Hydroquinones quinone synthesis

Quinone synthesis. Two laboratories12 have found that the adducts formed by addition of an aryl-, alkynyl-, or heteroaryllithium to a cyclobutenedione rearrange when heated (138-160°) to hydroquinones, which are usually isolated as the quinone after air or chemical oxidation. The rearrangement involves an interme-... 

Hydroquinones — quinones [1, 533-534, at end]. The most convenient synthesis of 4,5-dimethoxy-o-benzoquinone (8) involves oxidation of catchol (7) with lead dioxide (Riedel-deHaen) in the presence of sodium methoxide.7a... 

The facile interconversion of hydroquinone and quinones make this methodology well suited for use in quinone synthesis. Researchers at Hoffmann-La Roche developed a synthesis of ubiquinones based upon Brownbridge and Chan s work (see above) [81]. Accordingly, trichloroethylene and furan... 

One of the most exciting discoveries related to quinone/hydroquinone chemistry is thek synthesis by biosynthetic routes (12,13). Using bacterial enzymes to convert D-glucose [50-99-7] (7) to either 1,2- or l,4-ben2enediol allows the use of renewable raw material to replace traditional petrochemicals. The promise of reduced dependence on caustic solutions and the use of transition-metal catalysts for thek synthesis are attractive in spite of the scientific and economic problems still to be solved. 

Encouraged by the short synthesis of K vitamins, the chromium-mediated benzannulation was extended to the synthesis of vitamin E 68 [59]. The problem of imperfect regioselectivity of alkyne incorporation - which did not hamper the approach to vitamin K due to the final oxidation to the quinone - was tackled by demethylation of both regioisomeric hydroquinone monomethyl ethers 67 to give the unprotected hydroquinone. Subsequent ring closure yielded a-tocopherol (vitamin E) 68 (Scheme 39). 

The synthesis of the second Stille coupling partner 34 was efficiently achieved in three steps. First, 2-bromojuglone (36) [28] was protected as its methoxymethyl ether (46, Scheme 3.7). The quinone was reduced using sodium thiosulfate, and the resulting hydroquinone was protected with methoxymethyl chloride to afford the arene 47. Finally, stannylation using tetrakis-(triphenylphosphine)palladium and hexabutylditin [29] afforded the cross-coupling partner 34 in high yield. 

A large number of studies have investigated the metabolism of benzene per se or in relation to toxification and, particularly, myelotoxicity. Most evidence shows that benzene oxide (10.1, Fig. 10.8) is not the ultimate toxic species, as was initially believed. Indeed, phenol and quinone metabolites of benzene are more active in forming adducts with macromolecular nucleophiles and eliciting cellular toxicity. For example, the efficacy of benzene metabolites (see Fig. 10.8) to inhibit DNA synthesis in a mouse lymphoma cell line decreased in the order benzoquinone (10.17) > hydroquinone (10.16)... 

The palladium(II)-mediated oxidative cyclization is also applied to the synthesis of carbazole-l,4-quinone alkaloids. The required arylamino-l,4-benzo-quinones are readily prepared by arylamine addition to the 1,4-benzoquinone and in situ reoxidation of the resulting hydroquinone [131]. 

On the other hand, hydroquinone (3 pmol/L) prevented the staurosporine-induced apoptosis of HL-60 and the IL-3-dependent murine myeloblastic (32D) cell line it also prevented apoptosis of the 32D cells observed in the absence of IL-3. The myeloperoxidase inhibitor indomethacin opposed the effect of hydroquinone on staurosporine-induced apoptosis of HL-60 cells (Hazel et al., 1995, 1996b). Pretreatment of human leukaemia cells ML-1 with buthionine sulfoximine (100 pmol/L for 24 h), in order to decrease their glutathione content, increased the susceptibility of these cells to hydroquinone-induced inhibition of differentiation caused by phorbol acetate pretreatment with l,2-dithiole-3-thione, which induces reduced glutathione synthesis, prevented the differentiation inhibition of hydroquinone. Treatment of DBA/2 mice with 1,2-dithiole-3-thione, which increased the activity of quinone reductase of bone-marrow stromal cells by 50%, decreased the susceptibility of these cells towards hydroquinone (Trush et al., 1996). 

Hydroquinone or Quinone Benzene Several Past pilot-plant Paired synthesis or anodic oxidation + chemical reduction... 

Under different reaction conditions, phenols can be oxidized to p-quinones (equations 272600-602 and 273603), but in the case of phenol itself, insufficient selectivity has prevented, as yet, the commercial application of this potentially important synthesis of p-benzoquinone and hydroquin-one. The selectivity of p-benzoquinone, or p-quinol formation can be increased at the expense of oxidative coupling products by using a large excess of the copper reagent [Cu4Cl402(MeCN)3 or CuCl + 02 in MeCN] with respect to the phenolic substrate.604 The suggested mechanism involves the oxidation of the phenoxide radical (189) by a copper(II)-hydroxo species to p-quinol (190) which can rearrange (for R2 = H) to hydroquinone (191 Scheme 14), which is readily oxidizable to p-quinone.6... 

