Electrochemical Oxidation of Alcohols and Aldehydes to Carboxylic Acids Catalyzed by 4-Acetamido-TEMPO: An Alternative to "anelli" and "pinnick" Oxidations

Article abstract of DOI:10.1021/acscatal.8b01640

An electrocatalytic method has been developed to oxidize primary alcohols and aldehydes to the corresponding carboxylic acids using 4-acetamido-2,2,6,6-tetramethylpiperidin-1-oxyl (ACT) as a mediator. The method successfully converts benzylic, aliphatic, heterocyclic, and other heteroatom-containing substrates to the corresponding carboxylic acids in aqueous solution at room temperature. The mild conditions enable retention of stereochemistry adjacent to the site of oxidation, as demonstrated in a 40 g-scale synthesis of a precursor to levetiracetam, a medication used to treat epilepsy.

Full text of DOI:10.1021/acscatal.8b01640

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Article
Electrochemical Oxidation of Alcohols and Aldehydes
to Carboxylic Acids Catalyzed by 4-Acetamido-TEMPO
(ACT): An Alternative to "Anelli" and "Pinnick" Oxidations
Mohammad Rafiee, Zachary M. Konz, Matthew D. Graaf, Hannes F. Koolman, and Shannon S. Stahl
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b01640 • Publication Date (Web): 11 Jun 2018
Downloaded from http://pubs.acs.org on June 11, 2018
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Electrochemical Oxidation of Alcohols and
Aldehydes to Carboxylic Acids Catalyzed by 4-
Acetamido-TEMPO (ACT): An Alternative to
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"
Anelli" and "Pinnick" Oxidations
a
a
b
c,†
Mohammad Rafiee, Zachary M. Konz, Matthew D. Graaf, Hannes F. Koolman, and
Shannon S. Stahl *a
aDepartment of Chemistry, University of Wisconsin-Madison, 1101 University Avenue,
Madison, Wisconsin 53706, United States
bAbbVie, Process R&D, 1401 Sheridan Road, North Chicago, IL 60064, USA
cAbbVie, Discovery Chemistry and Technology, 1 North Waukegan Road, North Chicago, IL
6
0064, USA
ABSTRACT: An electrocatalytic method has been developed to oxidize primary alcohols and
aldehydes to the corresponding carboxylic acids, using 4-acetamido-2,2,6,6-tetramethylpiperidine
1
-oxyl (ACT) as a mediator. The method successfully converts benzylic, aliphatic, heterocyclic
and other heteroatom-containing substrates to the corresponding carboxylic acids in aqueous
solution at room temperature. The mild conditions enable retention of stereochemistry adjacent to
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the site of oxidation, as demonstrated in a 40 g-scale synthesis of a precursor to levetiracetam, a
medication used to treat epilepsy.
KEYWORDS: alcohols, aldehydes, carboxylic acids, oxidation, electrocatalysis,
electrochemistry, nitroxyl, aminoxyl
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Introduction
Oxidations of alcohols and aldehydes to carboxylic acids are widely used transformations in
organic chemistry.1-4 They are commonly featured in the synthesis of pharmaceuticals and other
industrial chemicals,5-8 and they are the focus of considerable attention for the conversion of
carbohydrates, sugars, and other biomass-derived feedstocks to value-added products.9-14 Classical
oxidation methods feature chromium and manganese oxide reagents;2,5 however, methods
employing organic aminoxyls in catalytic reactions used extensively,15-18 including applications to
the synthesis of complex molecules, such as natural products and pharmaceuticals. Methods
employing bleach (NaOCl) and TEMPO (2,2,6,6-tetramethylpiperidine N-oxyl) are especially
effective for alcohol oxidation, and a prominent example is the biphasic Anelli-Montonari
oxidation method that uses TEMPO and bromide as cocatalysts (Scheme 1A).19-25 Most of the
latter applications focus on production of aldehydes and ketones, but they have also been used to
prepare carboxylic acids.26-30 Sodium chlorite (NaClO
) has been shown to be an especially
2
2
effective oxidant for conversion of aldehydes to carboxylic acids. One of the most prominent
3
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examples of this reactivity is the so-called "Pinnick oxidation", which adapted from earlier
32
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34-37
precedents by Kraus and Lindgren and Nilsson (Scheme 1B).
