Hydrazination cyclizations with

The effect of the nature of the substituent at the acetylene bond is not so noticeable. Substitution reduces the C-3 activity due to polarization effects and steric factors. As aresult, in the cyclization with hydrazines and hydroxylamines an increase in the content of 5-substituted pyrazoles and isoxazoles is observed (81UK1252). As mentioned above, nonsymmetiic nitrogen-containing binucleophiles H2N—YH (Y = O, NMe, NPh) react with l-heteroalk-l-en-3-ynes in two alternative pathways by functions H2N and YH. 

Hippuric acid, cyclization to 2 phenyl-5 oxazolone with acetic anhydride, 47,101 Holarrhimine, 46, 61 Hydrazine, reaction with cinnamalde-hyde, 47, 99... 

Treatment of 5-(dichlorophenylmethyl)-3-phenyl[ 1,2,4]triazin-6( 1H)-one 357 or the respective ketone with hydrazine or phenylhydrazine gave 358, which were cyclized with acetic acid to pyrazolo[4,3-c][ 1,2,4]triazines 359 (84PHA504 85MI2) (Scheme 77). 

Treatment of 2-acetyl- or 2-formyl-benzimidazole 587 with hydrazines gave the corresponding hydrazones 588, which cyclized with ethyl chloro-formate to give [84JCR(S)384] triazinobenzimidazoles 589. 

Alkylation of chlorotheophylline with chloroacetonitrile gave 608 and cyclization with hydrazine gave [88CI(L)785] triazine derivative 609. Condensation of the latter with different aldehydes gave the corresponding hydrazones. 

Acylation of 965 gave 966, whose cyclization with hydrazine or phenyl hydrazine afforded [89IJC(B)829] triazolotriazines 967 or 968, respectively (Scheme 177). 

Poly(arylene ether ketone)s can also be modified by introducing the functional groups using similar approaches to polysulfones. For example, poly(arylene ether ketone)s were sulfonated.189 In addition, o-dibenzoylbenzene moieties in the poly(arylene ether)s can be transformed to heterocycles by cyclization with small molecules. These polymers can react with hydrazine monohydrate in the presence of a mild acid in chlorobenzene or with benzylamine in a basic medium.190 Another example of the use of the o-benzyl cyclization strategy is the intramolecular ring closure of poly(arylene ketone)s containing 2,2/-dibenzoylbiphenyl units to form poly(arylene ether phenanthrenes).191... 

Treatment of the hydrazine derivative 303 with triethyl orthoformate gives the cyclized compound 304 <1987AP765> (Equation 53). Similarly, treatment of hydrazine 305 with formic acid gives the tricycle 306 the formamide intermediate was not isolated <2001CHE1150> (Equation 54). 

Substituted 1,2,4-triazines were conveniently prepared in one pot by the condensation of amides and 1,2-diketones followed by cyclization with hydrazine hydrate <06MI67>. 

The parent heterocycle of pyrido[2,3-e][l,2,4]triazine and its phenyl derivative 39 were prepared (89JHC475) by cyclization with polyphos-phoric acid of 3-acyIhydrazino-2-aminopyridines 36, obtained by reduction of the corresponding 3-acylhydrazino-2-nitropyridines 35. Compounds 35 were obtained from 3-fluoro-2-nitropyridine 34 either by reaction with benzoylhydrazine or by reaction with hydrazine and subsequent for-mylation of the initially formed 3-hydrazino-2-nitropyridine 38. Attempts to prepare 38 from 3-chloro-2-nitropyridine gave 2-hydrazino-3-chloropyridine 37. These results could be explained by semiempirical calculations (CNDO and MNDO calculations). 

The triazinoquinolines 120 were obtained (80CZ203) by treating the phenacylquinolinium bromides with hydrazine. Cyclization of 2-hydrazi-nocinchoninic acid with pyruvic acid gave 121 (91KGS1227). 

The [l,2,4]triazolo[4, 3 3,4]pyrimido[2,l-c][l,2,4]triazines 253 were prepared (75G1029) by cyclization of hydrazine 251 with phenacyl bromides, which took place via 252. 

