1.3.4- Thiadiazoles review

A number of other heterocycHc diazo components such as thiazole, iadazole, thiophenes, and thiadiazole types (see Fig. 1), as well as heterocycHc couplers, ie, 6-hydroxy-2-pyridinone [626-06-2] barbituric acid [67-52-7] and tetrahydroquiaoline [25448-04-8] h.2L e been cited ia the Hterature (90,91). Reviews on disperse dyes have been pubUshed (92,93). 

The mechanism of the Hurd-Mori reaction has been discussed extensively in the review by Stanetty. The mechanism of the reaction was initially postulated by Hurd-Mori based on the isolation of intermediate 10. This intermediate was shown to transform into the desired thiadiazole upon heating in ethanol, either with or without acid. The reaction was thought to proceed via the four-membered intermediate 11, which would release the volatile ethylformate as a by-product. In 1995, Kobori and co-workers were able to isolate and determine crystallographically a very similar intermediate structure to 10 in their mechanistic studies of the reaction. ... 

Preparation of thiadiazoles via the Hurd-Mori cyclization has led to the synthesis of a variety of biologically active and functionally useful compounds. Discussion of reactions prior to 1998 on the preparation of thiadiazoles have been compiled in a review by Stanetty et al Recent syntheses of thiadiazoles as intermediates for useful transformations to other heterocycles have appeared. For example, the thiadiazole intermediate 36 was prepared from the hydrazone 35 and converted to benzofuran upon treatment with base. Similarly, the thiadiazole acid chloride 38 was converted to the hydrazine 39 which, upon base treatment, provided the pyrazolone, which can be sequentially alkylated in situ to provide the product 40. ... 

Papers dealing with this topic are exhaustively reviewed in Comprehensive Heterocyclic Chemistry I (84CHEC-I(6)235) and II (96CHEC-II(3)373). Nevertheless, little information is available on the 5-oxides. Recently, the heteroaromaticity of thiazole compared with isothiazole and thiadiazole 5,5-dioxide systems was studied (97MI1). Quantum-chemical calculations and X-ray studies were performed on 3,3 -di[l,3-thiazolidin-4-one] derivatives (95JCC(25)589) studied for their potential biological activity (97FA(52)43). 

Thiadiazole 5-oxides and 5,5-dioxides are the least studied among the four possible isomers of thiadiazole system. The main summary is in the first and the second editions of Comprehensive Heterocyclic Chemistry (84CHEC-I(6)447, 96CHEC-II(4)289). Apparently the 5-oxide and the 5,5-dioxide derivatives have not yet been reviewed. There are very few papers in the literature treating these derivatives, and most of these are regarding polycyclic systems. 

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 1,2,3-thiadiazole literature was extensively reviewed in CHEC(1984) <1984CHEC(6)447> and CHEC-II(1996) <1996CHEC-II(4)289>. It covered the literature up to 1996 and cited many excellent references to 1,2,3-thiadiazoles. A further review on the chemistry of 1,2,3-thiadiazoles, which gives a critical review of methods of synthesis and is accompanied by experimental procedures, appeared in Science of Synthesis <2004HOU(13)253>. Another review of 1,2,3-thiadiazoles also appeared in 2004 . An annual review of the chemistry of 1,2,3-thiadiazoles appears in Progress in Heterocyclic Chemistry (Chapter 5.5). This review covers the 1,2,3-thiadiazole literature up to 2006. 

A review on the chemistry of 1,2,4-thiadiazoles, which gives a critical discussion of methods of synthesis and is accompanied by experimental procedures, appeared in Science of Synthesis <2004HOU277>. An annual review of... 

The use of infrared (IR) as a technique for structure determination is not very common in recent times. The reviews by Kurzer <1965AHC(5)119, 1982AHC285> contain a table of IR spectral absorptions of 1,2,4-thiadiazoles which covers spectra published before 1982. Additional spectral data was published in CHEC(1984) <1984CHEC(6)463>. 

The only example of this kind is the thermal isomerization of 1-cyanocyclopentyl-iminosulfur dichloride into 3-chloro-4-(4-chlorobutyl)-l,2,5-thiadiazole. The reaction has been previously reviewed in CHEC(1984) <1984CHEC(6)513, 1973JOU2522>. 

Benzylic methylenes, 1,3-diketones such as diaroylmethanes and aroylacetones, alkenes and alkynes are all known to give 1,2,5-thiadiazoles when treated with a variety of sulfur sources and much of this work has been reviewed in CHEC(1984) and CHEC-II(1996). Recent developments are outlined below. 

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... 

