1. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Review of Organic Functional Groups (Functional Group Analysis) Carboxylic Acids Chapter 11

2. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Functional Group Analysis Carboxylic Acids Nomenclature Common nameIUPAC name Formic acidMethanoic acid Acetic acid (vinegar) Propionic acid Propanoic acid Ethanoic acid Lauric acid Stearic acid cis or Z stereochemistry 12 3  -3 NOTE: Z stereochemistry of natural products Methanoic acid

3. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Functional Group Analysis Carboxylic Acids Physical-Chemical Properties 1. Bonding: Intermolecular bonding - self van der WaalDipole-dipole High boiling points/melting points Intermolecular bonding H2OH2O Carboxyl solubilizing potential ~3 carbons(polyfunctional molecule)

4. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Functional Group Analysis Carboxylic Acids Physical-Chemical Properties 1. Bonding: Ethanol as a pharmaceutical solvent van der Waal Dipole-dipole Improved solubility 2. Acidity: The ability of a substance to donate a proton. Stability of anion acidity R - electron withdrawing acidity R - electron donating acidity

5. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Functional Group Analysis Role of Electron Withdrawing/Releasing Groups on Acidity Alkylcarboxylic acidsElectron donors/release Substituted Carboxylic acids Substituent Affects R = Actual pKa Carboxylic Acids pKa = 3.75H- CH 3 -pKa = 4.76 C2H5-C2H5- CCl 3 - pKa = 4.87 pKa = 0.64 Arylcarboxylic acidsElectron withdrawing aryl pKa = 4.21 pKa = 3.44 pKa = 4.38 Inorganic acids (H 2 SO 4, HCl, HNO 3 ) >> Aryl acids >Alkyl acids > Phenol > Aryl amines > Alkyl amines Nearly total dissociation in waterWeak dissociation in waterDissociation of conjugate acid in water Electron-withdrawing alkyl Electron donors/release

6. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Functional Group Analysis pH Consideration of Organic Functional Groups H 2 SO 4 HCl HNO 3 H 3 O ArOH RSO 2 NH 2 C O N H C O H 2 O ArNH 2 C NH NH 2 R AlkylNH 2 C NH NH 2 HNR NaOH, KOH ACIDS BASES I n c r e a s i n g A c i d i t y I n c r e a s i n g B a s i c i t y RCO 2 H N

7. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Functional Group Analysis Physical-Chemical Properties 3. Chemical reactivity: Salt formation Carboxylic Acids Soluble salts include:Insoluble salts include: Soluble salt’s affect on pH of aqueous media Salt of a weak acid (organic acids are weak) NaOH Salt of a strong base pH 7 pH of aqueous media predicted to be alkaline

8. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Functional Group Analysis Metabolism Carboxylic Acids -Phase 1:  -oxidation Unbranched fatty acids  -Phase 2: Glucuronidation UDPGA +

9. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Functional Group Analysis Metabolism Carboxylic Acids -Phase 2 Amino acid conjugation R-COOH + ATP + CoAR-CO-S-CoA + AMP Activated carboxylic acid +