Organic compounds -- part of the class 532-570 series – Organic compounds – Polycyclo ring system containing anthracene configured ring...
Patent
1997-07-01
1999-09-07
Kight, John
Organic compounds -- part of the class 532-570 series
Organic compounds
Polycyclo ring system containing anthracene configured ring...
C07C 49593
Patent
active
059489243
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a new 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 rheins 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 a number of stages, that is to say an addition, followed by an oxidation with silver oxide, in order to cause aromatization of the rings, and a demethylation. Moreover, the reaction involves the use of diazomethane, which has well-known disadvantages.
Synthetic routes to anthracyclinones by a cyclo-Diels-Alder addition reaction have also been described by M. Petrzilka and J. I. Grayson addition reaction of a diene with a quinone can be obtained by using a Lewis acid composed of the compound BF.sub.3.O(C.sub.2 H.sub.5).sub.2 as catalyst.
The process according to the present invention makes it possible to prepare substituted anthraquinones from 1,4-naphthoquinones in only two stages and with a satisfactory yield.
The anthraquinones which can be prepared by the process according to the present invention can be represented by the general formula (I) below: ##STR1## in which R represents a hydrogen atom or a linear or branched alkyl group containing 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 containing 1 to 5 carbon atoms, R.sub.1 represents a hydrogen atom, a hydroxyl group, a linear or branched alkoxy group containing 1 to 5 carbon atoms or an acyloxy group containing 1 to 5 carbon atoms, and R.sub.2 represents a hydrogen atom or a linear or branched alkyl group containing 1 to 5 carbon atoms.
In accordance with the process of the invention, a Diels-Alder reaction is carried out between a 1,4-naphthoquinone of general formula (II): ##STR2## in which R.sub.1 represents a hydrogen atom, a hydroxyl group, a linear or branched alkoxy group containing 1 to 5 carbon atoms or an acyloxy group containing 1 to 5 carbon atoms and X represents a hydrogen atom or a halogen atom,
and an acyclic diene of formula (III): containing 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 containing 1 to 5 carbon atoms and R.sub.3 represents a linear or branched alkyl group containing 1 to 5 carbon atoms or an acyl group in which the alkyl part is linear or branched and contains 1 to 5 carbon atoms,
and a saponification, aromatization and oxidation reaction is subsequently carried out.
In the above formula (II) representing the starting naphthoquinone, R.sub.1 preferably represents a hydroxyl or acetoxy group and X is a hydrogen atom or a chlorine atom. In the general formula (III) representing the acyclic diene, it is preferable for R to represent a hydrogen atom or a methyl group and R.sub.3 a methyl, acetyl or t-butylcarbonyl group.
The acyclic diene of formula (III) used in the reaction described above can be a butadiene derivative, such as an ester, and for example 1-acetoxy-1,3-butadiene or 1-acetoxy-3-methyl-1,3-butadiene.
Among the naphthoquinones of general formula (II), it is preferable to use juglone, represented by the formula (II) where R.sub.1 represents a hydroxyl group, or 3-chlorojuglone, represented by the same formula where X is a chlorine atom. Juglone can be prepared, for example, by oxidation of 1,5-dihydroxynaphthalene in the presence of an appropriate catalyst, as described in Patent SU-1,817,767, or with chromium oxide, by the method of G. Jesaitis et al., J. Chem. Ed., 49, 436 (1972), or alternatively by oxidation by means of atmospheric oxygen in the presence of a cobalt-based catalyst, such as salcomine, according to the method of T. Wakamatsu et
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Estanove Cyril
Pruvost Fran.cedilla.ois
Covington Raymond
Girex (Societe Anonyme)
Kight John
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