Phenylhydrazones rearrangement

Rearrangement into Pyrazolediones. L-f/lreo-2,3-Hexodiulosono-l,4-lactone 2,3-bis(phenylhydrazone) rearranged to l-phenyl-4-phenylazo-... 

The coupling of enamines with aromatic diazonium salts has been used for the syntheses of monoarylhydrazones of a-diketones (370,488-492) and a-ketoaldehydes (488,493). Cleavage of the initial enamine double bond and formation of the phenylhydrazone of acetone and acetophenone has been reported with the enamines of isobutyraldehyde and 2-phenylpropionalde-hyde. Rearrangement of the initial coupling product to the hydrazone tautomer is not possible in these examples. 

Another example of this rearrangement has been used to prepare 1,2,3-triazole 146 from furazanic phenylhydrazone 147 (Scheme 84) [93JCS(P1)2491]. Interestingly, furoxanic Z-phenylhydrazones 150 underwent thermal recyclization to 1,2,3-triazole A-oxides 152, evidently through intermediate 151. Treatment of the hydrazone 150 with rerr-BuOK leads to the nitromethyl derivative 149 [OOOMIl] (Scheme 84). Lead tetraacetate oxidation of 147 with subsequent Lewis acid treatment of the initially formed intermediate afforded indazole 148 (Scheme 84) (85JHC29). 

The phenylhydrazones of benzaldehyde and its homologues, (or of acetone) are readily autoxidised in solution and rearrange to give the azo-hydroperoxides, isolable as solids which may explode after a short time on standing, though not on friction or impact [1], Contact with flame or with cone, sulfuric or nitric acids also initiates explosion [2]. 

The role of substituents X on the mononuclear heterocyclic rearrangement (MHR) of 20 phenylhydrazones 54 of 3-benzoyl-5-phenyl-l,2,4-oxadiazole into the triazoles 55 (Equation 2) has been investigated, allowing the influence of X on the product distribution to be evaluated and first-order rate constants and Hammett correlations to be determined <1999T12885>. 

All primary nitro-compounds couple with diazobenzene, but instead of the expected azo-compounds, phenylhydrazones of a-nitro-aldehydes are formed by rearrangement of the molecule ... 

The mechanism of this elegant, surprising, and widely applicable synthesis of indole derivatives was only explained recently (R. Robinson). It must be assumed that the keto-phenylhydrazones, in tautomeric hydrazo-form, undergo a species of benzidine rearrangement which, like the latter, can often occur even in dilute acid solution, e.g. with the phenylhydrazone of pyruvic acid. 

Alkyl- and aryl-hydrazones of aldehydes and ketones readily peroxidise in solution and rearrange to azo hydroperoxides [1], some of which are explosively unstable [2], Dry samples of the p-bromo- and p-fluoro-hydroperoxybenzylazobenzenes, prepared by oxygenation of benzene solutions of the phenylhydrazones, exploded while on filter paper in the dark, initiated by vibration of the table or tapping the paper. Samples were later stored moist with benzene at —60°C to prevent explosion [3], A series of a-phenylazo hydroperoxides derived from the phenyl-or p-bromophcnyl-hydrazones of acetone, acetophenone or cyclohexanone, and useful for epoxidation of alkenes, are all explosive [4], The stability of several substituted phenylazo hydroperoxides was found to be strongly controlled by novel substituent effects [5],... 

The most useful route to indoles is the Fischer indole synthesis, in which an aromatic phenylhydrazone is heated in acid. The phenylhydrazone is the condensation product from a phenylhydrazine and an aldehyde or ketone. Ring closure involves a cyclic rearrangement process. 

About the same time a number of publications appeared on the complete synthesis of 7a, 7b, 30 and 31 using a different approach to build the alkaloid framework (Scheme 5 68M1364, 68M1584, 69JCA(C)2738). Phenylhydrazone 34 under Fischer reaction conditions was converted into indole 34a with subsequent successive transformations to pentacyclic derivative 35. Its acid-initiated rearrangement led to the formation of 7b and 30 in a ratio of 1 5. While 7b and... 

The cyclohexanone phenylhydrazone (512), obtained by reacting cyclohexanone (510) with phenylhydrazine (511), on indolization, furnished tetrahydrocarbazole 513 which, on dehydrogenation, afforded carbazole 514. The success of the reaction is dependent on the reagent used for indolization and the dehydrogenating agent. The mechanism for the formation of the tetrahydrocarbazole involves a tautomeric equilibrium and the formation of a new C-C bond via a [3,3]-sigmatropic rearrangement followed by elimination of ammonia (495,496,498) (Scheme 5.7). 

For the rearrangement of 5-aryl-substituted phenylhydrazones 180, kinetic data in dioxan-water at various pS" show the two expected reaction pathways uncatalyzed and base-catalyzed. Moreover, at each pS, the rearrangement rate depends on the substituent in the C(5)-aryl group electron-withdrawing substituents increase reactivity, whereas electron-... 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

Ketones of the 7r-deficient heterocycles form the usual derivatives, phenylhydrazones, semicarbazones, etc. The oximes undergo the Beckmann rearrangement (70JCS(B)1687). 

Only two classes appear to be known. The 1,2,5,6-system (599) is said to result from the treatment of the semicarbazide (598) with iron(III) chloride (28JIC439), and more recently it has been shown that benzoyl isothiocyanate adds to the phenylhydrazones of benzaldehyde and several ketones to give the l,3,4,6-oxatriazepine-5-thione system (600) (67JCS(C)952, 76JCS(P1)2243). The products rearrange to give (601) quantitatively on treatment with acid. 

The mechanism of the reaction, as shown in Scheme 7, involves a Claisen-like rearrangement via the enehydrazine tautomer of the phenylhydrazone. The reaction is acid-catalyzed and it seems likely that the intermediates retain at least one proton throughout the course... 

Xanthone is unreactive towards hydrazine and phenylhydrazine. The oxime is obtained by reaction of xanthione (xanthene-9-thione) with hydroxylamine, or from xanthone and hydroxylamine in pyridine. When the oxime is heated in water with phenylhydrazine, the phenylhydrazone is formed. In acid solution, xanthone reacts normally with 2,4-dinitro-phenylhydrazine but xanthone-1 -carboxylic acid (435) gives the pyridazinone (436), possibly via the hydrazone (57JCS1922). When the oxime is heated with phosphorus pentachloride it undergoes a Beckmann rearrangement to give the amide (437) (70MI22300). 

A) from D-mannose phenylhydrazone (B and C) a rearranged radical from (A) (D) from D-mannose phenylhydrazone [(CHsCO)20-C5H5-1% K-tert-BuO] (2.5 mM to 3.5 mM, in Me2SO-l% K-tert-BuO)... 

Figure 4 (A to C) shows changes in the ESR spectra obtained with D-mannose phenylhydrazone treated with 1% potassium terf-butoxide in methyl sulfoxide. The original three-line pattern (spectrum A), ascribed to the nitroxide radical, rearranges to a new pattern in about 15 minutes (spectrum B) this pattern remains steady for hours if the solution is kept in the absence of oxygen (spectrum C).

The formulas depicted may reflect radicals observed in the ESR spectra of the D-mannose phenylhydrazone in an alkaline solution (A and B, Figure 4) they show a possible path for the formation of the nitroxide radical and its rearrangement. The major steps in this pathway are ... 

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