Indoles In Water Research Articles

Heteroarylation of Organophosphonium Salts with Indoles in Water: Synthesis of Symmetrical and Unsymmetrical 3,3′‐Bisindolylmethane Derivatives.

AbstractA method for the synthesis of symmetrical and unsymmetrical 3,3′‐bis(indolyl)methanes (3,3′‐BIMs) has been developed through the direct heteroarylation of indolyl‐containing di(hetero)aryl phosphonium salts with indole derivatives in aqueous media. This metal‐free reaction proceeds smoothly under mild conditions, eliminating the need for hazardous solvents and expensive additives/catalysts typically used in conventional synthesis routes, thereby highlighting the synthetic practicality and efficiency of the process. The success of this approach is largely attributed to the role of water as a promoter, facilitating the C−P bond functionalization of the phosphonium salts. Furthermore, the reaction demonstrates a broad substrate scope, good functional group tolerance, and excellent scalability. Moreover, the protocol can also be extended to the synthesis of triindolylmethane compound and diarylmethylated indole.

Potassium persulfate-glucose mediated synthesis of 3,3′-Bis(indolyl)methanes from arylacetic acid and indoles in water

An efficient and eco-friendly method has been developed for the preparation of 3,3′-bis(indolyl)methanes from indoles and aryl acetic acid is reported. The in-situ conversion of aryl acetic acid to their corresponding carbonyl compounds, and subsequent condensation with indoles was prompted by K2S2O8 in presence of glucose in water. The metal-free reaction with room temperature conditions, and wide substrate scope with good functional group tolerance are the salient features of the developed methodology.

Manganese-catalysed C2 allylation and deuteration of indoles in water

Mn-catalysed C–H activation has emerged as a useful sustainable methodology for the formation of new C–C bonds. To date most of the protocols are described in organic solvents. Water as solvent, on the other hand, would be highly advantageous, but is often incompatible with organometallic chemistry. Herein, we describe the C–H activation of indoles using an unmodified, commercially available manganese catalyst in water. Two types of valuable allyl groups can be added and a good substrate scope is described. Substitution at the C-3 group is tolerated, allowing access to medicinally important frameworks, and the reaction works on a gram scale. Finally, harnessing the tolerance of water as the reaction medium, D2O can be used as an inexpensive source of deuterium for the C-2 labelling of indoles.

Potassium persulfate mediated oxidative dearomatization and C–H functionalization of indoles in water: Green and transition metal free approach for the synthesis of indolone derivatives

An operationally simple, transition metal-free “Greener Approach” for the synthesis of 2-(1H-indol-3-yl)-2,3’- bisindolin-3-one derivatives using K2S2O8 as an eco-friendly oxidant in water is described for electron rich and deficient indoles. Reactions in water and acetonitrile are done for confirming the intermediate and yield. The reaction proceeds through a radical pathway, confirmed by EPR, with C3 oxidative dearomatization followed by trimerization. Preliminary photophysical studies are done for selected compounds with donor-acceptor functional groups.

K2S2O8-glucose mediated oxidative coupling of alcohols with indoles for synthesis of bis(indolyl)methanes in water

We have performed K2S2O8-glucose mediated oxidative coupling of alcohols with indoles in water for synthesis of BIMs.

Efficient Synthesis of 3-(Arenesulfinyl)indoles in Water

Efficient Synthesis of 3-(Arenesulfinyl)indoles in Water

Friedel–Crafts-Type Alkylation of Indoles in Water Using Amphiphilic Resin-Supported 1,10-Phenanthroline–Palladium Complex under Aerobic Conditions

The palladium-catalyzed Friedel-Crafts-type alkylation of indoles in water has been achieved using amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG) resin-supported phenanthroline-palladium complexes in water under aerobic conditions, affording the corresponding products with good-to-high yield. The polymeric catalyst was also found to promote the C3-alkylation reaction to give a thermodynamic alkylation product with high selectivity. The polymeric catalyst was recovered and reused several times without any loss of catalytic activity.

