Carboxylic Acids
67
Carboxylic Acids Natural Products Nomenclature Acidity Preparation Reactions
description
Carboxylic Acids. Natural Products Nomenclature Acidity Preparation Reactions. Analgesics. Fats and Fatty Acids. Prostaglandins. Penicillins from mold. From Ergot Fungus. Common Nomenclature. I.U.P.A.C. Nomenclature. Dicarboxylic Acids. A Diacid. - PowerPoint PPT Presentation
Transcript of Carboxylic Acids
Carboxylic Acids
Natural ProductsNomenclature
AcidityPreparationReactions
Analgesics
ibuprofinHO2C
acetyl salicylic acid
CO2HOCCH3
O
(S)(+)-
Fats and Fatty Acids
CO2Hpalmitic acid (a fatty acid)
CH2
CH
CH2
OCR
OCR
O
O
O
OCR
a triglycerideR = n-C15H31
Prostaglandins
a prostaglandin
O
HO
CO2H
OHarachadonic acid
CO2Hcyclo-
oxygenase
natural mediators of inflammation
Penicillins from moldPenicillium chrysogenum
R= NH2 ampicillin
N
S
CO2H
PhCHCNHO
R
O
R = H penicillin G
From Ergot Fungus
(+) lysergic acid
N
NH
CH3HO2CH
Common Nomenclature
HCO2H
CH3CO2H
CO2H
CO2H
CO2H
Prefix
form
acet
propion
butyr
valer
prefix + ic + _acid
CO2HCl
-chlorovaleric acid
CO2H
CO2H
CO2H
capro
enanth
capryl
CO2Hpelargon
CO2Hcapr
CO2H
Cl Cldichloro--phenylcaprylic acid
I.U.P.A.C. Nomenclature
O
OHheptanoic acid
drop e from alkane and add "oic acid"
CO2H(Z) 2-methyl-2-pentenoic acid
CO2H
cyclopentanecarboxylic acid
CH2CO2H
Brp-bromophenylethanoic acidp-bromophenylacetic acid
Dicarboxylic AcidsHO2CCO2H or ethanedioic acid
HO2CCH2CO2H
HO2CCH2CH2CO2H
HO2CCH2CH2CH2CO2H
HO2CCH2CH2CH2CH2CO2H
HO2CCH2CH2CH2CH2CH2CO2H
oxalic acid
malonic acid
succinic acid
glutaric acid
adipic acid
pimelic acid
'
A Diacid
OH
O
O
HO
Br Cl
-bromo-'-chloroadipic acid2-bromo-4-chlorohexanedioic acid
Unusually High Melting and Boiling Points
Boiling Points
CH3COH
O
CH3CH2CH2OH
CH3CH2CHO
b.p. Co
118
97
49
CH3CH2OCH3 8
Acidity is due to Delocalization of the Charge in the Conjugate Base
Alcohol vs. Acid
e- Withdrawing Groups Enhance Acidity
Benzoic acids
CO2H
NO2
CO2H
CHO
CO2H
H
CO2H
OCH3
pKa: 3.41 3.75 4.19 4.46
CO2H
Cl
4.0
most deactivated most activated
Deprotonation
COH
O
+ NaHCO3
CO
O
Na
+ H2CO3
pKa 4.2 pKa 6.5
Carboxylic Acid Preparations
• Oxidation of 1o alcohols and aldehydes with Na2Cr2O7/H2SO4
• KMnO4 oxidation of alkylbenzenes
• Grignard reaction with CO2 (Carboxylation)• Hydrolysis of a carboxylic derivative:
e.g. acid chloride, acid anhydride, ester, amide, nitrile
Grignard Reaction with CO2
Br1) Mg, ether
2) CO2, -78oC3) H3O+
CO2H
Mechanism
CO2H
3) H3O+2) CO2, -78oC
1) Mg, etherBr
MgBr
C
O
OC
O
O MgBr
H+Mg
Hydrolysis of a Nitrile
BrKCN
CNH3O+
or 1) NaOH2) H3O+
CO2HSN2
Reduction of Carboxylic Acids
Carboxylic Acid Derivatives
Acid ChloridesAcid Anhydrides
EstersAmidesNitriles
Nucleophilic Acyl Substitution
Reactivity of Acid Derivatives
I.U.P.A.C. Nomenclature(uses carboxylic acid template)
O
Cl O
O O
O
OCH3
O
NH2
CN
pentanoyl chloride pentanoic anhydride
methyl pentanoate pentanamide
pentanenitrile
drop "ic acid" add "yl chloride" drop "acid" add "anhydride"
"alkyl" _ drop "ic acid" add "ate" drop "oic acid" add "amide"
drop "ic acid" add "e_nitrile"
Acid Chlorides
CCl
OOCH3
o-methoxybenzoyl chloride
O
Cl
(E) 2-octenoyl chloride
CH2CCl
O
CH3O
(p-methoxyphenyl)acetyl chloride
Acid Anhydrides
O
O O
butanoic anhydridebutyric anhydride
CO
C
O O
CH3
acetic benzoic anhydride
O OO
succinnic anhydride
OH
O
O
HO
succinnic acid
Esters
COCH2CH2CH3
O
O
O
(Z) cyclopentyl 2-butenoatepropyl benzoate
COCH2CH(CH3)2
O
isobutyl cyclohexanecarboxylate
CH2COCH2CH3
O
ethyl phenylacetate
Amides
CH3
CNH2
O
meta methylbenzamide
OH2N
2-ethyl-3-methylpentanamide-ethyl--methylvaleramide
CN(CH3)2
O
N,N-dimethylcyclopentanecarboxamide
HCN
O
HN-benzylformamide
Lactones (cyclic esters)
OH
O
HO
-hydroxyvaleric acid
O
O
-valerolactone
+ H2O
OH
O
OH-hydroxyenanthic acid
O
O
-enantholactone
+ H2O
Gamma Hydroxybutyrate
HO CO2H HO CO2 Na
or sodium -hydroxybutyratesodium 4-hydroxybutanoate
H3O+
O
O
+ H2O
-butyrolactone
(GHB)
-hydroxybutyric acid
CNS depressantas of 2000, Schedule I controlled substance
If mixed with ROH, the depressanteffects are enhanced
All Acid Derivatives can be Hydrolyzed
O O
OCH(CH3)2(CH3)2CHO
diisopropyl pimelate
HydrolysisH3O+ orin base
O O
OHHO
+ 2 (CH3)2CHOH
What are the 3 Hydrolysis Products?
