Unexpected highly chemoselective anodic ortho-coupling reaction of 2,4-dimethylphenol on boron-doped diamond electrodes

Article abstract of DOI:10.1002/ejoc.200600466

Anodic conversion of 2,4-dimethylphenol on boron-doped diamond (BDD) electrodes under solvent-free conditions results in an unusual highly selective formation of the desired 2,2′-biphenol, representing the best electrochemical synthesis for this particular compound. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200600466

FULL PAPER
DOI: 10.1002/ejoc.200600466
Unexpected Highly Chemoselective Anodic ortho-Coupling Reaction of
,4-Dimethylphenol on Boron-Doped Diamond Electrodes
2
[a]
[b]
[b]
Itamar M. Malkowsky, Ulrich Griesbach, Hermann Pütter, and
Siegfried R. Waldvogel*[
a]
Keywords: Electrochemistry / C–C coupling / Oxidation / Phenols / BDD electrodes
Anodic conversion of 2,4-dimethylphenol on boron-doped
diamond (BDD) electrodes under solvent-free conditions re-
sults in an unusual highly selective formation of the desired
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
2,2Ј-biphenol, representing the best electrochemical synthe-
sis for this particular compound.
Introduction
plated substrate and hydrolytic work-up after electrochemi-
cal conversion.
[
4]
The selective oxidative coupling reaction of simple
methyl-substituted phenols like 2,4-dimethylphenol (1) is
challenging because several by-products are formed. Be-
sides the desired biphenol 2, Pummerer’s ketone 3 repre-
sents usually the major product. Additionally, dehydrotri-
Results and Discussion
In order to simplify the process, the direct electrochemi-
mers with unique pentacyclic scaffolds (e.g. 4) are produced cal conversion of 1 was tested on a variety of different elec-
in significant amounts (Scheme 1).[
1]
trode materials. Initial experiments with boron-doped dia-
To overcome this lack of selectivity, we developed re- mond (BDD) electrodes revealed promising results for the
cently a template-directed electrochemical synthesis: The aspired ortho-coupling reaction. Surprisingly, the anodic
[
2]
phenols are converted to tetraphenoxy borate species,
conversion of 1 gave the biphenol 2 in almost exclusive
which represent superb substrates for the anodic transfor- selectivity of 18:1 for 2/3. (Scheme 1). Noteworthy, except
[
3]
mation. Although this process can be performed on a for traces of ketone 3, no other by-product was observed
large scale and exhibits excellent selectivity for 2, it requires when performing the electrolysis on BDD electrodes. These
a multi-step sequence, including the isolation of the tem- results were fully unexpected because BDD electrodes are
Scheme 1. Product diversity (major components) from the electrochemical oxidation of 1.
commonly used for total oxidation and mineralization of
[
5]
[
[
a] Kekulé-Institut für Organische Chemie und Biochemie,
Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
Fax: +49-228-73-9608
organic pollution in waste water. BDD electrodes exhibit
completely different characteristics compared to other car-
bon electrodes. The main features are unusual chemical and
electrochemical stability, a high overpotential for oxygen
E-mail: waldvogel@uni-bonn.de
b] BASF Aktiengesellschaft,
GCI/E-M311, 67056 Ludwigshafen, Germany
Eur. J. Org. Chem. 2006, 4569–4572
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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I. M. Malkowsky, U. Griesbach, H. Pütter, S. R. Waldvogel
FULL PAPER
evolution, and the capability of efficient anodic formation
Employment of glass flange connections offers the use of
of very reactive hydroxyl radicals.[ Recently, these proper- every planar type of BDD electrode, which is easily con-
6]
[
6]
ties led to the electrosynthesis of trimethyl orthoformate.
tacted by a metal foil on the back. Particular attention was
Furthermore, these particular electrodes were applied in the given to the sealing between BDD electrode and the flange
[
10]
oxidation of propargylic alcohols and aromatic side of glass. Several materials have been tested.
chains.
Best results
[
7]
were obtained by a sealing made of ethylene-propylene-
Therefore, the anodic conversion of 1 on BDD electrodes diene rubber (EPDM). This rubber is a highly resistant ter-
was systematically studied. Electrolysis cells for conversions polymer. The sealings were stamped out of a 2-mm EPDM
on BDD in aqueous media were developed by CSEM and sheet. Thermal stability was found up to 120 °C. Hot or-
described as Modular Electrochemical Cells for continuous- ganic and aggressive media as well as highly anodic poten-
[
8]
flow applications. These are specific in size and restricted tials seem not to affect the sealing over a long process time.
to relatively large electrodes. In order to work on a smaller The depicted cell geometry offers the possibility to heat the
scale and to apply various reaction conditions for prepara- electrolyte. Usually, a sand bath or silicon oil was applied.
tive purposes, a novel cell geometry was developed. The bo- The cooling jacket in the upper part kept the more volatile
ron-containing polycrystalline diamond layer (1–10 µm) components in the electrolysis vessel.
was employed on a silicon or niobium support as commer-
cially available. Despite the superior chemical stability of formations on BDD electrodes were applied in the oxidative
Initially, alcohols as common solvents for organic trans-
[
9]
the diamond layer, BDD electrodes create two challenges. coupling reaction of phenol 1 (Table 1).
