Basic Character & Preparation of Amines | Chemistry Class 12 - NEET PDF Download

BASIC NATURE OF AMINES

Key observations

• Aniline is less basic than ammonia. The phenyl group withdraws electron density from the nitrogen by resonance (and to a smaller extent by the inductive effect), so the lone pair on nitrogen is less available for protonation.
• Ethylamine is a typical aliphatic primary amine and shows basic behaviour, whereas acetamide (an amide) does not show appreciable basicity. In acetamide the lone pair on nitrogen is delocalised by resonance with the carbonyl group, making it less available to accept a proton.
• The basicity of a nitrogen atom in amines is affected by the s-character of the orbital that holds its lone pair: the smaller the s-character (that is, the more sp3 the nitrogen), the higher the electron density and the stronger the base; the greater the s-character (sp or sp2), the less basic the nitrogen. Examples in decreasing order of basicity (with respect to hybridisation and bonding context) are shown below.

The following illustrative orders are useful to remember:

• Hybridisation effect: CH3CH2CH2NH2 > H2C=CH-CH2NH2 > HC≡C-CH2NH2
• Alkyl vs aromatic: (CH3)2NH > CH3NH2 > NH3 > C6H5NH2
• Electron withdrawing groups such as a phenyl (C6H5-) or an acyl group attached to nitrogen decrease basicity by reducing electron density on nitrogen.
• Comparison of amides and amines: CH3CH2NH2 >> CH3CONH2 ≈ C6H5CONH2
•  Acylation of nitrogen (as in amides) reduces basicity due to resonance with the carbonyl.

Factors affecting basicity of amines (explanations and examples)

• Inductive effect: Electron-donating alkyl groups increase electron density on nitrogen and thus increase basicity; electron-withdrawing groups reduce basicity.
• Resonance (delocalisation): If the lone pair on nitrogen can delocalise into an adjacent π system (for example, in aniline or amides), basicity decreases because the lone pair is less available for protonation.
• Hybridisation: The lone pair in an sp3 orbital is held less tightly (lower s-character) and is more available for protonation than a lone pair in an sp2 or sp orbital. Hence aliphatic (sp3) > vinylic (sp2) > acetylenic (sp) in basicity.
• Solvation and steric hindrance: In solution (particularly in water) solvation stabilises the protonated form. Steric hindrance around nitrogen can reduce solvation of the protonated amine and therefore reduce observed basicity.
• Special cases: Amides (RCONH2) are much less basic than amines due to strong resonance of the nitrogen lone pair with the carbonyl group. Aniline is less basic than ammonia even though phenyl is an electron-releasing group by inductive effect; resonance withdrawal predominates.

METHODS OF PREPARATION OF AMINES

Primary, secondary and tertiary amines can be prepared by many methods. The following list gives important syllabus methods with brief explanations, typical reagents and relevant examples. Image placeholders appear at the same positions as in the original reference material to illustrate mechanisms or intermediate structures; these are retained here for use in class notes or print materials.

1. Hofmann (Hofmann) rearrangement / Hofmann degradation (preparation of primary amines from amides)

   Primary amines having one carbon atom less than the original amide are obtained when a primary amide is treated with bromine and aqueous alkali (or chlorine and alkali). The reaction proceeds via formation of an N-bromoamide, which loses a molecule of CO2 after rearrangement to give an isocyanate; hydrolysis of the isocyanate yields the amine.

   

   A typical reagent set and an outline of steps are often shown as:

   RCONH₂ + Br₂ + 4NaOH → RNH₂ + Na₂CO₃ + 2NaBr + 2H₂O (overall)

   
   

   The sequence includes formation of N-bromoamide, intramolecular rearrangement to an isocyanate (R-N=C=O) and hydrolysis to R-NH2 and CO2.

2. Curtius, Schmidt and Lossen rearrangements (rearrangements giving isocyanates → amines)

   These rearrangements involve migration (1,2-shift) of an alkyl or aryl group from carbon to nitrogen with loss of a leaving group; they produce isocyanates which on hydrolysis give primary amines. The leaving groups differ in each reaction:

   • Hofmann: leaving group is halogen (Br).
   • Curtius/Schmidt: leaving group is N2 (from azide).
   • 
   
   

   (a) Curtius reaction

   An acyl chloride is converted to an acyl azide (RCO-N3) (usually via reaction with NaN3); upon thermal decomposition (pyrolysis) the acyl azide loses N2 to give an isocyanate, which on hydrolysis yields the corresponding amine.

   RCOCl + NaN3 → RCON3 + NaCl

   
   
   

   (b) Schmidt reaction

   A carboxylic acid reacts with hydrazoic acid (HN3) in the presence of strong acid (e.g., conc. H2SO4) to give an acyl azide intermediate which rearranges to an isocyanate and on hydrolysis gives an amine.

