2.4- Dinitrophenylhydrazones cleavage

An improved method for the preparation of A" -3-ketones from 4-bromo compounds was described by Mattox and Kendall. This procedure involves dehydrobromination of the 2,4-dinitrophenylhydrazone and subsequent cleavage of the hydrazone with pyruvic acid ... 

The scope of this reaction was investigated by Djerassi, °° who showed that 4-bromo ketones in the series and 2-bromo ketones in the 5a series give unsaturated 2,4-dinitrophenylhydrazones in 80-90% yield on warming under nitrogen with 1.1 moles of 2,4-dinitrophenylhydrazine in acetic acid. Cleavage with pyruvic acid affords the pure unsaturated ketones in 60-70 % yield. 

In the same way, oxidative cleavage of 2,4-dinitrophenylhydrazones by (n-Bu4N)2S208 to the corresponding ketones was also reported . ... 

Oxidative cleavage of hydrazones. Carbonyl compounds can be regenerated from 2,4-dinitrophenylhydrazones, tosylhydrazones, or N-methyl-N-tosylhydra-zones in 80-95% yield by oxidation with sodium nitrite in TFA or HOAc (0-5°, 1-2 hours). In the case of tosylhydrazones, the other product of cleavage has been identified as tosyl azide, the product of reaction of tosylhydrazine with nitrous acid. 

The only other commonly reported technique is the acid-catalysed evolution of nitrogen gas. Typically, sulphuric acid is used as the catalyst . This is not totally reliable, however. Coombsreports that if carbon-nitrogen cleavage will yield a stable carbonium ion, then formation of HN3 predominates over loss of N2 and formation of imine. This is contradicted, however, by the report that i-butyl azide in the presence of sulphuric acid yields acetone-A-methylimine which subsequently hydrolyses to give acetone, isolated as its 2,4-dinitrophenylhydrazone. 

Reductive cleavage of 2,4-dinitrophenylhydrazones. Certain 2,4-dinitrophenyl> hydrazones of 3-ketosteroids can be cleaved under mild conditions if the nitro groups are reduced to amino groups by chromous chloride. Thus when the 2,4-DNP of 4,5a-dihydrocortisone 21-acetate in methylene chloride was shaken in a separatory funnel with chromous chloride and dilute hydrochloric acid for 15 min., workup of the organic layer afforded the ketone in 94% yield. Use of a water-immiscible solvent protects the released ketone an inert atmosphere if required can be provided with dry ice. Cortisone 2,4-DNP was cleaved in only 3-5 hrs. and the yield was 60%. DN P derivatives of A -diene-S-ones were completely resistant to hydrolysis. Contributed by Leon Mandell... 

The reagent is recommended for the cleavage of 2,4-dinitrophenylhydrazones of steam-volatile ketones by an exchange reaction. ... 

Cleavage of 2,4-dinitrophenylhydrazone and oximes. Keeney devised a semimicro colorimetric procedure for estimation of 2,4-dinitrophenylhydrazones which involved use of levulinic acid as acceptor molecule for regeneration of ketones from the derivatives by exchange. He found that hydrazones of nonconjugated ketones are split much more rapidly than are those of conjugated or aromatic ketones. 

Dinitrophenylhydrazones are cleaved by various oxidizing and reducing agents, and by exchange reactions. Some of the methods used for the cleavage of oximes should be applicable for DNP cleavage. 

Cleavage of 2,4-dinitrophenylhydrazones. Carbonyl compounds can be regenerated in high yield (80-95%) from the 2,4-DNP derivatives by treatment in DME with a 20% aqueous solution of TiCls at reflux temperature (N2). McMurry and Sylvestri consider that titanous ion reduces the nitro groups to amino groups and then cleaves the hydrazone N—N bond to generate an imine, which is then hydrolyzed readily to the carbonyl compound. 

Cleavage of tosylhydrazones. A mixture of phenylacetone tosylhydrazone and Am-berlyst 15 in 10 1 acetone/water stirred at room temp, for 24 h phenylacetone. Y 91%. The method is applicable to aldehydes (especially in the presence of 10 eqs. of paraformaldehyde) as well as ketones it is simple and cheap furthermore, acid-sensitive groups such as furyl derivs., esters or ethers are not affected. F.e. incl. cleavage of oximes, 2,4-dinitrophenylhydrazones and semicarbazones, s. R. Ballini, M. Petrini, J. Chem. Soc. Perkin Trans. I 1988, 2563-5. 

Regeneration of the parent carbonyl compound from tosylhydrazones and 2,4-dinitrophenylhydrazones can be carried out in high yield using sodium nitrite in trifluoroacetic acid. Deprotection of tosylhydrazones using thallium triacetate in acetic add is also elficient. Oximes yield the carbonyl product on treatment with bromine in aqueous sodium bicarbonate, and the same conditions can be used to hydrolyse tosylhydrazones if HMPA is present. Aqueous nitric acid was found to be superior to both sulphuric and hydrochloric adds for the cleavage of the hydrazones (90) to the corresponding cyclohexanones. ... 

The cleavage is carried out by heating the substance (10—20 mg) with 10 ml of 50% H2SO4 at 80 ""C in a small distillation apparatus. A stream of an inert gas is introduced into the apparatus, which carries the distilling vapors with it into a container with an acid 2,4-dinitrophenylhydrazine solution. The precipitated 2,4-dinitrophenylhydrazone is isolated and identified in the usual manner (see p. 221). 

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