1- Aroyl-2- hydrazines, synthesis

Some new approaches to the synthesis of pyridazino[3,4-c]pyridazines have been described. The pyrazolopyridazino[3,4-c]pyridazines (13 R = OMe, Me) and (14) are prepared by the reaction of /i-aroyl-a-(3-methyl-5(4//)-oxo-l-phenyl-4-pyrazolyl)propionic acid (12) with hydrazine or phenyl-hydrazine in butanol (Scheme 2) <90IJC(B)72>. 

After coupling of (hetero)aroyl chlorides 7 and terminal alkynes 4, hydrazines 29, and acetic acid are added and reacted in the same reaction vessel. Best results for the formation of pyrazoles 30 are obtained by dielectric heating in the micro-wave oven at 150°C for 10 min in the presence of methanol. Pyrazoles 30 are obtained in good to excellent yields, predominantly as colorless crystalline solids (Scheme 21) [113]. This concept has also been applied to the nonregioselective synthesis of 3,5-disubstituted pyrazoles 30 (R = H) upon conductive heating in the cyclocondensation step [114]. 

Recently, David Tupper [20] has reported the synthesis of 4-cyano p3crazole derivatives by starting with compounds similar to la. These workers have prepared 4-cyano pyrazole derivatives along with 5-amino pyrazole derivative by refluxing 3-dimethylamino-2-benzoyl-propenenitrile la with phenyl hydrazine or hydrazine in ethanol. However, the product was always a mixture of 4-cyano and 5-aminopyrazole derivatives. These workers have separated the mixture of p)rrazoles by column chromatography and observed that the reaction of hydrazine or phenyl hydrazine took place with 3-dimethylamino-2-aroyl-propenenitrile to furnished pyrazole carbonitrile as major and aminop3rrazoles as minor products. 

A consecutive three-component synthesis of pyrazoles [67] starting from (hetero)aroyl chlorides, terminal alkynes, and hydrazines represents an excellent entry to more sophisticated one-pot transformations on the regioselectively substituted heterocyclic core. For instance, the catenation of an electrophilic halogenation step led to a one-pot four-component synthesis of 4-halo pyrazoles 36 (halo = chloro or bromo) in good to excellent yield (Scheme 12.24) [68]. 

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