Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles

Herein, we report the successful syntheses of scarcely represented indole-based heterocycles which have a structural connection with biologically active natural-like molecules. The selective oxidation of indoline nucleus to indole, hydrolysis of ester and carbamoyl residues followed by decarboxylation with concomitant aromatization of the pyridazine ring starting from tetrahydro-1H-pyridazino[3,4-b]indole derivatives lead to fused indole-pyridazine compounds. On the other hand, non-fused indole-pyrazol-5-one scaffolds are easily prepared by subjecting the same C2,C3-fused indoline tetrahydropyridazines to treatment with trifluoroacetic acid (TFA). These methods feature mild conditions, easy operation, high yields in most cases avoiding the chromatographic purification, and broad substrate scope. Interestingly, the formation of indole linked pyrazol-5-one system serves as a good example of the application of the umpolung strategy in the synthesis of C3-alkylated indoles.

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Direct Sulfoxidation of Aromatic Methyl Thioethers with Aryl Halides by Copper-Catalyzed C(sp3)–H Bond Activation

Catalysts ◽

10.3390/catal9010105 ◽

2019 ◽

Vol 9 (1) ◽

pp. 105

Author(s):

Runsheng Xu ◽

Yueer Zhu ◽

Feixiang Xiong ◽

Suli Tong

Keyword(s):

Bond Activation ◽

Bond Formation ◽

Aryl Halides ◽

Biologically Active ◽

Mild Conditions ◽

Methyl Thioethers ◽

High Yields

A copper-catalyzed direct sulfoxidation reaction by C(sp3)–H bond activation has been developed. Starting from sample aromatic methyl thioethers with aryl halides, versatile biologically-active arylbenzylsulfoxide derivatives were efficiently synthesized in good to high yields under mild conditions. This new methodology provides an economical approach toward C(sp3)–C(sp2) bond formation.

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Highly Diastereoselective Synthesis of Tetrahydroquinoline Derivatives via [4 + 2] Annulation of Ortho-Tosylaminophenyl-Substituted Para-Quinone Methides and Cyanoalkenes

Frontiers in Chemistry ◽

10.3389/fchem.2021.764866 ◽

2021 ◽

Vol 9 ◽

Author(s):

Taiwei Dong ◽

Peifeng Wei ◽

Min Li ◽

Feng Gao ◽

Yuan Qin

Keyword(s):

Biologically Active ◽

Structural Motif ◽

Diastereoselective Synthesis ◽

Atom Economy ◽

Quinone Methides ◽

One Pot ◽

Reaction Performance ◽

High Yields ◽

Active Natural

As a privileged structural motif, tetrahydroquinoline skeletons widely exist in biologically active natural products and pharmaceuticals. In this protocol, a highly diastereoselective [4 + 2] annulation of ortho-tosylaminophenyl-substituted p-QMs and cyanoalkenes to construct tetrahydroquinoline derivatives has been successfully achieved. This strategy proceeds efficiently under mild condition, offering straightforward route to a variety of 4-aryl-substituted tetrahydroquinolines with high yields, excellent diastereoselectivities, broad functional group tolerance as well as gram-scale capacity. Moreover, a one-pot reaction sequence utilizing in situ generated p-QMs under the similar condition to build tetrahydroquinoline framework is smoothly conducted with good reaction performance as well as step and atom economy.

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Additive- and Oxidant-Free Expedient Synthesis of Benzimidazoles Catalyzed by Cobalt Nanocomposites on N-Doped Carbon

Synlett ◽

10.1055/s-0037-1610353 ◽

2019 ◽

Vol 30 (03) ◽

pp. 319-324 ◽

Cited By ~ 7

Author(s):

Zhaozhan Wang ◽

Tao Song ◽

Yong Yang

Keyword(s):

Functional Group ◽

Direct Synthesis ◽

Biologically Active ◽

One Pot ◽

Mild Conditions ◽

Wide Range ◽

High Yields

A one-pot direct synthesis of a wide range of biologically active benzimidazoles through coupling of phenylenediamines and aldehydes catalyzed by a highly recyclable nonnoble cobalt nanocomposite was developed. A broad set of benzimidazoles can be efficiently synthesized in high yields and with good functional-group tolerance under additive- and oxidant-free mild conditions. The catalyst can be easily recycled for successive uses, and the process permits gram-scale syntheses of benzimidazoles.

