Thiazole derivatives, 4-component reactions

A series of tetrasubstituted thiazole derivatives 28 has been prepared via a multi-component tandem protocol <07T10054>. Reaction of bis(aroylmethyl)sulfides 23 with aryl aldehydes and ammonium acetate in 1 2 1 ratio under solvent-free microwave irradiation affords 28 in good yields. This reaction presumably starts with Knoevenagel condensation of sulfide with 2 equiv. of aryl aldehydes to give 24. Michael addition with ammonia and concomitant cyclocondensation lead to 26. Base-catalyzed ring opening of 26 to 27 and ring... 

A one-pot, three-component reaction of isocyanides 45, dialkyl acetylenedicarboxylates 46 and ethyl 2-oxo-2-(l,3-thiazol-2-ylamino)acetates 44 provides easy access to 5H-[1,3]thiazolo[3,2- pyrimidinc derivatives 52 <07SL2703>. Presumably, addition of... 

A series of imidazo[2,l-6]thiazole derivatives 71 has been prepared through a catalyst-free three-component reaction in water <07TL7263>. Reaction of isocyanides 66, aryl aldehydes 67, and 2-aminothiazoles 65 in water at 70 °C produces the fused aminothiazoles 71 in good yields. 

Simple examples of this strategy, which for the synthesis of thiazoles is known as the Hantzsch synthesis, are shown below the syntheses of 2,4-dimethylthiazole where the heteroatoms are provided by thioacetamide, " and 2-aminothiazole, in which 1,2-dichloroethyl ethyl ether is utilised as a synthon for chloroethanal and the heteroatoms derive from thiourea. " The use of thioureas as the sulfur component with 2-chloroacetamides as the second unit gives rise to 2,4-diaminothiazoles. " Conversion of 1,3-diketones into their 2-phenyliodonium derivatives and reaction of these with thioureas produces 2-amino-5-acylthiazoles. The first step in such ring syntheses is 5-alkylation. " A useful variant is the use of an a-diazo ketone in place of the a-halocarbonyl component. " ... 

Some pyrrole derivatives have pleasant flavor. For example, pyrrole-2-carboxaldehyde gives a sweet and corn-like odor and 2-acetylpyrrole has caramel-like flavor. However, some pyrroles have been found to contribute to off-flavor of food products (24). Pyrroles have not received as much attention as flavor components as other heterocyclic Maillard reaction products such as pyrazines and thiazoles even though the number of derivatives identified is almost the same as that of pyrazines (Figure 1). Proposed formation mechanisms of pyrroles in the Maillard reaction systems are similar to those of thiophenes (Figures 2). 

The Ugi reaction19 is a four-component condensation requiring a carbonyl compound 8, an amine 29, a carboxylic acid derivative 30, and an isocyanide 31. The product from this mixture is a-aminoacyl amide 32 that again could be hydrolyzed to an a-amino acid. Pharmaceutically valuable thiazoles 33 have been elaborated from intermediates formed by this reaction sequence.20... 

S.2.2.2 MCRs Involving Imidazol-2-yUdenes or Imidazolin-2-ylidenes as Key Components Imidazol-2-ylidenes III can also achieve similar reactivity to thiazol-2-ylidenes II. In 2003, Nair and coworkers described the first-ever MCR of this family of NHCs, wherein two related carbenes reacted differently. As shown in Scheme 5.11, reaction of imidazol-2-ylidenes III (R=aryl) with DM AD and aldehydes afforded furanones 15. However, when more nucleophilic imidazolin-2-ylidenes IV (R=aryl) were used, under the same reaction conditions, 2-oxy-maleate derivatives 16 were obtained [16]. 

Thiols arising in the MaUlard reaction, mostly derived from heterocyclic compounds, such as furan, thiophene, thiazole and other heterocycles, are important flavour-active components of meat, coffee and many other foods. For example, 2-furanmethanethiol (furan-2-ylmethanethiol, furfuryl mercaptan) has an odour resembling roasted coffee, N- (2-mercaptoethyl) -1,3-thiazolidine (8-127), which is formed in the reaction of fructose with cysteamine, and has a very strong odour resembling popcorn. Its odour threshold is 0.005 ng/1 in air. 

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