Nitrile imides

Ammonium salt of any acid Acid amides Acid nitriles Imides of dibasic acids... 

Thioamides have been transformed into the corresponding nitriles. Treatment of primary thioamides by tellurium tetrachloride or selenium tetrachloride in combination with triethylamine affords nitriles.66 Treatment of primary amides and thioamides with l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) gives nitriles.67 Reactions of thioamides with metal carboxylates in organic solvents enables the selective preparation of nitriles, imides or amides depending on the substitution pattern of the starting material (Scheme 33).68... 

The addition of stabilized ylides, e.g. (63), to nitrile imides or oxides gave pyrazoles or isoxazoles respectively (Scheme 23), in extremely clean reactions which probably proceed by electrophilic attack of the dipole at the y-carbon of the phosphorane.66... 

Reactions involving the [4 + 1 + 1] principle, an example of which is shown in equation (136), are rather uncommon and of strictly limited utility [3 + 2 + 1] and [2 + 2 + 2] processes, on th,e other hand, are well known. Representative [3 + 2+1] three-bond formation processes are given in equations (137)—(141), from which it can be seen that the common situation is where ammonia, a substituted amine or formamide constitutes the one-atom fragment. Many [2 + 2 + 2] atom fragment syntheses are known and some are familiar reactions. Thus, the cobalt(I)-catalyzed condensation of nitriles and isocyanates with alkynes gives pyridines and 2-pyridones, often in excellent yield (e.g. equation 142), while the cyclotrimerizations of nitriles, imidates, isocyanates, etc., are well established procedures for the synthesis of 1,3,5-triazine derivatives (e.g. equation 143). Further representative examples are given in equations (144)-(147), and the reader is referred to the monograph chapters for full discussion of these and other [2 + 2 + 2] processes. Examination of the... 

N Compounds (without Amides. Nitriles. Imides N-cycles and N-hetarencs)... 

Arylmethylene)-5-phenyl-2(3/f)-furanones (22) react with nitrile imide 23, generated in situ, to give the spiropyrazones 24. The reaction was shown to be regioselective by and 13C NMR analysis of the reaction products. The spiropyrazoles 24 were converted by hydrolysis and methanolysis into the corresponding pyrazolecarboxylic acids 25 and car-boxylates 26, respectively (Scheme 7) [93JCR(S)80]. 

Far more interesting are the elimination sequences which lead to the generation of reactive heterocumulenes (ketenimines, carbodiimides, isocyanates, isothiocyanates) or 1,3-dipoles (nitrile oxides, nitrile imides, nitrile... 

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. 

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 cyclization of nitrile imides, having a nitro group attached to the o-position of the phenyl ring attached to carbon was already observed by Chattaway and Walker ( 2.23 structure of the isolated products LI was established recently by Gibson... 

Of course, this cyclization occurs via the intermediate nitrile imide. The hydrazidoyl bromide, obtained from benzaldehyde 4-quinazolyl-hydrazone and bromine, could not be isolated, and only the cyclization product has been obtained in good yield... 

If nitrile imides are generated in the presence of a nucleophilic olefin, the corresponding 1,3-cycloaddition products are isolated, usually in good yield (S3,60-70j example, from diphenylnitrile imide and methyl cinnam-ate a mixture of the isomeric pyrazolines LVI and LVII is obtained in 95 % yield ( ). 

In addition to activated olefins, other double-bond substrates, such as carbonyl and thiocarbonyl compounds and azomethines have been used ( ). Likewise, heterocumulenes, such as carbon disulfide, isocyanates, isothiocyanates, carbodiimides, and N-sulfinylamines have been added to nitrile imides ( ). While usually reaction occurs across one of the cumulative double bonds, with carbon disulfide only the bis-adduct LVIII could be isolated ( ). 

Griinanger and Langella ( ) and Huisgen and his co-workers have synthesized pyrazole derivatives in the reaction of nitrile imides with acetylene derivatives. 

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. 

Dehydrohalogenation of hydrazidoyl halides in the presence of furan gave rise to the formation of the 1,3-cycloadducts XLIII of furan and the corresponding nitrile imides ( ). 

When treated with heat or light nitrogen, can be eliminated from tetrazoles and 1,2,3-triazoles. Nitrile imides can be formed by photolysis or thermolysis of 2,5-disubstituted tetrazoles. The nitrile imides can then react... 

Acrylic acid derivatives as well as a,p-unsaturated nitriles, imides, phosphonates, and sulfones have been also studied as Michael acceptors for activated methylenes. Dixon et al. have demonstrated the efficacy of bifunctional cupreidine 125 (Fig. 2.12)... 

When the Neimentowski reaction is carried out under conventional reaction conditions, the yield and purity of the product are significantly affected by the reaction temperature, reaction time, and reagent ratios. As a result, numerous variations and modifications of this reaction have appeared in the literature since its initial discovery over 100 years ago, resulting in improved yields. Variations of the anthranilic acid component inelude the use of o-acylaminobenzamides, ammonium o-acylaminobenzoates, o-aeetamino-benzonitriles, ° methyl anthranilates, acetanthranils, and isatoic anhydrides in place of anthranilic acid. Conditions wherein the amide component has been replaced with either a nitrile, imidate, " thioamide, or amidine have been reported. Reaction conditions including acetic anhydride" and alkaline peroxide were also developed. More recently, reaction conditions under microwave irradiation have been reported.Details regarding these modifications are summarized below. 

Reaction of Anthranilic Acids or Isatoic Anhydrides with Nitriles, Imidates, Thioamides, or Amidines... 

C-Trifluoromethyl-N-phenyl nitrile imide reacts with MeNCS across its C=S bond to give a 14 % yield of the [3+2] cycloadduct... 

Benzimidazoles are reported to have anthelmintic [66], anticancer [67], and antiulcer activities [68]. Usually they are synthesized by the reaction of orffeo-phenylenediamines with aromatic acids, nitrile, imidates, or ortho-esters... 

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