Quantitative evaluation of the mechanism of electroreduction of benzoyl cyanides

Article abstract of DOI:10.1021/jo062181e

The mechanism of reduction of benzoyl cyanide, 6, p-methoxybenzoyl cyanide, 7, and p-chlorobenzoyl cyanide, 8, has been studied in acetonitrile (6 and 7), N,N-dimethylformamide (6), and acetonitrile containing water (all three compounds). The reaction proceeds by initial reduction to form the anion radical followed by dimerization to produce an intermediate dianion, the dianion of the dicyanohydrin of benzil. The latter loses cyanide to give the anion of the monocyanohydrin of benzil, which undergoes two parallel reactions: expulsion of cyanide to give the corresponding benzil and rearrangement to the monoanion of mandelonitrile benzoate. The addition of water brings about an increase in the dimerization rate constant and an associated increase in the amount of benzil that is produced. The standard potentials for the initial reduction step have been evaluated, and their dependence on the substituent is discussed. The dimerization rate constants have also been evaluated.

Full text of DOI:10.1021/jo062181e

Quantitative Evaluation of the Mechanism of Electroreduction of
Benzoyl Cyanides
Norma A. Mac ´ı as-Ruvalcaba and Dennis H. Evans*
Department of Chemistry, UniVersity of Arizona, Tucson, Arizona 85721
dheVans@email.arizona.edu
ReceiVed October 19, 2006
The mechanism of reduction of benzoyl cyanide, 6, p-methoxybenzoyl cyanide, 7, and p-chlorobenzoyl
cyanide, 8, has been studied in acetonitrile (6 and 7), N,N-dimethylformamide (6), and acetonitrile
containing water (all three compounds). The reaction proceeds by initial reduction to form the anion
radical followed by dimerization to produce an intermediate dianion, the dianion of the dicyanohydrin of
benzil. The latter loses cyanide to give the anion of the monocyanohydrin of benzil, which undergoes
two parallel reactions: expulsion of cyanide to give the corresponding benzil and rearrangement to the
monoanion of mandelonitrile benzoate. The addition of water brings about an increase in the dimerization
rate constant and an associated increase in the amount of benzil that is produced. The standard potentials
for the initial reduction step have been evaluated, and their dependence on the substituent is discussed.
The dimerization rate constants have also been evaluated.
Introduction
when X ) ArC(O)O, where the cleavage reaction gives aryloate
ion and acyl radical with some of the latter dimerizing to give
There are many examples in which removal from or addition
of an electron to a neutral molecule will result in labilization
of a given bond that allows a bond-cleavage reaction to occur.
In the case of reduction reactions, the bond cleavage can be
concerted with electron transfer, as in the reduction of alkyl
chlorides, bromides, and iodides. In most cases, however, the
anion radical exists as a true intermediate with the rate of bond
cleavage varying from very large (some aryl halides) to quite
small (nitroalkanes).1
9
-11
a benzil derivative.
There is a possibility that the benzil
compounds are formed by prior dimerization of the anion
radicals, followed by cleavage of the X substituent. Such is
definitely the case when methyl benzoate (X ) OCH3) is
reduced in the presence of magnesium ions, which promote the
dimerization. The resulting dimer expels methoxide to produce
1
12
benzil. Therefore, the timing of the bond cleavage is variable.
It occurs sometimes in the anion radical and sometimes after
dimerization. A reaction analogous to the dimerization pathway
has been reported for some diesters for which, depending on
structure, the dianion diradicals undergo cyclization with
A number of classes of compounds contain an acyl function
as in 1. When X ) Cl, the intermediate anion radical is short-
1
3
expulsion of alkoxide giving benzil.
(
4) Floest, J. C.; Pereira-Martins, E.; Troupel, M.; Perichon, J. Tetra-
hedron Lett. 1993, 34, 7571-7574.
5) Urove, G. A.; Peters, D. G.; Mubarak, M. S. J. Org. Chem. 1992,
(
5
7, 586-590.
(
(
6) Urove, G. A.; Peters, D. G. J. Org. Chem. 1993, 58, 1620-1622.
7) Urove, G. A.; Peters, D. G. J. Electroanal. Chem. 1994, 365, 221-
lived and the acyl radical formed by cleavage of chloride gives
228.
