Isoquinolinium cations

Nitration of isoquinoline with nitric and sulfuric acids occurs preferentially at positions 5 and 8, the former predominating, in the approximate ratio of 9 1 at 0 °C. The amount of 8-nitro isomer is slightly increased at higher temperatures. Electrophilic localization energies predict the reactivity order 5>8>others. Over the range 71—85% sulfuric acid it has been shown that the reaction proceeds via the isoquinolinium cations (Scheme 6) (63CI(L)1283, 60T(8)23, 57JCS2521). 

Radical attack on isoquinoline, as either free base or isoquinolinium cation, always occurs at position 1 and the method is not suitable for the preparation of benzo ring-substituted products. The same can be said of radical attack on the JV-oxides of quinoline and isoquinoline. 

The influence of substituents, including aza, on reactivity of the nitrogen atom in such systems have been considered in detail1 6,7,47 102,188 189 and may be correlated with Dewar—Grisdale calculations [Eq. (2)],6 33-190-192 or dual-substituent parameter [Eqs. (3) and (4)].6,7,47,188-190 Thus, analysis6 of pXa s (HzO, 25°) of substituted quinolinium and isoquinolinium cations according to Eq. (20) gave the results shown in Table V, where they are compared with those for substituted naphthoic acids (aq. EtOH, 25°). 

Small chromophores, such as -alkylquinolinium, and isoquinolinium cations can also be intercalated into the galleries of a-ZrP. In most cases, this did not bring about any change in the fluorescence spectra from that observed in solution (acetonitrile). The fluorescence decays of the intercalated compounds were, however, nonexponential and contained a very short-lifetime component. High loadings resulted in self-quenching of the fluorescence and this contributed to the shorter-lived component for the intercalated dyes [58],... 

There is no spectral evidence for pseudobase formation by the N-methyl-pyridinium cation in even the most basic aqueous solutions that are attainable. An oil which separates from solutions of this cation in concentrated aqueous base has been identified by PMR and IR spectroscopies as predominantly ionic N-methylpyridinium hydroxide.70 The UV spectra of the IV-methylquinolinium and N-methylisoquinolinium cations are pH-independent below pH 14, but both these cations undergo irreversible reactions in more basic aqueous solutions (Section V,D) so that pK + values are not directly measurable. Based on substituent effects in more highly substituted quinolinium and isoquinolinium cations, pKR+ values of 16.5 and 15.3 have been estimated26 for the N-methylquinolinium and Af-methyl-isoquinolinium cations respectively. The estimate for the latter cation is based on somewhat limited data and should be compared with pKR+ = 16.29, which has been measured in aqueous dimethyl sulfoxide solutions.90,91... 

It is clear from perusal of the data in Table VI that there is no overall general correlation between pJCR and /c0H or kH2o e.g., although the 2-benzyl-5-nitroquinolinium and 9-phenyl-10-methylacridinium cations have similar pKR values, the values of k0H for these two cations differ by a factor of 105. However, within series of very closely structurally related cations, useful linear rate-equilibrium correlations do exist.39 Thus, Fig. 4 displays linear relationships between log k0H and pXR+ for quinolinium and isoquinolinium cations. The correlation lines in this figure are given by Eqs. (30) and (31). These correlations cover six units of the p KR + scale and a... 

Fig. 4. Relationship between log /coH and p/C. for quinolinium ( ) and isoquinolinium ( ) cations. Cations are identified by numbers in Bunting and Norris38. Full lines correspond to Eqs. (30) and (31). (Reprinted with permission from Bunting and Norris,39 J. Am. Chem. Soc. 99, 1189 (1977). Copyright by the American Chemical Society.)...

An interesting feature of the kinetic data in Table VI is the relative insensitivity of the k0H/kHl0 ratio to substituent effects within a series of structurally related cations. Thus, for quinolinium and isoquinolinium cations, kOH/kH20 is within a factor of 2 of 2 x 107 M-1 for at least a 100-fold variation in each of k0H and kHl0. Similarly, km/kHl0 is the same within experimental error (2.4 x 105 M l) for the 10-methylacridinium cation and its 9-phenyl derivative despite a major structural variation at the site of nucleophilic attack and a resulting 400-fold difference in koH for these two cations. 

Pyridinium, quinolinium, and isoquinolinium cations are the major species undergoing electrophile substitution reactions under acidic conditions [90AHC(47)1]. As expected from Table XXIII, the electrophilic reaction of pyridinium ion occurs at the 3-position, and an electrophile attacks at the 5- and 8-positions of quinolinium and isoquinolinium cations. Electrophile reactivity of 1 is rather low because of its electron accepting character. Molecular orbital calculations of its orientation did not give a consistent conclusion. Electron density and superdelocalizability (electrophile) predict that position 1 will be the most reactive towards an electrophile, while inspection of the localization energy (electrophile) predicts that electrophilic reaction takes place at position 4. 

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 properties of pyrylium cations are best compared with those of pyridinium cations the system does not undergo electrophilic substitution nor, indeed, are benzopyrylium cations substituted in the benzene ring. This is a considerable contrast with the chemistry of quinolinium and isoquinolinium cations and is a comment on the stronger deactivating effect of the positively charged oxygen. 

Unlike the 3-oxidopyridinium betaines, about which much was reported last year, the analogous 3-imidopyridiniums, e.g. (55), do not give cyclo-adducts with electron-deficient or electron-rich alkenes. In addition, only resinous products are obtained with dimethyl acetylenedicarboxylate. The formation of pseudo-bases from quaternary pyridinium, quinolinium, and isoquinolinium cations has been reviewed. ... 

One strategy which has been successfully utilized in yohimbine alkaloid synthesis involves the use of cyclization reactions of either pyridinium or isoquinolinium cations to install the respective D or DE-ring units. Wenkert and his coworkers have popularized this methodology, as exemplified by their synthesis of hexahydroyohimbine (473) (Scheme 3.82) (131). In this sequence, AT-tryptophylpyridinium salt 468, prepared by reaction of 3-formylpyridine and tryptophyl bromide, was treated with the enolate anion of methyl aceto-acetate to afford isoquinolone 469. Methylation of this material provided isoquinolinium salt 472 which upon reduction followed by acid mediated cyclization provided yohimbane 473. This methodology represents a rather... 

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