Efficient electrocarboxylation of p-methylpropiophenone in the presence of carbon dioxide

Article abstract of DOI:10.1002/cjoc.201090104

In the one compartment electrochemical cell 2-hydroxy-2-p-tolyl-butyric acid methyl ester was electrosynthesized by electrochemical carboxylation of p-methylpropiophenone in the presence of carbon dioxide. Under galvanostatic conditions, the electrocarboxylation was influenced by supporting electrolytes, cathode materials, the current density, passed charge and temperatures. Application scope of the eletrocarboxylation system was then examined, and an excellent yield of 97% was obtained when the electrolysis was carried out in DMF-0.1 mol?L^-1 TEABr solution using cheap and environmentally benign nickel as the cathode under a controlled current density of 5.0 mA?cm^-2 until 2.8 F?mol^-1 charge passed through the cell at - 10 °C. The electrochemical behavior of p-methoxylacetophenone has been studied on the glassy carbon electrode by cyclic voltammetry and the probable mechanism was proposed accordingly.

Full text of DOI:10.1002/cjoc.201090104

FULL PAPER
Efficient Electrocarboxylation of p-Methylpropiophenone
in the Presence of Carbon Dioxide
Zhang, Kai(张凯)
Wang, Huan(王欢)
Wu, Laxia(吴腊霞)
Zhang, Jingbo(张静波)
Lu, Jiaxing*(陆嘉星)
Department of Chemistry, Shanghai Key Laboratory of Green Chemistry and Chemical Process,
East China Normal University, Shanghai 200062, China
In the one compartment electrochemical cell 2-hydroxy-2-p-tolyl-butyric acid methyl ester was electrosynthe-
sized by electrochemical carboxylation of p-methylpropiophenone in the presence of carbon dioxide. Under gal-
vanostatic conditions, the electrocarboxylation was influenced by supporting electrolytes, cathode materials, the
current density, passed charge and temperatures. Application scope of the eletrocarboxylation system was then ex-
amined, and an excellent yield of 97% was obtained when the electrolysis was carried out in DMF-0.1 mol•L－
1
TEABr solution using cheap and environmentally benign nickel as the cathode under a controlled current density of
5.0 mA•cm－ until 2.8 F•mol－ charge passed through the cell at －10 ℃. The electrochemical behavior of
p-methoxylacetophenone has been studied on the glassy carbon electrode by cyclic voltammetry and the probable
mechanism was proposed accordingly.
2
1
Keywords p-methylpropiophenone, electrocarboxylation, carbon dioxide, galvanostatic electrolysis
Introduction
or toxic reagents such as very strong bases, Grignard
reagents, etc.10 Therefore, electrochemical technology
can provide a valuable and desirable alternative for
synthesis of some important α-hydroxy acids within the
domain of green chemistry. Thanks to the electron
transfer between the electrode and the substrate mole-
cules, carbon dioxide with its intrinsic thermodynamic
stability can be readily activated by coupling with ani-
ons or radical anions to ensure introduction of a carbox-
ylic function onto an organic center upon conserving
intact the original carbon skeleton. Hence, electrocar-
boxylation offers an effective means of fixation and
utilization of the largest contributor to the greenhouse
effect under neutral and mild conditions, which makes
our work even more significant and meaningful.
Electrocarboxylation via electrochemical fixation of
carbon dioxide as a central, low-cost, widely available
C1-organic building block is a powerful tool for the
construction of carbon-carbon bond.1-3 Since the pio-
neering work of Wagenknecht in 1986,4 electrochemical
carboxylation of aromatic ketones has attracted a con-
siderable interest as a method of obtaining various
α-hydroxy acids (AHAs), which were extensively used
in cosmetic dermatology to cure skin disorders includ-
ing acne, warts, and psoriasis and to correct photoaged
skin.5-7 Among these successful examples, the critical
cathode utilized in many applications employed toxic
lead foil8 or highly expensive platinum9 to form
2-aryllactic acids and 2-hydroxy-2-alkylphenyl pro-
panoic acids, respectively. Despite these successes, the
development of the efficient and appropriate cathode
materials is still a challenge and has become a much
attempting research endeavor.
