Primary and Alkyl Amines

Primary Amines

• Primary amines have the formula RNH₂, where R represents an alkyl group.
• Ethylamine's structure includes a chain of two carbon atoms followed by a nitrogen atom bonded to two hydrogen atoms.

Formation of Alkyl Amines

• Alkyl amines can be produced through several methods.
• Halogenoalkanes are heated in a sealed tube with concentrated ammonia in ethanol solvent.
  • Reflux is not suitable because ammonia is too volatile.
  • An excess of ammonia is necessary during the reaction to favor the formation of a primary amine instead of an ammonium salt.
  • For example, the reaction using 1-chloroethane yields ethylamine and ammonium chloride.
• Amides can be reduced using LiAlH₄.
  • LiAlH₄ acts as the reducing agent.
  • Ethanamide is reduced to ethylamine.
• Nitriles are reduced using LiAlH₄.
  • Nitriles contain a -CN group.
  • Ethanenitrile can be reduced to ethylamine.
• Nitriles can also be reduced using H₂/Ni.
  • A nickel catalyst is used to reduce the nitrile with hydrogen gas.
  • Ethane nitrile is reduced to ethylamine.
• Phenylamine is produced through the reduction of nitrobenzene with tin and concentrated HCl.
  • The mixture is heated under reflux.
  • Sodium hydroxide is added to remove a proton from the -NH₃⁺ group.
  • The reaction converting nitrobenzene to phenylamine requires 6 reducing equivalents [H].

Basicity of Amines

• Amines are basic because the nitrogen atom has a lone pair of electrons that can accept a proton/hydrogen ion.
• Amines react with acids similarly to ammonia, and produce alkyl ammonium salts.
• Amines in water form an equilibrium, producing hydroxide ions and alkyl ammonium ions.

Factors Affecting Base Strength

• The ease with which the lone pair accepts a hydrogen ion affects base strength.
• The stability of the ions formed affects base strength.
• In ethylamine, the alkyl group pushes electrons away, increasing the negative charge on nitrogen.
• This makes the lone pair more attractive to hydrogen ions.
• Ethylammonium ion is more stable than ammonium because the charge is more spread out in ethylamine than in ammonia.
• Consequently, ammonia is a weaker base than ethylamine.
• In phenylamine, the amine group is directly attached to the benzene ring leading to delocalization of the lone pair into the pi system.
• This delocalization prevents the lone pair from combining with a hydrogen ion.
• The nitrogen atom is electronegative, drawing electrons towards itself.
• Phenylamine is a weaker base compared to ammonia and ethylamine.
• The basicity order is ethylamine > ammonia > phenylamine.

Reactions of Phenylamine

• The -NH₂ group activates the benzene ring, making it more reactive towards electrophiles.
• The -NH₂ group has a 2,4-directing effect, meaning new groups attach at the 2 and 4 positions.
• Phenylamine reacts with aqueous bromine at room temperature without a catalyst.
  • Bromine water is decolorized, and a white precipitate forms.

Phenylamine and Nitrous Acid

• Phenylamine reacts with nitrous acid (HNO₂), which is made in situ because it decomposes quickly.
• Reaction of phenylamine with nitrous acid when the reaction mixture is warm produces phenol.
• If the reaction is done at less than 5°C, a diazonium salt is produced.

Formation of Dyes

• Phenol first reacts with sodium hydroxide to produce sodium phenoxide.
• A cool solution of benzenediazonium chloride is added to the sodium phenoxide solution that has been cooled in ice.
  • The reaction produces a yellow-orange solution or precipitate.
  • The product of the reaction is an azo compound which is two benzene rings joined by a nitrogen bridge.
• In the coupling of an azo dye, the reaction occurs at the 4-position relative to the oxygen.
  • If that position is occupied it occurs instead at the 2-position.

Amides

• Amides contain the -CONH₂ group and are neutral.
• The lone pair on the nitrogen is delocalized into the pi bond between oxygen and carbon.
• Therefore, the nitrogen atom cannot attract a hydrogen ion.
• The delocalization makes the molecule more stable.

Formation of Amides

• Acyl chlorides react with ammonia to produce an amide and hydrogen chloride gas.
• Amides are organic compounds with the -CONH₂ group, named with the suffix -amide.
  • Propanamide is formed in the reaction with propanoyl chloride.
• The released hydrogen chloride reacts further with excess ammonia to produce ammonium chloride.

