Question

Design a synthesis route for the heterocyclic compound Pyridine starting from benzene as the starting material, using the commonly used reactions in organic chemistry and displaying the steps involved in the reactivity of each reaction.

Answer 1

To synthesize pyridine from benzene, we can follow the Chichibabin pyridine synthesis route. Here's a step-by-step synthesis route:1. Nitration of benzene:First, we need to introduce a nitro group  -NO2  to the benzene ring. This can be done by treating benzene with a mixture of concentrated nitric acid  HNO3  and concentrated sulfuric acid  H2SO4  at room temperature. This reaction will produce nitrobenzene.Benzene + HNO3  Nitrobenzene + H2O2. Reduction of nitrobenzene to aniline:Next, we need to convert the nitro group in nitrobenzene to an amino group  -NH2 . This can be done by reducing nitrobenzene using a mixture of iron  Fe  and hydrochloric acid  HCl  at elevated temperature. This reaction will produce aniline.Nitrobenzene + 6H  from Fe/HCl   Aniline + 2H2O3. Acylation of aniline:Now, we need to protect the amino group in aniline by converting it into an amide. This can be done by treating aniline with acetyl chloride  CH3COCl  in the presence of a base like pyridine. This reaction will produce N-acetylaniline.Aniline + CH3COCl  N-Acetylaniline + HCl4. Formation of ,-unsaturated ketone:Next, we need to form an ,-unsaturated ketone. This can be done by treating N-acetylaniline with ethyl acetoacetate  CH3COCH2COOEt  in the presence of sodium ethoxide  NaOEt  as a base. This reaction will produce an ,-unsaturated ketone.N-Acetylaniline + CH3COCH2COOEt  ,-Unsaturated ketone + EtOH5. Chichibabin pyridine synthesis:Finally, we need to cyclize the ,-unsaturated ketone to form pyridine. This can be done by heating the ,-unsaturated ketone in the presence of ammonia  NH3  and hydrochloric acid  HCl . This reaction will produce pyridine and a side product, acetylacetone.,-Unsaturated ketone + NH3 + HCl  Pyridine + Acetylacetone + H2O6. Purification of pyridine:The crude pyridine can be purified by distillation or recrystallization to obtain the desired heterocyclic compound, pyridine.In summary, the synthesis route for pyridine from benzene involves nitration, reduction, acylation, formation of an ,-unsaturated ketone, and Chichibabin pyridine synthesis followed by purification.