Arylnitrenium ions

These metabolites have been shown to produce arylnitrenium ions 8 under solvolytic conditions and McClelland and Novak have demonstrated, respectively... 

For phenylnitrenium ions, we85 and others 72,78,102 104 have computed that there is extensive positive charge delocalisation into the aromatic ring and arylnitrenium ions are best described as 4-imino-2,5-cyclohexadienyl-l-yl carbenium ions 18. 

From appraisal of their respective resonance stabilisation, arylnitrenium ions and alkoxynitrenium ions should form with similar facility. On account of the fact that A-acetoxy-A-acetyl arylamines 7 are penultimate carcinogens in the metabolism of aromatic amines, A-acyloxy-A-alkoxyamides 3 were designed to test their potential as DNA-damaging agents. 

Aromatic substitution, a quantitative treatment of directive effects in, 1, 35 Aromatic substitution reactions, hydrogen isotope effects in, 2, 163 Aromatic systems, planar and non-planar, 1, 203 N-Arylnitrenium ions, 36, 167... 

Nitrenium ions, 38, 70, see also IV-Acyloxy-IV-alkoxynitrenium ions Arylnitrenium ions... 

A different method of generating a nitrenium ion has been demonstrated the sulfur-nitrogen bond in (55) cleaves and then a novel intramolecular hydride shift to the arylnitrenium ion centre takes place. The nitrenium species (56) undergoes two nucleophilic additions to the double bond to give the product (57). Two studies concerning the physiological effects of nitrenium ions in vivo are reported. Products are formed from both the ion-paired nitrenium ion (59) and the free ion (60)... 

Nitrenium ions (or imidonium ions in the contemporaneous nomenclature) were described in a 1964 review of nitrene chemistry by Abramovitch and Davis. A later review by Lansbury in 1970 focused primarily on vinylidine nitrenium ions. Gassmann s ° 1970 review was particularly influential in that it described the application of detailed mechanistic methods to the question of the formation of nitrenium ions as discrete intermediates. McClelland" reviewed kinetic and lifetime properties of nitrenium ions, with a particular emphasis on those studied by laser flash photolysis (LFP). The role of singlet and triplet states in the reactions of nitrenium ions was reviewed in 1999. Photochemical routes to nitrenium ions were discussed in a 2000 review. Finally, a noteworthy review of arylnitrenium ion chemistry by Novak and Rajagopal " has recently appeared. 

Nitrenium ions, particularly the arylnitrenium ions, have been proposed as intermediates in deoxyribonucleic acid (DNA) damaging reactions that can ultimately convert a normal cell into a cancer cell. Carcinogenesis is a complex phenomenon. 

Figure 13.19. Isodesmic reactions used to assess relative stability of arylnitrenium ions toward addition by water.

Interestingly, it was also found that A -acetyl-A -arylnitrenium ions cyclize to form protonated benzoxazole derivatives (34). This reaction was found to have barriers of 4-11 kcal/mol in the gas phase. Although this finding has yet to be verified experimentally, it is significant in view of the fact that these nitrenium ions are frequently used in mechanistic studies of DNA damage. 

One general, and as yet unsolved problem, is understanding and predicting the regiochemistry of arylnitrenium ion addition to DNA bases. This reaction is complicated because phenylnitrenium ion has four potential sites of addition (Fig. 13.21) the nitrenium center as well as the ortho and para ring carbons. Likewise, DNA has numerous sites for electrophilic addition. In guanine bases alone, there is a possibility for addition to N7, 06, N2, or C8. 

Figure 13.20. Reactions predicted by DFT for N-acetyl-N-arylnitrenium ions.

Figure 13.29. Arylnitrenium ions from the photolysis of anthranilium ions.

In many studies, singlet arylnitrenium ions 69 have been generated in aqueous solutions. The primary decay route under such conditions is addition of water (or alcohols) to the para (70) and ortho positions (71) of the aromatic ring (Fig. 13 40).3 44.78,89,159-161 of y fater or hydroxide to the nitrenium center... 

Figure 13.40. Addition of nucleophiles to the ring carbons of arylnitrenium ions.

Figure 13.41. Addition of alcohols and water to arylnitrenium ions.

Arylnitrenium ions are likewise capable of adding to n nucleophiles. With substituted aromatics (e.g., toluene) there exists the possibility of three reactive sites on the nitrenium ion (the nitrogen, ortho- and para-ring positions), along with up to three possible sites on the arene (ortho, para, and meta in the case of a monosub-stituted trap). Thus in a typical case there is the possibility of nine distinct regio-isomers. Obviously, any synthetic utility of such chemistry relies on the ability of the reagents to react in a selective manner. 

There are several examples of arylnitrenium ion additions to alkenes (Fig. 13.54). For example, Dalidowicz and Swenton trapped A-acetyl-A-(4-methoxyphenyl)-nitrenium ion 112 with 3,4-dimethoxy-l-propenylbenzene and isolated products resulting from addition of the alkene to the ortho position of the nitrenium ion, giving cation 113, followed by its cychzation onto N (yielding 114) or the acetyl carbonyl group (yielding 115). 

Figure 13.57. Spin-specific chemistry of arylnitrenium ions.

Figure 13.58. Evidence for a triplet ground-state arylnitrenium ion.

A major concern in nitrenium ion research has been to characterize the hfetimes and reaction rates of these species in solution. Two techniques have been the mainstays of this research. The oldest and most generally applicable method to characterize arylnitrenium ion lifetimes in solution is to measure the relative yields of the stable products. The ratio of rate constants can then be inferred from the product ratios. 

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