A sacrificial alkene is often
included in these reactions to scavenge the hypochlorite byproduct of the reaction.
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A. Anelli oxidation of primary alcohols to aldehydes and carboxylic acids
cat. TEMPO/Br–
O
R
OH
R
O
or
NaHCO
3
, NaOCl
R
OH
B. Pinnick oxidation of aldehydes to carboxylic acids
O
O
NaClO
NaH
-methylbut-2-ene
2
/tBuOH
PO
R
H
2
4
R
OH
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Scheme 1. Common protocols for oxidation of aldehyde to carboxylic acid (1) and alcohol to aldehyde.
Electrochemical alcohol oxidation methods using organic aminoxyl mediators (i.e.,
electrocatalysts) have advanced considerably in recent years, and they provide a compelling
alternative to the more-traditional chemical methods.38 These methods are appealing, in part,
39
because they generate hydrogen gas as the sole byproduct of the reaction (eq 1). Electrochemical
methods for the oxidation of primary alcohols to carboxylic acids have been investigated primarily
for the conversion of mono/polysaccharides and other biomass-derived precursors.40-47 To our
knowledge, there are no reports of electrochemical aminoxyl-mediated methods for oxidation of
aldehydes. Moreover, preparative-scale oxidation of alcohols and aldehydes to carboxylic acids
with substrates bearing heterocycles and adjacent stereocenters that are commonly encountered in
pharmaceutical applications have not been investigated.
+
R
R
OH
O
O
or
+
H
2
O
TEMPO
+ (2) H2
(1)
R
OH
In a recent study, we demonstrated that the electrocatalytic activity of aminoxyl radicals is
more strongly affected by the redox potential of the aminoxyl than by its steric properties.48
Specifically, higher catalytic activity was observed for aminoxyls with higher potentials, and this
trend was evident even when comparing sterically hindered TEMPO derivatives to less-hindered
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aminoxyls such as ABNO (9-azabicyclo[3.3.1]nonane N-oxyl) and AZADO (2-azaadamantane N-
4
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oxyl). In electrocatalytic applications, the electrode potential may be tuned to match the redox
potential of the aminoxyl mediator, and the catalytic rate is controlled solely by the reactivity of
the oxoammonium species with the substrate. With chemical oxidants, such as bleach, the catalytic
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rate is often controlled by the rate of catalyst reoxidation. The low-cost aminoxyl, 4-acetamido-
TEMPO (ACT) was found to be a highly effective mediator for electrocatalytic oxidation of a
various simple alcohols. In the present study, we expand on these fundamental observations and
demonstrate the preparative-scale utility of ACT-mediated oxidation of primary alcohols and
aldehydes to carboxylic acids. Noteworthy outcomes include demonstration of the compatibility
of the reaction with pyridine-containing substrates and retention of stereochemical configuration
adjacent to an alcohol in the oxidation of a chiral alcohol to a carboxylic acid. The latter reactivity
is showcased in the oxidation of a key intermediate in the generic drug, levetiracetam.
Results and Discussion
For electrochemical oxidation by ACT and other aminoxyl radicals, aqueous carbonate buffer
(pH 8 to 11) is a suitable reaction medium that avoids the need for more-costly organic electrolytes
48
and makes the solution sufficiently basic to allow for fast oxidation of alcohols. In an effort to
explore an electrochemical aldehyde oxidation, we considered ACT under the same conditions.
