Thiazoles 2-acyl- from

Heterocyclic ring systems are also used to connect two anthraquinone groups. Typical examples include Cl Vat Red 10 (6.106), which is an oxazole derivative obtained from 2-amino-3-hydroxyanthraquinone and the appropriate acyl chloride, the similar thiazole derivative Cl Vat Blue 31 (6.107) and the oxadiazole derivative Cl Vat Blue 64 (6.108). 

Nucleophilic attack at sulfur is implicated in many reactions of 1,2,4-thiadiazoles <84CHEC-I(6)463> and in general soft nucleophiles attack at sulfur. For example, reaction of 3-hydroxy-5-phenyl-1,2,4-thiadiazole (23) with acetic anhydride in the presence of dbu at 130°C gives the thiazoles (31) and (32) <85JHC1497>. These products may be reasonably explained by the mechanism outlined in Scheme 9 in which the thiadiazole ring is opened by the acetic anhydride carbanion. There is some evidence that (32) may arise from attack of the carbanion on the A-acylated derivative (30a) (Scheme 9) <85JHC1497>. 

Bicyclic derivatives (133) of l,3-thiazol-4-imines have been prepared by treatment of (2-pyridylthio)acetonitrile with acid chlorides. The same compounds (133) are also formed from 5-acyl-2-mercaptopyridine, chloroacetonitrile, and acid chlorides. 

Direct thiation is used predominantly for the synthesis of annelated thiazoles, most often from heterocyclic acyl-amides. Examples are highlighted in CHEC-II(1996) <1996CHEC-II(7)49> no further examples have been reported in this period. 

The incorporation of complex side chains at the 7 position based on alkyloximes of 2-amino-thiazole-5-gyloxylamides has provided drugs with very wide antibacterial activity that extend to hitherto resistant species such as pseudomonas. The preparation of one of the simpler side chains involves, first, the formation of the methyl ether from the oxime obtained by the nitrosation of methyl acetoacetate. Chlorination of the product, for example with sulfuryl chloride, gives the intermediate (21-1). The aminothiazole ring is then formed by reaction of that with thiourea to give (21-2). The free acid (21-3) is obtained by saponification of the product. The protected acid chloride (21-5) is obtained by sequential acylation of the amino group with chloroacetyl chloride and then reaction with thionyl chloride. 

Acylation of the amine with the methoxime from aminothiazole-glyoxylate has a similar effect on broadening the antibacterial spectmm in the 3-methyl series. In this case, the amine group on the starting thiazole (21-3) is first protected by conversion to (28-2) by alkylation with thriphenylmethyl chloride. Condensation of the acid by the mixed anhydride method with 7-ADC A (26-6) leads to the corresponding amide. The trityl group is then removed to afford the antibiotic cefetamet (28-3) [34]. 

Sulfur Bake. The yellow, orange, and brown sulfur dyes belong to this group. The dyes are usually made from aromatic amines, diamines, and their acyl and nuclear alkyl derivatives. These may be used in admixture with nitroanilines and nitrophenols or aminophenols to give the desired shade. The color formed is said to be the result of the formation of the thiazole chromophore, evident in dye structure (1). 

Several new syntheses of thiazoles from thioureas have been developed in recent years. Werbel95 was able to prepare 2-aminothiazoles by reaction of thioureas with bis(/3-chloroethyl) ether. 1,3-Disubstituted thioureas, however, yielded disubstituted 4-thiazolines. In a German patent, Rcisinger96 reported that 2-aminothiazole was formed in 88% yield from thiourea and vinyl acetate in the presence of sulfuryl chloride. A method for the preparation of the 4-hydroxy-2-amino-thiazole (47), which probably exists in the tautomer shown, has been developed by Delaby et al.97 via the reaction of thiourea with jS-acyl-acrylic acid or its esters. Zbiral98 has observed that acylvinylphos-... 

As can be seen in the scheme below, a series of substituted 2-(2-aminothiazol-4-yl)-benzo[ ]furans with inhibitory activity for leukotriene B4 were made from benzofurans via acylation, followed by Hantzsch thiazole formation <070BC3083>. 2-Substituted benzo[ ]furans could also be generated via an aerobic oxidative coupling of 2-unsubstituted benzo[ ]furans with arenes through the palladium-catalyzed double C-H activation <07OL3137>. In addition, 2,3-diarylbenzo h I uran could be constructed by a palladium-catalyzed arylation of benzo[6]furan with an aryl chloride in the presence of a bulky, and electron-rich phosphine <07OL1449>. 

The mechanism of the condensation in Part D probably involves thioformylation of the metallated isocyanoacetate followed by intramolecular 1,1-addition of the tautomeric enethiol to the isonitrile. This thiazole synthesis is analogous to the formation of oxazoles from acylation of metallated isonitriles with acid chlorides or anhydrides. " Interestingly, ethyl formate does not react with isocyanoacetate under the conditions of this procedure. Ethyl and methyl isocyanoacetate have been prepared in a similar manner by dehydration of the corresponding IV-formylglycine esters with phosgene and trichloromethyl chloroformate, respectively. The phosphoryl chloride method described here was provided to the submitters by Professor U. Schollkopf and is based on the procedure of Bohme and Fuchs.The preparation of O-ethyl thioformate in Part C was developed from a report by Ohno, Koi/uma, and Tsuchihaski. 

Similarly, AT-acylthiazolium salts generated in situ from thiazoles and acyl chlorides react with... 

Rearrangement of A, A -bis-(a-aminoalkyl)dithioxamides (315), easily available from dithio-xamides, aromatic aldehydes, and secondary amines, gives in the presence of alkylating or acylating agents, the thiazole derivatives (316) (Equation (56)) <84N43>. 

Reductive cyclization occurs when a nitrodisulphide is heated with aqueous sodium sulphide (which reduces the nitro group) and carbon disulphide (review [B-52]). An acylated thiol forms a thiazole ring with an iV-carbonyl function when compound (10.2) is reduced with trielhyl phosphite (the formula of the product is incorrectly shown in the paper). Microbiologically useful -lactams can also be synthesized from the disulphide (10.3) by treatment with a two-molar proportion of certain phosphoranes at — 50°C in an intramolecular... 

A thiazole ring may also be constructed from a lactam thiocarbonyl and one of the following reagents DMAD [3177], a 2-bromoacrylic acid or its nitrile [20S1, 3509], an aryl isothiocyanate and an alkyne [2706, 2915], a reactive a-methylene ketone such as dimedone [3944], an acyl halide [2433] or a halo ketone which is prepared in situ [2475]. 

Anions derived from other isocyanides can be acylated (or thioformylated ), the products spontaneously closing to oxazoles " (thiazoles). 

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