Quinolines and Their Derivatives

As noted in Chapters 4, 5, and 7, compounds aimed at dismpting tyrosine kinases have been intensively studied as potential antitumor compounds. The quinoline-based inhibitor pelitinib (45) incorporates a Michael acceptor function in the side chain that can form a covalent bond with a nucleophile on the target enzyme. Such an interaction would result in irreversible inhibition of the target kinase. Reaction of the aniline (37) with DMF acetal leads to the addition of a carbon atom to aniline nitrogen in the form of an amidine (38). This intermediate is next reacted with nitric in acetic acid to form the nitrated product 

Neurokinins comprise a group of peptides involved in nerve transmission. Specific members of this class of mediators control such diverse functions as visceral regulation, and CNS function. The nonpeptide neurokinin antagonist talnetant (51), for example, is currently being evaluated for its effect on irritable bowel syndrome, urinary 

As noted previously, anticholinergic agents have undergone something of a renaissance due to their use as drugs to treat urinary incontinence. The synthesis of one of these muscarinic antagonsists starts with the classic 

Addition of the terpene, famesol, to cysteine residues near the end of protein chains is a cmcial process for transporting some proteins to the intended membrane compartment. This process thus plays an important role in cell proliferation. Inhibitors of the enzyme that catalyzes farnesyla-tion, famesyl transferase, provide yet one more mechanism for interrupting the multiplication of malignant cells. One of several synthesis of this agent 

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Fetzner, S., Bacterial Degradation of Pyridine, Indole, Quinoline, and Their Derivatives Under Different Redox Conditions.. Appl. Microbiol. Biotechnol., 1998. 49 pp. 237-250. 

Fetzner, S. Bacterial degradation of p3rridine. indole, quinoline, and their derivatives under different redox conditions, Appl. Microbiol. BiotechnoL, 49 237-250, 1998. 

The amination of heterocyclic bases such as pyridine, quinoline, and their derivatives by alkali amides furnishes a good method for obtaining the 2-amino compounds (50-100%). The scope and limitations of the reaction have been reviewed the procedure is illustrated by the preparation of 2-aminopyridine (76%). ... 

In more recent work, pyridine, quinoline, and their derivatives have been dimerized with the aid of specially prepared Raney nickel catalyst.301... 

Scheme 1232 Regioselective synthesis of benzo[h]pyrazolo[3,4-fc]quinolines and their derivatives.

Aromatic amine antioxidants are also known as rubber antiaging agents they have the largest production quantity and are used mainly in rubber products. These antioxidants have low prices and remarkable antioxidant effects however, they could change the color of products, which limits their application in light colored and white goods. Significant aromatic amine antioxidants are diphenylamine, jo-phenylenediamine, quinoline, and their derivatives or polymers, and they can be used in natural rubber, styrene butadiene rubber (SBR), chloroprene rubber, and isoprene rubber. 

Yet another multicomponent domino reaction assisted by MW irradiation has been developed for the rapid and regi-oselective synthesis of highly functionalized benzo[/i]pyrazolo[3,4-l ]quinolines and their derivatives [63] (Scheme 41). A mechanism explaining the formation of this compoxmd has been proposed by the autifors (Scheme 40). The resulting benzoquinoline products have been successfully converted into quinoxaline-fused benzo[/i]isoxazolo[5,4-l7]quinolines by reacting with benzene-l,2-diamine xmder MW irradiation. 

The environmental impact of quinoline and its derivatives was considered by evaluating their toxicity on Nitrosomonas and Nitrobacter [377], The combination of wet oxidation and biological treatment was found to improve the impact by almost complete oxidations of the organics. 

Kaiser, J.-P. Feng, Y., and Bollag, J.-M., Microbial Metabolism of Pyridine, Quinoline, Acridine, and Their Derivatives Under Aerobic and Anaerobic Conditions. Microbiological Reviews, 1996. 60(3) pp. 483-498. 

A two phase process, in which the feedstock (e.g., petroleum) was mixed with water and an organic solvent to improve denitrogenation of aromatic nitrogen compounds [102], led to an improvement of the process. Additionally, a surfactant was used to increase the interfacial area. Carbazole and quinoline and their alkyl derivatives were used as primary compounds for demonstration. The biocatalyst is used in resting stage and is continuously fed to the system to keep the reaction rate at an acceptable level. It was observed that quinoline was hardly removed under the conditions at which carbazole was decomposed and assimilated. 

Oximes and their derivatives are widely used in organic synthesis. A number of reviews are devoted to the chemistry and biological activity of oximes and their derivatives The synthesis, reactions and biological activity of oximes containing a heterocyclic substituent, e.g. furan and thiophene", indole and isatin, pyridine, pyrrole, quinoline and five-membered heterocycles with two heteroatoms have been reviewed. 

The main methods used for the synthesis of quinolines, isoquinolines and their derivatives... 

The Brpnsted acid catalyzed hydrogenation of quinolines with Hantzsch dihydropyridine as reducing agent provides a direct access to a variety of substituted tetrahydroquinolines (Table 4.2). The mild reaction conditions of this metal-free reduction of heteroaromatic compounds, high yields, operational simplicity and practicability, broad scope, functional group tolerance and remarkably low catalyst loading render this environment-friendly process an attractive approach to optically active tetrahydroquinolines and their derivatives (Table 4.3) (see page 176). ... 

