Quinoliniums

The nitration of phenylpyridines and related compounds has attracted attention for a long time, and measurements of isomer proportions have been made for several compounds of this type. Nitration occurs in the phenyl ring. For 2-phenylpyridine and 2-phenylpyridine i-oxide measurements of the dependence of rate of nitration upon acidity in 75-81 % sulphuric acid at 25 °C show that both compounds are nitrated as their cations (table 8.1). The isomer distribution did not depend significantly upon the acidity, and by comparison with the kinetic data for quinolinium ( 10.4.2) the partial rate factors illustrated below were obtained.They should be compared with those for the nitration of 2-nitrobiphenyl ( 10.1). The protonated heterocyclic groups are much... 

A more detailed study of the nitration of quinolinium (l) in 80-05 % sulphuric acid at 25 °C, using isotopic dilution analysis, has shown that 3-) 5-) 6-, 7- and 8-nitroquinoline are formed (table 10.3). Combining these results with the kinetic ones, and assuming that no 2- and 4-nitration occurs, gives the partial rate factors listed in table 10.4. Isoquinolinium is 14 times more reactive than quinolinium. The strong deactivation of the 3-position is in accord with an estimated partial rate factor of io for hydrogen isotope exchange at the 3-position in the pyridinium ion. It has been estimated that the reactivity of this ion is at least 10 less than that of the quinolinium ion. Based on this estimate, the partial rate factor for 3-nitration of the pyridinium ion would be less than 5 x io . 

TABLE 10.4 Theoretical and experimental partial rate factors for the nitration of the quinolinium ion... 

Numerous m.o.-theoretical calculations have been made on quinoline and quinolinium. Comparisons of the experimental results with the theoretical predictions reveals that, as expected (see 7.2), localisation energies give the best correlation. jr-Electron densities are a poor criterion of reactivity in electrophilic substitution the most reactive sites for both the quinolinium ion and the neutral molecule are predicted to be the 3-, 6- and 8-positions. ... 

Partial rate factors for the nitration of 4-hydroxyquinoline and its derivatives are given in table 10.6. Comparison with the values for quinolinium (table 10.4) show that the introduction of a 4-hydroxy or a 4-methoxy group into the latter activates the 6-position by factors of 3-3 X 10 and 1-6 X 10 , respectively, and the 8-position by factors of 29-5 and 23, respectively. What has been said above makes the significance of partial rate factors which may be calculated for 4-hydroxy-cinnoline uncertain. 

Among the W-oxides of this series of compounds isoquinoline 2-oxide shows the simplest behaviour on nitration. The acidity dependence of the rate of nitration (table 8.1), and comparison with the 2-methoxyiso-quinolinium cation (v, R = Me) (table 10.3) show the oxide to be nitrated as its conjugate acid (v, i = H) in 76-83 % sulphuric acid. The... 

Calculations for electrophilic substitution in the quinolinium ion can be compared with experiment, and for a range of values of h the predicted order of positional reactivities, s 8>6>3>7, agrees moderately well in a qualitative sense with the observed order of s 8>6>7>3 (table 10.3). Further evaluation of the method must await the results of more extensive calculations for a range of aromatic systems. 

In 1923, Mills introduced thiazole for the first time in the synthesis of methine dyes through a somewhat indirect route. In order to demonstrate the 2,4 -cyanine mechanism of formation by quinoline and quinaldine quaternary salts reacting together, Mills used other pairs of quaternary salts as 2-methylthiazolium with either quinolinium or benzothiazolium (42, 43). 

As a whole, 2 moles of quinolinium react with one of thiazolium together with 2 moles of base. This explains the traditional interest of making the condensation with an excess of quinolinium salt in order to get the maximum yield (50. 51). 

Quinolinium chloride in nitrobenzene reacts with excess bromine to give an 81% yield of 3-bromoquinoline (24). It seems likely that the 1,2-dibromo complex is actually being brominated. 

