Acridine alkylation

Acridine-9-thione alkylation, 2, 357 oxidation, 2, 357 tautomerism, 2, 356 9-Acridinium bromide reactions... 

An acridine with a radically different substitution pattern, interestingly, still exhibits antimalarial activity. Condensation of acetone with diphenylamine in the presence of strong acid affords the partly reduced acridine, 20. Alkylation with 3-chloro-dimethylaminopropane (via the sodium salt of 20) affords dimethacrine (21). ... 

Alkyl-3-ethoxy-4-[(mesyloxy)methyl]-l,4-dihydroisoquinolines 27 on treatment with potassium /Vrt-butoxide in dimethyl sulfoxide undergo ring expansion to 1/7-2-benzazepines.24 0 (For related ring expansions of acridines, see Section 3.2.1.4.1.5.) The 4-methyl and 4-methyl-l-phenyl derivatives 27a and 27b, respectively, yield mixtures of the 3-ethoxy-5-methyl- 28 and 3-ethoxy-4-methyl- 29 l//-2-benzazcpines cyclopropaquinolines are thought to be involved as intermediates (see Section 3.2.1.4.1.6.). In contrast, the 4-[l-(mesyloxy)ethyl] derivatives 27e and 27d yield only the 4,5-dimethyl-li/-2-benzazepines 29c and 29d. 

Kawabata Y., Tahara R., Imasaka T., Ishibashi N., Fiber-optic potassium ion sensor using alkyl-acridine orange in plasticized poly(vinyl chloride) membrane, Anal. Chem. 1990 62 1528. 

A particularly attractive feature of acridine (80d) is that this compound can be tracked through the parasite using confocal microscopy and this has enabled O Neill and coworkers to determine intraparasitic sites of protein alkylation". ... 

Substitution of the nine position is a common transformation for acridines. An optimized method for preparing the 9-carboxamides uses BOP/DMF <99SC4341>. Reaction of 9-isothioacridines with the sodium anion of diethylmalonate is followed by alkylation with bromoacetate to afford the spiro[dihydroacridine-9(10i/)-thiazolidines] <99H(51)137>. 

Acridine-4,5-diol was converted to the corresponding 18-crown-6 ligand by alkylation of the hydroxy groups with tetraethylene glycol di-p-tosylate <99T1491>. 

Nucleophilic reagents attack pyridine at the a-position to form an adduct that rearomatizes by dissociation (Scheme 1). Only very strong nucleophiles, e.g. NH2-, RLi, LAH, Na-NH3, react, and for the second step to afford a substitution product (5), conditions that favour hydride loss are required. Adducts formed with hydride ions (from LAH) or carbanions (from lithium alkyls) are relatively more stable than the others at low temperature, and dihydropyridines (6) can be obtained by careful neutralization. Fusion of a benzene ring to pyridine increases reactivity towards nucleophiles, and attack is now found at both a- and y-positions in quinoline (7) and at C-l in isoquinoline (8). This may be attributed to a smaller loss of aromaticity in forming the initial adduct than in pyridine, and thus a correspondingly decreased tendency to rearomatize is also observed. Acridine reacts even more easily, but nucleophilic attack is now limited to the y -position (9), as attachment of nucleophiles at ring junctions is very rare. 

Alkylation and acylation of thioacridone are difficult because the acridine thioethers and thioesters that are formed undergo hydrolysis in alkaline medium. Vlassa et al.191 and later Galy et a/.198 used PTC to prevent this hydrolysis, thus obtaining high yields (90-98%) of alkylation and acylation products. 

Alkyl radicals for such reactions are available from many sources such as acyl peroxides, alkyl hydroperoxides, particularly by the oxidative decarboxylation of carboxylic acids using peroxy-disulfate catalyzed by silver. Pyridine and various substituted pyridines have been alkylated in the 2-position in high yield by these methods. Quinoline similarly reacts in the 2-, isoquinoline in the 1-, and acridine in the 9-position. Pyrazine and quinoxaline also give high yields of 2-substituted alkyl derivatives <74AHC(16)123). 

The most frequently reported oxidation reaction of isatins is the oxidation with alkaline hydrogen peroxide to give anthranilic acids. This procedure has been both as a proof of structure of isatins and as a method of synthesis of anthranilic acids. The oxidation has been applied to alkyl 8"10 11 23 33>38-40>46 49>50>118halo n.18.35.36-38-40.47.10 .11 . 119,136,240 alkoxy,26,a8 39,47,75.io7,ii8,i36 trifluoromethyl,33,38,137 and nitro8,120,217 isatins. Use of N-substituted isatins led to N-substituted anthranilic acids.66,71,125,158,169,243 In the oxidation of 5-bromo-l-(y-carbethoxypropyl)-7-ethylisatin, 60 was isolated after treatment with ethanol and acid.11 Oxidation of isatin derivatives 61 led, after treatment with diazomethane, to the acridine derivatives 62.67 Application of this oxidation method to 7-hydroxyisatins gave rise to benzoxazo-lones (63).2,41... 

Acridines, dyes, alkylating Possible binding of chemical agents... 

It is known from electrochemical studies that fullerenes are easily reduced. Up to 6 electrons can be added reversibly [19], and, as mentioned earlier, the excited states are even more easily reduced. A large number of electron donors were investigated including aromatic and alkyl amines [29,43,79,119-140,152,161], ni-troxide radicals [57,117], suspensions of Ti02 [118], polyaromatic compounds, [19,127] organo-silicon compounds, [133,158] phenothiazine, [133] acridine [145,154], (3-carotene [141], tetrathiafulvalenes [146], tetraethoxyethene [147], phthalocyanines [148], porphyrines [151,153], NADH and analogues [150,154, 155], borates [156,159], and naphtoles [23] to name a few representative cases. 

The decreasing reactivity of the most familiar aromatic heterocyclic compounds with nucleophilic reagents may be illustrated by the following sequence quinoxaline > acridine > phenanthridine > isoquinoline > quinoline > pyridine. Acridine is alkylated in the 4-position, phenanthridine and quinoxaline in the a-position, isoquinoline in the 1-position, and quinoline and pyridine in the 2- or 4-positions. Weaker nucleophilic reagents seem to enter the 4-position of the pyridine and quinoline rings. If the addition occurs readily and in good yield, the intermediate dihydro derivative may sometimes be isolated otherwise, the product of the subsequent oxidation results. In synthetic work the dihydro derivative is usually directly oxidized. 

Visible light-activated phototropic compositions comprising a hexa-arylbi-imidazole and a bislalkylamino(acridine dye. Cohen, Robert L. (du Pont de Nemours, E. I., and Co.) U.S. 3,563,751 (Cl. 96-90 G 030), 16 Feb 1971, Appl. 20 Jul 1967, 5 pp. Acridine dyes of general formula I, where alkyl R2,R4 = H or... 

Charmantray F, Duflos A, Lhommea J, Demeunynck M (2001) Synthesis and study of 4-hydroxymethyl-3-(alkylamino)acridines as models of a new class of DNA-intercalating-alkylating agents. J Chem Soc 1 2962-2968... 

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