有机化学课件Chapter 13 Amines And Amides培训资料.ppt

13.5 Basicity of Nitrogen Compounds Thus, for an amine base with pKb = 5, its conjugate ammonium ion has pKa=9. 13.6 Solubility of Ammonium Salts When an amine is added to a solution of a strong acid such as hydrochloric acid, the amine nitrogen atom is protonated to produce an ammonium salt. RNH2 + HCl → RNH3+ + Cl- Ammonium salts are more soluble than amines because the nitrogen atom of an ammonium salt has a positive charge. 13.6 Solubility of Ammonium Salts This property is used by drug companies to manufacture compounds that will be soluble in body fluids. Drugs containing an amino group are often prepared as ammonium salts to improve their solubility in body fluids. For example, the solubility of procaine is only 0.5g/100ml, but the solubility of its ammonium salt is 100g/100ml. 13.6 Solubility of Ammonium Salts 13.6 Solubility of Ammonium Salts The ammonium salts of many drugs are more stable and less prone to oxidation than the amine itself. Procaine is most stable at pH 3.6 and becomes less stable as the pH is increased. The ammonium salts have higher melting points than the amines and have virtually no odor. 13.6 Solubility of Ammonium Salts For example, ephedrine melts at 79℃ and has a fishy odor. Its hydrochloride salt, used in cold and allergy medications, melts at 217℃ and has no odor. Amines can be separated from other substances by converting them to ammonium salts. 13.6 Solubility of Ammonium Salts Consider the separation of 1-chlorooctane from 1-octanamine, a mixture that can result from a synthesis of the amine by reaction of 1-chlorooctane with ammonia. Both compounds are insoluble in water. Adding HCl to a solution containing both compounds converts the 1-octanamine into its ammonium salt, whereas 1-chlorooctane is not affected. 13.6 Solubility of Ammonium Salts 13.6 Solubility of Ammonium Salts The 1-chlorooctane is physically separated from the aqueous acid solution. Then the acid solution is neutralized with sodium hydroxide to fo