2-Chlorothiazole

The amino group of 2-imino-3-phenyl-4-amino-5-carbethoxy-A4-thiazoline is very reactive and displaces the chlorine atom of various 2-chlorothiazoles (1577). 

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). 

This method has been applied to the synthesis of 4-methyl (659), 4-aryl (416, 519, 659), 4,5-dimethyl (137, 220, 221), 4,5-dialkyl (229, 681), 4-methyl-5-O-acetoxyethyl) (229), 4-methyl-5-(j3-carbethoxyethyl) (229), 4-ary 1-5-bromo (579), and 2-chlorothiazoles from the corresponding a-thiocyanatoketones (Table 11-28). 

The definition of crop residues for thiamethoxam and thiacloprid includes the parent and its metabolite fV-(2-chlorothiazol-5-ylmethyl)-fV -methyl-A"-nitroguanidine (designated the guanidine compound) for thiamethoxam, and 3-(6-chloro-3-pyridylmethyl)-l,3-thiazolidin-2-ylideneaminocarboxamide (designated the amide compound) for thiacloprid (Figure 3). 

Thiazole is a jt-electron-excessive heterocycle. The electronegativity of the N-atom at the 3-position makes C(2) partially electropositive and therefore susceptible to nucleophilic attack. In contrast, electrophilic substitution of thiazoles preferentially takes place at the electron-rich C(5) position. More relevant to palladium chemistry, 2-halothiazoles and 2-halobenzothiazoles are prone to undergo oxidative addition to Pd(0) and the resulting o-heteroaryl palladium complexes participate in various coupling reactions. Even 2-chlorothiazole and 2-chlorobenzothiazole are viable substrates for Pd-catalyzed reactions. 

The 4- and 5-chloro isomers are best made by selective reductive de-halogenation of 2,4- and 2,5-dichlorothiazoles (62BSF1735). 5-Bromo-2-chlorothiazole was made from the 2-amino-5-bromo derivative (45HCA985). Under homolytic conditions (NCS in the presence of dibenzoyl peroxide) 4-methylthiazole gave a mixture of the 5-chloro,... 

The reaction fails for 2-chloropyridine and 2-chlorothiazole under liquid-liquid biphasic conditions211 using a quaternary ammonium salt, probably because under such conditions the heterocyclic chloride is not reactive enough. 

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). 

Dry HC1 in ether converts 4-aryJ-A-4-thiazoline-2-one (96) to the corresponding 2-chlorothiazole (97) (Scheme 48) (230- 233. 234). Elec-... 

Dithiazolyl monosulfide (hydrochloride), to A-4-thiazoline-2-thione and 2-chlorothiazole, 405... 

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. 

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