Synthesis of Tetracyclic Fused Quinolines via a Friedel–Crafts and Beckmann Ring Expansion Sequence

2019 ◽  
Vol 72 (12) ◽  
pp. 945
Author(s):  
Hassan A. K. Abd El-Aal ◽  
Talaat I. El-Emary
Keyword(s):  
Carboxylic Acids ◽  
Ring Expansion ◽  
Molecular Scaffolds ◽  
Elemental Analyses ◽  
Key Steps

An efficient protocol for the construction of tetracyclic fused quinolines (pyrazole-fused azepino-, azocino-, and azonino[3,2-b]quinolinones) via consecutive Friedel–Crafts and Beckmann reactions has been developed. The key steps in the syntheses of these new molecular scaffolds involve acid-mediated cyclization of 2-(pyrazol-3-yl)quinoline based carboxylic acids 6a–c, 8, and 12 to ketones 13a–e, followed by Beckmann rearrangements of the corresponding oximes 14a–e to provide the tetracyclic-fused quinoline skeletons 15a–e. Structures of synthesised compounds without stereochemical implication were confirmed by NMR and elemental analyses.

Corrigendum to: Synthesis of Tetracyclic Fused Quinolines via a Friedel–Crafts and Beckmann Ring Expansion Sequence

2019 ◽  
Vol 72 (12) ◽  
pp. 990
Author(s):  
Hassan A. K. Abd El-Aal ◽  
Talaat I. El-Emary
Keyword(s):  
Carboxylic Acids ◽  
Ring Expansion ◽  
Molecular Scaffolds ◽  
Elemental Analyses ◽  
Key Steps

An efficient protocol for the construction of tetracyclic fused quinolines (pyrazole-fused azepino-, azocino-, and azonino[3,2-b]quinolinones) via consecutive Friedel–Crafts and Beckmann reactions has been developed. The key steps in the syntheses of these new molecular scaffolds involve acid-mediated cyclization of 2-(pyrazol-3-yl)quinoline based carboxylic acids 6a–c, 8, and 12 to ketones 13a–e, followed by Beckmann rearrangements of the corresponding oximes 14a–e to provide the tetracyclic-fused quinoline skeletons 15a–e. Structures of synthesised compounds without stereochemical implication were confirmed by NMR and elemental analyses.

Basic Chromium(III) Carboxylates: Reactions of Chromium(III) Chloride with Some Carboxylic Acids

1979 ◽  
Vol 34 (10) ◽  
pp. 1369-1372 ◽  
Author(s):  
Ramesh Kapoor
Keyword(s):  
Acetic Anhydride ◽  
General Formula ◽  
Carboxylic Acids ◽  
Magnetic Measurements ◽  
Molar Conductance ◽  
Strong Affinity ◽  
Elemental Analyses

Abstract Anhydrous chromium(III) chloride reacts with pure carboxylic acids (RCOOH where R = CH3, C2H5, n-C3H7, CH2Cl, CHCl2 and CCl3) to give basic trinuclear chromium(III) carboxylates of the general formula [Cr3O(OOCR)6]+Cl-. The reaction of CrCl3 with acetic anhydride, however, gives a partially substituted product, CrCl(OOCCH3)2.The formation of basic carboxylates has been attributed to the strong affinity of Cr3+ ions for water that they can abstract it even from pure carboxylic acids. Their addition compounds with ammonia have also been prepared. The compounds have been characterized by their elemental analyses, IR, molar conductance and magnetic measurements.

Some Derivatives of 1-Benzazepine. Part II

1974 ◽  
Vol 52 (4) ◽  
pp. 610-615 ◽  
Author(s):  
G. R. Birchall ◽  
A. H. Rees
Keyword(s):  
Carboxylic Acids ◽  
Ring Expansion ◽  
Hydrazoic Acid ◽  
Ring Contraction ◽  
Effect Of Substituents ◽  
Ring Expansion Reaction ◽  
Derivatives Of

We have investigated the ring expansion of some substituted 1,4-naphthoquinones by hydrazoic acid to yield new 1-benzazepine derivatives of the "azatropolone" type. Ring contraction of those products, which are 2,5-dihydro-3-hydroxy-2,5-dioxo-1-benzazepines, gives 4-quinolone-2-carboxylic acids. Some of the reactions of the new benzazepine system were investigated. Attempts to prepare substituted derivatives suitable for making 1-benzazatrop-5-one were not successful.The effect of substituents on the ring expansion reaction is discussed and an anomalous ring expansion to a 2,5-dihydro-4-hydroxy-2,5-dioxo-1-benzazepine is described and explained mechanistically.

