6-Hydroxy Picolinohydrazides Promoted Cu(I)-Catalyzed Hydroxylation Reaction in Water: Machine-Learning Accelerated Ligands Design and Reaction Optimization.

Hydroxylated (hetero)arenes are privileged motifs in natural products, materials, small-molecule pharmaceuticals and serve as versatile intermediates in synthetic organic chemistry. Herein, we report an efficient Cu(I)/6-hydroxy picolinohydrazide-catalyzed hydroxylation reaction of (hetero)aryl halides (Br, Cl) in water. By establishing machine learning (ML) models, the design of ligands and optimization of reaction conditions were effectively accelerated. The N-(1,3-dimethyl-9H- carbazol-9-yl)-6-hydroxypicolinamide (L32, 6-HPA-DMCA) demonstrated high efficiency for (hetero)aryl bromides, promoting hydroxylation reactions with a minimal catalyst loading of 0.01 mol % (100 ppm) at 80 °C to reach 10000 TON; for substrates containing sensitive functional groups, the catalyst loading needs to be increased to 3.0 mol % under near-room temperature conditions. N-(2,7-Di-tert-butyl-9H-carbazol-9-yl)-6-hydroxypicolinamide (L42, 6-HPA-DTBCA) displayed superior reaction activity for chloride substrates, enabling hydroxylation reactions at 100 °C with 2-3 mol % catalyst loading. These represent the state of art for both lowest catalyst loading and temperature in the copper-catalyzed hydroxylation reactions. Furthermore, this method features a sustainable and environmentally friendly solvent system, accommodates a wide range of substrates, and shows potential for developing robust and scalable synthesis processes for key pharmaceutical intermediates.

Effect of manganese substitution of ferrite nanoparticles on particle grain structure.

To investigate the influence of manganese substitution on the saturation magnetization of manganese ferrite nanoparticles, samples with various compositions (Mn x Fe3-x O4, x = 0, 0.25, 0.5, 0.75, and 1) were synthesized and characterized. The saturation magnetization of such materials was both calculated using density functional theory and measured via vibrating sample magnetometry. A discrepancy was found; the computational data demonstrated a positive correlation between manganese content and saturation magnetization, while the experimental data exhibited an inverse correlation. X-ray diffraction (XRD) and magnetometry results indicated that the crystallite diameter and the magnetic diameter decrease when adding more manganese, which could explain the loss of magnetization of the particles. For 20 nm nanoparticles, with increasing manganese substitution level, the crystallite size decreases from 10.9 nm to 6.3 nm and the magnetic diameter decreases from 15.1 nm to 3.5 nm. Further high resolution transmission electron microscopy (HRTEM) analysis confirmed the manganese substitution induced defects in the crystal lattice, which encourages us to find ways of eliminating crystalline defects to make more reliable ferrite nanoparticles.