Synthesis of 2-Mercapto-(2-Oxoindolin-3-Ylidene)Acetonitriles from 3-(4-Chloro-5 H-1,2,3-Dithiazol-5-Ylidene)Indolin-2-ones

Abstract

Alkylidene oxindoles are important functional moieties and building blocks in pharmaceutical and synthetic chemistry. Our interest in biologically active compounds focused our studies on the synthesis of novel oxindoles, bearing on the exocyclic double bond at the C8, CN, and S groups. Extending the potential applications of Appel’s salt, we developed a new synthetic approach by investigating the reactions of C5-substituted 2-oxindoles with 4,5-dichloro-1,2,3-dithiazolium chloride (Appel’s salt) to give original (Z)-3-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)indolin-2-one derivatives, and new 2-mercapto-(2-oxoindolin-3-ylidene)acetonitriles via a dithiazole ring-opening reaction. The work described in this article represents further applications of Appel’s salt in the conception of novel heterocyclic rings, in an effort to access original bioactive compounds. Fifteen new compounds were prepared and fully characterized.

Keywords: 1,2,3-dithiazole; 3-alkenyl-2-oxindole; Appel’s salt.

Figure 1

The (Z)-3-(4-oxo-4,5-dihydro-thiazol-5-ylidene)indolin-2-one pattern (I) [26,27], and synthesis targets 3-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)indolin-2-one (II) and (2-oxoindolin-3-ylidene)-2-mercaptoacetonitrile (III).

Scheme 1

Reactivity of Appel’s salt with (a) N-arylamines; and (b) active methylene compounds.

Figure 2

Retrosynthesis to 3-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)indolin-2-one derivatives (3) and original (2-oxoindolin-3-ylidene)-2-mercaptoacetonitriles (4).

Scheme 2

Synthesis of 3-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)indolin-2-ones (3a–3d) via the condensation of 2-oxindoles (2a–2d) with Appel’s salt (1).

Figure 3

Representation of the O–S attractive interaction, and selected mesomer forms for the (Z)-3-(1,2,3-dithiazol-5-ylidene)indololin-2-ones (Table 1, 3a).

Scheme 3

Dithiazole ring opening with sodium hydride or methyl magnesium bromide. Conversion of 3-(1,2,3-dithiazol-5-ylidene)indololin-2-ones (3a–d) into 2-mercapto-2-(2-oxoindolin-3-ylidene)acetonitriles (4a–d) and 2,2′-disulfanediylbis(2-(2-oxoindolin-3-ylidene)acetonitriles) (5a–5b).

Scheme 4

Proposed mechanisms according to the use of NaH (Path A) or methyl magnesium bromide (Path B).

Scheme 5

Synthesis of 2-(2-oxoindolin-3-ylidene) derivatives (6a–6d) via the ring opening of alkenyldithiazole (3a–3d) with supported triphenylphosphine.