Phthalazine salts

Phthalazine forms monoquaternary salts with alkyl halides. 1-Substituted phthalazines are quaternized predominantly at position 3, and the site of quaternization of 1,4-disub-stituted phthalazines is determined by the steric hindrance of both substituents. 

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,... 

There has been much interest recently in the reaction of a, o)-di-halogenoalkanes. 1,2-Dibromoethane reacts with phthalazine to give ethane 1,2-bis-phthalazinium dibromide (1), none of the mono salt being formed directly, but the same dibromo compound and a, a -dipyridyl give the cyclic compound 2. ... 

Although there has been interest recently in phthalazine quaternary salts, no work has been reported on the position of quatemization since the classic studies of Gabriel and co-workers. For the sake of completeness, it may be noted that 4-methylphthalazine (59) and methyl iodide gave the salt 60 alkaline degradation of 60 gave a... 

The Chemical Abstracts name for hydralazine hydrochloride is l(2H)-phthalazinone hydrazone monohydrochloride, starting with volume 80 previously the name 1-hydrazino-phthalazine monohydrochloride was used. The CAS Registry No. is [304-20-1] for the hydrochloride salt, [86-54-4] for the base. 

In a synthesis of nucleoside analogs, the sodium salts of phthalazine-l,4-dione, phthalazin-l(2//)-one, and two pyridazin-3(2//)-ones, prepared with sodium hydride in DMF, were alkylated with ( )-2,3-0-isopropylidene-l-0-(4-toluenesulfonyl)glycerol by a nucleophilic substitution of the tosyloxy group <1999AP327>. 

While 1,2-diazinones usually give N-alkylation, O-alkylation can be achieved by first transforming them into the trimethylsilyloxy-l,2-diazines or silver salts <1996CHEC-II(6)1>. This approach has been used by El Ashry to attach sugar moieties to the oxygen atom of phthalazin-l(2//)-one <2003CAR2291 >. 

The direct synthesis by anodic oxidation of a new series of electrically conducting poljnners is described.. Our polymers derive from sulfur and/or nitrogen containing hetero-cycles such as 2-(2-thienyl)pyrrole, thiazole, indole, and phthalazine. The anodic oxidation of these monomers is carried out in acetonitrile solutions containing tetrabu-tylammonium salts (TBA X ) ith X = BF, tetraethylammonium salt, TEA H C-C H -S0. Characterization of the materials by electrical conductivity, electron spin resonance, uv-visible spectroscopy, and cyclic voltammetry is discussed. 

I Pyridazines, pyridazinium salts, dihydropyridazines, tetrahydropyridazines, cinnolines and phthalazines... 

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

The quaternization of (benzo)pyridazines by alkyl halides (these systems are not readily susceptible to arylation) was reviewed in CHEC-I <84CHEC-l(3B)l>. Monoquaternization of pyridazines occurs more readily than other diazines but less readily than pyridine, reflecting the intermediate basicity/nucleophilicity of pyridazine. Diquaternization of pyridazine can only be achieved with oxonium salts, particularly Me30 BF4 . As with protonation and A-oxidation, mixtures of products are often obtained on quaternization of unsymmetrical pyridazines and have been the subject of theoretical studies. A number of 2-(ribofuranosyl)-3(2//)-pyridazinones have been prepared by stannic chloride catalyzed alkylation of 3-(trimethylsilyloxy)pyridazines with protected 1-0-ace-tylribofuranose <83JHC369>. The quaternization behavior of phthalazines is similar to that of pyridazines, but with cinnolines alkylation usually occurs at N-2, unless there is a particularly bulky substituent at C-3. 

Nucleophilic addition of 6-aryl-2,3-dihydroimidazo[2,l-A]thiazole to phthalazine can be achieved via an A-acyl salt of phthalazine (Scheme 15). This reaction is not restricted to the 4-fluorophenyl... 

The condensation of 1-hydrazinophthalazine with polycarbonyl compounds can give a variety of products (open chain, fused cyclic, and nonfused cyclic) depending in particular on the presence of acid <83JHC123I> and this has led to some inconsistencies in the literature. This type of reaction has now been studied in detail and, for example, the hydrochloride salt of hydralazine with acetylacetone has been shown to give l-(3,5-dimethylpyrazolyl)phthalazine, while the free base reacts (Scheme 61) to give a triazolo[3,4-a]phthalazine <87H(26)ll77,87H(26)1277,87H(26)1853>. 

In principle, the interaction of a phosphorus(III) ester with an co-haloalkylamine should lead to an (co-aminoalkyl)phosphonic diester or a phosphinic acid analogue (Scheme 11). Such examples in the classical Michaelis-Arbuzov mould have been widely reported, but success in their outcome depends on the relative nucleophilicities of nitrogen and phos-phorus(III) centres towards the displacement of halogen. The interaction of triethyl phosphite and a halogen-substituted tertiary amine, such as 2-chloroethyldiethylamine, does not lead to a phosphonic diester, and in this particular case the product is a piperazinium diquaternary salt. However, successful Michaelis-Arbuzov reactions have been carried out between the bis(bromomethyl)phthalazines 130 (to both the mono- and di-phosphonic acid stages) and the series of [co-(2-cyano-4-pyridine)alkyl]phosphonic diesters 132 (n = 1-4) have been prepared from the 4-pyridinealkyl bromides 131 as precursors to the phosphonoalkylpiperidinecarboxylic acids 133 . ... 

Ethynylation of pyridazine and phthalazine could be achieved using bis(tributylstannyl)acetylene via A -alkoxycarbonyl quartemary salts of the substrates, followed by treatment with trifluoroacetic acid [94MI557]. Reaction of pyridazines 26 with allyltributyltin have been found to afford 4-allyl... 

Ch. 5 4-Chloro-, 4-Alkoxy-, and 4-Phenoxycinnolines 6 Aminocinnolines 7 Cinnoline Quaternary Salts 8 Reduced Cinnolines Ch. 9 Cinnolines Containing Additional Fused Rings Ch. 10 Phthalazines Unsubstituted in the Hetero Ring Ch. 11 l-AUcyl-, 1-Aryl-, and 1,4-Diarylphthalazines Ch. 12 1-Hydroxyphthalazines... 

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