Interchange thioethers

In an earlier experiment, Jori et al. (14) reported that methionyl residues are important in maintaining the tertiary structure of lysozyme. The introduction of a polar center into the aliphatic side chain of methionine, as a consequence of the conversion of the thioether function to the sulfoxide, may bring about a structural change of the lysozyme molecule which, in turn, reduces the catalytic efficiency. When ozonized lysozyme was treated with 2-mercaptoethanol in an aqueous solution according to the procedure of Jori e al. (14), the enzyme did not show any increase in its activity. This may be explained in two ways. In one, such reactions are complicated by many side reactions, e.g. sulfhydryl-disulfide interchange, aggregation and precipitation of the modified enzyme (24-26). In the other, the failure to recover the activity of the enzyme may by associated with the extensive oxidation of other residues. 

The general scheme is sufficiently flexible to permit the interchange of the order of some of the steps. Thus alkylation of aniline thioether (30-3) with 3-chloro-l-diethylaminopropane leads to the intermediate (31-1). Ring closure as above by nucleophilic aromatic displacement leads to the antipsychotic dmg chlorproethazine (31-2) [32]. 

Thioamide formation benzodiazepinone, 505 heteiodiazepinone, 621 phosphorus pentasulf ide, 323, 600 Thioazole formation, nitrile addition, 301 Thiocarbamate formation, 588 phenol, 95 rearrangement, 517 Thioenol ether formation, 185, 517 addition-elimination, 554 Thioester formation, mixed anhydride, 184 Thioether formation, 241, 300, 413, 416 alkylation, 586, 588 aromatic displacement, 416 Thiohydantoin formation, 293 Thiol interchange, benzothiazole formation, 422... 

In striking contrast, when the reaction was carried out in methanol or benzene containing a small amount of a base such as aqueous NH3 or triethylamine (TEA) (Scheme 32), the N-2-C-3 interchange product, 4-phenylthiazole (52), was obtained in 90% yield along with a small quantity of the deprotonated photocleavage product (57), which was trapped by reaction with benzyl bromide to yield the ( /Z)-benzyl-thioether (58) <98JOC5592>. Conversion of 55-5d to 52-5d (Scheme 33) under these conditions confirmed that the transposition occurred via the... 

The fate of the isocyanide was suggested to depend on the nature of the substituent originally at C4 of the isothiazole ring. If the substituent is aromatic, the isocyanide is reprotonated at the isocyanide carbon to yield 32, which spontaneously cyclizes to the 4-subsituted thiazole 34, the observed N2-C3 interchange transposition product. If the substituent is not aromatic, 31 is reprotonated at sulfur to provide 33, which has a higher energy barrier to cyclization. In these cases, the isocyanosulfides can be observed spectroscopically and can be trapped as their N-formylaminobenzyl thioether derivatives. 

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