2.4.5- trisubstituted thiazole

Aralkyl or Alkylarylthiazoles and 2,4,5-Trisubstituted Thiazoles (Tables II-5 and II-6). Alkylthioamides and their substituted derivatives have been condensed with w-bromoacetophenones (28) to... 

The Gabriel s synthesis is also applicable when a polysubstituted thiazole is required (381, 550). Thus 2,4,5-trisubstituted thiazoles are obtained by treating the corresponding a-acylaminoketones with phosphorus pentasulfide for a few minutes at 100°C (550) or at higher temperature for heavier substituents (381). (Table 11-31). 

A highly flexible synthesis of 2,4,5-trisubstituted thiazoles (vi) by in situ hydrolysis and alkylation of 2,4-disubstituted-5-acetoxythiazoles (v) has been described by Qiao et al. [10]. 

Qiao Q, Dominique R, Goodnow R Jr (2008) 2,4-Disubstimted-5-acetoxythiazoles useful intermediates for the synthesis of thiazolones and 2,4,5-trisubstituted thiazoles. Tetrahedron Lett 49 3682-3686... 

Isothiouronium chlorides (317) undergo condensation reactions with formamidinium chloride (318a) or substituted formamide acetals (318b), and with acyl chlorides (319a) or anhydrides (319b) furnishing 2,5-disubstituted or 2,4,5-trisubstituted thiazoles in moderated yields (Scheme 79) <85S414>. 

A one-pot four-component solution phase procedure has been developed for the synthesis of 2,4,5-trisubstituted thiazoles 25 <05SL79>. The four components, the 3-substituted 3-bromo-2-isocyanoacrylate 18, the ketone or aldehyde 19, the primary amine 20, and the thiocarboxylic acid 21, can vary broadly, thus producing thiazoles with five potential diversity points. Presumably, condensation of 19 with 20 generates imine 22, which reacts regioselectively with 18 and 21 via the Ugi pathway. The intermediate Ugi product 23 is in... 

Condensation with higher thioamides (2,4-Disubstituted and 2,4,5-trisubstituted thiazoles)... 

Miyatake and Yashikawa S5mthesized numerous 2,4,5-trisubstituted thiazoles and gave low yield (16 to 40%) by the interaction of a-mercaptoketones on nitriles. Asinger and Thiel [54] utilized an aldehyde and ammonia as an alternative for nitrile. 

This method gives excellent yields for simple thiazoles however, for some substituted examples low yields have been reported as a result of dehalogenation of the a-haloketone during the reaction. Hodgetts and Kershaw have reported recently the re-giocontrolled synthesis of 2,5-disubstituted and 2,4,5-trisubstituted thiazoles from ethyl 2-bromo-5-chloro-4-thiazolecarboxylate using sequential Suzuki coupling reactions (Equation 36) [36]. 

The acylation with acid chloride and the urea formation with isocyanate of intermediate resin 16 afforded other substituent groups onto 4-aminothiazole. Under microwave (MW) irradiation reaction with isocyanate and acylation reaction with acid chloride, R -substituted thiazole resin 19 was obtained. Following conversion of sulfonyl resin 19 to sulfonyl resin 20 (mCPBA/CH2Cl2), substitution reactions promoted by treatment with appropriate amines (R R" N diversity elements) furnished the 2,4,5-trisubstituted thiazoles 2 (29 examples 36-25% isolated yields from Merrifield resin 1, >95% purities, Table 10.1). 

Unpublished results of solid-phase synthesis of 2,4,5-trisubstituted thiazoles in our laboratory. 

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