CHM 121: General Chemistry II - Amines

Introduction to Amines

• Definition: Amines are organic derivatives of ammonia ($NH_3$).

• Structure: They contain a nitrogen atom ($N$) attached to one or more alkyl groups (forming an Aliphatic amine) or aromatic groups (forming an Aromatic amine).

• Functional Group: The functional group is the amino group ($-NH_2$).

• General Formula: Identified as $R-NH_2$.

Classification of Amines

Amines are classified into three primary groups based on the number of carbon groups bonded to the nitrogen atom:

• Primary ($1^\text{o}$) Amines: Nitrogen is bonded to one carbon group (e.g., $CH_3-NH_2$).

• Secondary ($2^\text{o}$) Amines: Nitrogen is bonded to two carbon groups (e.g., $CH_3-NH-CH_3$).

• Tertiary ($3^\text{o}$) Amines: Nitrogen is bonded to three carbon groups (e.g., $(CH_3)_3N$).

Nomenclature of Amines

IUPAC Naming (Primary Amines)

The IUPAC system follows a method similar to naming alcohols:

• Identify the parent alkane chain.

• Drop the final "-e" from the parent alkane name and replace it with the suffix "-amine".

• Use a numerical locator to specify the position of the amino group ($-NH_2$) on the parent chain.

• Examples:

  • $CH_3-CH(NH_2)-CH_3$: 2-propanamine.

  • $CH_3-CH(Cl)-CH(NH_2)-CH_3$: 3-chloro-2-butanamine.

  • $H_2N-CH_2-CH_2-CH_2-CH_2-CH_2-CH_2-NH_2$: 1,6-hexanediamine.

Common Naming

Common names are constructed by listing the names of the alkyl groups attached to the nitrogen in alphabetical order, followed by the word "amine".

• Examples:

  • $CH_3-CH_2-NH_2$: ethylamine.

  • $CH_3-NH-CH_3$: dimethylamine.

  • $CH_3-N(CH_3)-CH_2-CH_3$: ethyldimethylamine.

Isomerism in Amines

Amines exhibit four types of isomerism:

• Chain Isomerism: Differences in the carbon skeleton (e.g., n-Butylamine vs. isobutylamine).

• Positional Isomerism: Differences in the location of the amino group on the same carbon chain.

• Metamerism: Occurs when different alkyl groups are attached to the same functional group.

  • Examples: Diethylamine ($C_2H_5-NH-C_2H_5$) and Methylpropylamine ($CH_3-NH-CH_2CH_2CH_3$) are metamers.

• Functional Isomerism: Isomers that belong to different amine classes (primary, secondary, or tertiary).

  • Example 1: n-Butyamine (a $1^\text{o}$ amine).

  • Example 2: Diethylamine (a $2^\text{o}$ amine).

  • Example 3: Ethyldimethylamine (a $3^\text{o}$ amine).

Methods of Preparation: General Synthesis

Ammonolysis of Alkyl Halides ($S_N2$)

This process involves the reaction of an alkyl halide ($R-X$) with ammonia or another amine. The alkyl halide must be primary ($1^\text{o}$) or methyl ($CH_3$).

• Substitution sequence: $R-X \rightarrow RNH_2 (1^\text{o}) \rightarrow R_2NH (2^\text{o}) \rightarrow R_3N (3^\text{o}) \rightarrow R_4N^+X^- (4^\text{o} \text{ salt})$.

• Specific Examples:

  • $CH_3CH_2CH_2CH_2Br + NH_3 \rightarrow CH_3CH_2CH_2CH_2NH_2$ (n-butylamine).

  • $CH_3CH_2CH_2NH_2 + CH_3Cl \rightarrow CH_3CH_2CH_2NHCH_3$ (methyl-n-propylamine).

  • Excess methyl iodide ($CH_3I$) reacting with ethylamine can result in a quaternary ammonium salt: $Et-N(CH_3)_3^+ I^-$.

Reductive Amination of Alkanals and Alkanones

Aldehydes (alkanals) or ketones (alkanones) react with ammonia or amines in the presence of a reducing agent to form higher amines.

• Reagents: Hydrogen gas with a Nickel catalyst ($H_2, Ni$) or Sodium cyanoborohydride ($NaBH_3CN$).

• Products:

  • Carbonyl + $RNH_2 \rightarrow 2^\text{o}$ amine.

  • Carbonyl + $R_2NH \rightarrow 3^\text{o}$ amine.

• Specific Examples:

  • Propiophenone + $CH_3CH_2NH_2$ with $NaBH_3CN \rightarrow$ 1-(N-ethylamino)-1-phenylpropane.

  • Cyclohexanone + $CH_3NH_2$ with $H_2/Ni \rightarrow$ cyclohexylmethylamine.

Reduction of Nitriles, Oximes, and Amides

Amines can be synthesized via the reduction of various nitrogen-containing functional groups using reducing agents ($[H]$):

• Nitriles (R-C \n\nequiv N) reduce to $1^\text{o}$ amines ($RCH_2NH_2$).

• Oximes ($RCH=NOH$) reduce to $1^\text{o}$ amines ($RCH_2NH_2$).

• Amides ($R-C(=O)-NR'R''$) reduce to $3^\text{o}$ amines ($RCH_2N-R'R''$).

Specific Preparation of Primary ($1^\text{o}$) Amines

Reduction of Nitroalkanes

Nitroalkanes are reduced to primary amines by boiling with tin ($Sn$) and concentrated hydrochloric acid ($HCl$) or by using hydrogen gas under pressure with a catalyst.

Reduction of Alkyl Cyanides (Alkanenitriles)

Alkanenitriles are converted into primary amines using:

• Sodium in absolute ethanol ($Na/\text{alcohol}$).

