Thiazoles 2-hydroxy— from

Anthraquinoneazoles. In contrast to the older yellow Algol dyes, which contain two thiazole rings (e g., 2,2-bisanthra [2,1 d thiazole-6,11-quinonyl), the red to blue oxazoles and thiazoles derived from l-aminoanthraquinone-2-carboxylic acid and 3-amino-2-hydroxy- or -mercaptoanthraquinones exhibit good lightfastness. The good fastness to atmospheric conditions and chlorine of the blue deriv-... 

In addition to the syntheses described above, many other processes for the use of formaldehyde in the production of dyes and dy e intermediates are described in the patent hterature. Recent patents,for example, includethe production of benzene-soluble azo dyes by coupling diazotized arj lamines with aromatic hydroxy compounds plus formaldehyde , preparation of vat dyes by condensation of formaldehyde with ST-dihy di O-l,2,T,2 -anthra-quinone azities , synthesis of nitroso dy es by. reacting formaldehyde viith p-X-alky laminonitrosoben2ene del i atives, formation of thiazole dyes from mercaptothiazoles, primary amines, and foimaldehyde , production of diphenyimethane intermediates , etc. 

In the first chapter, devoted to thiazole itself, specific emphasis has been given to the structure and mechanistic aspects of the reactivity of the molecule most of the theoretical methods and physical techniques available to date have been applied in the study of thiazole and its derivatives, and the results are discussed in detail The chapter devoted to methods of synthesis is especially detailed and traces the way for the preparation of any monocyclic thiazole derivative. Three chapters concern the non-tautomeric functional derivatives, and two are devoted to amino-, hydroxy- and mercaptothiazoles these chapters constitute the core of the book. All discussion of chemical properties is complemented by tables in which all the known derivatives are inventoried and characterized by their usual physical properties. This information should be of particular value to organic chemists in identifying natural or Synthetic thiazoles. Two brief chapters concern mesoionic thiazoles and selenazoles. Finally, an important chapter is devoted to cyanine dyes derived from thiazolium salts, completing some classical reviews on the subject and discussing recent developments in the studies of the reaction mechanisms involved in their synthesis. 

In this chapter we intend to outline the general methods by which the thiazolic ring is synthetized from open-chain compounds. The conversion of one thiazole compound to another is not discussed here, but in appropriate later chapters. Thus the conversion of thiazole carboxylic acids, halogeno-, amino-, hydroxy-, and mercaptothiazoles, to the corresponding unsubstituted thiazoles is treated in Chapters IV through VII, respectively. 

In a similar way, dl-2-(q-hydroxyalkyl)- and 2-(a-alkoxycarbonyl)-4-methyl-5-(/3-hydroxyethyl)thiazoles were synthetized from the corresponding thioamides and 4-hydroxy-3-bromo-2-pentanone (615). 

Similarly, 5-thiazole alkanoic acids and their salts are obtained from thioamides and /3-halo -y-keto acids (695). Thus thioarylamides condensed with 3-aroyl-3-bromopropionic acid (88) in isopropanolic solution in the presence of Na COs give first 4-hydroxy-2-aryl-A-2-thiazoline-5-acetic acid intermediates (89), which were dehydrated in toluene with catalytic amounts of p-toluene sulfonic acid to 2,4-diaryl-5-thiazole acetic acid (90) (Scheme 39) (657), with R = H or Me Ar = Ph, o-, m- or p-tolyl, o-, m-, or P-CIC6H4, 0-, m-, or p-MeOC(iH4, P-CF3C6H4, a-thienyl, a-naphthyl (657). 

Although not fully characterized, 2-carbethoxy-4-hydroxythiazole (230a), R, = C02Et, R2 = H, apparently results from the reaction of chloroacetonitrile with ethyl thiooxamate (2), Ri = C02Et (417). a-Chlorothioacids (232) condensed with thiobenzamide in the presence of carbon disulfide (542) yield the corresponding 2-phenyl-4-hydroxy-thiazole (234). The same product was obtained from 233 (Scheme 121). 

The replacement of 2-amino group by a hydrogen can be achieved by diazotization, followed by reduction with hypophosphorous acid (1-8, 13). Another method starting from 2-aminothiazole is to prepare the 2-halo-thiazole by the Sandmeyer reaction (prepared also from the 2-hydroxy-thiazole), which is then dehalogenated chemically or catalytically (1, 9, 10). 

Thiazolidine-2-thione, 4-hydroxy-synthesis, 6, 314 Thiazolidinethiones tautomerism, 6, 273 1,2,4-thiazoles from, 5, 776 Thiazolidine-2-thiones reactions... 

Vilsmeier-Haack formylation of 2-(4-methyl-l-piperazinyl)-4//-pyrido-[l,2-n]pyrimidin-4-one with a mixture of POCI3 and DMF at 95°C gave a 3-formyl derivative (93FES1225) while ethyl 4-oxo-6,7,8, 9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-2-acetate at 50 °C yielded a 9-dimethylaminomethylene-3-formyl derivative (01MI4). 3-Formyl-2-hydroxy-8-[2-(4-isopropyl-l,3-thiazol-2-yl)-l-ethenyl]-4//-pyrido[l,2-n]pyri-midin-4-one was obtained from the 3-unsubstituted derivative with oxalyl chloride-DMF reagent in CH2CI2 at room temperature for 3h (OlMIPl). 

