4th March 2016

Hydrodynamic Rocking Disc Electrode Study of the TEMPO-Mediated Catalytic Oxidation of Primary Alcohols

Sunyhik D. Ahn a, Adrian C. Fisher b, Antoine Buchard a,

Steven D. Bull a, Alan M. Bond c, and Frank Marken*a

a Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UKb Department of Chemical Engineering, University of Cambridge, New Museums Site, Pembroke

Street, Cambridge, CB2 3RA, UKc Monash University, School of Chemistry, Clayton, Vic 3800, Australia

To be submitted to Electroanalysis

Proofs to F. Marken

Email F.Marken@bath.ac.uk

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Abstract

The hydrodynamically thinned diffusion layer at a sinusoidally rocking disc is approximately

uniform and can be expressed in terms of a diffusion layer thickness δRoDE=9.0 D

13 v

16

√Θ f with D,

the diffusion coefficient of the redox active species, v, the kinematic viscosity, Θ, the total

rocking angle (here 90 degree), and f, the rocking frequency (ranging here from 0.83 to 25

Hz). For the one-electron oxidation of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in

aqueous carbonate buffer pH 9.5, it is shown that there is quantitative agreement between the

expression for the diffusion layer thickness and experimental data. Next, for seven primary

alcohols, the catalytic TEMPO-mediated oxidation mechanism is investigated under rocking

disc conditions. Chemical rate constants are evaluated (by varying the diffusion layer

thickness) employing the DigiElch4.F simulation package. Trends in the chemical rate

constants (compared with DFT calculations) suggest enhanced reactivity for methanol versus

higher primary alcohols and for aromatic versus non-aromatic primary alcohols. Rocking disc

voltammetry allows quantitative mechanistic analysis in the laminar flow regime.

Keywords: hydrodynamic electrochemistry, fuel cell, biofuel, electro-synthesis.

Graphical Abstract:

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1. Introduction

Hydrodynamic techniques in electrochemistry offer powerful tools for the investigation of

electron transfer processes coupled to homogenous chemical processes [1]. The rotating disc

electrode technique is the most commonly employed hydrodynamic tool. This method offers

approximately uniform diffusional access to the electrode surface [2] and has been applied in

many electrode kinetic studies [3,4]. In contrast, flow cells such as those with rectangular duct

configuration and with single [5] or dual [6] or micro-electrodes [7] offer additional

mechanistic insight due to the non-uniform nature of diffusion processes [8]. The non-uniform

nature of diffusion at the leading edge and at the trailing edge of electrodes in these flow cells

requires multi-dimensional computational algorithms to link the experimentally measured

steady state limiting currents [9,10] (or transients [11]) with the microscopic detail of the

electrode process. For uniformly accessible hydrodynamic electrodes (such as those used in

rotating disc or rocking disc voltammetry [12,13,14]) a one-dimensional simulation model based

on the knowledge of the average diffusion layer thickness can be sufficient [15]. Even cases of

turbulent mass transport with an in average uniformly accessible electrode (e.g. as observed

in sonoelectrochemistry [16]) have been reported to allow quantitative kinetic analysis based

on an approximate one-dimensional model [17]. Use of hydrodynamic techniques in electrode-

kinetic studies is desirable (i) to systematically vary the mass transport conditions, (ii) to

enhance mass transport and thereby remove time-dependence from data, and (iii) to minimize

current contributions from non-Faradaic processes. The rocking disc voltammetry tool

employed here offers an experimentally convenient alternative to rotating disc voltammetry

and is shown to provide rate constant data for an electrocatalytic (EC’) process.

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In the specific case of an electro-catalytic EC’ mechanism [18], the electro-catalyst (here

2,2,6,6-tetramethylpiperidine-1-oxyl or TEMPO, see Figure 1) is oxidised in the E-step at the

electrode surface (to give TEMPO+). The reactive mediator TEMPO+ is then converting the

substrate (here primary alcohols) to give product (here the corresponding aldehydes) in the C’

step. This re-generates the electro-catalyst and completes the catalytic cycle. The true nature

of the EC’ process can be much more complex in detail with multi-electron transfer steps

(e.g. two-electron conversion of primary alcohols) and additional comproportionation

processes (here TEMPO- reacting with TEMPO+, see Figure 1). However, this additional

complexity may have only little impact under conditions of uniform (one-dimensional) mass

transport and kinetic parameters are readily extracted. To obtain reliable kinetic information

and to match experimental data with a hypothetical mechanism it is desirable to (i) vary the

substrate concentration, (ii) vary the catalyst concentration, and (iii) vary the hydrodynamic

conditions. Multi-parameter simulation software (here, the commercial DigiElch 4.F package

is employed [19]) facilitates the global multi-parameter data analysis.

