2-Amino-4-phenylthiazole

The action of ammonia on N-(5-aryl-l,3-oxathioI-2-ylidene) tertiary iminium salts (7) affords linear intermediates that cyclize to 2-amino-4-phenylthiazoles (Scheme 7) (45). 

The crystal and molecular structures of 2-amino-4-phenylthiazole hydrobromide have been determined by radiocrystallography the angle between the thiazole and phenyl rings was found to be 19 . The major features are reported in Fig. VI-4 (142). 

Both carbonyl groups of terephthaldehyde are reported to react with the exocyclic nitrogen of 2-aminothiazole yielding 1.4-phenylene bis(2-methyleneamino)thiazole. The same report describes the reactions of 2-amino-4-phenylthiazole with terephth aldehyde and salicylaldehyde as yielding 64 and 65, respectively (Scheme 45) (215), whose structures are based on ultraviolet and infrared spectra. 

The metabolite of 2-amino-4-phenylthiazole (used as an anaesthetic for fish) was identified (223) as 2-amino-4-phenylthiazole 2-N, -d-glucopyranosiduronic acid (71) (Scheme 50). The formation of this compound probably involves the reaction of the exocyclic nitrogen on the Open-chain form of the acid. The isolation of this metabolite is part of a very Systematic study by Japanese researchers related to the anaesthetic... 

In acidic medium and at higher temperatures, condensation of 2-amino-4-phenylthiazole takes place when it reacts with benzaidehyde... 

Rumpf et al. (97) studied the ultraviolet spectra of products obtained when 2-amino-4 phenylthiazole is acylated by /3-chloropropionyl chloride and y-chlorobutyrylchloride and showed that their structures were 94 and 95, respectively (Scheme 66). The open-chain intermediate to 95, 2-(3-... 

Acetamidothiazole is nitrated in the same way (58, 378, 379). 2-Acetamido-4-phenylthiazole is reported to be nitrated on C-5 (380) as opposed to 2-amino-4-phenylthiazole, where nitration occurs on the phenyl ring (381). This latter result is not consistent with the other data on electrophilic reactivity in most cases 2-amino-4-arylthiazole derivatives react with electrophilic reagents at the C-5 position (see Sections rV.l.B and D). Furthermore, N-pyridy]-(2)-thiazolyl-2-amine (178) is exclusively nitrated on the thiazole ring (Scheme 113) (132, 382). 

Yields can be very good Beyer (402) reports a 90% yield when coupling 2-amino-4-phenylthiazole with the diazonium salt of aniline. The coupling of diazotized anilines under modified conditions has been reported in a work treating the preparation of antineoplastics (403). 

Amino-4-phenylthiazole when heated with Raney Ni is reported to yield acetophenone (469). In the course of a general study on reductive cleavage in heterocyclic systems Hoff et al. studied the reaction of 2-amino-4-methylthiazole with Na in liquid ammonia. Two equivalents of Na are necessary to obtain a mixture of 4-methyl-3-thiazoline (240) and... 

A variation of Hantzsch s synthesis, using thioureas in conjunction with a-diazoketones in place of a-halogenoketones, has proved to be generally applicable. In this manner, King and MUler (310) obtained 2-amino-4-phenylthiazole in 67% yield. A wide range of 4-substituted 2-aIkyl (or aryl) aminothiazoles and 2-arylimino-3,4-diarylthiazolines have been prepared by Hampel and Muller (627, 665, 666). 

Reaction of 2-amino-4-phenylthiazole with one equivalent of nitric acid in sulfuric acid at 3 to 5°C results in a mixture of products containing 2-amino-4-(4-nitrophenyl), 2-amino-5-nitro-4-(4-nitro-phenyl), and a small amount of 2-amino-5-nitro-4-phenylthiazole. Work-up of the reaction mixture after only 10 min gives the same products but in different proportions. The use of two equivalents of nitric acid produces about 90% of 2-amino-5-nitro-4-(4-nitrophenyl)thiazole (59JOC187). 

Condensation of 2-amino-4-phenylthiazole with 8-hydroxyquinoline (73) through the intermediacy of the formaldehyde Mannich base illus-... 

Fig. Vl-4. Geometry of thiazole ring in 2-amino-4-phenylthiazole hvdrobromide. Italicized values are interatomic distances (A) other numbers are angles in degrees. From Ref. ]42.

Acetamido-4-phenylthiazole is nitrated at position 5 of the thiazole ring [232], in contrast to 2-amino-4-phenylthiazole, which is nitrated in the phenyl ring [233], This agrees with existing data on the reactivity of thiazoles during electrophilic substitution. N-(2-Thiazolyl)-2-aminopyridine is nitrated exclusively in the thiazole ring [222],... 

The condensation of substituted 2>aminothiazoles with paraformaldehyde and acetophenone in boiling ethanol affords 40—50% yields of 2-(j3-benzoylethylamino)thiazoles (85). Schiff s bases (86), derived from 2-amino-4-phenylthiazole, are readily prepared and are reduced cata-... 

VcF, and Vff and couplings have been measured by Reiter et al for a series of 2-amino-4-phenylthiazoles and analysed together with nuclear Overhauser effects from the point of view of conformational preferences of these compounds. This was a part of their studies on molecular features crucial to the activity of pyrimidine benzamide-based thrombopoietin receptor agonists. 

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