Hydrazones 2,4-dinitrophenylhydrazones

The hydrazone, 2,4-dinitrophenylhydrazone, semicarbazone, and 3-p-toluenesulfonylhydrazone of 3-thietanone have been reported. The tosyl-... 

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. 

Interaction of formaldehyde with 2,4-dinitrophenylhydrazine in acid media causes 2,4-dinitrophenylhydrazone (DNPhydrazone) formaldehyde formation. Gas-chromatographic analysis of 2,4-DNP-hydrazone formaldehyde toluene extract with an electron holding detector makes it possible to detect it at the level of 0,001 mg/dm. Phenol is detected in the form of tribromphenol yield, the hexane extract of which undergoes chromatography with an electron holding detector which provides the level of phenol detection of 0.001 mg/dm (the limit of quantitative detection). 

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 2,4-dinitrophenylhydrazone is formed in ethanolic hydrochloric acid dehydration will then take place on heating only if the ketol dinitrophenyl-hydrazone remains soluble in the reaction mixture. 

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. 

Hydrazones treated with alkalis decompose to nitrogen and hydrocarbons [845, 923] Woljf-Kizhner reduction) (p. 34), and p-toluenesulfonylhydra-zones are reduced to hydrocarbons by lithium aluminum hydride [812], sodium borohydride [785] or sodium cyanoborohydride [813]. Titanium trichloride hy-drogenolyzes the nitrogen-nitrogen bond in phenylhydrazones and forms amines and ketimines which are hydrolyzed to the parent ketones. Thus 2,4-dinitrophenylhydrazone of cycloheptanone afforded cycloheptanone in 90% yield [202]. 

Timmen and Dimick (1972) characterized the major hydroxy compounds in milk lipids by first isolating the compounds as their pyruvic ester-2,.6-dinitrophenylhydrazones. Concentrations as weight percent of the compounds from bovine herd milk lipids were 1,2-DGs 1.43, hydroxyacylglycerols 0.61, and sterols 0.35. Lipolysis tripled the DG content. The usual milk fatty acids were observed, except that the DGs lacked 4 0 and 6 00, again indicating that these lipids were in part intermediates in milk lipid biosynthesis. With the large hydrazone group... 

The first reported preparation of this ring system involves an interesting two-step preparation starting with the dinitrophenylhydrazone (287). Reaction of this hydrazone with the amino ester (286) gives the intermediate hydrazone (288) in near quantitative yield. The intermediate can be cyclized to the ring closed product (135) by reaction with Raney nickel (62AP121). 

This method describes the quantitative determination of carbonyl compounds in fats and oils. It is based upon the formation of 2,4-dinitrophenylhydrazones of carbonyl compounds in the presence of a trichloroacetic acid (TCA) catalyst, followed by colorimetric determination of the hydrazone compounds (i.e., as quinoidal ions) in an alkanolic basic solution. 

An indirect vanadometric method of assay for camphor was developed. The method involves the formation of 2, -dinitrophenylhydrazone of camphor. The nitro groups in the hydrazone are then reduced to amines by treatment with vanadium sulfate (VSOl ) and the excess of the reagent is back titrated with sodium dichromate (NapCrpO-y). The entire procedure is carried out in a modified separatory funnel into which standard vanadate, 6tJ and zinc amalgam... 

Bisulphite addition compounds are given by all the 5-substituted furfurals with the exception of 2,5-diformylfuran. 5-Ethoxymethyl-furfural forms a diethyl acetal25 and the diacetates of 5-methylfurfural and 5-acetoxymethylfurfural have been obtained.65 The 5-substituted furfurals all condense with amino compounds to give a series of crystalline hydrazones, phenylhydrazones and substituted phenylhydrazones and the semicarbazones, oximes and anilides are also well-characterised derivatives. A feature of the 2,4-dinitrophenylhydrazones is that some... 

Direct GC analysis of hydrazones is carried out only with special derivatives, e.g., if the sensitivity of the determination is to be increased. GC retention data have been reported for phenylhydrazones [107], dinitrophenylhydrazones [108], and trichloro-phenylhydrazones [109] of different aldehydes and ketones. Particularly the last two types can be used to advantage in trace analysis using the ECD. 

Dinitrophenylhydrazones (DNPHs) were applied to the GC analysis of keto acids. As with carbonyl compounds, they are prepared by reaction with 2,4-dinitrophenylhydrazine and are also used mainly for the preliminary isolation of keto acids. They can be isolated from a dilute aqueous sample by adsorption on activated carbon and selective desorption [178] hydrazones of aldehydes with a methyl formate-dichloromethane mixture and hydrazones of keto acids with a pyridine-water azeotropic mixture. Hydrazones of acids are released from their pyridine salts with methanol containing hydrogen chloride. After... 

