Acridine reduction

The importance of radical ions and electron-transfer reactions has been pointed out in the preceding sections (see also p. 128). Thus, in linear hydrazide chemiluminescence (p. 103) or acridine aldehyde or ketone chemiluminescence, the excitation steps consist in an electron transfer from a donor of appropriate reduction potential to an acceptor in such a way that the electron first occupies the lowest antibonding orbital, as in the reaction of 9-anthranoyl peroxide 96 with naphthalene radical anion 97 142> ... 

The reduction of acridine to 9,10-dihydroacridine by the precursor [RuH(CO) (NCMe)2(PPh3)2]BF4 has been found to occur with the experimental rate law r=kcat [Ru][H2] and the postulated mechanism involves, as the determining... 

Nitrogen heteroaromatics are expected to be useful probases. The cathodic reduction of phenazine, (31), resembles closely that of (29a) [70,71], and the kinetic basicity of (31) is comparable to that of (29a) [54]. However, application of (31) as a PB in electrosynthesis has not been reported, and there is only a single report concerning the use of the radical anion of acridine, (32), as an EGB [72]. 

Reaction conditions used for reduction of acridine [430,476, partly hydrogenated phenanthridine [477 and benzo f]quinoline [477 are shown in Schemes 38-40. Hydrogenation over platinum oxide in trifluoroacetic acid at 3.5 atm reduced only the carbocyclic rings in acridine and benzo[h]quinoline, leaving the pyridine rings intact [471]. 

Quinoline and isoquinoline undergo reduction in a similar way to pyridine but with greater ease. Acridine may be polarographically reduced in both acid and alkaline solution. 

Protonated pyridines and derivatives readily undergo acylation at C-2 or C-4 (Table 28) (76MI20503). Acyl radicals are usually generated either by hydrogen abstraction from aldehydes (Scheme 210), or by oxidative decarboxylation of a-keto acids (Scheme 211). In the former case (Scheme 210) with acridine as the substrate, reduction can take place to give a dihydroacridine. 

Benzo ring reduction in acridine can be achieved in a variety of ways. 1,4,5,8-Tetrahydro-acridine is given by lithium in liquid ammonia and ethanol (Scheme 35) (69AJC1105). The symmetrical octahydroacridine (48) can be obtained by hydrogenation of acridine over platinum oxide in trifluoroacetic acid. The product is obtained in quantitative yield (Scheme... 

The hydrogenation of phenanthridine at 250 °C under pressure in the presence of a sodium-rubidium catalyst in benzene is reported to give octahydrophenanthridines. Acridine similarly forms a variety of reduction products (71JOC694). 

An interesting example where erroneous mechanistic conclusions were drawn from sensitization experiments is the photoreduction of acridine (17). Although irradiation of acridine in a variety of hydrogen containing solvents gave measurable reduction to acridan and diacridan, addition of benzophenone or acetophenone greatly enhanced the rate of this reaction.113... 

Photoreduction was quenched by high concentrations of biacetyl, slightly retarded by iodonaphthalene, but not affected by azulene or anthracene.113 These observations led to the unsatisfying conclusion that reduction proceeded via a triplet state which could be only selectively quenched. However, later work114 using flash photolysis showed that the benzophenone ketyl radical was generated upon irradiation of solutions of benzophenone and acridine, and that its predominant mode of disappearance was by reaction with... 

Reductions with noble metal catalysts proceed smoothly (at 20°C) when the bases are in the form of hydrochlorides the free bases tend to poison the catalyst. A pyridine ring is reduced more easily than a benzene ring thus, 2-phenylpyridine gives 2-phenylpiperidine (384), quinoline gives 1,2,3,4-tetrahydroquinoline (385) and acridine gives 9,10-dihydroacridine (386). 

Ozonolysis of acridine and reduction of the resulting dialdehyde with sodium borohydride gives the diol (179). This is esterified with excess methanesulfonyl chloride and the resulting diester reacts with aqueous ammonia to give the dihydropyrroloquinoline (180). This furnishes the pentacycle (181) with a quantitative yield for the final step (Scheme 55) (75JOC2140). 

Aryliodonium salts have been found to be coinitiators for photooxidizable dye sensitization (105). Smith polymerized aerylamide-bis(acrylamide) mixtures using acridine, xanthene, or cyanine dyes and, for example, diphenyllodonium chloride as an electron acceptor. Reduction of the salt results in the formation of phenyl radicals. 

Comminution also may be used to examine the stability of dispersed phases such as oil droplets. Depending on the viscosity of the product one simply mixes it or breaks it up in a solvent (usually water but, for example, use fresh soybean oil for chocolate), a buffer or the appropriate dyes (below). For instance, we mix easily dispersible foods (cream cheese, ice cream mix or tablespreads) with dyes on slides in a ratio of about 1 1 before examination. Where the dye is a diachrome (that is, highly colored) or is fluorescent in the absence of the substrate (for example, Acridine Orange) some attempt must be made to remove excess, uncomplexed dye molecules which might confound the interpretation. This can be done by reduction of the dye concentration or by making the preparation thinner. The advantage of these simple techniques is that a battery of microchemical tests to identify protein, lipid and carbohydrate can be completed on multiple samples in a very short time period. 

In the case of terpyridine and acridine derivatives, the bis(methylamines) are the most convenient intermediates. Substituted 4/-phenyl-2,2/ 6/,2"-terpyridines were prepared by reacting (ii)-propenons and iV-[2-(pyrid-2 -yl)-2-o octln l p ridinium iodide with ammonium acetate in acetic acid or in methanol. The terminal pyridine moieties were oxidized with 3-chloroperbenzoic acid to iV, A" -dio idcs followed by modified Reisserty-Henze reaction to obtain 6,6"-dicarbonitriles. The bis(methylamines) were obtained by reduction of the 6,6"-dicarbonitriles withborane (scheme 8 (Mukkala et al., 1993)). 

The first reduction wave for phenanthridine jV-oxide in dimethyl-formamide (at 25°) appears at — 1.774 (vs. s.c.e.) in good agreement with the HMO energy of the lowest vacant orbital277 a mechanism for the reduction has been proposed.278 No esr signal could be detected during controlled-potential electrolysis at the appropriate potential, perhaps because of the relative instability of the anion radical. This behavior, which is paralleled by isoquinoline, contrasts sharply with that of the oxides of other polynuclear N-heteroaromatic systems (e.g., quinoline and acridine).277... 

In a study of the lithium aluminum hydride reduction of a series of nitrogen aromatic heterocyclics, Bohlmann97 found that this metal hydride effected a conversion of acridine to 9,1O-dihydroacridine (91) in high yield and purity. The ultraviolet spectrum of the isolated dihydroacridine (Amax 288 mp, loge = 4.18) was confirmed by Braude et al.92 as a part of a study of the hydride donor properties of a series of aromatic nitrogen-heterocycles. These workers found that the dihydroacridine underwent a slow oxidation to acridine in air and a rapid hydrogen transfer in the presence of chloranil to form the quinol and acridine. The dihydroacridine was, however, quite stable under dry nitrogen. 

Acridine and 9,10-dihydroacridine (91) form bright yellow complexes however, such complexes have not been observed as direct reduction products of the metal hydride reduction of acridine. 

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