Pyridazine Chichibabin amination

This type of cyclization has been already illustrated by the formation of 7-azaindole on Chichibabin amination of 3-ethynylpyridine (Scheme 2). Similarly, 6-alkynyl-l,3-dimethyllumazines 137 (03RCB1403, 05JHC413) and 3-alkynyl-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6//,8//)-diones 140 (05JHC413, 03RCB441)... 

In 1972, Zoltewicz and Helmick reported the first evidence of anionic o-adducts in the Chichibabin amination reaction. The parent diazines a-adduct complex (pyrimidine, pyridazine and pyrazine) in KNH2-NH3/KMn04 (at low temperature 0 to 0 °C) are shown below. Despite the fact that the parent pyrimidine has three possible amination spots, 18 is the adduct formed and similarly for pyridazine and pyrazine, adducts 19 and 20 are formed under the aforementioned conditions. The regio-chemical outcome changes when these rings are substituted. 

The amidation of pyrido[2,3-cf]pyridazine with sodium amide occurs in position 2 to give 7. In such Chichibabin reactions, the product-determining loss of hydride ion appears to be mainly influenced by the negative charge on the adjacent N-atom 88 the higher charge density on the pyridine nitrogen of the pyrido[2,3-rf]pyridazine system favors ortho amination of the pyridine part.83... 

However, significant chemistry, particularly the application of ammonia/amide reactions has been reported since 1984. Thus, while pyridazine is resistant to the Chichibabin reaction, a variety of pyridazines form u-adducts in ammonia/potassium amide which can be oxidized by the addition of potassium permanganate to yield 4(5)-aminopyridazines, often in excellent yields. For example, dissolution of pyridazine in ammonia/potassium amide leads to the almost complete formation of the anionic adduct, which can be oxidized to give 4-aminopyridazine in excellent yield, while reaction of 3-phenylpyridazine (Scheme (9)) gives a mixture of the three isomeric amination products in which the 4- and 5-amino isomers predominate <82JHC1285>. 

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