(
8) Urove, G. A.; Peters, D. G. Electrochim. Acta 1994, 39, 1441-1450.
a number of products, often via coupling to form benzils that
are subsequently reduced.2-8 The same type of reaction occurs
(9) Lasia, A. J. Electroanal. Chem. 1973, 42, 253-259.
(10) De Luca, C.; Giomini, C.; Rampazzo, L. J. Electroanal. Chem. 1987,
2
38, 215-223.
(
1) Lund, H. In Organic Electrochemistry, 4th ed.; Lund, H., Hammerich,
O., Eds.; Marcel Dekker: New York, 2001; pp 969-1004.
2) Guirado, A.; Barba, F.; Manzanera, C.; Velasco, M. D. J. Org. Chem.
982, 47, 142-144.
3) Cheek, G. T.; Horine, P. A. J. Electrochem. Soc. 1984, 131, 1796-
801.
(11) Giomini, C.; De Luca, C.; Pelli, B.; Rampazzo, L. Ann. Chim. 1988,
78, 621-634.
(
(12) Pletcher, D.; Slavin, L. J. Chem. Soc., Perkin Trans. 2 1995, 2005-
1
2012.
(
(13) Mac ´ı as-Ruvalcaba, N. A.; Moy, C. L.; Zheng, Z.-R.; Evans, D. H.
J. Org. Chem. 2006, 71, 4829-4834.
1
1
0.1021/jo062181e CCC: $37.00 © 2007 American Chemical Society
Published on Web 12/15/2006
J. Org. Chem. 2007, 72, 589-594
589

Mac ´ı as-Ruvalcaba and Evans
FIGURE 2. Voltammogram of 0.92 mM benzoyl cyanide, 6, in
acetonitrile. Curve: background-corrected voltammogram. Points:
simulation.
FIGURE 1. Voltammograms of 2.40 mM benzoyl cyanide, 6, obtained
in acetonitrile. (A) 0.20, (B) 2.00, and (C) 20.0 V/s. Dotted curve in A
is for 2.00 mM benzil, also at 0.20 V/s.
Interesting results have been obtained for the reduction of
benzoyl cyanides, X ) CN,14 wherein references to chemical
reductions and their importance may be found. Preparative-scale
reduction in either acetonitrile or acetonitrile/water (82.5%
acetonitrile, v/v) gave principally, after workup, the correspond-
ing mandelonitrile benzoate in the former and the corresponding
benzil, 5, in the latter mixed solvent. The results were interpreted
in terms of the following reaction scheme.
FIGURE 3. Voltammogram of 2.40 mM benzoyl cyanide, 6, in
acetonitrile.
The key step in this scheme is the dimerization of the initially
formed anion radicals to form intermediate dianion 2. Proto-
nation of 2 gives the benzil dicyanohydrin, which sometimes
precipitated in the partially aqueous medium, thus protecting
FIGURE 4. Voltammogram of 0.92 mM benzoyl cyanide, 6, in
acetonitrile.
1
4
the benzil from further reduction. In the absence of added
water, the principal product is apparently the anion of the
mandelonitrile benzoate, 4, which is protonated during workup
In this article, we report on a mechanistic study of the
reduction of three benzoyl cyanides (p-X-C6H4C(O)CN with
X ) H, Cl, and OCH3) in which we evaluated thermodynamic
and kinetic parameters in the mechanism. We demonstrate that
the reaction proceeds by initial formation of the anion radical
followed by dimerization to produce the dimeric dianion, 2. This
dimeric dianion undergoes bond cleavage to give cyanide and
the anion of the monocyanohydrin of the benzil, 3. The latter
14
to give mandelonitrile benzoate, the product that was isolated.
Thus, the products are well established but no detailed study of
the mechanism of reduction of this type of compound has been
reported.
(
14) Okimoto, M.; Itoh, T.; Chiba, T. J. Org. Chem. 1996, 61, 4835-
4
837.
