Question

Propose a synthesis of the local anesthetic ambucaine from 4-nitrosalicylic acid, ethylene oxide, diethylamine, and 1-bromobutane.

Short answer

Question: Outline the three-step synthesis of the local anesthetic ambucaine using 4-nitrosalicylic acid, ethylene oxide, diethylamine, and 1-bromobutane as starting materials. Answer: The three-step synthesis of ambucaine involves the following steps: 1. Formation of 4-nitrosalicylic acid ethyl ester by reacting 4-nitrosalicylic acid with the alcohol generated from the reaction of diethylamine and ethylene oxide. 2. Formation of the ether linkage through the S_N2 reaction of hydroxy ethyl diethylamine (formed in step 1) with 1-bromobutane. 3. Formation of the tertiary amine by reacting the intermediate product from step 2 with diethylamine, resulting in the desired ambucaine product.

Step-by-step solution

Preparation of 4-nitrosalicylic acid ethyl ester

To form the ester linkage in ambucaine, we will need to react 4-nitrosalicylic acid with the alcohol formed after the reaction of diethylamine with ethylene oxide. Start by adding ethylene oxide to diethylamine to generate the corresponding hydroxy ethyl diethylamine. Then, react this intermediate with 4-nitrosalicylic acid in an esterification reaction, catalyzed by a small amount of a strong acid like concentrated sulfuric acid. This reaction will generate the 4-nitrosalicylic acid ethyl ester.

Formation of the ether linkage

Next, we need to form the ether linkage. This can be achieved through the reaction of hydroxy ethyl diethylamine (formed in step 1) with 1-bromobutane through an S_N2 reaction. Make sure to have a balanced ratio between the nucleophile (hydroxy ethyl diethylamine) and the electrophile (1-bromobutane) to ensure complete conversion.

Formation of the tertiary amine

The final step in the synthesis involves the formation of the tertiary amine in ambucaine. This can be achieved by reacting the product formed in step 2 with diethylamine in the presence of a suitable solvent, such as THF or DCM. This reaction is an S_N2 reaction, and the amine group will displace the bromide group in 1-bromobutane. This will yield the desired ambucaine product. After following these three steps, the synthesis of ambucaine from 4-nitrosalicylic acid, ethylene oxide, diethylamine, and 1-bromobutane should be achieved.