1.2.3.6- Tetrahydropyridazines, formation

Ahern and Gokel (1979) briefly mention that (jE -arenediazocyanides also react with a variety of dienes (cyclopentadiene, cyclohexadiene, butadiene, ( )-piperylene, etc.) in a [4+ 2]-cycloaddition reaction with formation of tetrahydropyridazines (Scheme 6-31). Here the two azo nitrogen atoms of the diazocyanide react as a dieneophile in a bis-aza Diels-Alder reaction. 

Azo compounds are reactive dienophiles. Indeed, one of the very first Diels-Alder reactions was the addition of diethyl azodicarboxylate to cyclopentadiene (equation 134)128 129. Other early examples of the reaction are the formation of tetrahydropyridazines from indazolone 252 and phthalazinedione 253 (equations 135 and 136)130. 

This method of nitrogen elimination from tetrahydropyridazines is frequently used in the synthesis of polycyclic systems. The thermolysis, as well as photolysis, of 2,3-diazabicy-clo[2.2.1]hept-2-enes gave bicyclo[2.1.0]pentanes via intermediate formation of cyclopenta-1.3-diyl, from which bicyclic compounds with one three-membered and one four-membered segment are formed this type of reaction is discussed in Houben-Weyl, Vol. E17b, pp 1089-1108 and 1163-1166. 

Symmetrically 3,6-disubstituted pyridazines yield homogeneous 4-substituted products, but if the substituents are different the formation of two different 4- and 5-substituted products is expected and was observed when ieri-butylmagnesium chloride was added to 3-methoxy-6-phenylpyridazine (58). The products were not separated, but the mixture was hydrolyzed with acid and the products were characterized as a-tert-butyl-3-phenyl-6-oxo-l,4,5,6-tetrahydropyridazine (62). The ratio of the isomeric adducts is approximately 2 1 and the preponderance... 

Upon heating a mixture of benzaldehyde and hydrazine salt in the presence of styrene (2 1 6 molar mixture), in addition to 1,5-diazabicyclo [3.3.0] octane, 3,5,6-triphenyl-l,4,5,6-tetrahydropyridazine was obtained as byproduct. The latter was the only product when a 2 1 2 ratio was used. The pyridazine formation is explained on the basis of cycloaddition of benzaldehyde azine to styrene, followed by tautomerization (87JOC2277). Similarly, other diazadienes add ethyl vinyl ether to give also 1,4,5,6-tetrahydropyridazines [83JCS(PI)1803j. 

Diphenyl-2,3,4,5-tetrahydropyridazine (XLIX) is structurally similar to a benzyl-hydrazone of propiophenone, and accordingly, a four-eletron polarographic wave is observed in acid solution with formation of L [306]. The electrode reaction is as follows ... 

Reaction of monosubstituted hydrazines with the readily available spirocyclic cyclo-propanedicarboxylates (163) gives 1-substituted l,4,5,6-tetrahydropyridazin-3(2/i)-ones (164) in a one-pot reaction (Scheme 123). Initial attack is thought to be a homo-Michael type of addition by the substituted hydrazine nitrogen decarboxylation occurs under the reaction conditions. The formation of the alternative pyridazinone (165) by attack of the unsubstituted hydrazino nitrogen was only observed (<5%) with (4-chloro-2-methylphenyl)hydrazine <93H(36)219>. 

This reaction has been modified to occur under solid-supported condition or under microwave irradiation. In addition, the base-promoted transformation from ketazine into pyrrole has also been established by the treatment of alkyl aryl ketazine with two equivalents of strong base, such as LDA. However, such reaction can lead to the formation of pyrrole, tetrahydropyridazine, or pyrazole, depending on the nature of ketazine. In general, the ketazine dianions with an electron-donating group at their carbon termini form pyrroles, whereas ketazine dianions without a substituent at the terminal carbon or with an electron-withdrawing group at the terminal carbon yield tetrahydropyridazines and pyrazoles. ... 

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