5-amino-phthalazine

Hydrazinophthalazine (137) with acetonylacetone gave l-[(2,5-dimethylpyr-rol-l-yl)amino]phthalazine (138) (substrate, AcOH synthonj slowly 65°C 3h 15%) analogs likewise. ... 

Phthalic anhydride and diethyl phthalate are easily converted with hydrazine into 4-hydroxyphthalazin-l(2/f)-one. Its substituted derivatives have been prepared using substituted hydrazines, substituted phthalic anhydrides, or diesters or disodium salts of substituted phthalic acids (Scheme 81). However, condensation of phenylhydrazine with phthalic anhydride gives only a small amount of the corresponding phthalazine, the main product being 2-anilinophthalimide. This can be rearranged in the presence of base into the phthalazine derivative. For the preparation of 2,3-disubstituted derivatives, 1,2-disub-stituted hydrazines are reacted with the appropriate phthalic anhydrides or phthaloyl chlorides. Derivatives of 4-amino- or 4-hydrazino-phthalazin-l(2iT)-one have been prepared either from the corresponding monothiophthalimide and 3-aminoisoindolin-3-one (1S4) or from ethyl 2-cyanobenzoate (155) and hydrazine hydrate (Scheme 82). Similarly,... 

In a similar manner to the formation of pyridazines from AT-aminopyrroles, cinnolines or phthalazines are obtainable from the corresponding 1-aminooxindoles or 2-amino-phthalimides. If the relatively inaccessible 1-aminooxindoles are treated with lead tetraacetate, mercuric acetate, r-butyl hypochlorite (69JCS(C)772) or other agents, cinnolones are formed as shown in Scheme 105. The reaction was postulated to proceed via an intermediate... 

Hydroxyphthalazin-l(2//)-one is obtained in a smooth reaction between phthalic anhydride and hydrazine hydrate and this is again the starting compound for many 1-substituted and/or 1,4-disubstituted phthalazines. The transformations of 1,4-dichloro-phthalazine, which is prepared in the usual manner, follow a similar pattern as shown for pyridazines in Scheme 110. On the other hand, phthalonitrile is the preferential starting compound for amino- and hydrazino-phthalazines. The most satisfactory synthesis of phthalazine is the reaction between a,a,a, a -tetrachloro-o-xylene and hydrazine sulfate in sulfuric acid (67FRP1438827), alt iough catalytic dehalogenation of 1-chloro- or 1,4-dichloro-phthalazine or oxidation of 1-hydrazinophthalazine also provides the parent compound in moderate yield. 

Dihydroxypyridazines are readily prepared from the diene 103 and DEAZD or PTAD,159 and the amino acid 104, a constituent of the Monamycin antibiotics, was synthesized from the Diels-Alder adduct of phthalazine-l,4-dione and penta-2,4-dienoic acid.160 These unusual amino acids can also be synthesized from the PTAD and parent HTAD adducts of penta-2,4-dienoic acid,161 and a variety of similar adducts, triazolo-pyridazines 105, has been synthesized from a wide range of 4-substituted 1,2,4-triazole-3,5-diones.162... 

The reaction of 1-amino-4,6-diphenylpyridine-2(l//)-thione (147) with dimethylformamide dimethyl acetal or triethyl orthoformate afforded 2-phenyl-4//-pyrido[2,l-a]phthalazine-4-thione (148) [81AQ(C)248],... 

Cyclic amino alcohols have been used in a Mitsunobu alkylation of 4-substituted phthalazin-l(2//)-ones <1996LA1477>. Mitsunobu alkylation has also been used to graft 6-chloropyridazin-3(2//)-one on a Wang resin. In this case competitive N- and O-alkylation is observed <2005JC0414>. 

Polyphosphoric acid (PPA) has recently been used for the intramolecular reaction of a properly positioned amino group with the carbonyl group of the lactam function of a pyridazin-3(2//)-one unit as exemplified by the ring closure of 2-(2-aminophenyl)phthalazin-l(2//)-one <2006T10018>. 

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