Synthesis of 1,2-diazine derivatives. VII. Substitution reaction of 3,6-dichloro-4-methylpyridazine was written by Mori, Kazuo. And the article was included in Yakugaku Zasshi in 1962.SDS of cas: 89640-81-3 This article mentions the following:
3,6-Dichloro-4-methylpyridazine (I) (30 g.) and 100 ml. 28% NH4OH in a sealed tube heated 20-4 hrs. at 120-40° and the product filtered off gave 3-chloro-4-methyl-6-aminopyridazine (II), m. 190-2° (EtOH) and the mother liquor gave the 5-Me analog (III) of II, m. 111-13° (hexane). MeONa (25 g. Na and 1.2 l. MeOH) and 163 g. I refluxed 7 hrs., 0.7 l. MeOH removed, the residue kept overnight, and the product filtered off gave 59 g. 3-chloro-4-methyl-6-methoxypyridazine (IV), m. 112-16° (MeOH), and the mother liquor gave 91 g. 5-Me analog (V) of IV, m. 68-70° (hexane). II (2.4 g.) and MeONa (0.5 g. Na and 50 ml. MeOH) in a sealed tube heated 12 hrs. at 165°, the MeOH removed, and the residue extracted with CHCl3 gave 1.5 g. 3-methoxy-4-methyl-6-amino- pyridazine, m. 83-5°. Catalytic reduction of 1 g. II or III in 100 ml. EtOH with 10% Pd-C gave 4-methyl-3-aminopyridazine- HCl, m. 264° (decomposition), or the 5-Me analog, m. 194° (decomposition). IV (2 g.), 80 ml. 28% NH4OH, and a small amount of bronze powder in a sealed tube heated 50 hrs. at 130-60° and the solution concentrated gave 4-methyl-6-amino-3-pyridazinol, m. 213°. IV (3 g.) and 100 ml. 28% NH4OH in a sealed tube heated 28 hrs. at 130-50° and the product concentrated gave 2 g. 4-methyl-6-chloro-3- pyridazinol (VI), m. 171°. Similarly, 2.3 g. V gave 1.5 g. 5-Me analog (VII) of VI, m. 227°. Catalytic reduction of VI gave 4-methyl- 3-pyridazinol, m. 157-8° and that of VII gave 5-methyl-3-pyridazinol, m. 154°. Catalytic reduction of IV gave 3-methoxy-4- methylpyridazine-HCl, m. 150° (decomposition). I (20 g.) and 80 ml. 40% Me2NH in a sealed tube heated 8 hrs. at 130° gave 4(or 5)-methyl-3-chloro-6-dimethylaminopyridazine, m. 126°. Oxidation of 13 g. I with K2Cr2O7 gave 11 g. 3-hydroxy-6-chloro-4-pyrid- azinecarboxylic acid (VIII), m. 210° (decomposition) (H2O). Similarly, oxidation of VII with CrO3 gave the 5-CO2H analog (IX) of VIII, m. 245° (decomposition). VIII (1.5 g.) in 20 ml. MeOH and several drops H2SO4 refluxed 5-8 hrs. and the product recrystallized (H2O) gave the Me ester of VIII, m. 132°. Similarly was prepared the Me ester of IX, m. 99-101°. Catalytic reduction of 2.5 g. VIII in 80 ml. MeOH with Pd-C gave Me 3-hydroxy-4-pyridazinecarboxylate (X), m. 159°. Similarly, IX yielded the 5-C02Me analog of X, m. 163°. In the experiment, the researchers used many compounds, for example, Methyl 6-oxo-1,6-dihydropyridazine-4-carboxylate (cas: 89640-81-3SDS of cas: 89640-81-3).
Methyl 6-oxo-1,6-dihydropyridazine-4-carboxylate (cas: 89640-81-3) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. The unsubstituted pyridazines are more resistant to eletrophilic substitution due to the nature of withdrawal of electron density from the ring by two heteroatoms, while the related electron deficiency of the ring makes pyridazine more easily attacked by nucleophiles.SDS of cas: 89640-81-3
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem