Thiazole, addition reactions

Tautomerism of the A-2-thiazoline-5-thiones has not been investigated intensively. A recent report shows that 2-phenylthiazo e-5-thiols exist in the thiol form in both polar and nonpolar solvents (563). This behavior is in contrast with that of corresponding thiazolones. Addition reactions involve only the exocyclic sulfur atom, and thiazole-5-thiols behave as typical heteroaromatic thiols towards unsaturated systems, giving sulfides (1533) (Scheme 80) (563),... 

Like pyridines (334), thiazoles undergo addition reactions with dimethyl acetylenedicarboxylate leading to 2 1 molar adducts, the structure of which has been a matter of controversy (335-339). 

Addition reactions of several thiazole and benzothiazole derivatives to DMAD have been reported. Thiazole (383a), for example, gives a 1 2 adduct (384a) on treatment with DMAD, whereas in the reaction of 2-ethylthiazole (383b), a S,6-dihydrothiazolo[3,2-a]azepine (385) is... 

The chemistry outlined in Schemes 8.32 and 8.34 illustrates the complexity of reactions that occur between thiocarbonyl compounds and diazo compounds. Heimgartner and co-workers (214-217) observed a similar reactivity pattern when they combined l,3-thiazol-5(477)-thiones (153) with diazoalkanes. When ethyl diazoacetate was used, additional reaction pathways occurred giving rise to a complex mixture of products (218). An interesting aspect of this chemistry involves... 

This procedure describes an example of the "aldehyde route". The addition of 2-(trimethylsilyl)thiazole (2-TST) to aldehydes occurs readily and does not require the presence of a fluoride ion source.10 The resulting secondary alcohol is as a rule isolated in very good yield. The sense of the diastereofacial selectivity of the addition reaction to chiral a-amino aldehydes can be controlled by differential protection of the... 

The carbon atoms of azole rings can be attacked by nucleophilic (Section 3.4.1.6), electrophilic (Section 3.4.1.4) and free radical reagents (Section 3.4.1.9.2). Some system, for example the thiazole, imidazole and pyrazole nuclei, show a high degree of aromatic character and usually revert to type if the aromatic sextet is involved in a reaction. Others such as the isoxazole and oxazole nuclei are less aromatic, and hence more prone to addition reactions. 

The reversed configuration of these adducts that was mistakenly assigned in our first report (Ref 57a) was timely corrected in a second paper (Ref 57b). For a commentary to this reaction, see A. Zamojski, Stereoselective aminohomologation of chiral a-alkoxy aldehydes via thiazole addition to nitrones. Application to the synthesis of W-acetyl-D-mannosamine, Chemtracts Org. Chem. 6 172 368 (1993). 

In an attempt to synthesize fused aromatic systems of a pentalene-like structure, Boekelheid and Fedoruk (332) submitted the dicyanomethyl ylide of thiazole (77) to the addition reaction with dimethyl acetylenedi-carboxylate (DMA). They unexpectedly observed the formation of a fused six-membered (80) rather than a five-membered-ring (78). This ylide (77) was readily afforded by the reaction of thiazole (73) with tetracyanoethylene oxide and then put into reaction with DMA. The initially formed thiazolopyrrole derivative (78) is strongly polarized by the gcm-dicyano group, and its pyrrole ring is spontaneously cleaved with proton elimination. The ring dosure of the intermediate (79) leads to the final stable derivative of 5-FT-thiazolo[3,2-a]pyridine (80). More recently. 

When the azomethine group is part of an electron-deficient ring, such as pyridine, pyrimidine or thiazole, the compounds exist as tetrazoles in the solid state, and at equilibrium with the azido form in solution . The equilibrium constants depend on the solvent, the nature of the substituents and the temperature . 2-Azido-4,6-dimethylpyrimidine (288a) thus exists in equilibrium with tetrazolo-pyrimidine (288b). Its chemical behaviour is, however, in accord with the azide structure 288a, including dipolar addition reactions and nitrene reactions . 

Thiamine is absorbed in the intestine by both active transport mechanisms and passive diffusion. The active form of the cofactor, thiamine pyrophosphate (thiamine diphosphate, TPP), is synthesized by an enzymatic transfer of a pyrophosphate group from ATP to thiamine (Figure 15-1). The resulting TPP has a reactive carbon on the thiazole ring that is easily ionized to form a carbanion, which can undergo nucleophilic addition reactions. 

Cyclizations of 5-alkyl-substituted 4-penten-l-oxyl radicals are faster and frequently more selective than those of terminal unsubstituted derivatives [48, 53]. This finding is in accord with the electrophilic nature of alkoxyl radicals in addition reaction to C-C double bonds. 5-Alkyl- or 5-phenyl-substituted 4-pentenoxyl radicals, such as intermediates 25 or 26, were generated from a number of different sources. For example, alkyl nitrites [39], A-alkoxypyridine-2(l//)-thiones [46], and A-alkoxy-(/ -chlorophenyl)thiazole-2(3/f)-thiones [54] in photochemically induced reactions, and A-alkoxyphthalimides [55] or type IV radical precursors [53] in thermally initiated reactions have been applied for this purpose (Scheme 6). 