Finally, the importance of quinolinium salts to dye chemistry accounts for the long, productive history of their synthesis. The reaction of A/-methylformanihde with ketones, aldehydes, ketone enamines, or enol acetates in phosphoryl chloride leads to high yields of /V-methylquinolinium salts (60). 

Other Radioprotective Chemicals. The bis-methylthio- and methylthioamino-derivatives of 1-methylquinolinium iodide and l-methylpyridinium-2-dithioacetic acid provide reasonable protection to mice at much lower doses than the aminothiols, which suggests a different mechanism of action (139). One of these compounds, the 2-(methylthio)-2-piperidino derivative of the l-methyl-2-vinyl quinolinium iodide (VQ), interacts with supercoUed plasmic DNA primarily by intercalation. Minor substitutions on the aromatic quinolinium ring system markedly influence this interaction. Like WR-1065, VQ is positively charged at physiological pH, and the DNA-binding affinities of VQ and WR-1065 appear to be similar. 

The 5-chloro in 5-deazaflavins is reactive (7SJHC181), but not the 8-chloro, in contrast to the flavin case (79LA1802), and 4-chloropyrimido[4,5-Z>]quinolinium salts are readily hydrolyzed (76JCS(Pl)l3l). 

Although in its reactions with several mesoionic systems diphenylthiirene dioxide (439) does not lose SO2 from the cycloadducts, in its reactions with pyridinium, quinolinium and isoquinolinium phenacylides it behaves as an acetylene equivalent. Thus, reaction of (439)... 

I-Methyl-4-[3(5)-pyrazolyl]quinolinium iodides (688) also failed to depress blood sugar levels significantly (69JMC1124). Neuroleptic-like effects of some /3-aminoketones (689) containing a pyrazole nucleus have been described in the literature (B-80MI40406). The... 

Pyrimido[4,5-6]quinolinium salts pseudo bases - ring opening, 3, 208 Pyrimido[4,5-6]quinolinium salts, 4-chloro-hydrolysis, 3, 214 Pyrimido[4,5-6]quinolinones synthesis, 3, 228 Pyrimido[4,5 -6]quinolin-5-ones synthesis, 3, 221-222 Pyrimidothiadi azoles reactions, 6, 533 Pyrimidothiazines synthesis, 4, 527 Pyrimidothiazinones mass spectra, 2, 23... 

Quinolinium 2-dicyanomethylene-1,1,3,3-tetracyanopropanediide dimensions, 2, 110 Quinolinium iodide, 1-alkyl-Ladenburg rearrangement, 2, 300 Quinolinium iodide, 1-methyl-Ladenburg rearrangement, 2, 300, 335 Quinolinium iodide, [l-methyl-4-[3(5)-pyrazolyl]-blood sugar level and, 5, 291 Quinolinium perchlorate, 1-ethoxy-hydroxymethylation, 2, 300 Quinolinium perchlorate, 1-methyl-nitration, 2, 318 Quinolinium salts alkylation, 2, 293 Beyer synthesis, 2, 474 electrophilic substitution, 2, 317 free radical alkylation, 2, 45 nitration, 2, 188 reactions... 

Quinolinium salts, l-(4-alkoxyphenyl)-2-methyl-synthesis, 2, 475 Quinolinium salts, aryl-Skraup synthesis, 2, 467 Quinolinium salts, 4-chloro-synthesis... 

Quinolinium salts, 2-ethoxycarbonyl-3-hydroxy-acetylation, 2, 544 Quinolinium salts, 1-methoxy-reactions... 

Organometallic reagents react with iminium salts to give C-alkylated products. The reactions can be divided into two categories the reactions of pyridinium, quinolinium, and isoquinolinium salts and the reactions of... 

A review of the literature prior to 1953 on reactions of pyridinium, quinolinium, and isoquinolinium salts is available (31). The reactions will be described here only briefly. The initial observation was that of Freund et al. (32-37), who found that treatment of various derivatives of hydra-stinine (15) with Grignard reagents yielded addition products, such as 16. 

Since the initial discovery there have been several investigations that have examined the Grignard reaction with quinolinium and isoquinolinium salts... 

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