Hydrazones reaction with carbonyl compounds

The semicarbiizoiic " " and para-loluenesulfonylhydrazonc " of diethyl l-formylmeth-ylphosphonate can be metallated with NaH in THF or DME for reaction with carbonyl compounds at room temperature, whereas the oxazine and dimethylhydra/inc -derivatives require metallation with n-BuLi in THF at low temperature. The oxazine protecting group is removed by sequential treatment with NaBH4 and aqueous oxalic acid at reflux. The pora-toluenesulfonyl-hydrazone participates in cyclization reactions with the release of sodium para-toluenesulfinate to produce pyrazoles (Scheme... 

S. It undergoes condensation reaction with carbonyl compounds forming hydrazones. 

The use of hydrazine and substituted hydrazines in the preparation of hydrazones by reaction with carbonyl compounds is well known. 

Other interesting regioselective reactions are carried out within the synthesis of nitrofurantoin. Benzaidehyde semicarbazone substitutes chlorine in chloroacetic ester with the most nucleophilic hydrazone nitrogen atom. Transamidation of the ester occurs with the di-protic outer nitrogen atom. Only one nucleophilic nitrogen atom remains in the cyclization product and reacts exclusively with carbonyl compounds. 

Most reactions with hydrazine are carried out with aldehydes and ketones in the presence of alkali. The reduction proper is preceded by formation of hydrazones that decompose in alkaline medium at elevated temperatures to nitrogen and compounds in which the carbonyl oxygen has been replaced by two hydrogens. The same results are obtained by alkaline-thermal decomposition of ready-made hydrazones of the carbonyl compounds. Both reactions are referred to as Wolff-Kizhner reduction [280]. 

Hydrazinolysis products obtained from oxazolones 528 are versatile synthetic intermediates and can be further elaborated to a variety of different heterocycles depending on the substituents and on the experimental conditions. For example, N-aminoimidazolones 529, isolated from reaction of 528 and hydrazine, have been acylated ° or condensed with carbonyl compounds to produce 530 and 531, respectively. On the other hand, ring-opening 528 with hydrazine affords a dehydroamino acid hydrazide 532. Condensation of 532 with aldehydes yields a hydrazone 533 that can be cyclized to an A -iminoimidazolone 534 (Scheme 7.168). ... 

Regiospecific and enantioselective aldol reactions 168) were also performed with SAMP (137). Lithiated hydrazones obtained from ketones (154) as described above were alkylated with carbonyl compounds and the adducts then treated with chloro-trimethylsilane. The resulting trimethylsilylethers (155) were finally oxidatively hydrolyzed to yield the chiral (3-hydroxyketones (156) (e.e. = 31-62%)168),... 

The most frequently used method of this type is the reaction of hydrazones (247) with diazonium compounds to afford formazans (248). These can be cyclized with carbonyl compounds in the presence of acid to yield verdazylium cations (252) which are reduced under basic conditions to give the verdazyls (253) which can be further reduced to the tetrahydro-l,2,4,5-tetrazines (254). The formazans (248) can be alkylated and the alkylfor-mazans (249) cyclized by heating or treatment with a base to form the tetrahydrotetrazines (250). It is not necessary to isolate the alkylated compounds (249) the complete reaction (248-250) can be carried out at room temperature in the presence of barium oxide or hydroxide in DMF. Oxidation of (250) provides a synthesis of verdazyls (251) (see Section 2.21.3.4.2). 

A variety of macrocyclic complexes which have adjacent nitrogen atoms (cyclic hydrazines, hydrazones or diazines) are formed by condensations of hydrazine, substituted hydrazines or hydrazones with carbonyl compounds. The reactions parallel in diversity those of amines, but are often more facile since the reacting NH2 groups is generally not coordinated and the electrophile is thus not in competition with the metal ion. The resulting macrocycles may be capable of coordination isomerism, since either of the adjacent nitrogen atoms can act as donor atom. 

Dinitrophenylhydrazones (DNPHs) were applied to the GC analysis of keto acids. As with carbonyl compounds, they are prepared by reaction with 2,4-dinitrophenylhydrazine and are also used mainly for the preliminary isolation of keto acids. They can be isolated from a dilute aqueous sample by adsorption on activated carbon and selective desorption [178] hydrazones of aldehydes with a methyl formate-dichloromethane mixture and hydrazones of keto acids with a pyridine-water azeotropic mixture. Hydrazones of acids are released from their pyridine salts with methanol containing hydrogen chloride. After... 

