CO2 anion-radical in organic carboxylations

Article abstract of DOI:10.1016/j.tetlet.2006.01.113

This letter shows a first approximation to the use of CO₂ anion-radical in the obtention of α-methyl and α-ethylcyanoacetic acids from propionitrile and butyronitrile, respectively, through a paired electrochemical reaction with CO₂. The electrosynthesis of α-chloro-phenylacetic acid from benzyl chloride and phenylacetic acid from toluene by another proposed pathway is also discussed.

Full text of DOI:10.1016/j.tetlet.2006.01.113

Tetrahedron Letters 47 (2006) 2171–2173
CO2 anion–radical in organic carboxylations
M. Dolores Otero, Belen Batanero and Fructuoso Barba*
Department of Organic Chemistry, University of Alcala´, 28871 Alcala´ de Henares (Madrid), Spain
Received 30 November 2005; revised 19 January 2006; accepted 23 January 2006
Abstract—This letter shows a first approximation to the use of CO2 anion–radical in the obtention of a-methyl and a-ethylcyano-
acetic acids from propionitrile and butyronitrile, respectively, through a paired electrochemical reaction with CO2. The electrosyn-
thesis of a-chloro-phenylacetic acid from benzyl chloride and phenylacetic acid from toluene by another proposed pathway is also
discussed.
Ó 2006 Elsevier Ltd. All rights reserved.
The CO2 reduction is a very important aim in the devel-
opment of alternative fuel sources and as possible means
of energy storage.1 However, the use of CO2 as a source
of carbon for the synthesis of organic molecules has not
yet been developed. Few papers on this topic have been
published, for instance, the preparation of cis- and
trans-1,2-cyclohexanedicarboxylate by reaction of
cyclohexene and CO2 anion–radical obtained by photo-
reduction of CO2;2 the nucleophilic addition of CO2
anion–radical (from gamma-irradiated formate ions) to
the C5–C6 double bond of N-substituted thymines;3
the reaction of CO2 anion–radical, also obtained by irra-
diation of aqueous solutions containing formate, with
substituted benzenes;4 or the obtention of cyanoacetic
acid via a paired electrosynthesis carried out in our
research group.5 At this paired reaction process takes
place the anodic oxidation of electrolyte anions and
subsequent reaction wÅith solvent molecules (aceto-
nitrile). The obtained CH2CN radicals are coupled
with cathodic CO2-reduced species, proceeding through
the medium-porosity glass-fritt diaphragm, to afford the
desired product.
When acetonitrile is replaced as the solvent by propio-
nitrile or butyronitrile, a-methyl-cyanoacetic acid or
a-ethyl-cyanoacetic acid are, respectively, obtained.
The a-propionitrile or a-butyronitrile radicals are
formed by anodic oxidation of the supporting-electro-
lyte anion with further HÅ abstraction from the solvent,
and are coupled with CO2 anion–radical molecules,
produced in the cathodic compartment.5 The a-position
attack in propionitrile and butyronitrile was determined
1
by H NMR.
Adjacent functional groups appear to weaken C–H
bonds: radicals next to carbonyl, nitrile or ether func-
tional groups, or centred on a carbonyl carbon atom,
are more stable than even tertiary alkyl radicals.
Whether the functional group is electron-withdrawing
or electron-donating is clearly irrelevant here: both types
seem to stabilize radicals.20
The obtained yields and current efficiencies on the
desired carboxylic acids are summarized in Table 1.
These electrolyses were carried out21 under constant cur-
rent conditions (300 mA, current density of 22 mA/
cm2). The facility of HÅ abstraction, from the radical
electrogenerated when the supporting electrolyte anion
is oxidized, was observed by electrolysis of a mixture
Numerous chemical,6–8 electrochemical,9–15 photoelec-
tro-chemical,16,17 direct photochemical18 and photocatal-
ytic19 systems have been developed for the reduction of
CO2 to a variety of products.
In this present letter, we extend the use of CO2 anion–
radical to the preparation of different carboxylic acids.
Table 1.
Solvent
Faradays circulated
through the cell
Yield
(g/F)
Current
efficiency (%)
Keywords: CO2 anion–radical; Carboxylation; Paired electrosynthesis.
Propionitrile
Butyronitrile
0.021
0.021
17.4
15.2
19.5
14.75
*
Corresponding author. Tel.: +34 91 8854617; fax: +34 91 8854686;
e-mail: fructuoso.barba@uah.es
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.113

