Synthesis of Pyridazines by Ring Transformation Reaction

Charles University in Prague The Faculty of Pharmacy in Hradec Králové The Department of Inorganic and Organic Chemistry Candidate: Hana Budilová Supervisors: Doc. RNDr. Věra Klimešová, CSc. Prof. Dr. Rainer Beckert Title of Diploma Thesis: Synthesis of Pyridazines by Ring Transformation Reaction Pyridazines are heterocyclic compounds with two adjacent nitrogen atoms. There are a lot of synthetic approaches to get pyridazine. A number of specific transformations from other heterocyclic systems have been reported. This thesis deals with the synthesis of pyridazines by transformation of a four-membered heterocycle. Some new derivatives of 1-methyl-3-(4-tolylamino)-4-(4-tolylimino)-6-(4'- substituted-phenyl)-1,4-dihydropyridazines were synthesized by a ring transformation of four- membered 2 -1,2-diazetine. This compound was obtained by a cycloacylation reaction of methylhydrazine and bis-oxalimidoyl chloride. NMR and mass spectrometry confirmed structures of prepared compounds. 1-Methyl-3-(4-tolylamino)-4-(4-tolylimino)-6-phenyl-1,4-dihydropyridazine had been previously proven to possess antimycobacterial activity. The new derivatives were tested against Mycobacterium tuberculosis My 331/88, M. avium My 330/88, M. kansasii My 235/80 and M. kansasii 6 509/96. MIC values of these compounds range..