2-substituted thiazoles

Table III-IO6 Thiazoles substituted by one polyfunctional group Table III-107 Thiazoles substituted by several polyfunctional groups...

Table III-124 Thiazoles substituted by several heterocyclic groups. ...

Thiazoles Substituted by Heterocydic Groups Nonadjacent to flie Tbiazole Ring... 

Table III-125 Thiazoles substituted by heterocyclic groups nonadjacent to the...

TABLE III-124. THIAZOLES SUBSTITUTED BY SEVERAL HETEROUYI.CIC GROUPS... 

TABLE III-125. THIAZOLES SUBSTITUTED BY HETEROCYCLIC GROUPS NONADJACENT TO THE THIAZOLE RING... 

The present procedure is illustrative of a mild and general method for preparing thiazoles substituted in the 4-position with electron-withdrawing substitutents such as carbethoxy, cyano, and p-toluenesulfonyl. Thus condensation of ethyl isocyanoacetate with various thiono esters affords the parent ethyl thiazole-4-carboxylate as well as a series of analogs bearing substituents in the... 

Fairly complex approaches have been used to construct thiazoles substituted with an enamine group. The cyclocondensation of l-tosyl-2,2-dichloroethenyl isothiocyanate 21 with various enamines such as 22 affords enamino substituted thiazoles such as 23 in high yields <00MI109>. 

Thiazoles substituted in the 2-, 4- or 5-position with an amino, hydroxy or mercapto group are in tautomeric equilibrium with the corresponding imino-, oxo- or thioxo-thiazo-lines (Scheme 57). A similar protomerism has been established for (4-phenylthiazol-2-yl)acetone (109 Scheme 58). 

The thiazole-substituted homoallylic alcohol 25 (Scheme 6) is a key intermediate, not only for RCM strategies, but also for other routes. Thiazole aldehyde 4 (Chapter 3) after homologation to enal 24 (90 % yield) [ 11,20) was subjected to asymmetric allylation with allylboron and tin reagents. Interestingly 25 with identical absolute stereochemistry was synthesized by Nicolaou et al. with (+)-IpC2B(allyl) in 96 % yield and > 97 % ee [13, 20], and by Danishefsky et al. with the enantiomeric (—)-Ipc2B(allyl) in 83 % yield and > 95 % ee [11], i.e. in one case an er-... 

Thiazoles Substituted by Heterocydic Gronps Nonadiacent to the Tiuazole Ring... 

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). 

Thiazoles substituted in the 4-position by a hydroxyl function occur preferentially as the aromatic form, as has been demonstrated by x-ray analysis <86AKZ688> and NMR studies <86AKZ685>. 

Thiazoles substituted in positions 2, 4, or 5 by hydroxy, thio, or amino groups are in tautomeric equilibrium with the corresponding oxo, thioxo, or imino thiazolines as discussed in Section 3.06.4. 

The reactivity of this class of compounds is discussed either in Section 3.06.5, whether the transformation occurs at the aromatic ring level or in Section 3.06.7, when the protomeric group (hydroxy, thio, or amino) is responsible for the reactivity. Thiazoles substituted by two of these groups also present prototropic tautomerism although with some restrictions (see Section 3.06.4). The reactivity of those compounds is discussed in Section 3.06.5 and Section 3.06.7, in a similar fashion to the monosubstituted derivatives. 

Chiral thiazole substituted aziridines are prepared in a diastereoselective fashion by adding lithiated (a-chloroalkyl)thiazoles to chiral imines <04T1175>. For example, treatment of racemic thiazole 115 with LDA and chiral imine 114 provides 116 in high diastereoselectivity. 

Imidazole is much more reactive towards nitration than thiazole, substitution taking place via the salt, as does nitration of alkylthiazoles. Thiazole itself is untouched by nitric acid/oleum at 160 °C but methylthiazoles are sufficiently activated to undergo substitution, the typical regioselectivity being for formation of more 5-nitro-than 4-nitro derivative " the 2-position is not attacked 4,5-dimethylimidazole is resistant to nitration. The much less reactive oxazoles do not undergo nitration. 

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