Cyclic voltammetry and chronoamperometry methods were used for the initial evaluation of the
catalytic activity. Figure 1 shows the cyclic voltammograms (CVs) and chronoamperograms of
ACT in the absence and presence of 4-pyridinecarboxaldehyde (1b). In the absence of 1b, the CV
of ACT exhibits one anodic peak and a related cathodic peak (Figure 1, black trace a). The anodic
+
peak corresponds to the one-electron oxidation of ACT to the oxoammonium species ACT , while
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the cathodic peak corresponds to the one-electron reduction of the electrochemically generated
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ACT to ACT. The ratios of the cathodic-to-anodic peak currents are near unity, consistent with
+
48
+
the good stability of the ACT under these conditions. In the presence of 1b, ACT mediates
catalytic oxidation of the aldehyde substrate to the corresponding carboxylic acid 1c (Figure 1,
blue trace b), resulting in a significant increase in the anodic peak current and a disappearance of
the cathodic peak. Complementary data were obtained by chronoamerometry. A
chronoamperogram of ACT in the absence of 1b (Figure 1, black trace c) shows a diffusion-
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controlled oxidation current corresponding to the oxidation of ACT to ACT at the electrode. The
presence of 1b leads to a >10-fold increase in the oxidation current (Figure 1, blue trace d) due to
the catalytic turnover of ACT.50
Figure 1. ACT-catalyzed electrochemical oxidation of 1b (top), cyclic voltammograms (left) and
chronoamperograms (right) of 1 mM ACT in the absence (a and c) and presence (b and d) of 20 mM 1b.
–
1
Scan rate is 10 mVs for cyclic voltammetry and applied potential is 0.70 V vs. Ag/AgCl for
chronoamperometry. Reaction conditions: aqueous carbonate buffer, NaHCO :Na CO (0.1 M each), pH
0.
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The area under the chronoamperogram traces corresponds to the charge consumed during the
experiment, as depicted by the shaded regions in Figure 1, and the turnover frequency of the
reaction (TOF = 1770) was derived from the ratio of consumed charge in the absence and presence
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of 1b. This analysis accounts for the fact that oxidation of ACT in the absence of aldehyde is a
one-electron process, while ACT-mediated aldehyde oxidation is a two-electron process,
corresponding to oxidation of the hydroxylamine to the oxoammonium (cf. Figure 1). A similar
approach was then applied to various other alcohols and aldehydes (Figure 2). The relative
reactivity of alcohols and aldehydes is different for different substrates. For example, as shown in
Figure 2a, the catalytic activity of ACT is lower for the oxidation of the solketal (2a) than for
oxidation of the corresponding aldehyde 2b. The relative reactivity of 2a and 2b is manifested in
the time course of a bulk electrolysis reaction (Figure 3), which shows formation of the carboxylic
acid product even at early time periods, with only a small build-up of the aldehyde during the
reaction. In contrast, ACT shows considerably higher activity with cyclopentanemethanol (3a)
than with the corresponding aldehyde 3b (Figure 2b). A quantitative comparison of several
substrate pairs analyzed in this manner is presented in Figure 2c.
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Figure 2. Cyclic voltammograms of 1 mM ACT in the absence (dotted line) and presence of 20 mM 2a (a,
dashed line), 20 mM 3a (b, dashed line), 20 mM 2b (a, solid line) and 20 mM 3b (b, solid line), scan rate
–
1
1
0 mVs . TOF of ACT toward oxidation of alcohols and aldehydes (c), applied potential 0.7 V vs.
Ag/AgCl. Reaction conditions: H O/CH CN (50:50) 0.05 NaHCO , 0.05 M Na CO
2
3
3
2
3
.
Figure 3. Concentration profiles of alcohol, aldehyde and carboxylic acid in the course bulk electrolysis
of 2a. Reaction Conditions: 1.5 1mmol and 5mol% ACT in aqueous carbonate buffer (15 mL), NaHCO
3
(0.1 M) Na
2
CO
3
electrolyte (0.1 M), pH 10, applied potential is 0.75 V vs. Ag/AgCl.
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There is no clear trend for electronic effects on the rate of alcohol oxidation. For example, 4-
hydroxymethylpyridine 1a is less reactive than benzyl alcohol 4a, thus favoring the more electron-
rich alcohol. The opposite trend is observed with solketal/cyclopentanemethanol (2a/3a), for
which the electron-deficient derivative 2a is more reactive. This discrepancy may be rationalized
by the multi-step mechanism involved in oxoammonium-mediated alcohol oxidation (Scheme 2),
in which electron-deficient substitutions should facilitate alcohol deprotonation during adduct
formation with the oxoammonium species, while the same substituents should have the opposite
effect on the hydride transfer step.2,52,53 For the aldehyde substrates, however, both substrate pairs,
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b/4b and 2b/3b, show a higher rate with the more electron-deficient derivative (1b and 2b). These
observations are readily rationalized by the need to generate the aldehyde hydrate in order to
oxidize the aldehyde to the carboxylic acid. The hydration equilibrium is strongly favored by the
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presence of electron-withdrawing substituents. For example, hydration constants for aldehydes
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1b and 4b have been reported to be 50 and 0.01, respectively, under neutral conditions. To probe
the latter effect further, electrochemical oxidation of 1b and 4b were compared at different pH
values. High catalytic TOFs were observed for ACT-catalyzed oxidation of 1b, with the electron-
withdrawing pyridyl group (Figure 4a). On the other hand, little catalytic activity was observed for
oxidation of 4b at pH 8.4 and 10. Only upon increasing the solution pH to 11.5 was significant
catalytic current observed (Figure 4b), albeit still much lower than that observed with 1b at similar
pH (Figure 4c).
