Acyl hydrazides

This reaction forms the basis of one method of terminal residue analysis A peptide is treated with excess hydrazine in order to cleave all the peptide linkages One of the terminal amino acids is cleaved as the free amino acid and identified all the other ammo acid residues are converted to acyl hydrazides Which amino acid is identified by hydrazmolysis the N terminus or the C terminus ... 

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

The rapid synthesis of 1,2,4-triazines has also been developed under microwave-assisted conditions [80]. Irradiation of a 1,2-diketone with acyl hydrazides and ammonium acetate for 5-10 min at 180 °C in a single-mode microwave reactor gave 3,5,6-trisubstituted 1,2,4-triazines in excellent yield and purity and reaction times that were reduced 60-300 fold over conventional conductive heating methodology (Scheme 22). 

The inverse electron demand Diels-Alder reaction has also been used to provide expedient access to unnatural 6-carboline alkaloids from 1,2,4-triazines, prepared by microwave-assisted MCR [92]. One-pot reaction of an acyl hydrazide-tethered indole 73, 1,2-diketone and ammonium acetate in acetic acid provided triazines 74 (see Sect. 3.2, Scheme 22), bearing an electron-rich dienophilic indole moiety (Scheme 31). By carrying out the... 

A different kind of triazine, 3,5,6-trisubstituted 1,2,4-triazines 166, were prepared by reaction of 1,2-diketones 164 with acyl hydrazide in the presence of ammonium acetate and acetic acid at 180 °C for 5 min under microwave irradiation in a sealed tube [107]. Different substituents can be introduced in the final triazines providing a general approach for this kind of heterocycles (Scheme 59). 

The acyl azide intermediates are prepared either by reaction of sodium azide with a reactive acylating agent or by diazotization of an acyl hydrazide. An especially convenient version of the former process is treatment of the carboxylic acid with ethyl chloroformate to form a mixed anhydride, which then reacts with azide ion.265... 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

In the context of preparing potential inhibitors of histone deacetylase, Vasudevan and a team from Abbott have described the cyclization of 1,2-diacylhydrazides to 1,3,4-oxadiazoles with Burgess reagent under microwave conditions (150 °C, 15 min) (Scheme 6.224 a) [232], A different approach was chosen by Natero and coworkers, who prepared 2-chloromethyl-l,3,4-oxadiazoles by treatment of acyl hydrazides with 1-chloro-2,2,2-trimethoxyethane (Scheme 6.224b) [401]. Here, the reagent was used as solvent and the mixture was heated by microwave irradiation at 160 °C for 5 min. 

A one-pot synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from acids and acyl hydrazides has recently been reported. The method involves an activation of an acid with carbonyl diimidazole followed by the addition of benzoyl hydrazide and then the addition of CBr4 and Ph3P. Under the conditions, the dehydration proceeds smoothly to provide the desired oxadiazoles in high yields <2006TL4827>. 

Reactions of pyrimido[4,5-3] [l,4]thiazines were discussed in CHEC-II(1996) <1996CHEC-II(7)737> more recently, reported reactions of this system involve nucleophilic substitution in a number of guises. Hemiaminals at C-3 react with ammonium acetate to form aminals (Equation 166) <1999CHE97>. The formation of acyl hydrazides from pyrimido[4,5-3][l,4]thiazine-2-carboxylic acids, along with their subsequent conversion to acyl azides and Curtius... 

Oxadiazol-Skelett herstellen. Die Cyclisierung erfolgt hier entwedcr durch Kondensation, wie bei 1,2-Diacyl-hydrazinen, Kohlcnsaure-(2-acyl-hydrazid)-estern, (Thio)Kohlensaure-(2-acyl-hydrazid)-amiden, oder oxidativ, wie mit Aldehyd-acylhydrazonen und Aldehyd-(2-ami-nocarbonyl-hydrazoncn) bzw. -[2-(amino-thiocarbonyl)-hydrazonen], Bei der Synthese von... 

Die Cyclodehydratisierung von Kohlensaure-(2-acyl-hydrazid)-amiden ist eine einfache Methode zur Synthese von 2-Amino-l, 3,4-oxadiazolen. Die Wasser-Abspaltung wird am besten durch Erhitzen mit Phosphoroxichlorid erreicht234. Dieses Verfahren liefert bei der Synthese von 2-Alkyl(Aryl)amino bzw. 2-Heteroalkyl-l, 3,4-oxadiazolen Ausbeuten von 50-90%234 235 413-415 z.B. ... 

Alkyl-2-ainino- bzw. 2-Amino-5-aryl-l,3,4-oxadiazole allgemeine Arbeitsvorschrift234 41S Man lost das Kohlensaure-(2-acyl-hydrazid)-amid in siedendem Phosphoroxichlorid und erhitzt 1 -3 h unter RiickfluB. Die abgekiihlte Losung wird langsam zu Eiswasser gegeben. 

Kohlensaure-(2-acyl-hydrazid)-amide konnen auch mit Thionylchlorid in guten Ausbeuten zu 2-Amino-l,3,4-oxadiazolen cyclodehydratisiert werden417. 

Gute Ausbeuten von 2-Hydroxy-1,3,4-oxadiazolen erreicht man auch durch Erhitzen von Kohlensaure-(2-acyl-hydrazid)-amiden oder 3-Acyl-l-aminocarbonyl-harnstoffen in Xylol424 oder Biphenyl422 ... 

Substituierte 2-Hydroxy-l,3,4-oxadiazole allgemeine Arbeitsvorschrift 424 Man erhit/t das Kohlensaure-(2-acyl-hydrazid)-amid in getrocknetem Xylol 24 h unter RuckfluB. Das Xylol wird i. Vak. entfemt und der Riickstand umkristallisiert Oder, wenn R1 = T ist, in Chloroform gelost und mit trockner ether. Salz-siiure versctzi, um das Hydrochlorid abzutrennen. 

Durch Cyclokondensation von semicyclischen Kohlensaure-(2-acyl-hydrazid)-amiden erhalt man anellierte 1,3,4-Oxadiazole. 

Die Synthese von 2-Amino-1,3,4-oxadiazolen aus Thiokohlensaure-(2-acyl-hydrazid)-amiden fiber Thiokohlensaure-(2-acyl-hydrazid)-imid-methylester hat trotz teilweise sehr guter Ausbeu-ten keine generelle praparativc Bedeutung. Nachteilig ist nicht nur eine zusatzliche Reaktions-stufe, sondern auch die unangenehme Methanthiol-Eliminierung. 

Mit Acyl-hydrazinen lassen sich ebenfalls 2-Amino-l,3,4-oxadiazole zunachst zu Kohlensau-re-bis-[2-acyl-hydrazid]-imiden261 654 734 spalten, die zu 1,2,4-Triazolen eyclisicrt werden konnen. 

Die RingdfTnung mit Kohlensaure-ester-hydraziden verlauft analog zu Kohlensaure-(2-acyl-hydrazid)-i mi d-(2-organooxycarbonyl-hydr azide n)735,736. 

Thio)Kohlensaure-amid-hydrazid-Hydrochloride spalten 2-Amino-l,3,4-oxadiazole zu Koh-lensaure-(2-acyl-hydrazid)-(2-ami nocar bo nyl-hydrazid)-imiden bzw. -(2-acyl-hy-drazid)-[2-(amino-thiocarbonyl)-hydrazid]-imid-Hydrochloriden, die sich z.B. mit 2N Natronlaugc zu 3-(Aminocarbonyl-hydrazino)- bzw. 3-[(Amino-thiocarbonyl)-hydrazino]-l,2,4-triazolen cyclisieren lassen737-784,785 ... 

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