Quinones reductive methylation

Reductive methylation of quinones.1 Dimethylarenes can be obtained in high yield by reaction of quinones with methyllithium (excess) in benzene to form a dimethyl dihydrodiol, which is reduced without purification with HI in refluxing acetic acid. 

By 1903, Emil Fischer had already appreciated that a proximate nucleophile can accelerate the rate of cleavage of an otherwise unreactive amide. Adaptation of such neighbouring group participation to relay deprotection is easy all that is required is a protecting group with a latent hydroxyl or amino function within easy bonding distance of the amide carbonyl, as illustrated in Scheme 8.27 by the reduction of the o-nitrophenylacetamide 27,1. The theme is capable of extensive variation. For example, 2-((/er/-butyldiphenylsilyloxy)methyl]benz-amides (27.2), 2-(acetoxymethyl)benzamides (273) and 3-methyl-3-(2,4,5-tri-methyl-3,6-dioxo-cycIohexa-l,4-dienyl) butyramides (27.4) all have latent hydroxyl nucleophiles that are released by silyl ether cleavage, ester hydrolysis and quinone reduction, respectively. 

Xanthones.—An efficient and convenient method of preparing xanthone in 99% yield is to heat o-phenoxybenzoic acid for 20 minutes at about 155 °C in molten sodium tetrachloroaluminate, obtained by fusing sodium chloride and aluminium chloride. Xanthones (283) were formed by cyclization of diphenyl ethers such as (282), which were prepared by addition of p-cresol to the quinone esters (281) followed by reductive methylation. ... 

Takamura, K. and Y. Hayakawa. 1968. Polarographic determination of acids by means of the reduction wave of quinones in methyl cellosolve solution. Anal. Chim. Acta 43 273-279. 

Radiolytic reduction reactions have been carried out on substrates such as quinones, benzophenone, methyl viologen, and nitroaromatic compounds. In [mtba] [TfjN], the principal reactions were reduction of the substrates by solvated electrons and organic radicals derived from the solvent For example, irradiation of benzoquinone (BQ) or duroquinone (DQ) resulted in the formation of the protonated semiquinone radical, with the proton formed by radiolysis of [mtba] [TfjN] (Equation 5.7). The addition of triethylamine to capture the protons resulted instead in the formation of the semiquinone radical anions (Equation 5.8). 

This derivative is prepared from an A-protected amino acid and the anthryl-methyl alcohol in the presence of DCC/hydroxybenzotriazole. It can also be prepared from 2-(bromomethyl)-9,10-anthraquinone (Cs2C03). It is stable to moderately acidic conditions (e.g., CF3COOH, 20°, 1 h HBr/HOAc, t,/, = 65 h HCI/CH2CI2, 20°, 1 h) Cleavage is effected by reduction of the quinone to the hydroquinone i in the latter, electron release from the -OH group of the hydro-quinone results in facile cleavage of the methylene-carboxylate bond. 

Porco s route to (—)-kinamycin C (3) began with 2,5-dihydroxybenzaldehyde (38), which was elaborated to the enone 35 by the sequence shown in Scheme 3.6. Regioselective bromination [25] followed by methylation and reduction of the aldehyde function afforded the primary alcohol 39. The alcohol 39 was dearomatized by treatment with bis(acetoxy)iodobenzene, to afford the quinone monoketal 41. Transketalization with 1,3-propanediol followed by silylation of the primary alcohol generated the silyl ether 42 in 72 % yield over three steps. 

Although phenanthrene is noncarcinogenic, some of its methylated derivatives exhibit significant activity as mutagens (52,53). The 1,2- and 3,4-dihydrodiols of phenanthrene were first synthesized by Jerina et al. (54) by a method involving reduction of the corresponding quinones with LiAlH. However, the yields in the rein Polycyclic Hydrocarbons and Carcinogenesis Harvey, R. ... 

Syntheses of the 1,2- and 7,8-dihydrodiols of 5-MC have been described (60,87,103). The 1,2-dihydrodiol (30a) is most efficiently prepared from l-hydroxy-5-MC (29a) by Method IV (87), with the difference that an a-phenol is employed rather than a 8-phenol as in previous examples. Oxidation of 29a with (KSO NO furnished a single isomeric quinone identified as 5-MC 1,2-aione (Figure 18). Formation of an ortho rather than a para quinone in the oxidation of an a-phenol with Fremy s reagent is unusual. Apparently the bay region methyl group serves to sterically block oxidative attack in the adjacent bay region site. Reduction of 5-MC 1,2-dione with NaBH in ethanol gave 5-MC 1,2-dihydrodiol. 

Addition of the arylamines 117 to 2-methoxy-3-methyl-l,4-benzoquinone 118 affords regioselectively the 5-arylamino-2-methoxy-3-methyl-l,4-benzo-quinones 119 (Scheme 37). Palladium(II)-catalyzed oxidative cyclization leads to the carbazole-l,4-quinones 28 [135,136],previously obtained by the iron-mediated approach (cf. Scheme 14). Regioselective addition of methyllithium to the quinones 28 provides carbazomycin G 29a and carbazomycin H 29b [96,135]. Reduction of 29a with lithium aluminum hydride followed by elimination of water on workup generates carbazomycin B 23a [135]. Addition of heptylmag-... 

Further reduction of quinones - acquisition of four or more hydrogens per molecule - was achieved with lithium aluminum hydride which reduced, in yields lower than 10%, 2-methyl-1,4-naphthoquinone to 1,2,3,4-tetrahydro-l,4-dihydroxy-2-methylnaphthalene and to l,2,3,4-tetrahydro-4-hydroxy-l-keto-2-methylnaphthalene [931]. Lithium aluminum hydride [931], sodium borohydride, lithium trie thy Iborohydride and 9-borabicyclo[3.3.1Jnomine [100] converted anthraquinone to 9,10-dihydro-9,10-dihydroxyanthracene in respective yields of 67, 65, 77 and 79%. 

The three-step sequence used to convert enone 65 to miltirone (56) is shown in Scheme 5.7 and consists of, first, a Wolff-Kishner reduction to convert the C(5) carbonyl moiety into a methylene, followed by deprotection of the aryl methyl ethers and oxidation to an ortho-quinone using ceric ammonium nitrate. The physical and spectroscopic data of our synthetic miltirone are identical with those reported for the natural material. 

C10H14Oj) C,H. An alternate route leading from 2,3-xylenol to this diether via nitrogen-containing intermediates was explored. The sequence involved the reaction of 2,3-xylenol with nitrous acid (4-nitroso product, mp 184 °C dec.), reduction with sodium dithionite (4-amino product, mp about 175 °C), oxidation with nitric acid (benzoquinone, mp 5 8 °C), reduction with sodium dithionite (hydro-quinone) and final methylation with methyl iodide. The yields were inferior with this process. 

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