Hydrazides from hydrazines

All the sulfonic acid hydrazides are made from hydrazine or semicarbazide and the appropriate sulfonyl chloride in the presence of an HCl acceptor such as ammonia. 

Pyridazinecarbohydrazides are prepared in the normal way from an ester or acid chloride and hydrazine or a substituted hydrazine, generally in good yields. Pyridazines with two ortho alkoxycarbonyl groups give cyclic hydrazides with hydrazine, which are pyridazinopyridazines. 

The reaction of Curtius, which is especially to be preferred in the case of the higher members on account of the favourable solubilities of the intermediate products, involves as its first stage the preparation of the hydrazide from an ester (or acid chloride). The hydrazide is then converted, usually very readily, by the action of nitrous acid into the azide. In many cases it is more convenient to prepare the azide by treating an acid chloride with sodium azide previously activated with hydrazine hydrate.1 Azides easily undergo thermal decomposition, the two azo nitrogen atoms being eliminated as elementary nitrogen. In this way, however, the same radicle is formed as was invoked above to explain the Hofmann reaction ... 

S-S Wang, ID Kulesha, DP Winter, R Makofske, R Kutny, J Meienhofer. Preparation of protected peptide hydrazides from the acids and hydrazine by dicyclohexylcarbo-diimide-hydroxybenzotriazole coupling. Int J Pept Prot Res 11, 297, 1978. 

Release of 4-Deacetylvinblastine Hydrazide from 4-Deacetylvinblastine Hydrazine-KS1/4S2 Conjugate as a Function OF Temperature and pH... 

Acid hydrazides from esters. Methyl and ethyl esters react with hydrazine to give acid hydrazides ... 

All technical processes for the synthesis of hydrazine yield either hydrazine in aqueous solution or hydrazine hydrate. Most applications can use hydrazine hydrate, but for some applications, for example, rocket propulsion, anhydrous hydrazine is necessary. The water can be removed by a chemical reaction followed by distillation or by azeotropic distillation with an auxiliary fluid. As water binding chemicals, calcium carbide, sodium hydroxide, calcium oxide, calcium hydride, barium oxide, barium hydroxide, and barium pemitride Ba3N4 have been used. The use of sodium or calcium metal and sodium amide is best avoided because of the formation of explosive hydrazides. Starting from hydrazine hydrate (64% hydrazine), sodium hydroxide is generally used... 

In general the synthesis of suitably protected amino acid and peptide hydrazides from the corresponding alkyl or aryl esters by reaction with hydrazine hydrate is carried out in alcohols or DMF at ambient temperature.P However, with C-terminal branched amino acids such as valine or isoleucine, or larger peptides, more vigorous conditions are required, i.e. higher temperature (25-80°C) and longer reaction times. To avoid formation of symmetrical bis(A-acyl-aminoacyl)hydrazides an excess of hydrazine hydrate or hydrazine is recommended, which also enhances the reaction rates. In this context, the solvent is known to play an important role, with alcohols being more appropriate than DMFP 0 or solvent mixtures such as dioxane/methanol.f l The use of hydrazine hydrate without any solvent has also been reported. ... 

In the case of the protected peptide alkyl ester containing Arg(N02), Asp(OtBu), Asp(OBzl), or Glu(OBzl), treatment with hydrazine hydrate results in side reactions, such as hydrazinolysis of side-chain functional groups. In order to avoid such side reactions, it is preferable to synthesize the protected peptide hydrazide from the corresponding substituted hydrazide. The representative substituted hydrazides for R C(0)NH-CHR -C(0)-NHNH-X are X = Z,b°3] c(0)OTrt,[i° l Boc,[i l Troc,[i l C(0)0CH2-4-pyridyl,b°d and C(0)OCMc2-CCl3.[ l... 

As described earlier (Section 4.4.1.1), the intermediates of the Curtius reaction are acyl azides, which themially rearrange to isocyanates. One of the classical procedures for the preparation of acyl azides consists of the formation of hydrazides from esters and hydrazine, followed by treatment of the hydrazides with nitrous acid, generated from sodium nitrite and acetic, hydrochloric or sulfuric acid. Acyl azides are commonly used in the crude state or in solution since they are thermally unstable and potentially explosive. 

The compounds from hydrazines and ketones or quinones (hydrazides) are so closely related to the azo-series, that one is almost compelled to place them under the same classification. 

Other reactions. The preparation of an acid hydrazide from an acid is illustrated by the reaction of p-toluenesulfonyl chloride with hydrazine hydrate in Iclrtihydro-... 

