Thiazole Gabriel synthesis

Gabriel synthesis, 7, 33 aziridines, 7, 81-82 thiazoles, 6, 302 Galanthamine structure, 4, 548 Galbacin NMR, 4, 574 Gelatin hardeners for... 

In analogy to thiophene formation (cf. p. 96), thiazoles (mainly of the 2,5-disubstituted type) are obtained from (a-acylamino)ketones by sulfurization with P4S10 and subsequent cyclodehydration Gabriel synthesis) ... 

Gabriel-Isay synthesis (pteridine) Gabriel synthesis (thiazole) 207 Gassmann synthesis (indole) 135 Gattermann synthesis, HCN-free 509 Gewald synthesis (thiophene) 97 Graebe-Ullmann reaction 266 Guareschi synthesis (2-pyridone) 384... 

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). 

TABLE 11-31. THIAZOLES FROM -ACYLAMINOKETONES AND PHOSPHORUS PENTASULFIDE (Gabriel s synthesis)... 

The Gabriel s synthesis has been further extended to alkoxythiazoles. Thus 2-alkoxy (or aryloxymethyl) 5-methyl (or phenyl) thiazoles (200) were prepared by refluxing the corresponding acylaminoketone (199) in dry pr3ridine in the presence of P2S5 (Scheme 105) (409). 

These a-acylaminoketones also provided a convenient synthesis of thiazoles on treatment with phosphorus pentasulfide (Gabriel s method). Although yields range from 45 to 80%, substituents are usually restricted to alkyl, aryl and alkoxy derivatives. Thus, reaction of the a-acylaminoketone (4) with P4S1Q gave the thiazole (5), and thiazole (7) itself was prepared in this manner in 62% yield from formylaminoacetal (6) (14CB3163). The corresponding 5-ethoxy compound was obtained from the a-formamidoester and phosphorus pentasulfide in an inert solvent. 

Acylamino ketones also provide a convenient synthesis of thiazoles on treatment with phosphorus pentasulfide (Gabriels method). Substituents are usually restricted to alkyl, aryl, and alkoxy derivatives. Thus, the -acylamino ketone 234 with P4S10 gave the thiazole 240. Lawessons reagent (LR) can be effectively used as the source of sulfur in these cyclizations (e.g., Scheme 116) <1996JME957, 2006TL2361, CHEC-III(4.06.9.1.3)682>. 

Several examples of this widely practiced name reaction have been applied in drug discovery abound. For example in a study describing the design and synthesis of inhibitors of hepatitis C virus (HCV) NS5B polymerase, thiazole intermediate was constructed via the Gabriel reaction, ... 

This reaction was originally designated by Gabriel [53] in 1910 phosphorus pentasulfide reacted with acylaminoketone (showed in below reaction) an equimolecular quantity to yield 2-phenyl-5-alkyl-thiazole. The reaction is analogous to the synthesis of additional five-membered oxygen and sulfur holding rings from 1,4-dicarbonyl compounds. 

Synthesis. The preparation of these heterocycles was accomplished using traditional methodology. 2,4-Disubstituted and 2,4,5-trisubstituted compounds were prepared via the Hantzsch (21) synthesis. The Gabriel (22) and Robinson-Gabriel (23) syntheses were used to prepare the 2,5-disubstituted thiazoles and oxazoles, respectively. The intermediate keto-amides could be converted into thiazoles by heating with P4S] q pyridine or with Lawesson s reagent (24). 

---