Figure 1. Mechanistic scheme of electrochemical TEMPO oxidation coupled to the catalytic oxidation of a primary alcohol. ke1 and ke2 are electrode kinetic constants, kc is the chemical rate constant for alcohol oxidation and kcomp. is the rate constant for the comproportionation of TEMPO- and TEMPO+ to give 2 TEMPO.

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The electro-catalytic mechanism of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) mediated

alcohol oxidations is investigated at the rocking disc electrode. The electrochemistry of

nitroxyl based free radicals is of broader interest and often seen as an alternative to metal-

based catalysis (organo-catalysis [20,21]). TEMPO derivatives alone or combinations of

TEMPO with metals [22,23] or with enzymes [24] provide versatile tools in bio-mass

conversion [25,26] and in electrosynthetic processing [27]. TEMPO usually is employed in

aqueous media as a homogeneous catalyst [28], but recently new methods for

“heterogenisation” of TEMPO have also been suggested via covalent attachment [29,30] or via

embedding into a polymer of intrinsic microporosity [31,32]. Mechanistic aspects of

electrochemical TEMPO mediated alcohol oxidations have been investigated with the

following key conclusions: (i) catalytic currents were affected by the pH [33], (ii) catalytic

currents increase non-linearly with the concentration of alcohol to reach a plateau as expected

for EC’-type processes, (iii) the rate limiting process at sufficiently high applied potentials is

a chemical step (as opposed to electrochemical), (iv) the driving force and rate for the

primary alcohol oxidation are linked to the reversible potential for TEMPO derivatives [34],

and (v) at high pH (>11) some TEMPO catalysts are irreversibly degraded by hydroxide ions

[27]. Further to these observations, it has been suggested that the overall mechanism for the

EC’ mechanism involves a homogeneous comproportionation step (see Figure 1 [35]) and that

the nature of the electrolyte (or buffer) ions present in solution may also affect the overall rate

of the catalytic process [25]. The rate limiting reaction step may depend on reaction

conditions and is still subject to debate [36]. Here, the underlying mechanism is assumed to

follow that originally proposed by Semmelhack [37] based on hydride transfer (see Figure 1)

in the rate limiting reaction step.

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Hydrodynamic rocking disc electrode voltammetry techniques have been suggested first as a

convenient method (avoiding sliding brush contacts) for the uniform electrodeposition of

solar cell components [13,14]. A dual-semi disc rocking electrode in generator-collector

mode was shown to lead to concentration modulation effects [38]. The experimental

conditions during “rocking” are very similar to those during “rotating” apart from the fact

that the electrode is not completing a full 360o rotation. Instead a “four-bar mechanism” [12]

is employed to only rock 45o forward and 45o backward (to result in an overall rocking angle

of Θ = 90o; see Figure 2). Although the flow conditions at the electrode surface are more

complex compared to those at the rotating disc electrode, an approximate quantitative

expression for the resulting limiting currents and for the diffusion layer thickness (assuming

laminar flow conditions) has recently been developed (equations 1 and 2, respectively [12]).

I RoDE=0.111 nFAc D23 ❑

−16 √Θf

(1)

δ RoDE=9.0 D

13 ❑

16

√Θ f

(2)

In these expressions the mass transport limited current at the rocking electrode, IRoDE, (or the

diffusion layer thickness RoDE) is expressed in terms of n, the number of electrons transferred

per redox active molecule diffusing to the electrode surface, F, the Faraday constant, A, the

electrode area, c, the concentration of the redox active solution species, D, the diffusion

coefficient of the redox active solution species, v, the kinematic viscosity, Θ, the total rocking

angle, and f, the rocking frequency (in Hz). In particular the expression for the diffusion layer

thickness RoDE is important in order to quantitatively assign chemical rate constants for

processes that occur within the diffusion layer of the electrode (vide infra).

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In this study, proof of principle data are provided for rocking disc voltammetry employed as a

tool to quantify electrochemical rate constants as well as for applying well-defined mass

transport conditions for electro-synthetic transformations. A set of seven primary alcohols are

investigated with TEMPO as a homogeneous electro-catalyst. Experimental chemical rate

constants are evaluated and compared to calculated DFT data (assuming a concerted hydride

transfer transition state as the kinetic limiting step [32]) to rationalise the higher reactivity

observed for the cases of methanol and aromatic substituents attached to the primary alcohol

carbon.

