2- Phenyl-7-methyl triazolo

Chloro-1 -methyl-5-phenyl-s-trizolo[4,3-a]quinoline A stirred mixture of 6triethyl-orthoacetate (0.925 g,0.0057 mol) and xylene (100 ml) was refluxed, under nitrogen, for 2 hours 40 minutes. During this period the ethanol formed in the reaction was removed by distillation through a short,glass helix-packed column. The mixture was concentrated to dryness In vacuo and the residue was crystallized from methanol-ethyl acetate to give 1.28 g of 7-chloro-1-methyl-5-phenyl-s-triazolo[4,3-a]-quinoline (83.9% yield). The analytical sample was crystallized from methylene chloride methanol and had a melting point 252.5°-253.5°C. 

The first single-crystal structure was reported for 6-methyl-3-phenyl-.r-triazolo[3,4-3]-l,3,4-thiadiazole in which the nucleus of the triazolothiadiazole system was planar confirming the aromatic character of the lOn-electron system <1974CSC7>. This is generally the case for the entire series of 5,5-fused heterocycles. 

For 2-methyl-5-phenyl-s-triazolo[3,4-61-1,3,4-thiadiazole (350) and 4-methyl-s-triazolo[3,4-6]benzothiazole (182, R = Me), dipole moments were found to be 4.96 and 5.98, respectively.435 For compounds containing only nitrogen as a heteroatom, dipole moment measurements have been used to study annular tautomerism (Section IV,A,1) using Eq. (36).356... 

Chloro-2-(3-methyl-4H-l,2,4-triazol-4-yl)benzophenone (Oxidation of 7-chloro-l-methyl-5-phenyl-s-trizolo[4,3-a]quinoline) A stirred suspension of 7-chloro-l-methyl-5-phenyl-s-triazolo[4,3-a] quinoline (2,94 g, 0.01 mol) in acetone (110 ml) was cooled in an ice-bath and treated slowly with a solution prepared by adding sodium periodate (2 g) to a stirred suspension of ruthenium dioxide (200 mg) in water (35 ml). The mixture became dark. Additional sodium periodate (8 g) was added during the next 15 minutes. The ice-bath was removed and the mixture was stirred for 45 minutes. Additional sodium periodate (4 g) was added and the mixture was stirred at ambient temperature for 18 hours and filtered. The solid was washed with acetone and the combined filtrate was concentrated in vacuum. The residue was suspended in water and extracted with methylene chloride. The extract was dried over anhydrous potassium carbonate and concentrated. The residue was chromatographed on silica gel (100 g) with 10% methanol and 90% ethyl acetate 50 ml fractions were collected. The product was eluted in fractions 10-20 and was crystallized from ethyl acetate to give 0.405 g of melting... 

In contrast to the ease of N-functionalization, shown in Scheme 1, the triazolopyridine nucleus is resistant to direct nuclear oxidation or electrophilic additions. Electrophilic additions will occur on aryl substituents for example, nitration of l-phenyltriazolo[4,5-c]pyridine (26) and sulfonation of 2-phenyl-2i/-triazolo[4,5-6]pyridine (28) occur exclusively in the para position of the phenyl ring <34LA(514)279, 38MI 710-01). Nuclear functionalization was observed when l-( -butyl)-5-methyl-tri-azolo[4,5-c]pyridinium iodide (30) was treated with potassium ferricyanide to afford triazolopyridin-4-one (31), as shown in Scheme 2. Similarly, the iodide (30) is converted by either phosphorus oxychloride-phosphorus pentachloride, or bromine or nitric acid to 7-substituted triazolopyridin-4-ones (32) <37LA(529)288>. 

The azene intermediate generated at 115 °C from 3-azido-4-benzylideneamino-5-methyl-s- triazole underwent an intramolecular cyclization at the azomethine linkage to form 1H- 6- methyl-2-phenyl-s-triazolo[3,2-c]-s- triazole (equation 44) (66JHC119). 

The destruction of heterocycles condensed to the 1,2,4-triazine ring can also be treated as a method of substituent modification. For example, the formation of 3-[acetoxy(phenyl)-methyl]-l,2,4-triazines 24 by treatment of [l,2,3]triazolo[5,l-c][l,2,4]triazines with acetic acid,340 and the degradation of the pyrimido[5,4-c]-1.2,4-triazines353 and pyrimido[4,5-e]-1,2,4-triazines to afford 25 and 26, respectively.331 354 Further reactions of this type are discussed in a previous review.8 For a synthesis of l,2,4-triazine-3,5,6-tricarboxylic acid from pyrrolo[2,l-c]benzo-l,2,4-triazine, see also Houben-Weyl, Vol. 4/1 b, p 643. 

