Mechanism of C-H bond activation by various Pd catalysts under milling conditions has been studied by in situ Raman spectroscopy. Common Pd precursors, that is PdCl , [Pd(OAc) ] , PdCl (MeCN) and [Pd(MeCN) ][BF ] , have been employed for the activation of one or two C-H bonds in an unsymmetrical azobenzene substrate. The C-H activation was achieved by all used Pd precursors and their reactivity increases in the order [Pd(OAc) ]

The mechanism of mechanochemical Pd II -catalyzed selective bromination of the carbon−hydrogen bond in azobenzene by N-bromosuccinimide (NBS) was investigated using in situ timeresolved Raman spectroscopy and quantum-chemical (density functional theory, DFT) calculations. Raman monitoring of the reactions in the presence of different amounts of Pd(OAc) 2 , ptoluenesulfonic acid (TsOH), and acetonitrile (MeCN) as solid and liquid additives provided direct evidence that the formation of the carbon−halogen bond in the solid state proceeds from catalytically active cyclopalladated intermediates that are monomeric in the presence of MeCN or dimeric without MeCN. The reaction pathway via the monomeric palladacycle is more efficient than the pathway via the dimeric palladacycle for the bromination of azobenzene, offering better yields and faster reactions. Both reaction routes require the presence of TsOH, which is involved in the formation of the active Pd II catalysts and palladacyclic intermediates, as well as in the activation of NBS. Four possible reaction mechanisms for the bromination of cyclopalladated azobenzene were investigated by DFT modeling. Three mechanistic pathways include (i) oxidative addition of the Br to Pd atom and (ii) reductive elimination by the 1,2-displacement of Br to the carbon atom. In one pathway, the transfer of Br to Pd occurs only after the initial displacement of the neutral ligand by NBS. In another, the Pd atom is inserted directly into the N−Br bond of NBS, and in the last one, Br + migrates spontaneously from the protonated NBS to Pd. In all three cases, the subsequent elimination step is remarkably lower in energy. In the fourth mechanism, Br + migrates from free NBS directly to the activated carbon, simultaneously with the Pd−C bond breaking. Besides NBS, the hydrogen bond complex NBS•••TsOH was also considered as the bromine source. None of the considered mechanisms can be definitely rejected on the basis of experimental findings and the current modeling level, and more than one could be operative depending on the reaction conditions.

The present study reports the synthesis and characterization of copper(ii) complexes with benzhydrazone-related ligands. They were screened for their cytotoxic activityin vitroin THP-1 and HepG2 human cancer cell lines.

Palladium C-H bond activation in azobenzenes with R1 and R2 at para-positions of the phenyl rings (R1=NMe2, R2=H (L1); R1=NMe2, R2=Cl (L2); R1=NMe2, R2=I (L3); R1=NMe2, R2=NO2 (L4); R1=H, R2=H (L5)) and their monopalladated derivatives, using cis-[PdCl2(DMF)2], has been studied in detail by in situ 1 H NMR spectroscopy in N,N-dimethylformamide-d7 (DMF-d7) at room temperature; the same processes have been monitored in parallel via time-resolved UV-Vis spectroscopy in DMF at different temperatures and pressures. The final goal was to achieve, from a kinetico-mechanistic perspective, a complete insight on previously reported reactivity results. The results suggest the operation of an electrophilic concerted metallation and deprotonation mechanism for both the mono-and dipalladation reactions, occurring from the coordination compound and the monopalladated intermediates, respectively. The process involves deprotonation of the C-H bond assisted by the presence of a coordinated DMF molecule, that acts as a base. For the first time, NMR monitoring provides a direct evidence of all the intermediate stages, that is: i) coordination of the azo ligand to Pd II center, ii) formation of the monopalladated species, iii) coordination of the monopalladated species to another Pd II unit, which finally result in the iv) formation of the dipalladated product. All of these species have been identified as intermediates in the dipalladation of azobenzenes, evidenced also by UV-Vis spectroscopy time-resolved monitoring. The data also confirms that the cyclopalladation of asymmetrically substituted azobenzenes occurs by two concurrent reaction paths. In order to identify the species observed by NMR and by UV-Vis spectroscopies, the final products, intermediates and the Pd II precursor have been prepared and characterized by X-ray diffraction, IR and NMR spectroscopies. DFT calculations have also been used in order to explain the isomerism observed for the isolated complexes, as well to assign their NMR and IR spectra.

The solvent-free ball-milling method for substitution of anionic ligands in organopalladium compounds was developed. Reactions of acetate, acetylacetonate, chloride, or tetrafluoroborate of mono-or dicyclopalladated azobenzenes with alkali salts of chloride, acetate and acetylacetonate yielded target products, some of which could not be obtained via direct C−H bond activation by Pd(II) precursors. The formation of products was monitored in situ by Raman spectroscopy and ex situ by NMR and IR spectroscopies and PXRD. The reported solid-state pathway provides easy access to organopalladium derivatives in high yields and in shorter reaction times than solvent-based protocols.