Dihydroacridines, oxidation

Dihydroacridine-10-carbaldehyde (4) is the major product (57%) from the oxidation of 1 l//-dibenz[7),e]azepine (3) with peracetic acid.222 1 l//-Dibenz[/),e,]azcpin-6(5/7)-one (5) is also formed along with trace amounts ( < 4 %) of 9-acridone-10-carbaldehydeand 5,6-dihydro-l 1H-dibenz[ >,< ]azepine-6,l 1-dionc. 

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. 

Anodic oxidation of 9,9-substituted 9,10-dihydroacridines in CH3CN-Bu4NC104 at a Pt electrode gives a cation-radical that dimerizes to a 2,2 -biacridine system such a dimer is further oxidizable to a quinonoid... 

The 3,6-diamino-9,10-dihydroacridine by oxidation with FeCI3 was converted to 3,6-diaminoacridine. 

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. Acridine is hydrogenated to 9,10-dihydro derivative over Raney Ni at 25°C and over copper-chromium oxide at 150°C in dioxane.9101 Over Raney Ni at 100°C, acridine or 9,10-dihydroacridine is hydrogenated to a mixture of as- and s-octahydro and dodecahydro derivatives. However, over copper-chromium oxide at 190°C, as-octahydro derivative is formed in high selectivity, although a small amount of dodecahydro derivative is also formed.9 The formation of... 

Scheme 12.15 Hydrogenation of acridine and 9,10-dihydroacridine over Raney Ni and Cu-Cr oxide.

Methyl- 10-hydroacridinyl radicals are involved in the electrochemical oxidation of 10-methyl-9,10-dihydroacridines with at least one of the 9-positions unsubstituted. If both 9-positions are substituted, 10-hydroacridinyl radicals are not involved since loss of a methylene proton from the initially formed 9,10-dihydroacridine cation-radical is impossible.261... 

Alkylation of acridine at C-9 occurs on reaction with O)-alkozyalkyl lithium compounds and subsequent oxidation of the resulting 9,10-dihydroacridine derivative (16). Various functional group interconversions are possible leading notably to acridines bearing phosphorus containing substituents at the 9-position (L. Horner and W. Hallenbach, Phosphorus and Sulphur, 1984, 173). 

A communication and full paper tell of the efficient photoreduction of 4-chlorobiphenyl to biphenyl by excitation of 9,10-dihydro-lO-methylacridine (163) or acriflavine (164) in aqueous acetonitrile containing sodium borohydride. A variety of alkyl halides, benzyl halides and chlorobenzenes were also reduced. The reaction proceeds by electron transfer from the excited state of the dihydroacridine to the chloroarene, chloride loss and hydrogen atom donation to the arene radical. Thus photoreduction of the arene is coupled with oxidation of the dihydroacridine to the acridinium salt the latter is reduced back to the dihydroacridine by the borohydride. 

For instance, UV and nuclear magnetic resonance (NMR) studies of the reaction between A-methylacridinium ion and primary aromatic amines have revealed the formation of unstable N-adducts under kinetically controlled conditions (—50°C). Their formation is especially favored in case of anilines bearing in the /jara-position an electron-donating substituent R. At temperatures above 0°C, these N-adducts are gradually converted into thermodynamically more favored C-adducts. Also it has been shown that when no oxidant is added, the A-methylacridinium cation acts as oxidant of both N- and C-adducts, thus giving the corresponding products and 10-methyl-9,10-dihydroacridine (Scheme 36) [11, 136]. 

Electron transfer processes, kinetics, and mechanisms for the oxidation of 10-methyl-9,10-dihydroacridine, as the model compound, and other 9-substituted l-methyl-9,10-dihydroacridines have been the subject of many studies [44, 207-211]. In particular, it has recently been found in our laboratory that nanocrystalline Ti02 with CdS nanoparticles embedded in its pores can accelerate the C-H functionalization of azaaromatic compounds. Indeed, the CdS/Ti02 composite proved to be an effective visible-light-driven photocatalyst for the oxidative step of the reaction of A -alkylacridinium salts with arylamines (Scheme 68). 

Thanks to this photocatalyst the Sn reaction can be performed in CH3CN at room temperature in the presence of air oxygen and a catalytic amount of Ti02 or CdS/ri02, provided the reaction mixture is irradiated with a daylight lamp. Also, it is worth noting that oxidation of intermediate dihydroacridines proceeds only in the presence of mineral acids, since the latter are involved into the catalytic oxidative... 

Scheme 68 A plausible catalytic cycle for oxidation of dihydroacridines...

An enantioselective a-alkylation of aldehydes (R-CH2CHO) gives a xanthenyl product (137, X = O) in up to 93% ee, using a simple organocatalyst (138) that activates the aldehyde via enamine catalysis, with subsequent addition of the stabilized benzyllc carbocation. This dehydrogenative alkylation uses dioxygen as oxidant and has been extended to the cases of thioxanthene and 10-methyl-9,10-dihydroacridine (i.e. 137, X = S and NMe). 29... 

Catalytic amounts of TEMPO are effective for the oxidative C-C coupling between 9,10-dihydroacridines with nitroalkanes, ketones, dimethylmalo-nate and malononitrile to afford coupling products 103 (Scheme 8.51). ... 

The same types of CDC reactions with a MacMillan catalysts 138 and 140 have been reported using anodic oxidation (Scheme 8.66) or aerobic oxidation (Scheme 8.67) to afford xanthenes, thioxanthenes and dihydroacridines bearing various aldehydes (139 and 141). The enantiomeric excesses (ee) of the coupling products in these reactions are not so high. 

Scheme 8.67 MacMillan catalyst- and aerobic oxidation-promoted CDC reactions of xanthene, thioxanthene and 10-methyl-9,10-dihydroacridine with various aldehydes.

Oxidative dehydrogenation with oxygen or air of N-heterocycles including dihydroacridine was developed using Pt nanowire catalyst and was performed under 1 bar of oxygen in methanol at 40 °C in quantitative yield (2013CCC2183). 

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