Amination of anthra[1,9-cd:5,10-c,d,]bisisoxazole by alkylamines

Treatment of the stable analogue of a 1,5-anthraquinone, namely, anthra[1,9-cd:5,10-c,d,]bisisoxazole, with primary and secondary amines in an inert atmosphere leads to the cleavage of one of the isoxazole moieties to afford 3(5)-alkylamino-7-amino-6 H -6- oxoanthra[1,9-cd ]isoxazoles. However, amination in the presence of air leads to (5)-alkylamino- anthra[1,9-cd:5,10-c,d,]bisisoxazole without cleavage of the isoxazole moiety.


Results and Discussion
We have found that bisisoxazole (1) reacts with aliphatic and cyclic amines at room temperature in an inert atmosphere.The reaction products either crystallized spontaneously or were isolated by dilution of reaction mixture with water (see Table ).
The reaction of bisisoxazole (1) with primary amines resulted in the formation of a mixture of substances, which were isolated by column chromatography.The aminations of substrate (1) by secondary amines proceeded in a much cleaner fashion.The structures of the 3(5)-alkylamino-7-amino-6H-6-oxoanthra[1,9-cd]isoxazoles (5−6) were confirmed by UV-, IR-, 1 H NMR-spectroscopic data and by their chemical transformations.For compounds (V−VI), vibrations of the NH-bond of primary amino group were observed at 3280-3440 cm −1 and vibrations of the C and vibrations of the C==O bond were at O bond were at 1635−1685 cm −1 .Electronic absorption spectra of compounds (5−6) are similar to those of 3-or 5-alkylamino-6H-6-oxoanthra[1,9-cd]isoxazoles 6 which have been previously reported.
The 1 H NMR spectra of isoxazoles (5−6) indicated the presence of a quinoid-type bonds, since the doublet signal for the proton at position 4 was found at higher field (6.2−6.4 ppm).The broad singlet signal of protons of the primary amino group was centered in CDCl3 at 6.9−7.0 ppm.The deamination of product Va led to 3-dimethylamino-6H-6-oxoanthra[1,9-cd]isoxazole (7a), which was shown to be identical to a previously synthesized sample. 6This fact confirmed the validity of structures 5−6.

Experimental Section
General Procedures.Electronic absorption spectra were recorded in ethanol on an SF-26 spectrometer.The IR spectra were recorded in KBr pellets on a Specord 75 IR spectrometer.The 1 H NMR spectra were recorded on a Bruker AM 400 spectrometer.All chemical shifts are given relative to SiMe4 as internal standard and for CDCl3 as a solvent.Melting points were determined on a Boetius melting-point apparatus.The progress of the reactions was ascertained by thin-layer chromatography on Silufol plates; eluent: toluene-acetone-hexane 10:1:1.
While stirring, 2 mL of 30% water solution of dimethylamine (or 2 mL of another amine such as butylamine, piperidine, morpholine, or cyclohexylamine) were added.The mixture was kept at 20−25 o C for 20−80 h during which time the solution acquired a violet coloration.The precipitate of 7-amino-3-dimethylamino-6H-6-oxoanthra[1,9-cd]isoxazole (5a) was collected by filtration and washed with ethanol.The other isoxazolones were isolated in the following way: the reaction mixture was heated to 50−60 o C, the solution was diluted with water (5−15 mL) and cooled to 0±5 o C. The obtained precipitate was collected by filtration, dried and purified by column chromatography (adsorbent: Al2O3; eluent: toluene).After removal of the solvent, the products (5b,c,d, 6) were characterized.