Phenylhydrazine, reaction with carbonyl

The reaction of these aldehydes, derived from periodate oxidation, with carbonyl reagents has also been investigated. Studies 147 148 were made on oxidized laminarin, a (1 —> 3)-linked polysaccharide, in which only the terminal residues had been oxidized. The addition of phenylhydrazine acetate detached the remainder of the terminal residue as glyoxal phenyl-osazone. When the aldehydic compounds derived from the periodate oxidation of raffinose and trehalose818a were reacted with p-nitrophenylhydrazine, the authors were surprised to find that one molecule of oxidized raffinose, containing six aldehydic functions, reacts with only three molecules of the reagent, and that the four aldehydic functions of the oxidized trehalose molecule react with only two. The reactions of periodate-oxidized carbo-... 

The amino pyrrole 29 derived from the reaction with phenylhydrazine <1998JOC9131> was found to undergo an acid-catalyzed intramolecular condensation with the carbonyl present to give the 3//-pyrrolo[l,2-A pyrazole 30 ring system in a good yield (75%) (Equation 2). 

Accordingly, diazobenzene and nitrous acid are related to each other in the same way as are phenylhydrazine and hydroxylamine the latter two substances, in fact, yield the same reaction products with carbonyl compounds as the former two do with the corresponding methylene derivatives. 

Most classes of VOCs found in indoor environments are sampled onto sorbents by adsorption but highly reactive VOCs like carbonyl compounds are sampled by chemical reactions with the sorbent. Thus aldehydes and ketones are sampled by their reactions with sorbent gels coated with 2,4-dinitro-phenylhydrazine to form stable hydrazones [38-40]. Similarly, formaldehyde has been sampled by its reaction with N-benzylethanolamine to give 3-benzyl-oxazolidine [41,42]. 

Aldehydes and ketones react with one equivalent of phenylhydrazine, forming phenylhydrazones (Section 18.6). Aldoses and ketoses, in contrast, react with three equivalents of phenylhydrazine, forming osazones. One equivalent functions as an oxidizing agent and is reduced to aniline and ammonia. Two equivalents form imines with carbonyl groups. The reaction stops at this point, regardless of how much phenylhydrazine is present. (Recall that the pH at which imine formation is carried out must be carefully controlled Section 18.6.)... 

Due to the presence of carbonyl, aldehyde or ketone radicals, sugars are capable of addition reactions with nucleophilic reagents such as phenylhydrazine (C6H5-NH-NH2). The addition of three phenylhydrazine molecules to an aldose (Figure 3.12) leads to the formation of osazone, a crystallized product with specific physicochemical characteristics, especially its melting point. This makes it possible to identify the corresponding sugar. 

Two reactions used in steroid chemistry were modified by Bennett for histochemical use. Frozen sections of either unfixed or formalin-fixed tissue were used, with no differences reported in their reactivity (see, however, Section V.2) the sections were 80 to 100 microns in thickness. In the first method, sections were treated with phenylhydrazine hydrochloride (1 %) in acetate buffer, pH 6 to 6.5, overnight. The formation of yellow phenylhydrazones indicated the presence of carbonyl groups. The pH of the solution was kept low enough to prevent extensive accumulation of the decomposition products of phenylhydrazine, which are yellow and soluble in lipid. In order to avoid reaction with ascorbic acid the sections were first oxidized briefly with iodine or indophenol. Since dehydro-ascorbic acid, which is formed by the oxidation of ascorbate, also forms phenylhydrazones, it is doubtful that this procedure had any value. However, since ascorbic acid and its oxidation product are soluble in most aqueous mixtures, they probably would not remain in sections as ordinarily treated. 

The large values of og for the reaction of phenylhydrazine, hydroxylamine and i-butylamine with carbonyl compounds reflect the important role of catalysis played by the solvated proton in this mechanism. Values of 2 of unity for the dehydration of carbinolamines derived from semicarbazide and aniline indicate that such dehydrations appear to be only specific acid catalyzed, except in fairly basic solutions where the concentration of hydronium ion is low . 

As might be expected, the carbonyl function in aldoses and ketoses undergoes condensation reactions with amine derivatives (Section 17-9). For example, treatment of o-mannose with phenylhydrazine gives the corresponding hydrazone, o-mannose phenylhydrazone. Surprisingly, the reaction does not stop at this stage but can be induced to continue with additional phenylhydrazine (two extra equivalents). The final product is a double phenylhydrazone, also called an osazone (here, phenylosazone). In addition, one equivalent each of benze-namine (aniline), ammonia, and water is generated. 

A four-component domino reaction of isatin 58, phenylhydrazine, 3-aminocrotononitrile 117, and cyclic 3-diketones/amide/thioamide 118 in an aqueous medium in the presence of ( )-camphor-10-sulfonic acid on heating at 100 °C for 2-3 h afforded the spiro-fused 2-oxindoles 119 (Scheme 39) [94]. The reaction was successfully extended to 5-chloro- and 5-nitroisatins. According to the proposed mechanism, an acid-catalyzed reaction of phenylhydrazine with nitrile 117 affords the 5-amino-3-methyl-l-phenyl pyrazole 111 that adds to the carbonyl carbon of isatin giving rise to an intermediate product 120. The acid-catalyzed reaction of this intermediate (that has been isolated) with carbonyl compounds 118 affords another intermediate compound 121, which eventually furnishes the final products 119 by cyclodehydration forming tetrahydropyridine ring followed by subsequent dehydration (Scheme 40). 

