Functional Derivatives of Carboxylic Acids. Nomenclature: the functional derivatives’ names are...
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Transcript of Functional Derivatives of Carboxylic Acids. Nomenclature: the functional derivatives’ names are...
Functional Derivatives of Carboxylic Acids
R CNH2
O
R CO
O
R CCl
O
R COR'
O
CO
R
acid chlorideanhydride
amide ester
R may be H or Ar
Nomenclature: the functional derivatives’ names are derived from the common or IUPAC names of the corresponding carboxylic acids.
Acid chlorides: change –ic acid to –yl chloride
Anhydrides: change acid to anhydride
CCl
OCH3CH2CH2C
O
Cl
butanoyl chloridebutyryl chloride
benzoyl chloride
H3C CO
H3C CO
O
O
O
O
O
O
O
ethanoic anhydrideacetic anhydride
phthalic anhydride maleic anhydride
Amides: change –ic acid (common name) to –amide
-oic acid (IUPAC) to –amide
Esters: change –ic acid to –ate preceded by the name of the alcohol group
CNH2
OCH3CH2CH2C
O
NH2
butanamidebutyramide
benzamide
CO CH2CH3
O
ethyl benzoate
CH3CH2CH2CO
O CH3
methyl butanoatemethyl butyrate
Nucleophilic acyl substitution:
R CZ
OR C
W
O+ :Z R C W
O
Z+ :W
-W = -OH, -Cl, -OOCR, -NH2, -OR'
R CO
= "acyl" group
R CZ
O
R CW
OH+ :ZH R C W
OH
ZH
+ HW + H+R C W
OH
ZH
RDS
R CW
OHR C
W
O+ H+
Mechanism: nucleophilic acyl substitution, acid catalyzed
1)
2)
3)
nucleophilic acyl substitution vs nucleophilic addition to carbonyl
aldehydes & ketones – nucleophilic addition
functional deriv. of carboxylic acids – nucleophilic acyl substitution
R CZ
OR C
W
O+ :Z R C W
O
Z+ :W
-W = -OH, -Cl, -OOCR, -NH2, -OR'
R CR'
O+ :Z R C R'
O
Z
YR C R'
OY
Z
Acid Chlorides
Syntheses: SOCl2
RCOOH + PCl3 RCOCl PCl5
COH
O+ SOCl2 C
Cl
O
benzoic acid benzoyl chloride
OH
O
+ PCl3Cl
O
3-methylbutanoic acidisovaleric acid
3-methylbutanoyl chlorideisovaleryl chloride
Acid chlorides, reactions:
1. Conversion into acids and derivatives:
a) hydrolysis
b) ammonolysis
c) alcoholysis
2. Friedel-Crafts acylation
3. Coupling with lithium dialkylcopper
4. Reduction
acid chlorides: conversion into acids and other derivatives
Cl
O H2O
OH
OHydrolysis
isovaleryl chloride3-methylbutanoyl chloride
isovaleric acid3-methylbutanoic acid
Ammonolysis CH3CH2 CCl
O NH3CH3CH2 C
NH2
O
propionyl chloridepropanoyl chloride
propionamidepropanamide
AlcoholysisC
O
Cl
CH3CH2OHC
O
OCH2CH3
benzoyl chloride ethyl benzoate
Schotten-Baumann technique – aromatic acid chlorides are less reactive than aliphatic acid chlorides. In order to speed up the reactions of aromatic acid chlorides, bases such as NaOH or pyridine are often added to the reaction mixture.
