Aminothiazole Derivatives

General Synthetic Methods for Thiazole and Thiazolium Salts 

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Halothiazoles are usually obtained from 2-aminothiazoles through the Sandmeyer reaction. Nevertheless, ammonolysis has sometimes proved useful for the preparation of 2-aminothiazole derivatives. Detweiler et al. (18) obtained 2-(u-pyridinylamino)thiazole (1) from 2-bromothiazole (Scheme 1). The reaction is easier if a nitro group occupies the 5-position of the thiazole ring (19-21). Ethylene diamine derivatives undergo this reaction with 2-haiothiazoles (22-24). 

Quaternary salts (33) obtained from aminothiazole derivatives liberate 2-imino-4-thiazolines in basic medium (Scheme 24). This reaction is general and independent of the nature of R in 33 (160-167). The same result was found when 2-propynylbromide (168) or 3-chloropropionic acid (169) were the quaternizing reagents. This method is particularly... 

Thus in neutral medium the reactivity of 2-aminothiazoles derivatives toward sp C electrophilic centers usually occurs through the ring nitrogen. A notable exception is provided by the reaction between 2-amino-thiazole and a solution (acetone-water, 1 1) of ethylene oxide (183) that yields 2-(2-hydroxyethylamino)thiazole (39) (Scheme 28), Structure 39... 

Thus the reactivity of 2-aminothiazole derivatives toward reactants bearing a sp C hybridized electrophilic center follows the general pattern ... 

The reaction of 2-aminothiazole derivatives with the 1,3,5-oxadiazine 2,4.6-trione shown leads to biuret derivatives (126) (Scheme 83) (287). 

Thiazolylureas are obtained by reaction between 2-aminothiazole derivatives and urea (see also p. 92). 

No systematic study of the free radical reactivity of aminothiazole derivatives has yet been reported. Their behavior, however, may be extrapolated from the detailed work performed on other thiazoles (see Chapter III. Section IX. 1). 

Amino-5-nitrothiazole, on treatment with arenesulfonyl halides and dimethylformamide at 140 C, gives (5-nitro-2-thiazolyl)amidme (274) (Scheme 168) (507, 508). The condensation products of the reaction of 2-aminothiazole derivatives with various aldehydes are grouped in Tables... 

A wide variety of applications has been proposed for aminothiazole derivatives from fungicides (Table VI-6) to a component of hair-waving lotions containing cosmetic resins for dyeing hair (733). The main applications cover the fields of agriculture, pharmacy, and photography or related activities. This section is only representative, not exhaustive, and can be completed with the indications given in Tables of Section VII. 

An interesting set of central nervous system properties has also been discovered and studied (Table VI-10). The work devoted to piscaine must be emphasized besides finding hypnotic properties of 2-amino-4-phenyl-thiazole on fish, the authors studied the structure of the metabolite, as well as the localization of the (radio labeled) metabolic product in various organs. Recently, thiazol-4-yl methoxyamine was shown to inhibit the development of morphine tolerance (1607). 5-Aminothiazole derivatives such as 419a were proposed as cardiovascular agents (1608, 1610). Substitution of the 5-aminothiazole radical on the cephalophosphorin structure gives a series of antibacterial products (1609). 

Beyond pharmaceutical screening activity developed on aminothiazoles derivatives, some studies at the molecular level were performed. Thus 2-aminothiazole was shown to inhibit thiamine biosynthesis (941). Nrridazole (419) affects iron metabohsm (850). The dehydrase for 5-aminolevulinic acid of mouse liver is inhibited by 2-amino-4-(iS-hydroxy-ethyl)thiazole (420) (942) (Scheme 239). l-Phenyl-3-(2-thiazolyl)thiourea (421) is a dopamine fS-hydroxylase inhibitor (943). Compound 422 inhibits the enzyme activity of 3, 5 -nucleotide phosphodiesterase (944). The oxalate salt of 423, an analog of levamisole 424 (945) (Scheme 240),... 

Some representative analytical uses of 2-aminothiazole derivatives are reported in Table VI-13. The use of azoderivatives of thiazoles in analysis has been reviewed (958). 

The use of 2-aminothiazole derivatives as dyeing compounds is direct related to the development of synthetic fibers. Some typical examples are given in Table VI-14. The importance of these dyes lies in their performance on acetate fibers. They have excellent fastness to gas fumes, produce a bright blue shade, and have a high tinctorial strength. Their only disadvantage is their relatively low light fastness, which does limit their application. 

Sulfathiazole is advised as an hair lotion additive defatting the hair and reducing formation of dandruff (1024). The polymeric 2-aminothiazoles derivatives (427) exhibit good thermal stability with decomposition in air starting at 350°C (1025). 

Only 2-aminothiazole derivatives are reactive enough toward diazonium salts to undergo the diazo-coupling reaction. The azo group fixes exclusively on the 5-position when it is free (Scheme 62) (351). 

The conversion of 2-aminothiazole derivatives into those unsubstituted in the 2-position was tried by the two available methods involving ... 

Salts and Esters of Dithioadds S-Aminothiazole Derivatives and Related Condensations... 

Similarly, 2-methyl-5-acetamidothiazoles were obtained from the corresponding nitriles, NCCH(R2)NHCOMe, in which Rj = hydrogen, or amido, methylamido, and dimethylamido groups (551, 571) (Table 11-33). 5-Aminothiazole derivatives (209), Rj = Me or Ph and Rj H,... 

TABLE 11-35 2-HYDROXV-5-AMINOTHIAZOLES DERIVATIVES FROM o-AMINONITRILE AND CARBON OXYSULnOE-... 

Aminothiazole derivatives (243) can be prepared by treatment of enamines of type 240 with sulfur and cyanamide at room temperature in ethanol (701) yields range from 30 to 70%, and no catalyst is required. Initial formation of the thiolated intermediate (241) is probably followed by addition of cyanamide, yielding 242 (Scheme 124). 

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