1.2.4- Triazoles, mesoionic

Besides being useful precursors to pyrroles pyridine-2-ones -4-ones, -4-thiones. and -4-imines 4-alkylidene-dihydropyridines thiophenes 1,2,4-triazoles thiapyrane-2-thiones, isoquinoline-3-ones isoben-zothiophenes and 4-mercaptoimidazolium hydroxide inner salts, mesoionic thiazoles are potentially useful in the construction of molecules with herbicidic (39). central nerve stimulating, and antiinflammatory properties (40,41). Application in dye synthesis has likewise been reported (42). 

Mesoionic compounds of the type designated (76AHC(19)l) as A are capable of isomerism. In one case in the 1,2,4-triazole series, isomerism of the pair (64) (65) has been demonstrated (67TL4261). 

Enamines and enolate anions react with benzofuroxan to give quinoxaline di-A -oxides (Scheme 38) (69AHC(10)1). Sydnones (274) with phenyl isocyanate give 1,2,4-triazoles (275) (76AHC(19)l), and from (276) the intermediate adduct (277) can be isolated (73JA8452). This is one of the few instances in which such primary cycloadducts have been isolated in the oxazole series of mesoionic compounds. 

Pyrazolino[2,3-c][l,2,3]triazoles, 5, 702 Pyrazolium hydroxide, l,2-dimethyl-3,5-diphenylanhydro-4-hydroxy-IR spectra, 5, 201 Pyrazolium salts dequatemization, 5, 269 H NMR, 5, 185 hydrogen exchange at ring carbon, 5, 245 mesoionic compounds, 5, 171 nitrodebromination, 5, 237 reactivity, 5, 217 reduction, 5, 68, 243 synthesis, 5, 156 UV spectra, 5, 199 Pyrazolium salts, amino-reactions, 5, 262 Pyrazolium salts, bromo-nucleophilic displacements, 5, 266 Pyrazolium salts, 1,2-dimethyl-deuteration, 5, 175, 245 hydrogen exchange, 5, 71 acid-catalyzed, 5, 239 reactions... 

Most of the reported 1,2,5,6-tetrazocine systems probably do not exist in the monocyclic form but rather as the tetraazapentalene betaine structure (see Introduction) 2 3 7"13 for the tetra-phenyl-substituted system, the compound does actually exist as the mesoionic tetraphenyl-[1,2.3]triazolo[l,2-h][l,2,3]triazole, as determined by H and 13C NMR spectroscopy.15 The following syntheses arc therefore questionable. 

The mesoionic tetrazole dehydrodithizone is transformed by iron penta-carbonyl into 4-phenyl-2-phenylazo-A2-l,3,4-thiadiazolin-5-one, presumably by a mechanism of ring opening, complexation, carbonyl insertion and subsequent ring closure (Scheme 128).193 Unfortunately, analogous processes do not occur on other mesoionic compounds in the 1,2,3-oxadiazole, s-triazole or tetrazole series, and the scope of this unusual carbonylation is probably limited. 

The novel mesoionic 1,2,4-thiadiazole 78 was reported to be the unexpected byproduct in the reaction of the triazole 76 with ferric chloride (the bicyclic compound 77 also gave the same result). Besides spectroscopic and X-ray diffraction evidence, a preparative proof for the structure of 78 was also provided <00JHC261>. 

Contrasting with the reported formation of fused [l,3,4]thiadiazole rings in the course of the reaction of 3-substituted-4-amino-5-thio-47/-[l,2,4]triazoles 83 with various isothiocyanates (cf. Section 11.07.8.3, Table 3), the reactions with methyl isothiocyanate and with phenylisocyanate afford 3,7-disubstituted-6,7-dihydro-57/-[l,2,4]triazolo[4,3-f] [l,2,4]triazole-6-thiones 110 and -triazole-6-ones 111, respectively (Equation 29) <1986MI607, 1992IJB167>.The same reaction of 4-amino-l-methyl-3,5-bis(methylthio)[l,2,4]triazolium iodide 112 with aryl isothiocyanates yields the mesoionic compounds 113 (Equation 30) <1984TL5427, 1986T2121>. 

Matsuda et al. described the cyclization to a mesoionic derivative of the title ring system <1995H(41)329>. The starting compound of the ring-closure reaction is the anion 416, which was easily obtainable from ethyl [l,2,4]triazol-1-ylacetate with potassium bromide. Upon heating this compound, ring closure to the zwitterionic 417 takes place in 40% yield. 

Linear triazenes are likely intermediates in some triazole syntheses and have been employed as precursors of a few triazoles the reaction is useful for preparing mesoionic triazolium-... 

The azetidinone (124) reacts with phenylhydrazine to give the mesoionic triazole (125) (Equation (48)) <83TL1035>. 

