Carbonyl compounds, reaction with hydrazine

Acetaldehyde can be isolated and identified by the characteristic melting points of the crystalline compounds formed with hydrazines, semicarbazides, etc these derivatives of aldehydes can be separated by paper and column chromatography (104,113). Acetaldehyde has been separated quantitatively from other carbonyl compounds on an ion-exchange resin in the bisulfite form the aldehyde is then eluted from the column with a solution of sodium chloride (114). In larger quantities, acetaldehyde may be isolated by passing the vapor into ether, then saturating with dry ammonia acetaldehyde—ammonia crystallizes from the solution. Reactions with bisulfite, hydrazines, oximes, semicarb azides, and 5,5-dimethyl-1,3-cyclohexanedione [126-81 -8] (dimedone) have also been used to isolate acetaldehyde from various solutions. 

The successful synthesis of 2-thienyl and substituted 2- and 3-thienyl-acetylenes in yields as high as 60-80% opened a wide variety of synthetic applications. Various addition reactions with carbonyl compounds or epoxides could be carried out with ease. Aliphatic as well as aromatic amine addition reactions, or condensation reactions with hydrazine or hydroxylamine could be easily performed. 

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that decompose in alkaline medium at elevated temperatures to nitrogen and compounds in which the carbonyl oxygen has been replaced by two hydrogens.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]. 

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. 

The stable crystalline complexes of various mono- and di-substituted hydrazines with 18-crown-6 have recently been described for the first time, and used for the formation of substituted hydrazones from carbonyl compounds in lipophilic solvents.An alternative procedure uses the carbonyl compound and the hydrazine with 0.1—1 equivalents of crown, and both variants give a fast reaction in a homogeneous non-aqueous phase. 

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). ... 

Treatment of l-morpholino-6-iminocyclohexene with hydrazine hydrate in the presence of ketones leads to 2,3,5,6,7,8-hexahydro-l,2,4-benzotriazine 4-oxides 156. In the absence of carbonyl compounds, this reaction affords the spirobicyclo compound 157 (75S794). 

The carbonyl compound to be reduced (0.1 mole) is placed in a 250-ml round-bottom flask with 13.5 g of potassium hydroxide, 10 ml of 85% hydrazine hydrate, and 1(X) ml of diethylene glycol. A reflux condenser is attached and the mixture is heated to reflux for I hour (mantle). After refluxing 1 hour, the condenser is removed and a thermometer is immersed in the reaction mixture while slow boiling is continued to remove water. When the pot temperature has reached 200°, the condenser is replaced and refluxing is continued for an additional 3 hours. The mixture is then cooled, acidified with concentrated hydrochloric acid, and extracted with benzene. The benzene solution is dried, and the benzene is evaporated to afford the crude product, which is purified by recrystallization or distillation. 

MW irradiation conditions [80]. More recently, however, Varma and Kocevar s group have shown that a solvent-free and catalyst-free reaction of hydrazines with carbonyl compounds is possible upon MW irradiation (Scheme 6.24) [81]. 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 household MW oven and the control experiments are conducted concurrently in separate open beakers the reactions can be essentially followed by visual observation when a melt is obtained [82],... 

For the replacement of oxygen by hydrogen in ketones and aldehydes the method of Kishner and Wolff is used as often as is that of Clemmensen. In the former method the hydrazone or semicarbazone of the carbonyl compound is heated for several hours—preferably in the presence of hydrazine hydrate—in a sealed tube or autoclave with sodium ethoxide at about 160°. The explanation of the reaction is that, under the catalytic influence of the ethoxide, the hydrazone is transformed into a diimine which then decomposes in the same way as does phenyldiimine (p. 286) ... 

A disadvantage of the traditional synthesis of A -alkyl-A -tosylhydrazones, particularly in the reaction of the tosylhydrazine with weakly electrophilic carbonyl compounds, is the instability of the hydrazine under the reaction conditions. However, A -alkylation of the tosylhydrazone (Table 5.23) under weakly basic condi-... 

Diazo compounds are photoreduced to hydrazines in the presence of silanes and stannanes in a process that apparently involves initial H-atom transfer to an excited state of the diazo compound.105 LFP studies of reactions of Bu3SnH with excited states of diazo compounds 40 and 41 found fast reactions. The singlet diazo species reacted with Bu3SnH about as fast as singlet carbonyl compounds, whereas the triplet diazo species reacted with tin hydride somewhat slower than triplet excited states of carbonyl compounds.100,105... 

The synthesis of isoxazolines and pyrazolines via the Michael addition of hydro-xylamine and phenyl hydrazine to chalcones and related enones was also reported with activated Ba(OH)2 as a basic catalyst (293) (Scheme 45). In both cases, reactions were performed at reflux of ethanol, and excellent yields (65-80%) with 100% selectivity to the heterocyclic compounds were observed. Steric hindrance associated with the carbonyl compound as well as the electronic character of the substituents in the aromatic ring slightly affected the yields of the heterocyclic compounds. 

Nitro compounds in presence of carbonyl group are selectively reduced to amines in the presence of Raney nickel catalyst. Hydrazine reduces nitrdes yielding hydrazones. Under controlled reaction conditions other functional groups, including nitroso and oxime, may be reduced. Many partially hydrogenated derivatives, such as azo-, hydrazo-, and azoxy compounds may be obtained by partial reduction with hydrazine. Reaction with chlorobenzene yields benzene. 

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). ... 

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