The brittle nature of crystalline silicon limits the mechani-
For sufficient conductivity of the electrolyte a protic sol-
cal stability of the support, causing occasionally loss of the vent and a supporting electrolyte were required (Table 1).
BDD electrode by friction. Furthermore, any contact with All electrochemical conversions gave the desired compound
the electrolyte has to be strictly eliminated, because silicon 2 only in modest yield. Except for 3, no other low-molecu-
or niobium suffer from corrosion. To allow only contact by lar-weight by-products could be isolated indicating that
[
11]
the resistant BDD surface an arrangement with flange fit- oligomeric species were predominantly formed.
These
tings was constructed (Figure 1). findings were additionally supported by notable low current
Figure 1. Flange electrolysis cell design for BDD electrodes (top) and assembly (bottom).
570
4
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Eur. J. Org. Chem. 2006, 4569–4572

Anodic Conversion of 2,4-Dimethylphenyl on Boron-Doped Diamond Electrodes
FULL PAPER
Table 1. Anodic treatment of 1 in organic solvents.[a]
Entry
Electrolyte
0.1  Bu NBF
0.1  NaOH in MeOH
0.1  H SO in MeOH
.1  Bu
tBuOH
.1  Bu
MeOH
2 [%][b] CE[c] [%] 2/3
1
2
3
4
4
in MeOH
17
15
15
7
6
10
10:1
3:2
4:1
2
4
Figure 2. Ammonium salts as supporting electrolytes in the oxi-
dation of 1.
0
4
4
NBF
4
4
in CH
in CH
3
CN/
Cl
O/tBu-
4
5
6
16
11
3
4
20:1
4:3
0
NBF
2
2
/
3
nol 2 was afforded as pure crystalline material. This is the
most efficient electrochemical access to this particular com-
pound. Variation of the ammonium salt resulted in the
FeSO
OMe
4 4 4 2
, Bu NHSO , H
n.d.
n.d.
[
(
[
a] Reaction conditions: 1.5 g 1, 35 mL electrolyte, BDD anode same selectivity but differed significantly in the current effi-
2
layer thickness: 1 µm), j = 20 mA/cm , nickel cathode, room temp.
cacy (Table 2, Entries 1, 2, and 3). On the 1 µm diamond-
coated silicon BDD, neutral electrolysis conditions em-
ploying 5 gave the best yields in the desired biphenol 2 (En-
try 1). However, the acidic ionic liquid 6 turned out to be
superior concerning the current efficacy of the phenolic oxi-
dation (Entry 2).The basic ammonia salt 7 lead to moderate
yields and inferior current efficacies (Entry 3). When
b] Determined from the crude product by GC using an internal
standard. [c] Current efficacy.
efficacies. The surface of the electrode stood intact when
performing the transformation in acidic or neutral media,
whereas basic electrolyte caused significant corrosion.
Within this study a variety of solvent mixtures and an iron-
based mediator were tested, but with less success (Table 1).
Significant amelioration was achieved when 1 was used
neat at higher reaction temperature. The yield as well as
the selectivity of the transformation could be considerably
improved (Table 2). A good conductivity was obtained by
addition of 11% of water and 6% ammonium salt (Fig-
ure 2). For a sustainable process development, reduction in
the amount of solvent is important and applying a green
additive like water will be beneficial. Despite of the large
excess of phenol a mediating role of water by preliminary
formed hydroxyl radicals can not be excluded. Moreover, a
mediated mechanism is confirmed by a slightly lower oxi-
dation potential for water of 1.23 V vs. SCE compared to
phenols with 1.3–1.65 V vs. SCE.[ The oxidation of 1 by
intermediate hydroxyl radicals is supposed to proceed im-
mediately, because no peroxides were detected in the elec-
trolyte.
10 µm-diamond-coated supports were employed for elec-
trolysis, the tetraalkylammonium methyl sulfate (5) gave
better results (Entry 4). Surprisingly, the nature of the sup-
port seems to play a crucial role for the current efficacy
(Entries 4 and 5). Because the very same chemoselectivity
for the transformation was observed, the loss of efficacy is
not based on the oxidative coupling step.
