3- Chloropyridazines. reaction with amines

Some modifications of amino and hydrazino groups were also performed. An amino group can be replaced in the reaction with amines, although in low yield.442 To the few known pyridazinonimines some new compounds have been added. The imines (203) are prepared from the corresponding pyridazinium salts and sodium hydride.443 Hydrazinopyridazines upon nitrosation are transformed into azido- or tetrazolopyridazines. The reaction can be complicated by aza-transfer reactions with a heterocyclic diazo compound. For example, 3-chloro-6-hydrazinopyridazine, when treated with 3-diazoindazole in methanol, is transformed into a mixture of 3-amino-6-chloropyridazine, 6-chloro-, and 6-methoxytetrazolopyridazine, indazole and its 3-amino and 3-azido derivatives.444... 

Dichloropyridazine 1-Oxide produces both isomers with alkoxides. However, the ratio is dependent on the size of the alkoxy group. In the reaction with sodium methoxide 80% of 6-chloro-3-methoxypyridazine 1-oxide and 7.5% of 3-chloro-6-methoxypyridazine 1-oxide are formed. Similar results are also obtained with sodium ethoxide, while sodium propoxide affords only 6-chloro-3-propoxypyridazine 1-oxide. Amines react similarly, while only chlorine at the 3-position can be substituted with an azido group to give 3-azido-6-chloropyridazine 1-oxide. 

Substituted 6-iodopyridazines were the first representatives studied <1995JOC748>. Interestingly, a free amino group is well tolerated and a comparison of Stille reactions on 6-iodo- 170 and 6-chloropyridazin-3-amine 171 with aryl(tributyl)stannanes remarkably revealed that the latter react substantially faster (Equation 28 and Table 7) <2000T1777>. 

The introduction of a second amino group by halogen replacement requires more drastic conditions. 3-Amino-6-chloropyridazine is converted into 3,6-diaminopyridazine in poor yield the reaction between 3,6-dichloropyridazine and most aliphatic amines stops at monosubstitution, but with aromatic amines 3-mono- and 3,6-disubstituted aminopyridazines have been obtained. Similarly, 3-alkylamino-6-chloropyridazines failed to react with aniline and 3,5-diamino-6-methoxypyridazine could not be produced from 3-amino-5-chloro-6-methoxypyridazine even at elevated temperatures. 

Use of other aminating agents, such as urea, is also successful. The Bucherer reaction gives aminopyridazines in low yield. Amination of 3,6-dichloropyridazine with sodium amide, reported to provide 5-amino-3-chloropyridazine, has been shown to give 6-chloro-3(2iI)-pyridazinone in low yield together with recovered starting material. ... 

It is well known that halomethyleneiminium salts, often prepared in situ (see Section 2.1.2.2) react with ammonium salts, primary amines, secondary amides, urea and IV-substituted ureas to afrbrd amidinium salts, from which the free amidines can be obtained by addition of bases. > 4 Some recent results are given below. Dimethylformamide chloride and other 7V,iV-disubstituted formamide chlorides were reacted with acetanilides, chloroacetanilides, 6-aminopenam derivatives, 2-aminopyrimidine, 4-aminouracil, 2-amino-4-chloropyridazine, 2-aminothiazole, 2-aminobenzothiazole and thiobenzamides to give the amidines via the amidinium salts. In the reaction of MA -disubstituted formamide chlorides with thiobenzamides the solvent seems to be decisive for the course of the reaction. In tertiary formamides the thiobenzamides are desulfurized to nitriles, whereas in CHCI3 or CCI4 amidinium salts (296 Scheme 45) are formed. From trimethylsilyl isocyanate and the fluorinated amine (297) the /V-fluorocarbonylamidine (298) is accessible. ... 

In a one-step transformation, 4-benzoyl-6-chloropyridazin-3-amine reacts with /V,/V-dimethyl-acetamide dimethyl acetal as condensation reagent to give 3-chloro-7V,iV-dimethyl-5-phenylpyrido[2,3-c]pyridazin-7-amine (13a) in 63% yield with other acetamide acetals, prepared from V Y V-dirnethylaceLamide dimethyl acetal and the corresponding dialkylamine (see Houben-Weyl, Vol. E5, p 138f), the reaction affords 3-chloro-5-phenylpyrido[2,3-c]pyridazines bearing various dialkylamino substituents at C7.19... 

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