The Physical and Chemical Properties, and Reactions of Amines

1. The Physical and Chemical Properties, and Reactions of Amines Chem-261

2. => Introduction • q. Dr Seemal Jelani

3. Classes of Amines • Primary (1): one C-N bond, 2 N-H bonds. • Secondary (2): two C-N bonds, 1 N-H bond. • Tertiary (3): three C-N bonds, no N-H bond. • Quaternary (4): four C-N bonds, nitrogen has a + formal charge. Dr Seemal Jelani

4. => Classify: Dr Seemal Jelani

5. Common Names Name the alkyl or aryl groups bonded to nitrogen, then add suffix -amine. diethylmethylamine cyclopentylmethylamine Diphenylamine => Dr Seemal Jelani

6. Amine as Substituent • On a molecule with a higher priority functional group the amine is named as a substituent. -aminobutyric acid or 4-aminobutanoic acid 2-methylaminophenol => Dr Seemal Jelani

7. IUPAC Names • Name is based on longest carbon chain. • -e of alkane is replaced with -amine. • Substituents on nitrogen have N- prefix. 3-bromo-1-pentanamine N,N-dimethyl-3-hexanamine => Dr Seemal Jelani

8. aniline N,N-dimethylaniline 4-methylanilineor p-toluidine => Aromatic Amines Amino group is bonded to a benzene ring. Parent compound is called aniline. Dr Seemal Jelani

9. Pyridine aziridine Pyrrolidine Pyrrole 2-methylpyridine Heterocyclic Amines The nitrogen is assigned the number 1. Dr Seemal Jelani

10. Structure of Amines Nitrogen is sp3 hybridized with a lone pair of electrons in an sp3 orbital. Dr Seemal Jelani

11. => Chirality of Amines Nitrogen may have 3 different groups and a lone pair, but enantiomers cannot be isolated due to inversion around N. Dr Seemal Jelani

12. => Boiling Points • N-H less polar than O-H. • Weaker hydrogen bonding. • Tertiary amines cannot hydrogen bond. Dr Seemal Jelani

13. 1,5-pentanediamine or cadaverine => Solubility and Odor • Small amines (<6 C) soluble in water. • All amines accept hydrogen bonds from water and alcohol. • Branching increases solubility. • Most amines smell like rotting fish. Dr Seemal Jelani

14. Basicity of Amines • Lone pair of electrons on nitrogen can accept a proton from an acid • Aqueous solutions are basic to litmus. • Ammonia pKb = 4.74 • Alkyl amines are usually stronger bases than ammonia • Increasing the number of alkyl groups decreases solvation of ion, so 2 and 3 amines are similar to 1 amines in basicity. Dr Seemal Jelani

15. Why is alkyl amine more basic than ammonia? Dr Seemal Jelani Alkyl Amine is more basic than ammonia because of the +I effect of the Alkyl group present It donates its electron cloud to the nitrogen group therefore nitrogen has a greater tendency to donate it lone pair of electrons This makes it more basic than ammonia where such a positive inductive effect is absent.

16. => Resonance Effects Any delocalization of the electron pair weakens the base. Dr Seemal Jelani

17. => Amine Salts • Ionic solids with high melting points • Soluble in water • No fishy odor Dr Seemal Jelani

18. Reactions of Amines Chem-261 Dr Seemal Jelani

19. Reaction of Amines • Amines are BASES! • React with acids and accept a proton (H+) to Form alkyl ammonium salts

20. Reaction of Amines • Amines are BASES! ?

21. Electrophilic Substitution of Aniline • -NH2 is strong activator, o-,p-directing. • May trisubstituted with excess reagent. • H+ changes -NH2 to -NH3+, a meta-directing deactivator. • Attempt to nitrate aniline may explode. => Dr Seemal Jelani

22. Aniline Substitution Dr Seemal Jelani =>

23. => Electrophilic Substitution of Pyridine • Strongly deactivated by electronegative N. • Substitutes in the 3-position. • Electrons on N react with electrophile. Dr Seemal Jelani

24. Alkylation of Ammonia Desired reaction is: + 2 NH3 + R—X R—NH2 NH4X

25. + – •• •• R R X X H3N H3N •• •• •• •• •• •• H H + + R H N H3N H R H3N N •• •• H H Alkylation of Ammonia Desired reaction is: + 2 NH3 + R—X R—NH2 NH4X via: + + then: + +

26. – + X R4N Alkylation of Ammonia But the method doesn't work well in practice.Usually gives a mixture of primary, secondary,and tertiary amines, plus the quaternary salt. RX RX NH3 RNH2 R2NH RX RX R3N

27. Example NH3 CH3(CH2)6CH2Br CH3(CH2)6CH2NH2 • As octylamine is formed, it competes with ammonia for the remaining 1-bromooctane. Reaction of octylamine with 1-bromooctane gives N,N-dioctylamine. (45%) + CH3(CH2)6CH2NHCH2(CH2)6CH3 (43%)

28. Gabriel Synthesis • gives primary amines without formation ofsecondary, etc. amines as byproducts • uses an SN2 reaction on an alkyl halide to formthe C—N bond • the nitrogen-containing nucleophileis N- potassiophthalimide

29. O – + K N NH •• •• O N-Potassiophthalimide • the pKa of phthalimide is 8.3 • N- potassiophthalimide is easily prepared bythe reaction of phthalimide with KOH O KOH •• O

30. O •• R X N R •• •• •• O – •• + X •• •• •• N-Potassiophthalimide as a nucleophile O SN2 – + N •• •• O

31. O + H2O N R •• O CO2H H2N R CO2H Cleavage of Alkylated Phthalimide • imide hydrolysis is nucleophilic acyl substitution acid or base +

32. Sulfa drugs are sulfonamides • that are antibacterial agents. => Formation of Sulfonamides • Primary or secondary amines react with sulfonyl chloride. Dr Seemal Jelani

33. => Oxidation of Amines • Amines are easily oxidized, even in air. • Common oxidizing agents: H2O2 , MCPBA. • Meta chloroperoxybenzoic acid • 2 Amines oxidize to hydroxylamine (-NOH) • 3 Amines oxidize to amine oxide (-N+-O-) Dr Seemal Jelani

34. primary amine tertiary amine => Reduction Dr Seemal Jelani

35. => Reduction of Nitro Compounds (1) • -NO2 is reduced to -NH2 by catalytic hydrogenation, or active metal with acid. • Commonly used to synthesize anilines. Dr Seemal Jelani

36. => Hofmann Rearrangement of Amides (1) In the presence of a strong base, primary amides react with chlorine or bromine to form amines with one less C. Dr Seemal Jelani