Question

Following is a retrosynthetic analysis for ibutilide, a drug used to treat cardiac arrhythmia. In this scheme, Hept is an abbreviation for the 1 -heptyl group.

Short answer

Answer: The main functional groups of ibutilide are the 1-heptyl group (Hept), aromatic ring, and sulfonamide. The key bonds that must be formed during its synthesis are the bond between the 1-heptyl group and the aromatic ring, and the bond between the aromatic ring and the sulfonamide group.

Step-by-step solution

Identify the functional groups and key bonds

Identify the main functional groups of ibutilide and the key bonds that must be formed during the synthesis. The functional groups are: 1-heptyl group (Hept), aromatic ring, and sulfonamide. The key bonds are the bond between the 1-heptyl group and the aromatic ring, and the bond between the aromatic ring and the sulfonamide group.

Choose the disconnections

Decide the suitable disconnections to break the molecule into simpler precursor fragments. In this case, we can disconnect the bonds between the 1-heptyl group and the aromatic ring, and between the aromatic ring and the sulfonamide group.

Identify the precursor fragments

After disconnecting the key bonds in step 2, we have three precursor fragments: 1) 1-heptyl group (Hept), 2) the aromatic ring, and 3) the sulfonamide group. These fragments will be combined in later steps to form ibutilide.

Plan the synthesis strategy

We can start the synthesis by forming the bond between the 1-heptyl group and the aromatic ring. This can be done through nucleophilic aromatic substitution (S_NAr) reaction, where the 1-heptyl group acts as a nucleophile and the aromatic ring acts as an electrophile. After this, the sulfonamide group can be introduced through another S_NAr reaction, where the sulfonamide acts as a nucleophile and the aromatic ring with the 1-heptyl group attached acts as an electrophile.

Perform the reactions

Follow the plan from Step 4 to perform the reactions and synthesize ibutilide: 1. Perform a nucleophilic aromatic substitution (S_NAr) reaction between the 1-heptyl group and the aromatic ring to form the intermediate compound with the 1-heptyl group attached to the aromatic ring. 2. Perform another nucleophilic aromatic substitution (S_NAr) reaction between the intermediate compound and the sulfonamide group to form ibutilide.