Thiazoles formation

Pyrroloj2,1 -b) thiazole, formation of, 36 as intermediate for dyes, 36 in synthesis of chain-bridged thiazolocyanines, 58... 

Another example of imidazo[2,l-b][l,3]thiazole formation was reported by Adib et al. in their publication concerning eco-friendly catalyst-free MCR in the water [133]. Reaction of cyclohexyl isocyanide with diverse aromatic aldehydes and 2-aminothiazoles in water at 70°C allowed the isolation of heterocycles 96 in good-to-excellent yields (Scheme 43). According to the spectral data, compotmds 96 were determined as single products of the MCR. 

Thiadiazole, formation, 312, 313, 445 Thiazole formation bromoester, 298-304 bromoketone, 565 Thiazolidinone formation beta lactam, disulfide cleavage, 552 nitrile addition, 301 Thiehopyridine formation, 586 Thienothiazinol formation, 593 Thioacetal formation, 130, 185, 248 glyoxylate, 355 ethyl mercaptopropionate, 447 Thioacid formation, thioformamidoyl chloride, 184... 

Azine approach. Cyclization of 5-amino-4(6)-pyrimidinethiones (456) proceeds in the usual way for this type of substituent arrangement. With phosgene, 2-oxo derivatives result and with xanthates, 2-thio derivates are formed (68CPB741). In (457), which has an amino and a mercapto group in the vicinal position to the 5-benzamido group, exclusive thiazole formation results with PPA (65JOC1916). 

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 stereochemistry of stereogenic centers linked to the thiazole C-2 is directly controlled by the rate of carbocation formation during thiazole formation from thioamide and a-bromoketones in the Hantzsch reaction <20010L3655>. 

In a synthesis of pateamine A, it was found that the optimum yield could only be obtained from a Hantzsch-type thiazole formation by isolation and purification of the nonaromatic intermediate. This was followed by dehydrogenation by treatment with TFAA, pyridine, and Hiinig s base, giving a 62% yield over the two steps (Scheme 25) <2004JA10582>. 

Figure 15 Mechanism of thiazole formation in Saccharomyces cerevisiae.

Our understanding of the enzymology of thiamin biosynthesis in bacteria is now at an advanced level the complete biosynthetic pathway in B. mbtilis has been reconstimted and all of the required enzymes have been structurally and mechanistically characterized. Thiazole formation in yeast is also relatively well understood. The formation of the thiamin pyrimidine in yeast is still poorly understood apart from the identification of PLP and histidine as precursors, nothing is known about the mechanistic enzymology of this complex process and... 

Thiazoles can be readily prepared from thiazolines either by oxidation (e.g., 13 to 14) <04CEJ71> or by bromination-elimination protocol (e.g., 15 to 16) <04H(63)773>. The exclusive formation of thiazole-thiazoline 16 indicates that the C-4 acyl group of the thiazoline is essential for the formation of thiazoles under CBrCb/DBU conditions. In the case of the thiazoline Weinreb amide 17, the thiazole formation is carried out using CBrC /DBU (17 to 20) or through a novel base-induced transformation presumably via aziridone 18 (17 to 19) <04T12139>. 

Cyclising dehydration of an a-acylaminocarbonyl compound is particularly important for oxazoles, and can be adapted for thiazole formation. 

Another application of the Hantzsch method is in the synthesis of the aminothiazole coupling partner in the synthesis of the antibiotic cefdinir. The reactive methylene carbon of ethyl acetoacetate is first functionalized to the oxime after which a-chlorination is brought about to furnish the chloro-oxime substrate for Hantzsch synthesis with thiourea. A,jV-Dimethyl aniline is used as a base in the thiazole formation. ... 

This reaction was first reported by Hantzsch and Weber in 1887. It is the formation of thiazole derivatives by means of condensation of a-haloketones (or aldehydes) and thioamides. Therefore, it is generally known as the Hantzsch thiazole synthesis. In addition, other names, including the Hantzsch synthesis, Hantzsch reaction, and Hantzsch thiazole reaction are also used from time to time. Besides thioamides, other thio-ketone derivatives such as thiourea, dithiocarbamates, and ketone thiosemicarbazone can also condense with a-halo ketones (or aldehydes) to form thiazoles. This reaction occurs because of the strong nucleophilicity of the sulfur atom in thioamides or thioureas, and normally gives excellent yields for simple thiazoles but low yields for some substituted thiazoles, as of dehalogenation. This reaction has been proven to be a multistep reaction, and the intermediates have been isolated at low temperatures, in which the dehydration of cyclic intermediates seems to be the slow step. It is found that a variety of reaction conditions might result in the racemized thiazoles that contain an enolizable proton at their chiral center, and it is the intermediate not the final product that is involved in the racemization. Therefore, some modifications have been made to reduce or even eliminate the epimeriza-tion upon thiazole formation. In addition, this reaction has been modified using a-tosyloxy ketones to replace a-haloketones. ... 

The power of this one-pot thiazole formation methodology is demonstrated in the synthesis of (-i-)-cystothiazole C (140BC8453). Reaction of... 

In contrast to the intermolecular Hantzsch reaction, which has been widely used, intramolecular examples have been scarce in the literature. Recently, an elegant Hantzsch macrocylization has been applied to the synthesis of IB-01211. ° Application of the Holzapfel-Meyers-Nicolaou modification to a-bromoketone-thioamide 27 brings about intramolecular thiazole formation with concomitant dehydration of the primary alcohol to give IB-01211 in moderate yield. This reaction is remarkable, especially considering the fact that the macrocyclization through amide formation at either bond a or b fails to produce any cyclized product. 

---