TEMPO-mediated electrooxidation of primary and secondary alcohols in a microfluidic electrolytic cell

Article abstract of DOI:10.1002/cssc.201100601

A general procedure for the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated electrooxidation of primary and secondary alcohols modified for application in a microfluidic electrolytic cell is described. The electrocatalytic system utilises a buffered aqueous tert-butanol reaction medium, which operates effectively without the requirement for additional electrolyte, providing a mild protocol for the oxidation of alcohols to aldehydes and ketones at ambient temperature on a laboratory scale. Optimisation of the process is discussed along with the oxidation of 15 representative alcohols. TEMPO and no salt in sight: A general procedure for the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated electrooxidation of primary and secondary alcohols modified for application in a microfluidic electrolytic cell is described. The reaction is performed at ambient temperature in buffered aqueous tBuOH without additional electrolyte. Copyright

Full text of DOI:10.1002/cssc.201100601

DOI: 10.1002/cssc.201100601
TEMPO-Mediated Electrooxidation of Primary and
Secondary Alcohols in a Microfluidic Electrolytic Cell
Joseph T. Hill-Cousins,[a] Jekaterina Kuleshova,[a] Robert A. Green,[a] Peter R. Birkin,[a]
Derek Pletcher,[a] Toby J. Underwood,[b] Stuart G. Leach,[c] and Richard C. D. Brown*[a]
A general procedure for the 2,2,6,6-tetramethylpiperidine-1-
oxyl (TEMPO)-mediated electrooxidation of primary and secon-
dary alcohols modified for application in a microfluidic electro-
lytic cell is described. The electrocatalytic system utilises a buf-
fered aqueous tert-butanol reaction medium, which operates
effectively without the requirement for additional electrolyte,
providing a mild protocol for the oxidation of alcohols to alde-
hydes and ketones at ambient temperature on a laboratory
scale. Optimisation of the process is discussed along with the
oxidation of 15 representative alcohols.
Introduction
In recent years, microflow reactors have received a great deal
of interest from synthetic chemists in both academia and in-
dustry[1] as they allow convenient synthesis on a 1 g scale with
improved selectivities and reduced reaction times. Electrolysis
can provide alternative routes to the synthesis of organic mol-
ecules,[2] but has never become a routine procedure in synthet-
ic laboratories. In the belief that electrolysis in a microflow en-
vironment can provide unique opportunities for convenient
synthetic procedures, we have recently initiated a programme
of research in microfluidic electrosynthesis[3] with the aim of
developing a range of simple, effective transformations for ev-
eryday use in the laboratory. This paper describes the modifica-
tion of a known electrosynthesis for the conversion of alcohols
to aldehydes and ketones, a reaction of fundamental impor-
tance in organic synthesis, so that it can be performed with
high selectivity and conversion in a microflow cell.
Figure 1. TEMPO-mediated electrochemical alcohol oxidation.
and secondary alcohols under microflow conditions, at ambi-
ent temperature, in an environmentally acceptable reaction
medium is reported.[9] The protocol is intended for the conver-
sion of alcohols with high selectivity on a laboratory scale
using a microfluidic apparatus. To our knowledge, this is the
first report of such a process.