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Metal(II) Schiff base complexes as catalysts for the high-regioselective conversion of epoxides to β-hydroxy nitriles in glycol solvents

Canadian Journal of Chemistry ◽

10.1139/v06-158 ◽

2006 ◽

Vol 84 (11) ◽

pp. 1575-1579 ◽

Cited By ~ 13

Author(s):

Hossein Naeimi ◽

Mohsen Moradian

Keyword(s):

Schiff Base ◽

Ring Opening ◽

Potassium Cyanide ◽

Biologically Active ◽

Schiff Base Complexes ◽

Mild Conditions ◽

Ring Opening Of Epoxides ◽

Facile Preparation ◽

High Yields

A facile preparation of 3-hydroxy propanenitrile derivatives is described involving ring opening of epoxides with potassium cyanide in glycol solvents in the presence of Schiff base complexes as catalysts. This method occurs under neutral and mild conditions with high yields and high regioselectivity. Thus, several β-Hydroxy nitriles, useful intermediates toward biologically-active molecules, are easily obtained at room temperature.Key words: β-hydroxy nitrile, Schiff base, epoxide, glycol, catalyst.

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Efficient Electrochemical N-Alkylation of N-Boc-Protected 4-Aminopyridines: Towards New Biologically Active Compounds

ISRN Organic Chemistry ◽

10.1155/2014/621592 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Marta Feroci ◽

Isabella Chiarotto ◽

Gianpiero Forte ◽

Giovanna Simonetti ◽

Felicia Diodata D'Auria ◽

...

Keyword(s):

High Reactivity ◽

Alkyl Halides ◽

Biologically Active ◽

Direct Reaction ◽

Antiprotozoal Activity ◽

Subsequent Reaction ◽

Mild Conditions ◽

High Yields ◽

By Products ◽

Very High

The use of electrogenerated acetonitrile anion allows the alkylation of N-Boc-4-aminopyridine in very high yields, under mild conditions and without by-products. The high reactivity of this base is due to its large tetraethylammonium counterion, which leaves the acetonitrile anion “naked.” The deprotection of the obtained compounds led to high yields in N-alkylated 4-aminopyridines. Nonsymmetrically dialkylated 4-aminopyridines were obtained by subsequent reaction of monoalkylated ones with t-BuOK and alkyl halides, while symmetrically dialkylated 4-aminopyridines were obtained by direct reaction of 4-aminopyridine with an excess of t-BuOK and alkyl halides. Some mono- and dialkyl-4-aminopyridines were selected to evaluate antifungal and antiprotozoal activity; the dialkylated 4-aminopyridines 3ac, 3ae and 3ff showed antifungal towards Cryptococcus neoformans; whereas 3cc, 3ee and 3ff showed antiprotozoal activity towards Leishmania infantum and Plasmodium falciparum.

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Biologically active natural products from Cassine viburnifolia

Planta Medica ◽

10.1055/s-0035-1556259 ◽

2015 ◽

Vol 81 (11) ◽

Author(s):

T Grkovic ◽

R Akee ◽

J Evans ◽

JM Collins ◽

B O'Keefe

Keyword(s):

Natural Products ◽

Biologically Active ◽

Active Natural

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Recent Developments on Synthesis of Indole Derivatives Through Green Approaches and Their Pharmaceutical Applications

Current Organic Chemistry ◽

10.2174/1385272824999201111203812 ◽

2020 ◽

Vol 24 (22) ◽

pp. 2665-2693

Author(s):

Dipayan Mondal ◽

Pankaj Lal Kalar ◽

Shivam Kori ◽

Shovanlal Gayen ◽

Kalpataru Das

Keyword(s):

Biological Activities ◽

Synthetic Methods ◽

Pharmaceutical Chemistry ◽

Indole Derivatives ◽

Biological Studies ◽

Recent Developments ◽

Pharmaceutical Industries ◽

Green Methodology ◽

Conventional Methods ◽

High Yields

Indole moiety is often found in different classes of pharmaceutically active molecules having various biological activities including anticancer, anti-viral, anti-psychotic, antihypertensive, anti-migraine, anti-arthritis and analgesic activities. Due to enormous applications of indole derivatives in pharmaceutical chemistry, a number of conventional synthetic methods as well as green methodology have been developed for their synthesis. Green methodology has many advantages including high yields, short reaction time, and inexpensive reagents, highly efficient and environmentally benign over conventional methods. Currently, the researchers in academia as well as in pharmaceutical industries have been developing various methods for the chemical synthesis of indole based compounds via green approaches to overcome the drawbacks of conventional methods. This review reflects the last ten years developments of the various greener methods for the synthesis of indole derivatives by using microwave, ionic liquids, water, ultrasound, nanocatalyst, green catalyst, multicomponent reaction and solvent-free reactions etc. (please see the scheme below). Furthermore, the applications of green chemistry towards developments of indole containing pharmaceuticals and their biological studies have been represented in this review.

