1,3,4-Thiadiazole-2,5-dione

Of particular interest is the reaction of 5,5-disubstituted sulfur diimides (188) with oxalyl chloride in dilute solution in the presence of triethylamine. The l,2,5-thiadiazole-3,5-dione (189) was formed in almost quantitative yield (72LA(759)107). 

Heating the 5-isocyano-l,3,4-thiadiazolo[3,2- ]pyrimidin-5-one 115 with 10% hydrochloric acid gave a mixture of the 5-imino-l,3,4-thiadiazolo[3,2- ]pyrimidin-7-one 116 (10%) and the l,2,4-triazolo[l,5-c]pyrimidine-5,7-dione 117 (35%) (91JHC489). Formation of 117 probably occurred through thiadiazole ring rupture of 116 and recyclizatioii with its imino function together with desulfurization (Scheme 43). 

The 3f/-pyrazole-3,5(4//)-diones (7), prepared by lead tetraacetate,29,30 or tert-butyl hypochlorite31,32 oxidation of malonic acid cyclic hydrazides, are generally less stable than the triazoles 5, and are not isolable. The monocarbonyl derivatives (8-10) have been reported.33-36 The unstable 1,3,4-thiadiazole-2,5-dione (11) has been generated and reacted in situ.31,3 ... 

It is the combination of exceptional reactivity and reasonable stability, either as a solid or in solution, that makes PTAD such an ideal dienophile. However, PTAD is decomposed to N2, CO and phenyl isocyanate by the action of UV light.61 The cyclic ADC compounds (6-23) all undergo the Diels-Alder reaction, although with the exception of phthalazine-l,4-dione (13, R = H), they have been used only occasionally. l,3,4-Thiadiazole-2,5-dione (11) is of comparable reactivity to PTAD,38 but like the other cyclic compounds (6-23) has the slight disadvantage in that it has to be generated in situ. 

Condensed derivatives are also known. Treatment of 2-amino-l,3,4-thiadiazoles with 2,3-dichloro-l,4-naphthoquinone or 6-chloroquinoline-5,8-dione yields 102 and 103, respectively (82H333, 91JIC529). 

The novel derivative 56 (m.p. 127-128 °C) has been prepared in high yield by reaction of the 1,2,5-thiadiazole 55 with thionyl chloride (Scheme 3) <2000JHC1269>. The intermediate 55 is made by alkaline hydrolysis of 4,6-dimethyl[l,2,5]thiadiazolo[3,4-,7 pyrimidine-5,7(4//,6//)-dione 54 <2000JHC1269>. 

Disubstituted and unsubstituted l,2,5-thiadiazolo[3,4- ]quinoxaline-4,9-diones (110) have been prepared in good yield by condensation of 5,6-diaminobenzo[c][l,2,5]thiadiazole with a-dicarbonyl reagents (Equation (62)) <92H(33)337>. These quinones were then converted into 1,2,5-thiadiazolo-, pyrazino-fused TCNQ analogues by condensation with malononitrile in the presence of TiCl4 in dry pyridine. The x-ray crystal structure determination of the product derived from compound (110 R1 = R2 = H) has been accomplished. 

The reaction of unsubstituted 2-amino-1,3,4-thiadiazole (131) with 1,3-dicarbonyl compounds is dependent on the nature of the dicarbonyl compound (Scheme 13). Thus, reaction of (131) with pentane-2,4-dione gives the 4,6-dimethyl-2-thiocyanatopyrimidine (132). The formation of (132) may proceed via the cation (132a). With ethyl acetoacetate, however, a mixture of (133) and (134) is formed, (133) also being converted into (134) on heating. 

Azole approach. 5,8-Dihydro derivatives of this ring system (734) are known. The latter can be prepared by [ 4+ 2] cycloadditions of l,3,4-thiadiazole-2,5-dione (723) and a 1,3-diene. The former is highly reactive and is generated in situ by oxidation of 1,3,4-thiadiazolidine-2,5-dione with copper(II) chloride or LTA (74JOC2951). 

The reaction of the 5,7-dione (17) with primary amines led to the formation of three different thiadiazole derivatives depending on the reaction conditions. The reaction with benzyl amine at 75-80° produced N-benzyl-4-ureido-1,2,5-thiadiazole-3-carboxamide (18a). Reaction of both 17 and 18a with benzylamine under reflux for 1 hour... 

Other dienophiles, e.g., l,3,4-thiadiazole-2,5-dione 2, 4,4-dialkyl-4//-pyrazole-3,5-diones 3, 3H-pyrazol-3-ones 4 and azoquinones 5 and 6 are prepared in situ by oxidation of the dihydro precursor with lead tetraacetate or fcrt-butyl hypochlorite (see Section 7.2.10.3.). 

As an alternative to 4-phcnyl- and 4-methyl-3//-l,2,4-triazole-3.5(4//)-dione the analog l//-1.3,4-thiadiazole-2,5-dione can be prepared in the presence of the diene by oxidation of the corresponding thiadiazolidine at low temperature39 40. The cycloadducts 7 with the more reactive dienes are formed in good yield and can be cleaved hydrolytically with lithium hydroxide in tetrahydrofuran-water39. 

Similarly, by using H-, 3,4-thiadiazole-2,5-dione, prepared in situ at — 78 =C in acetone by oxidation of the thiadiazolidinedione with (erf-butyl hypochlorite, the cycloadducts formed by reaction with E,E)- and (/ ,Z)-2,4-hexadiene are prepared in 67% and 75% yield, respectively49. On the other hand, the reaction with the (Z,Z)-diene at 95 C gives no Diels-Alder cycloadduct, but a mixture of products coming from the addition of hydrogen chloride to the intermediate diazetidine. 

Several benzimidazole-4,7-diones were synthesized and tested for antitumor activity (88JMC260). There is also a report on oxidation of 4-amino-or 4-aikoxybenzo-2,l,3-thiadiazoles with hydrogen peroxide in concentrated hydrochloric acid to give 5-chlorobenzo-2,l,3-thiadiazole-4,7-dione (88KGS114). 

---