1.2.4- Triazole, 3-nitro-, reaction with

Azidofurazans and -furoxans undergo dipolar cycloaddition reactions with unsaturated compounds, in some cases regiospecifically. Thus, reaction of 3-amino-4-azidofurazan with l-morpholinyl-2-nitroethene (toluene, reflux, 70 hours) gives 4-nitro-l,2,3-triazole 204 in 87% yield (99MI1, 000KGS406). Cycloaddition of the same azide to alkynes was accomplished by formation of a mixture of position isomers 205 and 206. Regiospecific addition was observed only in singular cases... 

An analogous reaction with 2, 3/,5 -triacetyluridine and mesitylenesulfonyl-3-nitro-triazole or triisopropylbenzenesulfonyl-3-nitrotriazole proceeds with the same high yield. Treatment of the nitrotriazolyl nucleoside with ammonia leads to 2, 3, 5 -triacetyl-cytidine.[194]... 

Azide 367 is prepared from 4-r -butyl-2-nitroaniline in 76% yield by its diazotization followed by treatment with sodium azide. In a 1,3-dipolar cycloaddition with cyanoacetamide, azide 367 is converted to triazole 368 that without separation is directly subjected to Dimroth rearrangement to give derivative 369 in 46% yield. Reduction of the nitro group provides ortfc-phenylenediamine 371 in 91% yield <2000EJM715>. Cyclocondensation of diamine 371 with phosgene furnishes benzimidazol-2-one 370 in 39% yield, whereas its reaction with sodium nitrite in 18% HC1 leads to benzotriazole derivative 372, which is isolated in 66% yield (Scheme 59). Products 370 and 372 exhibit potassium channel activating ability <2001FA841>. 

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%). 

Amino derivatives of 1,2,3- and 1,2,4-triazoles are useful precursors to the corresponding nitro-substituted triazoles. 3-Amino-1,2,4-triazole (98) undergoes diazotization on reaction with nitrous acid the resulting diazonium salt (110) can react with a range of nucleophiles, including an aqueous solution of sodium nitrite which yields 3-nitro-1,2,4-triazole (111). Diazotization of 3,5-diamino-l,2,4-triazole (112), followed by heating with an aqueous solution of sodium nitrite, yields 3,5-dinitro-1,2,4-triazole (113). ... 

Arylbenzotriazoles (797) are prepared via 2-nitro- and 2-amino-diphenylamines (Scheme 161). The 2-nitrodiphenylamines (796) are prepared from the appropriate aniline by reaction with 2-fluoronitrobenzene in the presence of KF <808215,85JCS(Pl)2725>. Azo-coupling of 2-amino-1-cyano-azulene (798) with p-tolyldiazonium chloride gives (799) (Scheme 162). Catalytic reduction of (799) quantitatively yields the diamino derivative (800), which on diazotization affords 9-cyano-azuleno[l,2-J]triazole (801) in 77% yield <85TL335>. 

Reaction of 1-azidoadamantane with nitro and sulfoxy olefins (Scheme 77, R = H or Ph and X = N02 R = Ph and X = SOPh) leads directly to the triazoles two isomers are obtained from the /i-nitrostyrene reaction with the 5-phenyl-1-adamantyltriazole as the major product.155 Likewise, triazoles are the only products formed in the reaction of aryl azides with /J-nitrostyrene (Scheme 77)294,295 however, unlike the azidoadamantane reaction, a... 

The reaction of 5-bromo-3-nitro-l,2,4-triazole and 3,5-dinitro-l,2,4-triazole with a variety of oxiranes yielded the expected 1-substituted imidazoles, and also resulted in the formation of 5,6-dihydrooxazolo[3,2-6]-s-triazoles upon treatment with base (75CHE612). The proposed pathway involves proton abstraction from the imidazole and subsequent attack of the oxirane on the N-anion followed by cyclization in a concerted fashion (equation 56). 2,4(5)-Dinitroimidazole reacts analogously with oxiranes to give isomeric nitro-imidazo[2,1 -f>]oxazoles in good overall yield (8UMC601). 

In contrast to reactions with alkynes [507] that are nonregioseletive, methylazide reacts regiospecifically with a-nitro-olefmes and forms only 4-nitro-5-phenyl-1,2,3-triazole after elimination of HN02 [557] (Scheme 101). 

It should be noted that 3-amino-4-nitrofurazan has been isolated as a side product of 1,2,3-triazole 1-oxide in all cases of this reaction. For example, 2-ethyl-4-ethylamine-5-nitro-l,2,3-triazole 1-oxide with excess ethylamine transforms quantitatively into nitroaminofurazan [565] (Scheme 107). 

Only the Diels-Alder-ene products are formed from 4-nitro- and 4-/crt-butylphenylethylene with 4-phenyl- or 4-methyl-6 from 2-vinylpyridines and 4-phenyl-7 and from 1-cyclopropyl-l-phenylethylene and 4-phenyl-3//-l,2,4-triazole-3,5(47/)-dione8. From benzylidenecyclopropane the double Diels-Alder adduct 5 was obtained exclusively on reaction with 4-phenyl-3tf-l, 2,4-t riazole-3,5 (4/f)-d ione9. 

The crystalline 1,2,4-triazole derivative 236, on reaction with aqueous ammonia, gives l-/8-arabinofuranosylcytosine (237). Heating the more reactive 3-nitro-1,2,4-triazole derivative 238 with the weakly basic aniline in pyridine, followed by subsequent hydrolysis with aqueous ammonia. 

Bis(hydroxymethyl)phosphonic acid esters that incorporated thymine were employed as a backbone to prepare short oligonucleotide chains. This chain was prepared by condensation of the bis(4,4 -dimethoxytrityl) protected phosphonic acid and iV or N -(2-hydroxyethyl)thymine in the presence of l-(2-mesitylenesul-fonyl)-3-nitro-l,2,4-triazole or by an Appel reaction with or N -(2-aminoethyl)thymine (89a-h). Selective removal of one DMT-group and phos-phitylation yielded the building blocks for solid supported synthesis of the short oligomers by the phosphoramidite approach. Holy has reported the synthesis of 8-amino and 8-substituted amino derivatives of acyclic purine nucleotide analogues. The 8-amino, 8-methylamino- and 8-dimethylamino-adenine and -guanine analogues of iV-(2-phosphonomethoxyethyl) and (S)-iV-(3-hydroxy-2-phosphono-methoxy-propyl) derivatives of purines (90a-i), were prepared by... 

Vicarious nucleophilic substitution (3.3.3) permits the introduction of amino groups para (or ortho if para blocked) to nitro groups by reaction with methoxyamine or 1-amino-l,2,4-triazole. In contrast, VNS substitution of 3-nitropyridine with benzyl chloroacetate proceeds at C-4. °... 

Some 5-nitro-2-thienyl-pyrazoles have been prepared for a study of their antimicrobial activity. The oximes of thienyl- and selenienyl-carboxamides, prepared from the nitriles and hydroxylamine, give 1,2,4-oxadiazoles by reaction with triethyl orthoformate in BFs etherate. Starting from cyano-thiophens and cyano-selenophens, thienyl- and selenienyl-triazoles and tetrazines were prepared. From the jS-diketone (184) the triheterocyclic (185) was obtained... 

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