Chapter 22, Problem 22.62P

A newer generation of antipsychotics, among them clozapine, are now used to treat the symptoms of schizophrenia. These drugs are more effective than earlier drugs in improving patient response in the areas of social withdrawal, apathy, memory, comprehension, and judgment. They also produce fewer side effects such as seizures and tardive dyskinesia (involuntary body movements). In the following synthesis of clozapine, Step 1 is an Ullmann coupling, a type of nucleophilic aromatic substitution that uses a copper catalyst.

1. (a) Show how you might bring about formation of the amide in Step 2.
2. (b) Propose a reagent for Step 3.
3. (c) Propose a mechanism for Step 4.
4. (d) Is clozapine chiral? If so, how many of the possible stereoisomers are formed in this synthesis?