6//-Imidazo -1,2,4-triazol-6-ones

Several interesting 1,2,4-triazole fused-ring systems have been reported. A facile synthesis of 3,5-dihydro-677-imidazo[l,2-fc]-l,2,4-triazol-6-ones 162 was obtained by an iminophosphorane-mediated annulation <06EJ04170>. 8-Trifluoromethyl-l,2,4-triazolo[4,3- >]pyridazines 163 has been prepared from 4-trifluoromethyl-4,5-dihydropyridazin-3-one... 

The reaction of 2-amino-l,3,4-thiadiazole 470 and 3-amino-l,2,4-triazole 472 with benzaldehyde and fe/V-butylisoni-trile gives imidazo[2,l-A [l,3,4]thiadiazoles 471 and imidazo[l,2- ][l,2,4]triazoles 473, respectively, in a one-pot process (Equation 110) <1998AG(E)2234>. 

The syntheses of only three members of this family of compounds, viz. pyrazolo[3,4- 1[l,2,3]triazoles, imidazo[4,5-f]-[l,2,5]thiadiazoles, and [l,3,2]dioxaborolo[4,5-, imidazoles, have been reported by more than one approach. The pyr-azolo[3,4- [l,2,3]triazoles remain the most common synthetic target among this family of compounds and have been accessed from monocyclic precursors by [5+0], [4+1], and [3+2] atom fragments. 

When the synthesis of a heterocyclic system containing a diazole fused onto l,2,3-triazin-4-one (e.g., imidazo[4,5-i [l,2,3]tnazin-4-one (Section 10.13.9.1.l(i)) and pyrazolo[3,4-rf [l,2,3]triazin-4-one (Section 10.13.9.1.1(ii))) or 1,2,3-triazole fused onto pyrimidin-4(7)-(di)one (e.g., [l,2,3]triazolo[4,5-rf pyrimidin-4(7)-(di)one (Section 10.13.9.1.l(iv))) is required, the synthesis of the six-membered ring is the most reliable method. There are several recent accounts of six-membered annulations onto 1,2,3-triazoles to give [l,2,3]triazolo[4,5-r/ pyrimidines (Section 10.13.9.1.l(iv)), which are valuable alternatives to 1,2,3-triazole annulation using nitrosation techniques <1996CHEC-II(7)489>. 

Phenylhydrazono-2-thiazolidinones are cyclized upon treatment with aliphatic and aromatic aldehydes to give thiazolo[4,3-c][l,2,4]triazol-5-ones (equation 22) (76ZN(B)380, 76ZN(B)853). Similar reactions of 2-(and 4-)phenylhydrazono-l-phenylhydantoins with aliphatic aqd aromatic aldehydes gave imidazo[2,3-c][l,2,4]triazoles and imidazo[4,3-c]-[l,2,4]triazoles (82H(19)1375>. 

In a one-pot reaction, a,a-disubstituted a-halo carbonyl compounds 1 (R, potassium thiocyanate, acetic acid, and monosubstituted hydrazines 3 are transformed into dihydro-lfT-imidazo[l,5- 7][l,2,4]triazole-2,5 (3H,6H)dithiones 8 (Scheme 1) (93TH, 01TH). With R =H, the reaction takes a different course (cf. Section 2.3). 

This ring system has been referred to on several occasions as s-triazolo[2,3-a]pyrazine and numbered as shown in formula 1 below. Ultraviolet spectra of several simple derivatives of the heterocycle have been recorded in cyclohexane and are useful in differentiating between derivatives of this ring system and the isomeric s-triazolo[4,3-fljpyrazines. In cyclohexane, 5,6-dimethyl-2-phenyl-s-triazolo[l,5-ajpyrazine has maxima at A (log e) 249 (4.65), 258 (4.62), 281 sh(3.91), 294(3.82), 301 sh (3.78), and 315 (3.55) nm. However, differences in UV spectra must be interpreted with caution. At least one supposed synthesis of s-triazolo[l,5-a]pyrazines, which was apparently supported by UV spectral data, has now been shown to give IH-imidazo[2,l-c]-s-triazoles (see Section II). 

