Aryl ketone hydrazones, reaction

The reaction of hydrazones with elemental fluorine can also be used for the synthesis of gem-in ally difiuorinated compounds (Table 4). The procedure, however, can have severe limitations it is only applicable to aryl ketone hydrazones (no reaction is observed with the hydrazones of benzaldehyde, cyclohexanone, or cyclopentanone), and mixtures ofdi- and monolluorinated compounds are obtained. In some cases, monofiuorinated derivatives are the only reaction products (entries 4 and 5). 

Similar intermediates are probably involved in the thionyl-chloride-promoted cyclization of 6-(benzylidene-l-methylhydrazino)-l,3-dimethyl-uracils (246 R = Me R = H) to pyrazolo[3,4-ff]pyrimidinediones (247). Less easily explained is the cyclization of hydrazones (246 R = Me R = H) to the oxazolo [5,4-f/]pyrimidines (245 X = 0) by sodium nitrite in boiling acetic acid. Undoubtedly, nitrosation at the 5-position is the initial step in these reactions, but thereafter events remain unclear. Interestingly, the ketone hydrazones (246 R = H, R = Me), on similar treatment, followed by reduction with sodium dithionite, furnish 6-aryl-l,3-dimethyl-lumazines (248) in low yields (10—15%). ... 

Fig, 8 Synthesis of alkenes through coupling of heterocyclic tosylhydrazones with aryl halides, (a) reaction from hydrazone (b) reaction from ketone... 

In an altogether different type of approach, the hydrazone is formed in situ as a lithium salt. Wilson et al. (80JHC389) described this approach in the one-pot synthesis of 5-aryl-2-phenylpyrazol-3-ones 72a-f from the corresponding hydrazones 65a-f (Scheme 20). The latter were obtained by condensing ketones 64a-f with phenylhydrazine. Treatment of hydrazones 65a-f with n-butyllithium in dry THF, followed by the addition of half a molar equivalent of diethyl carbonate 67 and then quenching the reaction mixture with hydrochloric acid, produced pyrazol-3-ones 72a-f, along with products 71. The yields of the products 72 are in the range 22-97%. Four intermediates—66a-f, 68a-f, 69a-f, and 70a-f— were proposed for this reaction. 

The hydrazones 1 used as starting materials are easily prepared by reaction of an aldehyde or ketone 8 with an aryl hydrazine 7 ... 

The hydrazone group is hydrolyzed (16-2) during the course of the reaction. Yields are high. Aryl iodides are converted to unsymmetrical diaryl ketones on treatment with aryImercury halides and nickel carbonyl ArH-Ar HgX-l-Ni(CO)4 ArCOAr... 

Aryl alkyl ketones are readily prepared by the Friedel-Crafts acylation process (see Section 6.11.1, p. 1006) and their Clemmensen reduction constitutes a more efficient procedure for the preparation of monoalkylbenzenes than the alternative direct Friedel-Crafts alkylation reaction (see below). Alternatively aldehydes and ketones may be reduced to the corresponding hydrocarbon by the Wolff-Kishner method which involves heating the corresponding hydrazone or semicarbazone with potassium hydroxide or with sodium ethoxide solution. 

Azoles can be produced from products of palladium-catalyzed hydrazone arylation and can serve as substrates for arylation reactions to produce N-aryl azoles. The Fischer indole synthesis uses N-ary I hydrazones, and these hydrazones can be generated by palladium-catalyzed chemistry. Benzophenone hydrazone was found by both the Yale and MIT groups to be a particularly effective substrate for palladium-catalyzed reactions, as summarized in Eq. (24) [140,141]. Reactions of benzophenone hydrazone with either aryl bromides or iodides occur in high yields using either DPPF- or BINAP-ligated palladium. These reactions are general and occur with electron-rich, electron-poor, hindered or unhindered aryl halides. The products of these reactions can be converted to hydrazones that bear enolizable hydrogens and are suitable for indole synthesis in the presence of acid and ketone [140]. 

Examples include the synthesis of 3-amino-l,2,4-oxadiazoles starting from 3-acylamino-5-methyl-l,2,4-oxadiazole <2002H811> and 2-aryl-l,2,3-triazoles from l,2,4-oxadiazole-3-ketone arylhydrazones <1999T12885, 2006JOC5616>. Oximes, hydrazones, formamidines, and thioureas of the furazan series also undergo base-catalyzed mononuclear rearrangements <2004RCB1121>. Nucleophilic attack at N(3) takes place in the benzofuroxan series. For example, reaction with secondary amines leads to o-nitroarylhydrazines (Scheme 55). 

Aryl diazomethanes and ethyl diazoacetate lose nitrogen completely when hydrogenated over palladium in neutral medium at room temperature and atmospheric pressure. Aryl diazoketones, however, under the same conditions, give the a-amino ketones which condense directly to the dihydropyrazines. The addition of acetic acid to the solvent for this later reaction permits the isolation of the amino ketone (Eqn. 19.32). With dilute hydrochlorie acid in the reaction mixture, complete loss of the nitrogen was observed. The hydrogenation of alkyl diazoketones in neutral or acetic acid solution results in hydrazone formation (Eqn. 19.33). ... 

P-Hydroxy tosylhydrazones, which are the products of a conventional aldol reaction between a dilithi-ated tosylhydrazone reagent and an aldehyde, can also be prepared by alternative routes. For example, Stork and Ponaras have described a procedure whereby an epoxy ketone is converted into an epoxy hydrazone. Subsequent addition of an alkyl- or aryl-magnesium bromide followed by hydrolysis yields either an a-alkyiated- or a-arylated-p-hydroxy ketone or an a,p-unsaturated ketone. Since the attack of the Grignard reagent on the epoxide occurs with inversion at the a-carbon, this reaction can be used to... 

Because of their predictable behavior and reactivity, thioacyl isocyanates comprise the bulk of this work, and extensive studies of their [4 + 2] reactions with olefins,83 enamines,84 enol ethers,843 thioacyl isocyanates,85 imines,85 1 86 carbodiimides,84387 isocyanates,843 azirines,88 /3-enaminoke-tones,89 dianils,86d azines,90 hydrazones,91 imidazoline-4,5-diones,92 aryl cyanates,93 disubstituted cyanamides,93 aldehydes,94 ketones,94 ketenes,94 alkyl or aryl iminodithiocarbonates,95 and the carbon-carbon double bond of ketenimines96 have been detailed. In an extensive comparative study of the [4 + 2] cycloaddition reactions of thioacyl isocyanates, the heterocu-mulenes bearing strong electron-withdrawing substituents were found to be more stable and less prone to participate in cycloaddition reactions.84 Representative examples are summarized in Scheme 9-IV. 

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