Phthalazines dicarboxylate

Since the pyridazine ring is generally more stable to oxidation than a benzene ring, oxidation of alkyl and aryl substituted cinnolines and phthalazines can be used for the preparation of pyridazinedicarboxylic acids. For example, oxidation of 4-phenylcinnoline with potassium permanganate yields 5-phenylpyridazine-3,4-dicarboxylic acid, while alkyl substituted phthalazines give pyridazine-4,5-dicarboxylic acids under essentially the same reaction conditions. 

A novel formal inverse-electron-demand hetero-Diels-Alder reaction between 2-aryl-a,/3-unsaturated aldehydes and ketones produces dihydropyran derivatives stereo-specifically.161 The inverse-electron-demand Diels-Alder reaction of 3,4-r-butylthio-phene 1-oxide with electron-rich dienophiles shows vyn-jr-face and endo selectivity.162 (g) The inverse-electron-demand Diels-Alder reaction of dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate with a variety of dienophiles produces phthalazine-type dihydrodiol and diol epoxides which were synthesized as possible carcinogens.163... 

Reaction of the fluoroborate salt of 3 (R = Ph) with dimethyl acetylene dicarboxylate gave the pyrrolo[2,l-a]phthalazine (25a). ... 

Dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate continues to be an important reagent in the inverse Diels-Alder reaction, and has been used in the synthesis of ningalin D <05JA10767>, dihydrodiol and diol epoxide of phthalazine <05T1545> and novel pyridazino-psoralen derivatives <05T4805>. 

In analogy to phthalazine syntheses, 5,7-dihydrofuro 3,4-A pyridinc (pyndine-2,3-dicarboxylic acid anhydride) and hydrazine readily condense in refluxing aqueous solution,42 refluxing acetic acid, or alternatively with lower yield in refluxing ethanol, to give pyrido[2,3-r/]-pyridazine-5,8(6/7,7//)-dione (la).78 A similar reaction is observed starting from pyridine-2,3-dicarboxylic acid anhydride and hydrazine hydrate in refluxing acetic acid.45... 

Tetramethyl pyridazine-3,4,5,6-tetracarboxylate, but not 3,6-dichloropyridazine or dimethyl phthalazine-l, 4-dicarboxylate, takes part in a Diels-Alder reaction with indole under very concentrated conditions (Scheme 31). The adduct produced after elimination of nitrogen aromatizes by ring opening and the resultant aniline attacks the adjacent ester group to give the phenanthridone... 

Ethoxycarbonylmethylphthalazinium bromide (173) with dimethyl acetylene-dicarboxylate gave dimethyl 3-ethoxycarbonylpyrrolo[2,l-a]phthalazine-l,2-dicarboxylate (174) (reactants, MeCN, NEts in MeCN dropwise, reflux, 4h 30%). ... 

The reactions of simple phthalazine A -oxides with dialkyl acetylenedicarbox-ylates have been studied in detail. For example, phthalazine 2-oxide (261) with dimethyl acetylenedicarboxylate (262) gave a separable mixture of l,2-dimethoxycarbonyl-2-phthalazinioethenolate (263) (or equivalent formulation) (4%), trimethyl pyrrolo[2,l-a]phthalazine-l,2,3-tricarboxylate (264) (11%), dimethyl 2-hydroxy-1,3-naphthalenedicarboxylate (265) (24%), dimethyl l,2-dihydro-l,2-epoxynaphthalene-2,3-dicarboxylate (266) (7%),... 

Amino-4-phenylphthalazin-2-ium mesitylenesulfonate (84) with dimethyl acetylenedicarboxylate gave dimethyl 6-phenylpyrazolo[5,l-o]phthalazine-1,2-dicarboxylate (85) (substrate, K2CO3, Me2NCHO, 20°C, 10 min synthon... 

Cyano ethoxycarbonyl (phthalazin-2-io)methanide (61) gave dimethyl 3-ethox-ycarbonylpyrrolo[2,l-fl]phthalazine-l,2-dicarboxylate (62) (for details and possible mechanism, see original). 

Benzo[b]phthalazine-l,4-dione (43) was synthesized from sodium naph-thalene-2,3-dicarboxylic acid hy dr azide and chlorine in diglyme at — 50 . It reacted with H202/alkali to give light with a quantum efficiency of about 5% of that of luminol and the same emission spectrum obtained from the starting hydrazide [55]. 

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