1.2.3.5- Oxatriazolium salts

Two types of nuclei with an oxygen and three nitrogen atoms are possible, namely 1,2,3,4-oxatriazoles (1) and 1,2,3,5-oxatriazoles (7). The neutral aromatic species have not yet been reported but 1,2,3,4-oxatriazolium salts (2) and mesoionic species (3)-(6) are known. 1,2,3,5-Oxatriazolium salts (8) and mesoionic compounds (9)-(12) are not yet known but 1,2,3,5-oxatriazolines (13) and (14) have been reported. The two types of oxatriazoles will be discussed in two separate sections. 

Of the possible structures 1-16 shown, the known structures are represented by 1,2,3,4-oxatriazolium salts 2, mesoionic derivatives 3-6, and 1,2,3,5-oxatriazolidines 15 and 16. Derivatives of A -1,2,3,4-oxadiazoline 7 have now been synthesized and are the first representatives of this particular ring system. 

CEA-3175 (1,2,3, 4-Oxatriazolium, -3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl) sulfonyljamino]-, Hydroxide Inner Salt)... 

The mesoionic compounds can be named in several ways. The systematic name for structure (4) is a 3-substituted anhydro-5-hydroxy-l,2,3,4-oxatriazolium hydroxide. Similarly, structure (5) is named a 3-substituted anhydro-5-thiolo-l,2,3,4-oxatriazolium hydroxide, and structure (6) a 3-substituted anhydro-5-amino-l,2,3,4-oxatriazolium hydroxide. Frequently used names for structure (4) are 3-substituted 5-hydroxy-1,2,3,4-oxatriazolium hydroxide inner salt Chemical Abstracts), 3-substituted l,2,3,4-oxatriazol-5-ylio oxide, or 3-substituted l,2,3,4-oxathiazolylium-5-olate. For practical purposes, the term mesoionic l,2,3,4-oxatriazol-5-one is often used. Analogously, (5) and (6) are named mesoionic l,2,3,4-oxatriazol-5-thione and mesoionic l,2,3,4-oxatriazol-5-imine, respectively. 

Anhydro-5-hydroxy-1,2,3,4-oxatriazolium hydroxides (4) are relatively stable at elevated temperatures under neutral and salt-free conditions. However, prolonged heating of (17) in the presence of lithium chloride gives rise to elimination of carbon dioxide with formation of an azide which can be trapped by 1,3-dipolar cycloaddition to an alkyne (Scheme 2) <68CB536>. 

Anhydro-5-hydroxy-l, 2,3,4-oxatriazolium hydroxides (4) are weak bases <82JCS(P2)70l>, but the corresponding salts have not been isolated. There are three possible sites of protonation leading to the structures (32-34 Y = O) but it is not known where protonation actually occurs (Scheme 9). 

Mesoionic 1,2,3,4-oxatriazolium-5-thiolates (172) are convenient starting materials for mesoionic thiatriazole 5-oxides. Thus arylhydrazines and carbon disulfide in ethanol yield arylhydrazinium dithiocarbamate salts, which are nitrosated with sodium nitrite in aqueous hydrochloric acid to give yellow l,2,3,4-oxatriazolium-5-thiolates (172). These heterocycles are isomerized by warming with ammonium hydroxide in ethanol to give colorless crystalline l,2,3,4-thiatriazolium-5-olates (173) (Scheme 36) <76CC306>. 

Substituted anhydro-5-hydroxy-l,2,3,4-oxatriazolium hydroxides 6 are relatively stable under neutral conditions in the absence of salt. The stability depends on the nature of the R2 substituent attached to the exocyclic nitrogen and decreases from very stable to moderately stable along the series RS02 > RNHCO> RCO> R <2002MI167>. 

The original synthesis of 3-substituted-anhydro-5-amino-l,2,3>4-oxatriazolium hydroxides relied on cyanohydra-zines or guanidinohydrazines that were converted to the nitrosocyanohydrazines 40 and 41 that then cyclized to give products 42 and 43 as their hydrochloride salts (Equation 6) <2002CRV1091>. 

Direct, reliable methods for synthesis of mesoionic 1,2,3,4-oxatriazoles 4-6 are well established. All rely on the transformation of acyclic starting materials. Thus, 3-alkyl-anhydro-5-hydroxy-l,2,3,4-oxatriazolium hydroxides 4 (R1 = alkyl) are readily obtained by nitrosation of semicarbazides followed by cyclization (Section 6.08.9). The 3-aryl-substituted analogues 4 (R1 = aryl) are prepared either by cyclization of arylazonitromethanes or by nitrosation and cyclization of arylhydrazonomethanesulfonate salts <1984CHEC(4)579, 1996CHEC-II(4)679>. 

Oxatriazolium-5-aminides (9) are structurally related to sydnon-imines (3). As with sydnonimines, the 5-imine derivatives are stable only as salts or in their N-acylated forms. 3-Cyclohexyl-1,2,3,4-oxatriazole-5-imine hydrochloride was first synthesized by Finnegan and Henry in 1965 [55]. The biological activity was reported by Masuda et al. in 1971 [56]. Oxatriazole-5-imines (9) have been reported to be an important class of NO donors and potent antiplatelet, fibrinolytic, thrombolytic, and bronchiectatic agents [57]. However, an extensive investigation of the NO-releasing and other biologi-... 

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