Ultrasound and plant-made catalyst speed quinoline synthesis

A team of chemists has developed a rapid, water-based method for making eight previously unreported quinoline-chromene compounds, according to reporting by ScienMag. The process uses ultrasound and a recyclable nanocatalyst prepared with help from butterbur, a medicinal plant.

The reaction produced the target molecules in 15 minutes at 25 degrees Celsius, with yields between 93 and 97 percent. It was described in the Journal of Saudi Chemical Society by Shahrzad Abdolmohammadi of Islamic Azad University in Tehran and collaborators from Azerbaijan, Jordan and India.

The result addresses a persistent challenge in medicinal chemistry: constructing complex molecules efficiently while reducing hazardous solvents, energy use and chemical waste. The new method combines an aqueous reaction medium, acoustic energy and a catalyst built from copper, zinc oxide and graphene oxide.

A three-part reaction in water

The compounds belong to the [1]benzopyrano[b]dioxolo[g]quinoline family. Their structures bring together three types of ring system: a benzopyran, also known as a chromene; a dioxole; and a quinoline. Such frameworks are important in drug research because related molecules have been associated with antibacterial, antiviral, antitumour and antiproliferative effects.

To make the new compounds, the researchers combined 4-hydroxycoumarin, different aromatic aldehydes and 3,4-(methylenedioxy)aniline. The mixture was placed in water and exposed to 80-watt ultrasound in the presence of a small quantity of Cu/ZnO@GO, a composite catalyst in which copper-doped zinc oxide particles are attached to graphene oxide.

The catalyst and ultrasound worked far better together than either component alone. Without a catalyst, the reaction produced a 20 percent yield after 300 minutes under reflux. Ultrasound without the nanocomposite produced 48 percent in 15 minutes. Under the selected conditions, however, the combined system reached a maximum yield of 97 percent using 0.05 grams of catalyst in 3 millilitres of water.

The researchers also tested ethanol, dichloromethane, acetonitrile and dimethylformamide. None performed as well as water. Several other catalysts were evaluated but did not match the nanocomposite’s results.

Ultrasound helps by creating and collapsing tiny bubbles in the liquid. This process, known as acoustic cavitation, generates brief areas of high temperature and pressure, improving contact between the reactants and the solid catalyst. Although these conditions are intense at a microscopic level, the reaction mixture itself remains at room temperature, avoiding the need to heat the entire vessel.

A catalyst grown with butterbur extract

The catalyst’s preparation was also designed around less hazardous chemistry. The team made the zinc oxide and copper-containing nanoparticles using an aqueous extract of Petasites hybridus, commonly called butterbur. The plant’s dried and powdered rhizome was steeped in boiling deionized water, and the resulting extract helped reduce and stabilise the forming nanoparticles.

Zinc acetate and copper chloride supplied the metal components. The particles were then combined with graphene oxide through another plant-extract-assisted growth step. Graphene oxide serves as a support because it offers a large surface area, chemical and thermal stability, and relatively low cost. Anchoring the metal-containing particles to that support helps keep the active material dispersed.

A range of analytical techniques confirmed the composite’s composition and structure. Infrared measurements identified zinc–oxygen and copper–oxygen bonds. X-ray diffraction detected the hexagonal wurtzite form of zinc oxide as well as copper-related signals. Electron microscopy showed roughly spherical particles attached to graphene oxide, while elemental analysis confirmed the expected ingredients.

The catalyst could also be recovered after use. Researchers separated it by centrifugation, washed it with ethanol and dried it before returning it to another reaction. It maintained its activity through at least four cycles without a substantial decline in performance, suggesting that repeated use could help limit both material consumption and cost.

Antioxidant activity among the new molecules

The researchers proposed that the reaction proceeds through several linked steps. The catalyst first activates the aldehyde, which reacts with the aniline component. 4-Hydroxycoumarin then adds to the resulting intermediate, followed by ring closure, loss of water and formation of the final fused structure.

The method tolerated aromatic aldehydes carrying electron-donating groups such as methoxy, hydroxy and methyl, as well as electron-withdrawing groups including bromo, chloro, cyano and nitro. Aliphatic aldehydes were less successful, apparently because their lower boiling points allow them to evaporate during sonication.

Four products were tested in a DPPH free-radical scavenging assay, which measures antioxidant activity through a colour change recorded at 517 nanometres. The researchers compared them with the commercial antioxidants BHT and TBHQ. TBHQ performed best overall, while compound 4e, containing a hydroxyl group on its aryl ring, showed activity close to BHT at 1,000 parts per million.

The biological testing does not establish that the compounds are medicines. It does indicate that the chemical family may merit further investigation, particularly because oxidative damage has been linked with conditions including diabetes, cancer, atherosclerosis and Alzheimer’s disease. The study’s main contribution is a fast synthetic platform that combines water, ultrasound, plant-assisted catalyst preparation and catalyst reuse in one process.