In the reaction of the available 1-tosyl-2,2-dihlorenamides with the Lawesson's reagent the derivatives of 4-tosyl-1,3-thiazole were shown to form containing a labile chlorine atom at the C 5 position. This fact was used for the synthesis of a number of the previously unknown bifunctionally substituted 4,5-thiazoles.Previously we studied the reaction of the enamides of type I with the highly basic amines [1] and sodium hydrosulfide [2], which leads to the derivatives of 5-amino-5-mercaptooxazole, the agonists of 5-NT6 receptors [3].In this work we for the first time studied the interaction of the enamides I with the Lawesson's reagent leading to the 2-R-4-tosyl-5-chloro-1,3-thiazole derivatives III. The chlorine atom in compounds III shows significant lability towards the action of the highly basic amines, sodium phenolate, and thiophenoxides, undoubtedly due to the influence of electronacceptor groups in the vicinal position to the halogen atom. The nature of the agent used as a rule does not affect the course of this reaction, the reaction products IV-VI can be isolated in a high yield (Scheme 1).Note that at the interaction of the thiazole IIIa unsubstituted in 2 position with the secondary amines and sodium tiophenoxides the replacement of the halogen atom occurs under the milder conditions and in a shorter time, but with lower yields. The interaction of compound IIIa with the highly basic primary amines is also complicated. The result of these reactions is apparently due not only to the nucleophilic substitution of the chlorine atom. The reaction includes obviously some other processes that in the case of primary amines result in a mixture of unidentified products, so this reaction requires more detailed study. In addition, analysis of the published data [4] suggests that in such systems a nucleophile can attack the C 2 center of the heterocycle. In this case, a possible mechanism involves a sequence of reactions: addition of the nucleophile to the activated double bond of the heterocycle (A), prototropic transformation (B), and cleavage of the chloride anion (C) and proton (D).The choice between two alternative structures (D and E) by means of NMR spectroscopy is difficult. We failed to accomplish identification also using the nuclear Overhauser effect, because the spatial arrangement of the tozyl group in the 4 and 5 sites and the rest of the nucleophile does not lead to the interaction between them in the NOE experiment, no effect was observed. Therefore, to prove the structure of the compounds IV-VI unambiguously, one of them (Va) was studied by the method of X-ray diffraction. The general view of the molecule Va and its main geometric parameters are shown in the figure.Bond lengths in the central thiazole heterocycle are close to usual for such compounds. Thus, the CS bonds distances are equal, and the length of the C 1 N 1 bond is close to that of the standard C=N double bond 1.28 Å, despite the conjugation in the heterocycle. The C-S 1 bonds are equal within experimental error, while the bonds C-S 3 a...
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