Naphthoquinone, addition

Nucleophilic Substitution Reactions. Many of the transformations reali2ed through Michael additions to quiaones can also be achieved usiag nucleophilic substitution chemistry. In some iastances the stereoselectivity can be markedly improved ia this fashion (100), eg, ia the reaction of ben2enethiol with esters (R = CH C O) and ethers (R = 3) 1,4-naphthoquiaones. 2-Bromo-5-acetyloxy-l,4-naphthoquiQone [77189-69-6J, R = Br, yields 75% of 2-thiophenyl-5-acetyloxy-l,4-naphthoquinone [71700-93-1], R = SC H. 3-Bromo-5-methoxy-1,4-naphthoquinone [69833-10-9], R = Br, yields 82% of 3-thiophenyl-5-methoxy-l,4-naphthoquinone [112740-62-2] R = SC H. ... 

Alkannin occurs in the roots of the plant as the alkah-sensitive ester of angelic acid (62). It may be extracted from the roots by using boiling light petroleum ether. Treatment of this extract with dilute sodium hydroxide gives a blue solution from which the dye is precipitated by the addition of acid. The cmde product is purified by vacuum sublimation (63). Its stmcture (11) is a hydroxylated naphthoquinone with a long, unsaturated side chain (64,65) it has the (3)-configuration. 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

A) -Naphthoquinone.—For the best results this preparation must be carried out rapidly. The vessels and reagents required should be made ready in advance. The oxidizing solution is prepared by dissolving 240 g. (0.89 mole) of ferric chloride hexahydrate in a mixture of go cc. of concentrated hydrochloric acid and 200 cc. of water with heating, cooling to room temperature by the addition of 200-300 g. of ice, and filtering the solution by suction. 

In his pioneering work, Sus (1944) assumed that the final product of photodediazoniation of 2,1-diazonaphthoquinone (10.75) is indene-l-carboxylic acid (10.79, not the 3-isomer 10.78). He came to this conclusion on the basis of some analogies (in addition to an elemental analysis). Cope et al. (1956) as well as Yates and Robb (1957) found that the infrared spectrum of the product was consistent with an a,P-unsaturated acid. Later, Melera et al. (1974) verified the structure 10.78 by H NMR spectroscopy. Friedrich and Taggart (1975) showed that the equilibrium between 10.78 and 10.79 at 233 K lies on the side of the latter, but 10.78 clearly predominates at or above 0°C. Ponomareva et al. (1980) showed that not only 2,1-, but also 1,2-diazo-naphthoquinone yields indene-3- and not -1-carboxylic acid. 

An interesting suggestion was made by Levine in 1969. He supposed that the ketene formed photolytically from 1,2-naphthoquinone diazide could react with unreacted 1,2-naphthoquinone diazide to form a spirolactone-type addition product. This suggestion was tested experimentally almost twenty years later by Huang and Gu (1988). They irradiated 1,2-naphthoquinone diazide in dioxane in the presence of pyrene as sensitizer with a high-pressure mercury vapor lamp (Scheme 10-103). They did indeed obtain the spirolactonespiro(naphtho[4,5 2/,l/]furano-2-one)-3 T -inde-... 

In addition to the oxidation-reduction potentials data, two sets of infrared carbonyl stretching frequencies were correlated with eqs. (2) and (30). Of these, one set, Pqq for 2-substituted 1,4-naphthoquinones, gave significant results, with Pr of about 50. While the other set did not give significant correlation, it contained only four points. Although the sharp difference between pr for vqq and pR for Ep correlations of 2-substituted 1,4-naphthoquinones is worthy of note, it should not be discussed until it is confirmed by further work. 

Effects of Allelochemlcals on ATPases. Several flavonoid compounds inhibit ATPase activity that is associated with mineral absorption. Phloretin and quercetin (100 pM) inhibited the plasma membrane ATPase Isolated from oat roots (33). The naphthoquinone juglone was inhibitory also. However, neither ferulic acid nor salicylic acid inhibited the ATPase. Additional research has shown that even at 10 mM salicylic acid inhibits ATPase activity only 10-15% (49). This lack of activity by salicylic acid was substantiated with the plasma membrane ATPase Isolated from Neurospora crassa (50) however, the flavonols fisetln, morin, myricetin, quercetin, and rutin were inhibitory to the Neurospora ATPase. Flavonoids inhibited the transport ATPases of several animal systems also (51-53). Thus, it appears that flavonoids but not phenolic acids might affect mineral transport by inhibiting ATPase enzymes. 

It was found that treatment of a mixture of 120 and 121 with tris(diethylamino-sulfonium) trimethyldifluorosilicate [TASF(Et)] resulted in smooth addition-elimination to the naphthoquinone to form the y-alkylation product 125 (85 %). TASF(Et) is a convenient source of soluble, anhydrous fluoride ion [47]. It is believed that exposure of 121 to TASF(Et) results in fluoride transfer to generate a hypervalent silicate anion, as depicted in structure 124. The transfer of fluoride between TASF(Et) and 121 may be driven by stabilization of the anionic species 124 by delocalization of the carbon-silicon bond into the LUMO of the unsaturated ketone. 1,4-Addition-elimination of this species to the naphthoquinone 120 would then form the observed product. 

Compounds 4-diazenylbenzosulfonate (13) and 1,2-naphthoquinone were not detected by HPLC under the catalytic conditions. The quinone was not detected because under these conditions 1,2-naphthoquinone is rapidly oxidized into phthalic acid plus two additional products just by H202 without participation of 1. 4-Diazenylbenzosulfonate 13 should be... 

