Quinoline isoquinoline

Crude oils contain nitrogen compounds in the form of basic substances such as quinoline, isoquinoline, and pyridine, or neutral materials such as pyrrole, indole, and carbazole. 

This method is exemplified by its application to quinoline, isoquinoline, cinnoline, and isoquinoline 2-oxide, which are nitrated as their conjugate acids. The rate profiles for these compounds and their N- or O-methyl perchlorates show closely parallel dependences upon acidity (fig. 2.4). Quaternisation had in each case only a small effect upon the rate, making the criterion a very reliable one. It has the additional advantage of being applicable at any temperature for which kinetic measurements can be made (table 8.1, sections B and D). 

The compounds to be discussed are the quinolines, isoquinolines, cinnolines, quinazolines, quinoxalines, and phthalazines. Once again, this is a family of compounds for which much qualitative, but little quantitative information is available. 

The first quantitative studies of the nitration of quinoline, isoquinoline, and cinnoline were made by Dewar and Maitlis, who measured isomer proportions and also, by competition, the relative rates of nitration of quinoline and isoquinoline (1 24-5). Subsequently, extensive kinetic studies were reported for all three of these heterocycles and their methyl quaternary derivatives (table 10.3). The usual criteria established that over the range 77-99 % sulphuric acid at 25 °C quinoline reacts as its cation (i), and the same is true for isoquinoline in 71-84% sulphuric acid at 25 °C and 67-73 % sulphuric acid at 80 °C ( 8.2 tables 8.1, 8.3). Cinnoline reacts as the 2-cinnolinium cation (nia) in 76-83% sulphuric acid at 80 °C (see table 8.1). All of these cations are strongly deactivated. Approximate partial rate factors of /j = 9-ox io and /g = i-o X io have been estimated for isoquinolinium. The unproto-nated nitrogen atom of the 2-cinnolinium (ina) and 2-methylcinno-linium (iiiA) cations causes them to react 287 and 200 more slowly than the related 2-isoquinolinium (iia) and 2-methylisoquinolinium (iii)... 

The presence of a cyano group seems to be important[649]. The reaction has been successfully applied to halides of pyridine, quinoline, isoquinoline, and oxazoles[650]. An interesting application is the synthesis of tetracyanoquino-dimethane (789) by the reaction of / -diiodobenzene with malononitrile[65l]. 

Pyridine, pyrrole, quinoline, isoquinoline and indole alkaloids Apply sample solution and place the TLC plate in an iodine vapor chamber for 18 h, remove the excess iodine in a stream of warm air. Characterization on the basis of the iodination pattern. [53]... 

The rate of amination and of alkoxylation increases 1.5-3-fold for a 10° rise in the temperature of reaction for naphthalenes (Table X, lines 1, 2, 7 and 8), quinolines, isoquinolines, l-halo-2-nitro-naphthalenes, and diazanaphthalenes. The relation of reactivity can vary or be reversed, depending on the temperature at which rates are mathematically or experimentally compared (cf. naphthalene discussion above and Section III,A, 1). For example, the rate ratio of piperidination of 4-chloroquinazoline to that of 1-chloroisoquino-line varies 100-fold over a relatively small temperature range 10 at 20°, and 10 at 100°. The ratio of rates of ethoxylation of 2-chloro-pyridine and 3-chloroisoquinoline is 9 at 140° and 180 at 20°. Comparison of 2-chloro-with 4-chloro-quinoline gives a ratio of 2.1 at 90° and 0.97 at 20° the ratio for 4-chloro-quinoline and -cinnoline is 3200 at 60° and 7300 at 20° and piperidination of 2-chloroquinoline vs. 1-chloroisoquinoline has a rate ratio of 1.0 at 110° and 1.7 at 20°. The change in the rate ratio with temperature will depend on the difference in the heats of activation of the two reactions (Section III,A,1). 

Quinoxalines undergo facile addition reactions with nucleophilic reagents. The reaction of quinoxaline with allylmagnesium bromide gives, after hydrolysis of the initial adduct, 86% of 2,3-diallyl-l,2,3,4-tetrahydroquinoxaline. Quinoxaline is more reactive to this nucleophile than related aza-heterocyclic compounds, and the observed order of reactivity is pyridine < quinoline isoquinoline < phenan-thridine acridine < quinoxaline. ... 

Just as there are heterocyclic analogs of benzene, there are also many heterocyclic analogs of naphthalene. Among the most common are quinoline, iso-quinoline, indole, and purine. Quinoline, isoquinoline, and purine all contain pyridine-like nitrogens that are part of a double bond and contribute one electron to the aromatic it system. Indole and purine both contain pyrrole-like nitrogens that contribute two - r electrons. 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

Halogenations of quinoline, isoquinoline, acridine, and phenanthridine will be discussed here. Reaction usually occurs in a homocyclic fused ring rather than in the 7r-deficient pyridine moiety, especially in acidic media. Relatively mild conditions suffice, but under more vigorous regimes radical involvement can result in heteroring halogenation. Substituents are able to modify reactivity and regiochemistry. 

