Anthraquinone from naphthoquinone

Intensive efforts have also been made to find an electrochemical process for the synthesis of 1,4-naphthoquinone starting from naphthalene. The aim of this work is to develop a new process for the production of anthraquinone from 1,4-naphthoquinone and butadiene. 

Fig. 6.17. Localization of label from shikimic acid in anthraquinones and naphthoquinones of Rubia tinctoria (modified from Haslam, 1974).

Anthraquinones and naphthoquinones are not exclusively formed via the polyketide biosynthetic route. They can also be derived from the shikimate pathway, e.g., the allelopathic naphthoquinone juglone from the walnut tree Juglans regia) and the anthraquinone alizarin from madder root Rubia tinctorium), which was used as purple dye. 

Styrene derivatives are commonly used addends in the photocycloaddition studies of 1,4-quinones. With Z- and -anethole, 1,4-benzoquinone (BQ), 1,4-naphthoquinone (NQ), and 9,10-anthraquinone in acetonitrile solvent yield spiro-oxetanes in which the trans-isomer (e.g., 4 from naphthoquinone) predominates. The process has been studied in detail by CIDNP techniques from which it is deduced that product formation proceeds from triplet radical ion pairs to the triplet biradical, and that there is no significant contribution from direct conversion of exciplex intermediates into the biradicals. Spiro-oxetane formation between simple alkenes and BQ generally has low regioselectivity but this is markedly improved with alkylidene cyclohexanes (Figure 87.3) such that the major isomer can be used as a new access to useful synthetic building blocks. For the BQ/homobenzvalene 5 system, however, where the difference in stability between the intermediate biradicals can be expected to be considerably less, the selectivity ratio for the spiro-oxetanes 6 and 7 is reduced to 3 1, respectively, and the addition to NQ yields only the cyclobutane derivative 8. Quadricyclane and norbornadiene undergo the same photocycloaddition reaction to BQ, affording the oxolane 9 and the spiro-oxetane 10. Evidence from CIDNP... 

Sequential applications of these methods yield naturally occurring anthraquinones, eg, macrosporin [22225-67-8] (86) in 83% yield from 2-chloro-6-methyl-7-hydroxy-l,4-naphthoquinone [76665-67-3] (87), which is produced in 78% yield from (26) (84). 

Anthraquinone is widely use in the manufacture of a range of dyes. Two possible routes for manufacturing anthraquinone are (1) from the reaction of 1,4-naphthoquinone with butadiene and (2) reaction of benzene with phthalic anhydride. Describe mechanisms for both these reactions and identify likely reaction conditions and any other reagents required. Compare the atom economy of the two routes. Identify three factors for each route that may influence the commercial viability. 

The 13C NMR spectral data for 9, 16, and 17 are shown in Table 2. The chemical shifts of carbonyl carbons of anthraquinones are characteristically observed at about 180 ppm.9 The chemical shifts for carbonyl carbons of 1,4-naphthoquinone and 1,4-benzoquinone appear at about 185 ppm, while those of carbonyl carbons adjacent to a methylene or methyl carbon are at about 200 ppm. The chemical shifts of the Cl and C4 of 9 are observed at 200.8 ppm and assigned to the 1,4-diketo form 9a. In the 13C spectrum of 17, the chemical shifts of carbonyl carbons are at 199.9 and 172.2 ppm. The former value corresponds to a carbonyl carbon adjacent to the methylene carbon, and the latter corresponds to the carbonyl carbon in the 9-position. The methylene carbons of 17 show two signals at 34.5 and 23.8ppm. From these results, 17 is considered to exist exclusively as an unsymmetrical 4,9-diketo form, 17a. Thus, these NMR spectral data suggest... 

The phytochemical reducibility of quinones was first demonstrated in the case of p-xyloquinone. This compound is worthy of interest since it is very easily formed from diacetyl by purely chemical means through a type of aldol condensation followed by ring closure. It is reduced to p-xylohydroquinone by fermenting yeast. Benzoquinone, thymoquinone and a-naphthoquinone similarly yield the corresponding hydroquinones. Tetrabromo-o-quinone and anthraquinone proved resistant to attack, while phenanthraquinone could be reduced phyto-chemically to phenanthrahydroquinone in poor yield (9%). Phytochemical reduction can also be accomplished in the dicyclic terpene series. According to unpublished experiments by Neuberg and Peiser, 2,3-dihy-... 

Both naphthoquinones and anthraquinones bearing annulated benzothiazine rings, as illustrated by compounds (4.16), (4.17) and (4.18), absorb in the near-lR. Unfortunately, the naphthoquinones tend to have low stability and products from both ring systems are strongly coloured, limiting their areas of application. 

Anthraquinones. A regioselective synthesis of polyhydroxyanthraquinones is based on Dicls-Alder reactions of I with chloro-substituted naphthoquinones. An example is the synthesis of 1,6-dihydroxyanthraquinone (3) from 3-chlorojuglone (2). Analogous syntheses arc possible by use of vinylogous kctcnc acetals related to I. 

The simplest quinones are o- and p-benzoquinone [(3) and (4) respectively]. This quinonoid structural feature is widespread in naturally occurring compounds isolated from moulds, fungi, lichens, plants and insects,52 which include not only substituted benzoquinones but also substituted polycyclic quinones [i.e. the substituted analogues of, for example, 1,2-naphthoquinone (5), 9,10-anthraquinone (6), and 9,10-phenanthraquinone (7)]. 

