Hydrazine with aldehydes and ketones

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). ... 

Lee, B., Lee, K.H., Cho, J. etal. (2011) Synthesis of azines in solid state reactivity of solid hydrazine with aldehydes and ketones. Organic Letters, 13, 6386-6389. 

Phenyl hydrazine condenses readily with aldehydes and ketones to give phenylhydrazonesy which, being usually crystalline compounds of sharp... 

HydraZones and Azines. Depending on reaction conditions, hydrazines react with aldehydes and ketones to give hydrazones (33), azines (34), and diaziddines (35), the latter formerly known as isohydrazones. 

Hydrazide groups react with aldehyde and ketone groups to form hydrazone linkages (Chapter 2, Section 5.1). Three BODIPY derivatives are available that contain a hydrazine group modification of carboxylate side chains. Biomolecules such as proteins that don t normally possess aldehyde residues can be modified to contain them by a number of chemical means (Chapter 1, Section 4.4). 

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that decompose in alkaline medium at elevated temperatures to nitrogen and compounds in which the carbonyl oxygen has been replaced by two hydrogens.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

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. 

Hydrazido(2-) and hydrazido(l-) complexes have also been shown to condense with aldehydes and ketones to give diazoalkane complexes containing the W=N—N=CRiR2 unit.387,388 Treatment of these complexes with LiAlFL, gives secondary amines and ammonia, whereas treatment with acid produces hydrazine, keto azines and N2-free tungsten compounds. Amines can also be produced from organohydrazido(2—) complexes.389,390... 

Imines of aldehydes are relatively stable while those of ketones are unstable. Derivatives of imines that form stable compounds with aldehydes and ketones include phenylhydrazine, 2,4-dinitrophenyl-hydrazine, hydroxylamine, and semicarbazide. 

The formation of oximes and hydrazones can be used to modify proteins due to some attractive properties, that is, some stability in aqueous media and compatibility with many functionalities of proteins [134], Their synthesis can be accomplished through the nucleophilic addition-elimination (condensation) of hydrazines and alkoxyamines with aldehydes and ketones, respectively. Typically, it has been used to modify the N-terminus [135-137] of peptides and proteins. For example, oxime formation has been used to modify BSA and diphtheria toxin with Shigella sonnei O-specific oligosaccharides [138],... 

A number of reactions of nitrogen-containing nucleophiles with aldehydes and ketones involve addition of the nitrogen to the carbon of the carbonyl group, followed by elimination of water to produce a double bond. Common examples are reactions of primary amines to produce substituted imines, reactions of secondary amines to produce enamines, reactions of hydrazine or substituted hydrazines to produce hydrazones, reactions of semicarbazides to give semicarbazones, and reactions of hydroxylamine to produce oximes. Usually these reactions are run with an acid catalyst. 

Semi-carbazid is an important reagent forming derivatives with aldehydes and ketones. Its name indicates that it is a hydrazine derivative of carbonic acid or of carbamic acid. It is also amino urea. 

A variation on this reaction is to use a substituted hydrazine, 2,4-dinitrophenylhydrazine (Figure 7.2.11). This is a heavier molecule and forms crystalline products with aldehydes and ketones more easily. It forms the corresponding 2,4-dinitrophenylhydrazone, and this reaction can be used to confirm the presence of a carbonyl compound. 

Phenyl hydrazine reacts with aldehydes and ketones, the two hydrogen atoms of the amido-groups unite with the oxygen atom of the CHO- or CO-groups, and are eliminated as water 2... 

Chemical reactivity is another way of testing the purity of a drug substance. Hydralazine hydrochloride is part of a class of compounds called hydrazine derivatives. It is well known that hydrazine derivatives react with aldehydes and ketones to give hydrazones.The test is conducted by taking a standard reaction of hydrazine with benzaldehyde and comparing it to the same reaction of hydralazine with benzaldehyde as in Scheme 4. By using an HPLC procedure, standard solutions of each derivative are injected, and by comparison of the peak responses, the amount of hydrazine is determined. 

Hydrazine and, more so, its 1,1-substitution products form with aldehydes and ketones derivatives that are often valuable from an analytical or preparative point of view. 

Compounds such as hydroxylamine (NH2OH), hydrazine (NH2NH2), and semicar-bazide (NH2NHCONH2) are similar to primary amines in that they all have an NH2 group. Thus, like primary amines, they react with aldehydes and ketones to form... 

Phenyl-substituted hydrazines react with aldehydes and ketones to form phenyl-hydrazones. 

The above reaction requires a 10 1 ratio of hydrazine to the ester groups. In the laboratory it can be carried out on a steam bath over a period of 2-3 hours. Approximately 60-80% of the ester groups convert. The hydrazides can form various hydrazones through reactions with aldehydes and ketones ... 

Figure 8 Analytical reagents with hydrazine for aldehyde and ketones.

Hydrazine reacts with aldehydes and ketones to give hydra-zones. Hydrazone derivatives react with aldehydes and ketone to give AT-substituted hydrazones. Hydroxylamine reacts with aldehydes and ketones to give oximes. Semicarbazone reacts with aldehydes and ketones to give semicarbazides. 

Hydrazine (97) is considered to be the parent of substituted hydrazine derivatives, such as 98, which react with aldehydes and ketones to form substituted hydrazone derivatives. An example is the reaction ofi JV-dimethylhydrazme (103) and 2-methylpropanal (isobut3rraldehyde, 102) to give the A JV-dimethylamine hydrazone 104 in 64% 3deld. Two important A Af-disubstituted hydrazine reagents are phenylhydrazine (PhNHNH2) and 2,4-dinitrophenylhydrazine (106), which react with aldehydes or ketones to give the corresponding hydrazone. 

---