Mechanochemical Conversion of Aromatic Amines to Aryl Trifluoromethyl Ethers

Increased interest in the trifluoromethoxy group in organic synthesis and medicinal chemistry has induced a demand for new, selective, general, and faster methods applicable to natural products and highly functionalized compounds at a later stage of hit-to-lead campaigns. Applying pyrylium tetrafluoroborate, we have developed a mechanochemical protocol to selectively substitute the aromatic amino group with the OCF3 functionality. The scope of our method includes 31 examples of ring-substituted anilines, including amides and sulfonamides. Expected SNAr products were obtained in excellent yields. The presented concise method opens a pathway to new chemical spaces for the pharmaceutical industry.Peer reviewe

Mechanochemical Transformation of CF3 Group : Synthesis of Amides and Schiff Bases

We communicate two mild, solvent-free mechanochemical coupling transformations of CF3 group with nitro compounds into amides or Schiff bases employing Ytterbia as a catalyst. This process proceeds via C-F bond activation, accompanied with utilisation of Si-based reductants/oxygen scavengers - reductants of the nitro group. The scope and limitations of the disclosed methodologies are thoroughly studied. To the best of our knowledge, this work is the first example of mechanical energy promoted transformation of the inert CF3 group into other functionalities.Peer reviewe

Mechanochemical Ni-Catalysed Arylation of Ortho-Hydroxyarylenaminones : Synthesis of Isoflavones

This work describes two new synthetic methods for the preparation of isoflavones following the Ni-catalysed domino arylation reactions of the vast range of ortho-hydroxyarylenaminones utilising aromatic bromides as well as carboxylic acids. The presented protocols tolerated significant variation of all coupling partners and enabled synthesis of isoflavone library of twenty-three representatives. This is the first communicated precedent where the mechanic energy was utilised in the synthesis of isoflavones following the domino cyclisation mode.Peer reviewe

Cu-Catalyzed Arylation of Bromo-Difluoro-Acetamides by Aryl Boronic Acids, Aryl Trialkoxysilanes and Dimethyl-Aryl-Sulfonium Salts : New Entries to Aromatic Amides

We describe a mechanism-guided discovery of a synthetic methodology that enables the preparation of aromatic amides from 2-bromo-2,2-difluoroacetamides utilizing a copper-catalyzed direct arylation. Readily available and structurally simple aryl precursors such as aryl boronic acids, aryl trialkoxysilanes and dimethyl-aryl-sulfonium salts were used as the source for the aryl substituents. The scope of the reactions was tested, and the reactions were insensitive to the electronic nature of the aryl groups, as both electron-rich and electron-deficient aryls were successfully introduced. A wide range of 2-bromo-2,2-difluoroacetamides as either aliphatic or aromatic secondary or tertiary amides were also reactive under the developed conditions. The described synthetic protocols displayed excellent efficiency and were successfully utilized for the expeditious preparation of diverse aromatic amides in good-to-excellent yields. The reactions were scaled up to gram quantities.Peer reviewe

Structural, Spectroscopic, Thermal, and Magnetic Properties of a New Dinuclear Copper Coordination Compound with Tiglic Acid

The first coordination compound of copper and tiglic acid named tetrakis(μ-tiglato)bis(tiglic acid)dicopper(II) was synthesized and crystallized from water solution. Its structure was determined and analyzed based on X-ray diffraction measurement. The paddle-wheel coordination system of the investigated compound was compared with other similar copper structures known in the literature. The Hirshfeld analysis was used for the detailed analysis of intermolecular interaction. The new compound was also characterized in terms of infrared absorption, thermal, and magnetic properties. The antiferromagnetic coupling of copper ions was found

New Derivatives of 5-((1-Methyl-Pyrrol-2-yl) Methyl)-4-(Naphthalen-1-yl)-1,2,4-Triazoline-3-Thione and Its Coordination Compounds with Anticancer Activity

A new ligand 5-((1-methyl-pyrrol-2-yl) methyl)-4-(naphthalen-1-yl)-1,2,4-triazoline-3-thione (C15) and its metal complexes with formulae: Mn(C15)Cl2MeOH (1), Fe(C15)Cl2MeOH (2), Ni(C15)Cl2MeOH (3), Cu(C15)2Cl2 (4) and Zn(C15)4Cl2 (5) have been synthesized. The C15 ligand and complexes were characterized by NMR, elemental analysis, FT-IR, EPR, magnetic and TGA studies. The anticancer activities of the organic ligand (C15) and complexes (1–5) were evaluated against human colon adenocarcinoma (HT29) and human lung (A549) cancer cell lines. The complex (1) exhibited potential activity at concentration of 794.37 μM (A549) and 654.31 μM (HT29) in both cancer cells. The complex (3) showed significant activity against the HT29 cancer cell line with an IC50 value of 1064.05 μM. This article highlights some of the metals that have become important in the development of new coordination complexes and the treatment of cancer. Additionally, for C15, the toxicity was predicted by ADMET analysis and molecular docking