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

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. 

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). 

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.). 

In general, hydrolysis of adducts of triazolinediones to the hydrazines requires rather vigorous conditions. To solve this problem, Corey613 and Beak61b have independently generated l,3,4-thiadiazole-2,5-dione, which can be trapped with reactive 1,3-dienes at 0°C or below [Eq. (19)]. 

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. 

Soni et al. (1982PINSA108) indicated that 2-amino-[l,3,4]thiadiazoles 65 with 2a gave 2-chloro-3-([l,3,4]thiadiazol-2-ylamino)-2,3-dihydro-[l,4] naphthoquinone intermediates 66 in 33-46% yields. They were further cyclized in acetic acid to 2-alkyl-naphth[2,3-r/]-iinidazo[2,3-l>]thiadiazolo-5,10-diones (67, Scheme 19,1982PINSA108). 

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). 

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 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. 

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). 

Chemical Properties of 1,2,5-Thiadiazoles. Lithiation and carbonylation of one methyl of 3,4-dimethyl-1,2,5-thiadiazole were described, followed by subsequent transformation into alcohol, mesylate, and vinyl derivatives. The reaction of 2,5-dicyclohexyl-l,2,5-thiadiazole-3,4-dione with RC6H4-SO2N3 gave the compounds (294 R = 4-MeO or 3-O2N). ... 

The next higher member of this series, C5OS 8, was generated by pyrolysis ofbenzo-[l,2-d 4,5-d]bis[l,2,3]thiadiazole-4,7-dione 7 or matrix photolysis of thiophenetetracarboxylic acid bis-thioanhydride 9. ... 

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