Three methods for making 4,5,6,7-tetrahydrotriazoIopyridines use two fragments to form the triazole ring. The lithium derivative of A/-nitro-sopiperidine reacts with benzonitrile to give the 3-phenyl derivative 19.28 Diazonium salts react with a-amino acids to give mesoionic triazole oxides if pipecolic acid is used, the product is a tetrahydrotriazolopyridine 3-oxide... 

Catalytic reduction of the derivatives of triazolopyridines invariably attacks the pyridine ring, leaving the triazole. There is no report of reduction of compound 1, but 3-nitrotriazolopyridine (154) gives as major product the tetrahydrotriazolopyridinamine 155.229 Reduction with palladium-charcoal takes a different course (see Section IV,F). The mesoionic derivatives of [l,2,4]triazolo[l,5-a]pyridine 156-15854 and 159230 are reduced to py-tetrahydro derivatives, as is compound 3,231 although it had previously been reported that 3-substituted derivatives of compound 3 were not reduced.65 Chloro[l, 2,3]triazolo[4,5-6]pyridine (160) is reductively dehalogenated with reduction of the pyridine ring by platinum or palladium catalysts.146 By addition of base the reduction can be stopped at compound 4 (see Section... 

The f-triazole ring is also produced by intramolecular cyclization of an azide substituent to an azo group in this way the mesoionic v-triazolo[4,5-d]-i>-triazole (58) was obtained by heating 4-azido-2-phenyl-... 

Potts and McKeough81 have recently obtained several interesting mesoionic azapentalenes 83, 84 by reaction of the appropriate 1,4-dicarbonyl compound with phosphorus pentasulfide. Compounds 83 and 84 can be written as dipolar structures, but participation of sulfur d-orbitals allows nonpolar forms to be envisaged. MO calculations neglecting rf-orbital participation predict the thieno[3,4-c]pyrrole system (84) to be very unstable.430 A related system 86 has been prepared by Japanese workers63 from the diamino-r-triazole (85) and sulfur dichloride. 

The hydroxytriazole 1-oxides 500 and 502 when treated with methyl iodide were methylated predominantly at the N-oxygen affording mesoionic anhydro l-methoxy-3-methyl-4-hydroxy- or 5-hydroxy-l,2,3-triazolium hydroxide 501 or 503 (Scheme 146) (1987ACSA(B)724). In both cases methylation at the C-hydroxy group took place to a minor extent giving rise to methoxy-substituted triazole 1-oxides 499 or 503, respectively. Under similar conditions 3-methyl 4-hydroxy-5-chloro-l,2,3-triazole 1-oxide 505 produced a 2 1 mixture of the C-methoxy and the N-methoxy derivatives 504 and 506. The mesoionic triazoles 501, 503, and 506 were dealkylated upon heating with 1-M sodium methoxide, reforming the hydroxy-substituted N-oxides 500, 502, and 505, respectively. 

Amino-l,3,4-thiadiazoIium salts (97) on treatment with alkali rearrange to mesoionic l,2,4-triazole-3-thiones (98) probably by deprotonation of (97), nucleophilic attack at C-5, followed by ring cleavage and recyclization to (98) (75SST(3)687, p. 690). ... 

A number of mesoionic 1,2,3,4-oxa- and -thia-triazoles, prepared by standard methods, were assessed for pesticidal and herbicidal activity (79BRP2015878). Pharmacological activity of mesoionic compounds has been reviewed (76AHC(19)l). 

Numerous structures containing the thiocarbonyl ylide dipole are conceivable. Incorporation of the thiocarbonyl ylide dipole into a bicyclic heterocyclic system is possible by the conversion of the cyclic thione (203) into the ring-fused mesoionic system (204). The thiocarbonyl ylide dipole (205) undergoes cycloaddition with both alkenic and alkynic electron-poor dipolarophiles in refluxing benzene or xylene so that, after extrusion of hydrogen sulfide or sulfur, respectively, from the initial 1 1 cycloadducts (206) and (207), a ring-fused pyridinone is formed. The method has been used for the annelation of pyridinones to the imidazole, 1,2,4-triazole, thiazole and 1,3,4-thiadiazole systems... 

Syntheses of fused mesoionic heterocycles such as [l,2,3]triazolo[l,5-a]-quinoline, -quinazoline, -quinoxaline, and -benzotriazine derivatives have been described <02T3185>. Cyclizations of alkyl 2-benzoylamino-(4,5-dicyano-1 //-1,2,3-triazol-1 -yl)propenoates gave [1,2,3]triazolo[l, 5-a]pyrazines <02H(56)353>. Reaction of triethyl N-( 1 -ethy 1-2-methy 1-4-nitro-l//-imidazol-5-yl)phosphorimidate with aryl isocyanates provided a route to 2-aryI-2//,4//-imidazo[4,5-fif][l,2,3]triazoles <02JCS(P 1)1968>. 2-(A,A-Diphenylamino)-4-hydrazino-6-... 

Also, reaction of N-aminoheterocycles 650 with arylcarbodiimides affords fused mesoionic 1,2,4-triazoles 651. ... 

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