OH
O
O
R
– N R
OH
B–
BH
H
O
O
N
R’
R’
or
H
+
R’
NHR2
or
OH
OH
R
R
O
X
R’
R’
OH
X = H or OH
Scheme 2. Oxidation of primary alcohol and aldehyde hydrate by oxoammonium.
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Figure 4. Cyclic voltammograms of ACT in the absence (dotted line) and presence of 20 mM 1b (a) and
20 mM 4b (b) at different pH values. The TOF of ACT for oxidation of 1b and 4b as a function of pH (c).
Solution conditions: CH
3
CN/H
2
O (70:30), change in pH was obtained by varying the ratio of the NaHCO
3
–
1
to Na CO electrolyte (total concentration 0.14 M). Scan rate is 10 mVs .
2
3
These voltammetric studies were then extended to bulk electrochemical oxidation of a variety
of other alcohols and aldehydes, using ACT as the catalyst (2.5 or 5 mol% loading) (Table 1). The
optimized conditions employ aqueous bicarbonate/carbonate solution, avoiding the need for
tetraalkylamonium salts or related less desirable electrolytes. A number of different benzylic and
aliphatic alcohols and aldehydes were converted to the corresponding carboxylic acids, including
a number of examples containing pyridine or quinoline units. For water-insoluble substrates, a
mixture of acetonitrile/water was used (entries 7 and 8). The only undesirable byproduct observed
from these reactions was a small amount of benzil (approx. 10% yield) in the oxidation
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Table 1. The substrate scope for ACT mediated formation of carboxylic acids.a
entry
1
substrate
product
OH
time (h)
13
yieldb
97%
OH
N
1
a
O
N
O
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95%
96%
N
1c
1
b
OH
OH
12
N
a
5
O
O
86%c
N
5c
8
N
5
b
OH
O
OH
12
83%
86%
5
6
N
N
6a
O
N
1
8
0
6c
6
b
OH
N
N
O
O
7d
8d
9
91%
7b
7c
4c
OH
O
O
87%e
8
5
4
b
O
O
91%
97%
O
O
HO
HO
8
a
8c
N
N
1
0
8
3
5
2
2
HO
HO
O
9
a
9c
OH
OH
OH
11
O
O
96%
99%
99%
1
0a
10c
O
OH
1
1
1
2
3
4
O
1
O
1a
11c
O
O
O
OH
OH
OH
O
2
O
a
2c
O
O
O
OH
9
9%
9
9% ee
O
O
S-2a (99% ee)
S-2c
a
Conditions: 1 mmol alcohol with 5 mol % ACT or 2 mmol aldehyde with 2.5% ACT, in 10 mL aqueous
b
carbonate buffer 0.1 M NaHCO
3
, 0.1 M Na
2
3
CO , pH 9.8-10.1, electrolysis at 0.7 V vs. Ag/AgCl.
c
d
Isolated yield. 0.2 M Na
2
CO
3
, pH 11.5; 6% diketone (dimer) observed. 40% acetonitrile was used for
e
substrate solubility. 0.2 M Na
2
3
CO , pH 11.5; 6% benzil observed.
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benzaldehyde and the analogous diketone in the oxidation of 3-pyridinecarboxaldehyde. By
running the reaction at higher pH, for example, using only Na
2
CO as the electrolyte (pH 11.5),
3
the yield of these dimeric side products decreased to approximately 6% (entries 4 and 8; see
Section 4 of the Supporting Information for details).
