Pyridazines intramolecular cycloaddition

Hexahydropyrido[l,2-6]pyridazin-8-ones 178 and a 2,3-tetramethylene derivative were formed on the intramolecular cycloaddition of 177, formed in situ by dehalogenation of hydrazones of the hex-5-enoic acid derivatives 176 [87JCS(P1)2511]. Intramolecular cycloaddition of hydrazones 179 in... 

An acetylenic side chain in 5-ethynyl-2 -deoxyuridine or its O-acetyl derivative is converted by this method into a new pyridazine ring (86JOC950). Intramolecular cycloaddition of 1,2,4,5-tetrazines with acetylenic side chain has been used to prepare various condensed heterocyclic rings (32) (85TL4355 86TL2747 87CZ16 88JOC1415). 

Further examples of inter- and intramolecular cycloaddition reactions of pyridazine A(-oxides have been reported. Flash vacuum pyrolysis of 6-benzylpyridazine 1-iV-oxide gave a low yield (14%)... 

Interestingly, Boger et al. found that intramolecular cycloadditions of tethered alkynes 359 and 361 proceeded under milder conditions than their intermolecular analogs, giving the expected fused pyridazines 360 and 362, respectively (Scheme 88) <1998JOC6329>. 

An intramolecular [4 + 2] cycloaddition is represented by a thermal conversion of allylphenoxy- and allyloxyphenoxy-pyridazines into xanthenes (80CPB198). 

Ab initio Hartree-Fock and density functional theory calculations were performed to study the transition state geometry in intramolecular Diels-Alder cycloaddition of azoalkenes 55 to give 2-substituted 3,4,4u,5,6,7-hexahydro-8//-pyrido[l,2-ft]pyridazin-8-ones 56 (01MI7). 

In an intramolecular variation of the pyridazine synthesis from 1,2,4,5-tetrazines and alkyncs (see Section C.5.),30 this [4 + 2] cycloaddition with inverse electron demand has been applied to the synthesis of 5,6,7.8-tetrahydropyrido[2,3-c]pyridazines.31 Thus, 6-substituted A -(pent-4-ynyl)-l,2,4,5-tetrazin-3-amines 1, obtained from 3-(methylsulfanyl)-l,2,4,5-tetrazines and pent-5-yn-l-amine, thermally cyclizes to give the corresponding 3-subsliluted 5,6,7,8-tetrahydropy-rido[2,3-c]pyridazines 2. Depending on the electron-withdrawing properties of the 6-substituent in the starting tetrazine 1, temperatures between 130 and 170°C are required.31... 

The synthetic strategy is simple by way of a nucleophilic aromatic substitution—normally using C-, 0-, S-, or A-nucleophiles (303)—a chain with the 27c-unit is anchored to the tetrazine ring (302). The subsequent intramolecular (4 -F 2) cycloaddition (304) (305) follows the normal course of Scheme 53. In most cases alkyne units have been used as the 27i-component, forming bicyclic pyridazines (305) directly. 

Intramolecular (4+2 cycloaddition reactions of pyridazino(4,S-with acetylenic side-chain dienophiles were found to provide convenient access to /-annelated phthalazine derivatives 94JHC(31)3571. Base-catalysed cycli-sation of pyrazoles (11) followed by oxidation was shown to yield cinnoline-4-carboxylic acid l-A/-oxides (13) (93CC1756). 

The pyridazino[4,S-thermal intramolecular [4+2] cycloadditions to yield/ annelated phthalazines (120) [94JHC357]. 

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