Pyridazine ring systems

Some derivatives of the [l,2,4]triazolo[4,3-3]pyridazine ring system 33 were subjected to a special type of nucleophilic substitution called vicarious nucleophilic substitution (VSN) <2006TL4259>. In the course of this transformation a formal substitution of az aromatic hydrogen atom - occurring via an addition-elimination mechanism - takes place. 

Reaction of l-aryl-3-carbethoxy-6-phenyl-l,4,5,6-tetrahydropyridazin-4-ones 718 with activated olefins such as benzalacetophenone, benzalacetone, 3-benzylideneacetylacetone, diethyl 2-benzylidenemalonate, and a-cyano-/3-phenylacrylic acid in the presence of an organic base like pyrrolidine, morpholine, piperidine, or triethylamine gave the corresponding 2,8-dihydro-l//-pyrano[2,3-t7 pyridazines 719-723, respectively. The 1-oxo- and 1-imino derivatives of the pyrano[2,3-r/ pyridazine ring system were also prepared from the respective 6-oxo or 6-imino derivative of the starting pyridazine 718 under the same conditions (Equation 60) <1989IJB733>. 

Only a few synthetic pathways to the pyridazino[l,2-a]pyridazine ring system are known. Most of these involve condensation of pyridazine derivatives which are unsubstituted at positions 1 and 2 with diacid chlorides (67JA4875), y-ketoacid chlorides (69JOC2720) and... 

The imidazo-pyridazine ring system forms the basis for a number of drugs in human and animal medicine. The synthesis of this system uses chemistry discussed in Chapter 43 to build the pyridazine ring. There we established that it was easy to make dichloropyridazines and to displace the chlorine... 

An indirect preparation of the imidazo[l,2-f)]pyridazine ring system has also been reported by valence isomerization of a tetrazolo[l,2-f>]pyridazine (70JOC1138). Treatment of 6-(2,2-dimethoxyethylamino)tetrazolo[l,5-f)]pyridazine (551) with polyphosphoric acid produces a 45% yield of 6-azidoimidazo[l,2-f>]pyridazine (547e). 

Free radical chlorination of the [l,2,4]triazolo[4,3-6]pyridazine ring system follows a stepwise introduction of the chlorine atoms in the following order of positions 3 > 8 > 7 > 6. This eventually leads to the perchloro derivatives (74MI4i50i). 

Oxidation of the [4,3-/ ]pyridazine ring system with potassium permanganate occurs by cleavage of the C(7)—C(8) bond. Thus, 3-phenyl-[l,2,4]triazoIo[4,3-f)]pyridazine was oxidized to 3-phenyl-l,2,4-triazole-5-carboxylic acid (74MI41501). 

The imidazo[4,5-d]pyridazine ring system has a mobile hydrogen which could give rise to two isomers in an unsymmetrically substituted molecule. 

The diazotization of 4-vinylpyridin-3-amines, followed by intramolecular azo coupling to the adjacent alkene moiety, affords the pyrido[3,4-c]pyridazine ring system 1 in low yield.104... 

Although not a typical reaction of the pyrido[4,3-c]pyridazine ring system, the acylation at N6 of 4,8-dialkyl-3-chloro-5,6,7,8-tetrahydropyrido[4,3-c]pyridazinc with numerous carboxylic acid chlorides is worthy of mention.142... 

Letsinger and Lasco6 reported the first authenticated synthesis of the pyrrolol l,2-6]pyridazine ring system. These authors demonstrate that, in methanol solution, pyridazines (192) would react readily with dimethyl acetylenedicarboxylate to give 5,6,7-tricarbomethoxypyrrolo-... 

The same double bond of this ring system (i.e., C(7)—C(8)) in the hydroxyphenyl derivative (37) was involved in cycloaddition with the enamine reagent (38) (Equation (7)). This reaction led to a derivative (39) of the 8H-pyrano[3,2- (]tetrazolo[l,5-(>]pyridazine ring system <93H(35)i33i>. 

The orbit molecular building system has been used for identifying the Fe " -complexing sites in the siderophore mandurapherrin containing the pyrazino[l, 2-6]pyridazine ring system <88HCA1528>. 

Stanovnik and co-workers " described one of the first syntheses of the oxazolo[5,4-c]pyridazine ring system 325 by treatment of the A-heteroaryl form-amidoxime 324 with A, iV-dimethylformamide dimethyl acetal (Scheme 1.88). When this reaction was repeated at reflux, the authors isolated a 5 4 mixture of 325 and 326. 

A simple one-pot procedure for the synthesis of imidazo-[l,2-a]pyridines (13) involves a novel condensation reaction of l-(arylacetyl)imidazoles (12) with dimethyl acetylenedicarboxy-late (eq 18). " Functionalization of 13 with hydrazine hydrate affords the imidazo[l,6]pyrido[2,3-pyridazine ring system (14). ... 

The problems with slow breakdown in soils that were identified for 6 were due in part to the chemical robustness of the tricyclic pyridazine ring system. To attempt to solve this problem we envisaged that heteroatom substitutions into the core... 

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