Whereas for the hexamethyl compound 150 only products formed by the linear route have been detected with a sizeable number of dienophiles (X=X inter alia TCNE, maleic anhydride, benzoquinone, 1,4-naphthoquinone, acrolein, methyl acrylate102), the parent system 4 undergoes threefold Diels-Alder addition in a star-shaped manner leading to 164 with dimethyl acetylenedicarboxylate and to 165 with fumaroyl chloride followed by methanolysis (equation 20)92. 

Michael addition of di- and tri-hydric phenols to /V-cinnamoylimidazoles followed by a lactonisation offers a route to 4-aryI-3,4-dihydrocoumarins and their [/]-benzologues <00S123>. The lactonisation of the naphthoquinone derivative 66 is sensitive to the acidic cyclising medium and it is possible to obtain the thermodynamically less stable o-quinone derivative exclusively (Scheme 44) <00TL3007>. Some related quinones have been obtained from 1-benzylisoquinolines via an arylnaphthoquinone <00T6O23>. 

Compounds showing vitamin K activity are substituted naphthoquinones. The parent compound, 2-methyl-1,4-naphthoquinone, does show some biological activity as do other similar but synthetic compounds. The production of the complete naturally active forms is thought to depend upon the addition of an isoprene chain at position 3 on the aromatic ring. Differences in this side chain produce the various K vitamins (Figure 12.10). A most important physiological role of vitamin K is in the synthesis of the blood clotting factors, II (prothrombin), VII, IX and X. 

Ethyl (6-Methoxy-l,2-naphthoquinonyl-6) Cyanoacetate. The above naphthoquinone (21.7 g) is added to a solution of 500 cc of ethanol and 14 cc of ethyl cyanoacetate, followed by the addition of 32 cc triethylamine. A deep purple color will develop and the mixture should be swirled for 4 min to dissolve the quinone completely. A solution of 75.9 g of potassium ferricyanide in 320 cc of water is then added to the solution, causing a thick dark complex to form and separate. Redissolve by adding a soluhon of 24 g of sodium carbonate in 1,600 cc of water. Swirl or stir and filter through diatomaceous filter aid. Acidify the filtrate with 100 cc of 6 M sulfuric acid to precipitate 34.8 g of red-orange powder, which is oven dried at 70°. Reciystallize from ethyl acetate to get 19.3 g, mp 157-158.5°. The remaining filtrate is evaporated to a small bulk and reciystallization from ethyl acetate gives an additional 2.8 g of product. 

Rueping has further developed this theme by showing that diarylprolinol ether 55 efficiently catalyses the addition of hydroxyquinones to a variety of a,P-unsatu-rated aldehydes as a method for the preparation of both 1,4- and 1,2-naphthoquinones with remarkable levels of enantioselectivity [98],... 

A. Liposomal amphotericin B was approved by the US. Food and Drug Administration to treat visceral leishmaniasis. Pentavalent antimony compounds, pentamidine, amphotericin B, and aminosi-dine (paromomycin) have all been demonstrated efficacious here. The liposomal amphotericin appears to be better taken up by the reticuloendothelial system, where the parasite resides, and partitions less in the kidney, where amphotericin B traditionally manifests its toxicity. In addition to being better tolerated by patients, it has proved to be very effective in India, where resistance to antimony drugs is widespread. This patient appears to have acquired his infection there, where many infected patients develop darkening of the skin, hence the name kala-azar, or black sickness. Albendazole, an anthelmintic, has no role here. Atovaquone, a naphthoquinone, is used to treat malaria, babesiosis, and pneumocystosis. Pyrimethamine-sulfadoxine is used to treat malaria and toxoplasmosis. Proguanil inhibits the dihydrofolate reductase of malaria parasites and is used in combination with atovaquone. 

A -Sulfonyl-2,2 -biindoles undergo a formal [4-I-2] cycloaddition with various dienophiles to produce indolocarba-zoles <2004TL4009>. Thus, reaction of 171 with A -benzylmaleimide in chlorobenzene in a sealed tube produces the cycloadduct in moderate yield (Equation 105) as the only observable product (Table 11). It is proposed that the reaction proceeds by an initial Michael addition, followed by a rapid cyclization and loss of the phenylsulfonyl group during the aromatization process. Similar cyclization reactions are observed with A -methylmaleimide, dimethylace-tylene dicarboxylate, and 1,4-naphthoquinone. 

The solid state photochemical reaction of indole with 1,4-naphthoquinone yielded 5H-dinaphtho(2,3-a 2, 3 -c)carbazole-6,ll,12,17-tetrone in addition to 2-(3-indolyl)-1,4-naphthoquinone which was also the only product in the solution photoreaction. Solventless thermochemical reactions of indole with phenanthrenequinone in the presence or absence of zinc chloride gave 10-(lH-indol-3-yl)-9-phenanthrenol and 9,10-dihydro-9-(lH-indol-3-yl)-10-(3H-indol-3-ylidene)-9-phenanthrenol or 10,10-di-lH-indol-3-yl-9(10H)-phenanthrenone, respectively. All of these products were only obtained in trace amounts in corresponding solution reactions, and are different from the adduct 10-hydroxy-10-(lH-indol-3-yl)-9(10H)-phenanthrenone obtained in the solution photoreaction (Wang et al., 1998). 

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