2172
M. D. Otero et al. / Tetrahedron Letters 47 (2006) 2171–2173
Cl
cathodic compartment:
CO2
e-
O
.
.
_
+ CO2
Cl
Ph CH-Cl
.
+
CO2
Ph
O
anodic compartment:
.
+
.
.
-H
O
-
-
Ph
Cl
Cl
+ CO2
Ph
Cl
Cl
- e
+
Ph CH-Cl
Ph
O
in solution:
.
_
.
Scheme 3.
COO -
CO2
Ph
Ph
Scheme 1.
.
O
-
.
- CO2
+ CO2
.
Ph CH2
Ph CH2-Cl
of acetonitrile/propionitrile (1:1) and acetonitrile/
butyronitrile (1:1). The obtained experimental results
showed that in the first case the ratio of cyanoacetic
acid/a-methyl-cyanoacetic acid was 3:1, however, in
the second one the ratio of cyanoacetic acid/a-ethyl-
cyanoacetic acid was 7.8:1. It means that the HÅ abstrac-
tion in acetonitrile is easier than the abstraction in the a-
position of propionitrile and the latter easier than HÅ
abstraction in butyronitrile.
Ph
O
-Cl-
O
.
.
-
Ph
+ CO2
Ph CH2
O
Scheme 4.
cess of acyloxy radicals, particularly derived from ali-
phatic acids.
The anodic oxidation of benzyl chloride22 at Pt anode
was performed under constant potential conditions
(+2.5 V(vs Ag/Ag+)) in acetonitrile/Bu4NBF4 as SSE
(solvent-supporting electrolyte). When, simultaneously
to this oxidation, the reduction of cathodically bubbled
CO2 is effected by using a medium-porosity glass-fritt
diaphragm, a-chloro-a-phenylacetic (36%) and a-phenyl
acetic (47%) acids are anodically obtained as the main
products. The formation of the first compound could
be rationalized, through a paired reaction similar to
those previously described by us (Scheme 1).23,24
The coupling of this new stable radical with another
CO2 anion–radical molecule also affords a-chloro-a-
phenyl acetic acid.
The formation of a-phenylacetic acid can be explained
as indicated in Scheme 4. The CO2 anion–radical can
act as a nucleophile towards benzyl chloride affording
another unstable radical, similarly to previously pro-
posed, which evolves to a benzyl radical and further
couples with a new CO2 anion–radical molecule leading
to the carboxylate.
However, cyclic voltammetry of benzylchloride only
shows an oxidation peak, corresponding to a 2eÀ pro-
cess, meaning that both 1eÀ processes take place almost
simultaneously, and the electrogenerated chlorobenzyl
radicals are immediately oxidized at the electrode sur-
face to chlorobenzyl cations, which are desorbed into
the homogeneous solution. On the other hand, CO2
anion–radicals proceeding from the cathode can react,
in the anolyte solution, with the electrogenerated
dichlorobenzyl cations to afford, as shown in Scheme
2, an unstable radical.
a-Phenyl acetic acid is obtained in small amounts in the
cathodic compartment, especially if the diaphragm has a
very big pore. Some benzyl chloride molecules diffuse to
the cathodic compartment to be reduced (easier than
CO2) to the corresponding anion, which reacts with a
CO2 molecule to afford a-phenyl acetate. The diffusion
of benzyl chloride causes two problems, the first is the
consumption of the substrate and the second is the fact
that, due to the more negative reduction potential of
CO2, it is not reduced in the presence of benzyl chloride.
In order to minimize this diffusion phenomenon, the
substrate was slowly added into the anodic compart-
ment during the reaction to avoid high concentration
of substrate in solutions. Under dilute conditions the
substitution reaction does not take place, whereas the
oxidation of benzyl chloride, in which we are interested,
is favoured.
This unstable radical can undergo homolytic fragmenta-
tion25 leading another more stable radical (see Scheme
3) in a similar manner to the decarbonylation of acyl
radicals26 or the extremely facile decarboxylation pro-
cathodic compartment:
.
_
-
CO2
+ e
CO2
Ph
The anodic oxidation of toluene, under the same experi-
mental conditions, has also been performed. In this case
N-benzyl-acetamide is obtained as the main product but
a-phenylacetic acid is also formed as a secondary prod-
uct (11%).
anodic compartment:
+
+
-H
Cl
Cl
Ph
Cl
- 2e -
in solution:
O
.
_
+
.
Cyclic voltammetry of toluene shows an oxidation peak
corresponding to a 2eÀ process. The electrochemical
formation of benzyl cations is supported by a Ritter
CO2
O
Ph
Cl
+
Ph
Scheme 2.