2. Experimental Details

2.1. Chemical Reagents

2,2,6,6-tetramethylpiperidine-1-oxyl (Fluka, 98%), methanol (Fisher Scientific, 99.99%),

ethanol (Sigma-Aldrich, 99.8%), butan-1-ol (Sigma-Aldrich, 99%), 2-pyridinemethanol

(Aldrich, 98%), 3-pyridinemethanol (Aldrich, 98%), hexan-1-ol (Aldrich, 98%), sodium

bicarbonate (Sigma-Aldrich, 98%), and sodium hydroxide (Sigma-Aldrich, 99.7%) were

obtained commercially and used without further purification. Solutions were prepared in

demineralized and filtered water taken from a Thermo Scientific water purification system

(Barnstead Nanopure) with a resistivity of 18.2 MΩcm (at 22 oC).

2.2. Instrumentation

For voltammetric studies, a microAutolab II potentiostat system (EcoChemie, Netherlands)

was employed with a KCl-saturated calomel reference electrode (SCE, Radiometer). For all

experiments, the reference electrode was placed approximately 2 mm from the working

electrode. The working electrode was a glassy carbon macrodisc electrode with a diameter of

3.0 mm (BAS). The counter electrode was a platinum wire. Rocking motion (90 degrees) of

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the working electrode was applied with an IKA Eurostar digital motor using an in-house

build device (see Figure 2). All experiments were conducted under ambient conditions at a

temperature of 22 ± 2 oC.

Figure 2. Schematic drawing of the motor-driven rocking disc system with a mechanism that results in a 90 degree total rocking angle.

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2.3. Simulation Procedure for Kinetic Analysis

Simulations for rocking disc experiments were performed assuming a 1D finite diffusion

model (hydrodynamic conditions, see parameter table in Electronic Supplementary Material),

using the diffusion layer thickness determined based on equation 2 from steady-state

experimental data for only TEMPO in aqueous 0.1 M carbonate buffer solution at pH 9.5.

The parameters for the catalytic mechanism were chosen as shown below (Table 1; see text).

The electron transfer kinetic constant ke1 and ke2 were obtained experimentally (ke1 = 1.0 × 103

m s-1, ke2 = 3.5 × 10-8 m s-1, see text) by simulating and fitting cyclic voltammetry data and the

separation of the oxidation and reduction peaks using DigiElch 4.F simulation software. The

transfer coefficients () were tentatively assumed to be 0.5 for both electron transfer steps.

Due to the alcohol to aldehyde reaction formally being a two-electron process, the first step

was selected as rate determining (to compare to experimentally determined rate constants)

and the second electron transfer was selected to be fast and essentially irreversible to not

affect the simulation. The production of two equivalents of protons in the alcohol oxidation

could affect the pH and thereby slow down the reaction for faster reaction rates, but this

effect has not been taken into account in the simulation (vide infra). The rate of

comproportionation of TEMPO+ and TEMPO- to 2 TEMPO (Figure 1) is assumed to be rapid

in aqueous alkaline conditions and was therefore set high such that it was not rate limiting.

The rate constant for the rate limiting step is the reaction of TEMPO+ with alcohol, the

chemical rate constant kc, is the only adjustable parameter to fit the theory to the experimental

data. All diffusion coefficients of substrates were approximated by literature values reported

for similar conditions, or estimated based on the Wilke-Chang expression [39] (see Table 1).

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Table 1. List of substrates and their diffusion coefficients used in simulations.

Molecular species Diffusion coefficient / m2 s-1 Reference

TEMPO/TEMPO-/TEMPO+ 0.62 × 10-9 experimental data, see text

methanol 1.4 × 10-9 [40]

ethanol 1.2 × 10-9 [41]

butan-1-ol 0.85 × 10-9 [42]

hexan-1-ol 0.70 × 10-9 Wilke-Chang estimate [39]

benzyl alcohol 0.82 × 10-9 [43]

2-pyridinemethanol 0.76 × 10-9 Wilke-Chang estimate [39]

3-pyridinemethanol 0.76 × 10-9 Wilke-Chang estimate [39]

