Anthrone synthesis

Metalation of N-phenyl-m-anisamide anthrone synthesis. A new anthrone synthesis involves metalation of 1 with 2 equiv. of n-BuLi and TMEDA in THF ( — 78 to —10°). The dianion 2 condenses with the aldehyde 3 to form the phtha-lide 4, which is converted into the anthrone 7 by classical reactions. This route is valuable for synthesis of unsymmetrical anthraquinones. ... 

This aldehyde synthesis is applicable to compounds of the aromatic series having a labile hydrogen atom (phenyl ethers,1 naphthols,2 dialkylanilines,3-4 naphthostyril,2 anthrones 2) and to certain hydrocarbons of requisite reactivity (anthracene,5-6 7 1,2-benzanthracene,6 3,4-benzpyrene,3 7 pyrene,8 styrene,9 and a, a-diarylethylenes 9). With polynuclear hydrocarbons the best results are secured by the use of a solvent such as o-dichloro-benzene. 9-Anthraldehyde has also been prepared by the action of hydrogen cyanide and aluminum chloride on anthracene in chlorobenzene.10... 

Regiospecific mono-C-alkylation (60-90%) of trimethylsilyl enol ethers is promoted by benzyltriethylammonium fluoride [34, 35]. A similar alkylation of tin(IV) enolates is aided by stoichiometric amount of tetra-n-butylammonium bromide and has been utilized in the synthesis of y-iminoketones [36]. Carbanions from weakly acidic carbon acids can be generated by the reaction of their trimethylsilyl derivatives with tetra-n-butylammonium triphenyldifluorosilicate [37] (see also Section 6.3). Such carbanions react readily with haloalkanes. Tautomeric ketones in which the enol form has a high degree of stabilization are O-alkylated to form the enol ether, e.g. methylation of anthrone produces 9-methoxyanthracene [26],... 

The hrst step in the preparation of the antidepressant maprotiline (33-5) takes advantage of the acidity of anthrone protons for incorporation of the side chain. Thus treatment of (30-1) with ethyl acrylate and a relatively mild base leads to the Michael adduct saponihcation of the ester group gives the corresponding acid (33-1). The ketone group is then reduced by means of zinc and ammonium hydroxide. Dehydration of the hrst-formed alcohol under acidic conditions leads to the formation of fully aromatic anthracene (33-2). Diels-Alder addition of ethylene under high pressure leads to the addition across the 9,10 positions and the formation of the central 2,2,2-bicyclooctyl moiety (33-3). The hnal steps involve the construction of the typical antidepressant side chain. The acid in (33-3) is thus converted to an acid chloride and that function reacted with methylamine to form the amide (33-4). Reduction to a secondary amine completes the synthesis of (33-5) [33]. 

Preparation of nearly all important anthraquinones starts from the following key intermediates anthraquinonesulfonic acids, nitroanthraquinones, and the products of nucleus synthesis, 1,4-dihydroxy-, 2-methyl-, and 2-chloroanthraquinone. The only exceptions are derivatives with condensed rings, e.g., benzan-throne and derived products, which are prepared directly from anthraquinone via anthrone. 

The reactivity and selectivity of cycloaddition can be considerably increased in intramolecular versions. The protocol was first demonstrated in the Diels-Alder reaction between anthrone 253416,417 and 4-hydroxy-2-butenoate mediated by phenylboronic acid (Equation (73)).418,419 Another method developed for the intramolecular cycloaddition is the synthesis of trienylboranes 256 by hydroboration of terminal alkynes (Equation (74)).419-422... 

This benzannelation provides the key step in a synthesis of the anthracycline 5. Thus reaction of the complex 2 with the acetylene 3 provides, after oxidation, the tetrahy-dronaphthol 4. The fourth ring of 5 is formed by ring closure to an anthrone followed by air oxidation (Triton B) to an anthraquinone. ... 

Anthraquinone dyes, 1, 331-332 Anthra[ 1,2-c][ 1,2,5]selenadiazole-6,11 -dione X-ray crystal structure, 6, 516 Anthra[2,3-6]thiophenes synthesis, 4, 905 Anthrazoline polymers, 1, 297 Anthrone, pyrazolo-, 1, 320 Anthrones, 1, 336-337... 

Applequist and Searle, seeking a synthesis of 9-fluoroanthracene, heated anthrone with sulfur tetrafluoride and hydrogen fluoride in methylene chloride for 16.3 hrs. at 69° but, surprisingly, obtained 10,10-difluoranthrone in high yield. 

The second product identified by Meyer, oxanthrone acetate (5, better 10-acetoxy-9-anthrone), was obtained in moderate amount by oxidation of 9-acetoxy-anthracene (3) with lead tetraacetate in acetic acid. Oxidation of (3) in refluxing benzene resulted in 1,4-addition to give the triacetoxy compound (4). This substance when heated in acetic acid is converted largely into lO-acetoxy-9-anthrone (5) by loss of acetic anhydride and to a lesser extent into 9,10-diacetoxyanthracene (7) by loss of acetic acid. If (4) is an intermediate in the oxidation of (3) in acetic acid lo (5), the acetoxy group in the product (5) must be attached to a different meso carbon atom (5) than in (3), and this inference was shown to be correct by oxidation of 2-methyl-9-acetoxyanthracene and identification of the product as 2-methyl-I O-acetoxy-9-anthrone by synthesis. Both (5) and (7) on further oxidation with lead tetraacetate in acetic acid yield anthraquinone, probably via the products of acetoxylation of (5) and 1,4-addition to (7). 

Figure 4. AF pathway FASs and their role in formation of norsolorinic acid anthrone. A. Domain structure of the FASs, HexA and HexB. B. Proposed complex formation for the initial steps in AF biosynthesis. Steps include hading of the HexA/HexB complex, synthesis of hexanpyl CoA, transfer ofhexanoylCoA to PksA, and iterative condensation to form the anthrone.

Yamaguchi has reported a related biomimetic synthesis of anthraquinones, summarized in Scheme Reaction of diester (165) with methyl acetoacetate dianion provides a tetraketo diester which is cy-clized by calcium hydroxide to obtain anthrone (166). Air oxidation in basic medium affords the anthra-quinone (167). 

Many of the more recent applications of intramolecular Friedel-Crafts acylation reactions have involved the synthesis of biologically active tetracycline derivatives. In the synthesis of aclacinomycin- the acid shown in equation (42) was cyclized efficiently to the anthrone using trifluoroacetic anhydride in dichloromethane and then converted immediately into the anthraquinone shown. 

Little is known about the biosynthetic origin of hypericin(s) they are related to the anthranoid metabolism and emodin anthrone is possibly their precursor. Synthesis in vitro of hypericin following alkaline dimerization of emodin and oxidation of its reduction derivative, emodine anthrone, has in fact been demonstrated [35,36]. 

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