1.2.4- Triazoles nucleophilic substitution

In contrast, substituents in 1,2,4-triazoles are usually rather similar in reactivity to those in benzene although nucleophilic substitution of halogen is somewhat easier, forcing conditions are required. 

Thieno[3,4-d][ 1,2,3]triazole, tetramethyl-synthesis, 6, 1015 Thieno[3,4-c][ 1,2,3]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... 

Tetranitro derivative 90 (z-TACOT Section 12.10.15.5) treated with methanolic sodium methoxide at ambient temperature does not lead to simple product of nucleophilic substitution of a nitro group but provides compound 92. Its formation can be rationalized by introduction of the methoxy group into the 1-position, followed by scission of the remote triazole ring of 91 to give the final product. Compound 90 subjected to the vicarious nucleophilic substitution (VNS) conditions using either hydroxylamine or trimethylhydrazinium iodide gives a very insoluble red solid, which was identified as l,3,7,9-tetraamino-2,4,8,10-tetranitrobenzotriazolo[2,l- ]benzotriazole 93 (Scheme 5) <1998JOC3352>. 

In the presence of KOH, /m(benzotriazol-l-yl)methane 729 reacts with nitrobenzenes to produce />-(/fc (bcnzo-triazol-lyl)methyl]nitrobenzenes 730 (Scheme 114) <1996TL347>. This vicarious nucleophilic substitution of hydrogen <1991S103> can be considered as a convenient way to />-nitrobenzaldehydes 731. Meta and para substituted nitrobenzenes do not react with compound 729 under these conditions, probably due to steric reasons, but 1-nitronaphthalene reacts producing a naphthalene analog of derivative 730. 

Nucleophilic substitution of the fluorine atom in 2-fluorobenzonitrile 30 by 1,2,4-triazole gave a 10 1 mixture of 2-[l,2,4]-triazol-l-yl benzonitrile 31 and the corresponding 4-isomer 32 in crude yield of 66% (Equation 6) <2004JME2995>. 

Unlike the 3-position, the 5-position is very susceptible to nucleophilic substitutions and additions. Thus, a series of publications report that 5-fluoroalkyl-l,2,4-oxadiazoles 94 undergo reaction with hydrazine or hydroxylamine to furnish 3-fluoroalkyl-l,2,4-triazoles 95 (X = NH) and 3-fluoroalkyl-1,2,4-oxadiazoles 95 (X = 0), a reaction that proceeds via addition of the nitrogen nucleophile to the 5-position (Scheme 9) <2005JOC3288, 2004EJ0974, 2003JOC605>. 

In many cases, the yields of these products are high. However, the use of /V-silylated triazoles as nucleophiles or the use of cyclic nitroso acetals (475) substituted at the C-3 atom leads to a noticeable decrease in the yield of the oximes. Therefore, steric hindrance in nitroso acetals and a decrease in nucleophilicity of A-centered nucleophiles result in an increase in the contribution of side reactions. It should be emphasized that C -nucleophiles, such as anions of nitro compounds, are not involved in coupling reactions with cyclic nitroso acetals (475). However, the products, which formally correspond to the C,C-coupling mechanism, can be prepared by the nucleophilic substitution of chlorine in compound (476 d) by a Sa/2 mechanism (Scheme 3.254, product (483c), the yield was 79%). 

DiazotriazoIe 28 (R = Ph) reacted with /-butyl alcohol and 2-propanol to give compounds 148 and 149 (Scheme 40) in comparable yields by carbenic C—H insertion and nucleophilic substitution, respectively [81DIS(B)(42)1892]. In the case of 2-propanol, an oxidation-reduction process, to give the parent triazole and acetone, was also observed to a smaller extent. Also, it was previously reported that 3-diazotriazole 28 (R = COOH) oxidizes primary and secondary alcohols to the corresponding aldehydes and ketones (1898LA33). 

The C(5) position of 1-substituted 1,2,3-triazoles is activated towards nucleophilic attack by a pyridine-like nitrogen, and the equivalent C(4) and C(5) positions of 2-substituted 1,2,3-triazoles are weakly activated. However, a suitable leaving group, such as a halogen, is generally required for nucleophilic substitution <88BSB573>. 

The nucleophilic substitution of 1,2,3-triazole is also activated by A-oxidation. In 3-substituted 1,2,3-triazole 1-oxides, a halogen substituent at C(4) is more reactive than one at C(5) <87ACS(B)724>. Therefore, the C(4) chlorine of compound (221) (Equation (19)) is displaced by methoxide under much milder conditions than the corresponding C(5) chlorine of (222) (Scheme 39), and the only C(5) bromine is displaced in the case of 4,5-dibromotriazole 1-oxide <88BSB573>. 