2.4. Density Functional Theory (DFT) Computation of Kinetic Barriers

Calculations were performed with Gaussian09 suites of code [44] and protocol rB3LYP/6-

311++G(d,p)/SCRF= (cpcm,solvent=water)/ temperature= 298.15. The nature of all the

stationary points as minima or transition states was verified by calculations of the vibrational

frequency spectrum. All transition states were characterized by normal coordinate analysis

revealing precisely one imaginary mode corresponding to the intended reaction. Full details

and summary tables can be found in the Electronic Supplementary Material. Full coordinates

for all stationary points, together with computed free enthalpies and vibrational frequency

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data, are available via the corresponding Gaussian 09 output files, stored in digital

repositories (DOI: 10.6084/m9.figshare.3079963 and DOI: 10.6084/m9.figshare.3079966).

These datasets will be made publicly available as soon as the article is accepted for

publication (see private links in the ESM for review process).

3. Results and Discussion

3.1. Rocking Disc Electrode Voltammetry I.: Oxidation of TEMPO in Carbonate Buffer

Voltammetric data for TEMPO oxidation at a 3 mm diameter glassy carbon electrode

immersed in pH 9.5 carbonate buffer are shown in Figure 3. Two prominent processes are

observed and assigned to P1: the oxidation of the free radical TEMPO to the cation (equation

3) and P2: the reduction of TEMPO to the one-electron reduced form TEMPO- with a pKA ≈

6.9 [45,46] (equation 4).

P1: TEMPO TEMPO+ + e- (3)

P2: TEMPO + e- TEMPO- (4)

From analysis of the midpoint potentials (obtained from the peak potentials with Emid = ½

Ep,ox + ½ Ep,red, see Figure 3), it is possible to obtain the approximate reversible potentials for

process P1 (TEMPO/TEMPO+ with Emid of +0.49 V vs. SCE) and for process P2

(TEMPO-/TEMPO with Emid of -0.20 V vs. SCE). From the peak-to-peak separation for

process P1, ca. 60 mV, it is inferred that electron transfer at the electrode | solution interface

is fast. In contrast, for the peak-to-peak separation for process P2, ca. 700 mV, it can be

concluded that electron transfer is essentially irreversible (although the shape of the

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voltammetric response suggests further complexity). Further analysis of the data was carried

out by comparison to simulation data (utilizing DigiElch 4.F software, see simulation data

presented as dashed line in Figure 3).

With the concentration of TEMPO in solution known (1 mM or 3 mM), initially the diffusion

coefficient for TEMPO was evaluated by matching the peak currents for process P1. The

resulting value, DTEMPO = 0.6 × 10-9 m2s-1, is in reasonable agreement with previous literature

values (DTEMPO = 0.77 × 10-9 m2s-1 [47]) and applied here for all three species: TEMPO+,

TEMPO, and TEMPO-. Next, the rate for heterogeneous electron transfer for process P1 was

selected high (103 m s-1) whereas the position of the reduction and oxidation peaks for process

P2 were matched to give an apparent standard rate constant for heterogeneous electron

transfer of ke2 = 3.5 × 10-8 m s-1. The dashed line in Figure 3 suggests reasonable agreement

between experiment and simulation employing these parameters.

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Figure 3. Cyclic voltammetric data obtained at a scan rate of 10 mVs-1 for (A) 1 mM and (B) 3 mM TEMPO dissolved in 0.1 M carbonate buffer pH 9.5. Comparison of experimental data (solid lines) with simulations (dashed lines, see text).

Under hydrodynamic conditions the nature of voltammetric processes changes from transient

(with peak responses) to steady state (with sigmoidal responses). Typical rocking disc

electrode voltammetry data are shown in Figure 4A. With increasing rocking rate, the shape

changes and the mass transport limited current increases. A quantitative “Levich-type”

expression for this type of process has been reported recently [12] (see equation 1) to link

I lim ¿¿ the hydrodynamic mass transport limited current to experimental parameters. As shown

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in the plot in Figure 4B, the limiting current is indeed linearly dependent upon the square root

of rocking frequency and in excellent agreement with the theory.

Figure 4. A) Cyclic voltammogram recorded at 10 mVs-1 of 1 mM TEMPO in 0.1M carbonate buffer pH 9.5 at (i) 0 Hz, (ii) 0.83 Hz, (iii) 1.67 Hz, (iv) 3.33 Hz, (v) 6.67 Hz and (vi) 16.67 Hz. B) “Levich plot” of the limiting current taken from cyclic voltammograms recorded at 10 mVs-1 at +0.9 V vs. SCE.

