# 20.3 Preparation of Amines This section outlines the primary methods for synthesizing amines, focusing on reactions involving alkyl halides and the reduction of various nitrogen-containing functional groups. For background on the structure and classification of amines, refer to . ### 1. By the Reaction of Alkyl Halides with Ammonia (Ammonolysis) When an alcoholic solution of ammonia is heated with an alkyl halide in a sealed tube at $100^{\circ} \mathrm{C}$, a nucleophilic substitution reaction occurs. Ammonia acts as a nucleophile, displacing the halide ion. However, the resulting primary amine is also nucleophilic and can further react with the alkyl halide. This process, known as **ammonolysis**, typically yields a mixture of primary, secondary, and tertiary amines, along with a quaternary ammonium salt. **Stepwise Reaction:** 1. **Formation of Primary Amine:** $$R-X + \ddot{N}H_3 \rightarrow [R-\mathrm{NH}_3]^+X^- \xrightarrow{NH_3} R-\mathrm{NH}_2 + \mathrm{NH}_4^+X^-$$ 2. **Formation of Secondary Amine:** $$R-\mathrm{NH}_2 + R-X \rightarrow [R_2\mathrm{NH}_2]^+X^- \xrightarrow{NH_3} R_2\mathrm{NH} + \mathrm{NH}_4^+X^-$$ 3. **Formation of Tertiary Amine:** $$R_2\mathrm{NH} + R-X \rightarrow [R_3\mathrm{NH}]^+X^- \xrightarrow{NH_3} R_3\mathrm{N} + \mathrm{NH}_4^+X^-$$ 4. **Formation of Quaternary Ammonium Salt:** $$R_3\mathrm{N} + R-X \rightarrow [R_4\mathrm{N}]^+X^-$$ ### 2. By the Reduction of Nitrogen-Containing Functional Groups Amines can be effectively synthesized by reducing functional groups that contain nitrogen. #### a. Reduction of Nitriles (Cyanides) Reduction of alkyl or aryl nitriles produces primary amines. * **Reagents:** Common reducing agents include lithium aluminum hydride ($\mathrm{LiAlH}_4$) or sodium metal in ethanol ($\mathrm{Na}/\mathrm{C}_2\mathrm{H}_5\mathrm{OH}$). **General Reaction:** $$R-\mathrm{C}\equiv\mathrm{N} \xrightarrow{\mathrm{LiAlH}_4 \text{ or } \mathrm{Na}/\mathrm{C}_2\mathrm{H}_5\mathrm{OH}} R-\mathrm{CH}_2-\mathrm{NH}_2$$ #### b. Catalytic Reduction of Nitriles Nitriles can also be reduced using hydrogen gas in the presence of a metal catalyst. * **Catalysts:** Common catalysts include Raney nickel (Raney Ni), platinum (Pt), or rhodium on alumina ($\mathrm{Rh}-\mathrm{Al}_2\mathrm{O}_3$). **General Reaction:** $$R-\mathrm{C}\equiv\mathrm{N} + 2\mathrm{H}_2 \xrightarrow{\text{Ni, Pt, or Pd}} R-\mathrm{CH}_2-\mathrm{NH}_2$$ **Example with Benzonitrile:** $$\mathrm{C}_6\mathrm{H}_5-\mathrm{C}\equiv\mathrm{N} + 2\mathrm{H}_2 \xrightarrow{\text{Raney Ni}} \mathrm{C}_6\mathrm{H}_5-\mathrm{CH}_2-\mathrm{NH}_2$$ *Benzonitrile to Benzylamine* #### c. Reduction of Nitro Compounds Both aliphatic and aromatic nitro compounds can be reduced to form primary amines. This is a particularly important method for synthesizing anilines. * **Reagents:** * **Chemical Reduction:** A metal (like tin, Sn, or iron, Fe) in the presence of a strong acid (like concentrated HCl). * **Catalytic Hydrogenation:** Hydrogen gas ($\mathrm{H}_2$) with a catalyst like palladium (Pd), platinum (Pt), or nickel (Ni). **Example with Nitrobenzene:** $$\mathrm{C}_6\mathrm{H}_5-\mathrm{NO}_2 + 6[\mathrm{H}] \xrightarrow{\text{Sn/HCl or Fe/HCl}} \mathrm{C}_6\mathrm{H}_5-\mathrm{NH}_2 + 2\mathrm{H}_2\mathrm{O}$$ *Nitrobenzene to Aniline (Phenylamine)* #### d. Reduction of Amides Amides can be converted to amines using two distinct methods that yield different products. **i. Reduction using $\mathbf{LiAlH_4}$** * When an amide is treated with the strong reducing agent lithium aluminum hydride ($\mathrm{LiAlH}_4$), the carbonyl group ($>\mathrm{C}=\mathrm{O}$) is reduced to a methylene group ($-\mathrm{CH}_2-$). * This reaction forms a primary amine while keeping the carbon chain length intact. **General Reaction:** $$R-\mathrm{CO}-\mathrm{NH}_2 \xrightarrow{1. \ \mathrm{LiAlH}_4 / \text{ Ether} \quad 2. \ \mathrm{H}_2\mathrm{O}} R-\mathrm{CH}_2-\mathrm{NH}_2$$ **ii. Hoffmann Degradation Reaction** * When an amide is treated with bromine ($\mathrm{Br}_2$) in the presence of a strong base (like KOH or NaOH), a degradation reaction occurs. * This reaction, known as the **Hoffmann degradation** or **Hoffmann bromamide reaction**, produces a primary amine with **one less carbon atom** than the starting amide. **General Reaction:** $$R-\mathrm{CO}-\mathrm{NH}_2 + \mathrm{Br}_2 + 4\mathrm{KOH} \rightarrow R-\mathrm{NH}_2 + \mathrm{K}_2\mathrm{CO}_3 + 2\mathrm{KBr} + 2\mathrm{H}_2\mathrm{O}$$ **Example with Acetamide:** $$\mathrm{CH}_3-\mathrm{CO}-\mathrm{NH}_2 + \mathrm{Br}_2 + 4\mathrm{KOH} \rightarrow \mathrm{CH}_3-\mathrm{NH}_2 + \mathrm{K}_2\mathrm{CO}_3 + 2\mathrm{KBr} + 2\mathrm{H}_2\mathrm{O}$$ *Acetamide to Methylamine*