• Lithium aluminium hydride ($LiAlH_4$ or lithium tetrahydroaluminate (III)) in ether solution.

Hoffman Degradation

This reaction involves warming an acid amide ($RCONH_2$) with liquid bromine ($Br_2$) and a concentrated aqueous solution of an alkali (Caustic Potash/$KOH$).

• Result: The product is a primary amine with one fewer carbon atom than the starting amide.

Gabriel Synthesis

A specialized multi-step method for producing pure primary amines:

• Step 1: Phthalimide is reacted with $KOH$ to form Potassium phthalimide.

• Step 2: Potassium phthalimide reacts with an alkyl halide ($R-X$) via $S_N2$ to form N-alkylphthalimide.

• Step 3: Hydrolysis or reaction with hydrazine ($NH_2NH_2$) in ethanol under reflux releases the primary amine ($R-NH_2$) and Phthalazine-1,4-dione.

Alkylation of Azide Ion

• Process: Reaction of alkyl halides ($R-X$) with the azide ion ($N=N=N^-$), which is a good nucleophile.

• Reduction: The resulting alkyl azide ($R-N=N=N$) is reduced using $Na/\text{alcohol}$ or $LiAlH_4$ to yield the primary amine ($RNH_2$).

Physical Properties of Amines

1. Odor: They have unpleasant, rotting fish-like odors, similar to ammonia.

2. Polarity: Amines are polar compounds. The electronegativity difference between Nitrogen and Hydrogen is approximately $3.0 - 2.1 = 0.9$.

3. Hydrogen Bonding:

   • $1^\text{o}$ and $2^\text{o}$ amines can form intermolecular hydrogen bonds ($N-H$).

   • These bonds are weaker than those in alcohols ($O-H$).

   • $3^\text{o}$ amines cannot form hydrogen bonds with themselves as they lack a hydrogen atom bonded to nitrogen.

4. Boiling Points: Standard ranking is Hydrocarbons < Amines < Alcohols.

5. Solubility: Most amines are soluble in water due to their ability to form hydrogen bonds with water molecules.

Chemical Properties and Basic Character

Basicity

• General Behavior: Amines act as weak bases, similar to ammonia.

• Reaction with Water: Ammonia forms ammonium hydroxide ($NH_4OH$). Similarly, amines form alkyl ammonium hydroxides: $R-NH_2 + H_2O \rightarrow R-NH_3^+ + OH^-$.

• Reaction with Acids: Amines react with acids to form water-soluble salts.

  • Example: $CH_3NH_2 + H_2O \rightleftharpoons CH_3NH_3^+ + OH^-$.

• Biological Context: Certain amines in human blood help maintain its slightly basic pH (approximately $pH = 7.4$).

Relative Base Strength

The strength of the base is measured by the ionization constant $K_b$:

• $K_b = \frac{[H:Base^+][OH^-]}{[:Base]}$

• Strength Ranking: Aliphatic amines > Ammonia > Aromatic amines.

• Typical $pK_b$ values:

  • Aliphatic Amines (e.g., Ethanamine): $pK_b = 3.0 - 4.0$. (Stronger organic bases, slightly stronger than $NH_3$).

  • Ammonia: $pK_b = 4.74$. ($K_b = 1.8 \times 10^{-5}$).

  • Aromatic Amines (e.g., Aniline): $pK_b = 8.5 - 9.5$. ($K_b = 10^{-9}$ or less; much weaker bases).

Acid-Base Reaction Examples

• Reaction (a): Diethylamine + $HCl \rightarrow$ Diethylammonium chloride ($(CH_3CH_2)_2NH_2^+Cl^-$).

• Reaction (b): Pyridine (cyclic amine) + $CH_3COOH \rightarrow$ Pyridinium acetate ($C_5H_5NH^+ CH_3COO^-$).

Advanced Chemical Reactions

Acylation of Amines

• $1^\text{o}$ and $2^\text{o}$ amines react with acid chlorides, acid anhydrides, and esters to produce amides.

• This occurs because $1^\text{o}$ and $2^\text{o}$ amines possess replaceable hydrogen atoms on the nitrogen.

Isocyanide (Carbylamine) Test

• Used specifically to detect the presence of a primary amine.

• Procedure: Warm the amine (aliphatic or aromatic) with chloroform ($CHCl_3$) and a few drops of alcoholic potassium hydroxide ($KOH$).

• Result: Formation of an isocyanide, recognizable by its extremely foul odor.

Reaction with Nitrous Acid ($HNO_2$)

• Nitrous acid is unstable and is prepared in situ using sodium or potassium nitrite and a dilute mineral acid ($HCl$ or $H_2SO_4$).

• Aliphatic Primary Amines: React to form an alkyldiazonium salt ($RN_2^+$).

• Decomposition: The alkyldiazonium ion is highly unstable and immediately decomposes into a nitrogen gas ($N_2$) and a carbonium ion ($R^+$).

• Products: The carbonium ion undergoes further reactions to produce a mixture of alcohols, alkenes, ethers, and nitroalkanes.

Coupling Reactions of Diazonium Salts

• Azo Compounds: Diazonium salts can undergo coupling reactions to form azo compounds containing the $-N=N-$ group.

• Properties: These molecule are highly conjugated and intensely colored (yellow, red, blue, orange, or green).

• Industrial Use: Critical in the dyestuff industry for wool and cotton.

• Specific Examples:

  • (4-hydroxyphenyl) azobenzene: A bright yellow or red solid.

  • Orange II: Synthesized from 2-naphthol.

  • Solubility: Often a $-SO_3^-Na^+$ group is added to the molecule to increase solubility and aid in linking the dye to polar fibers.