9- Aminobenzo acridines

Anthranilic acid (2-aminobenzoic acid) (see page 126) is another shikimate-derived compound which, as its CoA ester anthraniloyl-CoA, can act as a starter unit for malonate chain extension. Aromatization of the acetate-derived portion then leads to quinoline or acridine alkaloids, according to the number of acetate units incorporated (Figure 3.47). These products are similarly discussed elsewhere, under alkaloids (Chapter 6, page 376). 

Only a few examples of this ring system have been reported. Grout et al. [68JCS(C)2689] have cyclized N-acyl derivatives 191 of 9-aminobenzo[a]acridines to pyrido[4,3,2-W]acridines 192 by heating with AlCla/NaCl at 200-220°C (Scheme 32). 

Arynes are novel reaction intermediates that react with dienes or 1,3-dipoles to give the corresponding cycloadducts. Recently, many researchers have reported the reaction of benzyne prepared from 2-(trimethylsilyl)phenyl triflate or benzenedia-zonium carboxylate with imines, aminobenzoate, 2-aminobenzophenones, azides, and diazo compounds, which provides various N-containing cycloadducts, such as acridines, acridones, triazoles, and indazoles. Formally, the reaction proceeds in a [2-1-2], [3-1-2], or [4-1-2] manner. Benzyne is an extremely reactive species because of the presence of a strained triple bond and undergoes polar and pericycHc reactions. The lifetime of benzyne in the gas phase has been estimated to around 20 ns (2 X 10" s) by mass spectroscopic techniques. Some spectroscopic properties of benzyne have been determined by Orville Chapman using matrix isolation techniques (Scheme 7.20). 

A mixture of A,A-diphenylamine (0.03 mol), 4-aminobenzoic acid (0.06 mol) was heated in 230 g of polyphosphoric acid at 200 °C for 15 min. The reaction mixture was then poured onto ice and filtered or decanted. Treatment of the solution with 25% NaOH (aq) solution caused the precipitation of a solid (while the solution was still acidic) presumed to be the phosphate salt of 9-(4-aminophenyl)acridine. After filtration the solution was made strongly basic with NaOH and extracted with chloroform. Concentration of the chloroform yielded only trace amoimts of 5. The phosphate salt was shaken with 25% NaOH (aq) and chloroform and the chloroform concentrated to give a 24% yield of 5. 

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