A considerable number of methods are currently available
for the oxidation of alcohols to aldehydes and ketones, but
some of them involve harsh reaction conditions, low tempera-
tures and/or the use of toxic or hazardous reagents. Converse-
ly, stable organic nitroxyl radicals, particularly 2,2,6,6-tetrame-
thylpiperidine-1-oxyl (TEMPO, 3), have been identified as envi-
ronmentally benign catalysts for the oxidation of alcohols.[4]
The active species in the TEMPO-mediated oxidation of alco-
hols is the oxoammonium ion 4, which is typically generated
in situ with a stoichiometric co-oxidant, such as sodium hypo-
chlorite. The coproduct of alcohol oxidation, hydroxylamine 5,
is rapidly reoxidised to the TEMPO radical (3) in the presence
of oxygen[5] or by the cooxidant. The oxoammonium ion can
also be generated from TEMPO electrochemically through a
single electron transfer process at the anode (Figure 1).[6] Al-
though there is a good deal of literature precedent for the
TEMPO-mediated electrooxidation of alcohols, at present only
a few preparative procedures have been reported that use
TEMPO and its analogues[7] or other nitroxyl radicals[8] in a tra-
ditional batch cell. Herein, the development of a general pro-
cedure for the TEMPO-mediated electrooxidation of primary
Results and Discussion
The microfluidic experiments were conducted by using a
single channel microfluidic electrolysis cell[10] connected to a
[a] Dr. J. T. Hill-Cousins, Dr. J. Kuleshova, R. A. Green, Dr. P. R. Birkin,
Prof. D. Pletcher, Prof. R. C. D. Brown
School of Chemistry
University of Southampton
Southampton, Hampshire, SO17 1BJ (UK)
Fax: (+44)23-80594108
E-mail: rcb1@soton.ac.uk
[b] T. J. Underwood
Pfizer Ltd.
Sandwich, Kent, CT13 9NJ (UK)
[c] Dr. S. G. Leach
GlaxoSmithKline
Stevenage, Herts, SG1 2NY (UK)
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cssc.201100601.
326
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ChemSusChem 2012, 5, 326 – 331

Electrooxidation of Primary and Secondary Alcohols
commercially available flow system (FRX, Syrris), which also
permitted controlled heating of the cell.
pH values, subsequent electrochemistry was conducted in a
more environmentally desirable tBuOH/aqueous buffer (1:1)
mixed solvent system.[15] Further development of the TEMPO-
mediated flow electrochemical oxidation was guided by the
cyclic voltammetry studies described below.
Initial studies performed in a solvent mixture of acetonitrile
and an aqueous carbonate buffer as a homogeneous reaction
medium showed successful oxidation of benzyl alcohol (1a) to
benzaldehyde (2a) with high conversion in a single pass
(Table 1). The importance of a basic medium has been previ-
ously highlighted,[6d,7a,b] and the use of a partially aqueous
system ensured a more balanced electrochemical process,
where the desired anode transformation is given by Equa-
tion (1):
In many media, cyclic voltammograms have been reported
to show that TEMPO undergoes a reversible single-electron ox-
idation to the corresponding oxoammonium ion 4.[6,7d,f] It has
also been shown that in the presence of alcohols, the anodic
peak becomes irreversible; a small catalytic current is ob-
served, and the current density for the mediated oxidation of
the alcohol can be increased by the addition of a base.
RCH2OH þ 2 OHꢀ ꢀ 2 eꢀ ! RCHO þ 2 H2O
ð1Þ
In this work, cyclic voltammetry at a glassy carbon disc elec-
trode (area 0.07 cm2) was used to select the appropriate pH for
the electrosyntheses in the microflow cell. A cyclic voltammo-
gram recorded at 228C for TEMPO (2 mm) alone in tBuOH/H2O
(1:1) at pH 9.2 shows all the characteristics of a reversible
single-electron oxidation [curve (a), Figure 2]. Curves (b)–(e) are
the voltammograms for solutions containing TEMPO (2 mm)
with Equation (2)
4 OHꢀ ꢀ 4 eꢀ ! O2 þ 2 H2O
ð2Þ
as a competing reaction. The main counter electrode reaction
is given by Equation (3):
2 H2O þ 2 eꢀ ! H2 þ 2 OHꢀ
ð3Þ
Interestingly, production of gas bubbles in the flow channel
did not impede the performance of the cell under the condi-
tions employed, while the formed hydroxide ion ensured a pH
balance in the microchannel.[11]
For the reactions conducted in CH3CN mixtures, operating
with a constant current of 20 mA (ꢁ5 mA)[12] and a 30 mol%
TEMPO loading, a survey of temperature and pH indicated that
high conversion and selectivity could be realised at
pH 10.2[13,14] in the temperature range 22–308C (entries 1, 4
and 5 in Table 1). Further increase in temperature or pH gener-
ally resulted in reduced yield and selectivity, with small quanti-
ties of benzoic acid formed. However, due to concerns over
the hydrolytic and electrochemical stability of CH3CN at high
Figure 2. Cyclic voltammograms for solutions of TEMPO (2 mm) in tBuOH/
H2O containing Na2CO3/NaHCO3 at a scan rate of 50 mVsꢀ1 at 228C.