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
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5
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0
1
2
3
4
5
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0
1
2
3
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0
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9
0
The effect of pH on electrochemical aminoxyl-mediated alcohol oxidation has been
investigated in previous voltammetric studies,48,56,57 and faster rates are typically observed at
higher pH. Similar behavior was observed in the present reactions, as revealed by voltammetric
and chromonamperometric analysis of the pH dependence of ACT-mediated oxidation of
substrates 1a, 1b, 4a, and 4b (see Figure 4 and Figures S11 and S12 in the Supporting Information).
More thorough analysis of ACT-mediated oxidation of S-2a reveals the pH effects under bulk
electrolysis conditions (Figure 5). Higher current and more-rapid conversion of the substrate were
observed at pH 9.8 relative to the reaction conducted at pH 8.5; however, both experiments led to
high yields of product (97% and 99% at pH 8.5 and 9.8, respectively) and complete retention of
enantioselectivity (>99% ee). The latter observation is rationalized by the relatively short lifetime
and/or build-up of the aldehyde intermediate during the reaction (cf. Figure 3).
7
5
0
6
450
360
270
180
90
b
d
42
2
1
8
4
0
a
c
0
0
0.7
1.4
2.1
2.8
3.5
t (h)
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
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4
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5
5
5
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5
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5
6
Figure 5. Current traces observed (a and c) and associated charge consumed (b and d) during the bulk
electrolysis of solketal at pH 9.8 (0.1 M NaHCO
3
, 0.1 M Na
2
CO
3
for a) and 8.5 (0.2 M NaHCO
3
for
c). Reaction condition: 1 mmol solketal with 5 mol% ACT in 10 mL aqueous solution, applied potential
0.7 V vs. Ag/AgCl.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
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0
1
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3
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9
0
1
2
3
4
5
6
7
8
9
0
In order to demonstrate the synthetic utility and larger-scale viability of this approach, we
targeted the preparation of the carboxylic acid precursor to levetiracetam [(2S)-2-(2-oxo-1-
pyrrolidinyl)butanamide], a generic drug commonly used to treat epilepsy and potentially
5
8
beneficial for other central nervous system disorders like Alzheimer’s and autism. The chiral
alcohol 12a is readily obtained via condensation of the corresponding aminoalcohol and
butyrolactone, and oxidation of 12a to carboxylic acid 12c is one of several efficient routes that
has been demonstrated for the synthesis of levetiracetam.59-61 Under the pH 9.8 conditions
identified for the oxidation of solketal, voltammetric studies of 12a showed that ACT exhibits high
catalytic activity (Figure 6, trace b), and the carboxylic acid 12c was obtained in 87% isolated
yield and 87% ee following a 2 h bulk electrolysis (Figure 6, traces c and d).
Figure 6. Possible synthetic route for the synthesis of levetiracetam and cyclic voltammograms of ACT in
–
1
the absence (a) and presence of 13a (b). Conditions: 1 mM ACT, 20 mM substrate, scan rate 10 mV s .
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The current (c) and consumed charge (d) for the ACT catalyzed electrochemical oxidation. Reaction
condition: 1 mmol 12a, 5 mol% ACT in 10 mL aqueous solution, applied potential 0.7 V vs. Ag/AgCl.
Aqueous carbonate buffer, 0.1 M NaHCO
3
and 0.1 M Na
2
CO (pH 9.8), was used for both voltammetric
3
and electrolysis experiments.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
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5
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5
5
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0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
5
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7
8
9
0
The reaction was then tested under different conditions and reaction scales (Table 2). Changes
to the electrolyte concentration and reaction scale (1–14 mmol; entries 1–8) led to some variation
in the reaction time, but quantitative conversion of alcohol to carboxylic acid was observed in all
reactions. The alcohol 12a has good solubility in aqueous solution, allowing the concentration to
be increased up to 0.6 M (@ 10 wt%) (entry 4). Both controlled current and controlled potential
electrolysis were effective, and the reaction completion was indicated by either a sharp drop in the
current during controlled potential operation (cf. Figure 6, trace c) or a jump in the potential during
controlled current operation (see Figure S14 in Supporting Information). The reaction was also
6
2
effective using the commercially available ElectraSyn 2.0 apparatus (entry 6). At pH 9.8, with a
:1 ratio of NaHCO and 0.1 M Na CO (0.1 M each) as the electrolyte, a small drop in
enantioselectivity was observed during oxidation of the substrate 12a (95% ee) to the product 12c
1
3
2
3
(87% ee). Therefore, the reaction was re-optimized by using 1.1 equiv of NaHCO as the
3
+
electrolyte (pH 8.5). (Note: Oxidation of H to H
2
at the cathode counter electrode maintains the
pH during the reactions.) This less basic medium led to higher retention of enantioselectivity, and
oxidation of 12a on 40 g scale led to formation of 12c in 91% yield and 92% ee (Table 2, entry
9
).51
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2
2
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Table 2. Different reaction conditions for the oxidation of 13a to 13c.
