Transition-Metal-Free Dehydrogenation of Benzyl Alcohol for C-C and C-N Bond Formation for the Synthesis of Pyrazolo[3,4-b]pyridine and Pyrazoline Derivatives.

A series of cascade reactions that produce a range of functionalized aromatic heterocyclic compounds with pyrazole/pyrazoline cores have been developed. The method relies on a metal-free dehydrogenative process to produce in-situ benzaldehydes. The produced benzaldehyde was then allowed to react with some other substances, including acetophenone, pyrazole amine, and phenylhydrazine. The intermediate produced from these substrates underwent several chemical processes, including electrocyclization, the aza-Diels-Alder reaction, and the formation of intramolecular C-N bonds. These positive outcomes would open up the possibility of producing biologically active pyrazolo[3,4-b]pyridine and pyrazoline derivatives through a variety of possible reactions.

Dimethyl Sulfoxide-Assisted, Iodine- and Ascorbic Acid-Catalyzed One-Pot Synthetic Approach for Constructing Highly Substituted Pyrazolo[1,5-a]quinoline Thioether Derivatives.

A dimethyl sulfoxide-assisted and iodine/ascorbic acid-catalyzed simple approach to pyrazolo[1,5-a]quinoline thioether derivatives 22 is described. The compounds were identified using 1H NMR, 13C NMR, high-resolution mass spectrometry, and single-crystal X-ray diffractometry. The pyrazolo[1,5-a]quinoline thioether was synthesized in a stepwise fashion through aryl sulfenylation and benzannulation strategies. The generated heteroaryl thioether compounds 23 were exposed to the benzannulation path to produce pyrazolo[1,5-a]quinoline thioether 22. The benzannulation reaction proceeds by way of diazotization of the pyrazole amine derivative 23, radical generation by the removal of nitrogen, and eventually trapping of the aryl radical with the support of phenylacetylene 19. A catalytic amount of ascorbic acid aided the benzannulation reaction. There were several other control studies conducted, including trapping reactions with isopropenyl acetate, tetramethylpiperidine N-oxyl reactions, and reactions without phenylacetylene. Since a change in the substitution has previously demonstrated substantial bioactivity, the core structure of pyrazole was evaluated for functional group tolerance. A reasonable mechanism is then proposed, accompanied by the support of control experiments and scope. A Suzuki reaction was used to create an aryl/heteroaryl compound 35 from one of the synthesized compounds 22b. In the controlled oxidation reaction paths, molecule 22a was selectively transformed into the corresponding sulfoxide 32 and sulfone 33.

Metal- and Solvent-Free Cascade Reaction for the Synthesis of Amino Pyrazole Thioether Derivatives.

We developed an iodine-mediated cascade strategy to synthesize amino pyrazole thioether derivatives (11) in the absence of metals as well as solvents. The present approach provides amino pyrazole thioethers in a highly selective manner without the formation of diaryl sulfide and sulfenyl-enaminonitrile with broad substrate scope. The reactivity of nine sulfenylation sources and synthetic applications of the synthesized compounds have been demonstrated. Thus, the overall iodine-mediated multicomponent reaction (MCR) is more economically feasible, efficient, and environmentally benign.

Carbazole based Electron Donor Acceptor (EDA) catalysis for the synthesis of biaryl and aryl-heteroaryl compounds.

A highly regioselective, carbazole based Electron Donor Acceptor (EDA) catalyzed synthesis of biaryl and aryl-heteroaryl compounds is described. Various indole and carbazole derivatives were screened for the Homolytic Aromatic Substitution (HAS) reaction. Tetrahydrocarbazole (THC) was very efficient for the HAS transformation and proceeded via a complex formation between diazonium salt and electron rich tetrahydrocarbazole. The UV-Vis spectroscopy technique has been used to confirm the complex formation. The in situ generated EDA complex even in a catalytic amount is found to be efficient for the Single Electron Transfer (SET) process without any photoactivation. Biaryl compounds, 2-phenylfuran, 2-phenylthiophene, and 2-phenylpyrrole and bioactive compounds such as dantrolene and canagliflozin have been synthesized in moderate to excellent yields.

Correction: Carbazole based Electron Donor Acceptor (EDA) catalysis for the synthesis of biaryl and aryl-heteroaryl compounds.

Correction for 'Carbazole based Electron Donor Acceptor (EDA) catalysis for the synthesis of biaryl and aryl-heteroaryl compounds' by Rajendhiran Saritha et al., Org. Biomol. Chem., 2020, DOI: 10.1039/d0ob00282h.

An efficient method to access spiro pseudoindoxyl ketones: evaluation of indoxyl and their N-benzylated derivatives for inhibition of the activity of monoamine oxidases.

A simple, metal-free approach was developed to obtain novel pseudoindoxyl derivatives. The reaction was mediated by tBuOK on tetrahydrocarbazole 8 in dimethyl sulfoxide (DMSO) at room temperature through the hydroxylation of the indole double bond and a subsequent pinacol-type rearrangement. Spiro pseudoindoxyl compounds and their N-benzylated derivatives were assessed for their inhibitory activities against monoamine oxidase (MAO) enzymes. Based on half-maximal inhibitory concentration (IC50) values, 13 compounds were found to have higher inhibitory activity against MAO-B than against MAO-A. With regard to MAO-B inhibition, 11f showed the best inhibitory activity, with an IC50 value of 1.44 µM, followed by 11h (IC50 = 1.60 µM), 11j (IC50 = 2.78 µM), 11d (IC50 = 2.81 µM), and 11i (IC50 = 3.02 µM). Compound 11f was a competitive inhibitor with a Ki value of 0.51 ± 0.023 µM. In a reversibility experiment using dialysis, 11f showed effective recovery of MAO-B inhibition similar to that of safinamide. These experiments suggested that 11f was a potent, reversible, and competitive inhibitor of MAO-B activity.

Metal-free, regioselective, visible light activation of 4CzIPN for the arylation of 2H-indazole derivatives.

Highly regioselective organo photocatalysis of 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene) for the arylation of 2H-indazole is demonstrated. The present synthetic route provides a highly safe and easily accessible aniline precursor as an arylation reagent. The photoactivated 4CzIPN organocatalyst is found to be more efficient for single electron transfer without any organic base for the radical reaction. The carbazole-based photocatalyst (4CzIPN) with wide redox potential is stable and recyclable for further reaction transformations. Many indazole and aniline derivatives were used in the reaction and provided the arylated indazole derivatives in good to excellent yield.

TfOH mediated intermolecular electrocyclization for the synthesis of pyrazolines and its application in alkaloid synthesis.

TfOH mediated easy access to interesting pyrazolines starting from an aldehyde, phenylhydrazine and styrene has been developed. The scope of this synthetic methodology has been explored by synthesizing various 1,3,5-trisubstituted pyrazolines in very good yields with very high regioselectivity. The origin of regioselectivity has been explained by comparing the stability of possible intermediate carbocations. The synthetic utility of a green solvent has been explored by synthesizing some of pyrazolines in a DES medium. The synthetic application of the present methodology is employed in the synthesis of a pyrazoline alkaloid.