We recall that hydrazine and 2,4-dinitrophenylhydrazine react with carbonyl compounds to give hydrazones. However, monosaccharides do not give simple phenylhydrazone derivatives. After the initial formation of a phenylhydrazone, further reaction occurs to give the osazone, which has two molecules of phenylhydrazine incorporated into it. 

Derivatives of the Carbonyl Group. Not many reactions of the aldehyde or keto group of sugars are observed, because the carbonyl forms of sugars comprise only a fraction of one percent in the equilibrium mixture. They can be trapped, however, in a few reactions, e.g. by oximfe formation. Important for the identification of sugars is the reaction with phenylhydrazine or with substituted phenylhydrazines (E. Fischer), which involves two carbon atoms and results in osazones ... 

In the case of the reaction of substituted hydrazines, such as phenylhydrazine with glucose or certain other carbohydrates, one molecule of phenylhydrazine reacts with the terminal aldehyde group to form a phenylhydrazone. A second molecule of phenylhydrazine oxidizes the penultimate carbinol grouping to a carbonyl and a third molecule of phenylhydrazine converts this second carbonyl to a phenylhydrazone. This class of di-phenylhydrazones is called an osazone, a series of compounds not discussed in the present chapter. 

It has been shown by H naff (1963) that the rate of reaction of several carbonyl reagents (bisulphite, hydrazine, phenylhydrazine, semi-carbazide and hydroxylamine) with aqueous formaldehyde solutions is independent of the nature and concentration of the reagent, and is therefore determined by the rate of dehydration of methylene glycol. He obtained catalytic constants for hydrogen and hydroxide ions, and a detailed study of acid-base catalysis has been made by the same method by Bell and Evans (1966). 

The diphenyl derivative 388, R = R = Ph, has an absorption band at 1495 cm S which has been assigned to the carbonyl group. This assignment could be questioned. The following chemical reactions of the compound 388, R = R = Ph, may be noted (a) Raney nickel desulfurization followed by oxidation with manganese dioxide yields dibenzyl ketone,(b) hydrazine yields 3,5-diphenyl-4-hydroxypyrazole (390), (c) phenylhydrazine yields PhCH2COCPh=NNHPh," (d)... 

The carbonyl groups in 4//-thiopyrans 20a were easily reduced to diastereomeric hydroxy derivatives 606a.61,370 The reaction of 20a with benzylmagnesium chloride gave benzylidene derivatives 606b370 and with phenylhydrazine the corresponding SchifF bases 606c.61,99... 

The reaction of glucose with an excess of phenylhydrazine (phenyl-diazane) is particularly noteworthy because two phenylhydrazine molecules are incorporated into one of glucose. Subsequent to the expected phenyl-hydrazone formation, and in a manner that is not entirely clear, the —CHOH— group adjacent to the original aldehyde function is oxidized to a carbonyl group, which then consumes more phenylhydrazine to form a crystalline derivative called an osazone, or specifically glucose phenylosazone ... 

When unknown compounds are identified without the aid of spectroscopy classification tests are used. Reacting the carbonyl in a ketone or aldehyde with an amine (2,4 dinitro-phenylhydrazine) to form an inline is the easiest way to detect a ketone or aldehyde (Reaction l). The iinine that forms is a highly colored solid. The color of the solid also helps to indicate structural characteristics. Ketones and aldehydes with no conjugation tend to form itnines with yellow to orange colors, while highly conjugated ketones or aldehydes form imines with red color. 

By reaction of phenylhydrazine with enaminediones bearing an olefinic side-chain conjugated with the carbonyl, cyclization can be accomplished, depending on the solvent, to 3-vinylpyrazoles or to dihydropyridones282 (equation 208). 

The reaction of phenylhydrazine, and particularly substituted phenylhydrazines, with the carbonyl group of sugars is extensively utilized in their identification. The derivatives are called osazones if two molecules of phenylhydrazine add to one molecule of sugar, as in the case of glucose, and phenylhydrazones when one molecule... 

Synthesis of 4-amino-2-pyrazolin-5-ones is usually achieved by treatment of an a-amido-/3-aldehydo- or /9-ketoester with hydrazines according to the classical method for preparation of 2-pyrazolin-5-ones. Variants on this procedure consist of using an a-amidoester which has /9-substituents whose reaction is equivalent to that of a /9-carbonyl substituent. Such compounds are D-benzylpenicilloic acid a-methyl ester,1027 ethyl phenylpenaldate243 and the acetal of an a-amido-/9-formyl ester.59,243 Cornforth has isomerized 2-phenyl-4-hydrazino-methylidyneoxazolidone to 4-benzamido-2-pyrazolin-5-one. The same compound was obtained by treatment of 1-ethoxyvinyl-2-phenyl-oxazolidone with phenylhydrazine.319... 

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