The reaction is quantitative and at gram quantities, the hydrazone precipitates immediately due to its low solubility in the aqueous phase. The removal of the derivative from the aqueous phase shifts the equilibrium toward the formation of more derivate (Esterbauer, 1982). The dinitrophenylhydrazones absorb strongly in the region 360-390 nm. The spectrum of the 2-alkenals is shifted to 455 nm in ethanolic KOH (Fig. 5.9). 

As noted above, it is not easy to purify unsubstituted hydrazones. Therefore, reactions of hydrazone derivatives with iodine monofluoride have also been studied (Table 1). A-Methyl-and iV,iV-dimcthylhydrazones react more slowly than unsubstituted hydrazones with iodine monofluoride higher tempteratures are often required for their conversion into ge/w-difluorides (Table 1). The reason for this behavior is that elimination of iodomethane from the intermediates is less favorable (see Scheme 1, R = Me). The use of pure derivatives increases the yield in cases sensitive to hydrolysis (cf. entries 25 and 26). 2,4-Dinitrophenylhydrazones only react with iodine monofluoride at temperatures above O C. The yields are generally lower than in the case of unsubslituted hydrazones, and 2,4-dinitrophenylhydrazones formed from aldehydes are unreaetive. 

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. 

Why are 2,4-dinitrophenylhydrazones better derivatives then phenyl-hydrazones ... 

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. 

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... 

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. 

The milk and cream were centrifuged, and the fat fraction was removed. The fat was extracted with carbonyl free hexane, and the fat extract was immediately reacted with 2,4-dinitrophenylhydrazine. The carbonyl compounds formed respective 2,4-dinitrophenylhydrazones (2,4-DNPH). The hydrazones were separated into monocarbonyls and then further purified using thin layer chromatography (18). Alkanal 2,4-DNPH were analyzed by gas chromatography using a 1.83 m glass column (i.d. 4 mm) packed with 2% OV-1 on acid washed Chromosorb W ( 180-200 mesh) (18,19). ... 

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 ... 

Acetone hydrazone (1.5 g, 0.02 mole) is dissolved in 95% ethanol (10 ml) and treated with a solution of l-chloro-2,4-dinitrobenzene (4.0 g, 0.019 mole) in 95% ethanol (30 ml). The mixture is heated for 1 h under reflux, then cooled and filtered. The solid product is freed from a little adhering chlorodinitrobenzene by washing with a little warm ethanol and is then dried. One recrystallization from 95 % ethanol gives acetone 2,4-dinitrophenylhydrazone, m.p. 123°. 

A detour often leads easily to 2,4-dinitrophenylhydrazones of sterically hindered ketones when these derivatives cannot be prepared directly or only so with difficulty (e.g., dibutyl, dipentyl, or dinonyl ketone) the unsubstituted hydrazone is prepared and treated with l-chloro-2,4-dinitrobenzene (see page 464). 

Water-soluble hydrazones of aldehydes and ketones are obtained by means of iV-methylnicotinhydrazide /7-toluenesulfonate (9),928 the components being boiled for 15 min in anhydrous ethanol the products have sharp melting points and can be purified easily it is also easy to cleave them by acid and to convert them into the 2,4-dinitrophenylhydrazones in acid solution. 

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. 

It is possible to obtain derivatives of acylphosphonic diesters when less basic nucleophiles are employed " or from preparations carried out in anhydrous media. Thus, the phenylhydrazones and 2,4-dinitrophenylhydrazones of many esters are known and hydrazones and methylhydrazones of diethyl (l-oxoalkyl)phosphonates have been satisfactorily obtained through reactions in acetic acid. Hydrazones of (l-oxoalkyl)phos-phonic diesters have been employed in the synthesis of (17/-indole-2-yl)phosphonic esters, and the derivatives from dialkyl (2-oxoalkyl)phosphonates have been used to make indole-3-yl)- and [2-(l/f-indolemethyl)]-phosphonic esters by cyclization in polyphos-phoric acid. ... 

Let us focus here on determining the various carbony compounds. Figure 4.46 shows a HPLC chromatogram for the separation and detection of the first six homologous series of aldehydes as their 2,4-dinitrophenylhydrazone derivatives accomplished in the author s laboratory. The reaction of aldehydes and ketones with 2,4-nitrophenylhydrazine under mildly acidic conditions in water to form stable hydrazones is a well-known reaction in organic chemistry. The homologous series with R representing Ci, C2, C3, C4, C5, and Cg react as follows ... 

The method of determination of carbonyl groups in oxidized iPP was based on UV spectrophotometiic determination of 2,4-dinitrophenylhydrazones by means of the absorption band at X, = 365 nm Hydrazones originated in the reaction of oxidized iPP with... 

---