The Synthesis of Diquinone and Dihydroquinone Derivatives of Calix [ 4 ] arene and Electrochemical Characterization on Au ( 111 ) surface

Several new electroactive diquinone and dihydroquinone derivatives of calix[4]arene bearing anchor functional groups were designed, synthesized and characterized. A method for selective protection of the hydroquinone –OH groups with trimethylsilyl groups (TMS) either on lower-rim or on upper-rim was developed. Four selected molecules – with sulfide anchor groups and carboxylic anchor groups – were adsorbed onto Au(111) single crystal surface using ex-situ and insitu self-assembly methods. Adsorbed molecules were then electrochemically probed with cyclic voltammetry. All adsorbed molecules showed redox response which changed during cycling. After conditioning CVs stabilized and showed two distinct current peaks for all molecules. Synthesized and electrochemically probed molecules are of interest to: Li-ion batteries (as cathode materials and overcharge protection), beyond Li-ion batteries and redox-flow batteries.


Introduction
World energy consumption is continuously growing with electrical energy being the single largest consumer.Today roughly 68% of electrical energy is generated from the fossil fuels. 1 It is predicted that consumption of electrical energy will double in the next 30 years.Considering the limited natural resources and the environmental impact of the fossil fuels and its combustion products, the alternative sources of electrical energy together with electrochemical energy storage should be taken into account.Batteries, being the main representative of electrochemical energy storage, will play a key role in the future energy consumption cycle.
Over the past decades a tremendous work has been done on the field of the batteries.In particular, Li-ion batteries experienced the biggest boom among them, due to high specific energy (energy per unit weight) and high energy density (energy per unit volume). 2 However, recently the research was being diverted to the other battery chemistries too, in order to increase energy density and decrease the cost of the final product. 3One of the revived fields is the use of redox active organic molecules in the battery systems.Advantages of the redox active organic molecules are low cost, high specific capacity, abundance, flexibility, safety, recyclability and sustainability.Up to date, redox active organic molecules were used as: redox shuttles in Li-ion batteries, 4 active cathode materials, 5,6 and active anode materials. 7Depending on the nature of the system, redox active organic molecules can be: a) dissolved in the organic solvents -redox shuttles and redox-flow batteries, 8,9 b) grafted to the solid support -solid cathode in Li-ion batteries, [10][11][12][13] or c) free standing cathode material. 14Redox active organic molecules are chemically divided into: 6 organosulfur molecules, 15 organic free radical compounds, 16 and carbonyl compounds. 17The latter, having a quinone/hydroquinone as a key representative, are playing a significant role in electroactivity relevant to biochemistry, medicine and electrochemistry.Quinone derivatives were tested as cathode materials in Li-ion batteries [10][11][12]18 and redox-flow batteries. 19 lthough it was demonstrated that quinones are promising candidates for Genorio: The Synthesis of Diquinone and Dihydroquinone ... the use in energy storage, the field is still in its infancy.Motivated by above mentioned and the fact that there is a lack of fundamental understanding, we have focused on design of new quinone derivatives and electrochemical characterization.
In the present study, we examined several synthetic routes in order to synthesize quinone derivatives of calix [4]arene which could be then bound to the electrode materials and electrochemically tested.Calix [4]arene, 20 which was used as starting compound, is in particularly interesting for electrochemical applications, due to inherently opened cavities in the macrocycle.2][23] The letter is relevant to the enhanced accessibility of the active species in the energy conversion and storage systems.The crucial step in synthetic routes was the introduction of anchor functional groups.We have introduced carboxylic and sulfur containing anchor functional group.The latter is advantageous due to strong sulfur -noble metal interaction.Both, "short" anchors where redox active center would be close to the electrode surface and "long" anchors where center is further away from the electrode surface were introduced.By variation of the length we were hoping to investigate electrochemical reaction mechanisms.Successfully synthesized organic molecules were then anchored to the Au(111) single crystal surface using self-assembly protocol 24 and electrochemically probed.

