Carbonyl groups condensation with hydrazine

The product of condensation of a hydrazine and an aldehyde or ketone is called a hydrazone. Hydrazine itself gives hydrazones only with aryl ketones. With other aldehydes and ketones, either no useful product can be isolated, or the remaining NH2 group condenses with a second mole of carbonyl compound to give an azine. This type of product is especially important for aromatic aldehydes ... 

Dicarbonyl compounds with a double bond in the 2,3-position condense with hydrazine to give pyridazines (e.g. 91 — 92). If one of the carbonyl groups in the starting material is part of a carboxyl group or a potential carboxyl group, then reactions with hydrazines or hydroxylamine lead to pyridazinones or 1,2-oxazinones (e.g. 93 — 94 Z = NH, NPh, O). Similarly a cyano group leads to an amino or imino product. 

Two examples of monocyclic 1,3,4-oxadiazepines have been reported. The fully unsaturated compounds have, however, not been isolated, although the photolysis of pyrimidine. iV-oxides is known to involve such oxadiazepines as unisolable intermediates <69TL4899>. 2-Benzoylpropene or 2-benzoylpropanol condensed with hydrazine hydrate and an appropriate carboxylic acid to form the hydrazone esters (133), which were converted into the 6,7-dihydro-l,3,4-oxadiazepines (134) (30 72% yields) by intramolecular attack of the amino group to the ester carbonyl, followed by acid-catalyzed loss of water (Scheme 23) <84S342>. 

Carbonyl compounds condense with amines and related functional groups (e.g., hydrazines), with elimination of water, to yield C=N double-bonded products ... 

Scheme 4 shows in a general manner cyclocondensations considered to involve reaction mechanisms in which nucleophilic heteroatoms condense with electrophilic carbonyl groups in a 1,3-relationship to each other. The standard method of preparation of pyrazoles involves such condensations (see Chapter 4.04). With hydrazine itself the question of regiospecificity in the condensation does not occur. However, with a monosubstituted hydrazine such as methylhydrazine and 4,4-dimethoxybutan-2-one (105) two products were obtained the 1,3-dimethylpyrazole (106) and the 1,5-dimethylpyrazole (107). Although Scheme 4 represents this type of reaction as a relatively straightforward process, it is considerably more complex and an appreciable effort has been expended on its study (77BSF1163). Details of these reactions and the possible variations of the procedure may be found in Chapter 4.04. 

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. 

Dihydropyridines containing at position 3 a carbonyl group similar to oc,(3-unsaturated ketones can be involved in cyclocondensation reactions with 1,2-binucleophiles. Dihydropyridine 376 treated with hydroxylamine yields isoxazoline derivatives 377 [363, 382, 383, 384, 385, 386] (Scheme 3.122). Dihydro-l,2,4-triazolo[l,5- ]pyrimidine 378 reacts with hydrazine and hydroxylamine in the same manner, giving the condensation products 379 [387]. 

The synthesis 10 is straightforward the condensation is indeed regioselective and it doesn t matter which way round hydrazine reacts or indeed which carbonyl compound reacts first. The enamine will form so as to be in conjugation with the remaining carbonyl group. 

Hydrazones of compounds containing a carbonyl groups are also used for the GC of the latter (Scheme 4.18). They are prepared by the condensation of a substituted hydrazine with the carbonyl group, usually in the presence of an acid. The reaction conditions can vary at room temperature the reaction may take several hours. The hydrazones are then mostly isolated from the reaction misture by extraction with a suitable solvent. 

Weygand has suggested two possible mechanisms for osazone formation which depend on the occurrence of an Amadori rearrangement after initial condensation of the hydrazine with the carbonyl group.Both routes were presented and reviewed by Percival in Volume 3 of this Series. Since that time, Weygand s theory has remained valid. Criticism by Ruggli and Zeller was satisfactorily answered by Weygand and Reckhaus, who showed that... 

The 3,3 -bis(2-pyrazolin-5-ones) in which the rings are connected by carbon chains (Table VIII) are usually prepared by condensation of a hydrazine with an appropriate / ,/ -dioxodiester (eq. 84).419,462,1222,1225 Such bispyrazolinones linked by a carbonyl group have been prepared by pyrolysis of the calcium salt of 5-oxo-2-pyrazolin-5-one.1549... 

The carbonyl group at the 2-position shows a different character from the other carbonyl groups in the barbituric acid ring. The condensation of barbituric acid with hydrazine, phenyl-, 1,1-diphenyl-, and 2,4-dinitrophenyl-hydrazine led only to derivatives 106 or 107 (R = R = Ph R = H, R = Ph, 2,4-di-NOrC6H4).282... 

The course of the condensation reaction can be influenced by the presence of agents such as sodium hydrogen sulfite or hydrazine which react with carbonyl groups. For example, 2-phenylpyrimidine-4,5,6-triamine reacts with 2-oxopropanal at pH 7 to give 7-methyl-2-phenyl-pteridin-4-amine (3, 60%).51 However, when hydrazine is added to 2-oxopropanal prior to admixture with the pyrimidine, the only product which is obtained is 6-methyl-2-phenylpterid-in-4-amine (4).5 2... 

Several new reports utilizing the common strategy of condensation of 1,6-dicarbonyl compounds with hydrazine also appeared, in the context of a selective procedure for the reduction of only one carbonyl group in a,o)-dicarbonyl compoimds <90Mi 92i-0i>, and in the preparation of bicyclic initiators for radical block copolymerizations <85USP453230i, 85USP45565I2), as well as in the formation of precursors to fully unsatiu-ated 1,2-diazocines (16) <86BCJ1087>. 

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