Thiazole 5-acetamido

Reduction of 2.4-dimethyl-5-nitrothiazole with activated iron gives a product that after acetylation yields 25% 2.4-dimethyl-5-acetamido-thiazole (58). The reduction of 2-methyl 5-nitrothiazole is also reported (351 to give a mixture of products. The nitro group of 2-acetylhydrazino-5-nitrothiazole is reduced by TiCl in hydrochloric acid or by Zn in acetic acid (591. 

Platinum complexes, 161 Polarographic studies, 153, 154 of 2-aminothiazoles, 29 of 2-anilinothiazoles, 30 of 2-azothiazoles, 107, 108 Polyacrylonitrile, 105, 163, 164, 167 Polyamines, 156-168 Polycaprolactam, 156-168 Polyesters, 163, 165, 166, 167 Polyhalogenothiazole. reactivity of, 408-409 Polymers, e-caprolactam, butadiene, 438 Polymorphism, of sulfathiazole, 116 Positive colored image, 440 Postemergence activity, 134 Potassium salts, of acetamido thiazoles, 90 Potentiometric measurements, and amido-imido equilibrium, 116 and amino-imino equilibrium, 21 P.P.P. approximation, charge diagrams calculations by, 17... 

Salicylaldehyde, Schiff base with, 99 Salmonella typhi, 152 Salts, of acetamido thiazoles, 91 Sandmeyer reaction, in halothiazoles synthesis, 12... 

An intramolecular charge transfer toward C-5 has been proposed (77) to rationalize the ultraviolet spectra observed for 2-amino-5-R-thiazoles where R is a strong electron attractor. Ultraviolet spectra of a series of 2-amino-4-p-R-phenylthiazoles (12) and 2-amino-5-p-R-phenylthiazoles (13) were recorded in alcoholic solution (73), but, reported in an article on pK studies, remained undiscussed. Solvent effects on absorption spectra of 2-acetamido and 2-aminothiazoles have been studied (92). 

The fragmentation patterns of 2-acetamido-5-nitrothia2oie (17) and 2-diraethylaminothiazole are reported to be characterized by the stabilization brought by the amino group to the thiazole ring (137). The proposed fragmentation scheme (Scheme 19) displays two major features,... 

With the more acidic 2-acetamido-4-R-thiazoles. using the weaker base NaOH as condensation agent, a mixture of ring (45) and exocyclic N-alkylation (46) may be observed (Scheme 33) (121). Reaction of 2-acetamido-4-methylthiazole in alcoholic sodium ethoxide solution with a variety of alkylating agents has been reported (40-44). 

An alkyi group occupying the 4-position of the thiazole ring may condense if the 5-position is substituted. 2-Acetamido-4-methy]-5-nitrothiazole (80) and p-cyanobenzaldehyde when refluxed with small amounts of piperidine yield the 4-styryl derivative (81) (Scheme 57) (238, 239). 

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). 

Acetamido-4-methy)thiazole when enzymatically brominated is converted to a mixture of 2-acetamido-4-methyd 5-bromothiazole (200) and dibromacetamido-4-methyl-5-bro mo thiazole (201) (Scheme 127) (138, 436). 

The general pattern of alkylation of 2-acylaininothiazoles parallels that of 2-aminothia2ole itself (see Section III.l). In neutral medium attack occurs on the ring nitrogen, and in alkaline medium a mixture of N-ring and N-amino alkylation takes place (40, 43, 161. 163). In acidic medium unusual behavior has been reported (477) 2-acetamido-4-substituted thiazoles react with acetic anhydride in the presence of sulfuric acid to yield 2-acetylimino-3-acetyl-4-phenyl-4-thiazolines (255) when R = Ph. but when R4 = Me or H no acetylation occurs (Scheme 151). The explanation rests perhaps in an acid-catalyzed heterocyclization with an acetylation on the open-chain compound (253), this compound being stabilized... 

