With 2-chlorothiazole

For halothiazoles the conditions for selective deprotonations at the thiazole nucleus are quite variable depending on both the kind and position of the halogen atom (see Section 3.06.7.9.2). Thus, butyllithium deprotonates selectively 2-chlorothiazole at C-5 <90JCS(Pi)329> and 4-bromothiazole at the C-2 <92JCS(P1)215>. The same reaction cannot be carried out with 2-bromothiazole due to the halogen-lithium exchange much faster than with 2-chlorothiazole. Deprotonation at C-5 in 2-bromothiazole must be done with LDA <88CJC1617>. In a similar way 2,4-dihalothiazoles yield the... 

Reaction of (EtOfsPOCl with the sodium salt of A-4-thiazoline-2-one (93) in dry acetone provides the corresponding diethyl thiazolyl-2-phosphate (94) (Scheme 46) (220-223). (EtO) PSCl reacts in the same way with various A-4-thiazoline-2-ones (224-227). When phosphoryl chloride is used the reaction goes further, and 2-chlorothiazole is obtained (7, 193, 194, 217, 228-2.30). 

The C-S bond in purine derivatives undergoes cleavage under mild conditions by nucleophilic agents such as benzylmercaptan or glutathione in dimethylformamide with a phosphate buffer of pH 6.5 (277). The salt (110) of dithiazolylsulfide heated at 190 C yields the A-4-thiazo-line-2-thione (112) and 2-chlorothiazole (111) (Scheme 56) (278-280). 

Hydroxythiazoles give 2-chIorothiazole derivatives almost quantitatively upon treatment with phosphorus oxychloride (221, 229, 428). This constitutes a convenient synthesis method for these compounds when the conversion of 2-aminothiazoles to 2-chlorothiazole derivatives fails. Esters of thiocarbamic acid or thiourethanes also react with a-halocarbonyl compounds to give the corresponding 2-alkoxythiazoles (50, 68, 209, 272). 

With malonic acid in a mixture of pyridine and piperidine 2-phenyl-4-formyl-5-chlorothiazole yields 2-phenyl-5-chloro-4-thiazoleacrylic acid (103). 

In contrast to iV-disubstituted 3-hydroxyanilines which react with Vilsmeier reagent to give AWisubstituted salicylaldehydes, their heteroanalogous iV-disubstituted 2-amino-4-hydroxythiazoles (60) react with Vilsmeier reagent to give iV-disubstituted 2-amino-4-chlorothiazole-5-aldehydes (61) <96JPR51>. 

Selective halogen-metal exchange at the 5-position has been achieved with 2,5-dibromo-4-chlorothiazole at -90°C in THF(Scheme 95), although the results obtained were very dependent upon the nature of the electrophile used [92JCS(PI)215]. 

A mixture of 2-chlorothiazole (5.0 g), ethyl 2-(4-hydroxyphenyl)propionate (8.1 g), potassium carbonate powder (8.65 g) and dimethylformamide (80 ml) is stirred at 150°-155°C for 2.5 hours. The solvent is distilled out under reduced pressure. To the residue is added water and extracted with ether. The extract is washed with a 10% aqueous solution of sodium hydroxide and water and dried. The ether is evaporated. The residue is subjected to chromatography using silica gel and eluted with 50% benzene-hexane, benzene and 10% ether-benzene to yield ethyl 2-[4-(2-thiazolyloxy)-phenyljpropionate (5.8 g). 

Examples in which heterocyclic haloarenes have been used include the photostimulated reactions of 2-chlorothiazole, 2-chloro-4-methylthiazole and 2-chloro-5-methylthiazole with pinacolone potassium enolate which lead to the formation of mono- and bis-2-thia-zolyl ketones672 and a study of the reactions of 3-halo-2-amino derivatives of benzo[ ]thio-phene with the potassium salts of acetophenone, pinacolone and cyclohexanone which indicated that, under S l conditions, mainly reduction products were formed673. 

Treatment of a-thiocyano ketones at low temperature with dry HC1 in ether solution gives satisfactory yields of 2-chlorothiazole derivatives (Scheme 186). Under the same conditions hydrogen bromide leads to the corresponding 2-bromothiazoles. 

The halogen dance reaction is also applied to the synthesis of the 5-substituted 4-bromo-2-chlorothiazole derivatives 89 <07SL3016>. Treatment of 5-bromo-2-chlorothiazole with 1.2 equiv. of LDA at -80 °C brings about full conversion to the halogen dance product 88, which is trapped with various electrophiles to give the 5-substituted thiazoles 89. For example, 4-bromo-5-trimethylsilyl-thiazole is obtained in 71% yield when 5-bromo-2-... 

TT-Electron densities, correlation with proton chemical shift, of alkylthiazoles, 344 of phenylthiazoles, 345 Electronic charges, of thiazole, 31 of aminothiazoles, 44 of chlorothiazoles, 44 of methylthiazoles, 40 Electronic effects, of 5-substituents on quaternization, 390 Electronic paramagnetic resonance, 84 coupling constants for nitrothiazoles, 84 coupling constants for 2-thiazolyl radical, 84... 

Syntheses and properties of azoles with benzothiazolyl substituents 03KGS1443. Syntheses of 2-chloro-5-chloromethylthiazole and its use in the preparation of chlorothiazole neonicotinoids 04ZOR1759. 

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