Home Assignment #1; C403

1. Tricyclic pyrrole derivative 2.43 is a drug currently under development for the
treatment of schizophrenia. It is prepared by a Knorr
pyrrole synthesis. What are the structures of the two
starting materials required, and that of the intermediate
enamine?

2. Why is pyrrole aldehyde 2.44 less reactive to nucleophiles than, say, benzaldehyde?
Why is pyrrole alcohol 2.45 readily polymerised on exposure to acid?

3. Nitration of furan with nitronium tetrafluoroborate produces nitrofuran 2.33 directly.

Contrast this result to the two stage reaction necessary with acetyl nitrate, page 16.
Explain these observations.

4. What is the mechanism of this reaction?

5. Suggest a synthesis of oxazole 3.33.

6. A less general synthesis of oxazoles is the condensation of bromoketones with amides.

What is the mechanism for the formation of oxazole 3.44? How does 3.44 relate to the
oxazole which might be prepared from the same bromoketones by conversion to
correspondinmg aminoketone, N-formylation and cyclocondensation?

7. Carboxylic acid 3.46 has been extensively used in the preparation of semi-synthetic
penicillins and cephalosporins. Devise a synthesis of 3.46 from ester 3.45.

8. What is the mechanism for the formation of isothiazolone 4.39?

9. What general strategy might be employed to convert pyrazole to alcohol

4.40, a potent inhibitor of steroid biosynthesis.

10. What is the product resulting f r om oxidation of 4.41?

11. A synthesis of 2-cyanocyclohexanone 4.45 from cyclohexanone is shown below.

Formylation of cyclohexanone produces a mixture of keto/enol tautomers 4.42 and
4.43, the equilibrium lying to the side of the enol 4.42. Treatment with hydroxylamine
affords isoxazole 4.44, and base-induced fragmentation of the isoxazole ring affords
4.45. Explain the regioselectivity of the isoxazole formation, and the mechanism of the
fragmentation process.