Ch. 17 - Reactions at the Alpha-Carbon

Bruice8th EditionOrganic ChemistryISBN: 9780135213711Not the one you use?Change textbook

Bruice 8th Edition

Ch. 17 - Reactions at the Alpha-Carbon

Problem 90

Chapter 18, Problem 90

Amobarbital is a sedative marketed under the trade name Amytal. Propose a synthesis of amobarbital, using diethyl malonate and urea as two of the starting materials.

Verified step by step guidance

Step 1: Begin with diethyl malonate as the starting material. Perform a base-catalyzed alkylation reaction using ethyl bromide to introduce the ethyl group at the alpha-carbon of diethyl malonate. This step involves deprotonation of the alpha-carbon followed by nucleophilic substitution.

Step 2: Hydrolyze the diethyl malonate derivative under acidic or basic conditions to convert the ester groups into carboxylic acids. This step yields a malonic acid derivative with the ethyl group attached.

Step 3: Decarboxylate the malonic acid derivative by heating it. This removes one of the carboxylic acid groups, leaving behind a mono-carboxylic acid with the ethyl group attached.

Step 4: React the resulting mono-carboxylic acid with urea under acidic or basic conditions to form the barbituric acid core. This step involves a condensation reaction where urea contributes the nitrogen atoms to the cyclic structure.

Step 5: Perform a second alkylation reaction on the barbituric acid core using allyl bromide to introduce the allyl group at the nitrogen atom. This final step completes the synthesis of amobarbital.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Diethyl Malonate

Diethyl malonate is a versatile compound used in organic synthesis, particularly in the malonic ester synthesis. It contains two ester functional groups and is often employed as a nucleophile in alkylation reactions. Its ability to form enolates makes it a key intermediate in the synthesis of various compounds, including barbiturates like amobarbital.

Urea

Urea is a simple organic compound with the formula CO(NH2)2, and it serves as a key building block in the synthesis of many nitrogen-containing compounds. In the context of barbiturate synthesis, urea reacts with malonic esters to form barbituric acid, which can be further modified to produce sedatives like amobarbital. Its reactivity is crucial for forming the necessary carbon-nitrogen bonds.

Barbiturate Synthesis

Barbiturate synthesis involves the formation of a barbituric acid derivative through the condensation of urea and diethyl malonate. This process typically includes cyclization and subsequent modifications to yield various barbiturates, which are central nervous system depressants. Understanding the reaction mechanisms and functional group transformations is essential for proposing effective synthetic routes for compounds like amobarbital.

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Related Practice

Textbook Question

The following reaction is known as the benzoin condensation. The reaction does not take place if sodium hydroxide is used instead of sodium cyanide. Propose a mechanism for the reaction and explain why the reaction does not occur if hydroxide ion is the base.

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Textbook Question

A compound known as Hagemann's ester can be prepared by treating a mixture of formaldehyde and ethyl acetoacetate first with base and then with acid and heat. Write the structure for the product of each of the steps.

b. The second step is a Michael addition.

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Textbook Question

Alkylation of the following compound with methyl iodide under two different conditions forms two different ketoesters (A and B). Each ketoester forms a cyclic diketone (C and D) when treated with methoxide ion in methanol. a. Draw the structures of A and B, and indicate the conditions used in the alkylation reaction that cause that ketoester to be formed.

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