Synthesis of Crown Ethers Containing a Rubicene Moiety

Mario Smet and Wim Dehaen *Department of Chemistry, Katholieke Universiteit Leuven, Celestijnenlaan 200F, 3001 Heverlee BelgiumTel.: 32-16-327439, Fax: 32-16-327990, E-mail: Wim.Dehaen@chem.kuleuven.ac.be* Author to whom correspondence should be addressed.Received: 10 February 2000 / Accepted: 14 March 2000 / Published: 22 March 2000Abstract: A symmetrically disubstituted derivative of the highly fluorescing and photosta-ble rubicene was incorporated in a macrocycle using high dilution conditions and a hy-droxyrubicene was functionalized with a modified aminobenzo-15-crown-5.Keywords: rubicene, crown ethers, macrocycle synthesis.IntroductionRecently we have used the highly fluorescing and photostable rubicene as a core in dendrimerchemistry [1]. A new approach towards disubstituted rubicenes was devised [2]. A metal catalyzedring closure was found to afford heterocyclic analogues of rubicene and asymmetrically disubstitutedderivatives [3]. In this paper we wish to report some more applications of rubicene in systems havinggreat potential as supramolecular building blocks, namely macrocycles and crown ethers. Macrocyclescontaining a rubicene moiety could be interesting fluorescing units to be used in the synthesis of[n]catenanes [4]. On the other hand, crown ethers bearing a rubicene unit could be used as selectivecation sensitive fluorescence indicators.Results and DiscussionIn previous work we have reported the preparation and alkylation of 5,12-dihydroxyrubicene [1-2].Although alkylation of the latter compound with benzyl bromides proceeded quite smoothly, reaction


Introduction
Recently we have used the highly fluorescing and photostable rubicene as a core in dendrimer chemistry [1].A new approach towards disubstituted rubicenes was devised [2].A metal catalyzed ring closure was found to afford heterocyclic analogues of rubicene and asymmetrically disubstituted derivatives [3].In this paper we wish to report some more applications of rubicene in systems having great potential as supramolecular building blocks, namely macrocycles and crown ethers.Macrocycles containing a rubicene moiety could be interesting fluorescing units to be used in the synthesis of [n]catenanes [4].On the other hand, crown ethers bearing a rubicene unit could be used as selective cation sensitive fluorescence indicators.

Results and Discussion
In previous work we have reported the preparation and alkylation of 5,12-dihydroxyrubicene [1][2].Although alkylation of the latter compound with benzyl bromides proceeded quite smoothly, reaction of this rubicene derivative with simple aliphatic bromides and tosylates turned out to fail.However, we found that the use of more reactive bromoacetates or bromoacetamides afforded the alkylation products in very good yield.As we wished to use the 5,12-dihydroxyrubicene to prepare macrocycles, we decided to prepare the tetraethylene glycol derivative 2 by reaction of the tetraethylene glycol monotosylate 1 with bromoacetyl bromide (Scheme 1).The required monotosylate was prepared following the literature conditions [5].Compound 2 bears a bromoacetate moiety which could be substituted by 5,12-dihydroxyrubicene in refluxing acetone in the presence of K 2 CO 3 and 18-crown-6.Under these conditions the tosylate was not substituted.This fact was in accordance with our former observation of the low reactivity of 5,12-dihydroxyrubicene towards simple aliphatic tosylates.Even in DMF at 80°C, tetraethylene glycol ditosylate failed to react with 5,12-dihydroxyrubicene.However, the use of compound 2, allowed a very convenient preparation of the ditosylate 3. Subsequent reaction of this ditosylate with 1,5-naphthalenedithiol (which was prepared following the literature procedure [6]) under high dilution conditions and using Cs 2 CO 3 as the base, afforded the desired macrocycle 4.This compound was found to display a strong fluorescence (λ max = 560 nm).Both the rubicene containing compounds 3 en 4 were found to have excellent solubility in CH 2 Cl 2 and CHCl 3 .This behaviour is in sharp contrast with unsubstituted rubicene or the 5,12-dihydroxy derivative which essentially behave as pigments.In a second approach, we wanted to functionalize a rubicene with a crown ether derivative.There-fore, a rubicene with only one phenol function, such as 10, was required (Scheme 2).We decided to introduce a tert.-butyl group to enhance the solubility and hence the ease of synthesis and manipulation.The preparation of this compound 10 was achieved analogously to compounds previously prepared in our group (Scheme 2) [7].First, a solution of 4-methoxyphenylmagnesium bromide in THF was slowly added to a suspension of 1,5-dichloroanthraquinone (5) in THF, affording the monoadduct 6.To this compound, an excess of 4-tert.-butylphenyllithiumwas added yielding the diol 7. Reduction of the latter using NaH 2 PO 2 and KI in refluxing acetic acid afforded the substituted 9,10diphenylanthracene 8. Ring closure of this compound was achieved by a palladium catalyzed reaction as previously published [3].Finally, the obtained 5-tert.-butyl-12-methoxyrubicene9 could be deprotected by treatment with BBr 3 yielding the desired phenol 10.The yields of these reactions are all good to excellent.In order to be able to conjugate a crown ether to this phenolic compound 10, we prepared the bromoacetamide 12 by treatment of 4-aminobenzo-15-crown-5 (11) with bromoacetyl bromide (Scheme 3).The obtained bromoamide 12 was found to be sufficiently reactive to be coupled with the monophenol 10, affording the desired compound 13 in moderate yield.The latter was found to be highy fluorescing and further investigations to evaluate the influence of cations on the fluorescence are under way.

