Novel Route to 4‐(Adamantan‐1‐yl)quinoline Derivatives Based on the Friedländer Condensation

2,3,4‐Trisubstituted quinolines, substituted with adamantan‐1‐yl or (adamantan‐1‐yl)methyl in the 4‐position, were prepared from the corresponding admantan‐1‐yl 2‐aminophenyl ketones or admantan‐1‐ylmethyl 2‐aminophenyl ketones and ketones with an α‐CH₂ group. These reactions were carried out under neat conditions or in toluene, and the products were obtained in moderate‐to‐excellent yields. The scope and limitations of the examined procedures are discussed. All new compounds are fully characterized by IR and NMR spectroscopy and mass spectrometry. The molecular structures of five new quinolines, obtained via single‐crystal X‐ray diffraction analyses, are discussed.     

A Novel Preparation of 4‐Phenylquinoline Derivatives in Ionic Liquids

A novel preparation of 4‐phenylquinoline derivatives through acid‐catalyzed Friedländer reaction in ionic liquid ([bmim][BF₄]) is described. The preparative procedure presented in this paper is operationally simple and environmentally benign. The reaction media and the catalyst used can be recovered and reused for at least four times without loss in the catalytic activity.     

ZnCl2 supported on Fe3O4@SiO2 core–shell nanocatalyst for the synthesis of quinolines via Friedländer synthesis under solvent‐free condition

A magnetic nanocatalyst of Fe₃O₄@SiO₂/ZnCl₂ was prepared by supporting ZnCl₂ on silica‐coated magnetic nanoparticles of Fe₃O₄. This recoverable catalyst was used for the synthesis of quinolines via Friedländer synthesis from 2‐aminoaryl ketones and α‐methylene ketones under solvent‐free condition. The prepared catalyst was characterized by FT‐IR, TEM, SEM, XRD, EDX, ICP‐OES, VSM and BET. It was found that Fe₃O₄@SiO₂/ZnCl₂ showed higher catalytic activity than homogenous ZnCl₂, and could be reused several times without significant loss of activity.     

Catalyst Free Indirect Friedländer Synthesis of Substituted Quinolines from Alcohols in PEG‐400

The synthesis of substituted quinolines can be easily and greenly accomplished by the direct reaction between the corresponding aminoalcohol and ketone using PEG‐400 as reaction medium in the presence of a base, without any transition‐metal catalyst.     

Synthesis of Polysubstituted Quinolines Using Cyanuric Chloride as a Catalyst Under Aqueous Conditions

A mild, eco‐friendly and efficient route for the synthesis of quinolines and polycyclic quinolines via Friedländer annulation using cyanuric chloride as a catalyst under aqueous conditions is described.     

Iron‐Catalyzed α‐Alkylation of Ketones with Alcohols

A general and benign iron‐catalyzed α‐alkylation reaction of ketones with primary alcohols has been developed. The key to success of the reaction is the use of a Knölker‐type complex as catalyst (2 mol %) in the presence of Cs₂CO₃ as base (10 mol %) under hydrogen‐borrowing conditions. Using 2‐aminobenzyl alcohol as alkylation reagent allows for the “green” synthesis of quinoline derivatives.     

1H-Pyrazolo[3,4-b]quinolines: Synthesis and Properties over 100 Years of Research

This paper summarises a little over 100 years of research on the synthesis and the photophysical and biological properties of 1H-pyrazolo[3,4-b]quinolines that was published in the years 1911–2021. The main methods of synthesis are described, which include Friedländer condensation, synthesis from anthranilic acid derivatives, multicomponent synthesis and others. The use of this class of compounds as potential fluorescent sensors and biologically active compounds is shown. This review intends to summarize the abovementioned aspects of 1H-pyrazolo[3,4-b]quinoline chemistry. Some of the results that are presented in this publication come from the laboratories of the authors of this review.     

Tacrines as Therapeutic Agents for Alzheimer's Disease. V. Recent Developments

Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase inhibitor approved for AD treatment, did not stop the progression of AD, producing only some cognitive improvements, but exhibited secondary effects mainly due to its hepatotoxicity. Thus, the drug was withdrawn from the clinics administration. Since then, many publications have described non‐hepatotoxic tacrines, and in addition, important efforts have been made to design multitarget tacrines by combining their cholinesterase inhibition profile with the modulation of other biological targets involved in AD.     

