1,3-Thiazole-5 -thiones formation

Heimgartner s group investigated also the analogous thiirane formation of l,3-thiazole-5(4i /)-thiones 6.41 with phenyldieizomethane (Petit et al., 1994) and found the diastereoisomeric trans- and cw-thiiranes 6.47 and 6.48, respectively. They can be desulfurized stereospecifically with triphenylphoshine to the E)- and (Z)-benzylidene derivatives 6.49 and 6.50, respectively. Reaction of the same thiazole — thiones 6.41 with ethyl diazoacetate gives, however, a complex mixture of seven products (Kagi et al., 1994). 

Lewis acid SnCLj-assisted reaction between the l,3-thiazole-5-thione 434 and /ra r-2,3-dimethyloxirane led to the m 4,5-dimethyl-l,3-oxathiolane 435 The same Lewis acid enabled a second addition of /ra/ -2,3-dimcthyloxirane onto the C—N bond of the 1,3-thiazole ting of 434, leading to the formation of the tetrahydro-2//-thiazolo[2,3- ]-oxazole adduct 436 (Equation 200) <2000HCA3163>. Condensation of 2,4-dinitroimidazole, 8-bromotheophylline, and 8-bromoadenine with substituted methyloxiranes involved sequential A -alkylation-r/wo-substitution and furnished a series of 2,3-dihydro-imidazo[2,l- ]oxazole derivatives 437, 438, and 439 (Equations 201-203) <2000CCC1126, 2000EJ03489, 2005TL3561, 2004JHC51>. 

Meso-ionic l,3-diazole-4-thiones (103, R = Ph) have been prepared by 1,3-dipolar cycloaddition of phenylisothiocyanate to meso-ionic 1,3-oxazol-5-ones (66) and l,3-thiazol-5-ones (105). Another route to l,3-diazole-4-thiones is exemplified by the formation of the derivative (103, R = R = Me, R = R = Ph) from the methiodide (104) and methylamine. ... 

Thermolysis of a solution of epoxide 79 and l,3-thiazole-5(477)-thione derivative 80 in xylene led to the formation of three cycloadducts in 85% overall yield (22). It was expected that the geminal cyano groups of the epoxide would control the regioselectivity of the ring opening such that the anionic terminus of the dipole would be localized on that carbon. Regiochemical control led to a very selective... 

Like many other 1,3-dipoles (e.g., nitrile ylides, imines, and oxides) (7), thiocarbonyl ylides undergo head-to-head dimerization to give sterically crowded 1,4-dithianes. The first reported example involves the formation of 2,2,3,3-tetraphenyl-l,4-dithiane (18) from thiobenzophenone (5)-methylide (16) (17,28) (cf. Scheme 5.3). Other (5)-methylides are known to form analogous 1,4-dithianes (e.g., thiofluorenone (5)-methylide yields 172) (17). The (5)-methylides of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione (105) and methyl dithiobenzoate (60,104) dimerize to give compounds 173 and 174, respectively. 

Treatment of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione with ethyl diazoacetate gives, among other products, ethyl 1,3-thiazine carboxylate (179) (99). The formation of 179 has been rationalized by an acid-catalyzed addition of ethyl diazoacetate to the thiocarbonyl ylide 177 to first give intermediate 178, which undergoes a subsequent ring enlargement reaction via a Tiffeneau-Demjanov rearrangement. 

FVP at 600°C of l,3-thiazole-5(4//)-thiones 256 yields as main products the dithiazole derivatives 257 and as minor by-products the thiazete 258 and the disulfide derivatives 259 (Equation 5). A biradical intermediate has been suggested for the formation of azonylene 257 as well as for the other by-products <1998PJC1915>. 

Heimgartner and his group examined the behaviour of thioketones and l,3-thiazole-5-(4H)-thiones towards a-diazoketones at 50-90°C. A selective formation of 1,3-oxathiole was achieved, as a result of a [3+2] cycloaddition, subsequent nitrogen elimination to produce an acyl thiocarbonyl ylide, and 1,5-dipolar electrocyclisation. 

Cyclization occurs directly through catalysis by the acid liberated when a pyridine-2(lH)-thione is heated with an a-halo acid ester. The most convenient method for preparing the thiazole, however, seems to be the cyclization of (2-pyridinethio)acetic acids in acetic anhydride in the presence of pyridine. Without base catalysis the reaction is slow, which suggests a mixed anhydride intermediate. Mixed anhydride formation with ethyl chlorofor-mate in pyridine, or carboxyl activation by DCC in pyridine, gives the mesoionic product. The cyclization reaction and the chemical stability of the thiazole are adversely affected by a pyridine 6-substituent. The initially formed acylpyridinium salt (407) undergoes rapid tautomerization to the aromatic thiazole form equilibrium between the forms (407) and (408) is verified by rapid deuteration at C-2 (R1 = H) in AcOH-d (81H(15)1349). 

In the late 1980s, the reaction of organic azides and 1,3-thiazol-5-thiones (Scheme 10) to provide good yields of l,3-thiazole-5-imines (i.e., (58)) was interpreted mechanistically in terms of successive eliminations from the initially formed adduct of N2 and S via the thermally unstable thiaziridine (57) <88HCA1673>. Analogously, the photochemical reaction between aryl azides and /V-sulfinyl-anilines has been shown to yield mainly azoaromatics (59) (Scheme 11). The experimental results (including the formation of sulfur and sulfur dioxide from the presumably extruded sulfur monoxide) were interpreted in terms of the intermediacy of thiadiaziridine-1 -oxide (13). 

Thiazole-2-thione reacted with Br(CH2)3Br to give, mainly, a salt C6HgNS2" Br suggest a structure and a mechanism for its formation. 

The action of the appropriate alkali-metal salts yields 2-halogeno- (73) or 2-thiocyanato-derivatives (74) [and thence thiazoline-2-thiones (75)]. Sodiiun azide at — 5 "C produces thiazolo[3,2-rf]tetrazoles (76). Thiourea in acetonitrile at - 5 C reacts additively, affording yellow crystalline thiazol-2-yldiazo-isothiuronium tetrafluoroborates (77), but action of an excess of the reagent on either (72) or (77) caues loss of nitrogen and formation of the thiones (75). ... 

Meso-ionic Thiazoles.—Successive treatment of 5-acylamino-AMhiazoline-2-thiones (73) with methyl iodide and alkali yields products that have been recognized as meso-ionic 5-acylimino-2-methylthio-thiazoles (75) (see also these Reports, Vol. 2, p. 614). This formulation supersedes the thiazolium salt structure by which certain members of this series have previously been represented. The methylthio-group of (75) is readily replaced on treatment with nucleophilic reagents such as potassium hydrosulphide, di-cyanomethide ion, amines, etc., with formation of 2-substituted 5-acyl-amino-A -thiazolines [e.g. (76)]. ... 

Adam, W., Hartung, J., Okamoto, H., Saha-Moller, C.R., and Spehar, K., M-Hydroxy-4-(4-chlo-rophenyl)thiazole-2(3H)thione as a photochemical hydroxyl radical source. Photochemistry and oxidative damage of DNA (strand breaks) and 2 -deoxyguanosine (8-oxodG formation), Photochem. PhotobioL, 72, 619, 2000. 

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