Pyridazine, 3,4,6-trichloro-, reaction with

In some instances a carbon-carbon bond can be formed with C-nucleophiles. For example, 3-carboxamido-6-methylpyridazine is produced from 3-iodo-6-methylpyridazine by treatment with potassium cyanide in aqueous ethanol and l,3-dimethyl-6-oxo-l,6-dihydro-pyridazine-4-carboxylic acid from 4-chloro-l,3-dimethylpyridazin-6-(lH)-one by reaction with a mixture of cuprous chloride and potassium cyanide. Chloro-substituted pyridazines react with Grignard reagents. For example, 3,4,6-trichloropyridazine reacts with f-butyl-magnesium chloride to give 4-t-butyl-3,5,6-trichloro-l,4-dihydropyridazine (120) and 4,5-di-t-butyl-3,6-dichloro-l,4-dihydropyridazine (121) and both are converted into 4-t-butyl-3,6-dichloropyridazine (122 Scheme 38). 

Chlorinated 2H- pyrimido[l, 2-6 ]pyridazin-2-ones are known to undergo a variety of nucleophilic displacement reactions. Displacement of the chlorine atom in both the 4- and 7-positions of these compounds with methylamine and sodium methanethiolate is facile. Displacement of the chlorine atom in the 3-position does not occur. Therefore, 3,4,7-trichloro-2//-pyrimido[l,2-6]pyridazin-2-one (34) reacts with methanethiol in sodium methoxide to give 3-chloro-4,7-bis(methylthio)-2//-pyrimido[l,2-6]pyridazin-2-one (70) (71JOC3506). 

When chlorinated with an excess of phosphorus pentachloridc, 5,8-dichloropyrido[2,3-rf]pyridazine affords, dependent on the reaction temperature and time, the corresponding 3,5,8-trichloro, 2,3,5,8-tetrachloro or2,3,4,5,8-pentachloro derivatives 3, 4, and 5, respectively. The facility of introduction of a chloro substituent into the pyridine part decreases thus in the order position 3 > 2 > 4.8 7... 

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