In this paper, we report data on the electrolytic syn-
thesis of 2-hydroxy-2-p-tolyl-butyric acid methyl ester
by electrocarboxylation of p-methylpropiophenone in
the presence of carbon dioxide in good to excellent
yields by employing environmentally benign and much
cheaper nickel cathode (Eq. 1). Nevertheless, the only
conventional method of synthesis on which most indus-
trial processes are based consists of several dangerous
The mechanism of electrocarboxylation of aromatic
ketones has not been investigated in detail. Ikeda and
*
E-mail: jxlu@chem.ecnu.edu.cn.; Tel.: 0086-021-62233491; Fax: 0086-021-62232414
Received September 28, 2009; revised November 9, 2009; accepted December 23, 2009.
Project supported by the Project for Basic Research in Natural Science Issued by Shanghai Municipal Committee of Science (No. 08dj1400100) and
Shanghai Leading Academic Discipline Project (No. B409).
Chin. J. Chem. 2010, 28, 509— 513
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Zhang et al.
FULL PAPER
Manda11 once invoked the resonance structure of the
ketyl radical anion of a series of benzophenones to ex-
plain the influence of the substituted groups on the ex-
perimental results. As shown in Scheme 1, the authors
proposed the structure with the negative charge local-
ized on the carbon atom was likely to be predominant
and hence the carboxylation is very efficient when the
electron-withdrawing groups were present in the phenyl
rings. However, both resonance structures were impor-
tant with the molecule bearing electron-donating sub-
stituents. Then the carboxylation yield may decrease
and dimers or tars became crucial.
electrolysis was carried out in a mixture of p-meth－yl-
－1
1
propiophenone (0.1 mol•L ) and TEABr (0.1 mol•L )
in 10 mL of dry DMF in a one-compartment electro-
chemical cell equipped with a magnesium rod as the
sacrificial anode and a nickel cathode (area≈8 cm2)
－1
until 2.0 F•mol of charge was passed. During the
whole electrocarboxylation the electrolyte was saturated
with carbon dioxide, with the latter being passed
through vigorously for the duration of the entire synthe-
sis. At the end of the electrolysis, MeI as an alkylating
agent was added in 5-fold molar excess and the electro-
lyte was allowed to reflux at 50—60 ℃ for 5 h under
stirring. The esterification completed, the solvent was
distilled off under reduced pressure, and the residue was
acidified with aqueous HCl (20 mL) and extracted with
diethyl ether (20 mL×3). The combined organic layers
were then washed with saturated brine and dried over
MgSO4. After evaporating an almost pure 2-hydroxy-
2-p-tolyl-butyric acid methyl ester was isolated by col-
umn chromatography using petroleum ether/ethyl ace-
tate mixture as an eluent. The main features of the
aimed methyl ester identified by GC-MS, 1H NMR, and
13C NMR analyses were described in the following and
the yields were determined by GC with respect to the
starting material using n-decane/1,4-dioxane as an in-
Scheme 1
More recently, a slightly different mechanism in-
volving two carbon dioxide molecules, illustrated in
Scheme 2 has been more favored.12 The ketyl radical
anion reacts with CO2 via the oxygen atom to give a
species which undergoes immediate reduction and then
incorporates a second CO2 molecule. It is worth noting
that the actual carboxylation product is not the dicar-
boxylation anion but an α-hydroxy acid. The latter is
assumed to form by hydrolysis in the workup procedure.
In this paper, the results of mechanistic investigation of
electrocarboxylation are also described according to the
cyclic voltammogram of p-methylpropiophenone.
1
ternal standard. H NMR (CDCl3, 500 MHz) δ: 1.01 (t,
J＝7.4 Hz, 3H), 2.07—2.14 (m, 1H), 2.27—2.34 (m,
1H), 2.38 (s, 1H), 3.77 (s, 3H), 4.06 (s, 1H), 7.20 (d, J＝
8.1 Hz, 2H), 7.56 (d, J＝8.4 Hz, 2H); 13C NMR (CDCl3,
500 MHz) δ: 7.69 (s, 1C), 29.54 (s, 1C), 32.29 (s, 1C),
52.55 (s, 1C), 78.39 (s, 1C), 125.16 (s, 2C), 128.54 (s,
2C), 136.82 (s, 1C), 138.67 (s, 1C), 175.53 (s, 1C);
GC-MS m/z (%): 208 (1.4), 179 (0.6), 149 (100.0), 131
(1.9), 119 (21.0), 105 (1.8), 91 (14.5), 77 (2.3), 57
(33.7), 43 (1.7).
