Phenylhydrazine substituted

Hydrazine and its alkylated derivatives are used as rocket fuels in organic chemistry, substituted phenylhydrazines are important in the characterisation of sugars and other compounds, for example aldehydes and ketones containing the carbonyl group C=0. 

Heating of -keto esters or of 1 3-diketones with an equivalent amount of phenylhydrazine often yields substituted pjrrazolones or pjrrazoles respectively. The latter may serve as derivatives of enols. 

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,... 

Isothiazolium salts (59) react with phenylhydrazine to give pyrazoles (60) (72AHC(14)l) (see Section 4.02.1.6). When treated with hydrazine hydrate, 3-chloro-l,2-benzisothiazole gives di-(o-cyanophenyl) disulfide (73SST(2)556), but 2,1-benzisothiazole gives o-aminobenz-aldehyde azine (72AHC( 14)43). 2-Substituted saccharins give the expected o-sulfamoyl-benzohydrazides. 

If there is no phenyl substituent in the 3-position the amination ability decreases. The acyloxaziridine (104) yields only 11% of a semicarbazide derivative with piperidine. In the presence of strong bases an intramolecular amination competes. Compound (104) reacts with methoxide within a couple of seconds to give phenylhydrazine carboxylic ester (106), and with cyclohexylamine to give the substituted semicarbazide (107). A diaziridinone (105) is assumed to be the common intermediate, formed by an intramolecular reaction from deprotonated (104) (67CB2600). 

More recently, Tietze and Steinmetz (96SL667) used the patented polystyrene-resin methodology for for the solid-phase synthesis of a large number of diverse )3-keto esters 40a-h. These were reacted with phenylhydrazine in THF at room temperature to give hydrazones 41a-h that were then cychzed into 2-phenyl 5-substituted pyrazol-3-ones 42a-h by heating in toluene at 1(X)°C (Scheme 12). 

The use of substituted hydrazines, phenylhydrazine, and 2,4-dinitrophenylhydra-zine (68T4285 74JOC843) can give both 5- and 3-acetylenylpyrazole (Table VT). In this case, the direction of cyclization depends both on the hydrazine structure and the experimental conditions. 

The pseudo-ionone has a peculiar but not very pronounced odour it docs not oombine with bisulphite of sodium as most of the ketones of the higher series, but, in other respects, it possesses the ordinary characteristic properties of the ketones, forming, in particular, products of condensation with phenylhydrazine, hydroxyl-amine and other substituted ammonias. 

The product resulting from this reaction is dissolved in ether, the latter is evaporated and the residue subjected to the fractional distillation in vacuo. The fraction distilling under a pressure of 12 mm. at a temperature of from 125° to 135° C. is collected. This product may be still further purified by converting it by means of phenylhydrazine or other substituted ammonias into a ketone condensation product decomposable under the action of dilute acids. 

Removing the substituted hydrazine (58) leaves acetoacetic ester (57). Phenylhydrazine is available, so it is easier to make (59) and methylate afterwards. This removes the chemoselectivity problem as the more nucleophilic NH group attacks the more electrophilic ketone. 

Divalent Co substitution in copper amine oxidase revealed 19% of the native specific activity (for MeNH2) and 75% of the native reactivity toward phenylhydrazine. The major cause of this was a 68-fold increase in Km for 02. These investigations support the idea that electrons flow directly to bound 02 without the need for a prior metal reduction and that the Cu does not redox cycle but simply provides electrostatic stabilization during reduction of 02 to 02-. 1211... 

Hydrazones are also useful substrates in the preparation of pyrazoles. Reaction of N-monosubstituted hydrazones with nitroolefins led to a regioselective synthesis of substituted pyrazoles <060L3505>. lf/-3-Ferrocenyl-l-phenylpyrazole-4-carboxaldehyde was achieved by condensation of acetylferrocene with phenylhydrazine followed by intramolecular cyclization of the hydrazone obtained under Vilsmeier-Haack conditions <06SL2581>. A one-pot synthesis of oxime derivatives of l-phenyl-3-arylpyrazole-4-carboxaldehydes has been accomplished by the Vilsmeier-Haack reaction of acetophenone phenylhydrazones <06SC3479>. 

Henseke and Liebenow132 demonstrated that D-glucosone reacts with di-substituted hydrazines in alkaline conditions to form 1-hydrazones. They regarded this as indicating that a free aldehyde group is present in the osone. Since these hydrazones react with phenylhydrazine under acid conditions only, it was suggested that the potential carbonyl group at C2 is HC=N—N(CH3)Ph CHO CH(OH)s... 

Iwakawa et al. studied the reaction of 3-acetonyl-5-cyano-l,2,4-thiadiazole 72 with a series of 4-substituted phenylhydrazine hydrochlorides. When electron-donating substituents were used (e.g., methyl and methoxy) in the phenyl ring of the hydrazine, the reaction proceeded via a Fischer-indole mechanism to give indoles 73 as the sole product. In contrast, reaction of 72 with phenylhydrazine and 4-chlorophenylhydrazine gave only small amounts of indole 72, but much higher yields of the pyrazole 74. The authors described in detail the respective reaction mechanisms... 

A number of 2H-1,2,3-triazole 1-oxides 72 were prepared by chemists at the Cassella Company as potential NO-donors in view of their formal structural similarity with furoxan derivatives [18]. Derivative 72a was studied in depth. It was obtained by cupric sulfate oxidation of intermediate 79, derived from the action of the substituted phenylhydrazine 78 on the oximino acetoacetic acid amide 77 (Scheme 6.13). 

Phenylsydnone is the prototype of that class of mesoionic compounds called sydnones. On acidic hydrolysis it produces phenylhydrazine, whereas basic hydrolysis regenerates N-nitroso-N-phenylglycine. This sydnone undergoes a variety of electrophilic substitutions, including mercuration and... 

The reactivity of the keto group is not influenced by the substitution the reaction of 3-(trifluoromethylmercapto)-2-butanone with hydroxyl-amine hydrochloride gives the corresponding oxime in good yield. Cyclization of diketones and keto esters to pyrazole derivatives succeeds by the well-known method using phenylhydrazine ... 

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