Question

2. Calculate the theoretical yield (g) of Zyban hydrochloride

3. Write out the mechanism for the a-bromination of 1 (m-chloropropiophenone).

4. Step 2 is a substitution of bromine by t-butylamine. What type of substitution is occurring: SN1 or SN2 Explain based on the reaction’s substrate and solvent.

5. The reaction mixture from the substitution step 2 is extracted with diethylether to isolate the product. State layer (organic or aqueous) in which each of the following compounds will be present in the highest concentration. a. NMP___________________ b. Excess t-butylamine__________________ c. HBr______________________ d. Zyban free base (compound 3a____________________

6. Why are the ether extracts combined then extracted with water at the end of Step 2?

7. The HCl solution used in the final step was made by mixing 20 mL concentrated HCl (12.0 M) with 100 mL isopropyl alcohol. Why wasn’t an aqueous HCL solution used for this part of the synthesis?

8. Describe the pharmacology of Zyban.

Answer 1

4 substitution of bromine by t-butylamine follow SN1 mechanism due to steric crowding over there and formation of secondary carbocation

5 NMP in organic layer   b) t-butylamine in organic layer c) HBr in aqueous layer d) Zyban base compound is in organic layer

6 ether extracts combined to collect the product then extracted with water for work up at the end of Step .

7.

Since an excess of t-butyl amine is used in the reaction, care must be taken to thoroughly wash the ether solution of 3a with water to remove this reactant. Otherwise, when the hydrochloride salt is formed by addition of HCl to the ether solution of 3a,t-butylamine HCl (TBHCl),which is much less soluble in ether than bupropion HCl, will precipitate before or with 3b, the HCl salt of bupropion. If there is any more than a very small percentage of TBHCl contaminating 3b, even repeated conventional recrystallization (dissolving the amine salt in EtOH and adding ether to induce precipitation) may fail to remove it.