
Nylon 6.6
=>
Chapter 21 66
Synthesis of Nitriles
R C
O
NH2 R C NPOCl3
1°amide
R C N +R XNaCN Na
+X
-
alkyl halide
+Ar N N+ CuCN
Ar CN N2diazonium salt
R C
O
R'HCN
KCNR C R'
HO CN
aldehyde
or ketone
cyanohydrin =>
34
Chapter 21 67
Reactions of Nitriles
ketone
=>
amide acid
1°amine
Chapter 21 68
ThioestersMore reactive than esters because:
�-S-R is a better leaving group than -O-R
�Resonance overlap is not as effective.
=>
35
Chapter 21 69
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 70
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
H2O
NH C OH
O
a carbamic acid
ROHNH C OR
O
a urethane =>
36
Chapter 21 71
Polycarbonates
Long-chain esters of carbonic acid
=>
Chapter 21 72
Polyurethanes
A diol reacts with a diisocyanate.
=>