Ynamines and 1,3-thiazole-5(4H)-thiones undergo an addition reaction on heating in toluene, yielding mainly the thiazolylidene... 

The penem system has always been assembled by late formation of the thiazoline ring. No attempt to obtain penems by closing the azetidinone ring as the last step has ever been reported, though this strategy is well documented on penicillins [3, 4]. Approaches based either on the dehydrative condensation of thiazoline acetic acids 4 or on ketene addition to thiazoles 5, reactions known to... 

This reaction was first reported by Hantzsch and Weber in 1887. It is the formation of thiazole derivatives by means of condensation of a-haloketones (or aldehydes) and thioamides. Therefore, it is generally known as the Hantzsch thiazole synthesis. In addition, other names, including the Hantzsch synthesis, Hantzsch reaction, and Hantzsch thiazole reaction are also used from time to time. Besides thioamides, other thio-ketone derivatives such as thiourea, dithiocarbamates, and ketone thiosemicarbazone can also condense with a-halo ketones (or aldehydes) to form thiazoles. This reaction occurs because of the strong nucleophilicity of the sulfur atom in thioamides or thioureas, and normally gives excellent yields for simple thiazoles but low yields for some substituted thiazoles, as of dehalogenation. This reaction has been proven to be a multistep reaction, and the intermediates have been isolated at low temperatures, in which the dehydration of cyclic intermediates seems to be the slow step. It is found that a variety of reaction conditions might result in the racemized thiazoles that contain an enolizable proton at their chiral center, and it is the intermediate not the final product that is involved in the racemization. Therefore, some modifications have been made to reduce or even eliminate the epimeriza-tion upon thiazole formation. In addition, this reaction has been modified using a-tosyloxy ketones to replace a-haloketones. ... 

Addition of 2-thiazolyl lithium to ketone 22 afforded a single diastereoisomer with the required C-3 stereochemistry, 23, in 70% yield. The same exo-addition product, 23, was identified as the major component of 2 1 mixture of stereoisomers 23 and 24 obtained in a combined 48% yield in the reaction of ketone 22 with 2-TST. In contrast to the addition of 2-TST to ketone 7, which favours endo-addition (Figure 9), here the coupling yield is lower and the stereochemical preference of the reaction is for formation of exo-adduct 23. Based on the limited data available (here and ref 31), it would appear that the number of factors contribute to the stereochemical outcome of Aese addition reactions. xo-thiazole 23 was subsequently converted to 2-e/7/-aceric acid (Figine 13) as described for conversion of 18 into aceric acid. 

This reaction was originally designated by Gabriel [53] in 1910 phosphorus pentasulfide reacted with acylaminoketone (showed in below reaction) an equimolecular quantity to yield 2-phenyl-5-alkyl-thiazole. The reaction is analogous to the synthesis of additional five-membered oxygen and sulfur holding rings from 1,4-dicarbonyl compounds. 

The recent developments on the metallation chemistry of oxazoles and benzoxazoles, isoxazoles and benzisoxazoles, pyrazoles and indazoles, thiazoles and benzo-thiazoles, and isothiazoles, benzo[c]isothiazoles, and benzoMisothiazoles have been reviewed. The two-decade history of catalytic carbon-carbon bond formation via direct borylation of alkane C-H bonds catalysed by transition metal complexes has been reported. The alkane functionalization via electrophilic activation has been underlined. " Recent advances of transition-metal-catalysed addition reactions of C-H bonds to polar C-X (X=N, O) multiple bonds have been highlighted and their mechanisms have been discussed. The development and applications of the transition metal-catalysed coupling reactions have been also reviewed. - ... 

The interesting reactions where a free mercapto group is linked to the nitrogen atom of the thiazole (63), after the cleavage of a fused ring, is another illustration of the additive properties of the carbocation (Scheme 40). 

The same reaction performed in ether at 0°C (336) gives the same major adduct, but the structure proposed by Acheson et al. corresponds to 86, although such a structure is hardly compatible with the presence of an isolated low-field proton. Very recently, in a reinvestigation of these cyclo-additions of DMA to azoles (338, 339), Acheson et al. were able to establish the correct structure of the adducts on the base of CNMR spectra and X-ray diffraction studies. The adduct of thiazole is represented by formula 87, and it results from the rearrangement of the... 

With the exception of the nuclear amination of 4-methylthiazole by sodium amide (341, 346) the main reactions of nucleophiles with thiazole and its simple alkyl or aryl derivatives involve the abstraction of a ring or substituent proton by a strongly basic nucleophile followed by the addition of an electrophile to the intermediate. Nucleophilic substitution of halogens is discussed in Chapter V. 

Thioformamide is prepared in situ at 25 to 30°C. as described previously, and in the presence of magnesium carbonate (492. 512. 578). The mixture is then mildly heated on a water bath, and when temperature reaches 70°C, a-haloaldehyde is added in small quantities. At the end of this addition the reaction mixture is stirred for 2 hr at 100°C. Thiazoles were isolated in the usual manner by a double steam distillation. 

In addition to the reactions described in the preceding section, alkyl groups in the 2-positions of imidazole, oxazole and thiazole rings show reactions which result from the easy loss of a proton from the carbon atom of the alkyl group which is adjacent to the ring (see Section 4.02.3.1.2). 

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