1.2.5- Thiadiazol-3 -ones, synthesis

Acetanilides, benzoyl-colour couplers in colour photography, 1, 372 Acetanilides, pivaloyl-colour couplers in colour photography, 1, 372 Acetazolamide — see l,3,4-Thiadiazole-2-sulfonamide, 5-acetamido-Acetic acid, acetamidocyano-ethyl ester, 1, 307 Acetic acid, 2-acylphenyl-isochroman-3-one synthesis from, 3, 858 Acetic acid, 3-benzo[6]thiophenyl-biological activity, 4, 912 Acetic acid, l,2-benzoxazol-3-yl-electrophilic substitution, 6, 48... 

The Hurd-Mori 1,2,3-thiadiazole synthesis is the reaction of thionyl chloride with the N-acylated or tosylated hydrazone derivatives 1 to provide the 1,2,3-thiadiazole 4 in one simple step. ... 

The structure of only one 1,2,4-thiadiazole salt has been determined. Unambiguous synthesis of the imino compound obtained on alkali treatment of the salt formed by the reactions of methyl iodide with 5-amino-1,2,4-thiadiazole established that the salt possesses structure 7 136 pjjjg quatemization exactly parallels the reaction occurring in... 

The synthesis has been described mainly by building the thiadiazole onto a triazine ring. However, one report has used thiadiazole 981 as starting material. Reaction of 981 with ethyl pyruvate gave 982 that was... 

Reaction of /3-carbonyl amides with the Lawesson s reagent under microwave irradiation gave thiazoles in acceptable yields [37]. The reaction was the same one previously reviewed for the synthesis of thiophenes and was also employed for the preparation of thiadiazoles (Scheme 10, X = NH, Y = CH). 

The most common, convenient, and versatile synthesis of 1,2,3-thiadiazoles is the one discovered by Hurd and Mori in 1955 <1955JA5359>. This involves the reaction of thionyl chloride with acyl- or phenylsulfonylhydrazones or semicarbazones 54 that contain an a-methylene group this reaction affords a wide range of 1,2,3-thiadiazoles 55 (Equation 15). 

A parallel synthesis of 1,2,3-thiadiazoles employing a catch-and-release strategy has been reported using the Hurd-Mori reaction. A polymer-bound tosyl hydrazide resin reacted with a-methylene ketones to afford a range of sulfonyl hydrazones. Treatment of these sulfonyl hydrazones with thionyl chloride causes 1,2,3-thiadiazole formation and cleavage of the resin in one step <1999JOC1049>. 

Perhaps the earliest reported method for the synthesis of the 1,2,3-thiadiazole ring system was the one described by Pechmann and Nold in which diazomethane was reacted with phenyl isothiocyanate. Of the four possible isomers that could be obtained from the reaction, 5-anilino-l,2,3-thiadiazole 62 (R1 Ph, R2 = H) was the only product formed (Equation 16) <1896CB2588>. This method continues to be used as a route to 5-amino substituted 1,2,3-thiadiazoles. 4,5-Disubstituted 1,2,3-thiadiazoles have been produced in excellent yield by reaction of l,l -thiocar-bonyl diimidazole with ethyl diazoacetate <1988SUL155>. 

Amidines and cyclic amidines are also converted into 1,2,4-thiadiazoles by reaction with isothiocyanates, imino-sulfenyl chlorides, di- and trichloromethyl sulfenyl chlorides, and carbon disulfide in the presence of sulfur. Ureas, thioureas, guanidines, carbodiimides, and cyanimides react with chlorocarbonylsulfenyl chloride to produce 1,2,4-thiadiazol-5-one derivatives in another example of a type B synthesis <1996CHEC-II(4)307>. 

The oxidative cyclization of thioacylamidines 83 is one of the best methods for the synthesis of unsymmetrical 3,5-diaryl- or dialkyl-1,2,4-thiadiazoles 84 (Equation 23) <2004HOU277>. Typical oxidants used in the cyclization step include bromine, iodine, or nitric acid, and, more recently, hydrogen peroxide in the presence of perchloric acid has been used. N-Substituted thioacylamidines give rise to 1,2,4-thiadiazolium salts <1997JOC3480>. 

Type G syntheses are typified by the 1,3-dipolar cycloaddition reactions of nitrile sulfides with nitriles. Nitrile sulfides are reactive 1,3-dipoles and they are prepared as intermediates by the thermolysis of 5-substituted-l,3,4-oxathiazol-2-ones 102. The use of nitriles as dipolarophiles has resulted in a general method for the synthesis of 3,5-disubstituted-l,2,4-thiadiazoles 103 (Scheme 11). The thermolysis is performed at 190°C with an excess of the nitrile. The yields are moderate, but are satisfactory when aromatic nitrile sulfides interact with electrophilic nitriles. A common side reaction results from the decomposition of the nitrile sulfide to give a nitrile and sulfur. This nitrile then reacts with the nitrile sulfide to yield symmetrical 1,2,4-thiadiazoles <2004HOU277>. Excellent yields have been obtained when tosyl cyanide has been used as the acceptor molecule <1993JHC357>. 