Poly(arylene ether triazole)s have also been prepared by heterocyclic-activated displacement polymerization [36], The 1,2,4-triazole unit sufficiently activated, albeit weakly, aryl fluorides for nucleophilic displacement. Several 3,5-bis(4-fluorophenyl)-4-aryl-l,2,4-triazoles were polymerized with various bis-phenols to yield polymers with Tgs from 185 to 230 °C [36]. The 1,2,4-triazole unit appears to be one of the more weakly activating heterocycles towards nucleophilic substitution polymerization. 

Under acidic conditions, amino-substituted imidazoles and triazoles 135 (X = CH, N) underwent intramolecular nucleophilic substitution reaction to give 136 in yields depending on the C(2 ) substituent orientation <1999CAR190, 1999MI441>. Thiouridine derivative 73 (R = Me) (Scheme 12) cyclized similarly to 72 on treatment with hexamethyldisilazane(HMDS)-ammonium sulfate <1992NN603>. 

Methylsulfonyl)-3-phenyl-3//-l,2,3-triazol[4,5-d]pyrimidine 176 was prepared by the reaction of 175 with sodium methyl sulfide, followed by oxidation with potassium permanganate in acetic acid. A nucleophilic substitution reaction on 176 with potassium cyanide gave 182, but the same reaction did not take place on 175. Treatment of 176 with sodium methoxide... 

Alkylthio groups are sometimes replaced in nucleophilic substitutions, but such reactions are difficult in most neutral azoles. Thus, 3-alkylthio-l,2,4-thiadiazoles resist the action of aniline at 100C, ammonia at 120C, molten urea, and ammonium acetate. However, hydrazine attacks 3-methylthio-l,2,4-thiadiazole forming 3-amino-l,2,4-triazole 757. 

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. 

Nucleophilic substitution of the diazo group is practically the only method for the production of nitro derivatives of tetrazole [392, 436 143], 5-Nitrotetrazole itself was isolated and identified in the form of metallic salts [436-440, 442, 443], The mechanism of substitution of the diazo group by a nitro group in heterocyclic compounds has not been studied specially. As already mentioned, in many cases the reaction takes place as catalytic nucleophilic substitution and does not require the use of a catalyst (copper salts) [392,444], The results from investigation of the kinetics of the substitution of the diazonium group by the nitro group in compounds of the benzene series make it possible to suppose that the diazonitrite is formed intermediately and quickly reacts with a second nitrite anion [392,444], Some difference between the kinetics of the reaction of 3-diazonium-5-carboxy-l,2,4-triazole and 3-diazonium-5-methoxycarbonyl-l,2,4-triazole with sodium nitrite in hydrochloric acid and the analogous process in the benzene series is probably due to prototropic... 

There has been some interest in the chemistry of aminonitroazoles when used as high energetic compounds. Data concerning direct introduction of the amino group into the nitroazole cycle have been absent in the literature till the present time. We have studied the vicarious nucleophilic substitution of l-methyl-4-nitropyrazole and also l-mcthyl-4-nitroimidazole (Table 3.10), 4-nitro-2-phenyl-1,2,3-triazole (Table 3.24), and nitrobenzimidazoles (Table 3.25) under the effect of 1,1,1-trim-ethylhydrazinium halides and 4-amino-1,2,4-triazole by NMR spectroscopy (DMSO-<76) (Scheme 3.5) [220, 272-278] ... 

In the reaction of 3-nitro-5-R-l,2,4-triazolate-anion with 3,5-dinitro-l-(2-oxo-propyl)-l,2,4-triazole both the products of nucleophilic substitution in position 5 and condensed compounds [5-methyl-5-(3-nitro-5-R-l,2,4-triazol-l-yl)-5,6-dihydroxazolo[3,2-b]-l,2,4-triazoles] are formed. Their structures were established by H NMR and IR spectroscopy [585],... 

H NMR spectroscopy was used for the investigation of 2-(2,4-dinitrophenyl)-4-nitro-l,2,3-triazole [600], 4-amino-3-(4-nitro-l,2,3-triazol-l-yl)furazan [601], 2-aryl(heteryl)-4-acetylamino-5-nitro-l,2,3-triazoles [141, 177, 602-604], nucleophilic substitution in the series of 4,5-dinitro-2-alkyl-l,2,3-triazoles [605] and 4,5-dinitro-2-aryl-l,2,3-triazole-l-oxides [606],... 

Patent Vicarious Nucleophilic Substitution Using 4-Amino-1,2,4-Triazole,... 

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