   
   

   
   (c) Lossen rearrangement

   Hydroxamic acids (or their O-acyl derivatives) undergo the Lossen rearrangement: on activation (for example by formation of an O-acyl derivative) and treatment with base they rearrange to isocyanates which on hydrolysis give primary amines. Practically, hydroxylamine derivatives are converted into O-acyl hydroxamic derivatives and then heated with base to effect rearrangement.

   
   
   
3. Reduction of nitro compounds

   Nitroalkanes or nitroarenes are reduced to the corresponding amines. Common laboratory and industrial methods include catalytic hydrogenation (H2/Pd-C, H2/Ni) or chemical reduction (Fe/HCl, Sn/HCl, or using metal-acid combinations).

   
4. Reduction of nitriles

   Nitriles (R-C≡N) are reduced to primary amines (R-CH2NH2) using LiAlH4 in dry ether or by catalytic hydrogenation.

   
5. Reduction of amides

   Amides (RCONR'R'') may be reduced to corresponding amines. For example, acetamide reduced with LiAlH4 or with sodium in alcohol (in some cases) gives ethylamine. Hydrogenation over suitable catalysts at high pressure can reduce certain amides as well.

   
6. Reduction of oximes and aldoximes

   Aldoximes (R-CH=NOH) and ketoximes on catalytic hydrogenation (H2/Ni or H2/Pd) or by reduction with LiAlH4 or with Na/ethanol yield the corresponding primary or secondary amines depending on the substrate.

   
7. Hydrolysis of isocyanates

   Isocyanates (R-N=C=O) on hydrolysis give amines (R-NH2) with release of CO2. An example is the hydrolysis of ethyl isocyanate to ethylamine with caustic potash solution on heating.

   
8. Hydrolysis of isocyanides (isocyanides → amines)

   Isocyanides (isocyanides are also called isonitriles, R-NC) on acid hydrolysis give primary amines (R-NH2) with formation of formamide derivatives in some pathways; under appropriate conditions simple hydrolysis yields the amine.

   
9. Schmidt reaction (again, in specific contexts)

   In some texts the Schmidt sequence is listed separately as it can convert carboxylic acids directly to amines (via acyl azide and isocyanate intermediates). The acyl azide and alkyl isocyanate intermediates are commonly invoked.

10. Reaction of chloramine with Grignard reagent

    Alkyl magnesium halides (Grignard reagents) react with chloramine (or related nitrogen electrophiles) to give alkylamines after hydrolysis. For example, ethylmagnesium iodide with chloramine yields ethylamine on work-up.

    
11. Gabriel phthalimide synthesis (preparation of primary amines)

    This is a classic method for preparing primary amines without over-alkylation. Phthalimide is converted into its alkali salt, alkylated by an alkyl halide to give N-alkylphthalimide, and then hydrolysed (or treated with hydrazine) to liberate the primary amine. The method gives clean primary amines in good yields.

    
    
12. Laboratory preparation of ethylamine (example)

    Ethylamine can be prepared in the laboratory by the Hofmann bromamide reaction applied to propionamide (propionamide treated with bromine and potassium hydroxide), producing ethylamine (one carbon less than the amide carbon skeleton) after decarboxylation of the intermediate isocyanate.

    

Some additional practical notes and reagent choices

• Reduction of nitro compounds is one of the most commonly used practical routes to obtain aromatic and aliphatic amines on both laboratory and industrial scales.
• LiAlH4 is a very strong reducing agent useful for the reduction of nitriles, amides and oximes to amines, but it is moisture sensitive and requires dry ether solvents and careful work-up.
• Catalytic hydrogenation (H2 over Pd/C, Pt, or Raney Ni) is a convenient method for many reducible functional groups to give amines, especially on a larger scale.
• Rearrangement methods (Hofmann, Curtius, Schmidt, Lossen) are valuable when the synthetic aim is to shorten or shift the carbon skeleton relative to the nitrogen; these reactions proceed via isocyanate intermediates.

Summary (optional)

Amines are basic due to the lone pair on nitrogen, but their basicity depends on electronic effects (inductive and resonance), hybridisation, steric factors and solvation. Many synthetic routes exist to prepare amines: reductions of nitro, nitrile, amide and oxime groups; rearrangements (Hofmann, Curtius, Schmidt, Lossen) which form isocyanates followed by hydrolysis; Gabriel phthalimide synthesis for clean primary amines; and conversions involving Grignard reagents or isocyanides. Choice of method depends on the required amine type (primary/secondary/tertiary), functional group tolerance and desired carbon-skeleton changes.