Gd(OTf)3‐[Bmim][PF6]: A Novel and Recyclable Catalytic System for the Synthesis of Quinolines

A mild and efficient route for the synthesis of quinolines and polycyclic quinolines utilizing Gadolinium triflate (Gd(OTf)₃) as a novel catalyst via Friedländer annulation in ionic liquid 1‐n‐butyl‐3‐methyl‐imidazolium hexafluorophosphate [Bmim][PF₆] under mild conditions was described.     

Chiral biomimetic NADH models in the benzo[b]-1,6-naphthyridine series. A novel class of stable, reactive and highly enantioselective NADH mimics

The preparation of a new class of tricyclic models 1 based on a Friedländer reaction between chiral piperidine-2,4-diones 2 and azomethine 3 is reported. Alkylation of the lactam allowed to install various pendant arms on the chiral cyclic inducer. The so-obtained mimics 1a,d,f,g,h,k were involved in the reduction of methyl benzoylformate to furnish methyl mandelate in 4-87% ee (R). The presence of a coordinating pendant arm proved to be essential to reach optimum results in terms of enantioinduction. Asymmetric reduction of 2-benzoylpyridine with mimics 1d,f,g produced α-phenyl-2-pyridinemethanol in 30-84% ee (R).     

Towards new camptothecins. Part 2: Synthesis of the ABCD ring scaffold substituted by a carboxyl group in the 5-position

In the context of formation of camptothecins substituted by a carbonyl function on position 5 of cycle C, synthesis of a new keto tetrahydroindolizine was realized. This compound was obtained from the reaction of Bredereck's reagent with an indolizine derived from pyroglutamic acid. That yielded a dimethylaminovinyl group whose NaIO₄ oxidation gave a ketone. The indolizinone obtained was reacted in Friedlander condition to give the ABCD ring scaffold of camptothecins substituted by a methoxycarbonyl group on the 5-position. It was also shown that, if it is desired, a 5-carboxamide group does not need to be introduced at the beginning of the synthesis sequence.     

Synthetic Studies on Coenzyme Q10. Part 3

An efficient and stereoselective approach to the synthesis of coenzyme Q₁₀ is described (Scheme). The MeOCH₂‐protected p‐hydroquinone 4 containing the C₅ (E)‐allyl (tert‐butyl)dimethylsilyl ether moiety was obtained via a halogen–lithium exchange of the MeOCH₂‐proctected 2‐bromo‐5,6‐dimethoxy‐3‐methylhydroquinone 2 and subsequent addition to (E)‐(^tBuMe₂Si)‐OCH₂C(Me)=CHCH₂Br ( 3 ). The reductive desulfonylation of compound 8 , obtained from 4 via 5 – 7 , was successfully carried out by employing Li/EtNH₂.     

Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines

The Friedländer synthesis offers efficient access to substituted quinolines from 2-aminobenzaldehydes and activated ketones in the presence of a base. The disadvantage of this procedure lies in the fact that relatively few 2-aminobenzaldehyde derivatives are readily available. To overcome this problem, we report a modification of this process involving the in situ reduction of 2-nitrobenzaldehydes with Fe/AcOH in the presence of active methylene compounds (AMCs) to produce substituted quinolines in high yields. The conditions are mild enough to tolerate a wide range of functionality in both reacting partners and promote reactions not only with phenyl and benzyl ketones, but also with β-keto-esters, β-keto-nitriles, β-keto-sulfones and β-diketones. The reaction of 2-nitroaromatic ketones with unsymmetrical AMCs is less reliable, giving a competitive formation of substituted quinolin-2(1H)-ones from the cyclization of the Z Knoevenagel intermediate which appears to be favored when certain large groups are adjacent to the AMC ketone carbonyl.     

Studies on quinones. Part 25. Synthetic approaches to 6,9-dioxygenated-benzazepinones

The Schmidt and Beckmann rearrangement of 3,4-dihydro-4,4-dimethyl-1(2H)-naphthalenones bearing oxygenated groups at the 5,8-positions, and some of their oximes are reported. Depending upon the structure of the substrates and the reaction conditions 4,5-dihydro-3H-naphth[1,8-cd]isoxazol, benzazepin-2-one and 5,6-dihydro-7H-tetrazolo[1,5-a][2]benzazepine derivatives were generated.