Thiazole and its derivatives are conventionally prepared from lachrymatory, a-halo-ketones and thioureas (or thioamides) by Hantzsch procedure [146]. In a marked improvement, Varma et al. have synthesized the title compounds by the simple reaction of in situ-generated a-tosyloxyketones, from arylmethyl ketones and [hydroxy(tosyl-oxy)iodo]benzene (HTIB), with thioamides in the presence of K 10 clay using micro-wave irradiation (Scheme 6.43) the process is solvent-free in both the steps [147]. 

A smaller scale and less efficient synthesis of the phenyl derivative of 1 has been reported. The method described for the title compound 1 provides excellent synthetic access to the p-chlorophenyl-substituted thiazolethione 1. It offers higher yields in every step of the synthesis, reduces the amount of hydroxylamine hydrochloride used in Step A to a third and avoids the use of halogenated solvents and methanol. Further, only one purification step is necessary at the very end of the synthesis to afford pure thione 1. The protocol for N-hydroxy-4-(p-chlorophenyl) thiazole-2(3H)-thione has also been applied to syntheses of the respective p-substituted phenyl derivatives 7-9 from the respective acetophenones (Figure 2)... 

Nucleophilic attack at sulfur is implicated in many reactions of 1,2,4-thiadiazoles <84CHEC-I(6)463> and in general soft nucleophiles attack at sulfur. For example, reaction of 3-hydroxy-5-phenyl-1,2,4-thiadiazole (23) with acetic anhydride in the presence of dbu at 130°C gives the thiazoles (31) and (32) <85JHC1497>. These products may be reasonably explained by the mechanism outlined in Scheme 9 in which the thiadiazole ring is opened by the acetic anhydride carbanion. There is some evidence that (32) may arise from attack of the carbanion on the A-acylated derivative (30a) (Scheme 9) <85JHC1497>. 

The 6-benzylpyrido[4,3-, pyrimidine 145 was prepared by cyclizing the methyl carboxylate 612 with formamidine hydrochloride <2000DEP19900544>. The 2-butyl-6-(2-hydroxy-2-methyl-l-oxopropyl) analogue 615 was also prepared from cyclocondensation of ethyl ester 613 with BuC(NH)NH2 <1994USP5281602>. The trisubstituted analogue 616 was obtained from the reaction of 2-guanidino-4-(4-fluorophenyl)thiazole hydrobromide with iV,3-dibenzoyl-4-piperidone 614 <1995USP5405848>. 

Several new syntheses of thiazoles from thioureas have been developed in recent years. Werbel95 was able to prepare 2-aminothiazoles by reaction of thioureas with bis(/3-chloroethyl) ether. 1,3-Disubstituted thioureas, however, yielded disubstituted 4-thiazolines. In a German patent, Rcisinger96 reported that 2-aminothiazole was formed in 88% yield from thiourea and vinyl acetate in the presence of sulfuryl chloride. A method for the preparation of the 4-hydroxy-2-amino-thiazole (47), which probably exists in the tautomer shown, has been developed by Delaby et al.97 via the reaction of thiourea with jS-acyl-acrylic acid or its esters. Zbiral98 has observed that acylvinylphos-... 

Thiamin is synthesized in bacteria, fungi, and plants from 1-deoxyxylulose 5-phosphate (Eq. 25-21), which is also an intermediate in the nonmevalonate pathway of polyprenyl synthesis. However, thiamin diphosphate is a coenzyme for synthesis of this intermediate (p. 736), suggesting that an alternative pathway must also exist. Each of the two rings of thiamin is formed separately as the esters 4-amino-5-hydroxy-methylpyrimidine diphosphate and 4-methyl-5-((i-hydroxyethyl) thiazole monophosphate. These precursors are joined with displacement of pyrophosphate to form thiamin monophosphate.92b In eukaryotes this is hydrolyzed to thiamin, then converted to thiamin diphosphate by transfer of a diphospho group from ATP.92b c In bacteria thiamin monophosphate is converted to the diphosphate by ATP and thiamin monophosphate kinase.92b... 

The thioamide 44 was prepared in 78% yield from the treatment of Boc-D-Val-NH2 (43) with Lawesson s reagent in CH2C12. Thioamide 44 was then treated with KHCO3 and ethyl bromopyruvate from -40 °C to -20 °C in order to form the intermediate hydroxy-dihy-drothiazole 45 (not isolated) which was subsequently dehydrated with (Tfa)20 and 2,6-lutidine at -20 °C to form the dipeptide thiazole 46 in 73% yield based on thioamide. The product was ascertained to be essentially one enantiomer (>99% ee by chiral HPLC). 

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