Nitrogen Containing Organic Compounds - Preparation of Amines

• Amines are organic compounds that contain one or more nitrogen atoms bonded to carbon atoms.
• They can be prepared by various methods, such as:
  • Reduction of Nitro Compounds
  • Reduction of Amides
  • Gabriel Synthesis
  • Hoffmann Bromamide Reaction
  • Reduction of Nitriles

Reduction of Nitro Compounds

• Nitro compounds can be reduced to primary amines.
• The reduction is typically done using a reducing agent like:
  • Sodium amalgam (Na/Hg)
  • Zinc dust (Zn)
• The reaction can be represented as:
  • R-NO2 + 6[H] -> R-NH2 + 2H2O

Example: Reduction of Nitrobenzene

• Nitrobenzene can be reduced to aniline (phenylamine).
• The reduction is typically done using tin and hydrochloric acid (Sn/HCl).
  • C6H5NO2 + 6[H] -> C6H5NH2 + 2H2O

Reduction of Amides

• Amides can be reduced to primary amines.
• The reduction is typically done using a reducing agent like:
  • Lithium aluminum hydride (LiAlH4)
  • Sodium borohydride (NaBH4)
• The reaction can be represented as:
  • R-CONH2 + 4[H] -> R-NH2 + 2H2O

Example: Reduction of Acetamide

• Acetamide can be reduced to methylamine.
• The reduction is typically done using lithium aluminum hydride (LiAlH4).
  • CH3C(O)NH2 + 4[H] -> CH3NH2 + H2O

Gabriel Synthesis

• Gabriel synthesis is a method for the preparation of primary amines.
• It involves the reaction of an alkyl halide with phthalimide, followed by hydrolysis.
• The reaction can be represented as:
  • R-X + Phthalimide -> R-NH-Phthalimide
  • R-NH-Phthalimide + KOH/H2O -> R-NH2 + Phthalic Acid

Example: Gabriel Synthesis of n-Butylamine

• n-Butylamine can be prepared using Gabriel synthesis.
• 1-Bromobutane is reacted with phthalimide, followed by hydrolysis.
  • CH3(CH2)3Br + Phthalimide -> CH3(CH2)3NH-Phthalimide
  • CH3(CH2)3NH-Phthalimide + KOH/H2O -> CH3(CH2)3NH2 + Phthalic Acid

Hoffmann Bromamide Reaction

• Hoffmann bromamide reaction is a method for the preparation of primary amines.
• It involves the reaction of an amide with bromine and a strong base, followed by hydrolysis.
• The reaction can be represented as:
  • R-CONH2 + Br2 + KOH -> R-NH2 + KBr + H2O

Example: Hoffmann Bromamide Reaction of Acetamide

• Acetamide can be converted to methylamine using Hoffmann bromamide reaction.
• Acetamide is reacted with bromine and potassium hydroxide, followed by hydrolysis.
  • CH3C(O)NH2 + Br2 + KOH -> CH3NH2 + KBr + H2O

Reduction of Nitriles

• Nitriles can be reduced to primary amines.
• The reduction is typically done using a reducing agent like:
  • Lithium aluminum hydride (LiAlH4)
  • Sodium borohydride (NaBH4)
• The reaction can be represented as:
  • R-CN + 4[H] -> R-CH2NH2

Example: Reduction of Acetonitrile

• Acetonitrile can be reduced to ethylamine.
• The reduction is typically done using lithium aluminum hydride (LiAlH4).
  • CH3CN + 4[H] -> CH3CH2NH2

11. Hoffmann Bromamide Reaction of Acetamide

• Acetamide can be converted to methylamine using Hoffmann bromamide reaction:
  • CH3C(O)NH2 + Br2 + KOH -> CH3NH2 + KBr + H2O
• In this reaction, the amide group of acetamide is replaced by a bromine atom and a hydroxyl group.
• The reaction takes place in the presence of a strong base, such as potassium hydroxide.

12. Example: Hoffmann Bromamide Reaction of Acetamide

• Let’s consider the reaction between acetamide and bromine in the presence of potassium hydroxide.
• CH3C(O)NH2 + Br2 + KOH -> CH3NH2 + KBr + H2O
• Acetamide reacts with bromine and potassium hydroxide to form methylamine, potassium bromide, and water.

13. Reduction of Nitriles

• Nitriles can be reduced to primary amines.
• The reduction is typically done using a reducing agent like lithium aluminum hydride (LiAlH4) or sodium borohydride (NaBH4).
• The reaction can be represented as: R-CN + 4[H] -> R-CH2NH2

14. Example: Reduction of Acetonitrile

• Acetonitrile can be reduced to ethylamine.
• The reduction is typically done using lithium aluminum hydride (LiAlH4).
• The reaction can be represented as: CH3CN + 4[H] -> CH3CH2NH2

15. Reduction of Nitro Compounds

• Nitro compounds can be reduced to primary amines.
• The reduction is typically done using a reducing agent like sodium amalgam (Na/Hg) or zinc dust (Zn).
• The reaction can be represented as: R-NO2 + 6[H] -> R-NH2 + 2H2O

16. Example: Reduction of Nitrobenzene

• Nitrobenzene can be reduced to aniline (phenylamine).
• The reduction is typically done using tin and hydrochloric acid (Sn/HCl).
• The reaction can be represented as: C6H5NO2 + 6[H] -> C6H5NH2 + 2H2O

