Question

Show how the sequence of Michael reaction, hydrolysis, acidification, and thermal decarboxylation can be used to prepare pentanedioic acid (glutaric acid).

Short answer

Answer: To synthesize pentanedioic acid, start with ethyl acrylate and react it with the enolate formed from diethyl malonate via the Michael reaction. Then, perform hydrolysis under basic conditions to convert the ester groups to carboxylic acid groups, followed by acidification to obtain 3-oxohexanedioic acid. Finally, perform thermal decarboxylation to convert 3-oxohexanedioic acid to pentanedioic acid (glutaric acid).

Step-by-step solution

Analyze the structure of pentanedioic acid (glutaric acid) and determine the starting material for the first reaction in the sequence: the Michael reaction.

Pentanedioic acid (glutaric acid) has a structure of HOOC-CH2-CH2-CH2-COOH. To synthesize this target molecule, we can begin with the starting material of ethyl acrylate (CH2=CHCO2Et). The Michael reaction will involve an enolate reacting with this starting material.

Perform the Michael reaction with the appropriate enolate.

The enolate we will use should contain a nucleophilic carbon atom to attack the electrophilic carbon atom (the beta-carbon) of ethyl acrylate. We will use the enolate formed from diethyl malonate (CH2(CO2Et)2) under basic conditions, like EtONa or EtOK. The enolate reacts with ethyl acrylate via 1,4-addition, resulting in the formation of diethyl 3-oxohexanedioate.

Perform hydrolysis of the ester groups.

To convert the ester groups of diethyl 3-oxohexanedioate to carboxylic acid groups, we need to perform hydrolysis under basic conditions, using an aqueous solution containing a strong base, like NaOH or KOH. This will lead to the formation of the sodium salt of 3-oxohexanedioic acid.

Perform acidification of the sodium salt.

Once we have the sodium salt of 3-oxohexanedioic acid, we need to convert it back to the carboxylic acid form by acidification. This can be done by adding a strong acid, like HCl or H2SO4, to the solution. The resulting molecule will be 3-oxohexanedioic acid (HOOC-CH2-CH2-C(=O)-CH2-COOH).

Perform thermal decarboxylation.

Finally, to convert 3-oxohexanedioic acid to pentanedioic acid (glutaric acid), we need to perform thermal decarboxylation of the keto-acid group. This can be done by heating the molecule to a high temperature (around 200-300°C), which will cause the loss of one carboxylic acid group (CO2) from the molecule. The product of this reaction will be pentanedioic acid (glutaric acid) – HOOC-CH2-CH2-CH2-COOH.