Deprotonation thiazole

A key feature of the thiazole deprotonation chemistry is its potential as a latent formyl group in the assembly of tightly functionalized, chiral molecular architecture. The use of 2-(trimethylsilyl) thiazole (TST) as a formyl anion equivalent has been well investigated and popularized by... 

Potts et al. (333) condensed dipolarophiles (DMA, dibenzoylacetylene, ethyl propiolate) with ylides (81) obtained by quaternization of 4-methyl-thiazole with an a-bromoketone or ester and subsequent deprotonation. In fact the 1 1 molar adduct obtained (82) rearranged to a pyr-rolothiazine (83). One example of this reaction is described Scheme 49. 

Hydrogen exchange, in thiazole, especially deuteration, has been quantitatively investigated (379,380), but the mechanism of the reaction carried out at acidic or neutral pH corresponds to a protonation-deprotonation process (380), different from electrophilic substitution and is discussed in section I.3.E. 

Another interesting point is that both H-2 and H-5 in thiazole (139) deprotonate at about the same rate. This observation was also made at... 

In general, methyl groups in the 4- and 5-positions of imidazole, oxazole and thiazole do not undergo such deprotonation-mediated reactions, even when the ring is cationic. 

In one possible mechanism, oxidative addition of iodobenzene to Pd(0) gives Pd(II) intermediate 74, which subsequently inserts into thiazole regioselectively at the C(5) position to form the a-adduct of arylpalladium(II) 75. The order of reactivity is similar to the electrophilic substitution, which is known to be C(5) > C(4) > C(2) [74]. Treatment of the insertion adduct 75 with a base regains the aromaticity after deprotonation, giving rise to 73 along with Pd(0) for the next catalytic cycle. 

In the middle of the 1950s, Knott reported the synthesis of dyesmffs based on benzothiazole derivatives. Alkylation of Al-methylbenzo-l,3-thiazole-2-thione with a-bromoacetophenone and deprotonation of the resulting thiocarbonylium salt 5 yielded, after spontaneous desulfurization of the intermediate thiirane (7), the alkylidene derivative 8 (18) (Scheme 5.1). In order to rationalize the reaction, thiocarbonyl ylide 6 was proposed as the precursor of thiirane 7. To the best of our... 

The treatment of thiazole with n-butyl- or phenyllithium leads to exclusive deprotonation at C-2. When the 2-position is blocked, deprotonation occurs selectively at C-5. However, if the substituent at C-2 is an alkyl group, the kinetic acidities of the protons at the a-position and at the 5-position are similar. The reaction of 2,4-dimethylthiazole with butyllithium at -78°C yields the 5-lithio derivative (289) as the major product but if the reaction is carried out at higher temperature the thermodynamically more stable 2-lithiomethyl derivative (290) is obtained (Scheme 37). The metallation at these two positions is also dependent on the strength and bulk of the base employed (74JOC1192) lithium diisopropylamide is preferred for selective deprotonations at the 5-position. 

Thiazolylzinc halides have been employed as nucleophiles in Negishi couplings [12-14]. 2-Thiazolylzinc chloride was prepared by deprotonation of thiazole followed by treatment with ZnCl2. Subsequent Negishi coupling of thiazolylzinc chloride with 5-iodo-2 -deoxyuridine 8 elaborated the 5-substituted pyrimidine nucleoside 9 with the assistance of one equivalent of ZnCl2 [14]. 

The ion (113) is an oxidant in several reactions.128 In addition to the normal thiuram disulfides, isothiuram disulfide (116) also exists.129 However, no complexes are known in either a neutral or (for R = H) a deprotonated form. Numerous other ring systems exist in which a CS2 fragment is incorporated, e.g. rhodanines and thiazoles.1 They can act as neutral ligands in coordination compounds. 

Superacid-promoted dicationic species containing heteroaromatic rings, where positive charge centres migrate through consecutive deprotonation-reprotonation steps, undergo cyclization reactions followed by aromatization and superacid-promoted elimination of benzene (Scheme 10).31 The process leads to the synthesis of aza-polycyclic aromatic compounds in moderate to good yields. Seven examples include pirazole, oxazole, and thiazole heterocycles. 

Instead, only two reaction pathways are used to generate transition metal NHC complexes with thiazol-2-ylidene orbenzothiazol-2-ylidene (i) thermal cleavage of an electron-rich olefin in the presence of a suitable transition metal (see Figure 6.12) [40,41] and (ii) deprotonation of a thiazolium or benzothiazolium salt in the presence of a transition metal (see Figure 6.13) [40,42-44]. 

The oxicams have several potential metal-binding sites, i.e. the enolate, the carbonyl-O of the amide, the deprotonated amido-N and the N atom on the pyridine/thiazole/isoxazole... 

The approach of leveraging chirality at the imine nitrogen to impart enantioselectivity has also been used to advantage in the preparation of chiral heterosubstituted aziridines. Thus, when 2-(l-chloroethyl)-4-methyl-thiazole 671 is deprotonated with lithium diisopropylamide (LDA) and treated with the chiral aldimine 670, the aziridinyl thiazole derivative 672 is produced in excellent yield and diastereoselectivity (Scheme 164) <2004T1175>. 

---