Hydrazine, anhydrous reaction with hydrazones

Acetone phenyl-hydrazoue is first prepared by mixing phenyl-hydrazine (30 gms.) with acetone (18 gms.). The mixture becomes warm and water separates it is then heated on the water-bath for half an hour, and at the end of this time heated in a dish on the water-batli, to drive off acetone and steam. The hydrazone is then mixed with five times its weight of anhydrous zinc chloride, and heated under a reflnx condenser in an oil-bath at 180°. A vigorous reaction takes place, and when completed, the dark-coloured mass is distilled with steam. The a-methyl-indole collects in the receiver and soon solidifies to a pale yellow mass. It may be purified by recrystallisiug from ligroin. M.p. 59°. Yield is over 60 per cent, of that calculated. 

Hydrazone derivatives 258 of oxymorphone, naloxone, and naltrexone have been made by reaction with anhydrous hydrazine and designated oxymor-phazone (170), naloxazone (171), and naltrexazone (172). All three hydrazones exhibited a high binding affinity for in vitro rat brain receptor sites. 

Chirala-phenylalkanamines. The hydrazine [(R)-(-)-4] was transformed into the hydrazone [(R)-(-)-5] upon reaction with benzaldehyde in the presence of anhydrous MgS04 in dichloro-... 

Hydrazones. A useful procedure for preparation of hydrazones free from azines is exemplified by the preparation of acetone hydrazone.1 Acetone is first converted into acetone azine (b.p. 128-131°) by reaction with 100% hydrazine hydrate and potassium hydroxide this product is then converted into acetone hydrazone by reaction with anhydrous hydrazine2 and sodium hydroxide. 

Diazo compounds, precursors to carbenes, were prepared by the oxidation with active manganese(IV) oxide (or mercury(II) oxide) of the corresponding hydrazones which in turn were obtained from the corresponding ketones by the reaction with anhydrous hydrazine (or hydrazine monohydrate). This method was employed for the introduction of the diazo groups in most of our compounds... 

Reactions with Hydrazine. TIPSCl reacts with an excess of anhydrous hydrazine to form triisopropy Isilylhydrazine which can be used to prepare TIPS hydrazones (eq 20). TIPS hydrazones are unusually stable in air but readily form asymmetric azines upon treatment with TBAF and a slight excess of ketone or aldehyde (eq 20).31... 

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). ... 

The deoxygenation of aldehydes and ketones to the corresponding hydrocarbons via the hydrazones is known as the Wolff-Kishner reduction.28 Various modifications of the original protocols have been suggested. One of the most useful is the Huang-Minlon modification, which substituted hydrazine hydrate as a safer and less expensive replacement of anhydrous hydrazine. In addition, diethylene glycol together with sodium hydroxide was used to increase the reaction... 

The formation of acetophenone hydrazone has been accomplished by heating acetophenone with hydrazine or hydrazine hydrate,7 10 by heating acetophenone azine with anhydrous hydrazine, 11 by the reaction of a-dimethylaminoacetophenone vvilh hydrazine,5 and by the present method.4... 

Preparation of hydrazones. It usually is not possible to obtain a hydrazone in good yield by reaction of an aldehyde or ketone with hydrazine because of extensive formation of the azine. This difficulty is circumvented by conversion to the N,N-dimethylhydrazone, followed by exchange with hydrazine. The latter reaction is conducted by refluxing the N,N-dimethylhydrazone with a 2-3 fold excess of anhydrous hydrazine. 

A mixture of 112 g. (1.0 mole) of acetone azine and 32 g. (1.0 mole) of anhydrous hydrazine is placed in a 300-ml. round-bottomed flask fitted with a reflux air condenser and drying tube, and kept at 100° for 12-16 hours. Caution This reaction and the subsequent distillation should be carried out behind a protective screen.) The crude product is then rapidly distilled through a water-cooled condenser and the colorless fraction boiling at 122-126° collected, n D 1.4607 (Note 7). It weighs 111-127 g. (77-88%, Notes 7 and 8) and is essentially pure acetone hydrazone (Note 9). 

TMS methylpyrazole (279) is formed by the reaction of l,4-bis(TMS)-buta-l,3-diyne (207) with anhydrous hydrazine in abs. ethanol154. The reaction is initiated by a nucleophilic attack of hydrazine at carbon-1 of 207, forming a hydrazone via rearrangement and, after partial desilylation and ring closure, 279 can be isolated (equation 126). 

A method of almost universal applicability for the deoxygenation of carbonyl compounds is the Wolff-Kishner reduction While the earlier reductions were carried out in two steps on the derived hydrazone or semicarbazone derivatives, the Huang-Minlon modification is a single-pot operation. In this procedure, the carbonyl compound and hydrazine (hydrate or anhydrous) are heated (180-220 °C) in the presence of a base and a proton source. Sodium or potassium hydroxide, potassium-t-butoxide and other alkoxides are the frequently used bases and ethylene glycol or its oligomers are used as the solvent and proton source. Over the years, several modifications of this procedure have been used to cater to the specific needs of a given substrate. The Wolff-Kishner reaction works well with both aldehydes and ketones and remains the most routinely used procedure for the preparation of alkanes from carbonyl compounds (Table 9). This method is equally suitable for the synthesis of polycyclic and hindered alkanes. 

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