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Hantzsch Method

The first synthesis of thiazole was described by Arthur Hantzsch in 1887. This reaction in its most fundamental form as well as other forms with variations has been widely applied in the construction of a variety of molecules since then. In its most basic form, the reaction is illustrated in the scheme below and involves the use of an a-halocarbonyl compound with reactants comprising the N-C-S linkage. [Pg.307]

The reaction can also be carried out in the presence of all three carbon atoms being substituted with suitable alkyl or aryl groups. Moreover, it also works with thiourea instead of thioamide to yield the corresponding aminothiazole. [Pg.307]

Traditionally, the mechanism of this cyclization has been postulated to be as shown below wherein an intermediate i is formed via displacement of the halide, after which the nucleophilic nitrogen in ii adds intramolecularly [Pg.307]

The reaction has been employed in several molecules in drug discovery and development. For example, Ikemoto et al. have developed a practical route to a thiazole as part of their efforts toward a kilogram-scale synthesis of a P-adrenergic receptor agonist as a candidate for tihie treatment of obesity. The thiazole ring was assembled by allowing the haloketone and thioamide to react. [Pg.308]

An impressive application of the Hantzsch on process scale is the kilogram-scale synthesis of ravucanozole, a novel thiazole containing antifringal development candidate at Bristol-Myers Squibb. Ravucanozole [Pg.309]


The first member of the series. 2-imino-3,4-dimethyl-4-thiazoline (363) is obtained when the di-HBr salt of bis(methylformamidine)disulfide (362i is refluxed for 16 hr in acetone (Scheme 209) (700). The most common preparative methods involve direct heterocyclization by the Hantzsch method (see Chapter II. Section II.4), though the mechanism of this reaction suggests certain limitations according to the respective natures of R2, R3, and in 364 (Scheme 210). [Pg.122]

Microwave chemistry has been found to be a useful method for accelerating reactions or catalyzing reactions that are difficult to carry out by other methods. A modification of the Hantzsch method to directly obtain pyridines has been communicated. A dry medium using ammonium nitrate bentonitic clay system with microwave irradiation affords pyridines 96 in a single pot within 5 minutes. When the pyridine is not the major product (> 75% yield), the dealkylated pyridine 97 becomes an... [Pg.315]

Aryl-l,4-dihydropyridine-3,5-dicarboxylates are widely studied due to their use in the treatment of cardiovascular diseases. Most of these compounds are synthesized using the Hantzsch method (Section 4.2.3.4.2) but this is less suitable for the synthesis of unsymmetrical or chiral derivatives. Enzymatic desymmetrization of bis(ethoxycarbonyl-methyl)-l,4-dihydropyridine-3,5-dicarboxylates, using Candida antarctica lipase B, can generate enantiopure 1,4-dihy-dropyridines in reasonable to high yields with good enantiomeric selectivity <2000TA4559>. [Pg.317]

The extension of the Hantzsch method to other systems with a less usual substitution pattern, using tricarbonyl compounds, leads similarly to 2-phenylethylidene 1,4-dihydro-pyridines in low yield24 (equation 16). [Pg.530]

Thiazoleacetic acids, decarboxylation of, to alkyl thiazoles, 341 syntheses of, 207 by Hantzsch method, 341... [Pg.311]

Advancements in the Hantzsch method have appeared in the literature since 1982. An improved synthesis of the aryl- and alkylselenoamide precursors by reaction of the nitrile with aluminum selenide <85JOC384> or NaHSe prepared in situ from NaBH4 and selenium <93S870> has been reported. In particular the latter method aids in the synthesis of 2-alkylselenazoles because of the instability... [Pg.504]

The unsubstituted 5,5 -isomer (76) is not readily available by the Hantzsch method. It was first prepared (Scheme 29) by diazotization of a diamino derivative (53HCA354) obtained by a benzidine-like rearrangement (51CB518), and has since been prepared by cross-coupling of the chloro- and trimethylstannyl-thiazoles (87S185). The 4,4 -bis(ethoxycar-bonyl) derivative has been prepared from thiooxalic esters by reaction... [Pg.35]

The Hantzsch method has been used in the synthesis of the thiazole portion of thiamine. Vitamin Bi (9.25). 4-Methyl-5-hydroxyethy 1-1,3-thiazole (9.24) is prepared for this purpose and then quatemized at the pyridine-like nitrogen atom with a chloromethylpyrimidine derivative, the product being thiamine (Scheme 9.19). [Pg.230]

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. ... [Pg.311]


See other pages where Hantzsch Method is mentioned: [Pg.482]    [Pg.188]    [Pg.293]    [Pg.118]    [Pg.482]    [Pg.699]    [Pg.817]    [Pg.596]    [Pg.505]    [Pg.508]    [Pg.35]    [Pg.307]    [Pg.198]   


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Cyclization reactions with Hantzsch method

Hantzsch

Thiazole from Hantzsch method

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