Hydrazino compounds synthesis

The ability of hydralazine and similar hydrazino compounds to reduce blood pressure was reported by Gross et al (1) in 1950. Methods of synthesis were published by Druey and Ringier (2) in 1951, along with typical reactions displayed by the compound, including several reactions which later became the bases for analysis of hydralazine and its metabolites. The drug has been widely used for treatment of hypertension, and papers on its properties and methods for its determination have been published in many languages. 

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. 

With the synthesis of the benzylidene hydrazones of selenazoles, it was possible to prepare formazans containing a selenazole ring. Of the compounds already described (Section I,C,1), 2-benzylidene-hydrazino-4,5-diphenyl- and 2-benzylidenehydrazino-4-methyl-5-carb-ethoxy-selenazole were used to couple with diazonium salts in order... 

Trying to prepare precursors for the synthesis of 3-substituted [l,2,4]triazolo[5,l- ]benzothiazoles, 2-hydrazino-4-methylbenzothiazole 393 was submitted to reaction with formic acid, urea, carbon disulfide, and acetic anhydride to give compounds 230, 238, 89, and 394 (Scheme 45) <1998IJC(B)921>. 

Murakami et al. reported the total synthesis of 1-hydroxy-3-methylcarbazole (23) and murrayafoline A (7) by classical Fischer indolization of the O-methanesulfonyl phenylhydrazone derivative 614 (575). The compound 614 was prepared from the corresponding aminophenol 612 via 2-hydrazino-5-methylphenol p-toluenesulfonate... 

Amino groups react very easily with aldehydes or ketones, and with aldehydes in the presence of amines, they can be acylated by the usual acylating agents, and they react with amidacetals, Vilsmeier reagents and nitroso compounds (Scheme 12). As mentioned earlier, alkylation leads mainly to AT(2)-alkylated products. The hydrazino group reacts in the same way as the amino group with aldehydes or ketones, with acyl chlorides or carboxylic anhydrides, with sulfonyl chlorides, ortho esters, carbon disulfide and with nitrous acid. The last three reactions have mainly been used for the synthesis of condensed 1,2,4-triazines. 

Reaction of diaminoguanidine (478) with 1,2-dicarbonyl compounds (452) was used for the synthesis of 3-hydrazino-l,2,4-triazines (479) (78HC(33)189, p. 396). 

V-Phthalimidoaziridines may be obtained by reaction of alkenes with 7V-aminophthali-mide which has been treated with lead tetraacetate (equation 152)550-554. These compounds are useful in the synthesis of a-hydrazino acid derivatives which are inhibitors of amino acid metabolising enzymes. 

Synthesis of the copper complex31 [167780-70-3] (H, Na salt) involves coupling of a diazonium compound with a hydrazone [54] 2-(3-amino-4-hydroxyphe-nylsulfonamido)chlorobenzene is dissolved in hot water, to which dilute NaOH solution is then added. After addition of sodium nitrite, the solution is cooled to -5 °C and then added to a well-stirred mixture of HC1, water, and ice. The diazonium salt suspension is neutralized with NaHC03 and combined with the weakly acidic solution of the hydrazone formed with 2-hydrazino-5-sulfobenzoic acid and benzaldehyde in water. The reaction mixture is kept at 0-10 °C, and at pH 10-12 by dropwise addition of diluted NaOH. When the coupling is complete, the pH of the formazan solution is reduced to 8 with HC1, a dilute aqueous solution of copper tetraaminosulfate is added and the solution is stirred for several hours. The copper complex 31 is precipitated at 85-90 °C with NaCl, then filtered and dried. The resulting powder colors wool in clear, fast blue tones. 

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