Further extensions of the slilbene photocydizatinn are seen in analogous reactions of compounds containing the imine chro-mophore (e.g. 3,71 or an amide group (3.72). The amide reaction can be considered formally as giving a zwitterion intermediate, which undergoes proton shifts and oxidation to form the observed product. Non-oxidative cyclizations that start with either JV-vinyl aromatic carboxamides (C=C—N—CO—Ar) or N-aryl a. -unsaturated carboxamides (Ar—N—CO—C—C) have been extensively used to make quinoline or isoquinoline alkaloids and their derivatives a fairly simple example is given in (3.73). 

Survey of synthetic methods for quinolines, benzo[b]pyrans and their derivatives 616... 

Coffey, S, Six Membered Heterocyclic Compounds with a Single Atom in the Rind, Pyridine, Polyrnethyl-Epyridines, Quinoline, Isoquinoline and Their Derivatives, Elsevier Science, New York, NY, 1977. 

The dipole moments of some pseudoazulenes were determined by dielectric measurements. They are listed in Table II. The high values obtained (for comparison 6,6-dihydroindeno[2,1-b]quinoline has a dipole moment of 1.66 D whereas the corresponding 6-oxo compound has a value of approximately 1.6 D) are in accordance with quantum chemical calculations (see Section IV,B). The relatively high values of the dipole moments of unsubstituted pseudoazulenes and their derivatives show that some of the polar structures contribute to the resonance hybrid (Eq. 7). But in all cases the ring heteroatoms are localized at the positive end of the dipole. 

Directed metalation of -deficient azaaromatics strategies of functionalization of pyridines, quinolines, and diazines, 52, 187 gem-Dithienylalkanes and their derivatives, 32, 83... 

Nina A. Nedolya was born in Irkutsk (Russia) and educated in organic chemistry at the Irkutsk State University (Diploma 1972, PhD 1982, DSc 1998). From 1995 to 1999 she was associated with Prof. L. Brandsma at the Utrecht University (The Netherlands). In 1999 she obtained her second PhD from the Utrecht University. She is presently Head of the Research Group of Chemistry of Heterocyclic Compounds at A. E. Favorsky Irkutsk Institute of Chemistry. She is the author of over 210 review articles and research papers. She is also one of the inventors for 112 patents. She is interested in the chemistry of polyfunctional unsaturated heteroatomic systems (vinyl, allenyl, and alkynyl ethers and their derivatives, linear and cyclic heteropolyenes, hetero-cumulenes), including synthesis of important heterocycles, particularly pyrroles, thiophenes, thiazoles, imidazoles, dihydrofurans, dihydropyridines, pyridines, quinolines, dihydroazepines, and azepines, based on metallated allenes or alkynes and/or heterocumulenes. 

Klingsberg, E. and Newkome, G.R., Eds., Pyridine and Its Derivatives, Interscience, New York, 1960 Schoefield, K., Heteroaromatic Nitrogen Compounds Pyrroles and Pyridines, Butterworths, London, 1967 Hurst, D.T., An Introduction to the Chemistry and Biochemistry and Pyrimidines, Purines, and Ptreridines, J. Wiley, Chichester, UK, 1980 Plunkett, A.O., Pyrrole, pyrrolidine, pyridine, piperidine, and azepine alkaloids, Nat. Prod. Rep. 11, 581-590, 1994 Kaiser, J.P., Feng, Y., and Bollag, J.M., Microbial metabolism of pyridine, quinoline, acridine, and their derivatives under aerobic and anaerobic conditions, Microbiol. Rev. 60, 483-498, 1996. 

Chichibabin, A. E. A new method of preparation of hydroxy derivatives of pyridine, quinoline and their homologs. Ber. 1923, 56B, 1879-1885. 

However, in general, these active sites in cinchona alkaloids and their derivatives act in catalysis not independently but cooperatively that is, they activate the reacting molecules simultaneously. Furthermore, in many cases, the catalysis is also supported by a n-n interaction with the aromatic quinoline ring or by its steric hindrance. 

PANH (polycyclic aromatic nitrogen hydrocarbon) indole, carbazole, quinoline and their alkylated derivatives... 

Polycyclic aromatic compounds (PAC) are a significant environmental chemical group, with an associated health effect. PACs includes PAH (polycyclic aromatic hydrocarbon), PASH (polycyclic aromatic sulfur hydrocarbon), and PANH (polycyclic aromatic nitrogen hydrocarbon). The main PAHs are naphthalene, fluorene, phenanthrene, and their alkylated homologs PASHs are benzothiophene and diben-zothiophene PANHs are indole, carbazole, quinoline, and their alkylated derivatives (see Table 1). 

Nitrogen species are also divided through acidic extraction into basic species (such as aniline, quinoline, benzoquinoline, and their derivatives) and nonbasic species (such as indole, carbazole, and their derivatives) (see Table 3). 

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