Acridines, reduced

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). ... 

Acridine-9-carbonitrile 10-oxide (la 3.00g, 13.6 mmol) in benzene (1.8 L) in a quartz immersion well was irradiated for 3 h with a Hanovia high-pressure 450-W Hg lamp equipped with a Pyrex filter. The resulting solution was evaporated under reduced pressure and the residue was extracted with pentane (3 x 50 mL). The combined extracts were evaporated under reduced pressure at 20 C to give orange crystals yield 1.8 g (60%) mp 105-109 C (Et20/pentane). 

Mutagenicity data for benz[a]- and benz[c]acridine dlol epoxides and tetrahydroepoxldes reveals a deactivating effect of nitrogen dependent upon its position relative to the epoxide. Benz[a]acridine bay region dlol and tetrahydroepoxldes have significantly reduced mutagenicities relative to their... 

Several N-methyl-9-acridinecarboxylic acid derivatives (e.g., 10-methyl-9-acridinecarboxylic chloride and esters derived therefrom [39]) are chemiluminescent in alkaline aqueous solutions (but not in aprotic solvents). The emission is similar to that seen in the CL of lucigenin and the ultimate product of the reaction is N-methylacridone, leading to the conclusion that the lowest excited singlet state of N-methylacridone is the emitting species [40], In the case of the N-methyl-9-acridinecarboxylates the critical intermediate is believed to be either a linear peroxide [41, 42] or a dioxetanone [43, 44], Reduced acridines (acridanes) such as N-methyl-9-bis (alkoxy) methylacridan [45] also emit N-methylacridone-like CL when oxidized in alkaline, aqueous solutions. Presumably an early step in the oxidation process aromatizes the acridan ring. 

In the absence of distribution data (and knowledge of preferred conformation — at least in the axial phenyl examples), the significance of potency differences amongst the isomeric esters (LXXXIll-LXXXV) cannot, however, be judged. Of the more rigid reduced acridine congeners (LXXXVI), only the e-phenyl isomer has been obtained and this lacks hot-plate activity in mice [286]. 

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. 

The devastating mental deterioration that characterizes Alzheimer s disease has been attributed to a mishandling of the neurotransmitter acetylchohne. Inhibitors of acetylcholinesterase, the enzyme that catabolizes that substance, would be expected to help restore deficient acetylcholine levels. Several partly reduced acridines have shown some activity in treating Alzheimer s disease. At least one of these, tacrine (14-5), is now approved for use in patients. The initial step in the synthesis of the first of these consists of the sodium amide catalyzed condensation of isatin (14-1) with cyclohexanone. The reaction can be visualized by assuming the first step to involve an attack of amide on isatin to give an amido-amide such as (14-2) (note that no attempt has been made to account for charges). This can then react with... 

Oxidation of 5//-dibenz[6,/]azepines by Fremy s salt has been examined closely. At pH 7.5 the quinonoid dibenz[6,/]azepin-2-one is produced together with acridine-9-aldehyde (74CRV101). 3-Chloro-10,11 -dihydro-5//-dibenz[6,/]azepine yields a mixture of the quinoneimines (174 R=C1) and (175) which with sodium dithionite reduce to the corresponding chlorohydroxydihydrodibenzazepines (76JHC269). 

To come to a water-soluble, ditopic receptor model, Lehn etal. attached JV6-[24] crown-8 with an acridine-derived DNA-intercalator, so combining the anion binding strength of the first (in protonated state) [67] with the n-stacking capacity of the latter. Indeed, increased binding of ATP by 46 was observed as compared with the unsubstituted azacrown [68]. Additionally, the multifunctional host 46 catalyzes the hydrolysis of ATP [69] with a higher selectivity over ADP as compared with the parent crown but with a somewhat reduced eflectiv-ity. The reaction intermediate was shown to be the Af-phosphorylated crown. 

RCHO - RCOOCHy. This salt, in CH,OH containing N(C2H5)3, catalyzes a Mdox reaction in which aldehydes are oxidized to methyl esters, and certain organic Compounds such us acridine (2) and phenazine are reduced, lixamplcs ... 

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). 

Classes Of Sensitization, a. Photoreducible Dye Sensitization. In 1954 Oster (7) reported the first documentation of a dye-sensitized photoredox system. During the course of his work, Oster identified several classes of effective dyes, termed by him "photoreducible." These included examples of the classes of acridine, xanthine, and thiazine dyes. Figure 3 illustrates an example of each class, chosen in such a manner that the entire visible spectrum is covered by their absorption spectra. In Oster s work, identification of suitable activators (reduc-tants) to use in conjunction with the dyes was empirically determined. 

C) Non-reducible, Aminic (Aminocarboquinonic) Colouring Matters In this group are the amino-derivatives of di- and tn-phenyhne-thanes, with the acridine, quinoline and thiazole colouring matters, which are distinguished as indicated in Table L. 

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 pyridine ring is easily reducible. Hydropyridines are formed from pyridine and its derivatives, and piperidines by complete hydration. Quinoline and acridine are also easily converted into hydro-compounds. 

Acridine (123) is polarographically reducible both in acid and alkaline solution.144 In strongly acid solution a single one-electron wave is found, and from a preparative reduction compounds dimerized at C-9 were isolated.54 In less acid and in alkaline solution 2 one-electron waves are found, the latter probably resulting in 9,10-dihydroacridine (124). 

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