A subsequent route by Joule and his collaborators846 made use of the primary alcohol (118) corresponding to (116). This was manipulated as shown, and cyclized to the quinone (119) before completion of the carbon skeleton, the cyclization stage being accompanied by spontaneous aerial oxidation of the initially formed hydroquinone derivative. Finally, the methyl groups were introduced by reaction with methyl-lithium, and the synthesis was completed by reduction (with NaBH4). 

All three types of reactions can also be used for the production of substituted quinones and hydroquinones. For example, BASF has developed two laboratory processes for the synthesis of trimethyl-p-benzoquinone and trimethylhydroquinone. The latter is required for the synthesis of vitamin E. 

AUylation of quinones.1 In the presence of BF3 etherate various allyl tribu-tyltins add to benzo- and naphthoquinones to form a mixture of the corresponding quinones or hydroquinones. An example is the synthesis of ubiquinone (2). 

Alkylation of quinones with organocadmium reagents allows the synthesis of quinol derivatives, without any formation of hydroquinones or bis-addition products (Equation (178)).315 The regiochemistry of the addition is strongly... 

In the studies of the synthesis of the ansamycin antibiotic rifamycin S (13S), Corey and Clark [76] found numerous attempts to effect the lactam closure of the linear precursor 132 to 134 uniformly unsuccessful under a variety of experimental conditions, e.g. via activated ester with imidazole and mixed benzoic anhydride. The crux of the problem was associated with the quinone system which so deactivates the amino group to prevent its attachment to mildly activated carboxylic derivatives. Cyclization was achieved after conversion of the quinone system to the hydroquinone system. Thus, as shown in Scheme 45, treatment of 132 with 10 equiv of isobutyl chloroformate and 1 eqtuv of triethylamine at 23 °C produced the corresponding mixed carbonic anhydride in 95% yield. The quinone C=C bond was reduced by hydrogenation with Lindlar catalyst at low temperature. A cold solution of the hydroquinone was added over 2 h to THF at 50 °C and stirred for an additional 12 h at the same temperature. Oxidation with aqueous potassium ferricyanide afforded the cyclic product 134 in 80% yield. Kishi and coworkers [73] gained a similar result by using mixed ethyl carbonic anhydride. 

Looker et al used a modification of the Bbs persulfate oxidation procedure in which tetraethyl-ammonium hydroxide was used as the base in their synthesis of S,8-4uinoflavone. The phenol (65) was oxidized to the hydroquinone, primetin (66), which upon further oxidation with LTA affwded S,8-flavo-quinone (67) in 34% overall yield (Scheme 24). 

Derivatives of phenol or aniline can be oxidized to quinones, the yield and ease of oxidation depending on the substituents. If an amino or hydroxyl group is in the para position, the reaction proceeds readily, as illustrated by the synthesis of quinone from hydroquinone by oxidation with a sodium chlorate-vanadium pentoxide mixture (5>6%) or with chromic-sulfuric acid mixture (92%). A para halogen atom usually has a favorable effect. Any group in the para position is eliminated or oxidized. o-Quinones are usually prepared from the corresponding catechols. A survey of procedures for the synthesis of benzoquinones by oxidation has been made. ... 

As mentioned above, treatment of the aldol adducts 150 a/b with NMO produced the phenol 152. The interesting oxidation properties of NMO had previously been investigated by Sulikowski et al. on the model compound 157 [85] (Scheme 40). They observed the formation of the hemiacetal 159 in 60% yield and assumed attack of the nucleophilic N-oxide on the quinonemethide tautomer 158 (or on the anion of 158). A related reaction was observed in our group in which the diol 94 was methoxylated at C-6 to 95 by treatment with methoxide ions [82] (Scheme 27). An internal redox step is postulated to account for the reductive 0-N-bond cleavage with concomitant oxidation of the hydroquinone back to the quinone. Without the presence of perruthenate, aromatization with formation of a C-5 phenolic hydroxy group was observed, a reaction later exploited in the synthesis of angucycline 104-2 [87] (see Scheme 49). Thus, based on similar mechanistic principles, the chemical results of the NMO oxidations were quite different compound 147 gave the C-6 phenol 152 [86] whereas 157/158 were converted to the C-5 phenol 160 [85]. 

One of the identified stimulators was the terpenoid strigol 31 (Scheme 1.9). In attempts to develop an efficient tool to eradicate the witchweed (by artificially provoking its growth prior to the growth of com), numerous efforts were dedicated to the synthesis of 31 and its analogs. Later studies disclosed the presence of another active compound in the exudate of Sorghum, the substituted hydroquinone 32. As is typical for hydroquinone derivatives, 32 was found to be quite amenable to oxidation to quinone 33, which occurs readily in the soil. 

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