(a) pH 9.2 without added BnOH; (b) pH 9.2, BnOH (16 mm); (c) pH 10.6,
BnOH (16 mm); (d) pH 11.5, BnOH (16 mm); (e) pH 11.6, BnOH (16 mm).[14]
and benzyl alcohol (BnOH, 16 mm) at four pH values in the
range 9.2–11.6. In voltammograms (b)–(e), there is no cathodic
peak for the reduction of the oxoammonium ion on the re-
verse scan, which confirms a chemical reaction of the oxoam-
monium ion with the alcohol. Also, the anodic peak for the ox-
idation of TEMPO in the presence of BnOH has become a sig-
moidal wave, where the limiting currents are significantly
larger than the anodic peak in the absence of alcohol. Such re-
sponses are characteristic of a mediated oxidation of the alco-
hol, for which the catalytic cycle leading to the regeneration of
the electroactive species is relatively slow. Certainly, the limit-
ing currents are low compared to that estimated for the mass
transport-controlled oxidation of the alcohol, if the mass trans-
fer coefficient used was measured using the reduction of ferri-
cyanide as the model reaction.[10] The key observation from
Figure 2, however, is that the limiting current increases with in-
creasing pH, and the variation is a factor of five (Figure 3). This
represents a significant increase in the turnover rate of the
TEMPO catalyst and, hence, formation of aldehyde product,
and this is important in the context of microflow electrolysis.
Table 1. Electrolytic TEMPO-mediated oxidation of benzyl alcohol in
CH3CN/0.1m aqueous buffer (1:1).
Entry
pH[a]
T
[8C]
Conversion[e]
[%]
Yield of 2a[e]
[%]
Selectivity[f]
[%]
1
2
3
4
5
6
7
10.2[b]
11.2[c]
11.7[d]
10.2[b]
10.2[b]
10.2[b]
10.2[b]
22
22
22
25
30
35
50
71
75
82
76
85
88
88
71
65
61
76
81
73
70
100
87
74
100
95
83
80
[a] Measured pH of reaction mixture. [b] pH 9.16, buffer/CH3CN (1:1),
BnOH (0.1m), TEMPO (0.03m). [c] pH 10.14, buffer/CH3CN (1:1), BnOH
(0.1m), TEMPO (0.03m). [d] pH 10.83, buffer/CH3CN (1:1), BnOH (0.1m),
TEMPO (0.03m). [e] Yield and conversion were determined by using GC
against calibration curves of BnOH and benzaldehyde. [f] Yield based on
recovered BnOH.
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R. C. D. Brown et al.
Figure 4. Cell current vs. cell voltage curves in the microflow cell for
(a) tBuOH/H2O containing Na2CO3/NaHCO3, pH 11.5, after the addition of
(b) TEMPO (30 mm), and (c) TEMPO (30 mm) and BnOH (100 mm). Tempera-
Figure 3. Graph showing the effect of the pH value on the peak current for
the electrochemical TEMPO-mediated oxidation of BnOH in tBuOH/H2O.
ture: 298 K. Solution flow rate: 0.1 mLminꢀ1
.
