Structure Determination of Chloramphenicol or Chloromycetin
Synthesis of Chloramphenicol
Structure of chloramphenicol can be established on the basis of following chemical evidences-
1. Elemental analysis and molecular weight shows that the molecular formula of of chlorampheicol is C11H12O5N2Cl2.
2. Its absorption spectrum is similar to that of nitrobenzene.
3. The presence of a nitro group was confirmed by the reduction of chloramphenicol with tin and hydrochloric acid (Sn/HCl), followed by diazotization and then coupling to yield an orange precipitate with β-naphthol.
4. Chloramphenicol when reduced with palladium it gives a product which has an absorption spectrum very similar to that of para-toluidine and the resulting solution gives a positive test for ionic chlorine.
5. Hydrolysis in either acidic or alkaline medium, chloramphenicol produces dichloroacetic acid together with an optically active base C9H12O4N2.
C11H12O5N2Cl2 ---H3O+ ---> Cl2CHCOOH + C9H12O4N2
6. The resulting base was shown to contain a primary amino group, and on being treated with methyl dichloroacetate, the base regenerated chloramphenicol.
7. Chloramphenicol on treatment with acetic anhydride in pyridine is converted into a diacetyl derivative, whereas the base obtained from chloramphenicol yields a triacetyl derivative on similar treatment. This is suggesting that chloramphenicol probably contains two -OH groups.
8. When the chloramphenicol base is treated with periodic acid two molecules of the periodic acid are consumed with the formation of one molecule each of ammonia, formaldehyde and para-nitrobenzaldehyde respectively. However, these products may be accounted for provided the base is assumed to be 2-amino-1-p-nitrophenylpropane-1,3-diol.
On the basis of above evidences we can write the structure of Chloramphenicol as-
1. Elemental analysis and molecular weight shows that the molecular formula of of chlorampheicol is C11H12O5N2Cl2.
2. Its absorption spectrum is similar to that of nitrobenzene.
3. The presence of a nitro group was confirmed by the reduction of chloramphenicol with tin and hydrochloric acid (Sn/HCl), followed by diazotization and then coupling to yield an orange precipitate with β-naphthol.
4. Chloramphenicol when reduced with palladium it gives a product which has an absorption spectrum very similar to that of para-toluidine and the resulting solution gives a positive test for ionic chlorine.
5. Hydrolysis in either acidic or alkaline medium, chloramphenicol produces dichloroacetic acid together with an optically active base C9H12O4N2.
C11H12O5N2Cl2 ---H3O+ ---> Cl2CHCOOH + C9H12O4N2
6. The resulting base was shown to contain a primary amino group, and on being treated with methyl dichloroacetate, the base regenerated chloramphenicol.
7. Chloramphenicol on treatment with acetic anhydride in pyridine is converted into a diacetyl derivative, whereas the base obtained from chloramphenicol yields a triacetyl derivative on similar treatment. This is suggesting that chloramphenicol probably contains two -OH groups.
8. When the chloramphenicol base is treated with periodic acid two molecules of the periodic acid are consumed with the formation of one molecule each of ammonia, formaldehyde and para-nitrobenzaldehyde respectively. However, these products may be accounted for provided the base is assumed to be 2-amino-1-p-nitrophenylpropane-1,3-diol.
