Question

Show the probable mechanistic steps involved in the preparation of coumarin by the condensation of acetic anhydride with salicylaldehyde in the presence of sodium acetate as catalyst.

Short answer

The mechanism of coumarin synthesis by Pechmann condensation involves five key steps: (1) Formation of acetyloxonium ion from acetic anhydride and sodium acetate, (2) nucleophilic attack on acetyloxonium ion by salicylaldehyde, forming an ester intermediate, (3) intramolecular cyclization of ester intermediate, forming a cyclic compound, (4) rearrangement and tautomerization of the cyclic compound to form an enol ester, and (5) de-esterification of the enol ester to form the final product, coumarin.

Step-by-step solution

Formation of acetyloxonium ion from acetic anhydride and sodium acetate

Acetic anhydride reacts with sodium acetate to form acetyloxonium ion, which is a reactive species and acts as an electrophile. The reaction mechanism is as follows: \[CH_3CO_2Na + (CH_3CO)_2O \rightarrow CH_3CO_2CH_3 + CH_3CO_2^-\] This equilibrium reaction results in the formation of the acetyloxonium ion, which will participate in the subsequent nucleophilic attack by salicylaldehyde.

Nucleophilic attack on acetyloxonium ion by salicylaldehyde

The phenolic oxygen of salicylaldehyde acts as a nucleophile and attacks the electrophilic carbon of the acetyloxonium ion. The reaction is as follows: \[C_6H_4CHO(OH) + CH_3CO_2CH_3 \rightarrow C_6H_4CH(OC(O)CH_3)OH\] This reaction leads to the formation of an ester intermediate product.

Intramolecular cyclization of ester intermediate

In this step, the ester intermediate undergoes intramolecular cyclization. The phenolic oxygen attacks the electrophilic carbonyl carbon of the ester group, leading to the formation of a cyclic compound. \[C_6H_4CH(OC(O)CH_3)OH \rightarrow C_6H_4CH(O)OC(O)CH_3\] This cyclic compound has a five-membered ring which includes the oxygen atom.

Rearrangement and tautomerization of the cyclic compound

The cyclic compound undergoes rearrangement and tautomerization through proton shifts. The enol form of the cyclical compound is converted to a more stable keto form. \[C_6H_4CH(O)OC(O)CH_3 \rightarrow C_6H_4C(O)CH(OC(O)CH_3)\] This rearrangement and tautomerization result in the formation of an enol ester.

De-esterification to form coumarin

In the final step, the enol ester undergoes de-esterification with the help of sodium acetate. The ester bond is cleaved, and the reaction is as follows: \[C_6H_4C(O)CH(OC(O)CH_3) + H_2O \rightarrow C_6H_4C(O)CH(OH) + CH_3CO_2H\] The resulting product is coumarin. In conclusion, the preparation of coumarin from acetic anhydride and salicylaldehyde in the presence of sodium acetate as a catalyst involves a series of nucleophilic attacks, intramolecular cyclization, rearrangement, tautomerization, and de-esterification reactions. These mechanistic steps play crucial roles in the efficient synthesis of coumarin through Pechmann condensation.

Key concepts

Mechanistic Steps

In organic synthesis, understanding the step-by-step mechanism is key to mastering how reactions progress from start to finish. This process outlines every small change or movement of atomic groups in a reaction. Particularly, in the synthesis of compounds like coumarin, mechanistic steps map out the reaction path.
This includes all intermediates and transitions until the final product is achieved. Here, each step reveals how specific conditions and catalysts guide reactions. Therefore, detailing each phase helps us understand the role of every molecule involved.

Nucleophilic Attack

Among the pivotal steps in organic reactions, a nucleophilic attack stands out. This is where a nucleophile, an electron-rich species, targets an electrophile, an electron-poor site.
In the preparation of coumarin, the nucleophilic phenolic oxygen in salicylaldehyde attacks the acetyloxonium ion.

• The nucleophile is drawn to positively charged areas, forming new bonds.
• This step is crucial as it initiates the formation of intermediate products.

Ultimately, this step is essential for bond formation and the progression of organic synthesis to synthesize desired compounds.

Intramolecular Cyclization

Intramolecular cyclization involves a molecule forming a ring by connecting atoms within its own structure. During coumarin synthesis, the molecule's phenolic oxygen enables this cyclization.
This step is essential because:

• It creates a stable five-membered ring which stabilizes the molecule.
• Cyclization is driven by the role of atomic groups within the molecule.

By internal bonding, cyclization significantly affects the final structure and chemical properties of the compound, essential for the stability of compounds like coumarin.

Pechmann Condensation

The Pechmann condensation is a classic method for synthesizing coumarin derivatives. It involves the acid-catalyzed reaction of a phenol with a β-keto ester. In our example, acetic anhydride reacts with salicylaldehyde.
Key attributes include:

• This condensation style is known for its efficiency and simplicity in synthesizing coumarins.
• It utilizes straightforward reagents and conditions.

In the presence of a catalyst, such as sodium acetate, the reaction is driven forward, creating coumarin efficiently via rearrangements, cyclization, and de-esterification.