590 J. Org. Chem., Vol. 72, No. 2, 2007

Electroreduction of Benzoyl Cyanides
TABLE 1. Experimental Conditions and Simulation Parameters for Benzoyl Cyanide, 6, in Acetonitrile (Upper Part of the Table) and
Dimethylformamide (Lower Part of the Table)a
concentration/solvent
0.92 mM 6/CH3CN
2.40 mM 6/CH3CN
electrochemical reactions
E°
R
ks
E°
R
ks
•
-
AcylCN + e h AcylCN
-1.487
-1.555
0.5
0.5
0.24
0.03
-1.486
-1.566
0.5
0.5
0.14
0.03
•
-
Bz + e h Bz
chemical reactions
K
kf
kb
K
kf
kb
2-
8
8
8
5
4
-4
4
8
8
5
4
-4
2
(
AcylCN•- h (AcylCN)2
1.0 × 10
1.0 × 10
1.0 × 10
1.3 × 10
0.07
1.2 × 10
1.2 × 10
1.0 × 10
2.8
1.2 × 10
1.0 × 10
1.0 × 10
1.3 × 10
0.04
1.2 × 10
1.2 × 10
1.0 × 10
2.8
2
-
-
10
2
10
2
AcylCN)2 h BzCN + CN
1.0 × 10
1.0 × 10
-
8
8
BzCN h ManCN
BzCN h Bz + CN
2.8 × 10
2.8 × 10
-
9
4
4
9
4
4
1.8 × 10
1.4 × 10
1.8 × 10
1.4 × 10
•
-
•-
3
3
AcylCN + Bz h Bz + AcylCN
3.5 × 10
5.0 × 10
3.5 × 10
8.8 × 10
2
-5
-5
D of all species/cm /s
2.1 × 10
2.1 × 10
concentration/solvent
1.30 mM 6/DMF
3.75 mM 6/DMF
electrochemical reactions
E°
R
ks
E°
R
ks
•
-
AcylCN + e h AcylCN
-1.451
-1.518
0.5
0.5
0.10
0.01
-1.451
-1.518
0.5
0.5
0.10
0.01
•
-
Bz + e h Bz
chemical reactions
K
kf
kb
K
kf
kb
2-
8
3
-5
8
3
-5
2
2
(
AcylCN•- h (AcylCN)2
1.0 × 10
1.5 × 10
1.5 × 10
1.0 × 10
1.1 × 10
1.1 × 10
1.0 × 10
8.3 × 10
3.3 × 10
2
-
-
8
8
10
2
8
8
10
AcylCN)2 h BzCN + CN
1.0 × 10
1.0 × 10
30
1.0 × 10
1.0 × 10
8.3 × 10
3.3 × 10
1.0 × 10
1.0 × 10
30
1.0 × 10
-
-
4
-4
4
4
-4
4
BzCN h ManCN
BzCN h Bz + CN
D of all species/cm /s
8.3 × 10
8.3 × 10
-
6
6
1.0 × 10
1.0 × 10
2
-6
-6
5.7 × 10
5.7 × 10
a
The same values were used to fit all scan rates from 0.1 to 30 V/s. E° potentials are in V and refer to the formal potential of the ferrocenium/ferrocene
couple, ks in cm/s, second-order rate constants in M
compensated, and the remaining 20 Ω was applied in the simulation. For DMF, 240 Ω was electronically compensated, and 40 Ω was applied in the
simulation. AcylCN: benzoyl cyanide. AcylCN : benzoyl cyanide anion radical. Bz: benzil. Bz : benzil anion radical. Acyl(CN)2 : benzil dicyanohydrin
-
1
-1
-1
s , first-order rate constants in s . For acetonitrile, 120 Ω of solution resistance was electronically
•-
•-
2-
-
-
dianion. BzCN : anion of monocyanohydrin of benzil. ManCN : anion of mandelonitrile benzoate.
by a very small peak. The dotted curve in A is a voltammogram
of 2.00 mM benzil. The agreement of the peak potential for
benzil with that of the small second peak supports the conclusion
that some benzil is being formed in these low scan rate
experiments. At 2.00 V/s (B), the benzil reduction appears as a
very small shoulder on the main peak and also there is some
reversibility to the main peak. Finally, at 20.0 V/s (C), benzil
is not detected and there is a large anodic peak associated with
the main reduction peak.
A tentative assignment is that the main reduction peak is due
to the reduction of benzoyl cyanide to its anion radical (reaction
1
), which is followed by dimerization of the anion radical to
produce dimeric dianion intermediate 2. At larger scan rates,
the dimerization reaction is incomplete so that a large anodic
peak for oxidation of the anion radical (reverse of reaction 1)
is detected. Given sufficient time, 2 reacts to form some benzil,
FIGURE 5. Voltammogram of 2.15 mM benzoyl cyanide, 6, in
acetonitrile containing 0.33 M water.
