Thiophenol, relative reactivities

Fig. 4. Relative reactivities of cyclopropylideneacetates 1-3 towards thiophenolate anion compared to 3,3-dimethylacrylate [5b,c, 15b, 27]...

Table IV. Relative Reactivities of Vinylarenes toward Thiophenol at 70 .

The higher reactivity of 2-halogenothiazoles with respect to halogenopyridines can be related to the different aromaticity of the two systems, less for thiazole than for pyridine, for example, the relatively stronger fixation of the tt bond in the thiazole than in the case of pyridine. As the data reported in Table V-1 (footnote a) indicates, the free thiophenol is more reactive than the thiolate anion toward the 2-halogenothiazoles. This fact should be considered when one prepares the thiazolyl sulfides. 

Peptides typically are prepared for this ligation process using a-alkyl thioesters, because they are simple to make at the time of peptide synthesis. However, due to the relatively slow reaction kinetics of alkyl thioesters, most native chemical ligation processes have been catalyzed through the use of thiol compound additives, such as benzyl mercaptan or thiophenol (Dawson et al., 1997). These compounds react with the initial a-alkyl thioester to form another intermediate, an aryl thioester, which is more reactive toward the N-terminal cysteine on the other peptide to be coupled. A study... 

Bifunctional analogs of the [(CR)Zn]2+ (Fig. 6a) structure in which an auxiliary catalytic imidazole or thiophenol group has been incorporated (Fig. 40) exhibit enhanced reactivity for the intramolecular transesterification reaction of 2-hydro-xypropyl 4-nitrophenyl phosphate (HPNP) relative to the parent complex.222... 

However, disappointingly poor selectivities were observed with sulfur nucleophiles. The high reactivity of the sulfur nucleophiles resulted in rapid nucleophilic displacement reactions relative to the epimerisation process and this may explain the lack of selectivity (Scheme 1.12). Moreover, the results of DKR reactions using sulfur nucleophiles are in agreement with the observed dichotomy methyl thioglycollate and benzyl mercaptan behaved similarly to amines, whereas thiophenol (which should be in the form of the thiophenolate anion under the reaction conditions used) showed the same preferential reactivity as the metallated nucleophiles. 

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