Synthesis of α- and β-Carbolines by a Metalation/Negishi Cross-Coupling/SNAr Reaction Sequence

Carbolines are considered to be privileged scaffolds in medicinal chemistry. An efficient method for the synthesis of α- and β-carbolines from fluoropyridines and 2-haloanilines is reported. This streamlined procedure consists of a four-step directed ortho-lithiation, zincation, Negishi cross-coupling, and intramolecular nucleophilic aromatic substitution, providing access to a diverse set of functionalized carbolines. While the procedure is applicable to batch conditions, the generation of arylzinc intermediates in continuous flow has been demonstrated.

2,2′-(1,4-Phenylene)bis(7-nitro-1H-benzimidazole 3-oxide)

Bis(benzimidazol-2-yl-3-oxide)benzene derivatives have potential applications as energetic or photoactive materials. By using a two-step one-pot approach employing microwave heating as a tool, 2,2′-(1,4-phenylene)bis(7-nitro-1H-benzimidazole 3-oxide) (1) has been prepared in 94% yield. In the first step an SNAr reaction is performed using p-xylylenediamine as the central building block. Without isolating the intermediate, a base-mediated cyclization reaction follows in the second step. The product was isolated in analytically pure form by means of a pH-controlled precipitation.

Utilizing selective chlorination to synthesize new triangulenium dyes

Access to functionalization of new sites on the triangulenium core structure has been achieved at an early stage by chlorination with N-chlorosuccinimide (NCS), giving rise to two new triangulenium dyes (1 and 2). By introducing the chlorine functionalities in the acridinium precursor, positions complementary to those previously accessed by electrophilic aromatic substitution of the final dyes can be accesed. The chlorination is selective, giving only one regioisomer for both mono- and dichlorination products. For the monochlorinated acridinium compound a highly selective ring-closing reaction was discovered to generate only a single regioisomer of the cationic [4]helicene product. This discovery aspired further investigations into the mechanism of [4]helicene formation and to the first isolation of the previously proposed intermediate of the two-step SNAr reaction, key to all aza-bridged triangulenium and helicenium systems. A late stage functionalization of DAOTA+ with NCS gave rise to a different dichlorinated compound (2). The fully ring closed chlorinated triangulenium dyes 1, 2 and 3 show a redshift in absorption and emission relative to the non-chlorinated analogues, while still maintaining relatively high fluorescence quantum yields of 36%, 26%, and 41%, and long fluorescence lifetimes of 15 ns, 12.5 ns and 16 ns, respectively. Cyclic voltammetry shows that chlorination of the triangulenium dyes significantly lowers reduction potentials and thus allows for efficient tuning of redox and photo-redox properties.

Anticancer Activity of New 1,2,3-Triazole-Amino Acid Conjugates

A multistep synthesis was developed to prepare new 1,2,3-triazole-amino acid conjugates (6 and 7). These compounds contain the diaryl ether moiety and were synthesized via SNAr reaction under mild condition and in good yield. Their structures were confirmed by spectroscopic analyses (HR-MS, NMR, IR). These compounds showed significant antiproliferative activity (>30%) toward the breast MCF7 and liver HepG2 cancer cells lines at <10 µM concentration.

Nucleophilic Aromatic Substitution of Polyfluoroarene to Access Highly Functionalized 10-Phenylphenothiazine Derivatives

Nucleophilic aromatic substitution (SNAr) reactions can provide metal-free access to synthesize monosubstituted aromatic compounds. We developed efficient SNAr conditions for p-selective substitution of polyfluoroarenes with phenothiazine in the presence of a mild base to afford the corresponding 10-phenylphenothiazine (PTH) derivatives. The resulting polyfluoroarene-bearing PTH derivatives were subjected to a second SNAr reaction to generate highly functionalized PTH derivatives with potential applicability as photocatalysts for the reduction of carbon–halogen bonds.

Nucleophilic Aromatic Substitution of Polyfluoroarene to Access Highly Functionalized 10-Phenylphenothiazine Derivatives

Nucleophilic aromatic substitution (SNAr) reactions can provide metal-free access to synthesize mono-substituted aromatic compounds. We have developed efficient SNAr conditions for p-selective substitution of polyfluoroarenes with phenothiazine in the presence of a mild base to afford the corresponding 10-phenylphenothiazine (PTH) derivatives. The resulting polyfluoroarene-bearing PTH derivatives were subjected to a second SNAr reaction to generate highly functionalized PTH derivatives with potential applicability as photocatalysts for the reduction of carbon&ndash;halogen bonds.

Schiff base ligands derived from 1,2-bis(2'-nitro-/amino-phenoxy)-3-R-benzene and 2-hydroxy-1-naphthaldehyde and their Cu/Zn(II) complexes: Synthesis, characterization, X-ray structures and computational studies

The 1,2-bis(2'-nitrophenoxy)-3-R-benzene {R = H (1) CH3 (2) and OCH3) (3)} have been prepared from SNAr reaction between 1-fluoro-2-nitrobenzene and 3-R-catechol (aromatic diol), which are then reduced to corresponding diamines...