Quinolinium cations/salts

Acids and Lewis acids react with quinoline at the basic nitrogen atom to form quinolinium salts, and there is a question over the nature of the substrate for electrophilic attack, i.e. is it quinoline or the quinolinium cation The answer is not a simple one and appears to depend upon the reagents and reaction conditions. Thus, whereas acetyl nitrate at 20 °C gives mainly 3-nitroquinoline (Scheme 3.2), fuming nitric acid in concentrated sulfuric acid containing sulfur trioxide at 15-20 °C yields a mixture of 5-nitroquinoline (35%) and 8-nitroquinoline (43%) (Scheme 3.3). In the case of acetyl nitrate, the reaction may proceed by the 1,4-addition of the reagent to quinoline, followed by electrophilic attack upon the 1,4-dihydro derivative. 

However, the rate of nitration of quinoline in 80-99% sulfuric acid is of the same order as that of A-methylquinolinium salts, suggesting that here the quinolinium cation may be the target for attack. 

Representatives of all these distinct categories of charged or charge-separated species have been isolated from natural sources. Salts of cationic alkaloids are widespread in nature, among them pyridinium, quinolinium, and isoquinolinium alkaloids. Examples of monocationic alkaloids are Cryptaustoline (1) (Cryptocarya) and the antitumor active Avicine (2)... 

Electron impact mass spectrometry of the cyclobutanedione (24) gives rise to dimethylcarbene radical cation.35 Appearance energy measurements and ah initio calculations indicated that the radical cation lies 84 kJ mol 1 above the propene radical cation and is separated from it by a barrier of 35 kJ mol-1. Diarylcarbene radical cations have been generated by double flash photolysis of diaryldiazomethanes in the presence of a quinolinium salt (by photo-induced electron transfer followed by photo-initiated loss of N2).36 Absolute rate constants for reactions with alkenes showed the radicals to be highly electrophilic. In contrast to many other cation radicals, they also showed significant radicophihc properties. 

The reaction has been used to synthesize libraries of benzonaphthyridines 196, in high diastereoselectivity, from the cycloaddition of 1,4-dihydrop3Tidines with imines formed from aldehydes and anilines. When cyclic enol ethers were used as dienophUes, mixtures of diastereomers 197 were obtained. These compounds were oxidized to the corresponding quinolines 198 and were further transformed to the quinolinium salts 199 as shown in Scheme 36 [76]. Compounds 196 and 198 were tested for their ability to inhibit human propyl oligopeptidase (POP) and were found to have modest potencies. Much better results were obtained when the quinoline nitrogen was methylated to provide adducts 199. The cationic center improved the inhibitory activity of these compounds (Fig. 23). 

Similar problems arise with quinolinium salts as both C2 and C4 are susceptible to radical addition. Where either of these positions is blocked by a substituent, reactions often proceed in high yield. For example, Minisci et al. have described a useful method of formylating heteroaromatic bases which begins with an iron(II) promoted reduction of /-butyl hydroperoxide <86JOC536>. The /-butyloxy radical thus produced abstracts a hydrogen atom from 1,3,5-trioxane 34 giving intermediate 33. Union of 33 and the quinolinium salt 35 next produces radical cation 36, which is oxidised to 32 by iron(III) (Scheme 14). 

Nucleophiles, such as hydroxide, cyanide, and Grignard reagents attack the 2-position of pyridinium and the 1-position of isoquinolinium cations. Quinolinium salt reacts with nucleophiles at the 2- and 4-positions. Hydroxide attacks the 2-position, and cyanide attacks the 4-position. These results support the theoretical expectation. 

The thermodynamic stability of could clearly influence the position of this equilibrium. The importance of this effect is shown by the work of Reidel and Charles (23) who prepared salts of [(BTFA)4Eu] with 15 different substituted ammonium cations and observed a more than threefold change in laser threshold at 0°C. on going from piperi-dinium through quinolinium. The increase in threshold roughly parallels an increase in the pKb of the amine from which the cation is derived for those compounds with other than quaternary ammonium ions, and for the quinolinium salt these workers showed that the extent of dissociation to tris chelate is about 40%, as compared with 10% or less for the piperidinium compound. 

