Oxatriazol-5-imines

Although this was not appreciated at the time, these compounds were first handled by Busch and Becker in 1896.194 Their study continued until a more extensive report by Busch and Schmidt was published in 1929.195 However, Busch and his co-workers were apparently unaware of some closely related work reported by von Pechmann in 1896.187 These earlier studies have been interpreted by Farrar,188 extended by Christopherson and Treppendahl,196 and brought to a definitive conclusion by the Sheffield group.197 This history is an interesting facet of the development of the chemistry of meso-ionic heterocycles. 

In the early investigation194,195 of the nitrosation of 1,4-diphenyl-thiosemicarbazide (279, R = R2 = Ph), the product was obtained as deep red needles, m.p. 110°, and was allocated the remarkable 1,3-endoxyhydrazomethylene structure (280). Treatment of this deep red compound with warm aqueous alkali gave a colorless isomer, m.p. 157°, which was formulated as having one of the equally unacceptable structures 281 or 282.195 Recent investigations196,197 have established that nitrosation of 1,4-diarylthiosemicarbazides (279) yield the meso-ionic l,2,3,4-oxatriazol-5-imines (277), which are transformed by base into the meso-ionic isomers (278). These alkaline transformation products formulated as meso-ionic l,2,3,4-tetrazol-5-ones (278) are in fact identical (see Section VII, J, 1) with substances prepared, but not formulated, by von Pechmann many years ago.187 

Treatment of the JV-nitrosocyanides (283)198 or the W-nitrosoguanyl-hydrazines (284)199 with hydrogen chloride yielded the 1,2,3,4-oxatriazolium chlorides (285, X = Cl), which with aqueous sodium bicarbonate gave the meso-ionic l,2,3,4-oxatriazol-5-imines (277, R2 = H).198 Nitrosation of these compounds (277, R2 = H) gave the interesting JV-nitroso compounds (277, R2 = NO), and acylation gave the JV-acyl derivatives (277, R2 = RCO).198 

Their formulation (277) as meso-ionic heterocycles is supported by their dipole moments in benzene 108 277, R1 = R2 = Ph, p = 5.42 D 277, R1 = p-Cl. C8H4, R2 = Ph, p = 4.17 D 277, R1 = Ph, R2 = p-C1. C6H4, p = 6.29 D. Acid hydrolysis of the diphenyl derivative (277, R1 = R2 = Ph) gives the meso-ionic l,2,3,4-oxatriazol-5-one (271, R = Ph).196 An interesting aryl group exchange is achieved by a 1,3-dipolar cycloaddition reaction between meso-ionic l,2,3,4-oxatriazol-5-imines (277) and aryl isocyanates. Thus, the diphenyl derivative (277, R = R2 = Ph) and p-chlorophenyl isocyanate yields the product 277, R1 = Ph, R2 = p-Cl. C6H4.197 

4-OxatriazoleS-thiones (Anhydro-5-mercapto-l,2,3,4-oxatri-azolium Hydroxides) (286) 

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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. 

HNMR chemical shifts for substituents in mesoionic oxatriazole-5-thiones (86) (79JCS(Pl)732), oxatriazol-5-imines (87) (79JCS(Pl)736), mesoionic thiatriazol-5-ones (88) (79JCS(P1)732), thiatriazole-5-thiones (89) (79JCS(P1)732), thiatriazol-5-imines (90)... 

Oxatriazol-5-imines unsubstituted at the exocyclic nitrogen are amphoteric. Thus treatment of (87 R1 = H, R = Ph) with potassium hydroxide in ethanol gives a colorless crystalline salt (equation 64) (29CB1449). Christophersen and Treppendahl later found this to have the remarkable open-chain structure (104) and showed that the reaction is reversible. A pKa value of 6 has been estimated for compound (87 R1 = H, R = Ph) (72ACS858). 

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-... 

N-Morpholino-W-nitrosoaminoacetonitril as a nitric oxide ( N0) donor (Bohn and SchOnafin-GER 1989, Feelisch et al. 1989) formed from N-ethoxycarbonyl-3-morphlinosydnonimine (molsi-domin) via 3-morphlinosydnonimine by 02 formation is a safe vasodilator in man, but a potential nasal carcinogen in the rat, probably due to the vast smooth endoplasmic reticulum with its cytochrome P450 (Hadley and Dahl 1982, Adams etal. 1991). The question whether the new series of mesoionic 3-aryl substituted oxatriazole-5-imine derivatives (Lahteenmaki et al. 1998) have the same side effects is outstanding. 

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