This ring system was prepared by the alkylation of [ 1,4]benzothiazinone with ethyl bromoacetate followed by reaction with Lawesson s reagent and cyclization with hydrazine to give the thia analogue of 503 (91MI6). 

Formylation of indole-2-carbohydrazides 644 gave the formylindole-2-carbohydrazide 645, which cyclized with phosphorus oxychloride to the corresponding 1,3,4-oxadiazolylindole 646. Treatment of the latter with hydrazine, followed by cyclization with formic or acetic acid gave [l,2,4]triazolo[3, 4 -/][l,2,4]triazino[4,5-fl]indoles 652 and 653, respectively [90IJC(B)372],... 

The pyrazolotriazinecarboxylate 708 underwent cyclization with urea or thiourea to give (84PHA432) pyrazolopyrimidinotriazines 711, and with o-phenylenediamine, p-chloroaniline, or o-aminophenol to give quinolino-pyrazolotriazines 710. The reaction of the pyrazolo[5,l-c][I,2,4]triazine 709 with hydrazine hydrate gave 712, and its reaction with phenyl isothiocyanate gave 713 (83G219). 

Thiation of [l,2,4]triazino[3,2-h]quinazoline-3,10-dione 782 with phosphorus pentasulfide in pyridine proceeded selectively to give the 3-thioxo analogue 783. The latter was converted to the corresponding 3-methylthio derivative 784 by reaction with methyl iodide. Treatment of 784 with hydrazine gave 785, which was converted to 786 and 787 by cyclization with formic acid or carbon disulfide (90JHC591). Cyclization of 785 with sodium nitrite in hydrochloric acid gave 788 (90JHC591). 

The hydroxymethyl and carboxyl group of Ser can participate in pyrazole-ring formation, as shown in the transformation of A -protected L-Ser with the Mitsunobu reagent into a /3-lactone which afforded the N-protected serine hydrazide upon treatment with methyl hydrazine. Cyclization to 25 was achieved by diisopropyl azodicarboxylate (DIAD) and TPP [90H(31)79]. 

Very little work has been reported on the 1,3,4-selenadiazole system. Ring-opening of 1,3,4-oxadiazolium salts (132) with hydrogen selenide gives 1,2-disubstituted hydrazines (133) which are cyclized with perchloric or fluoroboric acid to give 1,3,4-selenadiazolium salts (134) (Scheme 9)... 

Hydrazone formation of pyridazine-3-hydrazines with aldoses, dialdofuranoses, and dialdopyranoses was studied by Stanovnik and co-workers. The respective hydrazones could be cyclized with Bt2 in MeOH or Pb(OAc)4 to j-triazolo[4,3-3]pyridazin-3-yl substituted polyols <1997JHC1115, 1998JHC513>. Similarly, 4-[(dimethylamino)-methylene]-l,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one was reacted with pyridazine-3-hydrazines and the resulting mixtures were subsequently treated with Pb(OAc)4. Besides j-triazolo[4,3-3]pyridazine formation also diazenes were obtained. This can be rationalized by the enehydrazine-hydrazone mixtures observed in the first reaction. For phthalazin-l-hydrazines only diazenes were obtained after oxidation <2005TA2927>. Also cyclizations of... 

Reaction of hippuric acid and A, A -dimethylacetamide in the presence of phosphorous oxychloride affords 4-[l-(dimethylamino)ethylidene]-2-phenyl-5(4//)-oxazolone 424 " ° that is converted to 4-benzoylaminopyrazolones 425 via ring opening and cyclization with hydrazines (Scheme 7.139). " ° 4-(A, Af-Dimethyl-aminomethylene)-2-substituted-5(477)-oxazolones react similarly. 

Similarly, reaction of hydrazine hydrate with pyridinedicarboxylates 281 in boiling alcohol, followed by cyclization of the resulting dihydrazides 282, gave the pyrido[3,4-r/ pyridazine-l,4-diones 283, where deacetylation has occurred during the formation of 282 (Equation 21) <1997T8225>. 

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