Thiazole oxides—

Furo[2,3-d]thiazoles Oxidation of furylthioureas 176 using bromine in acetic acid gives good yields of the furo[2,3-J]thiazoles 177 (Eq. (30)) (77CS199). 

Schneider, T.L., Shen, B., and Walsh, C.T., Oxidase domains in epothilone and bleomycin biosynthesis thiazoline to thiazole oxidation during chain elongation. Biochemistry, 42, 9722, 2003. 

T.L. Schneider, B. Shen, C.T. Walsh, Oxidase domains in epotlulone and bleomycin biosynthesis thiazoUne to thiazole oxidation during chain elongation. Biochemistry 42, 9722-9730 (2003)... 

Thus in neutral medium the reactivity of 2-aminothiazoles derivatives toward sp C electrophilic centers usually occurs through the ring nitrogen. A notable exception is provided by the reaction between 2-amino-thiazole and a solution (acetone-water, 1 1) of ethylene oxide (183) that yields 2-(2-hydroxyethylamino)thiazole (39) (Scheme 28), Structure 39... 

Reactions of the 2-amino-4,5-substituted thiazole (52) in acetic acid with ethylene oxide has been reported to give the N-exocyclic disubstitution product (S3) (201) in a 40% yield (Scheme 38). The reactive species in this reaction is probably the carbocation generated in acetic acid by ethvlene oxide. 

Scheme 55) (235. 236). -The product obtained (77) is probably formed via the protonated form of the thiazole, whose reactivity is treated in Section IV, 1. The light-yellow leucobase (77) is reported to be oxidized by PbOj to the red-black carbinol (78) (236). This condensation reaction is also successful when benzaidehyde is replaced by formaldehyde, bis(2-amino-4-phenylthiazolyl-5)methane (79 i beine obtained (Scheme 56) (237). 

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. 

Thiazole disulfides react with amines in the presence of oxidizing agents to yield 2-sulfenamidothiazoles (314). Results obtained in the ben-zothiazole series (323) indicate that they could be used as starting material to obtain 2-halosulfothiazoles. 

Thiazol-2-yl radicals have also been generated by silver oxide oxidation of thiazol-2-ylhydrazine in various aromatic solvents (Scheme 69). The... 

Thiazole is relatively resistant to oxidation, and very few reactions of this type have been recorded. Under photosensitized oxygenation, triphenylthiazole affords various products of ring cleavage depending on... 

Thiazole-N-oxides are prepared by the action at low temperature (-10°C) of hydrogen peroxide in acetic acid (474). 4-MethyIthiazole and 2,4-dimethylthiazole afforded the corresponding N-oxides with yields of 27 and 58%, respectively (Scheme 88). Thiazole-N-oxides without a methyl group in the 2-position are so unstable that they have a tendency to form 2-hydroxythiazoles and are decomposed by oxidation, whereas a 2-methyl group would prevent such rearrangement (474). 

The antibacterial [(5-nitrofuryl)vinyl]thiazole-N-oxides (193) were prepared by oxidizing the corresponding thiazoles with hydrogen peroxide or peracetic acid (Scheme 89) (475). 

Thiazole carboxylic acid hydrazides were prepared in a similar way (444, 445). Thus by refluxing thioacetamide or thiobenzamide with y-bromoaceto acetic ester arylhydrazones (83) for several hours in alcohol the 4-carboxythiazole derivatives (84) listed in Table II-ll were obtained (Scheme 36) (656). This reaction is presumed to proceed via dehydration of the intermediate, thiazoline-S-oxide. 

Various 4-, 5-, or 4,5-disubstituted 2-aryIamino thiazoles (124), R, = QH4R with R = 0-, m-, or p-Me, HO C, Cl, Br, H N, NHAc, NR2, OH, OR, or OjN, were obtained by condensing the corresponding N-arylthiourea with chloroacetone (81, 86, 423), dichloroacetone (510, 618), phenacyichloride or its p-substituted methyl, f-butyl, n-dodecyl or undecyl (653), or 2-chlorocyclohexanone (653) (Method A) or with 2-butanone (423), acetophenone or its p-substituted derivatives (399, 439), ethyl acetate (400), ethyl acetyl propionate (621), a- or 3-unsaturated ketones (691), benzylidene acetone, furfurylidene acetone, and mesityl oxide in the presence of Btj or Ij as condensing agent (Method B) (Table 11-17). 

The overall reactivity of the 4- and 5-positions compared to benzene has been determined by competitive methods, and the results agreed with kinetic constants established by nitration of the same thiazoles in sulfuric acid at very low concentrations (242). In fact, nitration of alkylthiazoles in a mixture of nitric and sulfuric acid at 100°C for 4 hr gives nitro compounds in preparative yield, though some alkylthiazoles are oxidized. Results of competitive nitrations are summarized in Table III-43 (241, 243). For 2-alkylthiazoles, reactivities were too low to be measured accurately. 

Little work has been carried out on thiazole N-oxides. These products are unstable and breakdown by autoxidation to give thiazolium-A -oxide sulfates and other decomposition products (264). They are prepared by direct oxidation with hydrogen peroxide, or by tungstic acid (264, 265) or peracetic acid (265-267). 

Only one reaction of thiazole N-oxides has been studied in detail. The rearrangement in acetic anhydride of 2,4-dimethylthiazoIe-3-oxide gave 2-acetoxy-4-methylthiazole and 4-acetoxymethyl-2-methylthiazole in a ratio of about 4.5 to 1(264). 

On account of the high degree of stability of the thiazole ring a large variety of substituted derivatives yield thiazolecarboxylic acids upon oxidation. The oxidation of a methyl group or a substituted methyl group to a carboxyl group has been accomplished in a few instances. 

The alkyl derivatives of thiazoles can be catalytically oxidized in the vapor phase at 250 to 400°C to afford the corresponding formyl derivatives (21). Molybdenum oxide, V2O5, and tin vanadate are used as catalysts either alone or with a support. The resulting carbonyl compounds can be selectively oxidized to the acids. 

Thus 2-phenyl-4(hydroxymethyl) thiazole upon oxidation with aqueous chromic acid yields 2-phenyl-4-thiazolecarboxylic acid (25,26). 

An other example is the oxidation of 4-(hydroxymethyl)thiazole with a mixture of nitric and sulfuric acids at -5°C (24, 27). 

Thiazole acid chlorides react with diazomethane to give the diazoketone. The later reacts with alcoholic hydrogen chloride to give chloroacetylthiazole (Scheme 16). However, the Wolff rearrangement of the diazoketone is not consistently satisfactory (82). Heated with alcohol in the presence of copper oxide the 5-diazomethylketone (24) gives ethyl 5-thiazoleacetate (25) instead of the expected ethoxymethyl 5-thiazolyl ketone (Scheme 17) (83). 

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