O
O
5% ACT
N
N
+ NaHCO
OH
2a (95% ee)
entry mmol V (mL)
3
+ H
2
O
+ CO + 2H
2 2
OH
1
12c
O
yielda
(ee)
base
(equiv)
t (h)
2.5
5.5
8.5
14
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
HCO – (1), CO32– (1)
87%
1
2
3
4
5
1
3
3
6
1
10
10
3
(87%)
HCO – (1), CO32– (1)
91%
3
10 HCO – (0.33), CO32– (0.33)
93%
96%
88%
3
HCO – (0.5), CO32– (0.5)
10
10
3
HCO – (1.1)
4
3
HCO – (1.1)
4
91%b
94%
6
7
8
9
1
3
10
10
3
HCO – (1.1)
11
14
29
3
14
245
70
HCO – (1.1)
93%
3
91%c
92%)d
HCO – (1.1)
1000
3
(
a
b
NMR yield, trimethoxybenzene was used as internal standard. The reaction was performed using
c
d
ElectraSyn 2.0. Isolated yield, enantiomeric excess was determined using chiral HPLC.
Conclusion
The results described herein show that ACT-mediated electrochemical oxidation of alcohols and
aldehydes provides an effective and scalable route to generate carboxylic acids, including
substrates that contain heterocycles and stereocenters adjacent to the alcohol. The protocol is quite
practical, as it uses aqueous reaction media, carbonate/bicarbonate base as the electrolyte, proceeds
at room temperature, uses an inexpensive catalyst, and is amenable to larger scale applications.
These features, combined with the environmentally benign nature of electrosynthesis, make it
highly appealing approach for the preparation of carboxylic acids, for example, in the
pharmaceutical industry. This feature is evident in the 40 g scale oxidation of 1-[(2S)-1-hydroxy-
2
-butanyl]-2-pyrrolidinone.
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AUTHOR INFORMATION
Corresponding Author
* stahl@chem.wisc.edu.
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Present Address
†
H. F. K.: Boehringer Ingelheim Pharma GmbH & Co. KG, Medicinal Chemistry, Birkendorfer
Strasse 65, 88397 Biberach an der Riss, Germany
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
xxx.
Experimental details, description of electrochemical reactions, additional electrochemical studies,
derivation of turnover frequencies (TOFs), NMR spectra of the products, and the chromatographic
characterization of enantiomeric excess, including Figures S1–S14. (PDF)
ACKNOWLEDGMENT
Financial support for this project was provided by AbbVie (organic chemistry applications) and
the Great Lakes Bioenergy Research Center (DOE Office of Science BER DE-FC02-07ER64494).
We thank IKA for their donation of an ElectraSyn 2.0 apparatus.
References
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39) For an example of non-electrochemical catalytic dehydrogenative conversion of alcohols to carboxylic
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(40) Schnatbaum, K.; Schäfer, H. J. Electroorganic Synthesis 66: Selective Anodic Oxidation of
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(44) Cha, H. G.; Choi, K.-S. Combined Biomass Valorization and Hydrogen Production in a
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(62) https://www.ika.com/laboratory-equipment/products/electrochemistry-kit/products/4265/electrasyn-
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TOC Graphic
NHAc
N
+
R
R
OH
O
ACT =
or
+ (2) H2
+ H O
ACT
2
R
N
OH
O
•
O
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OH
OH
OH
O
O
O
O
N
N
OH
O
N
OH
O
O
40 g scale
Precursor to levetiracetam
O
HO
O
HO
O
O
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