Results and Discussion
The synthesis scheme is summarized in the Scheme 1.In the first attempt we have tried to introduce "short" sulfur based functional groups to the upper rim of the calix [4]arene macrocycle.We hypothesized that using "short" functional groups would bring electroactive centers of the molecule closer to the electrode material and thus mitigate electron transfer.Following the scheme we started from the basic calix [4]arene which was selectively protected with n-propyl groups on sites 26 and 28.Protected product 1b was then oxidized to quinone derivative 2b and bromine was introduced to the unoccupied sites.We tried to substitute the bromine on compound 3b with thioacetyl anchor group but reaction conditions used, did not furnish desired product.We believe that side reaction is occurring on the carbonyl groups of quinone center.To avoid possible side reactions, we reduced 3b to hydroquinone 4b.In the next step, we tried to protect hydroxyl groups of hydroquinone with trimethylsilyl groups (TMS).Interestingly, on compound 5b, upper-rim hydroxyl groups were protected only, while lower-rim stayed intact when using either N,O-bis(trimethylsilyl)acetamide (BSA) or trimethylsilyl chloride (TMSCl) (in the presence of triethylamine (TEA) or bis(trimethylsilyl)amine (HMDS)).On the other hand, TMSCl in the presence of the NaH yielded 6b where lower-rim OH groups were selectively protected, while upper-rim groups stayed intact.This interesting phenomenon is probably a combination of steric effects and non-covalent interactions of Na + cations with calix [4]arene macrocycle.Despite the fact that we have failed to protect the hydroxyl groups of 4b with TMS, we have shown new selective synthesis strategy, which can be used in designing new molecules.However, the protection of -OH groups on 4b was successful when using less bulky n-propyl groups, yielding compound 7b 1 or methyl groups yielding 7b 2 .In the next step we introduced thioacetyl anchor groups and obtain compound 8.The product 8 was then subject to oxidation in order to obtain redox-active quinone centers.Standard oxidation procedures did not furnish desired product, so the synthetic path was abandoned.
Using alternative synthetic path, we targeted the introduction of sulfide anchor functional groups.We again started from calix [4]arene, which was selectively protected with benzyl groups to furnish compound 1a.Protected compound was then brominated on positions 5 and 17 to isolate product 9a.In the next step we protected remaining two hydroxyl groups on the lower-rim, which yielded product 10a 1 .Bromine functional groups on upper-rim were then substituted with methylsulfide group using an exchange protocol.The product 11a 1 with -SMe anchor groups was then subject to deprotection of benzyl groups at lowerrim using trimethylsilyl bromide (TMSBr).The attempt to oxidize the deprotected product 12a 1 and synthesize quinone derivative failed.Although the synthesis of the designed molecules did not yield the desired products, the intermediate products could be in the future tested for other applications such as redox shuttles.
After two unsuccessful trials of introducing sulfur anchor groups to the upper-rim of calix [4]arene, we decided to introduce sulfur anchor groups to the lower-rim.Once again we started with calix [4]arene, which was selectively protected with functional groups already bearing sulfur containing anchor groups.We have successfully introduced three different functional groups containing sulfide anchor centers -1d-g.All three compounds were then oxidized to final quinone derivative 2d-g in 10% to 58% yields.
For electrochemical comparison, the molecules with carboxyl functional groups at the lower-rim were also synthesized (Scheme 1).Slightly modified previously published method 25 yielded selectively protected calix [4]arene 1c with protected carboxyl groups.In the next step phenolic units were oxidized to yield the molecule 2c with quinone redox centers.In order to obtain carboxylic anchor groups, the tert-butyl groups were removed from 2c and molecule 13 was isolated.For electrochemical comparison, a reduced version -hydroquinone 14 was also synthesized from 13, applying Na 2 S 2 O 4 as a reducing agent.
Molecules 2f, 2g, 13 and 14 were then attached to the Au(111) single crystal surface using ex-situ (2f and 2g) and in-situ (13 and 14) self-assembly methods (Figure 1).Sulfide anchor groups in 2f and 2g were expected to bind to the gold through a dative bond.It was shown previously that sulfur can interact with Au(111) single crystal surfaces by donating the electron pair to the unoccupied Au orbitals. 26On the other hand in the case of the carboxyl anchor groups (13, 14), ion-metal interaction was expected.In this respect, pH of self-assembly system and surface charge of the metal surface are playing significant role, thus in-situ self-assembly method was applied.Adsorption of the carboxylates has also been extensively studied over the past decades where several successful grafting methods were shown, 27 including adsorption of electroactive anthraquinone-2carboxylic acid on gold surface. 28o evaluate the electrochemical response of the adsorbed molecules on the Au(111) single crystal surface, cyclic voltammetry (CV) was used.Molecules 2f, 2g, 13, and 14 on Au(111) were tested and their faradaic currents were measured.All chemically modified Au(111) electrodes showed specific faradaic response.Molecule 2f with long and bulky sulfide anchor groups showed stable redox activity in the potential region from 0.1V to 1.15V vs. reversible hydrogen electrode (RHE).The reaction is quasireversible (Figure 2).In the first cycle (Figure 2, black line) the anodic scan shows at least two peak potentials (Ep a ) at 0.65V and 0.88V while cathodic scan shows three peak potentials (Ep c ) at 0.77V, 0.56V, and 0.43V.Redox mechanisms of diquinone derivatives of cali [4]arene in aprotic organic solvents have been studied previously. 29uthors suggest that there are two consecutive one-electron transfers followed by simultaneous concerted twoelectron transfer, giving the ionized hydroquinone (Scheme 2).Another study noticed change of the mechanism in the presence of water to concerted four-electron transfer per two quinone units. 30According to above mentioned and recorded CV, we can presume that the mechanism of the 2f on Au(111) electrode could follow two consecutive one-electron transfers followed by concerted two-electron transfer in the first cycle.
However, after several cycles the shape of the CVs changed dramatically.Ep a at 0.88V lost intensity, while Ep a at 0.65V substantially increased.Similar was observed for the cathodic scan.Ep c at 0.43V diminished while Ep c at 0.56V increased.The reasons for the CV changes are unclear.One of the reasons could be, that the molecules on the Au(111) are rearranging and position of the redox centers are, in respect to the electrode, changing.Similar is happening with the molecules 2g on Au(111) surface.
Scan in the anodic direction reveals single Ep a at 0.88V while the reverse scan in the cathodic direction, single peak Ep c at 0.33V (Figure 3).After cycling in the defined potential window the Ep a shifted to 0.67V and Ep c to 0.56V.This was the most pronounced when we held the potential at -0.1V for 1h.The peak potential separation ΔEp is becoming smaller, thus one can conclude that reac-Figure 1. Self-assembled molecules at Au(111) single crystal surface.2f and 2g were attached to the surface using ex-situ self-assembly method, 13 was attached using in-situ self-assembly method.Scheme 2. Redox mechanism of electroactive diquinone derivatives of calix [4]arene with anchoring functional groups.
Genorio: The Synthesis of Diquinone and Dihydroquinone ... tion is getting more reversible.As mentioned above, the reason could be; the rearrangement of the self-assembled layer of the molecules on the Au(111) surface and change of the mechanism from two consecutive one-electron transfers followed by simultaneous concerted two-electron transfer to concerted four-electron transfer.In order to confirm that, extensive studies should be done, however, this is beyond the scope of this work.
The electrochemical investigation of the molecule with carboxylate anchor groups 13 on the Au(111) surfaces showed even more pronounced redox changes during cycling (Figure 4).To highlight the response of the redox electrochemistry of 13 the CV of pure Au(111) is overlaid in the Figure 4.The first scan of 13 on Au(111) exhibited distinct electrochemical response with at least four peaks.Redox processes are reversible with Ep a at 0.53V, 0.63V, 0.70V, and 0.88V and Ep c at 0.50V, 0.57V, 0.71V, and 0.86V.After the third cycle, CVs stabilized and did not change significantly.However, the difference between first and third cycle is significant.In the third cycle only one Ep a at 0.70V can be seen and two Ep c at 0.55V, 0.56V.Interestingly, when CV of 3 rd cycle of quinone derivative of calix [4]arene 13 was compared to CV of 1 st cycle of reduced version -a hydoquinone derivative of calix [4]arene 14 (Figure 5c and 5d), the CVs almost overlapped.One would expect to see overlapping of the CVs in the first cycles since we are probing the same molecule but in different oxidation state.However, the molecules on the surface are immediately reduced when electrode is immersed at lower potential.From above mentioned observation we can deduct that molecule 13 is rearranging on the surface and making more accessible to the protons from the electrolyte which are protonating phenoxide anion of the hydroquinone molecules.Once the film is thermodynamically stable the electrochemical response give the same results for either oxidized quinone 13 or reduced hydroquinone 14.
To evaluate the possible effect of the anchor groups, conditioned CVs of molecules 2f, 2g, 13 and 14 on Au(111) were compared (Figure 5).Surprisingly, all molecules exhibit similar electrochemical response with faradaic currents in anodic scan at Ep a -0.67V and cathodic scan at Ep c -0.56V.Although the ΔEp (0.11V) of the main electrochemical reaction is the same for all four compounds, there are differences between the CVs which indicate different mechanism either in the anodic scan for   2f and 2g or the cathodic scan for 13 and 14.According to previously published results, 30 one would expect that the reduction of all four diquinone compounds would undergo a concerted four-electron reduction in acidic aqueous media.However, the conditioning of the chemically modified Au(111) electrodes shows that all the diquinones; 2f, 2g, and 13 bearing different anchor groups exhibit their unique electrochemical response with additional waves.One of the reasons for such behavior could be a specific steric effect of the molecules where one-electron transfer reactions followed by protonation are shielded and thus reaction intermediates are more stable.According to above mentioned we cannot draw any solid conclusions on the effect of the length of the anchor groups.

