Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Review of Organic Functional...
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Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Review of Organic Functional Groups (Functional Group Analysis) Carboxylic Acids Chapter 11 Ibuprofen C H (CH 3 ) 2 CH-CH 2 CH 3 C O OH
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Transcript of Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Review of Organic Functional...
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Review of Organic Functional Groups (Functional Group Analysis)
Carboxylic Acids Chapter 11
Ibuprofen
CH
(CH3)2CH-CH2
CH3
C
O
OH
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Functional Group AnalysisCarboxylic Acids
Nomenclature Common name IUPAC name
Formic acid H C
O
OH Methanoic acid
Acetic acid(vinegar)
CH3 C
O
OH
Propionic acid CH2 C
O
OHCH3Propanoic acid
Ethanoic acid
(CH2)10 C
O
OHCH3
Lauric acid
(CH2)16 C
O
OHCH3
Stearic acid
HH
(CH2)7 (CH2)7 COOHH3C
Oleic acid
cis or Z stereochemistry
HH
CH2 (CH2)7 COOH
HH
CH2H3C
Linoleic acid
1 2
3
-3
HH
CH2 (CH2)7 COOH
HH
CH2
Linolenic acid
CH3(CH2)4
HH
CO2H
Arachidonic acid
NOTE: Z stereochemistry of natural products
COOH
Benzoic acid
R C
O
OH
Methanoic acid
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Functional Group AnalysisCarboxylic Acids R C
O
OH
Physical-Chemical Properties
1. Bonding:
R C
O
O HR C
O
O H
Intermolecular
bonding - selfR C
O
O H
RC
O
OH
van der Waal Dipole-dipoleDipole-dipole
High boiling points/melting points
R C
O
O H
H OH H O
H
H O
H
HOH
Intermolecularbonding
H2O
R C
O
O H O
HIon-dipole bonding
Carboxyl solubilizing potential ~3 carbons(polyfunctional molecule)
O
O H
O
OH
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Functional Group AnalysisCarboxylic Acids R C
O
OH
Physical-Chemical Properties
1. Bonding: Ethanol as a pharmaceutical solvent
CH2
C
O
O HCH2
H3C
OCH2
H3CH
OCH2
CH3
H
van der Waal
Dipole-dipole
Improved solubility
2. Acidity: The ability of a substance to donate a proton.
R C
O
OH + H2O H3O R C
O
O+
Stability of anion acidity
R C
O
OR - electron withdrawing acidity
R - electron donating acidity
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Functional Group AnalysisRole of Electron Withdrawing/Releasing Groups on Acidity
Alkylcarboxylic acids Electron donors/release
Substituted Carboxylic acids Substituent Affects R = Actual pKa
Carboxylic Acids R C
O
OH
pKa = 3.75H-
CH3- pKa = 4.76
C2H5-
CCl3-
pKa = 4.87
pKa = 0.64
Arylcarboxylic acids Electron withdrawing aryl pKa = 4.21
O2N pKa = 3.44
H3C pKa = 4.38
Inorganic acids (H2SO4, HCl, HNO3) >> Aryl acids >Alkyl acids > Phenol > Aryl amines > Alkyl amines
Nearly total dissociation in water Weak dissociation in water Dissociation of conjugate acid in water
Electron-withdrawing alkyl
Electron donors/release
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Functional Group AnalysispH Consideration of Organic Functional Groups COOH
R
COOH
R
COOH COOH
R
COOH
R
> > > >
Most acidic Least acidic
Most acidic Least acidic
R C
O
OH R C
O
OHHC
O
OH> >
H2SO4
HCl
HNO3
H3O
ArOH
RSO2NH2
CO
NH
CO
H2O
ArNH2
C
NH
NH2R
Alkyl NH2
C
NH
NH2HNR
NaOH, KOH
ACIDS
BASES
Increasing
Acidity
Increasing
Basicity
RCO2H
N
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Functional Group Analysis
Physical-Chemical Properties
3. Chemical reactivity: Salt formation
Carboxylic Acids R C
O
OH
R CO
OH
Acid
+ MOH
Base
H2OR CO
O M +
SaltR C
O
O
H OH H O
H O
H
OH
H
H
MH
OH
HO
H
HO
H
Soluble salts include:
Na
K
NH4
Ca2+
Mg2+
Other heavy metalsInsoluble salts include: Soluble salt
R CO
O M
Salt
Soluble salt’s affect on
pH of aqueous media
R C
O
OH
Salt of a weak acid (organic acids are weak)
NaOHSalt of a strong base
pH 7
pH 7
pH 7 pH of aqueous mediapredicted to be alkaline
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Functional Group Analysis
Metabolism
Carboxylic Acids R C
O
OH
-Phase 1: -oxidation
CH2 CO
OHCH2R
Unbranched fatty acids
CoA
CH2 CO
S-CoACH2R[O]
CH2 CO
S-CoACHRHO
R CO
OH CH3 CO
SCoA+
-Phase 2: Glucuronidation
UDP-glucuronosyltransferase (UGT)
UDPGA + R C
O
OH
O
COO
HO
OH
OH
Glucuronide
RC
O
O
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Functional Group Analysis
Metabolism
Carboxylic Acids R C
O
OH
-Phase 2 Amino acid conjugation
R-COOH + ATP + CoAacyl synthetase
R-CO-S-CoA + AMP
Activated carboxylic acid
CH2 CO
OHH2N
Glycine
R C S-CoA
O
transacetylase CH2 CO
OHHNC
O
R
Glycinate conjugate
R C S-CoA
O
CH (CH2)2H2N
Glutamine
COOH
C
O
NH2+transacetylase CH (CH2)2
HN
COOH
C
O
NH2C
O
R
Glutamate conjugate