Scheme 2
Results and discussion
Cyclic voltammetry of p-methylpropiophenone and
reaction pathway
In cyclic voltammetry, there was not any redox peak
from －1.4 to －2.8 V before addition o－f the substrate
Experimental
1
under N2 in DMF containing 0.1 mol•L TEABF4 at
General procedure for electrochemical analysis
glassy carbon electrode (Figure 1, curve a). In compari-
－1
Voltammetric measurements were carried out by us-
ing a CHI650C electrochemical station. Potential scan
was performed in a dry DMF solution containing tetra-
ethylammonium tetrafluoroborate (TEABF4) as a sup-
porting electrolyte in a one-compartment electrochemi-
cal cell equipped with a gas inlet, a glassy carbon elec-
trode as the working electrode, a platinum spiral as the
son, 0.01 mol•L p-methylpropiophenone gave rise to
thre－e successive reduction peaks at the scan rate of 0.1
1
V•s in the employed scan region with the intensity of
the first peak being noticeably higher than those of the
others (Figure 1, curve b). The first partially reversible
cathodic peak with Ep1＝－1.91 V corresponded to one
electron reduction of p-methylpropiophenone to the
corresponding anion radical. The second irreversible
peak at －2.30 V could be relevant to the transfer of the
second electron, resulting in the aromatic ketone dianion
formation. It was worth noting that the third reduction
peak with Ep3＝－2.57 V was newly found compared to
some previously studied electroreduction behavior of
aromatic ketones,12,13 which could be supposed to in-
－1
counter electrode and a Ag/AgI/n-TBAI (0.1 mol•L )
in DMF as the reference electrode. All experiments
were performed at 25 ℃ under an atmospheric pres-
sure.
General procedure for electrosynthesis
The preparative galvanostatic and potentiostatic
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Chin. J. Chem. 2010, 28, 509— 513

Electrocarboxylation of p-Methylpropiophenone
volve the third electron uptake of the whole phenyl ring1
since some unexpected ring carboxylation of aromatic
ketones has been reported.14,15 Studying the electro-
chemical activation of p-methylpropiophenone at higher
－1
sweep rate of 0.5 V•s showed an appreciable Ip in-
crease and negative Ep shift for all three reduction
waves (Figure 1, curve c). On the base of the evaluation
of Ia/Ic for the first cathodic peak, we estimated the
radi－cal anion of p-methylpropiophenone forming at 0.5
1
V•s (Ia/Ic＝0.36) was more stable than that forming
－1
at 0.1 V•s (Ia/Ic＝0.30) to undergo the second electron
uptake.
When the cyclic voltammograms were recorded after
the solution was saturated with CO2, there was an obvi-
ous growth of the first cathodic peak (presumably by
1.72 times) and its shift into more anodic region as well
as the complete disappearance of the other two cathodic
peaks and the anodic peak attributed to the first electron
transfer (Figure 1, curve d). The observed changes were
indicative of a fast chemical reaction of p-methylpropio-
phenone radical anion with carbon dioxide followed by
a second electron reduction16 since CO2 was a stronger
electrophile than p-methylpropiophenone. The first ca-
thodic peak shifted into the more positive potential re-
gion could be caused by subsequent chemical reactions
between the anion radicals and carbon dioxide and by
the formation of aromatic ketone complexs with CO2
molecule which were more reducible than the starting
material. Similar association of CO2 with ketones has
been revealed recently.15
Based on the understanding of the generalized
mechanism depicted in the previously reported electro-
carboxylation of the aromatic ketones,17,18 proposed
reaction pathways involving two CO2 molecules for the
present carborxylation are revealed in Scheme 3. In the
initial step of the reaction the ketone 1 took up an elec-
tron from the cathode to become an anionic radical 2.