Stone, G.M. The fate of maleic hydrazide in a burning cigarette, unpublished report. May 1957 Results presented in Harke et al. Pyrolyse von Maleinsaurehydrazid und Hydrazin [Pyrolysis of maleic hydrazide and hydrazine] Z. Lebensm. Unters.-Forsch. 153 (1973) 163-169. Thurm, V Untersuchungen iiber Pestizidriickstande auf Tabakwaren. 3. Mitt. Zum Ubergang von DDT und Dieldrin aus Tabakwaren in den Rauch [Investigations over pesticide residues on tobacco products. 3. Transfer of DDT and Dieldrin from tobacco products into the smoke] Die Nahrung 21 (1977) 335-338. 

In the above pyridazine formation, both nitrogen atoms in the ring originate from hydrazine. The actual existence of intermediate structures like 445 and 446, which are finally converted into methylpyridazinone 447, is also supported by the fact that 2-a-aminoethylbenzoic acid 450 heated with hydrazine turns into 4-methyl-1-phthalazone 453 in almost quantitative yield through hydrazide 451 and dihydrophthalazone 452 (91ZOR1120). 

A soln. of p-nitrobenzyl benzyloxycarbonyl-L-phenylalanyl-Nim.piperidinocarbo-nyl-L-histidylglycinate in abs. ethanol-dimethylacetamide allowed to react 15 hrs. at room temp, with 5 moles 100%-hydrazine hydrate -> benzyloxycarbonyl-L-phenylalanyl-L-histidylglycine hydrazide. Y 95%. F. e., also removal with NaOH, s. G. Jager, R. Geiger, and W. Siedel, B. 101, 3537 (1968) a,y -ethylenecarboxylic acid hydrazides from active esters s. R. Harada and H. Kondo, Bull. Chem. Soc. Japan 41, 2521 (1968). 

Acetone, butanone, cyclobutanone and similar ketones have been used to prepare Schiff bases from long-chain amines, aromatic amines, diamines, anriino-phenols and catecholamines in biological media [29-34], and from hydrazines in air [35], prior to separation by GC. When electron capture detection was used, penta-fluorobenzaldehyde was the chosen reagent. This procedure was applied to the analysis of traces of amines in water samples [36] and biological extracts [37,38], as well as hydrazine in tobacco smoke, technical maleic hydrazide and pyrolysis products [39]. 

Many alkyl and aryl phosphinic hydrazides (7.208d) and phosphoric hydrazides (7.208a) can be obtained from hydrazine and phosphinic chlorides or phosphorochloridates ((7.209) and (7.210)). Products of this kind are stable in alkaUne media, but under strongly acid conditions the P-N linkages are split. 

Lopes, C. C. Lopes, R. S. C. Cardoso, J. N. Alves Da Silva, J. Ferreira Gomes, L. Hydrazide catalytic production process from hydrazines and dicarboxylic acids in the presence of Lewis acids. PCX Int. Appl. WO 2005051870, 2005 Chem. Abstr. 2005,143, 26622. 

Formation of pyrazole derivatives from hydrazines, hydrazides, semicarbazides, and aminoguanidines by condensation with 1,3-dicarbonyl compounds substituted hydrazines yield two structurally isomeric pyrazoles ... 

The formation of hydrazides from the esters of disubstituted malonic esters becomes increasingly difficult with increase in the size of the substituents. Diethyl ben lmethylmalonate with excess hydrazine in... 

Azides contmning hydroxyl groups have been prepared by both the hydrazide and the sodium azide methods. The hydrazides of adds containing hydroxyl groups in the lactone-forming positions cmi usudly be produced from the corresponding esters or the lactones, but on treatment with add the hydrazides lose hydrazine and yidd the lactones. This behavior has su ested that the compounds are not true hydrazides (XV) but hydrazino lactones (XVI). However, the successful... 

The preparation of hydrazides from acid chlorides is an uncertain procedure which frequently ves rise to large quantities of secondary hydrazide." Indeed, the secondaiy hydrazide may be the only product if an unsuitable procedure is followed. The most successful method is to add slowly a chilled solution of the add chloride in ether to a well-stirred, chilled alcoholic solution of hydrazine hydrate containing considerably more than the 2 moles theoretic y required. The product is usually separated from the hydrazine hydrochloride formed at the same time by extracting the latter with water. Where the ester is extremely unreactive, this may be the only practicable method for preparing the hydrazide. On the other hand, if the acid chloride must be made, it is usually more expedient to convert it directly to the azide by reaction with sodium azide. 

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