However, the BDD electrodes exhibit an aging process.
In general, prolonged lifetime of the electrodes is achieved
by continuous reversion of polarity. Still, the polarity was
not reversed with regard to the oxidation of the nickel elec-
trode. After multiple runs the selectivity and the appearance
looked the very same, whereas the current efficacy dropped
from 43% to about 20–25% (e.g. for Entry 4). To enhance
the purity of 2 and to avoid the formation of overoxidation
products, a series of electrolyses were performed to a certain
conversion (Figure 3).
12]
Table 2. Anodic coupling reaction of 1 on BDD electrodes.[a]
Ammonium
salt
Entry
BDD
2
CE[c] 2/3
support, thickness [%][b] [%]
1
2
3
4
5
5
6
7
5
5
Si, 1 µm
Si, 1 µm
Si, 1 µm
Nb, 10 µm
Si, 10 µm
56
46
39
49
47
29
42
30
43
32
17:1
16:1
17:1
18:1
19:1
Figure 3. Progress of the oxidation of 1 on BDD electrode.
[
a] Reaction conditions: 30 g 1, 4 mL water, 2.2 g ammonium salt,
2
BDD anode, j = 10 mA/cm , nickel cathode, Q = 0.4 F per mol 1,
7
During the electrolysis the amount of 2 increases in a
linear fashion up to 0.3 F per mol 1. Then side reactions
appear limiting the amount of isolated 2. Thus, a partial
conversion of about 30% gives the best results. Because ex-
0 °C. [b] From the crude product after distillative removal of ex-
cess 1, determined by GC using internal standard. [c] Current effi-
cacy.
The electrolysis was only performed to a conversion of cess of 1 is easily recovered virtually no loss of material
about 0.4 F per mol 1 in order to depress the formation of occurs, creating a good basis for a continuous preparation
[
13]
by-products. For work-up excess of 1 was easily removed of 2. The elaborated protocol for the oxidative coupling
by a short-path distillation. The residue was then fractioned process was applied to a series of low-melting phenols.[
with water and tert-butyl methyl ether in order to remove Either no conversion was observed or the substrate was
the supporting electrolyte. Upon concentration of the or- completely destructed. Even in mixtures of several phenolic
ganic layer and slow addition of heptane the desired biphe- substrates the sole product that was detected was 2. The
14]
Eur. J. Org. Chem. 2006, 4569–4572
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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I. M. Malkowsky, U. Griesbach, H. Pütter, S. R. Waldvogel
FULL PAPER
reason for this exclusive substrate selectivity and the par- could be isolated by filtration and subsequent washings with hep-
tane (2×10 mL). The mother liquor was concentrated in vacuo and
a second crop was isolated as described above. Compound 2 was
ticular nature of 2,4-dimethylphenol (1) are unclear but cur-
rently under investigation.
obtained as colorless solid (6.3 g, 26 mmol, 49% referring to the
1
organic fraction). M.p. 135 °C (cyclohexane). H NMR (300 MHz,
CDCl
3
): δ = 2.27 (s, 12 H, CH
3
), 5.04 (s, 2 H, OH), 6.85 (s, 2 H,
(242.13): calcd. C 79.31,
Conclusions
4-H), 6.98 (s, 2 H, 6-H) ppm. C16H O
18 2
BDD electrodes are novel and appealing materials of H 7.49; found C 79.21, H 7.35.
organic electrochemistry, which give access to unusual selec-
tive reactions. Under controlled conversion almost no
overoxidation or mineralization is observed. The anodic
Acknowledgments
coupling reaction of 1 on BDD provides 2 in an excellent
The generous support by the BASF AG and the University of Bonn
is highly appreciated.
selectivity and represents the most efficient electrochemical
synthesis of this technically relevant biphenol. The electrol-
ysis is performed under solvent-free conditions; additional
water is required to enhance the conductivity. Partial con-
version provides the biphenol 2 in good quality. 2,4-Di-
methylphenol (1) is exclusively transformed by this proto- [2] I. M. Malkowsky, R. Fröhlich, U. Griesbach, H. Pütter, S. R.
col. Furthermore, an easy to handle electrolysis cell for
BDD electrodes in electroorganic synthesis was developed.
[
1] I. M. Malkowsky, C. E. Rommel, K. Wedeking, R. Fröhlich,
K. Bergander, M. Nieger, C. Quaiser, U. Griesbach, H. Pütter,
S. R. Waldvogel, Eur. J. Org. Chem. 2006, 241–245.
Waldvogel, Eur. J. Inorg. Chem. 2006, 1690–1697.
