Synthesis of pyridines from 1,5-dicarbonyls 11b Can the Paal-Knorr pyrrole synthesis be adapted to use a 1,5 dicarbonyl to make a pyridine? NH, fie —> LN N H NHS, HO & This method would need the cis- enone, and this is tricky to make. An alternative and easier approach would make a dihydropyridine, followed by a separate oxidation (cf. the pyridazine synthesis (slide 4b/5a) ® NH3, H [0] Se —> "Oe s, ‘0 Oo R™ SN7 SR [0] a —_> — | sc 0 0Synthesis of pyridines from 1,5-dicarbonyls 12a An alternative approach to oxidation of the dihydropyridine, is by using hydroxylamine as the source of nitrogen. The NV-hydroxydihydropyridine can undergo elimination of water to form the pyridine in situ ls, _NHOH, HE A) _tautomerise THechanism aR on slide 8b oxime Compare this with the N-aminopyrrole formation from a 1,4-diketone (slide 5b) H proton =~— 40. —— © 2 SNR N7 SR Using ammonia in place of H. H hydroxylamine ® (see slide 11b) (| H Weidonyece A A Se Of ] - LS this stage (H in } RON . r A HO | place of OH) HH,