5
, via reactions 3 and 5, as seen in curves A and B. Direct
detection of the anion of mandelonitrile benzoate, 4, formed in
reaction 4, is not possible as it is undoubtedly reduced at a
potential more negative that mandelonitrile benzoate itself,
reacts by two parallel paths: reversible expulsion of cyanide
to give the benzil, 5, and rearrangement to the anion of the
mandelonitrile benzoate, 4. We find that some benzil is produced
-
2.35 V versus ferrocene in N,N-dimethylformamide (DMF).15
Digital simulation of the voltammetric data was used to test
even in the absence of added water, a conclusion that is not
evident from the preparative electrolyses.14 Our observed
the validity of the suggested mechanism (reactions 1-5). To
see if the data are properly accounted for by a second-order
dimerization of the anion radicals of 6, data were obtained at
two different concentrations, 0.92 and 2.40 mM. It was found
enhancement of the rate of dimerization by added water helps
1
4
to explain the outcome of electrosynthetic procedures.
5
that the same value of the dimerization rate constant, 1.2 × 10
Results and Discussion
-1 -1
M
s , fits both sets of data. Examples of the fit of simulation
Figure 1 shows voltammograms for 2.40 mM benzoyl
cyanide, 6, in acetonitrile containing 0.10 M tetra-n-butylam-
monium hexafluorophosphate (Bu4NPF6). The scan rates were
to the data are shown in Figures 2 and 3. One can see that the
simulations properly account for the relatively larger anodic peak
0
.20 (A), 2.00 (B), and 20.0 V/s (C). At the slowest scan rate
(
15) Zheng, Z.-R.; Lund, H. J. Electroanal. Chem. 1998, 441, 221-
(A), the principal reduction peak is irreversible and it is followed
225.
J. Org. Chem, Vol. 72, No. 2, 2007 591

Mac ´ı as-Ruvalcaba and Evans
TABLE 2. Experimental Conditions and Simulation Parameters for Benzoyl Cyanide, 6, in Acetonitrile Containing 0.33 M Watera
concentration/solvent
0.65 mM 6/CH3CN + 0.33 M H2O
2.15 mM 6/CH3CN + 0.33 M H2O
electrochemical reactions
E°
R
ks
E°
R
ks
•
-
AcylCN + e h AcylCN
-1.451
-1.524
0.5
0.5
0.10
0.05
-1.448
-1.532
0.5
0.5
0.11
0.05
•
-
Bz + e h Bz
chemical reactions
K
kf
kb
K
kf
kb
2-
8
5
-3
2
8
5
-3
2
2
(
AcylCN•- h (AcylCN)2
1.0 × 10
1.0 × 10
1.0 × 10
5.0 × 10
5.8 × 10
2.5
3.1 × 10
1.0 × 10
4.6 × 10
7.0 × 10
1.3 × 10
4.7
3.1 × 10
1.0 × 10
4.6 × 10
1.4 × 10
2.2 × 10
1.9
1.0 × 10
1.0 × 10
1.0 × 10
5.0 × 10
3.7 × 10
2.5
3.1 × 10
1.0 × 10
4.6 × 10
7.0 × 10
1.3 × 10
3.8
3.1 × 10
1.0 × 10
4.6 × 10
1.4 × 10
3.5 × 10
1.5
2
-
-
8
10
7
8
10
7
AcylCN)2 h BzCN + CN
-
-
8
-1
4
8
-1
4
BzCN h ManCN
BzCN h Bz + CN
-
5
9
5
9
•
-
•-
-2
7
8
-2
7
8
AcylCN + Bz h Bz + AcylCN
•
-
Bz h prod
D of all species/cm /s
2
-5
2.2 × 10-5
1.3 × 10
a
The same values were used to fit all scan rates from 0.1 to 30 V/s. E° potentials are in V and refer to the formal potential of the ferrocenium/ferrocene
couple, ks in cm/s, second-order rate constants in M
the remaining 20 Ω was applied in the simulation. AcylCN: benzoyl cyanide. AcylCN : benzoyl cyanide anion radical. Bz: benzil. Bz : benzil anion
radical. Acyl(CN)2 : benzil dicyanohydrin dianion. BzCN : anion of monocyanohydrin of benzil. ManCN : anion of mandelonitrile benzoate anion.
