Chloro-l,2,4-triazoles

Chlorination of 1,2,4-triazoles may be carried out in organic solvents (diethyl ether, carbon tetrachloride) in the presence of acceptors of hydrogen 

5-Disubstituted 1,2,4-triazoles with the same R1 and R2 substituents react with chlorine to form 1-chloroderivatives 43. When R1 and R2 are different, the chlorine atom occupies the position close to an electron-donating substituent and far from an electron-accepting one (68MIP1 69KGS1114 72JPR923 90IZV2814). 

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Leaving groups at C5 of 2-substituted 1,2,3-triazoles are predicted to be the most reactive in nucleophilic aromatic substitution reactions following an AE mechanism (see Section 1.4.2). Accordingly, chlorine at C5 of 360 could be replaced by strong nucleophiles like methanethiolate or methoxide to give 377 or 378. The unactivated 2-phenyl-4-chloro-l,2,3-triazole 380 (R=Ph) was inert toward these nucleophiles (1981JCS(P1)503) (Scheme 115). 

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. 

Halogeno-l-methyl-l,2,3-triazoles undergo substitution reactions with amines, but the 4-halogeno analogs do not. 5-Chloro-l,4-diphenyl-l,2,3-triazole with sodium cyanide in DMSO gives the cyano derivative (63JCS2032). 1-Substituted 3-chloro- and 5-chloro-l,2,4-triazoles both react with amines. 

Methyl- and 2-phenyl-triazole 1-oxide (207) are silylated selectively at the 5-position with trimethylsilyl triflate to afford stable 5-trimethylsilyl derivatives (208) (Scheme 35). If the 5-position is blocked with a substituent, the 4-position is silylated. Thus, 5-chlorotriazole 1-oxide is converted to 5-chloro-4-trimethylsilyl-l,2,3-triazole 1-oxide in the presence of lithium tetramethylpiperidine. 

Chloro-l,2,3-triazole-4-carbonyl chloride (372) condenses with o-aminophenol in ethyl acetate... 

Thieno[3,4-triazoles synthesis, 6, 1042 Thieno[3,4-d][ 1,2,3]triazoles reactions, 6, 1036 synthesis, 6, 1044 Thienyl radicals generation, 4, 832 Thiepane, 2-acetoxy-synthesis, 7, 574 Thiepane, 2-chloro-nucleophilic substitution, 7, 573 synthesis, 7, 574 Thiepane, 2-methyl-synthesis, 7, 573 Thiepane, 2-phenyl-synthesis, 7, 573 Thiepane, 3,3,6,6-tetramethyl-cycloaddition reactions, 7, 574 Thiepanes, 7, 547-592 applications, 7, 591... 

Dechlorination of the 4-chloro or 5-chloro-l, 2,3-triazole 1-oxide 470 or 467 required treatment with nickel boride, which caused loss of the N-oxygen and furnished 478 (Scheme 139). 

While 5-chloro-l,2,3-triazole 1-oxide 467 reacted with sodium methox-ide with replacement of the chlorine (see Section 4.1.6.8), the corresponding bromo compound 468 under similar conditions afforded the cme-substitution product 483 as the main product (1987ACSA(B)724). A mechanism involving halogen dance and supported by control experiments is sketched in Scheme 142. The bromine in 468 is located at the less activated position with respect to nucleophilic displacement. On the other... 

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. 

Both direct and indirect syntheses of chloro-l,2,3-triazoles have been carried out. In the former approach, the reagent employed exerts an important influence on the product yield (Eqs. 2,3). A large number of additional combinations were tried but without synthetically useful results. It has also been shown that cyanogen chloride reacts with trimethylsilyl-diazomethane to give chloro-1,2,3-triazoles (Eq. 4) in fair yield. 

Bis(l-methylbenzotriazole)cobalt(II) nitrate, 3652 A-Chloro-4,5 -dimethy ltriazole, 1490 5-Cyano-4-diazo-4//-l,2,3-triazole, 1345... 

Cyclization of 2-phenyl-[l,2,3]triazole-4-carboxaldehyde hydrazone with POCI3 or SOCI2 has been shown to lead to 5-phenylpyrazolo[3,4-, [l,2,3]triazole in the case of the former and to a mixture of the 5-phenyl and the l-chloro-5-chlorophenylderivative <2005MI179>. 

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... 

Type cycloadduct 24 (Scheme 1) was obtained as the major product on cycloaddition of n-chloranil with l-ethoxycarbonyl-l/7-azepine <1982H(19)1197>. Treatment of 4-ethoxycarbonyl-5-chloro-l,2,3-thiadiazole with ethylenediamine under basic conditions occurs with heterocyclic ring opening/recyclization to form bis(triazole)-fused thiadiazepine 77 (R = COOEt) (Scheme 14). The benzo-fused analog was prepared by the similar reaction with o-phenylenediamine <1999CC2273>. 

The halogen metal exchange reaction between 7-bromo or 7-iodo-3-phenyltriazolopyrimidine 165 and butyllithium in iV,N,N, N -tetra-methylethylenediamine afforded the 7-lithio compound 166, whereas a similar reaction with the 7-chloro derivative 165 (R = H) gave the ring-fission product, 5-amino-l-phenyl-l//-l,2,3-triazole-4-carbonitrile 169 (91 CPB2793). Reaction of 166 with electrophiles such as benzaldehyde and ketones gave 170 and 167 respectively, together with 7,7 -bis[3-phenyl-3//-1,2,3-triazolo[4,5-d]pyrimidine] 168 (Scheme 34). 

Under analogous conditions 4,5-dimethyl-l,2,3-triazole yields unstable iV-chloro-4,5-dimethyltriazole 32b (R1, R2=Me). A-Chloro-4,5-diphenyl-1,2,3-triazole 32c (R1, R2=Ph), obtained by the chlorination of 4,5-... 

For other /V-halobenzotriazoles and l-chloro-4,5-diphenyl-l,2,3-triazoles 32c it is characteristic that [(M-N2)+] ions are observed together with the molecular ion [78JCS(P1)909 79JCS(CC)419]. 

Heating l-chloro-4,5-diphenyl-l,2,3-triazole 31c in acetonitrile decomposes it to benzonitrile, 2,3-diphenyl-3-(4,5-diphenyl-l,2,3-triazol-l-yl) azirine, and phenylchlorodiazomethane [79JCS(CC)419], This cleavage arises from the intermediate formation of the products of rearrangement of... 

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