It is necessary to hold the reaction temperature below —5° in order to prevent 1,2-rearrangement of the Reissert anion to 1-benzoyliso-quinoline [Isoquinoline, 1-benzoyl-].5... 

An interesting reaction of dimsyl anion 88 is the methylation of polyaromatic compounds. Thus naphthalene, anthracene, phenanthrene, acridine, quinoline, isoquinoline and phenanthridine were regiospecifically methylated upon treatment with potassium t-butoxide and DMSO in digyme or with sodium hydride in DMSO123-125. Since ca. 50% of D was found to remain in the monomethyl derivative 93 derived from 9-deuteriophenanthrene 92, the mechanistic route shown in Scheme 2 was suggested125. 

A series of diastereomeric platinum(II) complexes of the type c -[PtL2Y2]2+ (L - 3-bromopyr-idine, quinoline, isoquinoline Y = PEt3, Y2 = dppp, (/ )-(I )-2,2 -bis(diphenylphosphino)-l, l -binaphthyl (R-( I )-binap)) have been prepared by the reaction of c -[PtY2(OTf)2] (OTf=tri-trifluoromethanesulfonate) with two equivalents of the N-donor ligand.207 Related complexes have also been studied, for example when L = pyridine.208 Restricted rotation about the Pt—N bonds in many of the complexes is usually detected by NMR spectroscopy, with only [Pt(dppp)(isoquinoline)2]2+ (65) exhibiting dynamic behavior at ambient temperatures. The PEt3... 

In a subsequent study, Schnitzer and Spiteller [15] hydrolyzed each fraction with 2 M H2S04. After neutralization of the soluble materials, the latter were reduced with NaBH4 and then acetylated. The resulting acetates were analyzed by capillary gas chromatography/mass spectrometry, and identified by comparing their mass spectra with those of reference compounds of known structures and with literature data. Eighteen N-heterocyclics were identified. These compounds induded hydroxy-and oxy-indoles, quinolines, isoquinolines, aminobenzofurans, piperidines, pyrro-lines, and pyrrolidines. In addition, a number of benzylamines and nitriles were also identified. It is noteworthy that the N heterocyclics were isolated and identified without the use of pyrolysis. 

The oxidative degradations of binuclear azaarenes (quinoline, isoquinoline, and benzodrazines) by hydroxyl and sulfate radicals and halogen radicals have been studied under both photochemical and dark-reaction conditions. A shift from oxidation of the benzene moiety to the pyridine moiety was observed in the quinoline and isoquinoline systems upon changing the reaction from the dark to photochemical conditions. The results were interpreted using frontier-orbital calculations. The reaction of OH with the dye 3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-(l,8)(2//,5//)-acridinedione has been studied, and the transient absorption bands assigned in neutral solution.The redox potential (and also the pA a of the transient species) was determined. Hydroxyl radicals have been found to react with thioanisole via both electron transfer to give radical cations (73%) and OH-adduct formation (23%). The bimolec-ular rate constant was determined (3.5 x lO lmoU s ). " ... 

Elderfield, R. C. Heterocyclic Compounds, Elderfield, R. C., Ed. John Wiley Sons, Inc. New York, 1952, Vol. 4, Quinoline, Isoquinoline and Their Benzo Derivatives, pp. 25-29. (Review). 

Photochemical hydroxyalkylation has been carried out with pyri-dines, quinolines, isoquinolines,acridine, pyridazines, pyrimidines, ethoxyquinolinium salts,and imidazoles. It also occurs with iV-oxides the mechanism of Scheme 13 has been suggested for pyridazine iV -oxide. ... 

The ethyl radical directly attacks the heteroaromatic base, while the acetaldehyde acts as a source of acetyl radical. Photochemical oxy-alkylation has also been tried with ethers. The reaction has been successfully carried out with pyridines, quinolines, isoquinolines,cinno-lines, and quinoxalines. Particularly good yields were obtained with caffeine (16) (Scheme 14). ... 

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

The ESR hyperfine coupling constants have been established experimentally (67MI20402) for the pyridinyl radical (134 R = H) and deuterated analogues, produced by y irradiation of a solid solution of pyridine in ethanol at 77 K, but the signs of the couplings are not known experimentally and are made solely on the basis of Huckel MO calculations. INDO MO calculations on this radical, together with the radical anions of quinoline, isoquinoline and acridine h ve also been carried out (740MR(6)5). 

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