1,2,3-Thiadiazole thermolysis

Thermolysis of the 1,2,3-thiadiazoles (545) in the presence of carbon disulfide leads to the thiocarbonyl carbene (546) adduct, the ring-fused l,3-dithiole-2-thione (547) (76JOC730). 

They can be prepared by the thermolysis of 1,2,3-thiadiazoles or by reaction of ketenes with phosphorus pentasulfide.111-113... 

Unlike simple 1,2,3-thiadiazoles, 1,2,3-benzothiadiazoles do not form thioketenes on thermolysis or photolysis. Instead, they yield many products, depending on the conditions (Equation 3). The mechanisms of these reactions have been extensively studied <1984CB107>. 

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>. 

Thiadiazoles are also obtained when the thermolysis is carried out in the presence of isocyanates and carbodiimides <1996CHEC-II(4)307>. There have been no new reports of this type of rearrangement since the publication of CHEC-II(1996). 

Dithiazolyl radical 228 photochemically and thermally disproportionates to afford the 1,2,5-thiadiazole 229 and the unstable 1,2,3-trithiole 230 (Equation 54) <2000JCD3365>. Thermolysis of perfluoro-l,3A4(i2,2,4-benzodithiadia-zine 231 affords complex mixtures of heterocycles including perfluoro-2,l,3-benzothiadiazole 232 and 7,8-difluoro-benzo[l,2- 3,4-f ]bis[l,2,5]thiadiazole 233 (Equation 55) <2005EJI4099>. 

Thermolysis of 2,5-dihydro-l,3,4-thiadiazole 30 in CgDsCl solution at 20-35 °C gave spirothiiranes 43 and 44, O-hydrogen 0,0,A-ortholactone 45, the thio-A-ester 46, and 0,A,A-ortholactone 47 (Scheme 4) <1997HCA1260>. The ratio of these thermolysis products did not significantly vary between 23 and 35 °G. 

Thiadiazolin-2-imines can also be converted to thiadiazolin-2-ones in two steps <2004PS601, 2003HAC421, 2003PS1101>. The nitrosation of the thiadiazol-2-imines 87 with saturated nitrite in acetic acid at 0-5°C gave the iV-nitroso-l,3,4-thiadiazol-2(37/)imines 88 in 72% yield. Thermolysis of the latter in refluxing xylene gave the 1,3,4-thiadiazolin-2-one 89 in 78% yield (Scheme 8) <2003HAC421>. 

The thermolysis of l-([l,3,4]thiadiazol-2-yl)tetrazoles 133 gives rise to the loss of dinitrogen from the tetrazole ring and the formation of 2,6-diaryl[l,2,4]triazolo[5,l+][l,3,4]thiadiazoles 71 (Equation 39) <1985IJB908, 1990FA953>. (For another synthesis of compounds 71, see Section 11.07.8.1.5.)... 

Thermolysis of the thiadiazole (164) leads to elimination of isocyanate and sulfur giving the triazine derivative (167). If the thermolysis is carried out in the presence of phenols 2-aryl-benzimidazoles (168) are produced <85JCS(P1)1007>. The S—N bond of (157) is readily cleaved with both N- and C-nucleophiles. Thus, treatment of (157) with an excess of amine gives the sulfenamide (169) (Scheme 39) and reaction of (157) with active methylene compounds leads to derivatives of type (170) (Scheme 39) which on heating furnish (171). Cyanide ion inserts into the S—N bond of (164), probably via the intermediate (172) which immediately recyclizes to give the thiadiazinone (173) (Scheme 40) <85JCS(P1)1007>. 

The thermolysis of thioamides (183) with 7V-sulfinylsulfonamides (190) gives moderate yields of 1,2,4-thiadiazoles (Equation (27)), a competing and sometimes dominant side reaction is the formation of nitriles <84CHEC-I(6)463>. No new examples of this type of reaction have been found in the 12 years since 1984. 

A similar transformation occurs during the thermolysis of l-thiacarbamyl-5-phenyl tetrazole (286) to give 5-amino-3-phenyl-1,2,4-thiadiazole (287) (Equation (43)) <92JPR283>. 

