Synthesis of pyrimidines and 2-pyrimidones from 10a 1,3-diketones Retrosynthetic analysis reveals that ee can be made from an amidine and 1,3-diketones R? H R? 4 Yur * 7 = Ss Poy N r H. © 4 A Ré Reactions are normally conducted with acid or base catalysis, eg: R? HN NaQEt or A ° . 4 NaOH R’ + ye OS / sl 7 Analogous reactions can R’ be conducted with urea R? thiourea and guanidine HON HCl, EtOH g 2 heat ma + \=o BA 0 HNSynthesis of pyrimidines: mechanism 10b © HO R? Q 5 R? Hof He R HCI ® rR? — HN === R? Tt RI RI ) Re Ri NH é ° HN d proton transfer R? R? 7 4 HO] H y No UR —N. URt “440 20 R! Re 1 NH2 R? NH Re R’ R! Rt NH HO ° 0 > \ Re RS RS N proton N N transfer -H20 rer \—e! rot Sort “ke J \ ps HO: NH. H,0: N =N Ri © 2 “tN R! H R!Pyrimidines and pyrimidones: examples =o HN NaOH Ph: + ye PF =0 HN pivalamidine Ph NaOet Peta EtOH Me + NH Oo | HN PK guanidine Me, HCI, EtOH heat Me N-methyl thiourea eee NaOH Ph- + Fo —_—_—_ =o aN Ph phenyl thiourea 11a The amidine is a "bis- nucleophile" and the dialdehyde is a "bis- electrophile” The urea, thiourea, guanidine and amidine bis- nucleophilic components (reagents) may also be reacted with bis electrophiles such as 1,3- ketoesters, 1,3-diesters and 1,3-cyanoester