For a faster catalytic cycle, a shorter channel will suffice to give
high conversion. Inspection of Figure 3 also implies that the
highest rate for the oxidation of BnOH occurs at pH 11.5,
which is the pH value used in most electrosyntheses. A similar
pattern is observed for the cyclohexanol/TEMPO system. A
comparable trend in the kinetics of the catalytic cycle with pH
the oxidation of TEMPO to the oxoammonium ion. With the
solution containing both TEMPO and BnOH, the wave at 2.0 V
has an increased limiting current (from 14 to 58 mA) resulting
from the regeneration of TEMPO by reaction with the alcohol.
The oxidation wave is, however, drawn out along the cell volt-
age axis due to the unavoidable IR drop in this two electrode
cell, as well as the overpotentials at the two electrodes. In fur-
ther experiments, the limiting current increased with an in-
crease in either (a) solution flow rate or (b) temperature.
Hence, these experimental parameters may be used with other
alcohols to achieve full conversions in preparative electrolyses
when the rate of the TEMPO-mediated oxidation is lower.
Preparative electrolyses were performed by applying a con-
stant current below the limiting current seen in the above cur-
rent vs. voltage experiments to achieve a high current efficien-
was reported by Yamauchi et al. using
a fully aqueous
system.[16] However, they used lower concentrations of TEMPO
and alcohols and failed to recognise that at pH 13, the reaction
of the oxoammonium ion with hydroxide, is fast compared to
that with low concentrations of alcohol.[17]
The influence of temperature was also determined by using
cyclic voltammetry. Voltammograms were recorded for TEMPO
(2 mm) and BnOH (16 mm) at pH 11.5. Over the temperature
range 24–458C, the limiting current increased by a factor of 6.
Cell current vs. cell voltage plots were recorded directly in
the microflow cell. Although these remain instructive, it is im-
portant to recognise that these are not traditional voltammo-
grams: the current vs. potential response will vary along the
channel as the concentrations of TEMPO and alcohol change,
and the current will decrease towards zero as the exit is ap-
proached if a full conversion is achieved. Hence, the responses
are the integral of the currents along the channel plotted as a
function of applied cell voltage.
cy; for example, for electrolyses with
a flow rate of
0.1 mLminꢀ1 at 258C, the cell current was 20 mA. Further ex-
perimental support for operating the cell at a constant current
of 20 mA can be seen for a series of oxidations of cyclohexanol
(1l), for which a good balance of conversion and selectivity
was achieved (entry 2, Table 2).[18] Conversion is dependent on
the passage of charge, and at 10 mA a correspondingly low
conversion was obtained (entry 1, Table 2), whereas at higher
currents decreased yields and selectivities were observed (en-
Such current vs. cell voltage responses (Figure 4) were re-
corded in the microflow cell for (a) a solution of the tBuOH/
H2O containing buffer, pH 11.5; (b) the buffer solution also con-
taining 30 mm TEMPO; and (c) the buffer solution also contain-
ing 30 mm TEMPO+100 mm BnOH. In each case, the electroly-
ses were allowed to proceed for approximately 120 s prior to
recording the responses to achieve a steady state distribution
of both TEMPO and alcohol along the flow channel before the
cell current vs. cell voltage response was obtained by varying
the cell voltage at a rate of 25 mVsꢀ1. In this experiment, the
responses were recorded for a flow rate of 0.1 mLminꢀ1 and a
temperature of 258C. In the absence of TEMPO, no current is
observed until the cell voltage reaches 2.5 V, when oxygen
evolution commences and thereafter, with further increase in
cell voltage, the current increases steeply. When TEMPO is
present in solution, a well-formed oxidation wave is observed
at a cell voltage of approximately 2 V, and this corresponds to
Table 2. Influence of current on the conversion and selectivity for the
TEMPO-mediated oxidation of cyclohexanol measured at a constant flow
rate.[a]
Entry
Current
[mAꢁ5 mA]
Conversion[b]
[%]
Yield of 2l[b]
[%]
Selectivity[c]
[%]
1
2
3
4
10
20
30
40
54
86
82
89
41
85
72
72
76
99
88
81
[a] Reagents and conditions: flow rate=0.1 mLminꢀ1
,
258C, tBuOH,
NaHCO3/Na2CO3 buffer solution (pH 11.5). [b] Yield and conversion were
determined by using GC against calibration curves of cyclohexanol and
cyclohexanone. [c] Yield based on unreacted cyclohexanol.
