From thiazole acetic acids

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). 

The action of ammonia on N-(aryl-i,3-oxathiol-2-ylidine) tertiary im-inium salts (254) yields linear intermediates (255) that cyclize to 2-amino-4-phenyl thiazoles (256) on crystallization from acetic acid (Scheme 129) (730). 

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

This section is completed with a brief review of the synthesis and properties of this epimer (20) of the precursor of thiazole in bacteria. This pentulose is conveniently accessible by an unconventional route (Scheme 19). Methyl 2,3 4,6-di-O-isopropylidene-a-D-mannopyranoside, readily available from methyl ot-D-mannopyranoside, is converted to the ketonic glycoside by butyllithium in 91% yield, following a method first published by Klemer and Rodemeyer43 and scaled up by Horton and Weckerle.44 This was converted by means of lithium hydroxide in a water-ether mixture into 3,5-0-benzylidene-l-deoxy-D-eryf/iro-2-pen-tulose in 55% yield. Hydrolysis to the free pentulose (20) proceeded in 73% yield in aqueous acetic acid. This product was obtained as a syrup with a characteristic absorption band at 1705 cm 1 as a film. Thus, there is a fair proportion of the open-chain ketone under these conditions, as with the D-threo epimer.45... 

Li and co-workers introduced a rapid and efficient microwave-assisted method to prepare new disubstituted 1,3,4-thiazoles from 1,4-disubtituted thiosemicarbazides with the objective to obtain biologically active molecules. The intermediate l-aryloxyacetyl-4-(4-methoxybenzoyl)thiosemicarbazide was irradiated in an excess of glacial acetic acid in a domestic microwave oven and led to the formation of 2-(methoxybenzoyl-5-aryloxymethyl)-l,3,4-dithiazoles in good yields [30] (Scheme 20). 

Dimethylthiazole has been prepared from chloroacetone and thioacetamide,1 but forming the required thioacetamide in the reaction mixture is to be preferred since no additional manipulation is involved. The method here described is substantially that of E. Merck.2 Other substituted thiazoles can be prepared by practically the same method.2 2,4-Dimethylthiazole has been obtained by dry distillation of 2-methylthiazyl-4-acetic acid,3 and also by heating 2,4-dimethylthiazole-5-carboxylic acid with calcium oxide.4... 

Thiostrepton is a macrocyclic polypeptide antibiotic that is structurally different from vancomycin and teicoplanin. It is soluble in water and acetic acid. It is obtained from Streptomyces azureus bacterium. There are 17 chiral centers in this antibiotic, with 2 large cavities (A and B in Fig. 1). Five thiazole rings, 1 quinoline ring, 5 hydroxyl groups, 10 amide linkages, and 1 secondary amine make the molecule stereo-specific in nature. 

This sodium salt is dissolved in hot water, and the solution is brought to pH 4 by the addition of acetic acid, which causes the precipitation of 2-(4-chlorophenyl)thiazol-4-ylacetic acid. This is collected by filtration, washed with water, and dried in vacuo over phosphorus pentoxide. It has an M.P. 155-156°C (from ethyl acetate). 

Thiazole-2-acetic acid derivatives (92) are prepared from ethyl thiomalonamate (91), Ri=H, alkyl, phenyl (195, 295, 319), or monothiomalonamide as the thioamide reactant (Scheme 40) (80, 83, 279, 295, 352, 469). 

Thiazole derivatives are obtained from ethyl 3-amino-3-acylhydrazinopropenoate 21 in good yields <04H(63)259>. Treatment of 21 with thiourea and bromine in acetic acid... 

Condensation of the lactone (105) derived from 2,3-O-isopropylidene-/if-D-ribofuranosyl acetic acid with aminoguanidine gave the 1,2,4-thiazole homo C-nucleoside 703 (75JA436 81JOC3407) (Scheme 188). 

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