-
1
-1
-1
s , first-order rate constants in s . Solution resistance (120 Ω) was electronically compensated, and
•
-
•-
2
-
-
-
TABLE 3. Experimental Conditions and Simulation Parameters for p-Methoxybenzoyl Cyanide, 7, in Acetonitrile (Upper Part of the Table)
and Acetonitrile Containing 0.33 M Water (Lower Part of the Table)a
concentration/solvent
1.23 mM 7/CH3CN
2.50 mM 7/CH3CN
electrochemical reactions
E°
R
ks
E°
R
ks
•
-
AcylCN + e h AcylCN
-1.610
-1.687
0.5
0.5
0.15
0.07
-1.619
-1.687
0.5
0.5
0.15
0.07
•
-
Bz + e h Bz
chemical reactions
K
kf
kb
K
kf
kb
2-
8
4
-4
2
8
4
-4
2
2
(
AcylCN•- h (AcylCN)2
1.0 × 10
1.0 × 10
1.0 × 10
1.0 × 10
4.9 × 10
6.6 × 10
6.6 × 10
1.0 × 10
4.8 × 10
1.2 × 10
2.1 × 10
1.0 × 10
1.0 × 10
1.0 × 10
1.0 × 10
7.1 × 10
6.6 × 10
6.6 × 10
1.0 × 10
4.8 × 10
1.3 × 10
1.4 × 10
2
-
-
8
10
8
10
AcylCN)2 h BzCN + CN
1.0 × 10
1.0 × 10
-
-
8
3
-5
-4
9
8
3
-5
-4
9
BzCN h ManCN
BzCN h Bz + CN
4.8 × 10
4.8 × 10
-
8
4
8
4
1.2 × 10
1.3 × 10
•
-
•-
-2
8
-2
8
AcylCN + Bz h Bz + AcylCN
1.0 × 10
1.0 × 10
2
-5
-5
D of all species/cm /s
2.3 × 10
2.0 × 10
concentration/solvent
1.82 mM 7/CH3CN + 0.33 M H2O
3.70 mM 7/CH3CN + 0.33 M H2O
electrochemical reactions
E°
R
ks
E°
R
ks
•
-
AcylCN + e h AcylCN
-1.586
-1.675
0.5
0.5
0.23
0.12
-1.580
-1.671
0.5
0.5
0.23
0.12
•
-
Bz + e h Bz
chemical reactions
K
kf
kb
K
kf
kb
2-
8
5
-3
2
8
5
-3
2
2
(
AcylCN•- h (AcylCN)2
1.0 × 10
1.0 × 10
1.0 × 10
1.0 × 10
3.1 × 10
1.0 × 10
1.8 × 10
1.0 × 10
2.3 × 10
1.0 × 10
1.0 × 10
0.5
1.8 × 10
1.0 × 10
2.3 × 10
1.0 × 10
3.2 × 10
5.0 × 10
1.0 × 10
1.0 × 10
1.0 × 10
1.0 × 10
2.8 × 10
1.0 × 10
1.8 × 10
1.0 × 10
2.3 × 10
1.0 × 10
1.0 × 10
0.5
1.8 × 10
1.0 × 10
2.3 × 10
1.0 × 10
3.6 × 10
5.0 × 10
2
-
-
8
10
3
8
10
3
AcylCN)2 h BzCN + CN
-
-
8
-5
-4
9
8
-5
-4
9
BzCN h ManCN
BzCN h Bz + CN
-
8
4
8
4
•
-
•-
-2
8
8
-2
8
8
AcylCN + Bz h Bz + AcylCN
•
-
-9
-9
Bz h prod
D of all species/cm /s
2
-5
-5
2.0 × 10
2.2 × 10
a
Other conditions as in Table 2.
seen for the lower concentration (Figure 2), which in turn is
related to the fact that the relative rate of a second-order reaction
decreases with decreases in concentration.
of parameter values, but such adjustment would lead to poorer
fits at other scan rates.
The simulation parameter values used for 6 in acetonitrile
are listed in Table 1. Reactions 2-4 were treated as totally
irreversible reactions (large equilibrium constant). However, the
equilibrium constant for reaction 5 could not be made as large
Also included in the simulations was reaction 3 followed by
parallel reactions 4 and 5, which afford the two products reported
in the electrosynthetic work, 4 and 5.14 We also included the
one-electron reduction of benzil to its anion radical. The effect
of these reactions is difficult to see in Figures 2 and 3 because
there is no apparent shoulder for the reduction of benzil.
