Hydrazines, acyl derivatives

Hydrazine 835 underwent ring closure with one carbon cyclizing reagents to afford 837 and/or /V-acyl derivatives 836. The N-acyl derivatives underwent cyclization on treatment with phosphorus oxychloride. They were also prepared by the reaction of hydrazones 838 with thionyl chloride (84JHC1565). Compound 835 underwent ring closure with carbon disulfide and ethyl chloroformate to give 839 (Scheme 169). 

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. 

The synthesis of this ring system may be achieved by building the triazole onto a preformed pyrimidine ring. Cyclocondensation of ketoesters 330 with O-methylisourea (331) gave the pyrimidine 332, whose acylation gave the /V-acyl derivative 333, which can be cyclized with hydrazines to give 334 (89GEP3839711) (Scheme 64). 

Organic hydrazines or diazanes are substitution products of NH2—NH2 and have many properties similar to those of amines in being basic and forming acyl derivatives as well as undergoing alkylation and condensations with carbonyl compounds (Section 16-4C). Unsymmetrical hydrazines can be prepared by careful reduction of /V-nitrosamines. l,l-Dimethyldiazane is prepared in this way for use as a rocket fuel ... 

Treatment of the JV-nitrosocyanides (283)198 or the W-nitrosoguanyl-hydrazines (284)199 with hydrogen chloride yielded the 1,2,3,4-oxatriazolium chlorides (285, X = Cl), which with aqueous sodium bicarbonate gave the meso-ionic l,2,3,4-oxatriazol-5-imines (277, R2 = H).198 Nitrosation of these compounds (277, R2 = H) gave the interesting JV-nitroso compounds (277, R2 = NO), and acylation gave the JV-acyl derivatives (277, R2 = RCO).198... 

McFadyen-Stevens aldehyde synthesis.1 Use of this hydrazine in place of p-toluenesulfonylhydrazine for the McFadyen-Stevens synthesis of aromatic aldehydes has the advantage that decomposition of the intermediate acyl derivatives proceeds under mild conditions (K2C03 in refluxing CH3OH) however yields are unsatisfactory unless hydrazine is added. 

Nitro-4H-1 -benzopyrone reagieren mit Hydrazin-Hydrat (Ethanol 10 min, 20°) zu z, B..3(5)-(2-Hydroxy-phenyl)-5(3)-methyl-4-nitro-lH-pyrazol (88% Schmp. 201-2020)1187-, 188 ,37 analog verhalten sich Methyl- und Phenyl-hydrazin1187, mit Carbonsaure-hydraziden werden in hoher Ausbeute die 1-Acyl-Derivate erhalten. Der Acyl-Rest laBt sich durch Basen leicht abspalten1188. 

Carbohydrazides can be obtained from amides and hydrazine hydrate or substituted hydrazines. The products are mono- or di-acyl derivatives of hydrazine according to the reaction conditions, the proportions of the reactants, and the nature of any substituents already present on the hydrazine. 

The 0-acylated derivative underwent a 0 - N acyl migration from the 6-0 to the 1-amino group by treatment with hydrazine. Similarly the 3, 4 -dideoxy compound has been prepared More often Umezawa s method was used for the controlled 1 -N-acylation.Compound 102a which is easily obtained by cleavage of the oxazolidinone ring with Ba(OH)2 can be modified at the 1-amino function ... 

Within the last two decades, a number of chemical structures have been proposed as metal deactivators for polyolefins. These include carboxylic acid amides of aromatic mono- and di-carboxylic acids and N-substituted derivatives such as N,N -diphenyloxamide, cyclic amides such as barbituric acid, hydrazones and bishydrazones of aromatic aldehydes such as benzaldehyde and salicylaldehyde or of o-hydroxy-arylketones, hydrazides of aliphatic and aromatic mono- and di-carboxylic acids as well as N-acylated derivatives thereof, bisacylated hydrazine derivatives, polyhydrazides, and phosphorus acid ester of a thiobisphenol. An index of trade names and suppliers of a few commercial metal deactivators is given in Appendix A4. 

