Acyl hydrazine

The hydrolysis of l-alkyl-2-acyldiaziridines to A -alkyl-A -acyl-hydrazines possesses preparative interest. For example, A -cyclohexyl-A" -toluenesulfonylhydrazine [Eq. (51), yield 67% ] and 1-cyclohexyl-4-phenylsemicarbazide [Eq, (52) yield 73%] can be prepared by hydrolysis of the substituted diaziridines 46 and 62. ... 

Diphenyl-1 -acyl-hydrazine werden durch Lithiumalanat in siedendem Dibutylather bci 142° zu den 2-Alkyl- 1,2-diphenyI-hydrazinen und unter Spaltung der N-N-Bindung (s. S. 484) zu den N-Alkyl-anilinen reduziert4 ... 

Scheme 9 Synthesis of 1,3,4-oxadiazoles from acyl hydrazines and isocyanates...

A wide range of groups are tolerated in this position including esters, amides, thioesters, ureas, acyl hydrazines and carbamates exhibiting a wide range of potencies and microsomal stabilities (Table 6.2) [24, 33-36]. 

Disubstituted tetrazoles are conveniently prepared from acyl hydrazines (98) and diazonium salts.166 The reaction proceeds through the intermediate tetrazenes (99) followed by cyclization to the tetrazole (100) (Scheme 13). The intermediate can be isolated under mildly basic conditions. Symmetrically 1,2-diacylated hydrazines yield 1-substituted tetrazoles through the elimination of one of the acyl groups.166 - 168 Diformyl-hydrazine is a very convenient starting material for 1-substituted tetrazoles.166, Unsymmetrically 1,2-diacylated hydrazine usually results in mixtures.169... 

Aqueous NaOH (40%, 1.4 mol) is added with stirring at room temperature to the acyl-hydrazine (0.15 mol) and TEBA-C1 (0.5 g, 2.2 mol) in CHC13 (75 ml, 0.95 mol). The mixture is refluxed for 30 min and then poured into ice-water (150 g). The reaction mixture is neutralized at 0°C with cone. HC1 and the organic phase is separated from the precipitate. The aqueous phase and precipitate are extracted with CH2C12 (3 x 50 ml) and the combined organic solutions are dried (MgS04) and evaporated to give the diacyl-hydrazines. 

Spectral evidence" indicates an equilibrium between tetrahedral and octahedral Co" in iViV-dimethylacetamide and the equilibrium constant for [Co (tet)]/[Co (oct)] is reported at various temperatures. The complexes of acetylhydrazine (A), [CoA3]X2 (X = Cl or Br) and [Co(NCS)2A2]H20 and the tri-N-deuterio-analogue[Co(NCS)2(Ad3)2]D20 have been isolated and examined by i.r. Cationic complexes of JV-acyl hydrazines have been isolated with ligands in their keto-form, RCO-NH-NH2 however, the ligands also react in their enol form, RC(OH) = NNH2, forming neutral complexes (R = Me, Pr", Pr , or Ph). ... 

Acylated HPs were also prepared from 2-alkylthiopyrimidines and acyl-hydrazines and, further, cyclized in situ to triazolopyrimidines (58USP2852375). 

N-Acetyl derivatives of 3-phenyloxaziridine can also transfer their nitrogen function to nucleophiles. 2-(4 -Nitrobenzoyl)-3-phenyloxaziridine (69) converts piperidine to the acyl-hydrazine (101) in 92% yield within some minutes at room temperature (67JPR(36)86). Since (69) is stable in the absence of a nucleophile a nitrene is not involved in the reaction, which is assumed to occur by nucleophilic attack of the amine on the oxaziridine nitrogen. 

Fortunately, there is now a comprehensive body of knowledge on the metabolic reactions that produce reactive (toxic) intermediates, so the drug designer can be aware of what might occur, and take steps to circumvent the possibility. Nelson (1982) has reviewed the classes and structures of drugs whose toxicities have been linked to metabolic activation. Problem classes include aromatic and some heteroaromatic nitro compounds (which may be reduced to a reactive toxin), and aromatic amines and their N-acylated derivatives (which may be oxidized, before or after hydrolysis, to a toxic hydroxylamine or iminoquinone). These are the most common classes, but others are hydrazines and acyl-hydrazines, haloalkanes, thiols and thioureas, quinones, many alkenes and alkynes, benzenoid aromatics, fused polycyclic aromatic compounds, and electron-rich heteroaromatics such as furans, thiophenes and pyrroles. 