Conclusions
Specifically designed redox-active diquinone derivatives of calix [4]arene bearing various anchor functional were synthesized and fully characterized.Designed and synthesized electroactive molecules are particularly interesting for the energy conversion and storage systems e.g.Li-ion and beyond Li-ion batteries (cathode materials, redox shuttles), and redox-flow batteries.In an attempt to introduce thiol anchor functional groups on the upper-rim of the calix [4]arene macrocycle, we have developed the method where selective protection of the hydroquinone -OH groups either on lower-rim (6b) or on upper-rim (5b) was achieved.Further, we have successfully synthesized new derivatives of calix [4]arene with 1,4-dimethoxybenzene moieties (8) and 1-methoxy-4-(methylthio)benzene moieties (11a 1 and 12a 1 ) that are in particular interest for the non-aqueous redox flow batteries and as an overcharge protection for Li-ion batteries.We have also successfully synthesized diquinone derivatives of calix [4]arene with sulfide (2e, 2f, and 2g) and carboxylate (13 and 14) anchor groups on lower-rim of the macrocycle.Above mentioned molecules could be used as an active cathode component of the Li-ion and beyond Li-ion batteries.
Molecules 2f, 2g, 13 and 14 were then attached to the Au(111) single crystal electrode using ex-situ and in-situ self-assembly methods and electrochemically characterized.All the analyzed molecules gave redox response in 0.1M HClO 4 .It was noticed that electrochemical responses are changing during cycling for the molecules 2f, 2g, and 13.The positions of the peak potentials; Ep a and Ep c are shifting, increasing and decreasing.However, after conditioning the peak potentials; Ep a and Ep c stabilized and CVs did not change substantially.The conditioned CVs of 2f, 2g, 13 and 14 on Au(111) revealed two common peak potentials; Ep a at 0.67V and Ep c at 0.56V with the peak potential separation ΔEp -0.11V.The latter indicates that main redox mechanism of the different diquinone derivatives of calix [4]arene is similar while the presence of other peak potentials suggest that the full mechanism is complex and specific for the molecules tested.

