1.3- Thiazole-5 -thione oxides

A selective reaction was also observed in the heterocyclic series with 1,3-thiazole-5-(4ff)-thione oxides and alkyllithiums [107]. A more sluggish reaction was observed with Grignard reagents. 

Thiazole A -oxides can easily be alkylated on the oxygen. For example, Ar-(alkoxy)-5-(p-methoxyphenyl)-4-methylthiazole-2(377)-thiones were prepared from Ar-(hydroxy)-5-( -methoxyphenyl)-4-methylthiazole-2(3//)-thione tetraethylammonium salt and an appropriate alkyl chloride or tosylate in moderate to good yields <20060BC2313>. A -Methoxythiazole-2(377)-thiones were synthesized from the A -hydroxythiazole-2(3//)-thiones by treatment first with a tetraalkylammonium hydroxide in methanol and then methyl ra-toluenesulfonate in DMF <2005EJ0869>. 

Oxidation, already described in neutral and acidic media, may also be performed in basic medium. An alkaline solution of H2O2 reacts with 4-thiazoline 2-thione to yield thiazole-2-sulfonic acid (201-203), whereas alkaline oxidation performed with (NH )2S20g yields the disulfides (148). 

Because of their use in the rubber industry various sulfenamido thiazoles (131) have been prepared. They are obtained in good yields through the oxidation of A-4-thiazoline-2-thiones (130) in aqueous alkaline solution in the presence of an amine or ammonia (Scheme 66) <123, 166, 255, 286, 308, 309). Other oxidizing agents have been proposed (54, 148. 310-313) such as iodine (152), chlorine, or hydrogen peroxide. Disulfides can also be used as starting materials (3141. 

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. 

Monoalkyl aminium radicals cannot be prepared from PTOC carbamates 29 due to an equilibrium in solution favoring 2-mercaptopyridine-Ar-oxide and an alkyl isocyanate [Eq.(ll)]. With Af-(monoalkyl)thiazole-2-thione carbamates, TTOC carbamates, the equilibrium lies far to the side of the carbamate 84, and these precursors can be prepared from an isocyanate and Ar-hydroxythiazole-2-thione [Eq. (12)]. Under UV photoinitiation in acidic media, TTOC carbamates are efficient precursors for monoalkyl aminium cation radicals (Scheme 26). Monoalkylaminium radical 85 ey-clizes as efficiently as its analogous dialkylaminium radical 66, and the resulting carbon radical 86 can be trapped by a variety of radicophiles (91JOC1309) to prepare substituted pyrrolidines. 

Thione groups can often be eliminated by oxidation probably the sulfinic acid is the intermediate. Sometimes the sulfinic acid can be isolated (e.g., 740 741), but more often it spontaneously loses SO2. In this way, thiazoline-2-thiones give thiazoles, l,2-dithiole-3-thiones 742 are converted into 1,2-dithiolylium salts 743, l,3-dithiole-2-thiones 744 into 1,3-dithiolylium salts 745, 1,5-disubstituted imidazole-2-thiones into imidazoles <2003JHC229>, and 3-mercapto-l,2,4-triazoles into the parent triazole <2006S156>. In the pyrazole series, 746 also loses an A-methyl group to yield 747. 

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). 

The new dihydro-1,3-thiazino[3,2-a]pyridinium 9-oxide system [e.g. (59)] has been prepared by condensation of 3-hydroxypyrid-2-thiones with 1,3-difunctional propane derivatives (Scheme 10). Acid-catalysed dehydration of (59) in warm orthophosphoric acid or in cold sulphuric acid leads to the 1,3-thiazine (61) and to the isomeric thiazole (62) in the... 

The oxidation of P-imino thiones 9 with iodine or hydrogen peroxide gives 3,5-disubstituted iso-thiazoles 12 ... 

Recently, however, there has been increased interest in N-oxides for the generation of hydroxyl radicals in aqueous solution. This process has been reported for some nitrated N-oxides but is most often observed for tautomeric N-oxides, where the N-hydroxy form is significant. " "" The main application is in photobiology, as specific sources of hydroxyl radicals for DNA damage, both strand break and base modifications. N-Hydroxy-2-pyridone and 2-pyridinethione, - N-hydroxy-4-(4-chlorophenyl)thiazole-2(3H)-thione, " and pyrimido[5,4-g ]pteridinetetraone N-oxide (for which the path followed depends on conditions) " and related N-oxides " have been used for this purpose. 

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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