Green and Efficient Synthesis of 3-Pyrazolyl Indoles in Water

A green and efficient synthesis of 3-pyrazolyl indoles was developed by the cyclocondensation reaction of β-ethylthio-β-indolyl-α, β-unsaturated ketones with semicarbazide hydrochloride as hydrazine equivalent in the presence of 3 equiv. of PEG-400(1a/PEG mole ratio of 1:3) in reflux water. This procedure did not require toxic hydrazine and product purification, eliminating the use of toxic liquid chemicals.

Iron-Catalyzed C–H Sulfonylmethylation of Indoles in Water–PEG400

An iron-catalyzed C–H sulfonylmethylation of indoles in water–PEG400 has been developed using p-toluenesulfonylmethyl isocyanide. This protocol enables direct regioselective construction of Csp2–Csp3 bond at the C3 position of indoles with a broad range of substrate compatibility in moderate to good yields, which is cost-effective and environmentally friendly.

Shielding Effect of Micelle for Highly Effective and Selective Monofluorination of Indoles in Water.

Highly selective direct monofluorination of indoles and arenes was developed through an approach that allows site-specific solubility of substrate and fluorine source in the micelle. This approach was highly selective for a broad range of substrates with excellent functional group tolerance. Differences in binding constant and solubility of indoles and arenes in the micelle allowed the fine-tuning of selectivity. Control experiments suggested a radical pathway and provided insight into the role of micelles of the environmentally benign amphiphile PS-750-M. Dynamic light scattering experiments strongly indicated the site-specific solubility of the substrate and fluorine source. The methodology was successfully adapted to gram scale, and the E-factor established from a recycle study indicated that the process is environmentally responsible and sustainable.

Ultrasonication‐Assisted Synthesis of 3‐Substituted Indoles in Water Using Polymer Grafted ZnO Nanoparticles as Eco‐Friendly Catalyst

AbstractIndole based heterocyclic molecules are important and valuable structural unit that are present in various biologically active natural products, pharmaceuticals and agrochemicals. In this paper, zinc oxide nanoparticles were explored as catalyst for the synthesis of 3‐substituted indoles in water via ultra‐sonication. The stability of ZnO nanoparticles and their dispersion in water was enhanced by grafting it with a biodegradable polymer (poly lactic acid). The proposed methodology is capable of providing desired products in good yield (83‐97%) and 25 derivatives of indoles were synthesized. The green reaction metrics such as E‐factor (0.16) and atom economy (97%) show that the present protocol is sustainable and economical. Also, the reactions were carried out in water under environmentally benign conditions that avoids use of any additives or hazardous solvents.

Graphene oxide mediated thiolation of indoles in water: a green and sustainable approach to synthesize 3-sulfenylindoles

Graphene oxide, a green and recyclable catalyst, was developed to synthesize 3-sulfenylindoles in water.

A micellar catalysis strategy applied to the Pd-catalyzed C–H arylation of indoles in water

Surfactant-assisted, ligand-enabled selective C–H arylation of indoles in water under mild conditions using 1 mol% of [(cinnamyl)PdCl]2.

A New Amphiphilic Brønsted Acid as Catalyst for the Friedel–Crafts Reactions of Indoles in Water

A new amphiphile 1a featuring with two ‐NHSO2C4F9 sites is designed and synthesized as Brønsted diacid. The amphiphilicity arose from nano‐aggregations of hydrophobic fluorocarbon chains and extension of hydrophilic NH groups, confirmed by Tyndall effect and TEM. The acidity of 1a rivals to concentrated H2SO4, examined by the Hammett acidity function, 31P NMR and conductance titration. Compound 1a demonstrated excellent catalytic performance in the Friedel–Crafts alkylation of indoles in water. Reactive substrates, such as β‐monosubstituted vinyl ketones in 1,4‐addition and aldehydes in condensation, were quantitatively converted, and the products were easily isolated by filtration or extraction in 85–96 % yields. Additionally, there was no observation of effect of the acidity weakening of 1a on catalysis when poor‐reactive substrates were used, such as β,β‐disubstituted vinyl ketones in 1,4‐addition and ketones in condensation. The two kinds of reactions were practised very smoothly. The formed nano‐aggregations and the strong acidity of 1a were responsible for the highly efficient aqueous catalysis. Notably, 1a was recycled at least 3 times thanks to its amphiphilic structure. It was demonstrated the nano‐aggregations played a key role in the aqueous synthesis.