When A -nucleophiles such as ammonia, amines or hydrazine are subjected to acyl-transfer reactions, the corresponding Af-acyl derivatives - amides or hydrazides - are formed through interception of the acyl-enzyme intermediate by the iV-nucleophile (Schemes 2.1 and 3.21) [262]. Due to the pronounced difference in nucleophiU-city of the amine (or hydrazine) as compared to the leaving alcohol (R -OH) (Scheme 3.21), aminolysis reactions can be regarded as quasi-irreversible. Any type of serine hydrolase which forms an acyl-enzyme intermediate (esterases, lipases, and most proteases) is able to catalyze these reactirms. Among them, proteases such as subtilisin and peniciUin acylase and lipases from Candida antarctica and Pseudomonas sp. have been used most often. 

Amine salts acyl derivatives of primary or secondary amines aromatic amino-acids sul-phanilates naphthionates hydrazine derivatives some substituted ureas and thioureas (nitro-compoiinds may give the corresponding amine, when strongly heated). 

Salts of aromatic amines acyl derivatives of primary and secondary aromatic amines (often very slowly) high mol.wt. amino-acids hydrazine derivatives aryl ureas and aryl thioureas. 

IV. Ammoniiun salts of carboxylic adds, aldehyde-ammonias, amides, imides, nitriles. Acyl derivatives of bases (JV-substituted amides). Hydrazines, semicarbazide, hydroxyl-amine, their salts and carbonyl derivatives. Condensation products of aldehydes with ammonia or amines. 

Ammonium Salts of Carboxylic Adds Aldehyde-ananomas Anodes Inodes Nitriles Acyl Derivatives of Bases Hydrazines, Sendcarbazide, Hydroxylandne, their salts and carbonyl derivatives Condensation Products of Aldehydes with Amntonia or Andnes... 

Polyurethanes (PU) containing hydrazide fragments in their macrochains are of special interest for the development of new polymers. This is because (i) hydrazine and its derivatives are bifunctional reagents, readily forming polymers with various classes of organic multifunctional compounds and (ii) polymers based on hydrazine and its acylated derivatives are characterized by their valuable operational properties [2]. 

The product of this reaction is an imide (Section 20 16) a diacyl derivative of an amine Either aqueous acid or aqueous base can be used to hydrolyze its two amide bonds and liberate the desired primary amine A more effective method of cleaving the two amide bonds is by acyl transfer to hydrazine... 

Carboxylic acid hydiazides are prepared from aqueous hydrazine and tfie carboxylic acid, ester, amide, anhydride, or halide. The reaction usually goes poody with the free acid. Esters are generally satisfactory. Acyl halides are particularly reactive, even at room temperature, and form the diacyl derivatives (22), which easily undergo thermal dehydration to 1,3,4-oxadiazoles (23). Diesters give dihydtazides (24) and polyesters such as polyacrylates yield a polyhydrazide (25). The chemistry of carboxyhc hydrazides has been reviewed (83,84). 

Pyrazolo[3,4-d]pyridazines (555) can be prepared readily from hydrazines and pyrazoles substituted in positions 4 and 5 with an acyl and an ester group, or with two ester groups. 4,5-Pyrazolinediones have been used as starting materials for the synthesis of the quinoxaline derivatives (548) (see above) and of pyrazolo[3,4-e][l,2,4]triazines (556)... 

With Af-acyl or Af-sulfonyl hydrazines as nucleophiles, Zincke salts serve as sources of iminopyridinium ylides and ylide precursors.Reaction of the nicotinamide-derived Zincke salt 8 with ethyl hydrazino urethane 42 provided salt 43, while the tosyl hydrazine gave ylide 44 (Scheme 8.4.14). ° Benzoyl hydrazines have also been used in reactions with Zincke salts under similar conditions.Af-amino-1,2,3,6-tetrahydropyridine derivatives such as 47 (Scheme 8.4.15), which showed antiinflammatory activity, are also accessible via this route, with borohydride reduction of the initially formed ylide 46. ... 

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