Thiadiazole derivatives

Compounds belonging to systems 224, 225, 226, and 227 are known. Compound 224 was prepared from the phenolic precursor with nitric acid (27LA172) dichromate oxidation of the dihydroxy precursor yielded 225 (37LA38). Quinone 226 was obtained from the 4-chloro- or -bromo-5-hydroxy 

OFETs [75]. Vacuum-deposited thin film of 73a showed a higher mobility of 

80 shows intramolecular charge-transfer interactions and its hole mobility was in the range of 10 cm s [82]. Thiophene oligomers (81a,b and 82) inserted with benzothiadiazole exhibited p-type characteristics except its perfluoroalky-lated derivative 81c [83]. Vacuum-deposited thin films of 81b showed a hole mobility of 0.17cm s , while spin-coated films of 81b and 82 exhibited 

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Dimercapto-l,3,4-thiadiazole derivatives, accelerated by amines, are used to cross-link chlorinated polyethylene. Polyisobutylene containing brominated i ra-methylstyrene cure functionahty can be cross-linked in polymer blends with dimercapto-1,3,4-thiadiazole derivatives accelerated with thiuram disulfides. Trithiocyanuric acid is suggested for use in polyacrylates containing a chlorine cure site and in epichlorohydrin mbbers. 

Two Nitrogen Atoms and One Sulfur Atom. s -Triazolo[3,4-d]-l,3,4-thiadiazole derivatives 98Ft(48)561. 

The only heterocyclic seven-membered ring system with maximum unsaturation containing six heteroatoms is 1,3A4,5,2,4,6-trithiatriazepine (1). The methoxycarbonyl derivative 2 is a minor product (14%) of the complex reaction of tetrasulfur tetranitride with dimethyl acetylenedicarboxylatc in refluxing toluene, which gives mainly dimethyl l,2,5-thiadiazole-3,4-dicarboxylate (3, 67%) (see Houben-Wcyl, Vol. E8d, pl54ff which includes an experimental procedure). Two other products are the trithiadiazepine 4 (5%, see Section 4.4.1.1.1.) and the 1,2,4-thiadiazole derivative 5 (3%).385... 

Benzothiadiazoles 3 have been extensively studied. Fully aromatic mesoionic compounds such as 4 continue to be synthesized. A number of examples of 4,5-dihydro-l,2,3-thiadiazole derivatives such as compound 5 <1993JOC82> and more recently the phenyl derivative 6 <2003RJ01501> have been reported. The corresponding 2,3-dihydro-l,2,3-thiadiazoles have also been reported and Hurd and Mori reported the N-Z phenylsulfonyl derivative 7. The electron spin... 

Nucleophilic attack on 1,2,3-thiadiazole derivatives is restricted to attack at the 5-position. There are no examples where nucleophilic attack has occurred at the 4-position. 

A modified reaction mechanism to the one suggested by Hurd and Mori is proposed for the preparation of some thieno[2,3- 7][l,2,3]thiadiazole derivatives in order to explain the formation of a chlorinated by-product <1998J(P1)853>. 

Chemists have found numerous industrial applications for 1,2,3-thiadiazole derivatives. In particular, 1,2,3-thiadiazole derivatives have been used as insecticide synergists, herbicides, and polymer compounds. They have also been shown to have sedative, antibacterial, and antibiotic activity. Examples of these compounds were discussed in CHEC(1984) and CHEC-II(1996). 

The 1,2,3-thiadiazole derivative 85 was found to be a potent and selective antagonist of the adenosine A2a receptor <2004J M E4291 >. 

The 2-propanone 1,2,4-thiadiazole derivative 44 undergoes the Fisher indole synthesis to give a range of indoles 45 substituted with a 1,2,4-thiadiazole at the 3-position (Equation 12) <2000CPB160>. 

A number of ring systems have been converted into 1,2,4-thiadiazole derivatives. The most common include 5-imino-1,2,4-dithiazolidines, isoxazoles, oxadiazoles, and 5-imino-l,2,3,4-thiatriazolines. In general, a ring-opening reaction is followed by rotation and ring closure, or the heterocyclic ring may act as a masked 1,3-dipole which reacts with a suitable dipolarophile. 

The transformation of 1,2,4-thiadiazoles bearing a reactive substituent such as amino or halogen group in the 5-position is the most useful method for the synthesis of 5-substituted 1,2,4-thiadiazole derivatives. The latter compounds can be reacted with nucleophiles to afford a wide range of derivatives this is not the case for 3-halogen-substituted compounds. 

Amidines and amidoximes react with carbon disulfide and a mixture of carbon disulfide and sulfur to afford 5-mercapto-l,2,4-thiadiazole derivatives (see Section 5.08.9.3). 