As the solvent was dried and saturated with CO2 most of
2 underwent a nucleophilic attack on CO2 via the oxy-
gen atom to give an adduct 3, which was more easily
reducible than the starting ketone. Then further one-
electron reduction followed by incorporating a second
CO2 molecule led to the formation of 4. Through the
Figure 1 Cyclic voltammograms of p-methylpropiophenone in
DMF solution containing 0.1 mol•L－ TEABF4 at glassy carbon
1
electrode. (a) without p-methylpropiophenone; (b), (c) with 0.01
mol•L－ p-methylpropiophenone in the presence of N2 at v＝0.1
1
V•s－ 1 and v＝0.5 V•s－ 1, respectively; (d) as b in the presence of
saturated CO2, T＝25 ℃.
work-up procedure of acidification, in which a CO2 was
lost, 4 reacted to produce the aimed product 5. In the
electrolysis, the magnesium ions dissolved from a mag-
nesium anode could readily capture carboxylate ions 4
to form the corresponding magnesium carboxylates,19
upon which the esterified carboxylation product was
more favored than the hydride or dimer.
Electrochemical carboxylation of p-methylpropio-
phenone
Influence of supporting electrolytes The poten-
tiostatical electrocarboxylation of p-methylpropiophen-
one with CO2 to 2-hydroxy-2-p-tolyl-butyric acid meth-
yl ester in DMF solution employing stainless steel as the
cathode was conducted using various supporting elec-
trolytes as presented in Table 1. The potential was cho-
sen at the second reduction peak potential of －2.3 V.
As a result, for the studied supporting electrolytes, the
carboxylation yield decreased in an order of TEABr＞
TBABr＞TBAI＞TEABF4＞TEAI＞TEACl. The in-
fluence of supporting electrolytes composed of different
cations and anions was distinct under the same other
Scheme 3
Chin. J. Chem. 2010, 28, 509— 513
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www.cjc.wiley-vch.de
511

Zhang et al.
FULL PAPER
Table 1 Influence of supporting electrolytes on the potentio-
statical electrocarboxylation of p-methylpropiophenonea
Table 2 Galvanostatical electrocarboxylation of p-methylpro-
piophenone under various conditionsa
Entry
Supporting electrolyte
TEABr
Cathode
－2.3
－2.3
－2.3
－2.3
－2.3
－2.3
－1.9
Yieldb/%
Entry Cathode j/(mA•cm－ 2) Q/(F•mol－
)
T/℃ Yieldb/%
1
1
2
3
4
5
6
7
38
14
23
15
25
12
—
1
2
Ss
Cu
Ni
Ti
5.0
5.0
5.0
5.0
5.0
5.0
4.0
4.5
5.5
6.0
5.0
5.0
5.0
5.0
5.0
5.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.2
1.6
2.4
2.8
2.8
2.8
25
25
25
25
25
25
25
25
25
25
25
25
25
25
0
33
52
79
10
70
7
TEAI
TBAI
3
TEABF4
TBABr
4
5
Ag
C
TEACl
6
TEABr
7
Ni
Ni
Ni
Ni
Ni
Ni
Ni
Ni
Ni
Ni
58
66
57
41
41
61
81
83
93
97
a The electrolysis was carried out in DMF using the stainless steel
8
as the cathode until 2.0 F•mol－ charge was passed at 25 ℃;
1
9
p-methylpropiophenone, 0.1 mol•L － 1, p(CO2) ＝ 1 × 105 Pa;
b yields of the 2-hydroxy-2-p-tolyl-butyric acid methyl ester were
determined by GC with respect to the starting material.
10
11
12
13
14
15
16
operative parameters. The relative higher yield of 38%
was obtained with TEABr. From the view of practice,
the currents of controlled-potential electrolysis were
very small. Then much more unnecessary byproducts
were probably engendered. When the potential was
changed to the potential of the first reduction peak
(－1.9 V), no aimed product could be identified regret-
tably with an even smaller current (Entry 7).
