Quinolines reaction with

Quinoline may be prepared by heating a mixture of aniline, anhydrous glycerol and concentrated sulphuric acid with an oxidising agent, such as nitrobenzene. The reaction with nitrobenzene alone may proceed with extreme violence, but by the addition of ferrous sulphate, which appears to function as an oxygen carrier, the reaction is extended over a longer period of time and Is under complete control. 

Chemical Properties. The presence of both a carbocycHc and a heterocycHc ring faciUtates a broad range of chemical reactions for (1) and (2). Quaternary alkylation on nitrogen takes place readily, but unlike pyridine both quinoline and isoquinoline show addition by subsequent reaction with nucleophiles. Nucleophilic substitution is promoted by the heterocycHc nitrogen. ElectrophiHc substitution takes place much more easily than in pyridine, and the substituents are generally located in the carbocycHc ring. 

Owing to poor volatihty, derivatization of nicotinic acid and nicotinamide are important techniques in the gc analysis of these substances. For example, a gc procedure has been reported for nicotinamide using a flame ionisation detector at detection limits of - 0.2 fig (58). The nonvolatile amide was converted to the nitrile by reaction with heptafluorobutryic anhydride (56). For a related molecule, quinolinic acid, fmol detection limits were claimed for a gc procedure using either packed or capillary columns after derivatization to its hexafluoroisopropyl ester (58). 

Other secondary amines such as pyrrolidine, di- -butylamine, tetrahydro-quinoline, n-benzylamine, and piperidine were also found to be capable of effecting this reduction. Interestingly, morpholine does not reduce enamines as readily (47) and its acid-catalyzed reaction with norbornanone was reported (45) to give only the corresponding enamine (93), although trace amounts of the reduction product were detected when cyclohexanone was treated with morpholine under these conditions (47a). The yield of morpholine reduction product was increased by using higher temperatures. 

Methoxythiophene and 3-cyanothiophene have been prepared from 3-bromothiophene by means of a cupric oxide-catalyzed Williamson synthesis and by reaction with cuprous cyanide in quinoline, respectively. 

On the basis of its reaction with diazomethane, 2,4-dihydroxyquino-line was reported to exist as 4-hydroxyquinol-2-one in the solid state and as an equilibrium mixture of this form with 2-hydroxyquinol-4-one in solution. Using the infrared criteria for o- and p-quinonoid forms (see Section II,L), the spectra of 2,4-dihydroxy-pyridine and -quinoline indicated that both quinonoid forms, e.g., 12 (Z = NH) and 13 (Z — NH), were present and that the nonaroraatic form (43) was absent. ... 

Two interesting cases of quaternary salt formation are illustrated by compounds 88 and 90 (Z = CH) which contain fused quinoline and triazole rings. In these compounds both of the nitrogen atoms unique to the triazole ring possess lone pairs of electrons which are available for reaction. With compound 88 reaction occurs to give 89, but in... 

Okamoto et al. found that A-oxidation activates 4-halogeno-quinolines in the reaction with piperidine in aqueous alcohol by kinetic factors of 9 to 25, at 100°. This rate-enhancing effect is accompanied by a fairly large decrease in the enthalpy of activation (up to 10 kcal/mole in the chloro compounds), the effect of which is partly offset by a decrease in the entropy of activation. 

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

The work of Okamoto et on quinoline and quinoline-l-oxides (Table XI) provides the following relation of solvent to the rate of reaction with piperidine A 7oo/ aic. = 1.5-2.5 x = 80-200 x A benzene-... 

The isomeric thiazolo[5,4-g]quinoline skeleton was prepared from 6-chloro-quinoline-5,8-dione hydrochloride by reaction with thiourea, resulting in the 2-amino-4,9-dioxo-4,9-dihydroderivative 42 (91CCC1919). 

The nitration of l,2,5-selenadiazolo[3,4-/] quinoline 77 with benzoyl nitrate affords the 8-nitro derivative 78, whereas methylation with methyl iodide or methyl sulfate afforded the corresponding 6-pyridinium methiodide 79 or methosulfate 80, respectively (Scheme 29). The pyridinium salt 80 was submitted to oxidation with potassium hexacyanoferrate and provided 7-oxo-6,7-dihydro derivative 81 or, by reaction of pyridinium salt 79 with phenylmagnesium bromide, the 7-phenyl-6,7-dihydro derivative 82. Nucleophilic substitution of the methiodide 79 with potassium cyanide resulted in the formation of 9-cyano-6,9-dihydroderivative 83, which can be oxidized by iodine to 9-cyano-l,2,5-selenadiazolo [3,4-/]quinoline methiodide 84. All the reactions proceeded in moderate yields (81IJC648). 

The proposed structure of 97 isolated from broiled sardines was confirmed by straightforward synthesis starting from5,6-diaminoquinolines. After reaction with cyanogen bromide it afforded the 2-amino-imidazo[4,5-/]quinolines 99 (R = H, Me), which was then converted into its 3-A-methyl derivative 100 by... 

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