Hydrazonoyl chlorides

Another 1,7-dipolar cyclization leading to 1,2-benzodiazepines, but with the difference that a C-C bond is formed, is the ring closure of the nitrile imines 15 to give 17 by a [1,5]-sigmatropic shift of hydrogen in the intermediates 16. The nitrile imines are generated from the (2-vinylphenyl)hydrazonoyl chlorides 14."8 120... 

Et3N (0.137 mL, 0.98 mmol) was added slowly to a stirred solution of the hydrazonoyl chloride 9 (0.44 g, 1.91 mmol) in tetrachlorocyclopropcne (1 mL, 8.7 mmol) and the mixture was left at 20 C for 6-7d. Evaporation under reduced pressure, followed by layer chromatography (Et20/petroleum ether 1 4) of a solution of the residue in CI1C13. gave the yellow crystalline product yield 0.16 g (93 %) mp 97-97.5 C. 

Tri azo lino [4,3 -a] py ri mi din cs, pyrazolo[3,4-<7]pyridazines and isozazolo[3,4-<7]pyridazines have been synthesized from hydrazonoyl chlorides <06SC97>. 

Diphenylnitrilimine (DNPI) can be subjected to 1,3-dipolar cycloaddition with activated double bonds as dipolarophiles (Eq. 54). It can be generated in situ by reaction of hydrazonoyl chloride with a base. 

When 5-phenyl-l,2,4-triazole-3-thiol 437 reacts with bis-hydrazonoyl chloride, in ethanol in the presence of sodium ethoxide (or in refluxing choloroform in the presence of triethylamine), compound 47 is obtained (Equation 95) <2002MI7>. 

When bis-hydrazonoyl chloride is treated with 3-mercapto-l,2,4-triazole 431 (R = H) in ethanol in the presence of triethylamine at reflux, compound 34 is isolated in 52% yield (Equation 99) <2004JCR(S)264>. 

The cycloaddition of nitrilimines toward furo[3,4-c]thieno[2,3-r7]-pyrazoles has been investigated as a function of the electron-withdrawing or electron-donating character of the substituents attached to the aromatic rings <2000H(53)917>. For instance, nitrilimine 459, obtained in situ from hydrazonoyl chloride 458, by base treatment with silver carbonate in dioxane, when reacted with 460, gives a mixture of compounds 461 and 63 (Scheme 53) <2000H(53)917>. 

Bis-phenylhydrazono derivative of thiazolo[3,2-A [l,2,4]triazole 47 is obtained (Equation 108) by reacting bis-hydrazonoyl chloride with 1-benzoylthiosemicarbazide 467 <2002MI7>. 

Ring closure of triazinyl diester 276 was reported by Moderhack etal. <2002M1165>. This compound was treated with hydrazonoyl chloride in the presence of triethylamine in refluxing benzene. Formation of the intermediate 277 was anticipated, which, upon intramolecular cyclization, afforded the fused triazole 278 in medium yield (42%). Syntheses of other related compounds via modified synthetic routes have also been described. 

Reaction of 70 with morpholine gave hydrazonoyl chlorides 124 in good yield. When halides 124 were refluxed in 80% aqueous dioxane, they yielded the oxadiazoles 125, presumably via cyclization of the intermediate... 

Cyclization of C-ethoxycarbonyl-iV-heteroarylhydrazonoyl chlorides 5 also led to different products according to the reaction condition. Thus, the 7V-(5-pyrazolyl)hydrazonoyl chlorides 5f and g cyclized readily to give 174a and b, respectively, upon treatment with triethylamine in benzene... 

C-Acetyl- and C-ethoxycarbonyl-A/-(5-triazolyl)hydrazonoyl chlorides 10a and 10b did not cyclize upon refluxing in ethanol in the presence of triethylamine, but they yielded the ethyl hydrazonate esters 190a and 190b, respectively (80JHC209). 

The nitrilimines generated from Af-(3-phenylpyrazol-5-yl)hydrazonoyl chlorides 5a,f cycloadd carbon disulfide, phenylisothiocyanate, acetonitrile, and p-chlorobenzaldehyde in pyridine to provide the corresponding cycloadducts 218-221, respectively (77HCA2171). 