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Electrooxidation of Primary and Secondary Alcohols
tries 3 and 4, Table 2), suggesting the occurrence of competing
reactions as the current is increased. At pH 11.5, the tempera-
ture had a modest influence on the conversion and selectivity,
and further oxidations were performed at 258C. However, sec-
ondary aliphatic alcohols are known to be more difficult to oxi-
dise in TEMPO-mediated systems;[4] here, cyclohexanone is pro-
duced in 85% yield and 99% selectivity.
Table 3. TEMPO-mediated oxidation of a range of primary and secondary
alcohols in the electrolysis flow cell.[a]
Entry Alcohol
Product
Conv.[b] Yield[b] Selectivity[c]
[%]
[%]
[%]
Under the same conditions, benzyl alcohol was oxidised to
benzaldehyde in 87% yield and 98% conversion (entry 1,
Table 3). 30 mol% of TEMPO was required to achieve a favour-
able rate of product formation (30–100 mghꢀ1), conversion,
and selectivity for the TEMPO-mediated oxidation of benzyl al-
cohol in the flow cell. Reducing the amount of TEMPO led to
lower conversions and selectivities at the same current and
flow rate. The decreased selectivity observed at lower TEMPO
loading is likely to be a consequence of the observed increase
in cell potential under these conditions. Approximately 60% of
the catalyst could be recovered at the end of the reaction, and
future work will focus on the identification of nitroxyl radical-
mediated systems that may operate at lower catalyst loadings,
and/or facilitate catalyst recovery. Alternatively, high rates of
conversion and selectivity may be achieved at lower TEMPO
loadings by using a microfluidic cell with a longer path length
(increased electrode area).
1
2
98%[d] 87[d]
89
88%
88
92
100
92
3
4
100%
94%
94
100
5
6
81%
60%
81
60
100
100
7
8
59%
79%
50
68
85
85
A range of primary and secondary alcohols were oxidised
under the preferred conditions (see Table 3). In general, benzyl-
ic and allylic alcohols are more easily oxidised. Despite the
slower chemistry,[4] secondary alcohols were also oxidised with
high conversion and selectivity. In particular, more electron-
rich benzylic alcohols were oxidised very efficiently in the flow
cell with excellent yields and selectivities. The more sterically
hindered and electron-poor benzylic alcohols (entries 6 and 7,
Table 3, respectively) show lower conversion, but still high se-
lectivities (100 and 85%, respectively). Examples of substrates
containing other electrochemically active functionalities were
also included in our study. Although reduced selectivities were
observed for the oxidation of compounds 1g–i (entries 7–9,
Table 3), their corresponding aldehydes 2g–i were obtained in
acceptable isolated yields. The nitro and halogen groups pres-
ent in 1g and 1h, respectively, may react at the cathode in an
undivided cell such as this, although no other products were
isolated from the reactions. The benzylic alcohol 1e containing
a methanesulfonate ester was oxidised with high selectivity at
81% conversion (entry 5, Table 3).
9
68%
80%
50
77
50
96
10
11
12
73%
72[e]
99
99
86%[d] 85[d]
13
29%
21
72
14
15
52%
62%
48
57
92
92
[a] Conditions: flow rate=0.1 mLminꢀ1, 20 mA (ꢁ5 mA), ROH (0.1m),
TEMPO (0.03m), 258C. [b] Yields are reported for purified isolated prod-
ucts. Conversions are based on isolated recovered starting material.
[c] Yield based on recovered starting material. [d] Yield and conversion
were determined by using GC. [e] Olefin isomerisation was observed
1
[ratio (E/Z)=1.8:1, H NMR spectroscopy].
