Oxadiazole-2-thiones

4-Oxadiazole-2-thiones (Anhydro-2-mercapto-l,3,4-oxadiazolium Hydroxides) (156) 

4-oxadiazole-2-thione (156, R1 = Me, R2 = Ph) has a dipole moment of 9.10 D, which obviously supports its meso-ionic formulation.113 The meso-ionic l,3,4-oxadiazole-2-thiones (156) form methiodides (157)112 which are easily hydrolyzed, yielding the acyclic esters (160a). The meso-ionic l,3,4-oxadiazole-2-thione (156, R1 = Me, R2 

The existence of the isomeric meso-ionic compounds 156 and 162 has been recently established.102 103 The transformation 156 - 162, R1 = Me, R2 = Ph, is achieved by heating in ethanolic solution or with ethane-thiol in benzene this isomerization could well involve the betaine intermediate (163).102,103 

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In a study on reactions of 4-amino-3-( 1,3-di phenyl-l//-pyrazolM-yI)M,5-dihydro-[ 1,2,4]triazole-5( l//)-thionc 206 with different reagents, some novel [l,2,4]triazolo[3,4-/)][l,3,4]thiadiazepines 207-209 were obtained. The starting material 206 was prepared in good yield by the reaction of the oxadiazole thione 210 with hydrazine hydrate <2006ARK(X)137>. Results and reagents are shown in Scheme 31. 

Based on IR and NMR-spectroscopic studies [76AHC(S1), pp. 406, 414 94MI1027 96CHEC-II(4)267], 2-mercapto-l,3,4-oxadiazole prefers the thione form 195. 

Next, the hydrazides 41a-e were used in synthesis of different 1,2,3-triazole-3-thiones and l,3,4-oxadiazole-2-thiones. Thus, treatment of 41 e with phenyl isothiocyanate in boiling temperature for 4 h gave the thiosemi-carbazide solid, which separated and boiled directly with 5% NaOH for 3 h to provide, after neutralization with dilute HCl, 55 (67%). Similarly, treatment of 41d with 4-methoxyphenylisocyanate afforded 51 (62%). 

This time using hydrazine hydrate as the amine donor, reaction with l,3,4-oxadiazole-2-(3//)-thiones 223a-e under heating in ethanol yielded the corresponding l,2,4-triazole-2-(3//)thiones 224a-e (Equation 69 and Table 46) <2005EJM1156>. 

Table 46 Reaction of 1,3,4-oxadiazole-2-(3H)-thiones with hydrazine hydrate (Equation 69)... 

The treatment of imidazo-l,2,4-oxadiazol-5-thiones 142 (Equation 20) with ethanolic HC1 results in a retro-1,3-dipolar cycloaddition of the imidazo ring to give an azomethine ylide together with the 4,5-dihydro-l,2,4-oxadiazol-5-thiones 143 <2003PS881>. 

Rutavicius and Kuodis reported several examples of electrophilic alkylations of the ring nitrogen atom in 5-(4-pyridyl)-l,3,4-oxadiazol-2-thiones (Scheme 7) sometimes, the reaction on nitrogen was accompanied by alkylation on sulfur atom. The direction of substitution depended both on the structure of the initial reactants and on the reaction conditions <2002CHE852>. 

Similar reactions are also characteristic for 5-substituted-l,3,4-oxadiazol-2-thiones (Scheme 11) <1997CAR123, 2004MI147>. 

Microwaves were used to support S-arylation of 5-substituted oxadiazoline-2-thiones <2000BMC69> and <2000M1207>. 5-(4-Pyridyl)oxadiazoline-2-thiones treated with 2-haloesters also afforded A-alkyl derivatives <2000CHE851>. A similar reaction occurred in the case of 5-pyrazolyloxadiazoline-2-thiones <2000JFA5312>. Organophosphorus derivatives of 1,3,4-oxadiazole were obtained by the reaction of bis(oxadiazolinethiones) with 0,0-diethylchlorophosphate (Scheme 21) <1998JFA1609>. 

Compounds 190 on heating with ethanol/HCl convert to 4//[l,2,4]oxadiazole-5-thiones 191 (Equation 17) as a result of the ring opening in acid media <2003PS(178)881>. 

The reaction of 5-aryl-3-(chloromethyl)[l,3,4]oxadiazole-2(3//)-thiones 100 with hydrazine or methylhydrazine yields the corresponding 2,3-dihydro[l,2,4]triazolo[3,4-A][l,3,4]oxadiazole derivatives 102 <1984JCED477>. By analogy, hydrazine and phenylhydrazine convert the [l,2,4]triazole-2(3//)-thiones 101 into 3,7-dihydro-2//-[l,2,4 tria-zolo[4,3-r][ 1,2,4] triazoles 103 <1992PS99, 2002JCCS1035>. Finally, the azole-2(3//)-thiones 101 react with hydroxylamine to form the 3,7-dihydro[l,2,4]triazolo[5,l-d[l,2,4]oxadiazoles 104 (Scheme 8) <1992PS99>. 

The imidazo[4,5-i [l,2,3]oxadiazole-5-thione 228 has resulted from reaction between the 2-thioxoimidazolidin-4-one 229 and two equivalents of A -phenyliminophosphorane. The reaction also results in the formation of triphenylpho-sphine (TPP) and a proposed reaction mechanism is set-out in Scheme 47 <2006PS1615>. 

Artemov and Shvaika treated a number of 2-aryl-l,3,4-oxadiazole-5(4//)-thiones (293) with methylhydrazine (R = Me) and obtained a mixture of 1-methyl-1,4-dihydro-1,2,4,5-tetrazine-6(5/f)-thiones (294) and 4-methylamino-l,2,4-triazole-3-thiones (295 R = Me) (71KGS905). A similar reaction was reported by Konig and his coworkers, who treated 5-(4-pyridyl)-l,3,4-oxadiazole-2-thione (293 Ar = py) with hydrazine (R = H) and obtained a compound which was either the l,2,4,5-tetrazine-6-thione (294 R = H) or the 4-amino-l,2,4-triazole-3-thione (295 R = H) (54CB825,56GEP953801). 

An interesting but not synthetically useful reaction has been reported by Mloston and co-workers <2002CEJ2184>. The treatment of 2,2,4,4-tetramethylcyclobutan-l,3-dithione with dimethoxycarbene, generated by thermolysis of 2,2-dimethoxy-5,5-dimethyl-2,5-dihydro-[l,3,4]oxadiazole, led to the formation of 4-isopropyl-idene-3,3-dimethyl-thietane-2-thione in trace amounts (2% yield), together with other products (Equation 23). 

UV spectra of substituted 1,3,4-oxadiazoles are similar to those of similarly substituted benzenes, particularly in the case of 2-phenyl- and 2,5-diphenyl-l,3,4-oxadiazole (Amax (EtOH) 247.5 nm, log e 4.26, and 280 nm, log e 4.44 respectively). However, no absorption above 200 nm is shown by 1,3,4-oxadiazole itself and calculated values (Section 4.23.2.1) for its long wavelength absorption are in the region of 200 nm compared with Amax ca. 260 nm for benzene. 2-Methyl- and 2-ethoxycarbonyl-l,3,4-oxadiazole, and A2-l,3,4-oxadiazoline-5-thione have the following Amax (log e) values respectively 206 nm (2.62) (methanol), 243 nm (3.2) and 260 nm (4.12) (ethanol). 

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