With nucleophilic bases 3,7,7a-trimethyl-2,3,5,6,7,7a-hexahydro-17f-imidazo[l,5-Zi][l,2,4]-triazole-2,5-dione (130) and -2,5-dithione (129) the [3 -H 2] cycloelimination of the heterocumulene moiety from the triazole ring is followed by nucleophilic addition of the base to give 4-substituted 4,5,5-trimethyl-2,3,4,5-tetrahydro-l/7-imidazol-2-ones (135) and -2-thiones (136), respectively (Scheme 7) <93TH 805-01, 95FES379). 

Heated without solvent, the 5-amino-l-(l-carboxyalkyl)-3-methylthio-l//[l,2,4]triazoles (259) undergo cyclization to yield 5,6-dihydro-2-methylsulfonyl-4//-imidazo[l,2-Z>][l,2,4]triazol-5-ones (260) (Equation (71)) <85JHC385>. 

The 4-phenylhydrazonoimidazolidin-2-ones (284) undergo cyclocondensation with aldehydes to give the corresponding 2-phenyl-3,5,6,7-tetrahydro-2/7-imidazo[5,l-c][l,2,4]triazol-5-ones (285) (Equation (79)) <83JHC189>. 

Cyclocondensation of l-aryl-2-hydrazino-4,5-dihydro-3//-imidazol-5-ones (297) with carboxylic acids or carbonic acid derivatives gives the corresponding 7-aryl-6,7-dihydro-5//-imidazo[2,l-c][l,2,4]triazol-6-ones (298) (Equation (85)) <91MI 805-03,91MI 805-04>. 

The reaction of l-arylamino-4,4-dimethyl-5-methylene-2,3,4,5-tetrahydro-l//-imidazol-2-one (338 Y = O) and -2-thione (338 Y = S) with protic heterocumulenes affords 7,7,7a-trimethyl-3-aryl-2,3,5,6,7,7a-hexahydro-l/7-imidazo[l,5-fe][l,2,4]triazol-2,5-diones (339 X = Y = 0), and N-and 5-derivatives of these functions in 2- and 5-positions (Equation (104)) <93TH 805-oi, 95FES379>. 

Hydrazidoyl halides react with 2-amino[l,2,4]triazole to give 5-substituted 6-arylhydrazono-6//-imidazo[l,2-i][l,2,4]triazoles (350) and 6-arylhydrazono-5,6-dihydro-4//-imidazo[l,2-/>][ 1,2,4]-triazol-5-ones (351), respectively the latter products are not determined with respect to the tautomeric structures of the H-, 3H-, or 4/7-form (Scheme 32) <83JHC639>. 

Later, the regioselective alkenylation reactions of tetrahydro-6H-pyrido[l,2-a]pyrimidin-6-ones [51], imidazo[l,2-a]pyridines [52], and 1,2,3-triazoles [53] were conducted with the use of Pd(OAc)2/Cu(OAc)2 (Scheme 18.53, Scheme 18.54, and Scheme 18.55). 

In the reactions of iminophosphoranes with carbonyl and unsaturated compounds, both normal and abnormal aza-Wittig processes can be observed. Thus, the tandem aza-Wittig reaction of the iminophosphorane (6 with isocyanate or CS2 generated the 3,5-dthydro-6/f-imidazo[l,2-6]-l,2,4-triazol-6-ones in satisfactory yields, and the vinyl iminophosphorane (6 was transformed by normal aza-Wittig reactions to carbodiimides (as part of the synthetic route to 3,5-dihydro-6//-imidazo[l,2-i)]-l,2,4-triazol-6-ones). By contrast, a re-examination of the reaction of the iminophosphorane (67) with the aromatic isocyanate PhNCO showed that it gives an unexpected mixture of carbodiimides." In another example (Scheme 5), the... 

---