The Schiff bases (they may be also considered as specific hydrazones) play a great role in the chemistry of N-aminoazoles. In most cases, these compounds are obtained by cyclization of a suitable acyclic compound or by interaction of an N-aminoazole with carbonyl compounds aldehydes, ketones, or their acetals. Usually the reaction is carried out on heating components in acetic acid or in alcohol in the presence of catalytic amounts of a mineral acid. The use of j3-dicarbonyl compounds requires more drastic conditions. Thus, 1-aminobenzimidazoles (83KGS386) or 7-amino-theophiline (87KGS155I) reacts with acetylacetone at I75°C in the presence of anhydrous zinc chloride, yielding hydrazones of type 283. 

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 formation of hydrazones from the corresponding carbonyl compounds has been accomplished initially in toluene [88]. Treatment of hydrazone with alkali (KOH) accomplishes Wolff-Kichner reduction that proceeds in good yield under MW irradiation conditions [89]. Varma and Kocevar s group have shown that solvent-free and catalyst-free reaction of hydrazines with carbonyl compounds is possible on MW irradiation (Scheme 8.29) [90]. Interestingly, the general reaction proceeds smoothly even for solid reactants and is completed below the melting points of the two reactants, possibly via the formation of a eutectic. The reactions have been conducted in a household MW oven and the control experiments were conducted concurrently in separate open beakers the reactions can be essentially followed by visual observation when a melt is obtained [91]. 

Custer, T.G. Kato, S. Bierbaum, V.M. Howard, C J. Morrison, G.C. Gas-phase kinetics and mechanism of the reactions of protonated hydrazine with carbonyl compounds. Gas-phase hydrazone formation Kinetics and mechanism. J. Am. Chem. Soc. 2004,126, 2744-2754. 

The Wolf-Kishner reaction is the reduction of carbonyl groups to methylene groups by base-catalyzed decomposition of the hydrazone of the carbonyl compound. Alkyldiimides are believed to be formed and then collapse with loss of nitrogen. 

The most important condensation reactions used for analytical purposes in organic polarography are reactions of carbonyl compounds with the formation of (1) aldimines and ketimines, (2) semicarbazones, (3) hydrazones and (4) oximes. The reactions of carbon disulphide with amines and amino acids are also used (5). 

We recall that hydrazine and 2,4-dinitrophenylhydrazine react with carbonyl compounds to give hydrazones. However, monosaccharides do not give simple phenylhydrazone derivatives. After the initial formation of a phenylhydrazone, further reaction occurs to give the osazone, which has two molecules of phenylhydrazine incorporated into it. 

Hydrazine itself may be subjected to a variety of facile substitution reactions because of its great nucleophilic character. It may react with alkyl halides and activated aryl halides to yield substituted hydrazines. With acyl halides, esters, and amides it may form hydrazides. With carbonyl compounds, hydrazones form. Since hydrazine is bifunctional in nature, both amino groups may undergo reaction. In the case of the reaction of hydrazine with two moles of a carbonyl compound, the products are termed azines. ... 

The preparation of hydrazones by the reaction of hydrazine derivatives with carbonyl compounds is well known and extensively described in most laboratory manuals. A typical example, used in our laboratory, is the preparation of benzaldehyde p-nitrophenylhydrazine [51] given below. 

Other reactions show a more complex dependence on pH. In Chapter 14, we studied the reaction of various molecules, RNHj, with carbonyl compounds to give imines, hydrazones. 

Aldehydes and ketones may be converted into the corresponding primary amines by reduction of their oximes or hydrazones (p. 93). A method of more limited application, known as the Leuckart Reaction, consists of heating the carbonyl compound with ammonium formate, whereby the formyLamino derivative is formed, and can be readily hydrolysed by acids to the amine. Thus acetophenone gives the i-phenylethylformamide, which without isolation can be hydrolysed to i-phenylethylamine. 

Figure 1.70 AMBH is a hydrazide-containing compound that reacts with carbonyl groups to form hydrazone bonds. The free thiol can be used for subsequent conjugation reactions.

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