Pyridazines acid-catalyzed

In a different pattern, by using silylated acetylenes, substituted pyridazines are obtainable217 from the tetrazine derivative 401 in a diene-type reaction, first introduced by Carboni and Lindsey218. Via this reaction 4-TMS- (402) and 4,5-bis(TMS)-3,6-bis(methoxycarbonyl)pyridazine (403) can be achieved in very high yield, being inert against acid catalyzed desilylation (Scheme 59). 

A synthetic approach designed to produce pyridazino[4,5-c]pyridazinones unexpectedly yields pyrrolopyridazines, although in poor yields. The acid-catalyzed reaction between the hydrazine (101) and ketodiesters (102) results in formation of the pyrrolo[2,3-d]pyridazine (103) (Equation (31)) <92JHC1313>. 

Phenyl- and 5,8-diphenylpyrido[3,4-c/]pyridazine, as well as ethyl 5,8-diphenylpyrido[3,4-r/]-pyridazine-7-carboxylate, have been used as azadienes in inverse-electron-demand Diels-Alder reactions with 1-pyrrolidinocyclopent-l-ene or its six-membered homolog. After the aroma-tization of the intermediate dihydroisoquinolines by acid-catalyzed elimination of pyrrolidine or piperidine, this represents a route to isoquinolines 9.141- 164... 

Examples of Smiles rearrangements are known in the pyridazine series.402,545,546 The rearrangement occurs thermally or is base or less completely acid-catalyzed. Contrary to previous observations, alkaline treatment of 253 yields exclusively 254.545,547 Smiles rearrangement is observed also when the phthalimido derivative 255 is treated with hydrazine to give the hydroxyethylamino compound 256.548... 

As seen with pyridazines, palladium catalyzed coupling reactions were also frequently applied in the phthalazine field. For example, commercially available 1,4-dichlorophthalazine 185 was aminated to give 186 in good yield by aromatic nucleophilic substitution with A -methylpiperazine <01S699>. Then, 186 was coupled with various substituted arylboronic acids to obtain 187 by Suzuki-type cross-coupling reactions. Best results were obtained with electron-donating substituents on the arylboronic acid. 

Hydrazone 1042 (prepared from 2-amino-l,l,l-trifluoro-3-phenylsulfonyl-2-propanol) is one more NNCC binucleophile for the synthesis of chain-fluorinated pyridazines (Scheme 222) [626], In this case, two-step reaction of 1042 with a-diketones is used, including acid-catalyzed hydrazone formation and base-... 

Literature reports on diazaquinones derived from o-benzoquinone are very rare. Compound 74 was suggested to be a common intermediate formed during heating of 2,5-bis(diazo)-3,4-diketoadipate 73 with isopropanol and with various bases (76T269). Direct reduction of the intermediate with isopropanol provided pyridazine 75. A base-catalyzed benzilic acid rearrangement of 74 followed by decarboxylation of 76 afforded pyrazole 77 (Scheme 18). 

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