1.2.4- Triazoles sulfur-substituted

Various synthetic protocols were available for the preparation of 1,2,4-triazoles and derivatives thereof Efhcient synthesis of 3,4,5-tri-substituted 1,2,4-triazoles 171 was accompHshed from the reaction of guanidines 169 with 2,2,2-tri-chloroethylimidates 170 in PEG-400 (14TL177). 3,5-Diaryl-l,2,4-triazoles 173 were synthesized from a domino nucleophilic substitution/ oxidative cycfr-zation sequence from 2 equivalents of amidines 172 with copper catalyst, sodium bicarbonate as base, 1,10-phenanthroline as an additive, and K3[Fe(CN)6]/air as the oxidant (14T1635). Sulfur-substituted 1,2,4-triazoles... 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Thiadiazinotriazolopyrimidines can be prepared in several ways from the hydrazine-substituted thiadiazino-pyrimidine 186. Reaction with carbon disulfide gives the thione 187 reaction with either anhydrides or orthoformates with sulfuric acid gives the substituted triazoles 188, and reaction with cyanogen iodide gives the aminotriazole 189 (Scheme 47) <2004HC0335>. 

A general route to [l,2,4]triazolo[3,2-A][l,3]thiazines was discovered by Britsun etal. <2001ZOR1102, 2004KGS1256, 2004ZOR260>. In these publications, reaction of triazole thiones 332 with various substituted acrylic chlorides was reported to yield a series of ring-closed products 333 with the substituent of the reagent in the six-membered ring at the position adjacent to the sulfur atom. 

A direct aza-Wittig cyclization to triazolotriazine 176 (Scheme 67) takes place when triazinone 174 is treated with diphenylthiourea, the latter being substituted on the nitrogen. Elimination of triphenylphosphane sulfide from 175 makes 1,2,4-triazole accessible [86JCS(P1)2037]. When the nucleophilic attack continues on the sulfur, thiadiazoles are formed [86JCS(P1)2037]. 

In the reactions with phosphonio-a-methoxycarbonyl-alkanides, the products of type 261 derived from 1,3-cycloaddition can rearrange to the tautomeric lif-pyrazolo-triazole (87MI2). The reaction of 3-diazopyra-zoles and 3-diazoindazole with acyl-substituted phosphonium ylides led to pyrazolo-triazine and indazolo-triazine derivatives 266 instead of the expected triazole compounds (8IJHC675). In this case, the ylides, which can exist as phosphonium enolates, possess nucleophilic and electrophilic centers in a /8-relationship, giving [7 + 2] or [11 -I- 2]cycloaddition reactions. With dimethylsulfonio-a-aroyl-methanides, very complex, temperature-dependent mixtures were obtained, in some cases with sulfur retention (87MI3). 

Aminotriazoles which are appropriately substituted at the C(5)-position are important intermediates for the synthesis of 8-azapurines. These reactions have been reviewed <86AHC(39)ll7>. The pharmaceutically useful acyclonucleosides bearing 1,2,3-triazolines and 8-azapurines have been synthesized <888879). 4,5-Diaminotriazoles react with 1,2-dicarbonyl reagents to give 1,2,3-triazolo[4,5- )]pyrazines. 4,5-Diamino-2-phenyltriazole and sulfur monochloride afford the triazolo[4,5-c][l,2,5]thiadiazole (855) <86AHC(40)129>. The synthesis of triazolopyridines from triazoles has been described in a review <83AHC(34)79>. For further applications of substituted triazoles in preparations of complex heterocycles, see Section 4.01.4. 

N-substituted triazoles on treatment with sulfur give the thione <66MI 402-01, 70JCS(C)2403>, but the corresponding oxidation and amination reactions appear not to be known. 

When 3-substituted triazolo[4,5-rf]pyrimidines 102 are treated with sulfuric acid and a compound containing an active methylene group, triazolo[4,5-b]pyridines 103 are formed, presumably via the 5-amino-4-formyltriazole.193 Cyclization of the triazole 104 gives an aminocyanotria-... 

The isomeric 3-substituted 4-chloro-l,2,3-triazole 1-oxides 470 reacted in a similar fashion. The chlorine in 470 is situated in the position most reactive toward nucleophilic displacement and is substituted with sulfide when sulfur or Me2S2 is used as an electrophile (1987ACSA(B)724, 2009UP1). A mechanism is suggested in Scheme 144. 

The 3-substituted 1,2,3-triazole 1-oxides 448 were alkylated at the oxygen by trimethyloxonium tetrafluoroborate using liquid sulfur dioxide as the solvent affording hygroscopic 3-substituted l-methoxy-l,2,3-triazolium tetrafluoroborate 507 in high yield (1987ACSA(B)724).The reactivity of these salts has not been reported (Scheme 147). 

In general, the substituted benzophenone and substituted benzo-triazole ultraviolet absorbers were equally effective in protecting vinyl films during outdoor exposure in the absence of biocide. In the presence of the organic sulfur biocide failure was evident the arsine-epoxy adduct produced no adverse effect. The organic tin biocide was only slightly less effective (Table VI). 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

The C-H acidity is also the cause of the reaction of 1,2,4-triazole 4-imines with elemental sulfur [Eq. (12)]82-87 (see Section III,F). It is not clear whether this reaction is an electrophilic substitution or whether it proceeds via an intermediate ylid/carbene (94/95). 

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