Hydrazidoyl Halides

The chlorides derived from the reaction of aroyl phenylhydrazines with phosphorus pentachloride are recorded in the literature under a variety of names. While Chemical Abstracts lists these compounds as the phenyl-hydrazones of the corresponding acid chlorides (for example, benzoyl chloride phenylhydrazone for C H5CiCl)=NNHC H5), Beilstein uses the terms a-chlorobenzyliden phenylhydrazine or a-chlorobenzal phenyl-hydrazine for this compound. In view of the relationship of the chlorides I with the corresponding acid hydrazides (II), their hydrolysis products, the names hydrazide chlorides or hydrazidoyl chlorides are more appropriate. In order to preserve conformity of nomenclature, the latter name is used in this book. 

N-Phenylbenzhydrazidoyl chloride was first synthesized by v. Pech-mann in 1894. In their reactions hydrazidoyl chlorides bear a close resemblance to the other imidoyl chlorides. They have been used by Fusco and his co-workers to synthesize a variety of pyrazole derivatives, and recently Huisgen and his students utilized this class of compounds to generate the highly reactive nitrile imides. The latter compounds react as 1,3-dipoles with a wide variety of substrates to form the corresponding five-membered ring heterocycles, which are often quite difficult to synthesize by other routes. 

In addition to the N-arylhydrazidoyl chlorides, numerous N-substituted compounds, such as the N-carboxylic acid derivatives, have been synthesized. 

Although the reaction of the corresponding carboxylic acid hydrazides with phosphorus halides can be used to synthesize the compounds under discussion, several different methods have been utilized in the past to synthesize hydrazidoyl halides. For example, the coupling of benzdiazonium 

The reactivity of hydrazidoyl halides in nucleophilic reactions, as well as the ready elimination of hydrogen halides to afford the highly reactive nitrile imines renders this class of compounds quite useful in organic synthesis. 

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Electrochemical oxidation of hydrazidoyl halides (330) also affords 1,4-dihydro-1,2,4,5-tetrazines (104). A nitrilimine intermediate is not suggested for this reaction. The main process is the dehydrodimerization of the initially formed hydrazonyl radical, while a concurrent side-reaction leads to the l,4-dihydro-l,2,4,5-tetrazines (104), which are transformed into the corresponding cation radicals (336) on further oxidation (77IZV393, b-75MI22102). 

A synthesis of 4-cyano-2,3-dihydro-3-hydroxy-2,5-diphenyl-l//-l,2,3-diazaphosphole 3-oxide from hydrazidoyl halide PhC(Cl)=NNHPh and diethylphosphonoacetonitrile in the presence of sodium ethoxide was reported <2004PS(179)521 >. 

Hydrazidoyl halides in synthesis of N,O-heterocycles 80JHC833. Intramolecular [4 + 2]-cycloaddition with formation of O-heterocycles ... 

Heterocyclization of unsaturated S-containing compounds 86KGS291. Hydrazidoyl halides, synthesis of N,S-heterocycles from 83H(20)2239 ... 

Coordination chemistry of Se- and Te-heterocycles 81CRV365. Hydrazidoyl halides in synthesis of N,Se-heterocycles 80JHC833. 

A.S Shawali, Reactions of Hydrazidoyl Halides with Sulfur Compounds, Heterocycles 20, 2239 (1983). M.H. Elnagdi u. M.R.H. Elmoghayer, Adv. Heterocyci. Chem. 48, 223 (1990) Chemistry of Pyrazoles Condensed to Heteroaromatic Five- and Six-memhered Rings. 

Hydrazidoyl halides react with 2-amino[l,2,4]triazole to give 5-substituted 6-arylhydrazono-6//-imidazo[l,2-i][l,2,4]triazoles (350) and 6-arylhydrazono-5,6-dihydro-4//-imidazo[l,2-/>][ 1,2,4]-triazol-5-ones (351), respectively the latter products are not determined with respect to the tautomeric structures of the H-, 3H-, or 4/7-form (Scheme 32) <83JHC639>. 