O2N
O2N
COClpyridine
CH3CH2CH2OHO2N
O2N
CO
OCH2CH2CH3
3,5-dinitrobenzoyl chloride n-propyl-3,5-dinitrobenzoate
acid chlorides: Friedel-Crafts acylation
R CO
Cl+ ArH
AlCl3R C Ar
O+ HCl
phenone
CH3CH2CH2C
O
Cl CH3+
toluene
butyryl chloride
AlCl3CH3CH2CH2C
O
CH3 + ortho-
p-methylbutyrophenone
CH3CH2CH2C
O
Cl
butyryl chloride
+ NO2
AlCl3No reacton
acid chlorides: coupling with lithium dialkylcopper
R CO
Cl
+ R'2CuLi R C R'
O
ketone
CO
Cl+ (CH3CH2CH2)2CuLi C CH2CH2CH3
O
benzoyl chloride lithium di-n-propylcopper butyrophenone
CCl
O+
2CuLi
O
2,4-dimethyl-3-pentanoneisobutyryl chloride lithium diisopropylcopper
acid chlorides: reduction to aldehydes
R CCl
O LiAlH(t-BuO)3R C
H
O
CO
ClC
O
H
LiAlH(t-BuO)3
mechanism, nucleophilic acyl substitution by hydride :H-
R CCl
O1) + :H R C Cl
O
H
RDS
2) R C Cl
O
H
R CH
O+ Cl
Anhydrides, syntheses:
Buy the ones you want!
Anhydrides, reactions:
1) Conversion into carboxylic acids and derivatives.
a) hydrolysis
b) ammonolysis
c) alcoholysis
2) Friedel-Crafts acylation
O
O
O
phthalic anhydride
+ H2O
COOH
COOH
(CH3CO)2O + NH3 CH3 CNH2
OCH3 C
ONH4
O+
acetic anhydride
phthalic acid
acetamide
O
O
O
+ CH3CH2OH
succinic anhydride
CH2COCH2CH3
O
CH2COH
O
ethyl hydrogen succinate
ammonium acetate
2) anhydrides, Friedel-Crafts acylation.
(RCO)2O + ArHAlCl3
R COH
O+R C Ar
O
phenone
(CH3CO)2O + CH3AlCl3
H3C C
O
CH3 + CH3CO2H
acetic anhydridetoluene p-methylacetophenone
O
O
O
phthalic anhydride
+AlCl3
C
O
CO
OH
o-benzoylbenzoic acid
Amides, synthesis:
Indirectly via acid chlorides.
R COH
O SOCl2R C
Cl
O NH3R C
NH2
O
[ carboxylic acids form ammonium salts when reacted directly with ammonia ]
CH3CH2CH2CO2H CH3CH2CH2CO
Cl
PCl3 NH3CH3CH2CH2C
O
NH2butyric acid butyryl chloride butyramide
COOHPCl5
CCl
O NH3C
NH2
O
benzoic acid benzoyl chloride benzamide
Amides, reactions.
1) Hydrolysis.
R CNH2
O H2O, H+ or OH-
heatR C
OH
O
CH3CHCH2C
CH3
NH2
O
isovaleramide
+ H2OH+
heatCH3CHCH2C
CH3
OH
O
isovaleric acid
HN CHC
O
R
HN CHC
R
OHN CHC
R
OHN CHC
R
OHN CHC
R
OHN CHC
R
O
proteins are polyaminoacids
H2N CHC
R
OH
O
aminoacids
"peptide bond"
hydrolysis
Wool, hair, silk, spider web: fibrous proteins.
Silk is an extremely strong, thin, lightweight fiber, perfect for making sheer stockings for women as well as parachutes. It is made by the silkworm, a domesticated moth larva raised in Japan and China. During World War II a substitute material was needed and developed by DuPont – Nylon-66, a synthetic polyamide of adipic acid and hexamethylenediamine:
C(CH2)4C
O O
Cl
adipoyl chloride
+ H2N (CH2)6 NH2
hexamethylenediamine
C(CH2)4C
O O
NH (CH2)6 NHC(CH2)4C
O O
NH (CH2)6 NH
Nylon-66
Cl
Esters, syntheses:
1) From acids
RCO2H + R’OH, H+ RCO2R’ + H2O
2) From acid chlorides and anhydrides
RCOCl + R’OH RCO2R’ + HCl
3) From esters (transesterification)
RCO2R’ + R”OH, H+ RCO2R” + R’OH
RCO2R’ + R”ONa RCO2R” + R’ONa
Esters often have “fruity” or “floral” odors:
isopentyl acetate banana oil
n-pentyl butyrate apricot
isopentyl isovalerate apple
ethyl butyrate peach
ethyl heptanoate cognac
ethyl nonate flower bouquet
ethyl laurate tuberose
methyl butyrate pineapple
octyl acetate orange
C
O
OH
isovaleric acid
+ CH3CH2OH
ethyl alcohol
H+
C
O
O
ethyl isovalerate
+ H2O
SOCl2
C
O
Cl
isovaleryl chloride
+ CH3CH2OH
ethyl alcohol
C
O
O
ethyl isovalerate
+ HCl
“Direct” esterification is reversible and requires use of LeChatelier’s principle to shift the equilibrium towards the products. “Indirect” is non-reversible.
