Thiazole carboxylic acids, decarboxylation

Thiazole carboxylic acid (70), R, - Rj = H, can be also obtained from decarboxylation of 2,5-thiazole dicarboxylic acids. 

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 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... 

ACTIVATION PARAMETERS FOR DECARBOXYLATION OF THIAZOLE CARBOXYLIC ACIDS... 

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

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. 

Methylimidazo[2,l-h]thiazole-5-carboxylic acid was obtained by alkaline hydrolysis of the corresponding ethyl ester. Subsequent decarboxylation was achieved by heating with hydrochloric acid [92JCS(P1)2029]. 

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>. 

As in the case of <%-amino carboxylic acids, the zwitterions of N- and O-heterocyclic a-carboxylic acids can be decarboxylated thus <%-picolinic, thiazole-2-carboxylic, quinaldic, and chelidonic acid afford, respectively, pyridine, thiazole, quinoline, and 4-pyrone. Furan is best prepared by removal of carbon dioxide from pyromucic acid (2-furoic acid) by heat in early work this was effected by heating the acid in a sealed tube or with soda-lime, but Wilson19 has described a convenient method that involves only simple apparatus and affords the very good yields of 72-78% ... 

Maier and Endres showed [44] that irradiation of imidazole-2-carboxylic acid, matrix-isolated at 10 K, with a wavelength of 254 nm leads to decarboxylation and the formation of a complex between the parent imidazol-2-ylidene and carbon dioxide Maier applied a similar approach to the formation of the parent thiazol-2-ylidene. [45] This matrix-isolation approach is the only practical route to diaminocarbene derivatives with hydrogen substituents on the amino groups and it would be valuable to generate diaminocarbene itself this way. The precursor amidinoformic acid is known, [46] but is apparently too insoluble in suitable media for the matrix method to be applied. Both diaminocarbene [47] and the parent imidazol-2-ylidene [48] have been detected by neutralisation-reionisation mass spectroscopy. 

A series of novel dispirooxindolecyclo[pyrrolo[l,2-c]thiazole-6,5 -thiazolidine] derivatives (172) were obtained regioselectively by the 1,3-dipolar cycloaddition reaction of 5-arylidene-2-thioxothiazolidin-4-ones (171) as dipolarophiles with nonstabilized azomethine ylides, generated in situ via decarboxylative condensation of isatin (155) and thiazolidine-4-carboxylic acid (170) in ethanol under both classical refluxing and ultrasound irradiation (Scheme 8.54). Because of the advantages of ultrasonic irradiation of mild reaction conditions, short reaction times, and high efficiency, it is quite profitable to develop the 1,3-dipolar cycloaddition of azomethine ylides under these conditions (Hua et al. 2012). 

The decarboxylative arylation of thiazole- and oxazole-5-carboxylic acids with aryl halides occurs in the presence of a Pd/Ag system (Scheme 4.46) [51]. The azole-azole coupling also proceeds through decarboxylation and C-H bond cleavage (Scheme 4.47) [52]. 

The first enantiospecific route to this class of natural products was reported by Williard and de Laszlo (Scheme 43.47). The route started with the a,a-dichlorination of aldehyde 298 with enamine formation followed by chlorination with A-chlorosuccinimide (NCS) to afford 299 in 72% yield. The subsequent oxidation of aldehyde 299 with KMn04, followed by Kochi-Hunsdiecker decarboxylative chlorination of resultant carboxylic acid 300, afforded trichloromethyl ester 301 in 77% yield. Ester 301 was divergently converted into aldehyde 302 and carboxylic acid 303, both of which were mixed with thiazol-2-ylmethyl isocyanide and MeNH2 to promote Ugi condensation to yield (+)-demethyldysidenin 304, an enantiomer of the natural product, along with the C5-epiner. This work has led to the... 

Strecker aldehyde are generated by rearrangement, decarboxylation and hydrolysis. Thus the Strecker degradation is the oxidative de-amination and de-carboxylation of an a-amino acid in the presence of a dicarbonyl compound. An aldehyde with one fewer carbon atoms than the original amino acid is produced. The other class of product is an a-aminoketone. These are important as they are intermediates in the formation of heterocyclic compounds such as pyrazines, oxazoles and thiazoles, which are important in flavours. 

---