Triptycene quinones in synthesis: preparation of triptycene bis-cyclopentenedione

The preparation of triptycene bis-quinone 2 starting from a Diels-Alder reaction of 1,4-dimethoxyanthracene and p-benzoquinone is described. This compound was transformed to triptycene bis-cyclopentenedione 16 through a double hydroxyquinone – iodonium ylide formation-ring contraction sequence


Introduction
Triptycene quinones are triptycene derivatives in which at least one benzo group has been replaced by a quinonoid ring.Some representative structures of triptycene quinones are shown in Figure 1  Such compounds combining the rigid structure of triptycene with the redox potential of quinones find several applications in Chemistry.Triptycene quinones serve as building blocks for the construction of three-dimensional supramolecules 1 and liquid crystalline derivatives, 2 for the synthesis of electron-transfer compounds with porphyrins 3 and tetrathiafulavalene 4 serving as donors, and for the preparation of polymeric chemosensors. 5More recently pentiptycene quinones of type 3 were reported to form materials with monolayer assembly structure, 6 to find application as fluorescent chemosensors for metal ions, 7 and serve as building blocks for the construction of novel chain and channel networks. 8riptycene quinones exhibit also interesting biological activity: a variety of them decrease the viability of leukemic cells in vitro, 9 triptycene quinones with methoxy substituents exhibit antioxidant and anti-inflammatory properties, 10 while the reaction of triptycene diquinones with amines was reported to afford derivatives with potent anticancer and antimalarial activities. 11n relation to our interest in hydroxyquinones 12 we recently reported 13 the synthesis of triptycene hydroxyquinone 3 and its conversion through phenyliodonium chemistry to triptycene cyclopentenedione, 5.The latter reacts as a dienophile and dipolarophile affording polycyclic adducts 6 bearing the triptycene moiety (Scheme 1).The successful preparation of 5 prompted us to investigate the possibility of preparing the triptycene bis-cyclopentenedione 16 by applying the same methodology.We herein wish to report the results of our efforts.

Results and Discussion
The synthesis of 16 was based on the retrosynthetic route shown in Scheme 2, having as key steps the preparation of triptycene dihydroxy-bis-quinones 13 and hence bis-quinone 2, which was reported in the literature albeit without experimental details for its preparation.Triptycene bis-quinone 2 was prepared in three steps starting with a Diels-Alder reaction of 1,4-dimethoxyanthracene and 1,4-benzoquinone.The former is not commercially available and was prepared from quinizarin also in three steps (methylation and two subsequent reductions with NaBH 4 ) following a literature method. 15The Diels-Alder reaction did not work well in the solvents usually used for cyclization (toluene or xylene) but in refluxing acetonitrile the dehydro adduct 7 was isolated in reasonable yield.This adduct was acid-isomerised almost quantitatively to the corresponding hydroquinone derivative 8 which was effectively oxidized by (diacetoxyiodo) benzene to dimethoxy triptycene quinone 9. Finally, 9 was oxidativelydemethylated by ceric ammonium nitrate (CAN) to the desired bis-quinone 2 (Scheme 3).As was mentioned earlier, PhI(OAc) 2 was found to be very effective for the oxidation of hydroquinone 8 to quinone 9.The use of a more conventional oxidant, like potassium bromate, also gave the desired 9 in 60% yield, along with 15% of bis-quinone 2 and 10% of the bromo derivative 10, thus complicating the reaction (Scheme 4).In the next step bis-quinone 2 was converted under Thiele-Winter conditions to a mixture (1:1 estimated by 1 H-NMR spectroscopy) of the two possible hexaacetoxy triptycene isomers 11.Acid hydrolysis under various conditions did not lead to hexahydroxy isomers 12, as complex mixtures of partially acetoxylated compounds were always isolated.In contrast, hydrolysis under basic conditions afforded 2-hydroxy-1,4-anthraquinone 14 as the only isolable product (Scheme 5).It is possible that 11 is converted to dihydroxy bis-quinone isomers 13, as in a typical reaction for the preparation of hydroxy quinones from 1,2,4-triacetoxybenzenes. 12 Bis-quinone 13 affords 14 through a retro Diels-Alder reaction.This tendency of triptycene quinones to undergo retro Diels-Alder reactions under basic conditions has also been observed with other triptycene quinonic derivatives. 16n order to confirm the formation of 14, this hydroxy quinone was prepared by an independent method: available 1,4-dimethoxyanthracene was oxidatively demethylated to 1,4anthraquinone, which in turn was transformed to 1,2,4-triacetoxyanthracene 14a which was hydrolyzed to 14 (Scheme 6).Finally, the acetoxy groups of 11 were smoothly removed by LiAlH 4 to afford a reasonable yield of hexahydroxytriptycene isomers 12.This mixture was converted in a tandem oxidationaryliodination reaction to the corresponding mixture of bis-ylide isomers 15 using four equivalents of PhI(OAc) 2 .This mixture was subjected to thermal decomposition in refluxing acetonitrile and the target molecule triptycene bis-cyclopentenedione 16 was isolated in 7% yield (Scheme 7).Triptycene bis-cyclopentenedione 16 exists in solution in its tetraketo form, analogously to triptycene cyclopentenedione 17. 13 The two compounds exhibit similar spectroscopic 1 H-NMR and 13 C-NMR data, the main difference being the anisotropy of the protons of the methylene groups in 16 (Figure 2).We believe the reaction pathway to be essentially the same as that proposed for the thermal decomposition of aryliodonium ylides of 2-hydroxy-1,4-benzoquinones: 17  Highly reactive 18 undergoes hydrolysis with water present in the solvent and the resulting acid 19 decarboxylates to the desired triptycene bis-cyclopentenedione 16 (Scheme 8).This reaction pathway leads also to the preparation of 5 from the thermal degradation of the corresponding mono ylide.The formation of the intermediate ketene is supported by its trapping with methanol to form the corresponding ester. 13n conclusion we presented a reaction sequence for the preparation of triptycene biscyclopentenedione 16 based on hydroxyquinone-ylide formation chemistry.This compound, as well as its precursors, might serve as building blocks for the construction of polycyclic structures bearing the triptycene moiety.

Experimental Section
General Procedures.Melting points were determined on a Stuart Scientific Melting Point Apparatus SMP3 (230 Volts) and are uncorrected. 1H-NMR and 13 C-NMR spectra were recorded with a Bruker AM 300 (300 MHz and 75 MHz for 1 H and 13 C, respectively) in ca 5% solution of CDCl 3 using Me 4 Si as the internal standard.Mass spectra were recorded with a spectrometer VG-250 in 70eV, ESI.Elemental analyses were carried out in a Perkin-Elmer 2400-II elemental analyst.
Complicated mixtures of products were also the results of hydrolysis with aqueous NaOH.In this case the only isolable product (after column chromatography in 10-15% yields) was 2hydroxy-1,4-anthraquinone 14, mp 238-241 o C, lit. 18

Scheme 8 .
Scheme 8. Proposed reaction pathway for the preparation of 16.