In transesterification, an ester is made from another ester by exchanging the alcohol function.
CH3CH2CH2CO
OCH3
methyl butanoate
+
isopropyl alcohol
H+
CH3CH2CH2CO
O
isopropyl butanoate
+ CH3OHCHCH3
CH3CHCH3HO
CH3
CH3CH2CH2CO
OCH3
methyl butanoate
+
CH2ONa
benzyl alcoholCH3CH2CH2C
O
O+
CH2
CH3ONa
benzyl butanoate
Esters, reactions:
1) Conversion into acids and derivatives
a) hydrolysis
b) ammonolysis
c) alcoholysis
2) Reaction with Grignard reagents
3) Reduction
a) catalytic
b) chemical
4) Claisen condensation
COCH2CH3
O H2O; H+ or OH-
heatC
OH
O+ CH3CH2OH
ethyl benzoate
CH3CHC
CH3 O
O CH3
methyl isobutyrate
NH3CH3CHC
CH3 O
NH2
+ CH3OH
CH3CO
OCH2CH3+ OH
H+
CH3CO
O + CH3CH2OH
ethyl acetate cyclopentyl acetate
R C18O R'
O OH-
H2O, heat
H+
R COH
O+ R'18OH
OH-
R C
O-
18O
OH
R
Tracer studies confirm that the mechanism is nucleophilic acyl substitution:
H2C
HC
OOCR
OOCR'
H2C OOCR''
triglycerides, fats/oilstriesters of glycerol
NaOH, H2O
heat
H2C
HC
OH
OH
H2C OH
glycerol
+
RCOO-Na+
R'COO-Na+
R''COO-Na+
"SOAP"
Hydrolysis of a fat or oil is also called "saponification
Esters, reaction with Grignard reagents
R CO
O R''+ R'MgX
H2OR C R'
OH
R'
+ R''OH
3o alcohol
nucleophilicacyl substitution
R C R'
O
ketone
+ R'MgX
nucleophilicaddition
CH3CH2CH2CO
OCH3
methyl butanoate
+ MgBr
phenyl magnesium bromide
H2O
CH3CH2CH2C
OH
1,1-diphenyl-1-butanol
Esters, reduction
a) catalytic
b) chemical
RO R'
O+ H2, Ni NR
RO R'
O H2, CuO, CuCr2O4
150o, 5000 psiRCH2OH + R'OH
RO R'
O LiAlH4 H+
RCH2OH + R'OH
O
O
isopropyl isobutyrate
H2, CuO, CuCr2O4
150o, 5000 psi
OH
OH
+
isobutyl alcohol isopropyl alcohol
CH3CH2CO
O
phenyl propanoate
1. LiAlH4
2. H+ CH3CH2CH2OH +
OH
n-propyl alcohol phenol
Spectroscopy:
Infrared: strong absorbance ~ 1700 cm-1 for C=O
RCO2R 1740 ArCO2R 1715-1730 RCO2Ar 1770
Esters also show a strong C—O stretch at 1050-1300
Amides show N—H stretch at 3050 –3550 and N—H bend in the 1600-1640 region.
Nmr: NB in esters the protons on the alcohol side of the functional group resonate at lower field than the ones on the acid side.
RCOO—C—H 3.7 – 4.1 ppm
H—C—COOR 2 – 2.2 ppm