Hydrazones, addition

Diazo compounds are formed as reaction intermediates by oxidation of the hydrazones. Addition of hydrogen fluoride, generated during the oxidation process, to the diazo compounds gives the monofluorinated derivatives, probably due to the proximity of the nascent hydrogen fluoride to the diazo group. ... 

An earlier application of 1,4-conjugate additions employing azaallyllithium reagents formed from ketone dimethylhydrazones is Kelly s hydrazone version of the classical Knoevenagel route to substituted pyridine derivatives.71 In this chemistry, a mixed cuprate derived from a dimethylhydrazone lithio anion and copper thiophenoxide was first allowed to react with an a,p-unsaturated ketone. The product enolate can then be acylated or protonated to yield either a diketo hydrazone or a keto hydrazone. Addition of... 

With an a,p-unsaturated hydrazone, addition of a nucleophile can lead to a new alkene, in which the double bond has migrated to the position formerly occupied... 

Synthesis of hydrazines from hydrazones Addition of organometallic compounds to carbon-nitrogen double bonds... 

Silylation of Formyl Hydrazone. Addition of the ethyl Grignard reagent to formyl hydrazone 46 via in situ silylation using BSA provided the corresponding formyl hydrazine with excellent diastereoselectivity in favor of the desired 5, 5 -diastereoisomer 47 (eq 44). ... 

This goal might well be achieved by introducing an auxiliary that aids the coordination to the catalyst. After completion of the Diels-Alder reaction and removal of the auxiliary the desired adduct is obtained. This approach is summarised in Scheme 4.6. Some examples in which a temporary additional coordination site has been introduced to aid a catalytic reaction have been reported in the literature and are described in Section 4.2.1. Section 4.2.2 relates an attempt to use (2-pyridyl)hydrazone as coordinating auxiliary for the Lewis-acid catalysed Diels-Alder reaction. 

Some examples of the use of a temporary additional site of coordination have been published. Burk and Feaster have transformed a series of ketones into hydrazones capable of chelating to a rhodium catalyst (Scheme 4.7). Upon coordination, enanti os elective hydrogenation of the hydrazone is feasible, yielding N-aroylhydrazines in up to 97% ee. Finally, the hydrazines were transformed into amines by treatment with Sml2. 

Analogous to the oxidation of hydrazones to azo compounds, A-unsubstituted pyrazolidines are oxidized to A -pyrazolines. For example, the blcyclic pyrazolidine (415) when treated with silver oxide yields the pyrazoline (416) (65JA3023). Pyrazolidine (417) is transformed into the perchlorate of the pyrazolium salt (411) by reaction with mercury(II) acetate in ethanol followed by addition of sodium perchlorate (69JOU1480). 

Hexafluoroacetone azine accepts nucleophiles (ROH, RSH, R NH) in positions 1 and 2 to yield hydrazones [27] Phosphites give open-chain products via a skeletal rearrangement [22] Radical addition reactions are also reported [22] Treatment of tnfluoropyruvates with tosylhydrazine and phosphorus oxychlo-ride-pyndme yields tnfluoromethyl-substituted diazo compounds [24] (equation 3)... 

Katritzky and co-workers studied the mechanism of this reaction in detail. His work involved a NMR study of 16 reactions of methyl-, phenyl-, 1,2-dimethyl-, and l-methyl-2-phenylhydrazine with /3-keto esters. In many cases starting materials, intermediates, and products were detected simultaneously. Most reactions proceed by nucleophilic addition of the less hindered hydrazine nitrogen atom to the keto carbon of the keto ester. For example, the pathway given in Scheme 3 for the reaction of methyl 3-oxobutanoate 9 with methyl- or phenyUiydrazine 2 (R = Me or Ph) was found to be dominant. The initially formed addition product 10 dehydrates to hydrazone 11, which then isomerizes to hydrazone 12. Intermediate 12 then cyclizes to pyrazol-3-one 13, which tautomerizes to the kinetically more stable pyrazol-3-otie 14 [87JCS(P2)969]. 

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. 

Although the addition of hydrazine and its derivatives to acetylenic ketones has been studied in considerable detail, their interaction with hydrazones and mono-alkylhydrazones is less well known. Yandovskii and Klindukhova (74ZOR730) have studied the reaction between hydrazones and alkylhydrazones of aliphatic ketones with dipropynylketones and showed that hydrazones of acetone, methyl-ethylketone, and cyclohexane easily add to one of the triple bonds of dipropynylketone to form 4-methyl-1,1,3-trialkyl-2,3-diaza-l,4-nonadien-7-yn-6-ones (yields... 

Evidently, analogously to the mentioned cyclization of similar oximes to ben-zisoxazole derivatives (See Section II.A), reaction can take place only in compounds with suitable configuration. However, in case of hydrazones, due to the tautomeric equilibrium of both possible configurations, the reaction usually achieves complete conversion. The usual setup involves heating with the respective hydroxide if an ester group is present, it is partially or completely hydrolyzed to the corresponding acids, which, in addition, can also undergo decarboxylation. 

Isopropylidene and benzylidene hydrazones of the selenazoles w hich are unsubstituted in the 5-position react with p-nitrosodiethyl-and p-nitrosodimethyl-aniline in organic solvents on heating and the addition of acetic acid or pyridine. - Thus result crystalline, deeply colored, 2-hydrazono-5-(p-dialkylaminophenylimino)selenazoles (correspondingly substituted in the 4-position), details are given in Table VII. The presence of an aromatic residue in the 4-position of the selenazole ring appears to be needed to obtain crystalline compounds. 

Reaction of 2,3-dichlorobenzoyl chloride with cyanide ion leads to the corresponding benzoyl cyanide (141). Condensation of that reactive intermediate with aminoguanidine 142 leads to the hydrazone-like product 143. Treatment with base results in addition of one of the guanidine amino groups to the nitrile function and formation of the 1,2,4-triazine ring. The product, lamo-trigine (144), is described as an anticonvulsant agent [31]. 

Alternately, amifloxacin can be prepared via the ofloxacin/difloxacin route using an addition-elimination reaction with unsymmetiical N-methyl-N-formyl hydrazone to give 49 [14]. 

Chlorobenzaldehyde(2-nitrophenyl)hydrazone (3 g, 10.9 mmol) was heated under reflux with granulated tin (10 g) and coned hydrochloric acid (60 mL) for 1 h upon which an orange, clear solution was obtained, which became colorless on further heating. After the removal of tin, the solution was evaporated, almost to dryness, on a water bath to give a colorless, shiny, crystalline residue which was recrystallized (dil hydrochloric acid) to provide the hydrochloride mp 285 C. The free base was obtained as a colorless, crystalline mass after addition of NH3 to an aqueous solution of the hydrochloride, and was recrystallized (EtOH) to give shiny colorless plates mp 217-218 C. 

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