Thiazole derivatives, 4-component

Other interesting three-component cycloadditions are the following Sulfur dioxide and diazo compounds lead to episulfones (equation 75)" —in a special case to 4,5-dihydrothiepine S.S-dioxides" sulfur dioxide, ketene, and arylimine lead to thiazole derivatives (equation 76) sulfur dioxide, quinone, and alkenes lead to benzoxathiane derivatives (equation 77). 

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 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. 

As shown in Scheme 2, two heteroatom-carbon bonds are constructed in such a way that one component provides both heteroatoms for the resultant heterocycle. By variation of X and Z entry is readily obtained into thiazoles, oxazoles, imidazoles, etc. and by the use of the appropriate oxidation level in the carbonyl-containing component, further oxidized derivatives of these ring systems result. These processes are analogous to those utilized in the formation of five-membered heterocycles containing one heteroatom, involving cyclocondensation utilizing enols, enamines, etc. 

Thiamine is present in cells as the free form 1, as the diphosphate 2, and as the diphosphate of the hydroxyethyl derivative 3 (Scheme 1) in variable ratio. The component heterocyclic moieties, 4-amino-5-hydroxymethyl-2-methylpyrimidine (4) and 4-methyl-5-(2-hydroxyethyl)thiazole (5) are also presented in Scheme 1, with the atom numbering. This numbering follows the rules of nomenclature of heterocyclic compounds for the ring atoms, and is arbitrary for the substituents. To avoid the use of acronyms, compound 5 is termed as the thiazole of thiamine or more simply the thiazole. This does not raise any ambiguity because unsubstituted thiazole is encountered in this chapter. Other thiazoles are named after the rules of heterocyclic nomenclature. Pyrimidine 4 is called pyramine, a well established name in the field. A detailed account of the present status of knowledge on the biosynthesis of thiamine diphosphate from its heterocyclic moieties can be found in a review by the authors.1 This report provides only the minimal information necessary for understanding the main part of this chapter (Scheme 2). 

Since their commercial introduction during the 1940s as components of proprietary detergents and laundry preparations, these products have found extensive usage in the whitening of paper and textile materials. Disperse FBAs are available for whitening hydrophobic fibres and solvent-soluble FBAs impart fluorescence to oils, paints, varnishes and waxes. Approximately 75% of commercially established FBAs are stilbene derivatives with inherent substantivity for paper and cellulosic textiles, but the remainder come from about twenty different chemical classes. These include aminocoumarins (6%), naphthalimides (3%), pyrazoles and pyrazolines (each about 2%), acenaphthenes, benzidine sulphones, stilbene-naphthotriazoles, thiazoles and xanthenes (each about 1%). FBAs of these and other chemical types are discussed in detail in Chapter 11 of Volume 2. 

The range of colours obtainable in monoazo dyes made by conpling representative derivatives of these amino heterocycles with para conpling tertiary amines is shown in Fignre 2.8. The diazo components from the thiazole and thiophene rings are especially important in the prodnction of bright bine azo dyes. ... 

The dysideathiazoles A-E (331-335) are a series of polychlorinated amino acid derivatives from Pacific Island collections of D. herbacea. The structures were determined by X-ray analyses and the absolute configurations were determined by X-ray crystallography of a brominated derivative [301]. Herbamide A (336), a chlorinated amide was isolated from a Papua New Guinean sample of D. herbacea as a minor component [302]. D. herbacea from the southern Great Barrier Reef contained a thiazole (337) amongst other known metabolites [303]. A Dysidea sp. 

Many disazo dyes with derivatives of aniline as the terminal component (e g., 44, 45) have been described in the literature, but only a few have become industrial products. Replacement of the central benzene ring by heterocycles such as thiazole or thiophene causes marked bathochromic shifts. 

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). 

A heterocyclic sulfur-containing compound, 2-methyl-thiophene, was identified in boiled crayfish tail meat and pasteurized crabmeat. Thiazole and 3-methylthiopropanal were identified in the crayfish hepatopancreas. Heterocyclic sulfur-containing compounds play important roles in generating meaty aromas in a variety of meat products and are considered important volatile aroma components of marine crustaceans (12— 14). The 2-methylthiophene could be an important flavor cemponent in boiled crayfish tail meat. Both thiazole find 3-methylthiopropanal were important contributors to the desirable meaty aroma associated with crayfish hepatopancreas. The 3-methyl-thiopropanal, identified in boiled crayfish hepatopancreas, is derived from Strecker degradation of methionine (15), and has been considered to be an important cemponent in basic meat flavor (16). Pyridine was detected in the headspace of the hepatopancreas from freshly boiled crayfish. Pyridine and 2-ethylpyridine have been previously reported as components in the atmospheric distillate from a sample of crayfish hepatopancreas frozen for three months (2). 

Much earlier, Mulders267 had treated cysteine (0.01 mol) and cystine (0.1 mol) with ribose (0.025 mol) in phosphate buffer, pH 5.6 (35 ml), and diethyleneglycol (200 ml) under reflux at 125 °C for 24 h, identifying 45 components, including seven thiazoles, one of which was the 2-acetyl derivative. 

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... 

The nonribosomal cyclic peptide leucamide A, 352, was isolated from the marine sponge Leucetta microraphis from the Great Barrier Reef of Australia <2002JOC4989, 2002JOC1636>. It was isolated as the principal active component and found to inhibit the growth of three tumor cell lines (stomach carcinoma, liver carcinoma, liver carcinoma with mutated p53). The compound is composed of seven amino acids and amino-acid-derived residues L-leucine, oxazole, L-alanine, methyloxazole, thiazole, L-valine, and L-proline. 

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... 

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. " ... 

Another application of the Hantzsch process is found in the synthesis of a monobactam antibiotic, Tigemonam. The monobactams are follow-ups to the penicilMns, both families being unique as derivatives of azetidinones (beta-lactams). Tigemonam also possesses a thiazole ling, which component is synthesized as in Scheme 9.20 from thiourea (shown in the -SH tautomeric form) and the chloroketone 9.26. 

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