Data in Figure 4B can be used to confirm the diffusion coefficient for TEMPO (vide supra).

The kinematic viscosity of the electrolyte solution is approximated here to be the same as

pure water (1.0 × 10-6 m2s-1 at 20 0C). Taking the gradient of the linear plot in Figure 4B and

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applying equation 1 yields DTEMPO = 0.62 (± 0.06) × 10-9 m2s-1. This value is in good

agreement with the value attained from fitting transient voltammetry data (vide supra). When

evaluating the diffusion layer thickness based on equation 2 and employing the DigiElch

simulation tool, it is now possible to model the steady state voltammetric data as well as

coupled homogeneous reactions, which may occur within the diffusion layer of the rocking

disc electrode.

3.2. Rocking Disc Electrode Voltammetry II.: TEMPO-Mediated Oxidation of Ethanol in

Carbonate Buffer

In the presence of ethanol as a primary alcohol, the TEMPO-mediated 2-electron oxidation to

ethanal is observed as an increase in the mass transport controlled limiting current in rocking

disc voltammetry data. Figure 5A shows the increase in current going from 0 mM to 15 mM

ethanol substrate concentration. The mass transport limited current does not scale linearly

with substrate concentration as would be expected for a very fast catalytic reaction. This is

consistent with homogenous TEMPO catalysis and a tell-tale sign for a chemical reaction

step limiting the current at high substrate concentrations. Figure 5B shows that increasing the

rocking frequency (or decreasing the diffusion layer thickness) also increases the mass

transport limited current. However, the current due to the catalytic process relative to the

mass transport limited current for TEMPO oxidation only decreases. A convergence of

limiting currents for all substrate concentrations at higher rocking rates shown in Figure 5D.

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Figure 5. (A) Cyclic voltammograms (scan rate 10 mVs-1, rocking rate of 1.67 Hz) for oxidation of 1 mM TEMPO in 0.1 M carbonate buffer pH 9.5 with (i) 0 mM, (ii) 5 mM, (iii) 10 mM and (iv) 15 mM ethanol. (B) As above, but with 5 mM ethanol and rocking rate of (i) 0.83 Hz, (ii) 3.33 Hz, (iii) 6.67 Hz and (iv) 16.67 Hz. (C) Cyclic voltammograms (scan rate 10 mVs-1, rocking rate 1.67 Hz) with 5 mM ethanol. Comparison of experiment with simulation data for kc = 20 M-1s-1. (D) “Levich plot” showing experimental limiting current data at +0.9 V vs. SCE for cyclic voltammetry data plots for 5 mM (■), 10 mM (▲) and 15 mM (●) ethanol compared with simulation for kc = 20 M-1s-1 and DEtOH = 1.2 × 10-9 m2s-1 [41] for 5 mM (+), 10 mM (x), and 15 mM (_) ethanol.

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The proposed model for the overall reaction is shown in the reaction scheme in Figure 1. The

rate constant kc for the alcohol oxidation step is responsible for the additional current in the

presence of ethanol and an approximate simulation model can be used to describe the overall

process. However, a first approximate value for this rate constant can be obtained already by

extrapolation of data in Figure 5D towards very slow rocking rates. Dashed lines are used to

indicate the estimated limit of purely kinetic current Ikin where the underlying mass transport

controlled oxidation current for TEMPO becomes insignificant. An approximate equation for

this case can be based on the assumption that the reaction layer for ethanol oxidation equals

the diffusion layer for TEMPO oxidation [48] close to the electrode surface (see equation 5).

I kin=nF DTEMPO A [TEMPO ]√ kc [ethanol ]Dethanol

(5)

In this equation the kinetic current Ikin is related to n, the number of electrons shuttled by

TEMPO (here n = 2 due to the hydride transfer mechanism), F, the Faraday constant, DTEMPO

and Dethanol, the diffusion coefficients for TEMPO and ethanol, A, the geometric electrode

area, and the concentrations of TEMPO and ethanol. For parameters applied in experiments

in Figure 5D and with a rate constant kc = 20 M-1s-1, the currents indicated as dashed lines are

calculated (consistent with the low rocking rate limit). A global evaluation of kc for data

obtained under hydrodynamic conditions is possible when employing a digital simulation

tool.