17. Reduction of Amides

• Amides can be reduced to primary amines.
• The reduction is typically done using a reducing agent like lithium aluminum hydride (LiAlH4) or sodium borohydride (NaBH4).
• The reaction can be represented as: R-CONH2 + 4[H] -> R-NH2 + 2H2O

18. Example: Reduction of Acetamide

• Acetamide can be reduced to methylamine.
• The reduction is typically done using lithium aluminum hydride (LiAlH4).
• The reaction is represented as: CH3C(O)NH2 + 4[H] -> CH3NH2 + H2O

19. Gabriel Synthesis

• Gabriel synthesis is a method for the preparation of primary amines.
• It involves the reaction of an alkyl halide with phthalimide, followed by hydrolysis.
• The reaction can be represented as: R-X + Phthalimide -> R-NH-Phthalimide
• R-NH-Phthalimide + KOH/H2O -> R-NH2 + Phthalic Acid

20. Example: Gabriel Synthesis of n-Butylamine

• n-Butylamine can be prepared using Gabriel synthesis.
• 1-Bromobutane is reacted with phthalimide, followed by hydrolysis.
• The reaction is represented as: CH3(CH2)3Br + Phthalimide -> CH3(CH2)3NH-Phthalimide
• CH3(CH2)3NH-Phthalimide + KOH/H2O -> CH3(CH2)3NH2 + Phthalic Acid

Nitrogen Containing Organic Compounds - Preparation of Amines

21. Reductive Amination

• Reductive amination is a versatile method for the preparation of primary, secondary, and tertiary amines.
• It involves the reaction of a carbonyl compound (aldehyde or ketone) with an amine and a reducing agent, such as sodium cyanoborohydride (NaBH3CN) or sodium triacetoxyborohydride (NaBH(OAc)3).
• The reaction can be represented as:
  • R-CHO + R’-NH2 + NaBH3CN -> R-CH2NH-R’ + NaCN + NaBH4
  • R-COR’ + R’’-NH2 + NaBH(OAc)3 -> R-CH(NH-R’’)COR’ + NaOAc + NaBH4

22. Example: Reductive Amination of Benzaldehyde with Methylamine

• Benzaldehyde can be converted to N-methylbenzylamine using reductive amination.
• The reaction is typically done using methylamine and sodium cyanoborohydride.
  • C6H5CHO + CH3NH2 + NaBH3CN -> C6H5CH2NHCH3 + NaCN + NaBH4

23. Hofmann Rearrangement

• The Hofmann rearrangement is a method for the preparation of primary amines.
• It involves the reaction of a primary amide with bromine and a strong base, followed by hydrolysis.
• The rearrangement leads to the isocyanate intermediate, which then hydrolyzes to form the primary amine.
• The reaction can be represented as: RCONH2 + Br2 + KOH -> R-NC + KBr + H2O
• R-NC + H2O -> R-NH2 + CO2

24. Example: Hofmann Rearrangement of Acetamide

• Acetamide can be converted to methylamine using the Hofmann rearrangement.
• Acetamide is reacted with bromine and potassium hydroxide, followed by hydrolysis.
  • CH3C(O)NH2 + Br2 + KOH -> CH3NC + KBr + H2O
  • CH3NC + H2O -> CH3NH2 + CO2

25. Curtius Rearrangement

• The Curtius rearrangement is a method for the preparation of primary amines.
• It involves the reaction of an acyl azide with a reducing agent, such as triphenylphosphine (PPh3), followed by hydrolysis.
• The rearrangement leads to the isocyanate intermediate, which then hydrolyzes to form the primary amine.
• The reaction can be represented as: RCO-N3 + PPh3 -> R-NCO + PPh3O
• R-NCO + H2O -> R-NH2 + CO2

26. Example: Curtius Rearrangement of Acetyl Azide

• Acetyl azide can be converted to methylamine using the Curtius rearrangement.
• Acetyl azide is reacted with triphenylphosphine (PPh3), followed by hydrolysis.
  • CH3CO-N3 + PPh3 -> CH3-NCO + PPh3O
  • CH3-NCO + H2O -> CH3NH2 + CO2

27. Ammonolysis of Esters

• Ammonolysis of esters is a method for the preparation of primary amines.
• It involves the reaction of an ester with ammonia, followed by hydrolysis.
• The reaction can be represented as: RCOOR’ + NH3 -> RCONH2 + R’OH
• RCONH2 + H2O -> R-NH2 + R’COOH

28. Example: Ammonolysis of Ethyl Acetate

• Ethyl acetate can be converted to ethanolamine using ammonolysis.
• Ethyl acetate is reacted with ammonia, followed by hydrolysis.
  • CH3COOC2H5 + NH3 -> CH3CONH2 + C2H5OH
  • CH3CONH2 + H2O -> CH3NH2 + CH3COOH

29. Reactions of Amines

• Amines can undergo various reactions, such as:
  • Nucleophilic substitution reactions
  • Acylation reactions
  • Diazotization reactions
  • Oxidation reactions

30. Example: Nucleophilic Substitution Reaction of Methylamine

• Methylamine can undergo nucleophilic substitution reactions with alkyl halides.
• In the presence of a base, such as sodium hydroxide (NaOH), methylamine reacts with an alkyl halide to form a substituted amine.
  • CH3NH2 + CH3Br + NaOH -> CH3NHCH3 + NaBr + H2O