DE921386C - Process for the preparation of naphthodianthrone derivatives containing hydroxyl groups - Google Patents

Description

Process for the production of naphthodianthrornd.erivaten containing hydroxyl groups It is well known that the extracts of St. John's wort (Hypericum perforatum) are widely used in the treatment of mental and nervous disorders. Hypericin was recognized as an effective principle of this drug. Rockmann et al. Received this red dye in a crystallized form (Naturwissenschaften, 27, p. 550, 1939, and Annalen der Chemie, 553, p. I, 1942) and clarified its constitution (Naturwissenschaften, 37, p. 540 , 1950) The invention now relates to a process for the synthesis of hypericin and related hydroxyl group-containing naphthodianthrone derivatives.

One starts with oxyanthraquinones halogenated in the i-, position, the can be etherified and which are also substituted by methyl groups. .You are in a known manner according to U 1 l m a n n z. B. with copper powder in nitrobenzene converted to i, i-dianthraquinonyl @ derivative. With further reductive treatment in acidic or alkaline means, e.g. B. with Kupier and, concentrated sulfuric acid, Nickel and concentrated sulfuric acid, or zinc and glacial acetic acid, are obtained through reductive linkage of the keto groups intermediate a helianthrone derivative, which by further ring closure in the desired Methylnap'hthodianthronderiv at passes.

You can z. B. from i-bromemodine or its ether via the 2, 2'-dimethyl-4, 4'-5, 5'-7, 7 @ -hexaoxy-i, i'-dianthraquinonyl to hypericin, get the 2, 2'-dimethyl-4, 4'-5, 5'-7, 7'-hexaoxy-naphthodianthrone.

In an analogous manner, you can z. B., starting from any i-halo-oxy- or -alkoxyanthraquinone, through nuclear linkage in the i position to the oxydianthraquinonyl and from there via the helianthrone derivative to the corresponding one Oxynaphthodianthrone come.

EXAMPLE 5 g of i-halo-emodine trimethyl ether are melted together with 3 g of naphthalene in a glass tube which is 0.5 cm wide and 20 cm long and is sealed on one side. After adding 20 g of electrolytic copper activated with iodine, the mixture is heated to 24 ° in a salt bath for 21/2 hours. Finally the temperature is increased to 300 °. Extraction of the melt with chloroform and purification by chromatography on aluminum oxide gives 2,2'-dimethyl-4, 4'-5, 5'-7, 7'-hexamethoxy-i, i'-dianthraquinonyl in yellow prisms with melting point 335 to 338 °.

ig 2, 2'-dimethyl-4, 4 # -5, 5'-7, 7'-hexamethoxyi, i'-dianthraquinonyl are heated with 100 g of pyridinium hydrochloride for 51/2 hours to 170 to igo °. The product is extracted with soda solution and the 2,2'-dimethyl-4, d-5, 5 @ -7, 7'-hexaoxy-i, i'-dianthraquinonyl is precipitated by acidification. It crystallizes in orange-red needles that melt at 360 ° with decomposition.

50 mg of 2, 2'-dimethyl-4, 4'-5, 5'-7, 7, * -hexaoxyi, i'-dianthraquinonyl are in 170 ccm of sulfuric acid after the addition of 750 mg of copper bronze in a layer 1 to 2 cm thick exposed for 4 days using a 2oo watt lamp at a distance of 20 cm. The now red fluorescent solution is filtered from the copper through glass wool and poured onto ice. The resulting precipitate is adsorbed onto gypsum from tetrahydrofuran. In addition to the unchanged starting material, a red-black powder is obtained, which is identified as such by comparing the absorption bands with the natural hypericin. Synthetic natural Hypericin Hypericin Pyridine 6 0 3 ((587)) 556 6 0 3 559 52o Final absorption. from 545 concentrated green, red green, red Sulfuric acid fluorescence fluorescence 65z Final absorption 651 598 from 605 Acetic anhydride and green, red green, red Pyroboracetate fluorescence fluorescence after heating 632 584 632 583 Reduction product acety- lated, in xylene with chloranil dehydrated 623 573 623 573 The 2, 2'-dimethyl-4, 4 -5, 5'-7, 7'-hexamethoxyi, i'-dianthraquinonyl can also be converted directly into the hexamethyl ether of hypericin by exposure to sulfuric acid with copper and, after demethylation, into this itself .

The 6-halo-emodine compounds used as starting materials in the example can be obtained either by halogenating emodin (Beilstein, Handbuch der organ. Chemie, Vol. 8, 523) or purely synthetic z. B. after W. K. Anslow and H. Raistrick (Biochemical Journal 35, iOoö [1941]) from 3, 5-dimethoxyphthalic anhydride, the with m-cresol and aluminum chloride to form 3,5-dimethoxy-2- (2'-oxy-4-methylbenzoyl) benzoic acid is condensed. By bromination or chlorination (Biochemical Journal 35, 1008 [19q.1]) obtained the derivatives halogenated in the 5'-position (chlorine compound Mp 23o to 235 ° from glacial acetic acid; Bromine compound mp 26o °).

The 3, 5-dimethoxy-2- (2'-oxy-4'-methyl-5'-chlorobenzoyl) benzoic acid obtained or the corresponding bromine compound are in a known manner with 7o / o oleum, however, three times the amount of boric acid (based on the material used) was added is, to i-chloro-emodine-dimethyl ether (red-brown blame from mp 23o to 235 °) or converted to i-bromo-emodine-dimethyl ether. The alkali salt of these compounds will suspended in acetone and heated by 11/2 hours with excess dimethyl sulfate alkylated on the reflux condenser to give i-halo-emodine-trimethyl ether (i-chloro-emodine trimethyl ether, Mp. 213 to 215 °, from glacial acetic acid).

Claims (2)

PATENT CLAIMS: -i. Process for the production of hydroxyl groups containing naphthodianthrone derivatives, characterized in that in i-position halogenated oxy- or alkoxyanthraquinones, which are also substituted by methyl groups are, through core linkage according to U 11 m a n n to an i, i'-dianthraquinonyl derivative converts and this, if alkyl ethers were used as starting material, after previous dealkylation, by treatment with reducing agents, e.g. B. with Copper and concentrated sulfuric acid, to a helianthrone derivative and taking at the same time Exposure to UV rays converts to the methylnaphthodianthrone derivative. 2. Procedure according to claim i, characterized in that emodin halogenated in the i-position or emodine ether by nucleus linkage according to U 11 m a n n to the 2, 2'-dimethyl-4, 4'-5, 5 @ -7, 7 @ -hexaoxy- or alkoxydianthraquinonyl converts and this, if alkyl ethers were used as starting material, after previous dealkylation by Treatment with reducing agents, e.g. B. with copper and concentrated sulfuric acid under simultaneous irradiation with UV rays, converts to hypericin. Dressed Publications: Chemical Reports 83, 473, 591.