Chemical Name 7-[2-Methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetamido]-cephalosporanic acid... 

To this solution was added at one time the above-obtained ethyl acetate solution at -15°C, and the resulting mixture was stirred for 1 hour at -10°C to -15°C. The reaction mixture was cooied to -30°C, and water (80 ml) was added thereto. The aqueous layer was separated, adjusted to pH 4.5 with sodium bicarbonate and subjected to column chromatography on Diaion HP-20 resin (Mitsubishi Chemical Industries Ltd.) using 25% aqueous solution of isopropyl alcohol as an eluent. The eluate was lyophilized to give 7-[2-methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetamido] cephalosporanic acid (syn isomer) (1.8 g), MP 227°C (decomp.). 

Suzuki et al. (24) identified a minor biotransformation product of 2-amino- -phenylthiazole in rainbow trout and carp as 2-acetamido-it-(V-hydroxyphenyl )-thiazole (Figure 1). They were unable, however, to demonstrate the presence of this metabolite in the medaka. These authors also suggested that the effectiveness of the 2-amino-A-phenylthiazole as a fish anesthetic is related to the rate at which the drug is activated by biotransformation. 

Acetazolamide Acetazolamide is 5-acetamido-l,3,4-thiadiazole-2-sulfonamide (9.7.5). The synthesis of acetazolamide is based on the production of 2-amino-5-mercapto-l,3, 4-thiadiazole (9.7.2), which is synthesized by the reaction of ammonium thiocyanate and hydrazine, forming hydrazino-N,N -( ji-(thiourea) (9.7.1), which cycles into thiazole (9.7.2) upon reaction with phosgene. Acylation of (9.7.2) with acetic anhydride gives 2-acetylamino-5-mercapto-l,3,4-thiadiazol (9.7.3). The obtained product is chlorinated to give 2-acetylamino-5-mercapto-l,3,4-thiadiazol-5-sulfonylchloride (9.7.4), which is transformed into acetazolamide upon reaction with ammonia (9.7.5) [24,25]. 

The secondary amino group of 3-(Al-ethylaminomethyl)-7-[2-(2-amino-thiazol-4-yl)-2-(Z-1 -carboxy-1 -methylethoxyimino)acetamido]ceph-3-em-3-carboxylic acid was arylated with 8-methylthiopyrido[l,2-a]pyrimidi-nium salt in dimethylformamide in the presence of triethylamine at 40°C (89MIP2). 

Sulfenamidothiazoles heated in acetic anhydride rearrange to 2-acetamido-5-thiophenoxythiazoles (337) (Scheme 193) (32, 456, 457). Only decomposition products are found when these conditions are applied to 336 with X = C1 or methyl. Substitution in the 4-position of the thiazole ring (R = methyl, phenyl), however, favors the rearrangement (see p. 82). 

From the ease of mercuriation of mono,- di-, and trimethylthiazoles, the positional reactivity order is indicated to be 5 > 4 > 2 (60CA24661c). Surprisingly, 2-acetamido-4-methylthiazole is said not to mercuriate (59JIC434), though the 5-position should be strongly activated it may be sterically hindered. Steric hindrance must be partly responsible for the reactivity order for substituted thiazoles 2-Ph- > 4-Me-2-Ph- > 2-Me-thiazole in this work the 4,5-dimethyl compound was unreactive [72CA(76)72617]. 

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],... 

Other ESR studies include 2,2 -diamino-4,4 -bithiazole and 2,2 -bis(acetamido)-4,4 -bithiazole copper(ll) complexes <2000SRI1653>, patellamide A derivatives, and their copper(ii) compounds <2002CEJ1527>, endothelial nitric oxide synthase and its reaction with thiazole-containing ligand <1996JBC32563>. 

The synthesis of the 2-(guanidinomethyl)thiazole (466), a homologue of the important 2-guan-idinothiazole (see Section 3.06.12.2), has been described starting from acetamido thioacetamide and... 

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