Carbon-hydrogen bonds hydrazones

Hydrogen shifts are often observed in thermal isomerizations of vinylaziridines. Heating of compounds 221 at 180 °C produced mixture of 3-pyrrolines 222 and hydrazones 223 (Scheme 2.54) [87]. The formation of 223 can be explained in terms either of a concerted hydrogen shift as depicted in 224 or of diradical intermediates 225, both of which would be followed by thermal isomerization of the (Z)-carbon-carbon double bonds to provide the ( ) isomers 223. 

The reaction of alkyllithium reagents with acyclic and cyclic tosylhydrazones can lead to mixtures of elimination (route A) and addition (route B) products (Scheme 22). The predominant formation of the less-substituted alkene product in the former reaction (Shapiro Reaction) is a result of the strong preference for deprotonation syn to the N-tosyl group. Nucleophilic addition to the carbon-nitrogen tosyl-hydrazone double bond competes effectively wiA a-deprotonation (and alkene formation) if abstraction of the a-hydrogens is slow and excess organolithium reagent is employed. Nucleophilic substitution is consistent with an Su2 addition of alkyllithium followed by electrophilic capture of the resultant carbanion. 

Until about 30 years ago, hydrazones derived from carbonyl compounds were not used in organic synthesis. They were used only for analytical purposes , and as protecting groups of aldehydes and ketones ". Corey investigated dimethylhydrazones of ketones and aldehydes with a-hydrogens, and found that they undergo deprotonation with LDA or BuLi in THF at the a-carbons to the hydrazonic moiety in 90-100% yield. The formed lithium compounds, used as enolate anion equivalents, create new carbon-carbon bonds in their reaction with different electrophiles such as alkyl halides or oxiranes, ketones and aldehydes (equation 21). 

The presence of the double bond (carbonyl group C 0) markedly determines the. chemical behavior of the aldehydes. The hydrogen atom connected directly to the carbonyl group is not easily displaced. The chemical properties of the aldehy des may be summarized by (1) they react with alcohols, with elimination of H2O, to form ace t i (2) they combine readily with HCN to form cyanohydrins, (3) they react with hydroxylamine to yield aldoximes (4) they react with hydrazine to form hydrazones (5) they can be oxidized lulu fatty acids, which contain die same [lumber of carbons as in the initial aldehyde 5) they can be reduced readily to form primary alcohols. When bcnzaldchydc is reduced with sodium amalgam and HjO, benzyl alcohol C,f l - -C f I Of I is obtained. The latter compound also may be obtained by treating benzaldehyde with a solution of cold KOH in which benzyl alcohol and potassium benzoate are produced. The latter reaction is known as Cannizzaro s reaction. 

Thus to permit cyclization, there must be at least one hydrogen a to the C=N bond. If there is only one, the product will be a 3,3-disubstituted-3H-indole. However, if both substituents at the hydrazone carbon have one or more a-hydrogens, product mixtures can result. Generally, it is expected that the more branched substituent is more likely to be involved in cyclization, so typically phenylhydrazones derived from methyl alkyl ketones give 2-methylindoles. However, the selectivity is subject to the reaction conditions and with certain reagents the selectivity can be reversed to favor the 2-alkylindole. 

Hydrogen cyanide adds to the carbon-nitrogen double bonds present in various aldehyde and ketone derivatives, like those in imines, hydrazones, oximes, and Schiff bases. In each instance, a new carbon-carbon linkage is formed. Thus, the reaction of dry hydrogen cyanide with an imine... 

The carbon-nitrogen double bonds of oximes and hydrazones are hydrogenated to form the corresponding amines by heterogeneous catalytic hydrogenation. 

Numerous asymmetric catalytic hydrogenations of carbon-nitrogen double bonds have been carried out. Some of the substrates used are oximes and hydrazones, but most of the reactions were carried out using Schiff s bases of ketones. a-Keto acids are precursors of a-amino acids in biosynthesis, and therefore a-keto acids have been used for the asymmetric syntheses of a-amino acids. ... 

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