Treatment of C-ethoxycarbonyl-N-(2-benzimidazolyl)hydrazonoyl chloride 21c with phenylhydrazine was reported (82MI1) to give hydrochloride salt 273. Another report (83MI1) indicated that this same reaction afforded a product that was assigned structure 274. The structure of this product needs to be reinvestigated. 

Reaction of N-5-(3-phenylpyrazolyl)hydrazonoyl chlorides 5 with potassium cyanide in ethanol were reported to give different products. Thus, whereas reaction of 5a with potassium cyanide yielded 324 (77JHC227), reactions of /V-(5-pyrazolyl)hydrazonoyl chlorides 5f (77JHC227) and 5g (89MI1) yielded the pyrazolo-as-triazine derivatives 325a and b. Also, reaction of potassium cyanide with 5k yielded 325c (77JHC227). 

Likewise, the sulfonylhydrazones 337a-c prepared from reactions of sodium benzenesulfinate with hydrazonoyl chlorides 20a-c in ethanol at room temperature cyclized in situ to give 338a, 338b, and 339, respectively (87MI1). 

Substituted tetrazoles react rapidly with salt 20 at room temperature to give hydrazonoyl chlorides 80 in high yield <2002J(P1)1535>. 5-Aminotetrazole reacts further to afford extended bis(imino)dithiazole 81 (Scheme 7). The proposed mechanisms include the attack of a tetrazole nitrogen on the carbon atom of Appel salt followed by opening... 

A study of the 1,3-dipolar cycloaddition of pyrazines, pyrimidines and l//-pyrimidinthiones with nitrilimines (80), generated in situ by dehydrohalogenation of the corresponding hydrazonoyl chlorides (79), was carried out. Reaction of pyrimidine-2( l//)-thiones (81) and -4(l//)-thiones with nitrilimines in benzene at reflux gave spiro[pyrimidine-2(l//), 2 (3 f/)-[ 1,3,4]thiadiazoles... 

A new efficient synthesis of dihydro-1,3,4-benzotriazepin-5-ones is referred to in a report by Al-Abadelah et al. The strategy is based on ring construction starting with the reaction of anthranilic acid and the hydrazonoyl chlorides 292 to give compounds 293, followed by CDI-mediated cyclisation to 294. While 294 could also exist as the tautomer 295, single crystal X-... 

Upon base treatment with silver carbonate, isoxazolyl-substituted hydrazonoyl chlorides underwent a sequential intra-intermolecular nitrilimine 1,3-dipolar cycloaddition, leading to tetracyclic pyrazolidines (Equation 6) <2000H(53)831>. 

Various benzimidazole derivatives can be fused between the C-2 and N-1 positions in order to build novel heterocyclic ring systems. For example, the reaction of 2-cyanomethylbenzimidazole 73 with hydrazonoyl halides 74 in the presence of triethylamine led to the formation of pyrrolo[l,2-a]benzimid-azoles 76 (Scheme 16) [60]. It has been suggested that the reaction starts with the nucleophilic substitution of the halogen by the benzimidazole carban-ion to give intermediate 75, which upon cyclization via elimination of water gives the desired cyclic pyrrolobenzimidazoles 76. On the other hand, the reaction of hydrazonoyl chlorides 77 with 2-cyanomethylbenzimidazole 73 in sodium ethoxide afforded pyrazole-3-carboxylate 80, which upon treatment under triethylamine yielded the pyrazolopyrrolobenzimidazole 81. The product was also obtained by the direct reaction of 2-cyanomethylbenzimidazole 73 with hydrazonoyl chlorides 77 in the presence of triethylamine. 

Prior treament of hydrazonoyl chloride with a base is necessary to generate the reactive species DPNI, which subsequently adds to electrophilic double bonds. The overall reactions were performed by simultaneous impregnation of hydrazonoyl chloride and dipolarophile on KF/alumina as basic system. DPNI is formed in situ and reacts in a one-pot procedure (Scheme 26). 

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