Radical Tropolone Biosynthesis

2020 ◽  
Author(s):  
Tyler J. Doyon ◽  
Kevin Skinner ◽  
Di Yang ◽  
Leena Mallik ◽  
Troy Wymore ◽  
...  
Keyword(s):  
Active Site ◽  
Building Blocks ◽  
Ring Expansion ◽  
Heme Iron ◽  
Active Site Residues ◽  
Molecular Scaffolds ◽  
Radical Ring ◽  
Full Characterization ◽  
Dynamics Simulations ◽  
Functionally Diverse

<div> <div> <div> <p>Non-heme iron (NHI) enzymes perform a variety of oxidative rearrangements to advance simple building blocks toward complex molecular scaffolds within secondary metabolite pathways. Many of these transformations occur with selectivity that is unprecedented in small molecule catalysis, spurring an interest in the enzymatic processes which lead to a particular rearrangement. In-depth investigations of NHI mechanisms examine the source of this selectivity and can offer inspiration for the development of novel synthetic transformations. However, the mechanistic details of many NHI-catalyzed rearrangements remain underexplored, hindering full characterization of the chemistry accessible to this functionally diverse class of enzymes. For NHI-catalyzed rearrangements which have been investigated, mechanistic proposals often describe one-electron processes, followed by single electron oxidation from the substrate to the iron(III)-hydroxyl active site species. Here, we examine the ring expansion mechanism employed in fungal tropolone biosynthesis. TropC, an α-ketoglutarate- dependent NHI dioxygenase, catalyzes a ring expansion in the biosynthesis of tropolone natural product stipitatic acid through an under-studied mechanism. Investigation of both polar and radical mechanistic proposals suggests tropolones are constructed through a radical ring expansion. This biosynthetic route to tropolones is supported by X-ray crystal structure data combined with molecular dynamics simulations, alanine-scanning of active site residues, assessed reactivity of putative biosynthetic intermediates, and quantum mechanical (QM) calculations. These studies support a radical ring expansion in fungal tropolone biosynthesis. </p> </div> </div> </div>

Radical Tropolone Biosynthesis

2020 ◽  
Author(s):  
Tyler J. Doyon ◽  
Kevin Skinner ◽  
Di Yang ◽  
Leena Mallik ◽  
Troy Wymore ◽  
...  
Keyword(s):  
Active Site ◽  
Building Blocks ◽  
Ring Expansion ◽  
Heme Iron ◽  
Active Site Residues ◽  
Molecular Scaffolds ◽  
Radical Ring ◽  
Full Characterization ◽  
Dynamics Simulations ◽  
Functionally Diverse

<div> <div> <div> <p>Non-heme iron (NHI) enzymes perform a variety of oxidative rearrangements to advance simple building blocks toward complex molecular scaffolds within secondary metabolite pathways. Many of these transformations occur with selectivity that is unprecedented in small molecule catalysis, spurring an interest in the enzymatic processes which lead to a particular rearrangement. In-depth investigations of NHI mechanisms examine the source of this selectivity and can offer inspiration for the development of novel synthetic transformations. However, the mechanistic details of many NHI-catalyzed rearrangements remain underexplored, hindering full characterization of the chemistry accessible to this functionally diverse class of enzymes. For NHI-catalyzed rearrangements which have been investigated, mechanistic proposals often describe one-electron processes, followed by single electron oxidation from the substrate to the iron(III)-hydroxyl active site species. Here, we examine the ring expansion mechanism employed in fungal tropolone biosynthesis. TropC, an α-ketoglutarate- dependent NHI dioxygenase, catalyzes a ring expansion in the biosynthesis of tropolone natural product stipitatic acid through an under-studied mechanism. Investigation of both polar and radical mechanistic proposals suggests tropolones are constructed through a radical ring expansion. This biosynthetic route to tropolones is supported by X-ray crystal structure data combined with molecular dynamics simulations, alanine-scanning of active site residues, assessed reactivity of putative biosynthetic intermediates, and quantum mechanical (QM) calculations. These studies support a radical ring expansion in fungal tropolone biosynthesis. </p> </div> </div> </div>

One Pot Synthesis of 6-(4-carboxy-3-methyl-2-phenylquinolin-6-ylsulfonyl)-3-methyl-2-phenylquinoline-4-carboxylic Acids from Dapsone and α-ketobutyric Acid by a Doebner Reaction

2016 ◽  
Vol 40 (12) ◽  
pp. 715-717 ◽  
Author(s):  
Negar Moshref Javadi ◽  
Javad Azizian
Keyword(s):  
Biological Activity ◽  
Carboxylic Acids ◽  
Anticancer Agents ◽  
Spectroscopic Data ◽  
Aromatic Aldehydes ◽  
Reaction Conditions ◽  
One Pot ◽  
Promising Alternative ◽  
Elemental Analyses ◽  
Operational Simplicity

A series of new 6-(4-carboxy-3-methyl-2-phenylquinolin-6-ylsulfonyl)-3-methyl-2-phenylquinoline-4-carboxylic acids were synthesised by a one-pot reaction of dapsone, α-ketobutyric acid, and aromatic aldehydes in the presence of CuBr2 as a catalyst. Operational simplicity, mild reaction conditions, and eco-friendly procedure make this novel protocol a promising alternative for the preparation of quinoline-4-caboxylic acid derivatives. The structures of the products were established by elemental analyses and spectroscopic data. The biological activity of the new sulfone dimers was evaluated as having the potential for use as anticancer agents.

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