The oxidation of amidinothioureas by a range of oxidizing agents to give 3,5-diimino derivatives is still one of the most versatile methods for the synthesis of N-linked derivatives (see Section 5.08.9.4). An alternative method which gives symmetrical derivatives is the oxidation of A-arylthioureas to produce Hector s bases which readily isomerize to give 3,5-diamino-l,2,4-thiadiazoles (see Section 5.08.9.2). 

The synthesis of 1,2,5-thiadiazoles from amino acetonitrile salts 172 was reviewed in CHEC-II(1996). Owing to the ready formation of 2-amino acetonitrile salts from aldehydes via a one-pot Strecker synthesis, this synthetic pathway... 

Acylation of l,3,4-thiadiazol-2-(3//)-ones is also possible although competitive reaction with the ring nitrogen atoms is often observed. This reaction has been reviewed in the Houben-Weyl Science of Synthesis <2004HOU(13)349>. 

Aldehydes react with hydrazine hydrate and sulfur in a high yielding one-pot synthesis of 2,5-dialkyl- and 2,5-diaryl-1,3,4-thiadiazoles via a diazene intermediate (see Section 5.10.9.2.1) <1980LA1216, 1983JHC1399>. Although this synthetic procedure is rare, examples can be found in CHEC-II(1996) <1996CHEC-II(4)379>. 

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. 

The last example for the synthesis of this ring system discussed in this section is somewhat different from the previous ones as it presents formation of a positively charged thiadiazolo[3,2-tf][l,3,5]triazinium salt as published by Okide 1994JHC535 the 2 amino 5 alkyl[l,3,4]thiadiazole 167 was reacted with l chloro l,3 bis(dimethylamino) 3-phenyl-2-azaprop-2-enylium perchlorate (a reagent which was synthesized by the same author earlier <1992JHC1551>) to give the quaternary salt 168 in moderate yield (45%) (Scheme 32). 

Pechmann and Nold utilized the reaction of diazomethane with phenyl isothiocyanate for one of the earliest syntheses of a 1,2,3-thiadiazole <84CHEC-I(6)447>. This method continues to be used <82MI 407-0l> for the synthesis of 5-amine substituted 1,2,3-thiadiazoles (34), and 4,5-disubstituted... 

Wolffs synthesis of 1,2,3-thiadiazoles from diazoketones is also one of the earliest methods for forming this ring. Others have used this method with minor modifications to produce an array of... 

Although introduced over 40 years ago, Hurd and Mori s synthesis of 1,2,3-thiadiazoles remains the most widely used for the synthesis of 1,2,3-thiadiazoles. The simplicity of the method has contributed to its popularity. A variety of ketones and aldehydes have been converted into their corresponding hydrazones (tosyl and acyl), and thioamides have been converted into thio-carbazonate esters. The carbonyl derivatives are then treated with thionyl chloride to yield 1,2,3-thiadiazoles in high yields. When one is faced with the task of synthesizing new 1,2,3-thiadiazoles, Hurd and Mori s method should always receive attention. 

A useful method for the synthesis of 5-chloro-l,2,4-thiadiazoles (206) is the reaction of amidines with trichloromethylsulfenyl chloride (see Equation (30)). 3-Halo derivatives (349) (X = Cl, Br, I) (Equation (57)) have been obtained in moderate yields from the corresponding amines (348) via the Sandmeyer-Gatterman reaction <84CHEC-I(6)463>. 3-Chloro-l,2,4-thiadiazolin-5-ones (350) and (351) can be prepared by reacting chlorocarbonylsulfenyl chloride with carbodiimides or cyanamides respectively (Scheme 79) <84CHEC-I(6)463>. 

The synthesis and preliminary biological activity of substituted 7-alkylseleno-l,4-dihydro[l,6]naphthyridines have been reported <2000DOC218> along with their further synthetic ttansformations <2001RCB122>. There have also been reports of the preparation of selenium-containing fused heterocycles. The C=0 function in benzothiophen-3-ones, 3,4-dihydrothiopyrano[3,2-. ]benzothiophen-4(2//)-ones, and 3,4-dihydro-2//,5//-thiopyrano[2, 3 4,5]thiopyrano[3,2-/ ]ben-zothiophen-4-ones reacts with selenium dioxide and thionyl chloride to give fused 1,2,3-selena and thiadiazoles via their semicarbazones <1999IJB308>. 

Kidwai, M., Kumar, P., Goel, Y. and Kumar, K., Microwave assisted synthesis of 5-methyl- 1,3,4-thiadiazol-2-ylthio/tetrazol-l-yl substituted pyrazoles, 2-azetidinones, 4-thiazolidinones, benzopyran-2-ones and 1,3,4-oxadiazoles, Indian. J. Chem., Sect. B, 1997, 36, 281. 

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