Crude 5-methyl-3-phenyl-v-triazolo[3,4-a]pyrimidin-7(4H)-one heated 2 hrs. at 140 7-methyl-3-phenyl-v-triazolo[3,4-a]pyrimidin-5(4H)-one. Y ca. 100%. Reverse rearrangement in the presence of piperidine s. D. R. Sutherland, G. Tennant, and R. J. S. Vevers, Soc. Perkin I 1973, 943. 

Chemicel Name 8-Chloro-1 methyl-6-phenyl-4H-s-triazolo[4,3-a] [1,4]benzodiazepine Common Name —... 

Chloro-2-[l-methyl-4-phenyl(thiosemicarbazido)]quinoxaline (275) gave 7-chloro-3-methyl[ 1,2,4]triazolo[4,3-fl]quinoxalin-3-ium-1 -thiolate (276) (Me2... 

A series of novel l-substituted-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-ones 1 were synthesized by the cyclization of 2-hydrazino-3-phenyl-quinazolin-4(3H) 2 with various one carbon donors. The starting material 2-hydrazino-3-phenylquinazolin-4(3H)-one 2, was synthesized from aniline 7 by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs all the test compounds protected the animals from histamine-induced bronchospasm significantly, whereas the compound l-methyl-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-one lb (percentage protection 70.7%) was found to be equipotent with the reference standard chlorpheniramine maleate (percentage protection 71%). These compounds show negligible sedation (5%) when compared to the reference standard (26%). Hence they could serve as prototype molecules for future development [1,4,5]. 

The Schiff base derivatives 73 of the 3-hetaryl-substituted 4-amino-3-thiol-l,2,4-triazoles, on treatment with acetic anhydride, undergo cyclization to give the corresponding 3-substituted-5-acetyl-5,6-dihydro-6-phenyl[l,2,4]triazolo[3,4-7][l,3,4]thiadiazoles 76 (Equation 16) <1990IJB135>. Similar treatment of 4-(A-bcnzoylamino)-4,5-dihydro-l-methyl-3-mcthylthio-1 //-[ 1,2,4 triazolc-5-thione 77 leads to the [l,2,4]triazolo[3,4-4][l,3,4]thiadiazolium trifluoromethanesulfonate 78 (Equation 17) <1986LA1540>. 

Reaction of 4-chloro-5-methyl-6-phenyl-2-pyrimidinamine (566) with formylhydrazine yielded a mixture of triazolo[4,3 c]pyrimidine (567) and its [l,5-c]isomer 568 (83USP4405780), and boiling 566 with formylhydrazine in DMF containing a 3-A molecular sieve afforded 567 (81GEP3029871) (Scheme 110). 

As previously mentioned, the methyl group of 2-(p-tolyl)-s-triazolo-[l,5-a]pyridine is inert under the conditions of the Anil Synthesis. However, introduction of a chlorine atom in ortho position to this methyl group enables reaction to be carried out at 20°-30°C (Section II,E,3). Thus, for example, from 2-(3-chloro-4-methylphenyl)-j-triazolo[l,5-a]pyridine (19) and Schiff s base 171, the stilbene 172 is formed. In the case of 2-phenyl-7-methyl-j-triazolo[l,5-a]pyridine (173), however, reaction with 171 gives the styryl derivative 174, without additional activation of the methyl group.19... 

Compound 98 was condensed with o-aminothiophenol, 2-aminoethanol, or cystamine in refluxing diphenyl ether through an intermolecular cyclization with the elimination of two molecules of water to give the polyfused derivatives 101-103, respectively. Also, the reactions of 98 with dimethylthiomethylenemalononitrile in boiling dimethylforma-mide (DMF) were studied. The dimethylthiomethylenemalononitrile was prepared via the reaction of malononitrile with CS2 with 2 equiv of methyl iodide in a one-pot reaction using liquid-liquid phase-transfer catalysis (PTC) technique (NaOH/dioxane/tetrabutylammonium bromide (TBAB)). The product of this reaction was identified as 8-cyano-9-imino-7-methylthio-6-oxo-3-phenyl-5,6,8,9-tetrahydro-77/-pyrano[3,2-/][l,2,4]-triazolo[3,4-A][l,3,4]thia-diazepine 104 (Scheme 10). 

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