Ring-opening hydrolysis of spiro-epoxyoxindoles using a reusable sulfonic acid functionalized nitrogen rich carbon catalyst

Abstract

Controlling the product selectivity of a ring-opening hydrolysis reaction remains a great challenge with mineral acids and to an extent with homogeneous catalysts. In addition, even trace amounts of metal impurities in a bioactive product hinder the reaction progress. This has necessitated the development of robust and metal-free catalysts to offer an alternative sustainable route. We report a nitrogen-rich sulfonated carbon as a catalyst derived from an inexpensive precursor for the synthesis of bioactive vicinal diols of spiro-oxindole derivatives. The well-characterized catalyst shows wide generality with different electronic and steric substituents in the substrates under mild reaction conditions. Hot filtration test confirms no leaching of the acid moiety and the catalyst could be reused for four cycles with retention of activities.

Fig. 1. (a) Examples of biological important spirocyclic oxindoles, (b) examples of 3-hydroxy, 3-substituted-2-oxindole derivatives.

Fig. 2. Preparation of sulfonic acid functionalized nitrogen-rich carbon SO₃H@N–C/CB₆.

Fig. 3. (a) FTIR analysis (b) TGA analysis of Cal-CB₆ and SO₃H@N–C/CB₆.

Fig. 4. XPS profile (a) survey, (b) C 1s, (c) O 1s, (d) S 2p of SO₃H@N–C/CB₆.

Chart 1. Optimization of reaction conditions^a. Reaction conditions (a): Catalyst (20 mg), N-benzyl spiro-epoxyoxindole (0.2 mmol), H₂O (300 μL), dry CH₃CN (0.5 mL), time 24 h. (b): Catalyst (20 mg), N-benzyl spiro-epoxyoxindole (0.2 mmol), H₂O (300 μL), solvents (0.5 mL), time 24 h. (c): Catalyst (mg), N-benzyl spiro-epoxyoxindole (0.2 mmol), H₂O (300 μL), dry CH₃CN (0.5 mL), Time 24 h. ^aConversion was determined by gas chromatography.

Fig. 5. Substrate (0.2 mmol), H₂O (300 μL), catalyst (20 mg), CH₃CN (0.5 mL), 50 °C. Conversion was determined by gas chromatography.

Fig. 6. (a) Alcoholysis and (b) hydrochlorination of spiro-epoxyoxindoles using SO₃H@N–C/CB₆. Substrate (0.2 mmol), nucleophile (300 μL in case of 2j and 2.2 equiv. in 2k), catalyst (20 mg), CH₃CN (0.5 mL), 50 °C. Conversion was determined by gas chromatography.

Fig. 7. Thermal ellipsoid plot depicting the crystal structure of hydrolysis products (2A, 2B, 2C, 2E and 2G; 40% probability factor for the thermal ellipsoids).

Scheme 1. A plausible mechanism for the ring-opening hydrolysis of spiro-epoxyindoles catalyzed by SO₃H@N–C/CB₆

Fig. 8. Reusability study of SO₃H@N–C/CB₆ catalyst for the hydrolytic ring-opening reaction of spiro-epoxyoxindoles.