The thermolysis of 4-benzyl-5-sulfonyliminothiatriazolines (318) in the presence of a variety of nitriles yields 5-imino-l,2,4-thiadiazolines (320). These reactions have been interpreted as proceeding via a thiaziridinimine intermediate (319) (Scheme 70) <76JOC3403>. 1,2,4-Thiadiazoles are also obtained when the thermolysis is carried out in the presence of isocyanates to give (321) and carbodiimides to give (322) <84CHEC-I(6)463>. 

Photoelectron spectroscopy was used by French workers to follow the thermolysis of 2-azido-thiadiazoles <88CJC2830> (see also Section 4.10.6.1). No publications related to fluorescence were found. 

As reported before (see Section 4.14.6.1, Scheme 19), thermolysis of oxathiazolines (169) proceeds via a retro 1,3-dipolar cycloaddition to produce the carbonyl compound and the nitrile sulfide intermediate. Trapping reactions have been carried out with DMAD, ECF (ethyl cyano formate), and benzonitrile to give respectively isothiazoles (170) and thiadiazoles (171) and (172). However in two particular cases (R = 4-MeOC6H4, 4-ClCgH4, thermolysis in the presence of benzonitrile gives (172) and the thiadiazole (173) in very low yields. It has been suggested that the latter arises... 

Thieno[2,3-r 1-l,2,3-thiadiazoles 40a-f heated with CS2 in a double compartment autoclave produced thieno[2,3-rfl-l,3-dithiol-2-thiones 41a-f <2001MOL145>. In addition to the thermolysis product 41e, thieno[2,3- / -l,2,3-thia-diazoles 40e also produced bisthieno[2,3-/ 2, 3 -< ][l,4]dithiine 42 in 36% yield (Equation 3). 

With a few exceptions these species dimerize readily [60, 119, 174-176], and most of the methods applicable to the synthesis of monomers involve thermolytic processes such as the flash thermolysis of 1,2,3-thiadiazoles [177,178], or of 5-silylated ketenedithioacetals [179]. 

The most convenient sources of species 89 are 1,2,3-thiadiazoles 91, which are valence tautomers of the unknown a-diazothioketones. Loss of nitrogen from 91 may be achieved by irradiation or by thermolysis. Larsen and coworkers383 examined the irradiation of 91 in the presence of diethylamine and isolated N, IV-diethylthioacetamide in high yield, which implies trapping of thioketenes during photolysis. Mechanistic studies excluded thiirene as the intermediate in the photolysis at 150 K (equation 95). 

The thermolysis of 1,2,4-oxathiazolines 20, as well as their interaction with benzylamine, produces nitriles of the corresponding benzoic acids. When compounds 20 were treated with Ph3P, the same nitriles and Ph3P=S were obtained. Oxidation of compounds 20 with MCPBA gives an inseparable oily epimeric mixture of the corresponding A-oxides 21 in the approximate ratio 3 1. 1,2,4-Thiadiazoles 100 were formed through the contact of compounds 20 with silica gel or Lewis acids (Scheme 23) <2003TL2517>. 

Partially and perfluorinated thioketones and thioaldehyde were stabilized as anthracene adducts (70). The adducts (70) were prepared in moderate yield from the corresponding carbonyl compounds with P4S10 or Lawesson s reagent in the presence of anthracene under toluene reflux. The generated thiocarbonyl compounds are not accessible in bulk due to their tendency towards polymerization. By thermolysis of the anthracene adducts (70) in the presence of C,N-bis(triisopropylsilyl)nitrilimine (NI), 1,3,4-thiadiazole derivatives (71) were obtained. Also, 1,3-dipolar cycloaddition with bis(trimethylstannyl)diazomethane (BTSD) to give consecutive products (72) from a 1,2-metallotropic migration of primary adducts was discussed. [95LA95]... 

A notable aspect of the chemistry of the annelated [l,2,3]thiadiazoles is their characteristic thermolysis to [1,3]-diradicals (Scheme 14). Trapping of the diradical from thiadiazolo[4,5-6]pyridine (83) with carbon disulfide afforded pyridyl dithiolthione (84), which on hydrazinolysis afforded the air-unstable 2,3-pyridinedithiol (85) <78PJC2039>. 

The majority of 1,2,3-thiadiazole chemistry has been directed toward the study of thermal and photochemical reactions. Upon thermolysis 1,2,3-thiadiazoles afford a number of varied products (77T449, 77JOC575) as illustrated in equation (1). The mechanism of formation of the myriad of products has received considerable attention. 

