Theoretical Prediction and Explanation of Reaction Site Selectivity in the Addition of a Phenoxy Group to Perfluoropyrimidine, Perfluoropyridazine, and Perfluoropyrazine

Perfluoroaromatics, such as perfluoropyridine and perfluorobenzene, are privileged synthetic scaffolds in organofluorine methodology, undergoing a series of regioselective substitution reactions with a variety of nucleophiles. This unique chemical behavior allows for the synthesis of many perfluoroaromatic derived molecules with unique and diverse architectures. Recently, it has been demonstrated that perfluoropyridine and perfluorobenzene can be utilized as precursors for a variety of materials, ranging from high performance polyaryl ethers to promising drug scaffolds. In this work, using density functional theory, we investigate the possibility of perfluoropyrimidine, perfluoropyridazine, and perfluoropyrazine participating in similar substitution reactions. We have found that the first nucleophilic addition of a phenoxide group substitution on perfluoropyrimidine and on perfluoropyridazine would happen at a site para to one of the nitrogen atoms. While previous literature points to mesomeric effects as the primary cause of this phenomenon, our work demonstrates that this effect is enhanced by the fact that the transition states for these reactions result in bond angles that allow the phenoxide to π-complex with the electron-deficient diazine ring. The second substitution on perfluoropyrimidine and on perfluoropyridazine is most likely to happen at the site para to the other nitrogen. The second substitution on perfluoropyrazine is most likely to happen at the site para to the first substitution. The activation energies for these reactions are in line with those reported for perfluoropyridine and suggest that these platforms may also be worth investigation in the lab as possible monomers for high performance polymers.

Crystal structure of diethyl 2-amino-5-{4-[bis(4-methylphenyl)amino]benzamido}thiophene-3,4-dicarboxylate

In the title compound, C31H31N3O5S, the regioselective substitution of the thiophene is confirmed with the amine and the amide at the 2- and 5-positions, respectively. In the molecule, the thiophene ring is twisted by 12.82 (3)° with respect to the aromatic ring of the benzamido group. Intramolecular N—H...O hydrogen bonds are present involving the N atoms of the primary amine and the amide groups, forming S(6) ring motifs. In the crystal, centrosymmetrically related molecules are linked by pairs of N—H...O hydrogen bonds involving the amide carbonyl O atoms and the primary amine N atoms to form dimers of R 2 2(16) ring motif.

Microwave-Assisted Synthesis of Mono- and Disubstituted 4-Hydroxyacetophenone Derivatives via Mannich Reaction: Synthesis, XRD and HS-Analysis

An efficient microwave-assisted one-step synthetic route toward Mannich bases is developed from 4-hydroxyacetophenone and different secondary amines in quantitative yields, via a regioselective substitution reaction. The reaction takes a short time and is non-catalyzed and reproducible on a gram scale. The environmentally benign methodology provides a novel alternative, to the conventional methodologies, for the synthesis of mono- and disubstituted Mannich bases of 4-hydroxyacetophenone. All compounds were well-characterized by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The structures of 1-{4-hydroxy-3-[(morpholin-4-yl)methyl]phenyl}ethan-1-one (2a) and 1-{4-hydroxy-3-[(pyrrolidin-1-yl)methyl]phenyl}ethan-1-one (3a) were determined by single crystal X-ray crystallography. Compound 2a and 3a crystallize in monoclinic, P21/n, and orthorhombic, Pbca, respectively. The most characteristic features of the molecular structure of 2a is that the morpholine fragment adopts a chair conformation with strong intramolecular hydrogen bonding. Compound 3a exhibits intermolecular hydrogen bonding, too. Furthermore, the computed Hirshfeld surface analysis confirms H-bonds and π–π stack interactions obtained by XRD packing analyses.

Catalytic enantioselective and regioselective substitution of 2,3-indolyldimethanols with enaminones

2,3-Indolyldimethanols as a new class of indolyldimethanols have been designed, and the first catalytic asymmetric substitution of 2,3-indolyldimethanols has been established by using cyclic enaminones as nucleophiles.

Brønsted acid-catalyzed regioselective reactions of 2-indolylmethanols with cyclic enaminone and anhydride leading to C3-functionalized indole derivatives

An abnormal regioselective substitution of 2-indolylmethanols with nucleophiles has been established to afford C3-functionalized indole derivatives in high yield and regiospecificity (40 examples, up to 99% yield).

Synthesis, characterization, and aggregation properties of functionalized polyfluorinated metallo-phthalocyanines

The reaction of 4-(2′,3′,4′,5′,6′-pentafluorobenzyloxy)phthalonitrile with 2,2,3,3,4,4,5,5-octafluoropentanol leads to the formation of 4-[2′,3′,5′,6′-tetrafluoro-4′-(octafluoropentoxy) benzyloxy]-phthalonitrile. The reaction was achieved by regioselective substitution reaction of the p-fluorine atoms of pentafluorobenzyloxy group by perfluoroalkoxy group. The tetramerization of the new dinitrile derivative in the presence of zinc, cobalt, copper or manganese salts results in the corresponding phthalocyanines. The prepared compounds have been characterized by elemental analyses, FT-IR, UV-vis, 1 H NMR, 13 C NMR, 19 F NMR and mass spectroscopies, consistent with the proposed structures. The influence of solvent and concentrations on the aggregation of the phthalocyanine complexes was studied by electronic spectroscopy.