Metal Free Mono‐ and 2,3‐Bis‐sulfenylation of Indoles in Water with Sodium Sulfinates as a Sulfur Source

AbstractAn iodine‐PPh3 mediated sulfenylation of indoles in water with stable and odorless sodium sulfinates as the sulfur source is described. The reaction could afford monosulfenylated indoles in moderate to excellent yields under metal free conditions. Moreover, double C—H sulfenylation of indoles at 2‐ and 3‐positions has also been achieved by using excess sodium sulfinates under the optimized reaction conditions.

Graphene oxide: An efficient recyclable solid acid for the synthesis of bis(indolyl)methanes from aldehydes and indoles in water

An efficient synthesis of bis(indolyl)methanes from aldehydes with indoles through graphene oxide -catalyzed Friedel-Crafts alkylation is developed. The reaction proceeds in water by using graphene oxide as the single catalyst to provide the desired products in good to excellent yields. Also, this methodology has a broad substrate scope, and is environment friendly and cost economic.

ChemInform Abstract: A Highly Enantioselective Thiolation of Sulfonyl Indoles to Access 3‐sec‐Sulfur‐Substituted Indoles in Water.

AbstractVinylogous imine intermediates generated in situ from sulfonylindoles undergo asymmetric 1,4‐addition with trityl mercaptan (I) to form the title compounds with good to excellent enantioselectivities.

A highly enantioselective thiolation of sulfonyl indoles to access 3-sec-sulfur-substituted indoles in water.

A highly enantioselective approach for the synthesis of 3-alkyl- indole or indoline derivatives with a functional thiol group is presented. The chemistry is based on the asymmetric 1,4-addition of thiol to vinylogous imine intermediates, which are generated in situ from sulfonylindoles. The broad substrate transformation proceeds with high yields (up to 96%) and enantioselectivity (up to 98% ee) in a water-compatible system.

Water-medium C–H activation over a hydrophobic perfluoroalkane-decorated metal-organic framework platform

The use of water as reaction medium in the heterogeneous activation of C–H bonds has numerous advantages in terms of environmental benign, safety and cost efficiency impact. However, it is severely hampered because the reactants are difficult to dissolve in water and contact with the active sites of heterogeneous catalysts. Herein, we choose perfluoroalkane-functionalized mesoporous metal-organic framework (MOF) NU-1000 as a hydrophobic platform to encapsulate ultrafine palladium nanoparticles (Pd NPs) for C–H activation in water. The resultant Pd NPs stabilized by the perfluoroalkane exhibited high activity and regioselectivity in the direct C–H arylation of indoles in water. The introduction of perfluoroalkane chains into the mesoporous pores of NU-1000 provides hydrophobic surfaces to facilitate access of the reactants to the active sites to guarantee the high activity.

Starch as a green source for Fe3O4@carbon core–shell nanoparticles synthesis: a support for 12-tungstophosphoric acid, synthesis, characterization, and application as an efficient catalyst

12-Tungstophosphoric acid (PW) immobilized on carbon-coated Fe3O4 nanoparticles (Fe3O4@C-PW) was prepared through a combination of hydrothermal and chemical co-precipitation. The intermediate carbon layer, which was produced from starch as a green material, protects the magnetic core and also improves the dispersion and catalytic activity of the nanoparticles. Characterization of this catalyst was investigated by high resolution transmission electron microscopy (HRTEM), Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometry, and the acidic properties were studied by NH3-temperature programmed desorption and potentiometric titration. The HRTEM image showed that the catalyst had a well-defined core–shell structure with an average particle size of 50 nm. The characterization data derived from FT-IR reveal that basic structure and geometry of the Keggin anion are preserved after synthesis of Fe3O4@C-PW. The as-prepared Fe3O4@C-PW was used as a nanocatalyst for the synthesis of various bis(indolyl)methanes and β-functionalized indoles in water. The catalyst can be recovered simply using an external magnetic field and reused several times without appreciable loss of its catalytic activity.