amine

Examples of amine in the following topics:

• Preparation of 2º & 3º-Amines

  • Gives 2º-amines.
  • Gives 2º & 3º-amines.
  • (iii) Reduction of amide derivatives of 1º & 2º-amines.
  • Gives 2º & 3º-amines.
  • As with the previous method, 1º-amines give 2º-amine products, and 2º-amines give 3º-amine products.

• Amines

  • The prefix "amino-" or the suffix "-amine" is used when naming an amine compound.
  • Tertiary amines are amines whose hydrogens have been completely replaced by organic substituents.
  • Finally, cyclic amines are those in which the nitrogen has been incorporated into a ring structure, effectively making it either a secondary or tertiary amine.
  • Aliphatic amines, which are amines connected to an alkyl chain, display solubility in organic polar solvents.
  • Thus, the basicity of an amine can be expected to increase with the number of alkyl groups on the amine.

• Electrophilic Substitution at Nitrogen

  • Since this reaction produces HBr as a co-product, hydrobromide salts of the alkylated amine or unreacted starting amine (in equilibrium) will also be formed.
  • If a 1:1 ratio of amine to alkyl halide is used, only 50% of the amine will react because the remaining amine will be tied up as an ammonium halide salt (remember that one equivalent of the strong acid HX is produced).
  • Both the starting amine and the product amine are nucleophiles.
  • Even 3º-amines may be alkylated to form quaternary (4º) ammonium salts.
  • As shown in the following equations, 1º and 2º-amines react to give sulfonamide derivatives with loss of HCl, whereas 3º-amines do not give any isolable products other than the starting amine.

• Boiling Point and Water Solubility

  • Since 1º-amines have two hydrogens available for hydrogen bonding, we expect them to have higher boiling points than isomeric 2º-amines, which in turn should boil higher than isomeric 3º-amines (no hydrogen bonding).
  • Indeed, 3º-amines have boiling points similar to equivalent sized ethers; and in all but the smallest compounds, corresponding ethers, 3º-amines and alkanes have similar boiling points.
  • The water solubility of 1º and 2º-amines is similar to that of comparable alcohols.
  • As expected, the water solubility of 3º-amines and ethers is also similar.
  • Differences associated with isomeric 1º, 2º & 3º-amines and the influence of chain branching

• Reaction of Amines with Nitrous Acid

  • Nitrous acid (HNO2 or HONO) reacts with aliphatic amines in a fashion that provides a useful test for distinguishing primary, secondary and tertiary amines.
  • Under the acidic conditions of this reaction, all amines undergo reversible salt formation:
  • This happens with 3º-amines, and the salts are usually soluble in water.
  • The N-nitrosamines formed from 2º-amines are carcinogenic, and are not generally useful as intermediates for subsequent reactions.
  • Depending on ring substitution, 3º-Aryl amines may undergo aromatic ring nitrosation at sites ortho or para to the amine substituent.

• Nomenclature and Structure of Amines

  • The third and fourth compounds in the row are 2º and 3º-amines respectively.
  • This system names amine functions as substituents on the largest alkyl group.
  • The simple -NH2 substituent found in 1º-amines is called an amino group.
  • Finally, a common system for simple amines names each alkyl substituent on nitrogen in alphabetical order, followed by the suffix -amine.
  • Thus, Serotonin and Thiamine are 1º-amines, Coniine is a 2º-amine, Atropine, Morphine and Quinine are 3º-amines, and Muscarine is a 4º-ammonium salt.

• Acidity of Amines

  • We normally think of amines as bases, but it must be remembered that 1º and 2º-amines are also very weak acids (ammonia has a pKa = 34).
  • pKa is being used as a measure of the acidity of the amine itself rather than its conjugate acid, as in the previous section.
  • The same factors that decreased the basicity of amines increase their acidity.
  • The first compound is a typical 2º-amine, and the three next to it are characterized by varying degrees of nitrogen electron pair delocalization.

• Preparation of 1º-Amines

  • Although direct alkylation of ammonia by alkyl halides leads to 1º-amines, alternative procedures are preferred in many cases.
  • The resulting 3º-alkyl-substituted urea is then hydrolyzed to give the amine.
  • One important method of preparing 1º-amines, especially aryl amines, uses a reverse strategy.
  • This nitration reaction gives a nitro group that can be reduced to a 1º-amine by any of several reduction procedures.
  • The Hofmann rearrangement of 1º-amides provides an additional synthesis of 1º-amines.

• Important Reagent Bases

  • Most base reagents are alkoxide salts, amines or amide salts.
  • Since alcohols are much stronger acids than amines, their conjugate bases are weaker than amide bases, and fill the gap in base strength between amines and amide salts.
  • Barton's base is a strong, poorly-nucleophilic, neutral base that serves in cases where electrophilic substitution of DBU or other amine bases is a problem.

• Oxidation States of Nitrogen

  • Amine oxides are prepared by oxidizing 3º-amines or pyridines with hydrogen peroxide or peracids (e.g.
  • Amine oxides are relatively weak bases, pKa ca. 4.5, compared with the parent amine.
  • The nitrogen-containing product is a hydroxyl amine.
  • For such a mechanism, the beta-hydrogen and amine oxide moieties necessarily have a syn-relationship.
  • Cope elimination of diastereomeric amine oxides, such as those shown in examples #2 & 3 above, provide proof of the syn-relationship of the beta-hydrogen and amine oxide groups.