Graphene Oxide and Its Functionalized Derivatives as Carbocatalysts in the Multicomponent Strecker Reaction of Ketones

The development of synthetic methods that afford high yields of the target products with a minimal environmental footprint is a major goal in organic synthesis. The use of carbocatalysts is attractive owing to their low cost and high natural abundance. Carbocatalyts have been applied in the oxidative aromatization and preparation of heteroaromatic compounds such as pyridine, imidazole, and pyrimidine. Recently, graphene oxide (GO) has attracted interest as a new carbocatalyst in organic transformations. The capability of GO to catalyze organic transformations is due to the presence of oxygencontaining functional groups on its aromatic scaffold, which can act as soft acids or mild oxidants. For example, GO mediates the oxidation of various hydrocarbons, olefins, and sulfides and catalyzes Michael-type Friedel–Crafts reactions, azaMichael additions, the hydration of alkynes, and ring-opening polymerization. Its amphiphilic character allows it to act as a phase-transfer reagent. Sulfonated graphene (S-graphene) has shown promise for the hydrolysis of esters. One of the most important multicomponent reactions is the Strecker reaction to synthesize a-amino acids through the formation of a-amino nitriles. It is the key step in the preparation of various natural products such as saframycin A 15] and ecteinascidin 743. Conventional homogeneous and heterogeneous catalysis is generally performed with the use of harsh Brønsted acids and toxic metal complexes. The efficient, clean, three-component Strecker reaction of ketones is challenging. A few heterogeneous catalysts have been previously reported for the Strecker reaction of ketones. These included zeolite Al-MCM-41, solid-supported gallium triflate, tin-ion-exchanged montmorillonite, supported Co–SBA-15, and organometallic hollow spheres bearing bis(N-heterocyclic carbene)–palladium. These reactions typically require the use of toxic metals, long reaction times, and microwave irradiation. Herein, we evaluate various functionalized GOs in the Strecker reaction to correlate the efficiency of the catalysts to the acidity of the differently treated GOs. We show that S-graphene and GO, operating under solvent-free and near-room-temperature conditions, provide much better yields than conventional solid catalysts. A wide range of functionalities can be introduced onto GO through covalent reactions. For example, sulfonate groups can be introduced to increase the acidity of GO. Herein, we abbreviate this as S-graphene (Figure 1). GO and S-graphene were synthesized by using reported procedures, and in the latter case, the sulfonate groups were covalently tethered onto reduced GO. The functionalities in the various GO derivatives were determined by FTIR spectroscopy (Figure 1b), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA) (see the Supporting Information). The amount of Brønsted acid groups in GO and S-graphene was confirmed by acid–base titration. The titration results revealed that the GO sample contained 0.0073 mmolmg 1 carboxylic acid groups, whereas the S-graphene sample contained 1.5 mmolg 1 acid groups. This value is considerably higher than that of commercially available solid acid Nafion NR 50 (0.80 mmolg ). The pH values of dispersions containing the same weight of S-graphene and GO were 2.6 and 4.2, respectively, at approximately 0.5 mgmL , which is consistent with the expected trend that sulfonate is the most acidic group. The various GO derivatives were examined for their catalytic activities in the Strecker reaction. In a typical experiment, a mixture of the aldehyde or ketone, the amine, and trimethylsilyl cyanide under neat conditions was allowed to react in the presence of the catalyst (Figure 2). A good yield was obtained within 1 h if the reaction was performed under neat conditions at room temperature, whereas a small amount of diethyl acetal was found if ethanol was used as the solvent. Upon completion of the reaction, the catalyst was recovered by simple filtration. The good catalytic yield with aldehydes motivated us to validate our protocol with ketones. Acetophenone, aniline, and TMSCN were used as the reactants in a model reaction to produce a-amino nitrile. Interestingly, phenyl-2-phenylaminopropanenitrile was obtained in 94% yield by using 40 wt% GO at 50 8C, and the yield was improved to 97% by using 12 wt% Sgraphene at room temperature; all reactions were performed under neat conditions. The control experiments, which were performed in the absence of a catalyst, yielded no product other than 2% imine after 1 h. In Figure 2, the catalytic activities of different GO derivatives are compared with those of some typical solid acid catalysts. It is clear that GO and S-graphene show the highest catalytic [a] Dr. A. Sengupta, Dr. C. Su, Dr. C. Bao, C. T. Nai, Prof. K. P. Loh Department of Chemistry and Graphene Research Centre National University of Singapore 3 Science Drive 3, Singapore (Singapore) E-mail : [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cctc.201402254.