Organic compounds -- part of the class 532-570 series – Organic compounds – Polycyclo ring system containing anthracene configured ring...
Patent
1998-10-02
2000-05-02
Dees, Jose' G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Polycyclo ring system containing anthracene configured ring...
552265, 552266, 552268, C07C 49593, C07C 5018, C07C 4600
Patent
active
060574615
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a novel process for the preparation of substituted anthraquinones from 1,4-naphthoquinones and to the application of the products obtained as intermediates in the synthesis of products exhibiting therapeutically useful properties.
The preparation of anthraquinones, such as chrysophanol, by addition of 6-methoxy-4-methylpyrone to a naphthoquinone such as juglone, according to the Diels-Alder reaction, has been described by M. E. Jung et al., J.C.S. Chem. Comm., 95 (1978). However, this process requires several stages, that is to say an addition, followed by an oxidation with silver oxide, to cause aromatization of the rings, and a demethylation. Furthermore, the reaction involves the use of diazomethane, which has well known disadvantages.
Patent GB-A-2,190,080 discloses a process for the preparation of anthraquinones by the reaction of a butadiene derivative with a naphthoquinone in the presence of a catalyst based on a transition metal but this process has to be carried out in a chamber kept under high pressure.
The routes for the synthesis of anthracyclinones by a Diels-Alder cycloaddition reaction have also been described by M. Petrzilka and J. I. Grayson [Synthesis, 753 (1981)]. According to these authors, the regiospecific addition reaction of a diene to a quinone can be produced by using, as catalyst, a Lewis acid consisting of the compound BF.sub.3 .multidot.O(C.sub.2 H.sub.5).sub.2.
The process according to the present invention makes it possible to prepare substituted anthraquinones represented by the general formula (I) hereinbelow: ##STR3## from 1,4-naphthoquinones in only two stages and with an excellent yield.
In the general formula (I) hereinabove, R represents a hydrogen atom or a linear or branched alkyl group comprising 1 to 5 carbon atoms, a chloromethyl group, a --COCl group, a --COOR' group or a --CH.sub.2 OR' group where R' is a hydrogen atom or a linear or branched alkyl group comprising 1 to 5 carbon atoms, R.sub.1 represents a hydrogen atom, a hydroxyl group, a linear or branched alkoxy group comprising 1 to 5 carbon atoms or an acyloxy group comprising 1 to 5 carbon atoms and R.sub.2 represents a hydrogen atom. If appropriate, an acetylation can be carried out in order to obtain the compound of formula (I) where R.sub.2 is an acetyl group.
In accordance with the process according to the invention, in a first step, a Diels-Alder reaction is carried out between a 1,4-naphthoquinone of general formula (II): ##STR4## in which R.sub.1 represents a hydrogen atom, a hydroxyl group, a linear or branched alkoxy group comprising 1 to 5 carbon atoms or an acyloxy group comprising 1 to 5 carbon atoms and X represents a hydrogen or halogen atom,
and an acyclic diene of general formula (III): comprising 1 to 5 carbon atoms, a chloromethyl group, a --COCl group, a --COOR' group or a --CH.sub.2 OR' group where R' is a hydrogen atom or a linear or branched alkyl group comprising 1 to 5 carbon atoms and R.sub.3 represents a silyl group of formula --Si(R.sub.4).sub.3 where R.sub.4 is a linear or branched alkyl group comprising 1 to 5 carbon atoms,
in order to obtain a substituted 1, 1a, 4, 4a-tetrahydroanthraquinone [sic] of general formula (IV): ##STR5## in which R, R.sub.1 and R.sub.3 have the definitions indicated hereinabove,
and then an oxidizing deprotection reaction is carried out, by means of the Jones reagent, on the tetrahydroanthraquinone of general formula (IV), in order to obtain the desired anthraquinone, represented by the general formula (I) shown hereinabove.
The oxidizing deprotection reaction is preferably carried out by reaction with a mixture of potassium dichromate and aqueous sulfuric acid in a solvent, such as acetic acid, ethyl ether, dimethyl sulfoxide or dichloromethane, in the presence of a phase transfer agent, such as a quaternary ammonium salt, or alternatively a ketone and preferably acetone.
In the above formula (II) representing the starting naphthoquinone, R.sub.1 preferably represents a hydroxyl or acetoxy group and X is preferably
REFERENCES:
patent: 5723675 (1998-03-01), Joo et al.
M.E. Jung et al., J.C.S. Chem. Comm., pp. 95-96, 1978.
Petrzilka and J.I. Grayson, Synthesis, pp. 753-760, 1981.
G. Jesaitis et a., J. Chem Ed., 49, pp. 436-437, 1972.
T. Watamatsu et al., Synthetic Communications, 14, pp. 1167-1173, 1984.
Krohn, Leibigs Ann. Chem., 1981, pp. 2285-2297 (Abstract Only).
Krohn et al., Tetrahedron, vol. 40, No. 19, pp. 3677-3694.
Thomas et al., J. Org. Chem. vol. 53, No. 18, pp. 4201-4209.
Database WPI XP 002008450.
Boisvert et al., Regiospecific Addition of Monooxygenated Dienes to Halo Quinones, J. Org. Chem., 53,4052-59, 1988.
Kraus et al., A Formal Total Synthesis of Aklavinone Tetrahedron Letters, 27, 1873-76, 1986.
Laugraud et al., Regioselective Synthesis of 2- and 3- (Phenylthio)juglone Derivatives, 1557-60, 1988.
Estanove Cyril
Pruvost Fran.cedilla.ois
Dees Jos,e G.
Girex
Pryor Alton
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