Science of Synthesis

Haider, N.; Holzer, W., Science of Synthesis, (2004) 16, 208.

Introduction of alkylamino and dialkylamino substituents is conveniently achieved by heating a chloropyridazine [less commonly used precursors are other halopyridazines, and nitro-, (alkylsulfanyl)-, (alkylsulfonyl)-, alkoxy-, or siloxypyridazines] with the appropriate amine, which is employed either neat or as a solution in an alcohol or a suitable aprotic solvent, and using either an excess of the amine or an additional base as an acceptor of the liberated acid. Numerous examples of such transformations can be found in Houben–Weyl, Vol. E 9a, pp 632, 633, and in the more recent literature.[‌350‌,‌355‌,‌474‌,‌501‌,‌518‌,‌538‌,‌549‌–‌559‌] For the preparation of (dimethylamino)pyridazines, heating of the corresponding chloropyridazines in dimethylformamide is an efficient method.[‌352‌] On the other hand, transformation of such precursors into (primary) pyridazinamines as well as (arylamino)pyridazines is not as straightforward, as a consequence of the lower nucleophilicity of the corresponding reactants, ammonia or arylamines. Direct ammonolysis of halopyridazines requires heating with ammonia in a closed vessel and often gives only moderate yields;[‌155‌,‌333‌,‌463‌,‌475‌] however, the amino function can be conveniently obtained by reduction of azidopyridazines[‌355‌,‌440‌,‌550‌,‌560‌,‌561‌] (which are easily prepared from halopyridazines and sodium azide) or hydrazinopyridazines,[‌481‌,‌561‌–‌565‌] taking advantage of the much higher nucleophilic reactivity of azide or hydrazine as compared to ammonia (see Sections ‌16.8.4.3.2.4‌ and ‌16.8.4.3.2.5‌).

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References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 88/8, 888.
• 8.Meeeee-Meee, (8888) 88/8, 888.
• 8.Meeeee-Meee, (8888) M 88e8, 8.
• 8.Meeeee-Meee, (8888) M 8e, 888.