For digital simulation, all parameters such as the rate of electron transfer, the

comproportionation rate, all diffusion coefficients, and all concentrations are known (see

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experimental) and fixed. Only the reaction rate constant kc is adjusted to match simulation

with experimental data. Figure 5C shows the close to quantitative agreement between theory

and experiment for the oxidation of 5 mM ethanol at a rocking frequency of 1.67 Hz. A good

agreement of experiment and theory is obtained for kc = 20 M-1s-1. Data for the analysis of

experiments with five different rocking rates and three different concentrations of ethanol are

summerised in Figure 5D. The global fit between experimental and simulation data (with a

single set of parameters) is satisfactory as it deviates by less than 6% for all concentration of

ethanol at all rocking frequencies. The deviation at the lowest rocking frequency of 0.83 Hz

is the worst at around 6% deviation for all three concentrations. Generally, the trends in

limiting currents with rocking rate and with concentration are reproduced by the simulation

and the rate constant kc appears valid (as does the mechanism). The main error in the

simulation is likely to be associated with the estimated diffusion coefficient for the alcohol.

3.3 Rocking Disc Electrode Voltammetry III.: Slow TEMPO-Mediated Oxidation of

Alcohols in Carbonate Buffer

In order to generate a larger data set of chemical rate constants, the rocking disc electrode

voltammetry data were recorded for a range of primary alcohols. Data for butan-1-ol, hexan-

1-ol, benzaldehyde, and 3-pyridine-methanol are shown in Figures 6, 7, 8, 9, respectively.

For butan-1-ol, a relatively good match of experiment and simulation is seen for 5 mM

substrate concentration with less than 3% deviation (Figure 6B). However, at higher substrate

concentrations of 10 mM and at 15 mM butan-1-ol, the deviation increases to around 5% and

6%, respectively. For butan-1-ol kc is 18 M-1s-1, which is similar to the value for ethanol.

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Figure 6. (A) Cyclic voltammogram (scan rate 10 mVs-1, rocking rate of 1.67 Hz) for oxidation of 1 mM TEMPO in 0.1 M carbonate buffer pH 9.5 in the presence of (i) 5 mM, (ii) 10 mM, and (iii) 15 mM butan-1-ol. (B) “Levich plot” of experimental limiting currents at +0.9 V vs. SCE for 5 mM (■), 10 mM (▲), and 15 mM (●) butan-1-ol compared with simulated currents for 5 mM (+), 10 mM (x), and 15 mM (_) butan-1-ol with a rate constant of kc = 18 M-1s-1 and DBuOH = 8.5 × 10-10 m2s-1 [42].

A similar pattern of experimental versus simulation data is seen for hexan-1-ol (Figure 7).

With approximately 4% deviation between simulation and experimental data at 5 mM

substrate concentration the match of simulation with data is good. This deviation increases to

10% at 15 mM hexan-1-ol concentration at slow rocking rates. This could be an indication of

substrate solubility and aggregation issues in the aqueous electrolyte solution affecting the

proposed mechanistic scheme. Most likely an error in the diffusion coefficient estimates

could account for the deviation between experiment and simulation at higher substrate

concentrations. However, the value of kc = 20 M-1s-1 is essentially the same as kc for ethanol.

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Figure 7. (A) Cyclic voltammogram (scan rate 10 mVs-1, rocking rate of 1.67 Hz) for oxidation of 1 mM TEMPO in 0.1 M carbonate buffer pH 9.5 with (i) 0 mM, (ii) 5 mM, (iii) 10 mM, and (iv) 15 mM hexan-1-ol. (B) “Levich plot” of experimental limiting currents at +0.9 V vs. SCE for 5 mM (■), 10 mM (▲), and 15 mM (●) hexan-1-ol compared with simulated currents for 5 mM (+), 10 mM (x), and 15 mM (_) hexan-1-ol for a rate constant of kc = 20 M-1s-1 and DHxOH = 7 × 10-10 m2s-1 (estimated [39]).

For benzylalcohol (see Figure 8), the fit between simulation and experimental data is good

for all substrate concentrations and in particular at lower rocking frequencies. There are some

deviations at higher rocking frequency, which rises to around 10% at 16.7 Hz for all substrate

concentrations. Inspection of rocking disc electrode voltammetric data in this case shows that

for higher rocking rates the limiting current is not fully reached, which may account for this

deviation. The corresponding current suppression effect could be associated with faster mass

transport affecting adsorption of substrate and product at the electrode surface or with an

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onset of pH gradient effects (due to the weak buffer). The rate constant, kc = 55 M-1s-1,

evaluated for benzylalcohol is increased relative to that of ethanol.

