Chapter 18.12, Problem 29ATS

Discovery of the antibiotic sulphanilamide led to rapid development of a large number of structurally related sulphonamides. Some of these were useful leads to compounds with other medicinal properties. Amongst these, sulfasalazine was active in the treatment of ulcerative colitis, a potentially fatal disease of the colon. As a medicinal chemist, you are about to carry out the synthesis of sulfasalazine, starting from aniline. Give the chemical names and draw the chemical structures of the reagents you will need to use for the all the steps marked (a)-(d). Aniline HO₂C HO (a) N=N- ACHN Ac represents CH3CO Sulfasalazine SO,NH S0,C1 N (b) (d) H₂N- SO,NH (c) N [Oro] SO,NH N Step (a) in question 5 above results in the para product only. Explain why this occurs.

Show how to prepare the following aromatic amines by aromatic nitration, followed by reduction. You may use benzene andtoluene as your aromatic starting materials.(a) anilin

Several sulfonylureas, a class of compounds containing RSO2NHCONHR, are useful drugs as orally active replacements for injected insulin in patients with adult-onset diabetes. These drugs decrease blood glucose concentrations by stimulating b cells of the pancreas to release insulin and by increasing the sensitivity of insulin receptors in peripheral tissues to insulin stimulation. Tolbutamide is synthesized by the reaction of the sodium salt of p-toluenesulfonamide and ethyl N-butylcarbamate . Propose a mechanism for this step.