1. Synthetic Materials and General Synthetic Procedures
Reactions were performed in dried glassware under Ar atmosphere, unless stated otherwise.Precursor calix [4]arene was prepared according to literature procedures. 31   Au(111) single crystal (MaTecK) was annealed in UHV at 550 °C after ion bombardment with 1 kV Ar + ions at 5 × 10 -6 mbar.The cycle was repeated at least two times.Au(111) single crystal was then transferred to a homemade annealing apparatus and annealed at 700 °C in 3% H 2 /Ar atmosphere for 30 min.The surface of the Au(111) single crystal was protected with H 2 O droplet (30μL) and transferred to a vial for self-assembly.

3. Self-assembly
»Ex-situ« method.Au(111) was immersed into ∼80 μM solution (solvent mixture CH 2 Cl 2 : EtOH 1 : 9) of adsorbate molecules 2f and 2g at room temperature for 30 min.Adsorbate solutions; were always freshly prepared.After self-assembly the Au(111) was removed from the solution and washed with EtOH, i-PrOH in Milli-Q H 2 O, and dried in Ar atmosphere.
»In-situ« method.The surface of Au(111) single crystal was immersed into an electrochemical cell with 0.1 M HClO 4 with ∼80 μM concentrations of 13 and 14.
The system was hold at 0.2 V vs Ag/AgCl for 10 min.

Electrochemistry
A standard three-compartment electrochemical cell containing 0.1 M HClO 4 (OmniTrace Ultra™ from EDM), Au wire as a counter electrode and Ag/AgCl as a reference electrode was used.In each experiment, the electrode was immersed (hanging meniscus technique) at 0.07 V in a solution saturated with Ar and cycled between 0.07 V and 1.17 V versus the reversible hydrogen electrode (RHE).The sweep rate for all measurements was 50 mVs -1 .Electrode potentials are given versus the RHE.Autolab potentiostat was used in the electrochemical measurements.