Figure 8. (A) Cyclic voltammogram (scan rate 10 mVs-1, rocking rate of 1.67 Hz) for oxidation of 1 mM TEMPO in 0.1 M carbonate buffer pH 9.5 with (i) 0 mM, (ii) 4.85 mM, (iii) 9.89 mM, and (iv) 14.6 mM benzylalcohol. (B) “Levich plot” of experimental limiting currents at +0.9 V vs. SCE 4.85 mM (■), 9.89 mM (▲), and 14.6 mM (●) benzylalcohol compared with simulated currents for 4.85 mM (+), 9.89 mM (x), and 14.6 mM (_) benzylalcohol fora rate constant of kc = 55 M-1s-1 and Dbenzylalcohol = 8.21 × 10-10 m2s-1 [43].

When investigating 3-pyridinemethanol (Figure 9), the deviation between experiment and

numerical simulation at lower rocking frequencies appears acceptable. The deviation again

increases at the highest rocking frequencies to over 10% for all three substrate concentrations.

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The deviation at high rocking rates again is associated with the limiting current only very

gradually increasing, possibly due to an adsorption effect when using relatively large

aromatic substrate molecules in aqueous environment or the onset of pH gradient effects. The

value for kc, 122 M-1s-1, is further increased when compared to that for benzaldehyde.

Figure 9. (A) Cyclic voltammogram (scan rate 10 mVs-1, rocking rate of 1.67 Hz) for oxidation of 1 mM TEMPO in 0.1 M carbonate buffer pH 9.5 with (i) 0 mM, (ii) 4.7 mM, (iii) 9.5 mM, and (iv) 14 mM 3-pyridinemethanol. (B) “Levich plot” of experimental limiting currents at +0.9 V vs. SCE for 4.7 mM (■), 9.5 mM (▲), and 14 mM (●) 3-pyridinemethanol compared with simulation data for 4.7 mM (+), 9.5 mM (x), and 14 mM (_) 3-pyridinemethanol for a rate constant of kc = 122 M-1s-1 and D3PM = 7.6 × 10-10 m2s-1 (estimated [39]).

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3.4. Rocking Disc Electrode Voltammetry IV.: Fast TEMPO-Mediated Oxidation of

Alcohols in Carbonate Buffer

Data for 2-pyridine-methanol and for methanol are presented in Figures 10 and 11,

respectively. When compared to other substrates, the overall fit between experimental data

and simulated catalytic currents is relatively poor, although rate constants of kc = 215 M-1s-1

and kc = 217 M-1s-1 are obtained indicative of fast catalysis. The experimental limiting

currents for both 2-pyridinemethanol and methanol appear to be almost independent of

rocking frequency at substrate concentrations 10 mM and 15 mM (see Figures 10 and 11).

The experimental currents are lower than those predicted by the simulation, and this deviation

is more severe for higher substrate concentrations. In this case, the lack of buffer capacity for

the weak carbonate buffer at pH 9.5 may play a significant role. The lack of adequate pH

control is likely to impact on experimental data in particular for fast reaction rates and for

higher concentrations of substrate. The values for kc obtained here are realistic, but probably

somewhat underestimate the true rate constant values.

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Figure 10. A) Cyclic voltammogram recorded at 10 mVs-1 of 1 mM TEMPO in 0.1 M carbonate buffer pH 9.5 at a rocking rate of 1.67 Hz, with (i) 0 mM, (ii) 5 mM, (iii) 10 mM and (iv) 15 mM 2-pyridinemethanol. B) Levich plot of experimental limiting currents at +0.9 V vs. SCE extracted from cyclic voltammetry data for 5 mM (■), 10 mM (▲) and 15 mM (●) 2-pyridinemethanol compared with currents predicted from simulation (5 mM (+), 10 mM (x) and 15 mM (_)) assuming a rate constant of kc = 215 M-1s-1 and D2PM = 7.6 x 10-10 m2s-1

(estimated [39]).

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Figure 11. A) Cyclic voltammogram recorded at 10 mVs-1 of 1 mM TEMPO in 0.1 M carbonate buffer pH 9.5 at a rocking rate of 1.67 Hz, with (i) 0 mM, (ii) 5 mM, (iii) 10 mM and (iv) 15 mM methanol. B) “Levich plot” of experimental limiting currents at +0.9V vs. SCE extracted from cyclic voltammogram plots for 5 mM (■), 10 mM (▲) and 15 mM (●) methanol compared with currents predicted from simulation (5 mM (+), 10 mM (x) and 15 mM (_)) assuming a rate constant of kc = 217 M-1s-1 and DMeOH = 1.4 × 10-9 m2s-1 [40].