Allylic alcohols 1j and 1k (entries 10 and 11, Table 3) were
oxidised in 77 and 72% yields, with excellent selectivities for
aldehyde products, whereas aliphatic alcohols, with the excep-
tion of cyclohexanol (1l, entry 12, Table 3), were slower to oxi-
dise under these conditions (entries 14 and 15, Table 3). Gener-
ally, the selectivity remained excellent, with only traces of the
corresponding carboxylic acids observed during the oxidation
of aliphatic alcohols 1n and 1o. The conversion of (ꢀ)-men-
thol (1m), a particularly hindered secondary alcohol, not sur-
prisingly showed poor conversion to the respective ketone 2m
(entry 13, Table 3). Current efficiencies were commonly ap-
proaching 100%, although for a few alcohols that were oxi-
dised more slowly the current efficiency dropped to 40–60%.
Increasing the residence time in the electrolysis cell by re-
ducing the flow rate to 0.05 mLminꢀ1 led to reduced selectivi-
ties at the same current (20 mA), with overoxidation to the cor-
responding acids becoming more prominent for alcohols 1 f,
1n and 1o. A higher yield of ketone 2m could be achieved in
this manner (38%), but the selectivity of the reaction was re-
duced significantly. This can be understood by the rate-limiting
reaction of the alcohol with oxoammonium ion 4; an increase
in total cell potential was observed, extending into the range,
where side reactions become more prevalent as was evident
from the cell current vs. cell voltage studies described above
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329

R. C. D. Brown et al.
(eluent EtOAc/hexane=1:4) affording the title compound 2d
(92 mg, 47 mmol 94%) as a colourless solid. Physical and spectro-
scopic data were consistent with reported values.[20] m.p. 74–758C
(lit.[20] 71–728C); 1H NMR (400 MHz, CDCl3, 258C): d=9.87 (s; 1H,
CH), 7.13 (s; 2H, CH), 3.94 (s; 3H, OCH3), 3.94 ppm (s; 6H, 2ꢁ
OCH3); 13C NMR (100 MHz, CDCl3, 258C): d=191.0 (C=O), 153.6 (2ꢁ
C), 143.6 (C), 131.7 (C), 106.7 (2ꢁCH), 61.0 (CH3), 56.3 ppm (2ꢁ
CH3); IR (Neat): n˜max =1681 cmꢀ1 (C=O). Additionally, alcohol 1d
(6 mg, 0.03 mmol, 6%) was recovered.
(Figure 4). Despite the slightly lower conversion for some of
the examples, the oxidation protocol allows for the production
of approximately 30–100 mg of aldehyde or ketone per hour,
depending on the substrate. The reactions do not require
added tetraalkylammonium salts as electrolyte and are very
clean, with generally only starting material and catalyst present
in crude reaction mixtures in addition to the desired product.
Conclusions
Acknowledgements
An electrocatalytic TEMPO-mediated process has been devel-
oped for the oxidation of primary and secondary alcohols to
aldehydes and ketones, respectively, in a microfluidic electroly-
sis cell. This alcohol oxidation allows a mild and convenient
laboratory scale synthesis in an aqueous tBuOH system at am-
bient temperature. The scope of the process has been evaluat-
ed through the oxidation of 15 representative alcohols, many
of which delivered high conversions and selectivities in a
single pass through the cell.
The authors acknowledge financial support from EPSRC contract
number EP/G02796X/1, Pfizer Ltd. and GlaxoSmithKline for a
CASE award (R.A.G.) and the European Regional Development
Fund (ERDF, ISCE-Chem & INTERREGIVa program 4061). We also
acknowledge the advice and support of Syrris Ltd. as partners in
this project.
