Hydrazines, aldehyde additions

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... 

Oximes, hydrazines and semicarbazones. The hydrolysis products of these compounds, t.e., aldehydes and ketones, may be sensitive to alkali (this is particularly so for aldehydes) it is best, therefore, to conduct the hydrolysis with strong mineral acid. After hydrolysis the aldehyde or ketone may be isolated by distillation with steam, extraction with ether or, if a solid, by filtration, and then identified. The acid solution may be examined for hydroxylamine or hydrazine or semicarbazide substituted hydrazines of the aromatic series are precipitated as oils or solids upon the addition of alkali. 

An excellent synthetic method for asymmetric C—C-bond formation which gives consistently high enantioselectivity has been developed using azaenolates based on chiral hydrazones. (S)-or (/ )-2-(methoxymethyl)-1 -pyrrolidinamine (SAMP or RAMP) are chiral hydrazines, easily prepared from proline, which on reaction with various aldehydes and ketones yield optically active hydrazones. After the asymmetric 1,4-addition to a Michael acceptor, the chiral auxiliary is removed by ozonolysis to restore the ketone or aldehyde functionality. The enolates are normally prepared by deprotonation with lithium diisopropylamide. 

Alternatively, chiral hydrazones can be prepared from chiral aldehydes, e.g., 161, which underwent addition of allyltrichlorosilane in DMF to give the homoallylic hydrazine 162 with high yield and excellent diastereoselectiv-ity [76] (Scheme 25). 

Once a molecule is modified with a hydrazine reagent and another molecule is modified with the benzaldehyde compound, they may be combined to form the final conjugate, which will result in a hydrazone linkage between the two molecules. In addition, chemoselective ligation using aldehyde/hydrazine reactions may be done to immobilize biomolecules. In this regard, one modified component may be a surface and the other one an antibody, protein, or oligonucleotide destined for immobilization onto the surface. 

Intermolecular cross aldolization of metallo-aldehyde enolates typically suffers from polyaldolization, product dehydration and competitive Tishchenko-type processes [32]. While such cross-aldolizations have been achieved through amine catalysis and the use of aldehyde-derived enol silanes [33], the use of aldehyde enolates in this capacity is otherwise undeveloped. Under hydrogenation conditions, acrolein and crotonaldehyde serve as metallo-aldehyde enolate precursors, participating in selective cross-aldolization with a-ketoaldehydes [24c]. The resulting/ -hydroxy-y-ketoaldehydes are highly unstable, but may be trapped in situ through the addition of methanolic hydrazine to afford 3,5-disubstituted pyridazines (Table 22.4). 

The azines represent another class of organic compounds which, in principle, should be reducible to azo compounds. The method is attractive since, with the availability of anhydrous hydrazine, azines are readily prepared from a wide variety of ketones and aldehydes. Evidently, introduction of 1 gram-molecule of hydrogen into an azine molecule has only recently been accomplished (see Section 6, Procedure 8) [73], Two preparations involving the 1,4-addition of chlorine to an azine system have been carried out and are illustrated here. 

In the latest development of his elegant work with hydrazone derivatives, Andrew Myers of Harvard reports (J. Am. Chem. Soc. 2004,126, 5436) that Sc(OTf), catalyzes the addition of l,2-bis(r-butyldimethylsilyl)hydrazine, to aldehydes and ketones to form the t-butyldimethylsilylhydrazones. Addition of tBuOH/tBuOK in DMSO to the crude hydrazone effects low temperature Wolff-Kishner reduction. Alternatively, halogenation of ketone hydrazones can lead to vinyl halides such as 11, or the 1,1-dihalo derivatives, depending on conditions. Halogenation of aldehyde hydrazones provides the 1,1-dihalo derivatives such as 13. 

The reaction of aldehydes with disubstituted hydrazines gives, via the addition product (380), the azomethine imine intermediate (381), which dimerizes to the hexasubstituted hexahydrotetrazine (377 Scheme 21). 

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