The preparation of thiadiazoles 180 from 1-cyanoformamide 177 (2-nitrilo-acetimidic acid), or its alkyl esters 178, using disulfur dichloride under mild conditions was previously reviewed in CHEC(1984) and CHEC-II(1996). The synthesis of thiadiazoles from the thioesters 179, formed by the addition of alkylthiols to cyanogens, was more recently investigated (Equation 36) <1998JME379>. In several cases, the esters 178 or thioesters 179 prepared from cyanogen were not isolated but added directly to disulfur dichloride <1996W038431, 1998JME379>. 

The introduction of sulfur between two ortho amino groups is the oldest and still the most commonly used route to benzo- and heteroarene-fused 1,2,5-thiadiazoles. The reaction has been extensively reviewed in both CHECK 1984) and CHEG-II(1996). The in situ preparation of Ar-sulfinylanilinc via /3-elimination of chloroform from trichlorometh-anesulfinamides 200 was recently supported by trapping with 1,2-benzenediamine to give the benzothiadiazole 2 in 85% yield (Equation 43) <1997TL487>. 

The survey of the uses of 1,2,5-thiadiazoles has appeared previously in CHEC(1984) <1984CHEC(6)513>. Recently, a review on the chemistry of thiadiazole A-oxides also highlighted their applications <2002AHC71>. 

The chemistry of 1,3,4-thiadiazole and its derivatives has been previously covered in both CHEC(1984) <1984CHEC(6)545> and CHEC-II(1996) <1996CHEC-II(4)379>. A major review which covers the synthetic chemistry of the ring system up to 2002 has also appeared <2004HOU(13)349>. Since 1991 advances in the chemistry of 1,3,4-thiadiazole have been annually reviewed in Progress in Heterocyclic Chemistry <1991PHC149>. 

Tautomerism was reviewed quite extensively in CHEC(1984) <1984CHEC(6)545> and CHEC-II(1996) <1996CHEC-II(4)379>. The tautomeric ability of the 2-mercapto-5-methyl-l,3,4-thiadiazole 9 was studied by its reaction with the electrophilic Cl3 FnCSCl <2003JP01>. 2-Mercapto-5-methyl-l,3,4-thiadiazole 9 was considered to exist mainly as the thione tautomer however, electrophilic substitution occurred on the thiol (Scheme 1). 

No examples of direct oxidation of the 1,3,4-thiadiazole ring sulfur to sulfoxide or sulfone have been reported. A3-l,3,4-Thiadiazoline 1-oxide and 1,1-dioxide, however, can be obtained by indirect methods that are reviewed in CHEC(1984) <1984CHEC(6)545>. 

The thermal decomposition and cycloaddition reactions of 2,5-dihydro-1,3,4-thiadiazoles are reviewed in Sections... 

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>. 

Two other results should be reviewed here, too. The substituted thiadiazolo[3,2-trifluoromethyl groups) was described by Sokolov and Aksinenko <2003IZV2053> 2-amino-5-methyl[l,3,4]thiadiazole 165 was heated with iV-ethoxycarbonyl-bis-trifluoroacetone imine in DMF in the presence of />-toluenesulfonic acid to yield the cyclized product 166 in good yield (77%). 

Sakya, S. M. Hurd-Mori 1,2,3-Thiadiazole Synthesis In Name Reactions in Heterocyclic Chemistry, Eds, Li, J. J. Corey, E. J. Wiley Sons Hoboken, NJ, 2005, 199—206. (Review). 

Some typical rearrangements in this series have been reviewed in a different context, concerning 1,2,4-thiadiazole chemistry [82AHC(32)285]. 5-Amidinothiadiazoles 240, obtainable from the 5-amino-3-methyl-l, 2,4-... 

Aminotriazoles which are appropriately substituted at the C(5)-position are important intermediates for the synthesis of 8-azapurines. These reactions have been reviewed <86AHC(39)ll7>. The pharmaceutically useful acyclonucleosides bearing 1,2,3-triazolines and 8-azapurines have been synthesized <888879). 4,5-Diaminotriazoles react with 1,2-dicarbonyl reagents to give 1,2,3-triazolo[4,5- )]pyrazines. 4,5-Diamino-2-phenyltriazole and sulfur monochloride afford the triazolo[4,5-c][l,2,5]thiadiazole (855) <86AHC(40)129>. The synthesis of triazolopyridines from triazoles has been described in a review <83AHC(34)79>. For further applications of substituted triazoles in preparations of complex heterocycles, see Section 4.01.4. 

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. 

Carbon-13 NMR is often a more useful tool than H NMR for the elucidation of heterocyclic structures in which there are few or no ring protons. For symmetrically substituted 1,2,3-thiadiazoles the carbon adjacent to the nitrogen atom is expected to have a lower field chemical shift than the carbon atom adjacent to the sulfur atom, as exemplified in a previous review <84CHEC-I(6)447). Several examples that follow this rule are illustrated in Table 6. A number of 4- and 5-substituted 1,2,3-thiadiazoles were studied by C NMR spectroscopy and the incremental effects of substituents... 

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