Synthetic procedures and spectral data
Bromoacetate 2 Tetraethyleneglycol monotosylate (1) (22g; 63 mol) and Et 3 N (9.6 g; 95 mmol) were dissolved in CH 2 Cl 2 ( 130 mL) and placed under argon atmosphere.The mixture was cooled to -20°C.Through a septum, bromoacetyl bromide (19 g; 95 mmol) was added and the resulting dark suspension was left at room temperature for 1 h.The suspension was poured on crushed ice (ca.150 g) and the mixture was washed with a solution of HCl (3 x 50 mL; 2 M) and water (2 x 50 mL).The organic layer was dried over MgSO 4 and the solvent was evaporated in vacuum.The desired bromoacetate 2 was obtained as a light brown oil (24 g; 81%) after column chromatography (SiO 2 ; CH 2 Cl 2 -ethyl acetate 1:1): ).

Cyclophane 4
Ditosylate 3 (0.55 g; 0.48 mmol) and 1,5-naphthalenedithiol (92 mg; 0.48 mmol) were dissolved in DMF (50 mL).The resulting solution was added over a period of 24 h to a vigourously stirred suspension of Cs 2 CO 3 (0.47 g; 1.4 mmol) in DMF (300 mL) at 70°C under argon atmosphere by means of an infusion pump.After complete addition, the mixture was stirred for another 12 h at 70°C.After cooling to room temperature, the solvent was evaporated in vacuum and the cyclophane 4 was obtained as a dark red oil (0.13 g; 27%) after column chromatography (SiO 2 ; CH 2 Cl 2 -ethyl acetate 1:1):

Crown ether derivative 13
Hydroxyrubicene 10 (0.11 g, 0.28 mmol), bromoacetamide 12 (0.13 g, 0.33 mmol) and K 2 CO 3 (92 mg, 0.66 mmol) were suspended in acetone (4 mL) and the mixture was placed under argon.The stirred suspension was maintained at reflux temperature for 72 h.After cooling to room temperature, the reaction mixture was poured in water (5 mL) and extracted with CH 2 Cl 2 (2 x 5 mL).The organic layers were combined and dried over MgSO 4 .After column chromatography (SiO 2 ) with EtOAc/CH 3 OH 1:1 as the eluent, the desired crown ether 13 was obtained as an amorphous solid (79 mg, 39% Scheme 1.