Heteroaromatic cations undergo reduction when treated with 1,4-dihydronicotinamide. An early study showed that the 10-methylacridinium ion (87) was rapidly reduced in a redox reaction to the 9,10-dihydro adduct by 1,4-dihydronicotinamides (M Scheme 18). A variety of systems including py-ridines, isoquinolines, quinolines and phenanthridines have been studied using this and related procedures. The selective reduction of pyridinium and quinolinium salts with 1-benzyl-1,2-dihydro-isonicotinamide (89) has been achieved. The selective conversion to the thermodynamically more stable 1,4-dihydro species (90 Scheme 18) is rationalized by the reversibility in the formation of the kinetic products (i.e. the 1,2-adducts) in the presence of pyridinium ions. In the pyridinium case 1,6-di-hydro adducts were also observed in some cases. Reactivity in such systems is sometimes hindered due to hydration of the dihydropyridine system. This is particularly so in aqueous systems designed to replicate biological activity. Dihydroazines derived from isoquinolines and 3,5-disubstituted pyridines have been reported to overcome some of these difficulties. ... 

Similar photoinduced dimerizations and ligand substitutions in the presence of additives such as triphenylphosphine are observed with ion-pairs salts of Mn(CO)s and V(CO)6" with cobaltocenium or other cationic acceptors such as Ph2Cr", pyr-idinium, quinolinium, etc [118]. Most importantly, all photochemical transformations of the various carbonyl metallate salts are initiated by actinic light that solely excites the charge-transfer absorption bands of the contact ion pairs whereas local excitation of the separate ions is deliberately excluded. 

An advantageous method for the conversion of 2- and 4-methyl substituted pyridinium and quinolinium salts (120) into their corresponding 2,4,6-triaryl-phenyl derivatives (121) in good yields has been developed by Zimmermann [158]. The anhydrobases of 121 were discussed as the key intermediates of this pyrylium ring transformation they attack the pyrylium cation 122 in the initial step as carbon nucleophiles of the enamine type (see Scheme 56). The reaction... 

Y. Yagci, A. Kornowski, and W. Schnabel, A-Alkoxy-pyridinium and A-alkoxy-quinolinium salts as initiators for cationic photopolymerizations. J. Polym. Sci. A Polym. Chem. 1992, 30(9), 1987-1991. 

The ideas described above were applied in Ref. 6 to the analysis of experimental data on complex conductivity of TCNQ salts with asymmetric cations - quinolinium /Qn/ and acridizinium /Adz/. It was supposed that the structural disorder caused by randomly oriented cations produced the localization, and the temperature dependence of 6 was attributed to the effect of phonons on the localization. 

A select set of cationic heteroaromatic azadienes including acridizi-nium, isoquinolinium, quinolinium, and isoxazolium salts have been shown to participate as useful 47t components of [4+ + 2] cycloadditions. These systems have been discussed in Chapter 9, Section 10. 

It has also been suggested that the reduction by 1,4-dihydropyri-dine derivatives proceeds by a one-step hydride transfer mechanism (HT-mechanism), which seems to be contrary to the ET-mechanism described above. This assertion is mostly based on the results from the reduction of cationic substrates such as quinolinium salts, acridinium salts, and protonated Schiff bases (Srinivasan et al. 1982). For example, Ostovic et al. (1983) reported that the value of the kinetic isotope effect does not change significantly for the reactions with a series of substrates with which equilibrium constants change widely. 

In addition, microwave irradiation accelerated this transformation by at least 8-fold. Additives, in particular a quinolinium salt, were found to facilitate the intramolecular reaction of diynes that would not otherwise macrocyclize, apparently through an intermolecular noncovalent 7t-cation/arene inter-action. " It is noteworthy that RCM also can be assisted with such additives. These studies have positioned the Glaser-Hay reaction for investigation in the preparation of macrocycles from more complex substrates. 

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