Inhibitors of cysteine protease cathepsin K, for the treatment of osteoporosis, have been reported. The 1,2,4-thiadiazole derivative 131 showed nanomolar activity <2004JME5057>. 

Thiadiazole derivatives have been found to be useful as additives for lubricating greases and as vulcanization agents <1996CHEC-II(4)307>. No new applications of this type have been reported since the publication of CHEC-11(1996). 

Chlorophenyl)-4-phenyl-l,2,5-thiadiazole 128 was prepared from 3-trifluoromethylsulfonyloxy-4-phenyl-1,2,5-thiadiazole 127 by palladium-catalyzed cross-coupling reaction with the tributyl(4-chlorophenyl)stannane (Equation 20) <1996H(43)2435>. The addition of lithium chloride improves the yield. The 3-chloro- and 3-bromo-l,2,5-thiadiazole derivatives were also reactive, but only the bromo compound gave the product in comparable yield (see Section 5.09.7.6). 

Substituted 1,2,5-thiadiazole derivatives were found to be potent pesticides <1995WO03306, 2005W006858>, and... 

The thiadiazole thione 112 was treated with an alkyl halide in sodium hydroxide to afford the thiadiazole derivatives 113 in 35-92% yields (Equation 35, Table 3) < 1999JME1161 >. This reaction results in the aromatization of the reduced thiadiazoline ring (see Section 5.10.9.5.1). The 2-(methylsulfanyl)-l,3,4-thiadiazoles can be S-demeth-ylated to afford 1,3,4-thiadiazole-2-thiones <1994JHC1439>. 

Condensation reactions of TV-substituted thioureas in dimethyl sulfoxide or methanol in the presence of DMSO-H+-X produce 1,2,4-thiadiazole derivatives (Scheme 64).150 151... 

Ring opening of the tricyclic thiadiazoloquinazolone derivative 84 was described by Santagati et al. <1994PHA880> the transformation is shown in Scheme 10. When this compound was heated with sodium hydroxide in a mixture of ethanol and dioxane, the central pyrimidine ring underwent hydrolytic ring opening, and the substituted thiadiazole derivative 85 was formed. 

A reductive ring opening of a linearly fused thiadiazole derivative 92 was reported by Nawrocka and Stasko <1997PJC792>. Reaction of this compound with sodium borohydride in methanol under heating afforded the iV-aminoquinazolone-thione 93. 

One procedure for the synthesis of these title ring systems appeared recently <2003S1079>. Yadav and Kapoor described that the transformation of some oxadiazole and thiadiazole derivatives bearing specially substituted methylsulfinyl side chain 131, when reacted with thionyl chloride, give ring-closed compounds 134. The reaction was carried out in pyridine under reflux conditions in 74-79% yield. As shown in Scheme 25, the authors assume that the first step is the formation of the sulfonium salt 132 which undergoes cyclization with hydrogen chloride and sulfur dioxide elimination to 133 and, finally, demethylation of this intermediate leads to the final product 134. 

Because of its importance in biological areas, special efforts have been made with the synthesis of the thiazolo[2,3-t]-[l,2,4]thiadiazole derivative 308 <2001BML1805>. The pathway started from the benzothiazole derivative 305 which was treated with chlorosulfonylacetyl chloride to form an intermediate 306, which underwent cyclization to a second intermediate 307 with hydrogen chloride elimination. The last step is the attack of the first intermediate 306 at the thiadiazine carbon atom to form the final product 308. 

The optical spectra of the selenodiazole appended porphyrazines 169, 171, and 172 show maxima of Q bands that are closer to those obtained from phthalocyanines, whereas they differ by 30-40 nm from those of thiadiazole derivatives (174). No splitting of the Q bands was observed for the... 

Sulfur monochloride and N - (26) or N - (27) substituted amides of 2-aminoacids afforded different 1,2,5-thiadiazole derivatives l,2,5-thiadiazol-3(2H)-ones 28 (1979NLP7712033,1992CHP680220,1994JPP06306063) and mesoionic 1,2,5-thiadia-zolium-3-olates 29 (1981JCS(P1)1033 Scheme 15). 

Benzothiadiazoles have been extensively studied and their chemistry reviewed <84CHEC-I (6)447>. Fully aromatic mesoionic compounds such as (3) continue to be synthesized and studied but no review focusing on such systems has appeared. Very few examples of nonaromatic 1,2,3-thiadiazole derivatives such as (4) <93JOC82> and (5) exist and the area has not been reviewed. 

The treatment of thiurets (diimino-l,2,4-dithiazolidines, (297)) with aromatic amines results in ring opening to form thiocarbamylguanidines (298) and sulfur cyclization to 3,5-diamino-1,2,4-thiadiazole derivatives (299) can occur spontaneously or upon oxidation (Scheme 67) <84CHEC-1(6)463 >. 

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