Question

Question. The following drugs are synthesized using the methods in this chapter and in previous chapters. Devise a synthesis for each, starting with any compounds containing no more than six carbon atoms.

1. Phenacetin, used with aspirin and caffeine in pain-relief medications.
2. Methamphetamine, once considered a safe diet pill, but now known to be addictive and destructive to brain tissue.
3. Dopamine, one of the neurotransmitters in the brain. Parkinsons’s disease is thought to result from a dopamine deficiency.
   

Short answer

4-aminophenol undergoes reaction with sodium hydroxide and ethyl bromide in the first step, as sodium hydroxide acts as base, it abstracts acidic hydrogen from phenolic group and forms oxygen anion which acts as a nucleophile and attacks at ethyl bromide to form product, and further treatment with acetyl chloride leads to acetylation of amino group which eventually leads to formation of phenacetin

Formation of phenacetin

Step-by-step solution

Step-1. Explanation of part (a):

4-aminophenol undergoes reaction with sodium hydroxide and ethyl bromide in the first step, as sodium hydroxide acts as base, it abstracts acidic hydrogen from phenolic group and forms oxygen anion which acts as a nucleophile and attacks at ethyl bromide to form product, and further treatment with acetyl chloride leads to acetylation of amino group which eventually leads to formation of phenacetin

Formation of phenacetin

Step-2. Explanation of part (b):

Bromobenzene on reaction with Grignard reagent and epoxide undergoes reaction in which firstly a carbanion forms, that is, benzene carbanion which attacks on the epoxide and epoxide ring opens up, the attack of carbanion occurs at less substituted carbon of epoxide and product is formed. Further, treatment with sodium hypochlorite oxidises alcoholic group to ketonic group and after reduction with sodium triacetoxyborohydride and reaction with methylamine, we get our required product.

Formation of methamphetamine

Step-3. Explanation of part (c):

Pyrocatechol on treatment with methyl iodide and aluminum chloride, undergoes substitution reactionof methyl at para position of pyrocatechol. The directive influence of hydroxyl group directs the incoming electrophile at para position. Further, on treatment with N-bromosuccinimide and light, benzylic bromination occurs. Then, on treatment with potassium cyanide, substitution reaction occurs and at last on reduction with hydrogen with platinum as catalyst, we get the required product that is, dopamine.

Formation of dopamine