However, at low scan rates there is a small peak or shoulder
that must be reproduced by the simulation. An example is shown
in Figure 4. It should be emphasized that the same set of
simulation parameter values was found to fit all of the scan
rates, from 0.10 to 30 V/s. Thus, the quality of the fit for any
given scan rate, say Figure 4, might be improved by adjustment
15
(i.e., some reversibility was needed). Reaction 3, which forms
the anion of the monocyanohydrin of benzil, was treated as being
extremely fast with the rate constants for reactions 4 and 5 being
adjusted to achieve good fits. The inclusion of the homogeneous
exchange reaction between the anion radical of benzoyl cyanide
and benzil was found to improve the quality of the fits. Other
examples of the fits of simulations to the voltammograms of 6
in acetonitrile are included in the Supporting Information
(Figures S1 and S2).
592 J. Org. Chem., Vol. 72, No. 2, 2007

Electroreduction of Benzoyl Cyanides
TABLE 4. Experimental Conditions and Simulation Parameters for p-Chlorobenzoyl Cyanide, 8, in Acetonitrile Containing 0.33 and 0.66 M
a
Water
concentration/solvent
2.20 mM 8/CH3CN + 0.33 M H2O
2.19 mM 8/CH3CN + 0.66 M H2O
electrochemical reactions
E°
R
ks
E°
R
ks
•
-
AcylCN + e h AcylCN
-1.368
-1.401
0.5
0.5
0.09
0.08
-1.348
-1.395
0.5
0.5
0.09
0.08
•
-
Bz + e h Bz
chemical reactions
K
kf
kb
K
kf
kb
2-
8
8
8
4
5
-3
8
8
8
5
5
-3
2
(
AcylCN•- h (AcylCN)2
1.0 × 10
1.0 × 10
1.0 × 10
9.0 × 10
0.27
5.7 × 10
1.0 × 10
2.0 × 10
3.0 × 10
1.0 × 10
1.4 × 10
5.7 × 10
1.0 × 10
1.0 × 10
1.0 × 10
2.0 × 10
0.16
8.0 × 10
1.0 × 10
2.5 × 10
8.0 × 10
2
-
-
10
8
10
8
AcylCN)2 h BzCN + CN
100
100
-
-
BzCN h ManCN
BzCN h Bz + CN
2.0
2.5
-
9
4
8
4
8
3.3 × 10
3.0 × 109
1.5 × 10
•
-
•-
8
8
AcylCN + Bz h Bz + AcylCN
3.7 × 10
1.0 × 10
6.3 × 10
2
-5
-5
D of all species/cm /s
1.3 × 10
a
Other conditions as in Table 2.
voltammetry. Examples of fits of voltammograms of 6 in DMF
are included in the Supporting Information (Figures S3 and S4).
1
4
In the electrosynthetic work, it was demonstrated that the
formation of benzil is enhanced by adding water. An example
of a voltammogram of 6 in acetonitrile containing 0.33 M water
is shown in Figure 5, where the benzil peak is much more
pronounced than in the absence of added water. Fits of
simulations to the voltammograms were successful over the
range of 0.1-30 V/s, and the simulation parameters are shown
in Table 2. In this case, the addition of water causes an increase
in the rate constant for dimerization of the anion radicals by
about a factor of 25.
A similar effect of water was seen with aromatic aldehydes,16
where it was shown that enhanced dimerization rates correlated
with the hydrogen bond donating capability of the additive,
water in the present case. To achieve adequate fits, it was
necessary to include slow loss of the anion radical of benzil,
an observation that was confirmed by studies of benzil itself.
Other examples of fits of simulations to the voltammograms of
FIGURE 6. Voltammogram of 3.70 mM p-methoxybenzoyl cyanide,
, in acetonitrile with 0.33 M water.
7
6
in acetonitrile with 0.33 M water are given in the Supporting
Information (Figures S5 and S6).
It was found that even more benzil is formed on the
voltammetric time scale when 6 is studied in acetonitrile/water
14
(
85% acetonitrile, v/v). In the electrosynthetic work, this mixed
solvent also produced the highest yields of benzil. Due to the
complexity of the voltammetric response, we did not attempt
to fit the voltammograms.
