Thiazol-2-carboxylic acid

Claisen ester condensation, 6, 279 Thiazolecarboxylic acid chlorides reactions, 6, 279-280 Thiazolecarboxylic acid hydrazides synthesis, 6, 280 Thiazolecarboxylic acids acidity, 6, 279 decarboxylation, 6, 279 reactions, S, 92 6, 274 Thiazole-2-carboxylic acids decarboxylation, S, 92 Thiazole-4-carboxylic acids stability, S, 92 Thiazole-5-carboxylic acids decarboxylation, S, 92 Thiazole-4,5-dicarboxylic acid, 2-amino-diethyl ester reduction, 6, 279 Thiazole-4,5-dicarboxylic acids diethyl ester saponification, 6, 279 Thiazolediones diazo coupling, 5, 59 Thiazoles, 6, 235-331 ab initio calculations, 6, 236 acidity, S, 49 acylation, 6, 256 alkylation, S, 58, 73 6, 253, 256 analytical uses, 6, 328 antifogging agents... 

The only problem for the matrix-isolation of 21 consisted in the non-availability of a reasonable diazo precursor molecule suited for this technique. But since we already had experience with the preparation of 2,3-dihydrothiazol-2-ylidene46 (see below) by photofragmentation of thiazole-2-carboxylic acid we tried the same method with imidazole-2-carboxylic acid (20). Indeed, irradiation of 20 with a wavelength of 254 nm leads to decarboxylation and the formation of a complex between carbene 21 and CO2. This is shown by the observation that the experimental IR spectrum fits only with the calculated spectrum of complex 21-CC>2 (calculated stabilization energy relative to its fragments 4.3 kcal mol-1). The type of fixation of CO2 to 21 is indicated in the formula S-21 C02. 

Reduction of the carboxylic acid group passes through the intermediate aldehyde. For a number of examples in the heterocyclic series, the aldehyde becomes a major product because it is trapped as the hydrated vfc.-diol form. Examples include imidazole-2-caiboxylic acid [139], thiazole-2-carboxylic acid [140] and pyridine-4-carboxylic acid [141] reduced in dilute aqueous acid solution. Reduction of imidazole-4-carboxylic acid proceeds to the primary alcohol stage, the aldehyde intermediate is not isolated. Addition of boric acid and sodium sulphite to the electrolyte may allow the aldehyde intermediate to be trapped as a non-reducible complex, Salicylaldehyde had been obtained on a pilot plant scale in this way by... 

The dihydrothiazol-2-ylidene (4) was generated by photolysis of matrix-isolated thiazol-2-carboxylic acid.12 Calculations suggested that the barrier to isomerization to thiazole is about 42.3 kcal mol 1 and that the carbene resembles the related imidazol-2-ylidene in structure. An ab initio study of hydroxyoxiranone predicted that the decarboxylation of the zwitterion (5) to form hydroxycarbene (6) would be favourable in vacuo but not in water.13 A theoretical study showed that dihalosulfenes (X2C=S02) are best viewed as dihalocarbenc-SO complexes with a carbon-sulfur bond order of approximately zero.14 hi a study directed at the elusive thionformic acid (7), tandem mass spectrometric methods were applied to isomeric ethyl thioformates.15 The results suggest that the radical cations generated have the carbene structure [(HS)C(OH)]+ ... 

The relatively easy decarboxylation of many azolecarboxylic acids is a result of inductive stabilization of intermediate zwitterions of type 608 (cf. Section 3.4.1.8.1). Kinetic studies show that oxazole-2- and -5-carboxylic acids are both decarboxylated via the zwitterionic tautomers. Thiazole-2-carboxylic acids, and to a lesser extent -5-carboxylic acids, are decarboxylated readily thiazole-4-carboxylic acids are relatively stable. Isothiazole-5-carboxylic acids are decarboxylated readily, the 3-isomers less so while the 4-isomers require high temperatures. The 1,2,4-, 1,2,5-, and 1,3,4-thiadiazolecar-boxylic acids are also easily decarboxylated their stability is increased by electron-donating substituents. Most 1,2,3-triazolecarboxylic acids lose carbon dioxide when heated above their melting points. Decarboxylation of 2-hydroxytetra-zole-5-carboxylic acid requires severe conditions (HC1, reflux, 90 h) to produce 2-hydroxytetrazole (40%) <1999TL6093>. 

Thiazol-2-ylidenes are less well studied than their imidazole and triazol analogues. Only one isolated and structurally characterised example is known in the literature, the 3-(2,6-diis opropylphenyl)thiazol-2-ylidene synthesised by Arduengo et al. in 1997 [2] (see Figure 6.8). The parent compound, 2,3-dihydrothiazol-2-ylidene, was generated in an argon matrix at 10 K from thiazol-2-carboxylic acid as the starting material [33] (see Figure 6.9). 

The activation parameters for decomposition of several thiazole carboxylic acids have been reported and they are tabulated in Table 51. The lower enthalpy of activation for thiazole-2-carboxylic acid (V) compared to its 5-isomer (VI) may be explained on the basis of stability of the developing anionic site in the activated complex. In the 2-isomer the anionic site is developed between the two electron withdrawing atoms, nitrogen and sulfur. In contrast, only the nitrogen atom is adjacent to the developing anionic site in the 5-isomer. Decarboxylation of 2-thiazo-lylacetic acid apparently gives VII as the initial product which isomerizes to... 

Aldehydes are usually more easily reduced than carboxylic acids, but as in the previous case the aldehyde may exist in aqueous solution predominantly as the hydrate [Eq. (2)]. The hydrates are reduced at more negative potentials than carboxylic acids. Several other systems have been found to behave similarly [16,17] pyridine-2- and -4-carboxylic acid, imidazole-2-carboxylic acid, and thiazole-2-carboxylic acid. In the last case the yield is low due to competing reduction of the ring. Yields of aldehyde are better at low temperatures due to the slowing of the dehydration reaction. In neutral or basic solution there is electroanalytical evidence for dimerization in the reduction of pyridine-4-carboxylic acid [18]. 

Thiazole and its simple alkyl or aryl derivatives are not polarographically reducible. Substitution in the thiazole ring with electron-attracting groups may render the nucleus reducible. Derivatives of thiazole-2-carboxylic acid are reducible in alkaline solution, and the reduction is assumed to take place in the nucleus [282]. 

Some derivatives of both thiazole and benzothiazole have been studied by IR spectroscopy. In particular, an extensive study has been carried out with thiazole-2-carboxylic acids and the corresponding carboxylate ions <88Mi 306-01 >. The infrared spectra of 2,3-disubstituted 1,3-thia-zolidin-4-ones have been studied and the majority of the absorption bands assigned <93PS(78)223>. The tautomerism of thiazoles substituted in 2- and 4-position by amino, thio, and hydroxy groups was examined by infrared spectroscopy (85JPR25l> (see Section 3.06.4.4). 

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