Acridizinium ion

Although it is possible to have a polar cycloaddition with a cation containing only carbon and hydrogen, the majority of those which have been found to undergo 1,4-cycloaddition are aromatic quaternary salts. The acridizinium cation (1) used in the first polar cycloaddition reaction of a quaternary salt has been used in the largest number of polar cycloaddition studies to date. The acridizinium ion (1) is particularly suitable for such a study since it is easily prepared, is stable (permitting sealed... 

The yields of product isolated when para-substituted styrenes were allowed to react with the acridizinium ion (Table I) are not indicative of the rates of reaetion. In an experiment patterned after that used by Sauer and Wiest in the first demonstration of the existence of cycloaddition with inverse electron demand, it was shown that the relative rates of addition of para-substituted styrenes to the acridizinium nucleus were as follows CHgO, 4.3 CHg, 1.7 H, 1.0 NOg, 0.34 or in the order expected from the nucleophilicity of the styrenes. 

In the first cycloaddition reaction of the acridizinium ion, that with maleic anhydride, it had been observed that addition had occurred with great stereoselectivity, although it iVas not ascertained whether the product (4) was syn or anti with respect to the benzenoid ring. It was later demonstrated by use of NMR and IR evidence (derived from the... 

Not shown in Table I are several adducts obtained by cycloaddition of the acridizinium ion with 5,6-endo-substituted norbomene derivatives. These adducts each have two (imequally shielded) methylene hydrogen atoms which make simple the NMR analysis of mixtures of syn (8) and anti (9). When the 5,6-endo chain (R) was of the type... 

Significant synthetic application of the reaction products of the acridizinium ion with alkenes has been made by Fields et Although... 

Although dimethyl acetylenedicarboxylate was reported earlier not to undergo cycloaddition with the acridizinium ion, it was later... 

Another important observation by Fields et al ° was that the acridizinium ion (25) will undergo cycloaddition with benzyne, affording... 

Fields cf oZ. have pointed out that the differences observed between the rate of cycloaddition of ketene acetal with the acridizinium ion and that of various acridizinium benzologs qualitatively parallels those which are encountered when the rate of cycloaddition of maleic anhydride with... 

The most recent extension of the 4 + 2 cycloaddition to aromatic quaternary salts has been carried out with isoquinolinium salts (42), in effect, dispensing with ring A of the acridizinium ion. Although there was an earlier claim that the addition of an ynamine to 2-methyl-isoquinolinium iodide led to a 2 1 adduct, the assigned structure... 

Change in the Rate of Cycloaddition Produced by Substitution at the Meso Positions of the Acridizinium Ion... 

Fig. 1. Plot of log hjk vs. o-constants for reaction of styrene with the acridizinium ion. See Westerman and Bradsher t by permission of American Chemical Society.

The simplest quinolizinium derivative which reacts with cyanide ion is the acridizinium ion (3) (58JCS3067,59JA1938) it gives an unstable product (Scheme 11) which was not isolated, but was dehydrogenated by bromine to afford what was believed to be the 6-cyanoacridizinium ion (23). 

With the benzo[Z>]quinolizinium (acridizinium) ion, ring opening has not been observed instead an unstable substance believed to be a piperidinylbenzoquinolizine was obtained (Scheme 14). 

The stereochemistry was presumed to be cis (69T397). Reduction of quinolizinium ion in ethanol with sodium borohydride gave a mixture of tetrahydro and hexahydro products. The reduction of the acridizinium ion (3) in water at 100 °C with sodium borohydride... 

While there appear to have been no deliberate efforts to bring about radical reactions with quinolizinium and its congeners, there remains the possibility that such might occur. In particular, the phenomenon of halogenation of the acridizinium ion (3) in the central nucleus at 100 °C (Section 2.10.2.1.2) may possibly have a radical explanation. 

Although the quinolizinium ion (1), like naphthalene, does not undergo photodimerization, its linear benzo derivative, the acridizinium ion, like anthracene, does so readily (Scheme 27) (57JOC1740). The photodimer dissociates when heated in ethanol. It has been reported that both the dimerization and dissociation in methanol are light-catalyzed and that the quantum yields for the two reactions are 0.23 and 0.49 respectively (78JPR739). 

The discovery that benzyne (Scheme 30) adds to acridizinium ion to produce an azoniatrip-tycene (34) which, on reduction with sodium borohydride followed by hydrolysis, affords anthracene, offers a new route to the synthesis of related hydrocarbons (71JOC3002). This, the Fields anthracene synthesis, has already found application in the preparation of 1,4,5,8,9-pentamethylanthracene (75TL4639). 

Although no 4-aminoquinolizinium derivatives are known, a benzo derivative, 6-amino-acridizinium ion (72 Scheme 50), has been prepared (67JOC733). In the presence of hydroxide ion the amino group loses a proton to form a benzo[6 ]quinolizin-6-imine (73). Alkaline hydrolysis opens the ring to give the amide (74). 

The first synthesis of the benzo[6]quinolizinium ion (Scheme 98, Table 9, example 1) was by hydrobromic acid-catalyzed cyclization of the quaternary salt formed between 2-pyridinecarbaldehyde and benzyl bromide. Aromatic cyclodehydration has continued to the present as almost the only method used for the preparation of the acridizinium ion, its derivatives and benzo analogs. Because of its instability, 2-pyridinecarboxaldehyde has been replaced by more efficient derivatives. The first of these was the oxime (example 2) which not only gave a better overall yield, but also made possible the isolation of a crystalline intermediate (181 Z = NOH). The disadvantages are that it is not suitable for high temperature cyclizations involving polyphosphoric acid, and some products (182) (e.g. example 10, Table 10) may tend to form double salts with hydroxylamine hydrobromide. 

The acridizinium ion adds to various dienophiles to give products of the type (393 Scheme 39). 

Pyridone on irradiation in concentrated solution gives the dimer (437) 2-aminopyridine behaves similarly. The acridizinium ion (see Scheme 39) like anthracene undergoes [4 + 4] photocycloaddition... 

Rates of addition of styrene to 9-substituted acridizinium ions have been measured,199 and the work was extended via substituted styrenes to a multiple structure-reactivity relationship.200... 

Sulfonation of acridizinium ion (11.11) occurs at the 10-position in 82% yield (66JOC565). Phenanthridin-6-one sulfonates exclusively at the 2-position at 150°C (57JA5479), steric hindrance presumably preventing 4-substitution. 

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