M. D. Otero et al. / Tetrahedron Letters 47 (2006) 2171–2173
2173
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O
CH3
CH2+
O
.
-
- 2e-
-H+
CO2
+
- CO2
CH2
CH3CN
.
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Acta 2002, 339, 224.
+
Ph
N
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R. J. Electroanal. Chem. 2001, 516, 23.
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H2O
O
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˜
COO-
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Chem. Soc. 1991, 113, 8753; Lehn, J.-M.; Ziessel, R. J.
Organomet. Chem. 1990, 382, 157.
Ph
N
H
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J.-M. J. Am. Chem. Soc. 1991, 113, 8455.
Scheme 5.
16. Memming, R. In Topics in Current Chemistry; Steckhan,
E., Ed.; Springer: Berlin, 1988; Vol. 143, p 79, and
references cited herein.
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reaction with the solvent, acetonitrile, to give N-benzyl-
acetamide. The formation of a-phenylacetic acid is
rationalized in Scheme 5, and is similar to the formation
of a-chloro-a-phenylacetic acid.
The possibility of an electron-transfer in solution, in the
last step of the carboxylations described in this letter, is
not discarded.
20. Organic Chemistry; Clayden, J., Greeves, N., Warren, S.,
Wothers, P., Eds.; Oxford University Press, 2001; p 1027.
21. A concentric cell with two compartments, separated by a
porous (D3) glass-frit diaphragm, and equipped with a
magnetic stirrer, was employed. The catholyte was satu-
rated by bubbling CO2. A platinum plate was used as
cathode and a platinum net as anode. The solvent-
supporting electrolyte system (SSE) was a nominally
anhydrous 0.05 M solution of tetrabutylammonium tetra-
fluorborate in acetonitrile. The volumes of catholyte and
anolyte were 15 and 45 mL, respectively.
22. Benzyl chloride was electrolyzed under controlled poten-
tial conditions at +2.5 V, using the separated cell
described in Ref. 21. When the reaction was finished the
solvent in the anolyte chamber was removed under
reduced pressure. The residue was extracted with ether/
(5% NaHCO3 solution) and the aqueous phase neutralized
with 5% HCl solution and further extracted with ether.
This second organic phase was dried over Na2SO4 and
concentrated by evaporation. The obtained yields (36%
a-chloro-a-phenyl acetic and 47% a-phenylacetic acid)
are relative to the alkaline aqueous phase.
We can conclude that these processes, once optimized,
open a new and interesting alternative to the use of car-
bon dioxide in organic synthesis.
Acknowledgements
This study was financed by the Spanish Ministry of Sci-
ence and Education CTQ2004-05394/BQU. B.B. thanks
to the Spanish Ministry of Science and Technology, for
the ‘Ramon y Cajal’ financial support.
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