O
O
C
O
N(CH2CH3)2
Two hydrolyzable groups
H3O+
products are carboxylic acid(s) + conjugate acid of the LGs
O
O
C
O
N(CH2CH3)2
H3O+ OH
CO2H
+ HN(CH2CH3)2
+ HO
O
Draw the Hydrolysis Products
CH2CNHO
NO
SCH3
CH3
CO2-K+
H3O+
penicillin G
Hydrolysis of Penicillin
CH2CO2H
CO2H N
NH2S
CO2HH
CH2CNHO
NO
SCH3
CH3
CO2-K+
H3O+
penicillin G
Aspartame
HOCCH2CHCNHCHCOCH3
O
NH2 CH2
O O
H3O+ HOCCH2CHCOH
O O
NH2
H2NCHCOH
CH2
OHOCH3
aspartic acid
phenylalanine
methanol
Nucleophilic Acyl Substitution
Nucleophilic Acyl Substitution
LG
O
+ Nu LG
O
Nu
O
Nu+ LG
LG = Cl , OCCH3 , OCH3 , NH2
O
best worst
Hydrolysis of an Acid Chloride
Acid Chloride Preparation
COH
OCCl
O
+ SO2+ HCl
SOCl2
in N
O
OH SOCl2, pyridine CCl
O
C OH
O
+ HCl+ SO2
S
O
ClCl
C OH
OS
O
ClCl
C OH
OS
O
ClC
O
OS
O
Cl
Cl
pyr:
C O
OS
O
Cl
Cl
With Acid Chlorides, No Catalyst is Needed
Anhydride Prep.
Cl
OHO
O
O
O O H
Cl
O
O O H Cl
O
O O + HCl
addition
elimination
deprotonation
Ester Preparationfrom an acid chloride
Amide Preparationfrom an Acid Chloride
Amide from Anhydride
Fischer Esterification
Flavors and FragrancesO
O
O
O
O
O
O
O
O
O
O
O
apple
pear
banana
"juicy fruit"
rum
COCH3
O
NH2
COCH3
OOH
O
O
O
O
orange
honey
wintergreen
grape
peach
Intramolecular Fischer Esterification - GHB
HOO
OHH3O+
O
O
+ H2O
HOO
OHH3O+
O
O
+ H2O
HOO
OH
HHO
O
OH
H
O H
OHHO
O
OHHOH
O
OHH2O
H+ trans.
Lactam (cyclic amide) Formation
-Lactams as Antibiotics
Acid Catalyzed “Olysis” Reactions
O
OCH2C6H5
H3O+
NH3, H+(pH 4)
methanolysis
CH3OH, H+
aminolysis
hydrolysis
+ C6H5CH2OH
COH
O
CNH2
O
COCH3
O
Transesterificationa Methanolysis
OCH2C6H5
O
OCH3
O
CH3OH, H+
+ C6H5CH2OH
OCH2C6H5
O
OCH3
O
CH3OH, H+
+ C6H5CH2OH
H+
O
OCH2C6H5
H
HOCH3
OH
OCH3
OCH2C6H5
H
OH
OCH3
OCH2C6H5
HH+ trans.
OCH3
O HCH3OH
Aspirin Synthesis
CO2H
OH CH3COCCH3
O O
H2SO4 (aq)
OCCH3
CO2H O
+ CH3CO2H
CH3COCCH3
OHO
CO2H
OH CH3COCCH3
O O
H2SO4 (aq)
OCCH3
CO2H O
+ CH3CO2H
H+
CO2H
OCOCCH3
OH
CH3H
O CO2H
OC
CH3
OH
OCCH3
H
O
+ CH3CO2H
OCCH3
CO2H OH
H+ transf.
OH2
Basic Hydrolysis Saponification
Basic Hydrolysis of an Amide
Mechanism
+ HN(CH2CH3)2
CN(CH2CH3)2
O
NaOH, H2OOH
C
O
OH
N(CH2CH3)2C
O
OH+ N(CH2CH3)2
C
O
O NaH+
acidcarb.
CO2H
CCl
O
COCCH3
O O
COCH3
O
CNH2
O
1) LiAlH4
2) H3O+
CH2OH
CH2OH
CH2OH
CH2OH
CH2NH2
+ HCl
+ CH3CH2OH
+ H2O
+ CH3OH
LiAlH4 Reductions
Reduction of Esters with LiAlH4
DIBAHDiisobutyl Aluminum Hydride
Reduction of an Ester to an Aldehyde
COCH2CH3
O
1) DIBAHin toluene
CH
O
+ CH3CH2OH
Al
H
CH2CH(CH3)2(CH3)2CHCH2
DIBAH
2) H3O+