Keywords: alcohols · aldehydes · electrolysis · flow chemistry ·
oxidation
Experimental Section
The microfluidic electrolytic cell was supplied by Syrris Ltd[19] and
was intended for application alongside its range of microflow
equipment. In consequence, the cell holder had similar dimensions,
solution connections, etc. to other Syrris microreactors. The elec-
trolysis cell was constructed from two rectangular electrode plates
(5.3 cmꢁ4.0 cmꢁ0.2 cm thick). The anode was carbon-filled polyvi-
nylidene fluoride (PVDF, type BMA5, Wilhelm Eisenhuth GmbH,
Germany, electrical resistivity in plane 180 mWmꢀ1), and the cath-
ode was stainless steel (grade 316 L, Castle Metals UK Ltd). The
perfluoroelastomer (FFKM, TRPlast 330B, 500 mm thick) spacer had
a ‘snaking’, microchannel of designed pattern cut into it to give an
extended channel length and to enhance the convection within
the channel. The steel electrode had a patterned, recessed channel
(depth 250 mm) machined into it to allow it to accept the pat-
terned spacer and thereby permit facile alignment of the inter-
electrode spacer; it also incorporated two fluid inlet/outlet holes.
The design provided a channel path length of 70 cm, combined
with a channel depth of approximately 200 mm (with the spacer
fitted into the recessed channel of the electrode and the cell com-
pressed) and a channel width of 0.15 cm, giving a cell volume of
approximately 0.21 cm3. The total electrode surface area in contact
with the fluid was 10.5 cm2 per electrode. The pumps and sample
injection loop were supplied by Syrris (FRX), and the pumps could
deliver 0.01–9.99 cm3 minꢀ1 with an accuracy of 1%.
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General Procedure for Oxidation Reactions
3,4,5-Trimethoxybenzaldehyde (2d): A solution of the alcohol 1d
(100 mg, 0.50 mmol) and TEMPO (23 mg, 0.15 mmol) in tBuOH
(2.5 mL) and aqueous buffer solution [Na2CO3 (0.1m)/NaHCO3
(0.1m)=8:2; 2.5 mL) was passed through the electrolytic cell at a
flow rate of 0.1 mLminꢀ1. The electrolysis was performed under a
constant current of approximately 20 mA, and the cell temperature
was maintained at 258C. The reaction solution was collected, 2m
HCl (10 mL) was added, and the resulting mixture extracted with
EtOAc (3ꢁ10 mL). The combined organic extracts were dried
(Na2SO4) and the solvent removed in vacuo. The residue was puri-
fied by performing flash column chromatography on silica gel
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330
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[14] The reported pH values for the reaction mixtures were measured by
using a pH meter.
[15] A recently published green chemistry solvent guide classifies acetoni-
trile as a “useable” solvent, whereas tBuOH is considered to be a “pre-
ferred” solvent on the basis of safety and environmental considerations
(see Ref. [4f]).
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[9] Other nitroxyl radicals were evaluated, but under the conditions de-
scribed proved less effective than TEMPO.
[17] An in depth discussion of the mechanism of the TEMPO oxidation will
be reported elsewhere.
[10] A comprehensive study on the cell performance will be reported else-
where.
[11] An in depth discussion of the effect of gas bubbles on the performance
of the electrolytic flow cell is outside the scope of the current article
and will be published separately.
[12] In an effort to develop an accessible system, a less expensive power
supply was used for the experiments as opposed to a more expensive
potentiostat. Consequently, there is an inherent error in the reported
current as a result of the accuracy of the unit.
[18] Although there is a significant error in the applied current and the use
of a more sensitive power supply may allow for a more accurate deter-
mination of the optimal current, it was considered that the overall
effect on the efficiency of the reaction would be very small. As a result,
no further current dependency studies were conducted.
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[13] Sodium carbonate/bicarbonate buffer solutions were made up accord-
ing to Delroy: G. E. Delory, Biochem. J. 1945, 39, 245–245. Details are
provided in the Supporting Information.
Received: September 27, 2011
Revised: January 9, 2012
ChemSusChem 2012, 5, 326 – 331
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemsuschem.org
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