Reactions with Primary Amines

• A primary amine contains an -NH₂ group bonded to an alkyl group.
  • Methylamine (CH₃NH₂) is an example.
• The reaction between a primary amine and acyl chloride forms an N-substituted amide.
  • N-methylpropanamide is formed when using methyl amine as an example.
• The hydrogen chloride produced reacts with excess primary amine.

Hydrolysis

• When an amide is heated with a dilute acid, a carboxylic acid and ammonium ions (NH₄⁺ or RNH₃⁺) are formed.
  • Ethanamide with hydrochloric acid produces ethanoic acid and ammonium chloride.
  • N-methylethanamide with hydrochloric acid produces ethanoic acid and methylammonium chloride.
• When heated with sodium hydroxide, amides will form a carboxylate salt and ammonia or an amine.
  • Ethanamide heated with sodium hydroxide produces sodium ethanoate and ammonia.
  • N-methylethanamide heated with sodium hydroxide produces sodium ethanoate and methylamine.

Reduction

• Amides can be reduced to primary amines using LiAlH₄, followed by treatment with dilute acid.
  • For instance, propanamide (CH₃CH₂CONH₂) is reduced to propylamine.

Amino Acids

• Amino acids contain a carboxylic acid (-COOH) and an amine (-NH₂) group.
• The general structure includes a central carbon atom bonded to an amino group, a carboxyl group, a hydrogen atom, and an R group.

Acid/Base Properties and Zwitterions

• Amino acids contain both an acidic (-COOH) and a basic (-NH₂) group.
• Zwitterions are formed when the carboxylic acid donates a proton to the amine group.
  • They contains both a positive and negative charge.
• A zwitterion has no overall electrical charge, but contains charged parts.
• In water, proton transfer occurs to form a charged ion.
• The NH₃⁺ group donates a proton to OH⁻ ions to form water when alkali is added.
  • It results in a negative charge, and loses zwitterionic properties.
• The COO⁻ group accepts a hydrogen ion when acid is added resulting in a positive charge.
  • This loses zwitterionic properties.
• If alkali is added to the positive amino acid ion, the -COOH group proton is donated to OH⁻ ions to form water.
  • The -COOH proton is more acidic and reforms the zwitterion.
• The amino acid has no overall charge when exactly the right amount of alkali is added.
  • During electrophoresis, the amino acid won’t travel towards the cathode or anode.
  • Isoelectric point is the pH at which the amino acid does not move during electrolysis.

Peptide Bonds

• A peptide bond is formed during a condensation reaction between two amino acids.
  • A molecule of water is lost in the process.
• A dipeptide is formed when two amino acids combine.
• A tripeptide forms when three amino acids join together.

Electrophoresis

• Electrophoresis can be used to separate amino acids.
  • A moistened filter paper is placed on a microscope slide.
  • Crocodile clips are attached to each end and connected to a battery.
  • A drop of amino acid solution is added to the middle.
  • The apparatus is left for a period of time to separate.
  • Ninhydrin is sprayed to make the amino acid solution visible, then dried and warmed.
• A gel soaked in buffer solution, with troughs to hold the amino acid solution can be used in place of filter paper.

Analyzing Electrophoresis Results

• Zwitterions don’t move toward the anode or cathode, indicating a pH at the isoelectric point.
• Amino acids that travel toward the cathode (negative electrode) are positively charged.
  • This occurs when an amino acid has an extra amine group in the R group, giving a net charge of 1+.
• Amino acids that travel toward the anode (positive electrode) are negatively charged.
  • In these molecules an extra carboxylic acid in the R group provides the net charge of 1-.
• Smaller ions travel faster because there is less resistance to their movement.
• In a low pH buffer, the -COOH groups stay as -COOH and NH₂ groups become -NH₃⁺.
  • All amino acids are positively charged and will move towards the cathode.
• In a high pH buffer, the -COOH groups donate a proton and become -COO⁻.
  • All amino acids are negatively charged and move towards the anode.
• Electrophoresis can also be used to separate peptides based on relative molecular mass.
  • Peptides are treated with SDS and heated to denature them.
  • The molecules become amino acid chains surrounded by negative charges and move towards the anode during electrophoresis.
  • Smaller molecules move faster.