2.4- Dinitrophenylhydrazone from ketones

According to the studies performed by the Bundesanstalt fur Materi-alprufung, Germany (BAM), this compound may explode when dry, but in the presence of 20% water there is no longer any danger of explosion. It is widely used in analytical organic chemistry for the preparation of dinitrophenylhydrazon and its derivates from ketones and aldehydes. 

Dinitrophenylhydra2ones usually separate in well-formed crystals. These can be filtered at the pump, washed with a diluted sample of the acid in the reagent used, then with water, and then (when the solubility allows) with a small quantity of ethanol the dried specimen is then usually pure. It should, however, be recrystallised from a suitable solvent, a process which can usually be carried out with the dinitrophenylhydrazones of the simpler aldehydes and ketones. Many other hydrazones have a very low solubility in most solvents, and a recrystallisation which involves prolonged boiling with a large volume of solvent may be accompanied by partial decomposition, and with the ultimate deposition of a sample less pure than the above washed, dried and unrecrystal-lised sample. 

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 ... 

Imine formation from such reagents as hydroxylamine and 2,4-dinitro-phenylhydrazine is sometimes useful because the products of these reactions— oximes and 2,4-dinitrophenylhydrazones (2,4-DNPs), respectively—are often crystalline and easy to handle. Such crystalline derivatives are occasionally prepared as a means of purifying and characterizing liquid ketones or aldehydes. 

When present in macro quantities, aldehydes and ketones can be determined by conversion to the 2,4-dinitrophenylhydrazone which can be collected and weighed. When present in smaller quantities (10 3M or less), although hydrazone formation takes place, it does not separate from methanol solution, but if alkali is added an intense red coloration develops the reagent itself only produces a slight yellow colour. Measurement of the absorbance of the red solution thus provides a method for quantitative determination. 

Many organic chemicals are analyzed by RPC. These include various arylhydroxylamines as the N-hydroxyurea derivative with methyl isocyanate (614) alkyl- and alkoxy-disubstituted azoxybenzenes (6t5), n-alkyl-4-nitrophenylcarbonate esters ranging in length from methyl to octyl (616), 4-nitrophenol in the presence of 4-nitrophenyl phosphate (617), ben-zilic acid, and benactyzine-HCI using ion-pair chromatography (618), as well as aniline and its various metabolites (619), stereoisomers of 4,4 -dihydroxyhydrobenzoin (620), and aldehydes and ketones as the 2,4-dinitrophenylhydrazones (621). The technique has also been used to analyze propellants and hydrazine and 1,1-dimethylhydrazine were quantitita-vely determined (622, 623). 

Acetylthiophene (methyl 3-thienyl ketone) [1468-83-3] M 126.2, m 57 , 60-63°, b 106-107°/25mm, 208-210 /748mm. Recrystd from pet ether (b 30-60°) or EtOH. 2,4-dinitrophenylhydrazone crystallises from CHCI3, m 265°, and the semicarbazone crystallises from EtOH, m 174-175°. [JACS 70 1555 1948]. 

A red 2.4 dinitrophenylhydrazone is obtained from the reaction of an unknown with an amine. Of the following four structures, which ketone or aldehyde could have formed this iinine ... 

You should already be familiar with approximately half of the reactions listed in Table 9.2 from your introductory class. Moreover, you have probably tried to prepare an oxime, a phenylhydrazone, a 2,4-dinitrophenylhydrazone, or a semicarbazone. These compounds serve as crystalline derivatives with sharp and characteristic melting points for identifying aldehydes and ketones and for distinguishing them. When spectroscopic methods for structure elucidation were not available, such a means of identification was very important. 

The alternative procedure strikingly demonstrates the catalytic effect of hydrochloric acid, but it is not applicable to a substance like diethyl ketone, whose 2,4-dinitrophenylhydrazone is much too soluble to crystallize from the large volume of ethanol. The first procedure is obviously the one to use for an unknown. 

Dinitrophenylhydrazones. All aldehydes and ketones readily form bright-yellow to dark-red 2,4-dinitrophenylhydrazones. Yellow derivatives are formed from isolated carbonyl groups and orange-red to red derivatives from aldehydes or ketones conjugated with double bonds or aromatic rings. 

Regeneration of carbonyl compounds from certain derivatives.1 Ketones can be recovered in satisfactory yield from the phenylhydrazones, p-nitrophenyl-hydrazones, tosylhydrazones, oximes, and semicarbazones by reaction with 1 equivalent of (C6H5SeO)20. 2,4-Dinitrophenylhydrazones and N,N-dimethyl-hydrazones are inert under even rather vigorous conditions. The reagent can also be used to regenerate aldehydes from oximes or tosylhydrazones. 

The esters also react readily with aryl hydrazines to give aryl hydrazone derivatives. Examples of the latter were first synthesized (prior to the availability of tetraalkyl carbonylphosphonates) from tetraalkyl methylenebisphosphonates and aryl diazonium salts, analogously to the phosphonoglyoxylate hydrazone synthesis described in a previous section. First made as possible precursors in a ketone synthesis, several of these compounds, converted to free acid salts by treatment with BTMS followed by dicyclohexylamine in methanol, proved to have unexpected inhibitory activity vs the pyrophosphate-dependent phospho-fructokinase of the parasite T. gondii, which causes a potentially lethal opportunistic infection in immunocompromised persons such as AIDS patients [94]. In fact, the 2,4-dinitrophenylhydrazone of carbonylbisphosphonic acid (as the tetrasodium salt) dramatically abated toxoplasmosis lesions in infected human foreskin fibroblasts [94]. Animal toxicity in this compound, probably arising from in vivo hydrolysis to the highly toxic hydrazine, precluded its future development, but the result remains an interesting lead. 

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. 

ADDITION TO CHAPTER XV Following the epimerization (at C-14) of l-bromo-/ -thebainone-A 2 4-dinitrophenylhydrazone to 1-bromothebainone-A 2 4-dinitrophenylhydra-zone [3] (see Chap. XXVIII), it has been shown that in acetic acid or sodium ethoxide solution / -thebainone-A is converted into an equilibrium mixture of /3-thebainone-A and thebainone-A [xxi], the equilibrium favouring the latter ketone. Utilizing this reaction a method has been developed for the preparation of thebainone-A in good yield from dihydrothebaine- [xxn] [4]. 

Hydrazine too reacts with activated aryl halides as readily as ammonia or amines. The important carbonyl reagent 2,4-dinitrophenylhydrazine is obtained in 80% yield from an aqueous-alcoholic solution of l-chloro-2,4-dinitrobenzene and hydrazine.555 Moreover, hydrazones can be arylated in the same way, which can be of interest when the 2,4-dinitrophenylhydrazones cannot be prepared with ease directly from the ketone. The conversion of acetone hydrazone into the 2,4-dinitrophenylhydrazone556 will be described here as a typical example ... 

The concentration of aldehydes and ketones in the photooxl-dlzed films was estimated from the extent of formation of the yellow 2,4 dinitrophenylhydrazones. The results are presented in Table I along with the results of other measurements. 

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