carboxylic acids
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 PresentationTRANSCRIPT
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+