3.5. Comparison of Rocking Disc Electrode Voltammetry Data with DFT Calculation of

the Hypothetical Transition State for Hydride Transfer

In order to rationalise trends in reactivity of TEMPO+ towards primary alcohols, it is

instructive to explore computational methods. Recently, some of us investigated by DFT

calculations [32] the reaction between various primary alcohols and a derivative of the

TEMPO+ cation, associated with a NaCO3- anion originated from the buffer used

25

experimentally. As expected from a strong oxidant, the oxidation of alcohols to aldehydes by

TEMPO+ was shown to be thermodynamically favoured (ΔG ≤ -200 kJ mol -1). Our

calculations revealed that the key hydride transfer step from the primary alcohol to the

TEMPO+ cation could occur via a concerted transition state, in which the NaCO3- buffer

anion “activate” the alcohol via deprotonation, with activation barriers low enough for the

reaction to happen readily at room temperature. These barriers were used to estimate catalytic

rate constant and showed good agreement with experimental trends. In the present study, the

same level of theory was used (see experimental details) for the calculation of the concerted

hydride transfer (nominally a 2-electron process) from the C-H of various primary alcohols

(activated by NaCO3- buffer anion) to the oxygen of TEMPO+ cation (see Figure 12B). As

previously, the hydride transfer was found to be strongly thermodynamically favoured and

activation barriers low enough for the reaction to happen readily at room temperature (see

experimental details and ESM). Failing to include the buffer anion in the model resulted in

activation barriers impossible to achieve at room temperature. An alternative pathway

involving the formation of a cyclic intermediate was also examined but not selected because

of higher activation barriers (see ESM). Using the proposed concerted hydride transfer as the

kinetic limiting step, activation energy (EA) barrier values were obtained and plotted as

Boltzmann coefficients versus the experimentally measured chemical rate constants kc in

Figure 12A.

26

Figure 12. (A) Double logarithmic plot of the Boltzmann coefficient exp(-EA/RT) from DFT calculations versus the experimental chemical rate constant kc. (B) Drawing of the type of transition state chosen for DFT optimisation.

For all simple aliphatic primary alcohols except methanol a cluster of points is observed. For

methanol a significant increase in reaction rate is predicted by DFT approximately consistent

with the experimental observation. All aromatically substituted primary alcohols are

predicted to be faster reacting in agreement with experiment, although no simple correlation

from data is apparent. Both, experimental methods and computational methods will have to

be further refined (including an in-depth investigation of other possible mechanistic pathways

27

and solvent effects) to provide further insight into the TEMPO-mediated oxidation

mechanism.

4. Conclusions

The rocking disc electrode technique has been utilized to investigate a complex catalytic

mechanism of TEMPO-mediated oxidation of primary alcohols in aqueous carbonate buffer.

A catalytic mechanism was used to obtain catalytic rate constants for methanol, ethanol,

butan-1-ol, hexan-1-ol, benzyl alcohol, 2-pyridinemethanol and 3-pyridinemethanol. The rate

limiting step is the chemical reaction between TEMPO+ and the alcohol substrate (with

assumed rapid comproportionation between TEMPO- and TEMPO+ species to give 2

TEMPO). Primary alcohols with aromatic substituents and methanol are found to be more

reactive than aliphatic alcohols (consistent with DFT theory). For substrates with faster

chemical kinetics (3-pyridinemethanol and methanol) a greater deviation between experiment

and theory is observed (less well defined limiting currents), which is likely to be caused here

by insufficient pH control. Further work will be required to establish a broader portfolio of

experimental values for further mechanistic analysis. The rocking disc voltammetric method

promises an experimentally convenient and reliable hydrodynamic tool for kinetic studies.

Acknowledgements

SDA thanks Inochem Ltd and the University of Bath for support for a studentship. ACF and

FM thank the National Research Foundation Singapore under its Campus for Research

Excellence and Technological Enterprise (CREATE) programme for funding this research.

28

AB thanks Roger and Sue Whorrod for funding and the EPSRC NSCCS (chem826) and the

University of Bath (Balena cluster) for computing resources.

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