Carbonimidoyl dihalides Imidoyl halides Haloformamidines Haloformimidates Halothioformimidates Hydroxamoyl halides Hydrazidoyl halides... 

The coupling of diazonium halides with suitable halogenated activated methylene groups is an excellent method of synthesis of a variety of acyl and aroyl hydrazidoyl halides. This method has been used by Favrel and by Dieckmann and Platz to synthesize the acetyl derivative (IV). 

The halogenation of the arylhydrazones of arylaldehydes is an excellent method of synthesis of hydrazidoyl halides. However, halogenation of the ring attached to nitrogen can not be avoided. For example, reaction of benzaldehyde phenylhydrazone (XI) with bromine in glacial acetic acid... 

The hitherto-synthesized hydrazidoyl halides are listed in Tables I and II. 

Hydrazidoyl halides are solid compounds which contain a reactive halo group. The halo group participates readily in nucleophilic reactions (see Section IV) and perhaps elimination of hydrogen halide occurs prior to substitution. The elimination of hydrogen halide affords the highly reactive nitrile imides XXXIV, which Huisgen and his co-workers (35,60-70j have utilized in a wide variety of 1,3-cycloaddition reactions. 

The characteristic spectral feature of the hydrazidoyl halides is their C=N double bond absorption in the infrared, which appears at 1580-1610 cm- (69,81,84)... 

The reaction of hydrazidoyl halides with water is rather sluggish, most likely due to their insolubility in water ( ), because in dioxane rapid reaction to the corresponding carboxylic acid hydrazides PCXXV) has been observed ( ). 

The hydrolysis of hydrazidoyl halides in hydrochloric acid gives rise to the formation of the corresponding arylhydrazines Reduction... 

Hydrazidoyl halides, upon treatment with sodium acetate or sodium benzoate, yield the N-substituted rearrangement products XXXVII (1 27,28 ... 

Although the corresponding thio compounds should be readily available from hydrazidoyl halides and hydrogen sulfide or mercaptans, respectively, these reactions are not reported in the literature. However, Fusco and Musante investigated the reaction of thiocarbonic acid 0-esters with hydrazidoyl bromides. 

Recently, Barnish and Gibson ( ) treated hydrazidoyl halides, substituted in the o-position of the phenyl ring attached to nitrogen by fluoro and bromo groups, with potassium thioacetate, and the authors obtained 1,3,4-benzothiadiazine derivatives XXXVIII. 

The reaction of hydrazidoyl halides with ammonia, primary and secondary amines, and hydrazines occurs as expected to produce the corresponding substitution products XXXIX (5-10,14,17,18,20,21,22,27,30,31,33,... 

In the reaction of hydrazidoyl halides XLIV with secondary amines decarboxylation occurs, and the substitution products XLV are isolated ( ). 

Tertiary amines afford either amine salts or ylides upon mixing with hydrazidoyl halides ( 5,76,88 ... 

Similarly, reaction of hydrazidoyl halides with sodium cyanate ( ), potassium selenocyanate and sodium azide has been reported. For example, decarboxylation occurs when the carboxylic acid derivative XLIV is treated with sodium azide, and the tetrazole derivative XLVI is isolated... 

The reaction of hydrazidoyl halides with potassium cyanide yields the nitriles XLVII ( ). 

The reactions of hydrazidoyl halides with a variety of activated methylene compounds, such as ethyl cyanoacetate, diethyl malonate, malononitrile, etc., have been used to synthesize a huge variety of pyrazole derivatives ( . 4- 8.52.74-75 ... 

Further work related to the cyclization of the nitrile imides, generated from N-o-nitroarylhydrazidoyl bromides, has appeared ( ), and the reaction of hydrazidoyl halides with azide ion and phenylhydrazine has been studied. Lozinskii et al. have shown that chlorooxalylarylhydrazidoyl chlorides (see Chapter 7) react with azide ion preferentially on the halo group attached to the carbonyl group. 

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