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Synthetic Routes for 1,4-disubstituted 1,2,3-triazoles: A Review

Current Organic Chemistry ◽

10.2174/1385272823666190514074146 ◽

2019 ◽

Vol 23 (8) ◽

pp. 860-900 ◽

Cited By ~ 8

Author(s):

Chander P. Kaushik ◽

Jyoti Sangwan ◽

Raj Luxmi ◽

Krishan Kumar ◽

Ashima Pahwa

Keyword(s):

Solid Phase ◽

Click Reaction ◽

Biological Activities ◽

Triazole Ring ◽

Copper Catalysts ◽

Biologically Active ◽

Pharmaceutical Chemistry ◽

Biological Targets ◽

Synthetic Routes ◽

High Yields

N-Heterocyclic compounds like 1,2,3-triazoles serve as a key scaffolds among organic compounds having diverse applications in the field of drug discovery, bioconjugation, material science, liquid crystals, pharmaceutical chemistry and solid phase organic synthesis. Various drugs containing 1,2,3-triazole ring which are commonly available in market includes Rufinamide, Cefatrizine, Tazobactam etc., Stability to acidic/basic hydrolysis along with significant dipole moment support triazole moiety for appreciable participation in hydrogen bonding and dipole-dipole interactions with biological targets. Huisgen 1,3-dipolar azide-alkyne cycloaddition culminate into a mixture of 1,4 and 1,5- disubstituted 1,2,3-triazoles. In 2001, Sharpless and Meldal came across with a copper(I) catalyzed regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles by cycloaddition between azides and terminal alkynes. This azide-alkyne cycloaddition has been labelled as a one of the important key click reaction. Click synthesis describes chemical reactions that are simple to perform, gives high selectivity, wide in scope, fast reaction rate and high yields. Click reactions are not single specific reaction, but serve as a pathway for construction of simple to complex molecules from a variety of starting materials. In the last few decades, 1,2,3-triazoles attracted attention of researchers all over the world because of their broad spectrum of biological activities. Keeping in view the biological importance of 1,2,3-triazole, in this review we focus on the various synthetic routes for the syntheisis of 1,4-disubstituted 1,2,3-triazoles. This review involves various synthetic protocols which involves copper and non-copper catalysts, different solvents as well as substrates. It will boost synthetic chemists to explore new pathway for the development of newer biologically active 1,2,3-triazoles.

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The Molecular Diversity Scope of Urazole in the Synthesis of Organic Compounds

Current Organic Synthesis ◽

10.2174/1570179416666190925162215 ◽

2019 ◽

Vol 16 (7) ◽

pp. 953-967 ◽

Cited By ~ 1

Author(s):

Ghodsi M. Ziarani ◽

Fatemeh Mohajer ◽

Razieh Moradi ◽

Parisa Mofatehnia

Keyword(s):

Biological Activities ◽

Biological Properties ◽

Biologically Active ◽

Microtubule Assembly ◽

Heterocyclic Molecules ◽

Biological Perspective ◽

Highly Active ◽

Anti Inflammatory ◽

High Yields ◽

Short Time

Background: As a matter of fact, nitrogen as a hetero atom among other atoms has had an important role in active biological compounds. Since heterocyclic molecules with nitrogen are highly demanded due to biological properties, 4-phenylurazole as a compound containing nitrogen might be important in the multicomponent reaction used in agrochemicals, and pharmaceuticals. Considering the case of fused derivatives “pyrazolourazoles” which are highly applicable because of their application for analgesic, antibacterial, anti-inflammatory and antidiabetic activities as HSP-72 induction inhibitors (I and III) and novel microtubule assembly inhibitors. It should be mentioned that spiro-pyrazole also has biological activities like cytotoxic, antimicrobial, anticonvulsant, antifungal, anticancer, anti-inflammatory, and cardiotonic activities. Objective: Urazole has been used in many heterocyclic compounds which are valuable in organic syntheses. This review disclosed the advances in the use of urazole as the starting material in the synthesis of various biologically active molecules from 2006 to 2019. Conclusion: Compounds of urazole (1,2,4-triazolidine-3,5-dione) are the most important molecules which are highly active from the biological perspective in the pharmaceuticals as well as polymers. In summary, many protocols for preparations of the urazole derivatives from various substrates in multi-component reactions have been reported from different aromatic and aliphatic groups which have had carbonyl groups in their structures. It is noted that several catalysts have been synthesized to afford applicable molecules with urazole scaffolds. In some papers, being environmentally friendly, short time reactions and high yields are highlighted in the protocols. There is a room to synthesize new catalysts and perform new reactions by manipulating urazole to produce biologically active compounds, even producing chiral urazole component as many groups of chiral urazole compounds are important from biological perspective.

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