Moderate yields of thiadiazoles (255) also have been obtained by the thermolysis of mixtures of thioamides (253) and A-sulfinylsulfonamides (259 Scheme 91) (62AG135). The manner in which the proposed intermediate (260) is converted into (255) has not been discussed and the mechanism of this reaction deserves further study. TV-Arylthioureas (261) form 1,2,4-thiadiazole derivatives (73) ( Hector s bases ) in good yields when oxidized with acidic hydrogen peroxide or other oxidizing agents (nitrous acid, iron(III) chloride) as indicated in Scheme 92 (65AHC(5)119). Evidence for the intermediate formation of dithio-... 

Alkyl azides readily undergo 1,3-dipolar cycloaddition to arylsulfonyl isothiocyanates (375) to yield thiatriazolines (376). Thermolysis of (376) in the presence of isocyanates or carbodiimides produces 1,2,4-thiadiazole derivatives (378) and (379), respectively. The intermediate formation of a thiaziridinimine (377) has been postulated as indicated in Scheme 137 (75JOC1728, 75S52). The use of isothiocyanates as dipolarophiles produces dithiazolidines (380) instead of the thiadiazole derivatives. In these reactions the intermediate thiazirine (377) functions as a 1,3-dipole with the positive charge primarily localized on sulfur. It was recently proposed that the reaction of oxaziridines (381) with isothiocyanates produces a similar thiazirine intermediate (382) which reacts in a different regiospecific manner with isothiocyanates to produce 1,2,4-thiadiazole derivatives (383) and (384 Scheme 138) (74JOC957). 

A more recent method which provides 3,5-disubstituted products (301) of unequivocal structure involves the thermolysis of a 5-substituted l,3,4-oxathiazol-2-one (338) in the presence of a nitrile (usually in excess) (Scheme 143) (77JOC1813). Best yields are obtained when the intermediate nitrile sulfides (70TL1381) are generated in the presence of nitriles which are electron deficient (see Scheme 122). Another excellent method for the synthesis of C-linked 1,2,4-thiadiazoles involves the amidation of thioacylamidines (353) as indicated in Scheme 144 (80JOC3750) (also see Scheme 117). 

Thermolysis of the 1,3,4-oxathiazolines (130 R1 = Ar, X = O, Y = S) gives a ketone and a nitrile sulfide (see Section 4.34.3.4.1 Scheme 29). The latter can be trapped with DMAD to give isothiazoles (93) or with Et02CCN to yield 1,2,4-thiadiazoles (96 R2 = C02Et). Trapping with ethyl propynoate leads to a mixture of the two possible isomeric isothiazoles, their ratio (1.31-1.34) being apparently independent of R2, R3 and of the aryl substituent (80CC714) (compare with Section 4.34.3.2.6). 

A similar reaction occurred as a result of flash vacuum thermolysis of 5-alkyl-4-phenyl-l,2,3-thiadiazoles <2004ARK61>. Thermolysis of 4-phenyl-5-propyl-l,2,3-triazole at 340°C gave the two 1,4-dithiins 113 and 114 shown in Scheme 18. Diradicals, equilibrated with a thiirene and a carbene, were postulated intermediates. 

Reaction of thioketones 317 with an excess of diazomethane 318 gave 2,5-dihydro-l,3,4-thiadiazoles 319. Thermolysis of 319 in refluxing benzene for 2h gave thiocarbonyl 3 -methylides 320, which underwent electro-cyclization to give corresponding thiiranes 321 (Scheme 92) <2005EJ01519>. 

Phenyl-l,3,4-oxathiazol-2-one (370), prepared from primary amides and tri-chloromethanesulfenyl chloride, undergoes a ready thermal elimination of carbon dioxide with the formation of the nitrile sulfide ylide (371). This can be trapped by a wide variety of unsaturated dipolarophiles, and with an alkyne provides a ready route to isothiazoles (372) (see Chapter 4.17). Applications to 1,2,4-thiadiazole synthesis are described in Chapter 4.25. Thermolysis of l,3,4-oxadiazolin-5-ones (500 C/10 mmHg) results in the loss of CO2 and generation of the corresponding nitrilimine (78JOC2037). 

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