Ketone hydrazones, preparation

Excellent simple (90-100%) and induced diastereoselectivities (92-100%) were observed in the syntheses of 3,4-disubstituted 5-oxoalkanoates using, instead, various substituted aldehydes and ketones to prepare the chiral hydrazones. 

Hydrazones prepared from (S)- l-amino-2-(methoxymethyl)pyrrolidine (242) and acyclic ketones have been shown to undergo deprotonation and alkylation with almost complete asymmetric induction at the a-center (79AG(E)397). The ant alarm pheromone, (+)-(5)-4-methyl-3-heptanone (245), was prepared from the metallated hydrazone of diethyl ketone (243) by alkylation with n-propyl iodide and subsequent cleavage of the crude product via its JV-methyl iodide with acid (Scheme 52). The optical purity of the product was >99%. 

Ketone hydrazones can be converted into aliphatic diazo compounds which are, in contrast to nonfluorinated analogs, quite stable at room temperature. 2-Diazo-l,l,1-trifluoropropane is obtained as a solution in diethyl ether or pentane by the oxidation of l,l,l-trifluoropropan-2-one hydrazone using silver oxide.243 Analogously, phenyl trifluoromethyl ketone hydrazone is oxidized to the diazo compound 6 by mercury(II) oxide in alkaline media.362 Bis(per-fluoromethyl)- 7 and bis(perfluoroethyl)diazomethane are prepared by lead(IV) acetate oxidation of the corresponding hydrazones in benzonitrile solution at 0-25 c.244,245... 

The use of branched ketones enables preparation of 3//-indolium salts. For instance, condensation of the ketone 331 with the hydrazine 332, followed by Fischer indolization of the resulting hydrazone 333 with perchloric acid, afforded the product 334 (Equation 96) <2000JHC1571>. The hydrazine components may also be generated from anilines in a one-pot variant of this route <2004JHC103>. 

Crooks and Robinson have used this method to prepare 2,3-dimethyl-5-azaindole in 14.5% yield from isobutyraldehyde 4-pyridylhydrazone, obtaining none of the expected 3,3-dimethyl-5-azaindolenine. The ethyl methyl ketone hydrazone gave the same azaindole in 51.5% yield. These authors also suggest that the 3,3-dimethyl-7-azaindolenine reported by Kelly and Parrick is in fact the rearranged product 2,3-dimethyl-7-azaindole. There is no evidence to date to support either structure. 

Nickel peroxide, an undefined black oxide of nickel, is prepared from nickel sulfate hexahydrate by oxidation in alkaline medium with an ozone-oxygen mixture [929] or with sodium hypochlorite [930, 931, 932, 933]. Its main applications are the oxidation of aromatic side chains to carboxyls [933], of allylic and benzylic alcohols to aldehydes in organic solvents [929, 932] or to acids in aqueous alkaline solutions [929, 930, 932], and of aldehydes to acids [934, the conversion of aldehyde or ketone hydrazones into diazo compounds [935] the dehydrogenative coupling of ketones in the a positions with respect to carbonyl groups [931] and the dehydrogenation of primary amines to nitriles or azo compounds [936]. 

As an example of Kishner5 s method, n-propylcyclobutane can be prepared from. cyclobutyl ethyl ketone hydrazone as follows 511... 

The oxidation of hydrazones has provided two new methods for the preparation of substituted diazomethanes. Ketone hydrazones, upon treatment with sodium in ether and subsequent aerial oxidation, gave diazomethanes (52) in excellent yields (Scheme 50). Similarly, hydrazonoethylidene derivatives yield diazoethylidenes (53) upon oxidation with Mn02 (Scheme 51). ... 

Reaction with Aldehydes and Ketones. Classical preparations of aryl and alkyl hydrazones with hydrazine lead to mixtures of hydrazones and azines (eq 2). 

Hydrazones. Reaction of hydrazine with aldehydes and ketones is not generally useful due to competing azine formation or competing Wolff-Kishner reduction. Exceptions have been documented. Recommended conditions for hydrazone preparation are to reflux equimolar amounts of the carbonyl component and hydrazine in n-butanol. - A more useful method for simple hydrazone synthesis involves reaction of the carbonyl compound with dimethylhydrazine followed by an exchange reaction with hydrazine. For substrates where an azine is formed, the hydrazone can be prepared by refluxing the azine with anhydrous hydrazine. gem-Dibromo compounds have been converted to hydrazones by reaction with hydrazine (eq 6). ... 

A considerable number of examples will be found in the text in which halo-genated and other substituted olefins are produced. Their modes of fonnation do not usually differ in principle from the corresponding unsubstituted case. However, some special methods have been used, for example, the direct preparation of halo olefins from ketones with phosphorous hahdes, or via hydrazones. 

An improved method for the preparation of A" -3-ketones from 4-bromo compounds was described by Mattox and Kendall. This procedure involves dehydrobromination of the 2,4-dinitrophenylhydrazone and subsequent cleavage of the hydrazone with pyruvic acid ... 

Nevertheless, derivatives of the 11-ketone have been prepared in special cases. Thus the ethylene ketal of 3a,20) -dihydroxypregnan-l l-one is obtained in 50% yield by prolonged reaction according to the direct procedure. Ketals of A/B aromatic-11-ketones are formed by exchange dioxolanation. 11 -Semicarbazones have not been prepared, but hydrazones... 

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