Also investigated were p-methoxybenzoyl cyanide, 7, and
p-chlorobenzoyl cyanide, 8. When studied in acetonitrile in the
absence of added water, the behavior of 7 was similar to that
of 6 though the peak assigned to the reduction of 4,4′-
dimethoxybenzil was somewhat more pronounced. The dimer-
4
-1 -1
ization rate constant, 6.6 × 10 M s , was about five times
larger than that seen for 6. As expected, both the standard
potentials for reduction of 6 and for reduction of the corre-
sponding benzil are shifted ca. 0.13 V in the negative direction
due to the electron-donating properties of the methoxy substi-
tutent. Simulation parameters are given in Table 3, and examples
of fits of simulations to the voltammograms of 7 in acetonitrile
are presented in the Supporting Information (Figures S7
and S8)
As with 6, the reduction of 7 is affected by added water.
Figure 6 shows a voltammogram of 3.70 mM 7 with 0.33 M
water, which reveals a pronounced peak for reduction of the
corresponding benzil. In this case, water again has the effect of
increasing the dimerization rate constant but only by about a
factor of 3 compared to that of 6. The standard potentials are
FIGURE 7. Voltammogram of 2.19 mM p-chlorobenzoyl cyanide, 8,
in acetonitrile with 0.66 M water.
Data were also obtained for two concentrations of 6 in DMF,
and the best-fit simulation parameter values are also included
in Table 1. The most notable feature is that the average
3
-1 -1
dimerization rate constant, 1.3 × 10 M s , is an order of
magnitude smaller than that observed in acetonitrile. The same
trend has been observed in the dimerization of anion radicals
of aromatic aldehydes.16 Thus, at any given scan rate, less dimer
is formed and consequently less benzil is detected in the
(
16) Van Kirk, C. C.; Fioravanti, G.; Mattiello, L.; Rampazzo, L. B.;
Mac ´ı as-Ruvalcaba, N. A.; Evans, D. H. J. Electroanal. Chem. 2005, 582,
51-155.
1
J. Org. Chem, Vol. 72, No. 2, 2007 593

Mac ´ı as-Ruvalcaba and Evans
more negative than those of 6 by about 0.14 V. Simulation
parameters are also given in Table 3, and other examples of
fits of simulations to the voltammograms of 7 in acetonitrile
with 0.33 M water are given in the Supporting Information
and without added water. The same mechanism was found to
hold for benzoyl cyanide in DMF. The mechanism consists of
the initial formation of anion radicals that undergo a relatively
rapid dimerization reaction. The resulting dimer dianion, 2, loses
cyanide to produce the anion of the monocyanohydrin of benzil,
3. This final species participates in two parallel reactions: loss
of cyanide to form benzil, 5, and rearrangement to the anion of
mandelonitrile benzoate, 4. We have found that small amounts
of benzil are formed in the absence of added water, and,
(Figures S9 and S10).
We were not able to fit the voltammograms of chloro
derivative 8 for acetonitrile with no added water. The principal
difficulty is that the peak for reduction of 4,4′-dichlorobenzil
is not well resolved from the main reduction peak. Somewhat
clearer results were obtained in the presence of water. Figure 7
shows data for 2.19 mM 8 in acetonitrile with 0.66 M water at
14
consistent with the electrosynthetic results, benzil formation
is enhanced in the presence of water.
1
.00 V/s. Data with 0.33 M added water were also fit by
simulation; the simulation parameters for both water concentra-
tions are given in Table 4, and other examples of fits of
simulations to the voltammograms of 8 in acetonitrile with 0.33
and 0.66 M water are given in the Supporting Information
Experimental Section
Chemicals and Reagents. The solvent for electrochemistry was
acetonitrile or N,N-dimethylformamide, and the electrolyte was 0.10
M tetrabutylammonium hexafluorophosphate. Sources and treatment
(Figures S11 and S12).