－10
DMF, 10 mL; TEABr, 0.1 mol•L－ 1; p-methylpropiophenone,
a
0.1 mol•L－
;
b as depicted in Table 1.
1
Influence of the nature of the electrode Since the
constant potential electrolysis was not so effective as
expected, the following electrocarboxylation of p-meth-
ylpropiophenone was performed under the controlled
current densities. The nature of the cathodic material
had an important influence on the carboxylation yield of
the electrolysis.20 Among common cathode materials,
the nickel (Ni) was much better than the others and 79%
of 2-hydroxy-2-p-tolyl-butyric acid methyl ester was
obtained. The employment of a silver cathode (Ag) de-
creased the yield a little to 70%. However, other cath-
ode materials such as copper (Cu) and stainless steel (Ss)
were much inferior and gave lower yields of the desired
product. The cathodes of graphite (C) and titanium (Ti)
were even worse. A comparison of the effect of these
cathodes under similar conditions was summarized in
Table 2 (Entries 1—6).
Figure 2 Effect of the current density on electrocarboxylation
of p-methoxylacetophenone.
Influence of the current density Appreciable dif-
ference in the yield of the product was found at the end
of the electrosynthesis under various current densities
(Table 2, E－ntries 7—10). The best current density was
the carboxylation yield too.21
Influence of the passed charge The electrocar-
boxylation of p-methylpropiophenone is a two-electron
reduction reaction, which means the theoretic charge of
2
－1
5.0 mA•cm on the electrodes of Mg-Ti and the elec-
this reaction is 2.0 F•mol . As the presence of the
trolysis at a higher or a lower current density resulted in
both lower yields (Figure 2). On one hand, the larger the
current density was, the more negative the electrode
potential would be. Therefore there would be other un-
needed reactions on the electrode surface, such as the
non-Faradaic current, the Faradaic efficiency can not
achieve 100%. Consequently more over the theoretic
charge is usually needed to improve the yield. The elec-
trocarboxylation under various passed charges was then
examined (Table 2, Entries 3 and 11—14). As shown in
Figure 3, the best yield of 83 % was obtained when the
＋
reduction of CO2 or dissolved Mg2 , which would de-
－1
crease the carboxylation yield. On the other hand, the
lower the current density was, the more positive the
electrode potential would be. So the proportion of the
Faradaic current would be declined, which decreased
passed charge reached 2.8 F•mol . Before the point of
－1
2.0 F•mol , the yield increased rapidly with the incre-
ment of the passed charge. Increasing electricity from
－1
2.0 to 2.8 F•mol was slightly effective for improving
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Chin. J. Chem. 2010, 28, 509— 513

Electrocarboxylation of p-Methylpropiophenone
tion-another electron reduction-another chemical reac-
tion) process.
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Figure 3 Effect of the charge passed on electrocarboxylation of
p-methoxylacetophenone.
the yield.
Influence of the temperature To investigate the
effect of the temperature, the electrocarboxylation was
carried out at 25, 0 and －10 ℃ respectively (Table 2,
Entries 14—16). An enhancement in yield was obtained
by decreasing the temperature, that is to say, by in-
creasing the CO2 concentration.22 An almost excellent
yield of 97% was achieved finally at －10 ℃. It
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Conclusion
In conclusion, we have developed a simple and effi-
cient electrochemical route with nickel cathode for elec-
trocarboxylation of p-methylpropiophenone to 2-hydr-
oxy-2-p-tolyl-butyric acid methyl ester in CO2-saturated
DMF solution. We have shown that various conditions,
such as the supporting electrolyte, cathode material,
current density, charge passed and temperature, can af-
fect the yield of carboxylic acid ester. After optimizing
the synthetic parameters, the highest yield of 97% was
achieved on Mg-Ni el－ectrodes under a constant current
2
－1
density of 5 mA•cm until 2.8 F•mol of charge
passed through the cell at －10 ℃. The electrochemical
behavior of p-methylpropiophenone was investigated by
cyclic voltammetry and the mechanism has been pro-
posed on the basis of the results, which suggested a
typical ECEC (one electron reduction-chemical reac-
(E0909281 Pan, B.; Dong, H.)
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