Organic Chemistry II The Chemistry of Amines

1. Organic Chemistry IIThe Chemistry of Amines Dr. Ralph C. Gatrone Department of Chemistry and Physics Virginia State University

2. Chapter Objectives • Nomenclature • Properties • Preparation • Reactions • Spectroscopy

3. Nomenclature • Alkyl amines • Aryl amines

4. Alkyl Amines and Aryl Amines • Much of their chemistry is similar • Differences are substantial

5. Nomenclature • Primary Amines • Add the word amine to the akyl substituent • Replace e with suffix “amine” in parent • Use “amino” as substituent when two functional groups are present

6. Nomenclature • Secondary and Tertiary Amines • Symmetrical – add “di” or “tri” to alkyl group • Unsymmetrical – N-substituted primary amine

7. Aryl Amines • Phenylamine

8. Heterocyclic Amines

9. Heterocyclic Amines

10. Properties of Amines • Similar to ammonia • sp3 hybridized N • Tetrahedral geometry • Can be chiral • Generally not resolvable • due to pyramidal inversion process • Barrier to inversion is ~25kJ/mol

11. Properties • Amines with < 5 carbons are water soluble • Readily hydrogen bond • Highly associated structures • Higher boiling points than alkanes of similar MW • Low MW amines have distinctive fish-like odor • Pentane-1,5-diamine (cadaverine) has disgusting odor

12. Industrial Applications • Insecticides • Pharmaceuticals

13. Basicity of Amines • Nitrogen has lone pair of electrons • Dominates chemistry of amines • Basic and nucleophilic • React with acids accepting a proton • React with alkyl halides • Stronger bases than alcohols and ethers • Kb values indicate base strength • Large Kb (small pKb) indicates stronger base • Generally consider the pKa of ammonium salt

14. pKa value

15. Some Amines and pKa Valuesof the ammonium ion

16. Basicity • Aryl amines are less basic than alkyl amines • The N in amides are non-basic • Poor nucleophile as well • Primary and secondary amines are acidic as well • pKa value is approximately 40

17. Basicity • Aryl amines are less basic because the lone pair is often delocalized in the aromatic ring • Substituents on ring can make the nitrogen more or less basic • Electron donating groups increase basicity • Electron withdrawing groups decrease basicity

18. Preparation of Amines • Reduction

19. Preparation of Amines • Nucleophilic substitution

20. Preparation of Amines • Reductive Amination of Ketones/Aldehydes • Reaction proceeds via the imine • NH3, primary and secondary amines work

21. Reactions of Amines • Alkylation and Acylation of Amines • Most general reactions • Fully covered elsewhere

22. Reactions of Amines • Hoffmann Elimination • Alkene formation • NH2 is poor leaving group • Reaction requires making it a better LG • Hoffmann Elimination coverts amine into quaternary ammonium salt by reacting with CH3I

23. Hoffmann Elimination Details

24. Aromatic Substitution of Amines • NR2 strongly activating • o, p directing • Often get poly substituted products

25. Aromatic Substitution of Amines • Friedal-Crafts akylation • Does not work with amines • Fridal-Crafts acylation • Does not work with amines • Amides provide less reactive alternative to amines which allow substitution to occur

26. Substitution of Amides

27. Substitution of Amides • Amide provides • Less activating, o,p directing substituent • Readily removed if needed using aqueous base