1-sulfonyl 1,2,3-triazoles

As already mentioned, 1,2,3-triazoles are very stable heterocycles. However, those that bear a strong electron-withdrawing group at N1 are known to undergo ring-chain tautomerization. The ring-chain isomerism of 1 -sulfonyl 1,2,3-triazoles can be exploited in synthesis. As reported recently, 1-sulfonyl triazoles could serve as... 

Thus, in the presence of a dirhodium(II) tetraoctanoate catalyst, 1-sulfonyl triazoles react with nitriles, forming imidazoles [123]. The reaction proceeds at 60-80 °C with conventional heating or can be performed in a microwave reactor, and generally provides imidazoles in good to excellent yields (Scheme 7.11 A). The sufonyl group can be readily removed, revealing the parent NH-imidazole. Alternatively, sulfonyl imidazoles can be converted to 1,2,5-trisubstituted imidazoles by simple alkylation (Scheme 7.11B). 

Scheme 7.11 Synthesis of imidazoles via rhodium-catalyzed transannulation of 1-sulfonyl triazoles.

The copper(I)-catalyzed synthesis of 1-sulfonyl triazoles and their subsequent transannulation with nitriles can be combined into a one-pot two-step synthesis, thus further simplifying the experimental procedure (Scheme 7.12). The catalytic amount of copper remaining in the reaction mixture after the first step evidently does not interfere with the formation or reactivity of the carbene complex. 

Recently, it was reported that sulfonyl triazoles can give unwanted side reactions with protected guanosine and uridine (363). 

A series of azomethine yUdes have been generated through a rhodium-catalyzed reaction between sulfonyl triazoles and functionalized pyridines (Schane 3.141) [150]. Using this approach, an array of sterically and electronically diverse azomethine ylides were generated by systematic modification of the precursors. In addition to the isolation of these intriguing species, they were also used as intermediates in the preparation of 1,4-diazepines through a one-pot multicomponent reaction involving an internal activated alkyne such as dimethyl acetylenedicarboxylate. 

Dihydro-3-methoxy-4-methyl-5-oxo-A/-[[2-(tri-fluoromethoxy)phenyl]sulfonyl]-1H-1,2,4-triazole-1-carboxamide, sodium salt... 

In ref. [127] an investigation was made on the rate of phosphortriester formation and the percentage of sulfonated products in the cases of mesitylenesulfonyl-3-nitro-1,2,4-triazole (V), 2,4,6-triisopropylbenzenesulfonyltetrazole, and 2,4,6-triisopropylbenzene-sulfonyl-3-nitro-1,2,4-triazole (VI) as condensing agents. 

Ref. [152] discusses the transformation of a dinucleoside pyrophosphate into a reactive azolide with an azole (e.g., 3-nitro-1,2,4-triazole or tetrazole). With quinoline-8-sulfonyl chloride the concomitantly formed phosphordiester can be converted back to the dinucleoside pyrophosphate (see scheme on the next page). 

A regiospecific solid-phase synthesis of 3-methylthiazolo[3,2-c][l,2,3]triazole 105 has been achieved using poly-styrene-sulfonyl hyrazide resin (PS-Ts-NHNH2) 287. The reaction of resin 287 with l-thiazol-2-yl-ethanone in 5% TiCU/MeOH provides hydrazone 288 and subsequent treatment of this latter compound with morpholine at 95 °C gave fused triazole 105 in 60% yield (Scheme 29) <2004TL6129>. 

The reaction of 2-anilino-l,4-naphthoquinone 374 with benzoylacetic acid hydrazide gives 3-hydrazino-pyrazolyl derivative 375, that is acetylated to produce 5-[[l,4-dihydro-l,4-dioxo-3-(phenylamino)-2-naphthalenyl]sulfonyl]-3-methyl-6-phenyl-5/7-pyrazolo[5,l-c][l,2,4]triazole 51. This latter derivative is also obtained in 51% yield from reaction of 374 with benzoylacetic acid hydrazide in the presence of a mixture of acetic acid-sodium acetate <2004PS(179)1907> (Scheme 39). 

Upon heating in dimethylformamide (DMF) at reflux temperature, the 4-thioureido-5-sulfonyl[l,2,4]triazoles 74 undergo cyclization to [l,2,4]triazolo[3,4-7][l,3,4]thiadiazoles 75 (Equation 15) <1983S411, 1988IJB576,... 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

Toluene-p-sulfonyl azide adds to electron-deficient acetylenes and to phenylacetylene at 80°-100° over a period of several days. The azide adds much more readily to ynamines, - refiecting the electronic compatibility of these components. The triazoles so formed are labile and exist in equilibrium with open-chain diazo tautomers (Section IV, G) the adduct with ethoxyacetylene exists entirely in the diazo form. Other sulfonyl azides have been reacted with arylacetylenes, but yields of triazoles are generally poor. ... 

Sulfonyl azides are exceptional in that they do not normally give triazoles with activated methylene compounds nucleophilic attack by the carbanion is usually followed by loss of the sulfonamide anion, giving a diazo compound as the product. Possible mechanisms for the reaction are illustrated (Scheme 8) for diethyl malonate. Attack of the carbanion on the terminus of the azide gives the anion of the linear triazene (1). 

Closure to the triazoline certainly occurs in many systems, since products are isolated which can only have been formed by this route. Occasionally these products include w-triazoles for example, 4-phenyl-triazole is isolated in moderate yield from the reaction of the aldehydes (3) with toluene-p-sulfonyl azide (Scheme 9). ... 

Triazoles have also been obtained when the carbon atom adjacent to the activated methylene group carries a nitrogen function (i.e., amides, nitriles, amidines, and imines - ). In many of these cases it is impossible to decide, without N-labeling experiments, whether the third nitrogen of the triazole ring is derived from the toluene-p-sulfonyl azide or from the activated methylene compound. With amides, amidines, and nitriles, the first possibility seems more reasonable, but with imines, the third nitrogen is that of the imino group (Scheme... 

The reaction is most effective with azides bearing electron-withdrawing groups, such as nitrophenyl, toluene-p-sulfonyl, and ethoxy carbonyl. Sulfonyl azide adducts give iV-unsubstituted triazoles, the substituent being lost on aromatization. The triazole which is isolated as a minor product of the reaction of 1,1-dimethoxyethylene with ethoxycarbonyl azide has been assigned a 2/7-triazole structure it is likely that other ethoxycarbonyltriazoles formed by this route also have 2H-structures. 

A 1-toluene-p-sulfonyl substituent is reported to be removed by boiling the triazole in ethanol. Many triazole syntheses involving cycloaddition of toluene-p-sulfonyl azide give the NH triazole directly. 

Aminothiazole[3,2-fe][l,2,4]triazoles are readily bis-N-acylated (Ae20, reflux). The 5-alkylation of thiazolo[3,2-b][l,2,4]triazoles with chloro- and aeetoxymethylcephem was also reported (91MI2). An 5-alkylated thia-zolo[3,2-fe][l,2,4]triazole was converted to a sulfonyl ehloride and aminated (88EUP244098). 

The 3-alkylthio groups in 1,2,4-thiadiazoles are difficult to replace. Thus, 3-alkylthio-l,2,4-thia-diazoles resist the action of aniline at 100°C, ammonia at 120°C, molten urea and ammonium acetate however, hydrazine attacks 3-methylthio-l,2,4-thiadiazole (142) forming 3-amino-1,2,4-triazole (143) (Equation (21)) <65AHC(5)119>. In contrast to 3-alkylthiogroups, 5-sulfonyl groups in... 

---