Compounds with an N-terminal protected azaamino acid residue can be produced by using acylated hydrazines, those with Boc and Z groups being favored. 319 Tosyl-protected compounds can likewise be prepared however, attempts to remove the tosyl protecting group using sodium in liquid ammonia were unsuccessful. 19 ... 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

The small-molecule-based machine conceived by von Delius, Geertsema, and Leigh [45] is a linear (for reviews, see [46], [100]) motor based on dynamic covalent chemistry [19-24] (forming, breaking, and reforming of dynamic covalent bonds with relatively fast equilibration in response to stimuli), namely on acyl-hydrazone and disulfide exchanges. The motor consists of a track that has four functional groups disposed alternately aldehyde-thiol-aldehyde-thiol which are the positions 1,2, 3, and 4 of the track, a walker NH2-NH-CO-(CH2)5-SH which has the feet A (hydrazide or acyl-hydrazine) and B (thiol), and a placeholder with a foot C of type thiol (Fig. 10). 

Hydrolysis is an important route of metabolism for esters, amides, carbamates, and acyl hydrazines. Aspirin is rapidly converted to salicylic acid this may be further metabolised to gentisic acid (5-hydroxysalicylic acid), conjugated with glucuronic acid or glycine, or excreted unchanged. 

The one-pot, three-component synthesis of 1,2,4-triazoles from primary amines, acyl hydrazines and dimethoxy-A(-A(-dimethylmethanamine [84] was utilized for the preparation of compounds 235 (Scheme 41), which were evaluated for their anticonvulsant and neurotoxic properties [85]. The anticonvulsant activity was measured in mice by the maximal electroshock test (MES) and the neurotoxicity in mice by the rotarod neurotoxicity test (Tox). The majority of the compounds... 

Under certain conditions, amides can add directly to alkenes to form V-alkylated amides. Sulfonamides react in a similar manner. 3-Pentenamide was cyclized to 5-methyl-2-pyrrolidinone by treatment with trifluorosulfonic acid. Acyl hydrazine derivatives also cyclized in the presence of hypervalent iodine reagents to... 

Acyl azides may generally be prepared by nitrosation of acyl-hydrazines with nitrous acid nitrosyl chloride and organic... 

A less used route to the substrate is the treatment of an acyl hydrazine RCONHNH2 (formed from an ester and hydrazine) with nitrous acid. Detailed compilations and reviews list the many hundreds of examples of the rearrangement recorded up to 1961. The... 

A-nitrosamides behave in acid solution like A-nitrosamines they are reduced to acylated hydrazines. In this way alkylhydrazines may be prepared from primary amines by the following reactions [216]. 

The reduction of acyl hydrazines has been investigated very little. Polarography of 4-pyridine carboxylic acid hydrazide in acid and neutral solution shows that it is reduced in two, two-electrons steps [141]. The result of controlled potential electrolysis is cleavage of the N-N bond to form 4-pyridine-carboxamide, which then undergoes reduction to the aldehyde in the second step. Other hydrazides of heterocyclic carboxylic acids behave analogously. 

Pellizzari reaction. Formation of substituted 1,2,4-triazoles by the condensation of amides and acyl hydrazines. When the acyl groups of the amide and acylhydrazine are different, interchange of acyl groups may occur, with formation of a mixture of tri azoles. 

The treatment of acyl hydrazine derivatives with phosgene gives 1,3,4-oxadiazole-5-ones... 

Four acyl hydrazine metabolites were Isolated from the feces of sheep dosed at 50 mg/kg with the anthelmintic, -toluoyl chloride phenylhydrazone (36, Figure 4). Collectively, these amide derivatives (acylation by stearic, palmitic, myristic, and laurlc... 

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