[
[
[
3] I. M. Malkowsky, C. E. Rommel, R. Fröhlich, U. Griesbach,
H. Pütter, S. R. Waldvogel, Chem. Eur. J., DOI: 10.1002/
chem.200600375.
4] E. Rommel, I. M. Malkowsky, S. R. Waldvogel, H. Pütter, U.
Griesbach, PCT Int. Appl. WO 2005075709 A2 20050818,
Experimental Section
2005.
General Remarks: All reagents were used in analytical grades. Sol-
vents were desiccated if necessary by standard methods. Melting
points were determined with a Melting Point Apparatus SMP3
5] A. Morao, A. Lopez, M. T. Pessoa de Amorim, I. C. Gon-
calves, Electrochim. Acta 2004, 49, 1587–1595; C. Levy-Clem-
ent, N. A. Ndao, A. Katty, M. Bernard, A. Deneuveville, C.
Comninellis, A. Fujishima, Electrochim. Acta 2002, 47, 3509–
3513.
(Stuart Scientific, Watford Herts, UK) and were uncorrected. Mi-
croanalysis was performed with a Vario EL III (Elementar-Ana-
lysensysteme, Hanau, Germany). NMR spectra were recorded with
[
[
[
6] R. Fardel, U. Griesbach, H. Pütter, C. Comninellis, J. Appl.
Electrochem. 2006, 36, 249–253 and literature cited therein.
7] U. Griesbach, D. Zollinger, H. Pütter, C. Comninellis, J. Appl.
Electrochem. 2005, 35, 1265–1270.
8] Modular Electrochemical Cell (CSEM, Neuchâtel, Switzer-
land): W. Haenni, C. Faure, P. Rychen, PCT patent WO 02/
a Bruker ARX 300, (Analytische Messtechnik, Karlsruhe, Ger-
1
many) by calibration on CHCl
3
with δ = 7.26 ppm for H NMR;
chemical shifts were expressed in ppm. Gas chromatography was
performed with a Shimadzu GC-2010 (Shimadzu, Japan) using a
HP 5 column (Agilent Technologies, USA; length: 30 m, inner dia-
meter: 0.25 mm, film: 0.25 µm, carrier gas: hydrogen). GC cali-
bration was accomplished with analytically pure 3,3Ј,5,5Ј-tet-
ramethyl-2,2Ј-biphenol (2) and (E)-stilbene as internal standard.
088430 A1, 2002.
[9] 1 µm BDD on Si: Adamant Technologies, La-Chaux-de-Fonds,
Switzerland; 10 µm BDD on Si or Nb: CONDIAS GmbH, It-
zehoe, Germany.
[
10] Diverse silicon materials and PTFE have been applied. Either
the electrochemical stability was not sufficient or leaching was
observed after prolonged electrolysis.
Anodic Oxidation of 2,4-Dimethylphenol: 2,4-Dimethylphenol (1)
3 4
(35.2 g, 0.29 mol), water (4.8 mL) and (Et) MeNSO Me (5) (2.4 g)
were mixed in a nondivided electrolysis cell equipped with a BDD
[11] Oligomeric and polymeric species were isolated as deep brown
colored material but not further characterized.
[12] G. W. Morrow, in Organic Electrochemistry (Eds.: H. Lund, O.
Hammerich), Marcel Dekker, New York, 2001, 4th ed., chapter
anode and a nickel cathode. At 70 °C, a galvanostatic electrolysis
2
with a current density of 10 mA/cm was performed. After 11760 C
(ca. 0.4 F per mol 1) the electrolysis was stopped and excess of 1
1
6, pp. 589–620, and literature cited therein.
was recovered by a short-path distillation. The remaining crude
product was dissolved in water (50 mL) and tert-butyl methyl ether
[
13] I. M. Malkowsky, S. R. Waldvogel, H. Pütter, U. Griesbach,
PCT Int. Appl. WO 2006077204 A2 20060727, 2006.
14] The following substrates were tested under the described condi-
tions: ortho-cresol, para-cresol, sesamole, 4-tert-butylphenol, 4-
allyl-2-methoxyphenol, 2-methoxy-4-methylphenol.
Received: May 31, 2006
(
30 mL). The layers were separated and the aqueous layer was ex-
tracted with tert-butyl methyl ether (2×30 mL). The combined or-
ganic layers were washed with brine (80 mL), dried (MgSO ), and
[
4
concentrated in vacuo yielding a brown oil (12.9 g). Upon slow
addition of heptane (20 mL) the desired product crystallized and
Published Online: August 9, 2006
4572
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Eur. J. Org. Chem. 2006, 4569–4572