Ketone 2,4-dinitrophenylhydrazones

Brady s reagent A solution of 2,4-dinitro-phenylhydrazine sulphate in methanol. Gives characteristic crystalline yellow to deep red 2,4-dinitrophenylhydrazone products with aldehydes and ketones. 

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. 

Note. The 2,4-dinitrophenylhydrazones of many higher aldehydes and ketones may be insoluble in most solvents. In this case, Mter them off, wash with ethanol, dry and take the m.p. attempted recrystallisation may cause partial decomposition. (M.ps., pp. 530-540.)... 

Dinitrophenylhydrazones. Small quantities may be prepared with the class reagent described in Section XI,7,4. A more satisfactory procedure is given under Aliphatic Ketones, Section 111,74,7. 

Dinitrophenylhydrazones. For experimental details, see under Aliphatic ketones. Section 111,74,7. 

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. 

Methylsulfinyl -pentyl ketone gives a quantitative yield of methyl -pentyl ketone as a colorless liquid, mp of the 2,4-dinitrophenylhydrazone 73-74°. 

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. 

The identification and quantification of potentially cytotoxic carbonyl compounds (e.g. aldehydes such as pentanal, hexanal, traw-2-octenal and 4-hydroxy-/mAW-2-nonenal, and ketones such as propan- and hexan-2-ones) also serves as a useful marker of the oxidative deterioration of PUFAs in isolated biological samples and chemical model systems. One method developed utilizes HPLC coupled with spectrophotometric detection and involves precolumn derivatization of peroxidized PUFA-derived aldehydes and alternative carbonyl compounds with 2,4-DNPH followed by separation of the resulting chromophoric 2,4-dinitrophenylhydrazones on a reversed-phase column and spectrophotometric detection at a wavelength of378 nm. This method has a relatively high level of sensitivity, and has been successfully applied to the analysis of such products in rat hepatocytes and rat liver microsomal suspensions stimulated with carbon tetrachloride or ADP-iron complexes (Poli etui., 1985). 

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]. 

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). 

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

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]. 

When the same reaction is performed with adamantanone dinitrophenylhydrazone (DNP) or adamantanone O-mcthyloxime (OMO), the yields of 2,2-difluoroadamantanc are 65 and 50%, respectively. 4-tert-Butylcyclohexanone is converted via its azine, DNP or OMO into 4-tert-butyl-l.l-difluorocyclohexanc in 65, 75 or 50% yield, respectively. Similar results are obtained with aliphatic straight-chain ketones. Decan-2-one azine and decan-2-one DNP can be transformed into 2,2-difluorodecane in 60 and 80% yield. Deactivated aromatic rings, e.g. in 3-nitroacetophenone, do not undergo bromination with bromine trifluoride and the action of 2 equivalents of bromine trifluoride on 3-nitroacetophenone O-methyloxime results in 90% yield of 1-(1. l-difluorocthylj-S-nitrobenzene.122... 

The 2,4-dinitrophenylhydrazone derivative of Fraction 3b, ketonic part, was prepared, and a mixed melting point with an authentic derivative of cyclohexenone was not depressed, m.p., 167°-168°C. [literature, 163°C. (I)]. 

Pyridine base eliminations of a-bromo ketones cannot be recommended for general use because of the side reactions already discussed. The semi-carbazone-pyruvic acid method should be employed if strict absence of isomerization is required in the dehydrobromination of 2- or 4-bromo-3-ke-tones. This procedure is not applicable for the preparation of A1,4-3-ketones, due to rearrangement. The use of semicarbazide for the dehydrobromination of 6-bromo-A4-3-ketones is reported to be satisfactory for the preparation of A4,6-3-ketones65 but appears to be a neglected approach. (The corresponding 2,4-dinitrophenylhydrazones cannot be cleaved.)... 

Derivatization is a procedure in which analyte is chemically modified to make it easier to detect or separate. For example, formaldehyde and other aldehydes and ketones in air, breath, or cigarette smoke25 can be trapped and derivatized by passing air through a tiny cartridge containing 0.35 g of silica coated with 0.3 wt% 2,4-dinitrophenylhydrazine. Carbonyls are converted into the 2,4-dinitrophenylhydrazone derivative, which is eluted with 5 mL of acetonitrile and analyzed by HPLC. The products are readily detected by their strong ultraviolet absorbance near 360 nm. 

A convenient synthesis of lonchocarpin (206) and similar compounds is the Knoevenagel condensation of a 6-acetylchromene (207) with benzaldehyde (7iJCS(C)796, 71JCS(C)8U>. Carbonyl groups present in chromenes as aldehydes or ketones form oximes and 2,4-dinitrophenylhydrazones <77HC(31)11). 

An anecdote illustrates Tishler s drive. The total synthesis of cortisone, as devised by Lewis Sarrett, comprised approximately 30 steps and required weeks of intense and painstaking effort. Max was in charge of the first commercial production of cortisone in the pilot plant. One of the final steps is the isomerisation of a double bond into conjugation with the 3-ketone function with the formation of a 2,4-dinitrophenylhydrazone, causing the development of a brilliant, scarlet color. Tishler was inspecting the first production run. To his horror, he spotted a bright-red liquid leaking near the vessel. "I hope that s blood ", he exclaimed. Actually, Max was very concerned for individuals, beneath a rather formidable exterior. 

The most widely used protective groups for aliphatic and alicyclic aldehydes and ketones are (a) cyclic acetals and (b) cyclic dithioacetals and hemithio-acetals. The use of semicarbazones, oximes and 2,4-dinitrophenylhydrazones (for preparation see Section 9.6.13, p. 1257) is less common but has found application in certain instances where the more vigorous methods required for deprotection are not detrimental. 

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