Acid hydrazides, from esters

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

Carboxylic acid hydrazides from esters COOR -> CONHNHa... 

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. 

Carboxylic acid hydrazides from carboxylic COOR -> CONHKHj acid esters... 

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). 

Carboxylic acid hydrazides from carboxylic acid esters GOOR -v CONHNHg with cis-frans-rearrangement s. 17, 413... 

Subst. carboxylic acid hydrazides from carboxylic acid cyanomethyl esters... 

Place 1 0 ml. of hydrazine hydrate (CAUTION corrosive chemical) in a test-tube fitted with a short refiux condenser. Add 10 g. of the methyl or ethyl ester dropwise (or portionwise) and heat the mixture gently under refiux for 15 minutes. Then add just enough absolute ethanol through the condenser to produce a clear solution, refiux for a further 2-3 hours, distil oflF the ethyl alcohol, and cool. Filter oflF the crystals of the acid hydrazide, and recrystallise from ethanol, dilute ethanol or from water. 

Sulfobenzyl esters were prepared (cesium salt or dicyclohexylammonium salt, Na03SC6H4CH2Br, DMF, 37-95% yield) from A -protected amino acids. They are cleaved by hydrogenolysis (H2/Pd), or hydrolysis (NaOH, dioxane/water). Treatment with ammonia-or hydrazine results in formation of the amide or hydrazide. The ester is stable to 2 M HBr/AcOH and to CF3SO3H in CF3CO2H. The relative rates of hydrolysis and hydrazinolysis for different esters are as follows ... 

Amides are stable compounds. The lower-melting members (such as acetamide) can be readily purified by fractional distillation. Most amides are solids which have low solubilities in water. They can be recrystallised from large quantities of water, ethanol, ethanol/ether, aqueous ethanol, chloroform/toluene, chloroform or acetic acid. The likely impurities are the parent acids or the alkyl esters from which they have been made. The former can be removed by thorough washing with aqueous ammonia followed by recrystallisation, whereas elimination of the latter is by trituration or recrystallisation from an organic solvent. Amides can be freed from solvent or water by drying below their melting points. These purifications can also be used for sulfonamides and acid hydrazides. 

Certain 1,3,4-oxadiazole and 1,2,4-triazole glyphosate derivatives have been conveniently prepared in a faster, more efficient manner by heating the thionoester intermediates 73 with the appropriate acid hydrazide (61). These versatile thionoesters 73 have been synthesized in nearly quantitative yield from the readily available nitrile 31a, described previously, through the intermediate imidate ester 72. The oxadiazole products such as 70 obtained using this procedure were identical to those obtained from the HHT approach. 

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 ... 

Isocarboxazid Isocarboxazid, 2-benzylhydrazid-5-methyl-3-isoxazolecarboxylate (7.2.6), can be synthesized from acetylacetone, which on nitrosation with nitrous acid gives 5-methyl-isoxazol-3-carboxyhc acid (7.2.2). Esterification of this product gives the ethyl ester of 5-methyl-isoxazol-3-carboxyhc acid (7.2.3). The synthesized ester (7.2.3) is further reacted with benzylhydrazine, to give isocarboxazide (7.2.6), or with hydrazine, which forms 5-methyl-isoxazol-3-carboxylic acid hydrazide (7.2.4). Reacting the latter with benzaldehyde gives hydrazone (7.2.5), which is further reduced to the isocarboxazide (7.2.6) [46,47]. 

N 24.78%. Two isomers are described in the literature 2,4-Dinitrobenzoic Acid Hydrazide (2,4 -Dinitrobenzoic Acid Hydrazide), orn-yel cryst (from abs ale), mp 231-3° was prepd in small quant by treating the methyl or ethyl ester of 2,4 -dinitrobenzoic acid with hydrazine sulfare(Ref 3)... 

Dinitrobenzoic Acid Hydrazide(called 3.5-Di-nitro-benzoylhydrazid in Ger), yel ndls(from ale), mp 158° was prepd by heating the ethyl ester of... 

A closely related reaction of general applicability is the Curtius rearrangement222 of acyl azides. The rearranging species in the Schmidt reaction (see p. 898) is in fact also a protonated acyl azide these azides are readily prepared by the action of nitrous acid on acyl hydrazides which are themselves formed from esters and hydrazine (Section 9.6.17, p. 1269). On heating in aprotic solvents the acyl azides decompose to yield the corresponding isocyanates in good yield. 

Syntheses from Acid Hydrazides and ortho Esters... 

Bisoxadiazoles are formed from bis(mono)imido ester hydrochlorides and mono(bis)carboxylic acid hydrazides when the free ester is used, an amidrazone (27) is often formed which cyclizes with the elimination of ammonia to give 28.73 The reaction proceeds in the presence of higher boiling solvents or by mixing the reactants at a temperature higher than 100°, the imido esters forming first in the reaction mixture. The reaction of semicarbazide [Eq. (2), R = NH2] with imido esters does not, of course, lead to 2-amino-1,3,4-oxadiazoles but to the isomeric l,2,4-triazolin-3-ones.72 The reaction of N-substituted imidochlorides with aromatic acid hydrazides in the... 

The course of alkylation may be influenced by the pH of the reaction medium as shown in the case of chloroacetic acid or its ester as alkylating agent. Maleic hydrazide A-alkylates at pH < 8 to form 86, but at pH > 8 0-alkylation (87) or A,0-dialkylation (88) with two equivalents of the alkylating agent can take place. Compound 88 may be formed from 86 indirectly. 6-Chloro-3(2H)-pyridazinone... 

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