Quinones of the more reactive, polycyclic, aromatic systems can usually be obtained by direct oxidation, which is best carried out with chromium(vi) compounds under acidic conditions. In this way 1,4-naphthoquinone, 9,10-anthraquinone and 9,10-phenanthraquinone are prepared from naphthalene, anthracene and phenanthrene respectively (Expt 6.128). Also included in this section is the reduction of anthraquinone with tin and acid to give anthrone, probably by the sequence of steps formulated below. 

Several synthetic compounds containing the naphthoquinone skeleton, such as 2-(4-cyclohexylcyclohexyl)-3-hydroxy- 1,4-naphthoquinone [169], are effective in the treatment of coccidial infection. Two structurally related antibiotics WS-5995A (36) and WS-5995B (37a), isolated from S. auranticolor sp. nov. near Tokyo, efficiently protect Eimeria tenella (a species of coccidia) infection. An inactive component WS-5995C (37b) can be readily converted to the active (36) by simple dehydration [ 170-172]. Compound (36), the structure of which resembles the aforementioned benz[a]anthraquinone antibiotics, is the first example of a 5//-benzo[d ]naphtho[ 2,3-6 ]pyran ring system found in nature. 

From about 1930 onwards, developments in the field of naphthoquinone dyes concentrated on the use of naphthazarin and intermediates for the preparation of violet, blue, and green acid and disperse dyes [1]. More recently there has been interest in the synthesis and color and constitution properties of simple colored naphthoquinones, stimulated by the fact that such dyes have similar tinctorial properties to the anthraquinones but a smaller molecular size. The naphthoquinones provide a useful alternative to the anthraquinones for certain specialized applications, e g., as pleochroic dyes with improved solubility for liquid-crystal displays. As a result, research interest in these chromogens remains unabated, even though they have failed to make any major impact as textile dyes [2-8],... 

Eleven 9,10-anthraquinones with various substituents, seven 1,4-naphthoquinones, 1,2-naphthaquinone and five 1,4-benzoquinones were used as QA. These quinones provide a series of RCs with a variation of the reaction exothermicity, - AG , from 0.11 to 0.9 eV. The rates of intraprotein electron transfer from various Qa to (BChl)J were found to be virtually temperature independent from 5 to 100 K and to decrease severalfold from 100 to 300 K. Only a small change of the rate upon the — AG° variation was found when reaction was made more exothermic than in the native RC. As the reaction was made less exothermic, the rate decreased notably without becoming temperature dependent. 

Although 2-hydroxy-5-tcrt-butylazobenzene (29) exists as a true azo compound, annelation of the benzene ring results in 1,2-naphthoquinone 1-phenylhydrazone (35, R = H) and 1,2-naphthoquinone 2-phenylhydrazone (34, R = H) being in a prevailing tautomeric form in compounds derived from 1-naphthol and 2-naphthol. 4-Hydroxyazobenzene (32) and l-hydroxy-4-phenylazonaphthalene (36, R = H) exist in DMSO as true azo compounds. Next step in annelation of the benzene ring in the passive component led to anthracene derivatives. These compounds exist almost completely in hydrazone tautomeric forms (>95%) irrespective of the fact they were formally derived from 1-hydroxyanthraquinone or 2-hydroxyanthraquinone.50 15N chemical shifts show nicely the dramatic changes for compounds 32, 36, (R = H) and 1,4-anthraquinone phenylhydrazone (44). 

Binapthoquinones include the phototoxic phytotoxin cercosporin from the fungus Cercospora (two Phe Q moieties linked by two Phe—Phe links and an MD link). Hypericin (two anthraquinones linked by three Phe—Phe linkages) is a bianthraquinone from Hypericum species (Hypericaceae). Hypericin is a phototoxic protein kinase inhibitor that causes light-dependent ovine facial eczema. Benzonaphthoquinones include the der-matitic cypripedin (Phe Phe QJ. Lichen 7-chloroemodin is a novel chloroanthraquinone and the fused tricyclic pyrano-a-naphthoquinone (3-lapachone (Phe oQJ C50) is a reverse transcriptase inhibitor with antimicrobial and cytotoxic activity. 

Gordon and Danishefsky [112] used the reaction of a chromium Fischer car-bene complex 164 with a cycloalkine 163 to build the naphthoquinone core 165 (Dotz reaction, review [113]), a procedure often used for synthesis of the linearly condensed anthracyclinones (e.g., [114]). The quinone ketone 165 has nucleophilic and electrophilic centers correctly positioned to furnish a ben-zo[fl]anthraquinone. However, treatment with NaH or Triton B gave the spiro-compounds 166 as a mixture of two stereoisomers. These products evidently arose from Michael addition of the ketone enolate to the naphthoquinone double bond. But the weaker base DBU induced cyclization at ambient temperature to the benzo[a]anthraquinone 167 in 65% yield (Scheme 42). The primary aldol adduct apparently eliminated water and the resulting dihydrobenzo[a]anthraquinone aromatized under basic conditions in the presence of air. This is an instructive example of the influence of the base on the cyclization mode. 

The Diels-Alder reaction of the exocyclic diene derivative 920 obtained from 919, with 1,4-naphthoquinone, gave 921 and thus allowed a further functionalization of this molecule by another anthraquinone moiety (Scheme 139) <1999CG2433>. 

---