Hydrazide-hydrazones

CN 4-pyridinecarboxylic acid hydrazide, hydrazone with 0-2-deoxy-2-(methylamino)-a-L-glucopyranosyl-... 

Amino-4,5-dihydro-5-hydroxy-l,2,4-triazine (82B) exhibits a temperature-dependent equilibrium with the open-chain hydrazide-hydrazone derivative 82A in CDCI3 solution, as shown by the H-NMR data (85LA78). 

CN 4-pyridinecarboxylic acid hydrazide, hydrazone with 0-2-deoxy-2-(methylamino)-a-i.-glucopyranosyl-(1— 2)-0-5-deoxy-3-C-formyl-a-i.-lyxofuranosyI-l(l—>4)-A/,V-bis(aminoiminomethyl)-r>-streptamine... 

Norman has tabulated the constants for various derivatives of the uronic acids and has summarized previous work on their identification. The free acids or their lactones have been used for the purpose of identification. The quinine, brucine, and cinchonine salts" have also been used for this purpose, although their isolation in pure form is hindered by the presence of the corresponding alkaloidal salts of the low polymers of the acid. Some of the complex hydrazines have been used to identify the acids. p-Bromophenylhydrazine has been frequently used for this purpose. One difficulty in the use of hydrazines is that they may form numerous types of derivatives such as salts, hydrazides, hydrazones and osazones. 

Hydrazide-hydrazones 1 are cyclized by treatment with orthocarboxylates, imidates, or ami-dines in methanol to give l,4-dihydro-l,2,4,5-tetrazines 2 (see Houben-Weyl, Vol. E8c, p 622), which are oxidized by manganese(IV) oxide, mercury(II) oxide, 1,4-benzoquinonc, or air to afford 1,2,4,5-tetrazines 4 the yield is always below 10%.156 The predominant products of the reactions of 1 arc 1.2,4-triazol-4-amines 3.157... 

Reaction of the hydrazide-hydrazone 12 with 3,4-dichloro-5-hydroxyfuran-2(5/f)-one (mu-cochloric acid), 3,4-dibromo-5-hydroxyfuran-2(5//)-one, or 3-hydroxyisobenzofuran-l (3H)-one (phthalaldehydic acid) followed by treatment with manganese(IV) oxide yields the condensed 1,2,4,5-tetrazines 13 and 14, which are transformed into the 1,2,4,5-tetrazines 15 and 16 by oxidation with potassium permanganate in methanol.162-163... 

The identification of the uronic acids is difficult (68). The alkaloidal salts frequently are used cinchonine and brucine have value for glucuronic acid. Various hydrazines have been used to prepare derivatives, but often the products are complex, for hydrazides, hydrazones, and osazones are formed. A common method of identification is to convert the uronic acids by mild oxidation to the dibasic acids. 

Special reactions of hydrazides and azides are illustrated by the conversion of the hydrazide (205) into the azide (206) by nitrous acid (60JOC1950) and thence into the urethane (207) by ethanol (64FES(19)105Q) the conversion of the same azide (206) into the N-alkylamide (208) by ethylamine the formation of the hydrazone (209) from acetaldehyde and the hydrazide (205) and the IV-acylation of the hydrazide (205) to give, for example, the formylhydrazide (210) (65FES(20)259). It is evident that there is an isocyanate intermediate between (206) and (207) such compounds have been isolated sometimes, e.g. (211). Several of the above reactions are involved in some Curtius degradations. 

Steroid ketones Apply the sample solution followed by Girard s reagent (0 1% tnmethylacetyl hydrazide in 10% acetic acid) and allow to react for 15 h in an atmosphere of acetic acid Then dry at 80 °C for 10 mm and after cooling chromatograph the hydrazones that have been formed [81]... 

Isonicotinic acid hydrazide forms fluorescent hydrazones with ketosteroids. 

In about 5-10 minutes a clear solution resulted, whereupon slow crystallization occurred and the temperature rose to about 6°-7°C. The crystallization was permitted to continue overnight at 5°C, and the very fine precipitate was then isolated by centrifugation and in the centrifuge washed with water, ethanol, and ether, yielding the dihydrate of DL-seryl-(2,3,4-trihydroxy-benzylidene) hydrazide hydrochloride, which melted at 134°-136°C and was poorly soluble in cold water, but very readily dissolved in hot water. The condensation was also effected in absolute ethanol yielding the anhydrous form of the hydrazone, which melted at 225°-228°C. 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

Formaldehyde hydrazones react with N,AT -thiocarbonyldi-1,2,-4-triazole to give hydra-zones of thioglyoxalyl-1,2,4-triazoles, which react readily under displacement of 1,2,4-triazole with nucleophilic reagents such as amines and hydrazines but also with less nucleophilic compounds, including hydrazones, sulfonylhydrazides, thiosemicarbazides, and hydrazides.[10]... 

Figure 1.70 AMBH is a hydrazide-containing compound that reacts with carbonyl groups to form hydrazone bonds. The free thiol can be used for subsequent conjugation reactions.

Figure 1.107 The N-terminal aldehyde group on a peptide formed from periodate oxidation of serine or threonine residues can be conjugated with a hydrazide-containing molecule to produce a hydrazone bond.

Aldehyde-containing macromolecules will react spontaneously with hydrazide compounds to form hydrazone linkages. The hydrazone bond is a form of Schiff base that is more stable than the Schiff base formed from the interaction of an aldehyde and an amine. The hydrazone, however, may be reduced and further stabilized by the same reductants utilized for reductive amination purposes (Chapter 3, Section 4.8). The addition of sodium cyanoborohydride to a hydrazide-aldehyde reaction drives the equilibrium toward formation of a stable covalent complex. Mallia (1992) found that adipic acid dihydrazide derivatization of periodate-oxidized dextran (containing multiple formyl functionalities) proceeds with much greater yield when sodium cyanoborohydride is present. 

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