At 0.33 M water, where comparison among the three
17
of the solvents and electrolyte have been described. Benzoyl
compounds is possible, the dimerization rate constant decreases
cyanide, 6, was a commercial sample. Benzoyl cyanides 7 and 8
were prepared by reaction of 0.02 mol of the corresponding benzoyl
chloride with 0.023 mol of cuprous cyanide according to the
methodology described by Oakwood and Weisgerber and were
purified by column chromatography with 90:10 hexane/ethyl acetate
mixture as eluent, followed by recrystallization from hexane (7,
5
-1 -1
in the order X ) Cl (8) (5.7 × 10 M s ) > X ) H (6) (3.1
5
-1 -1
5
-1 -1
×
10 M s ) > X ) CH3O (7) (1.8 × 10 M s ). This
1
8
small effect may be due to the ability of the electron-
withdrawing substituent to lower the energy of the transition
state where the two negatively charged acyl anions, ArC(O) ,
-
1
9
20
mp 58.7-59.9 °C, lit. 56.5-57.5 °C, lit. 59.0 °C; 8, mp 41.5-
come together to dimerize. Interestingly, in the absence of added
water the trend is reversed for 6 and 7 (see Tables 1 and 3). In
the case of the chloro derivative with 0.33 M water, the standard
potentials for reduction of 8 and its corresponding benzil are
shifted in the positive direction by 0.08 and 0.12 V, respectively,
compared to those of 6. These shifts, of course, are caused by
the electron-withdrawing nature of the chloro substituent. Also,
for 6 and 7 the standard potentials for the benzoyl cyanide/
benzoyl cyanide anion radical couple and for the benzil/benzil
anion radical couple are shifted slightly (12-40 mV) toward
less negative potentials in acetonitrile with 0.33 M water
compared to that with no added water. These shifts reflect
hydrogen-bonding interactions of water with the anion radicals.
All three compounds, 6-8, were studied in the electrosyn-
2.3 °C, lit. 41-42 °C,19 lit. 42.0 °C ).
20
4
Electrochemical Cells, Electrodes, and Instrumentation. These
were as described earlier.17 The working electrode was a 0.3-cm-
diameter glassy carbon electrode whose area was determined to be
2
0
.0814 cm . The reference electrode was a silver wire immersed
4 6 3
in 0.10 M Bu NPF /0.010 M AgNO in acetonitrile. The potential
of this reference electrode was periodically measured versus the
reversible ferrocene/ferrocenium potential, and all potentials re-
ported in this work are with respect to ferrocene. Evaluation of the
solution resistance has been described.17 The temperature was
maintained at 298 K.
Variation of the scan rate, V, was done in such a way that there
was an approximately linear variation in log V. Thus, for scan rates
between 0.1 and 30 V/s, the values chosen were 0.1, 0.2, 0.3, 0.5,
1, 2, 3, 5, 10, 20, and 30 V/s (log V ) -1, -0.699, -0.523, -0.301,
0, 0.301, 0.477, 0.699, 1, 1.301, 1.477).
thetic work, and the yields of benzil obtained in acetonitrile/
water were very similar, 62-67%.14
Digital simulations were conducted with the aid of DigiElch,
version 2.0, a free software package for the Digital simulation of
common Electrochemical experiments (http://www.digielch.de).
Part of the solution resistance was compensated electronically, and
the remainder was included in the simulation program.
Conclusion
2
1
The electrochemical reduction of three benzoyl cyanides has
been shown to occur by reactions 1-5 in acetonitrile both with
(
17) Mac ´ı as-Ruvalcaba, N. A.; Evans, D. H. J. Phys. Chem. B 2005,
Acknowledgment. Support of this research by the National
Science Foundation, Grant CHE 0347471, is gratefully ac-
knowledged.
1
09, 14642-14647.
(
18) Oakwood, T. S.; Weisgerber, C. A. Org. Synth. 1944, 24, 14-16.
(19) Cao, Y.-Q.; Du, Y.-F.; Chen, B.-H.; Li, J.-T. Synth. Commun. 2004,
3
4, 2951-2957.
20) Olah, G. A.; Arvanaghi, M.; Surya Prakash, G. K. Synthesis 1983,
36-637.
(
Supporting Information Available: Examples of fits of
simulation to background-corrected voltammograms of 6-8 under
various conditions (Figures S1-S12). This material is available free
of charge via the Internet at http://pubs.acs.org.
6
(21) (a) Rudolph, M. J. Electroanal. Chem. 2003, 543, 23-29. (b)
Rudolph, M. J. Electroanal. Chem. 2004, 571, 289-307. (c) Rudolph, M.
J. Electroanal. Chem. 2003, 558, 171-176. (d) Rudolph, M. J. Comput.
Chem. 2005, 26, 619-632. (e) Rudolph, M. J. Comput. Chem. 2005, 26,
6
33-641. (f) Rudolph, M. J. Comput. Chem. 2005, 26, 1193-1204.
JO062181E
594 J. Org. Chem., Vol. 72, No. 2, 2007