Anodic cyanation of β-dicarbonyl compounds

Article abstract of DOI:10.1055/s-2005-872685

Several β-dicarbonyl compounds were electrochemically oxidized in a methanolic solution in the presence of sodium cyanide and sodium methoxide to yield the corresponding α-cyano-β-dicarbonyl compounds in moderate to good yields. Presumably, a two-electron

Full text of DOI:10.1055/s-2005-872685

LETTER
2507
Anodic Cyanation of b-Dicarbonyl Compounds
Anodic Cyanation of
b
i
-Dicarb
t
onyl
C
s
ompound
u
s
hiro Okimoto,* Kaori Numata, Yukio Takahashi, Masayuki Hoshi, Kenta Tomozawa, Takamasa Shigemoto
Department of Applied and Environmental Chemistry, Kitami Institute of Technology, Koen-cyo 165, Kitami, Hokkaido 090-8507, Japan
Fax +81(157)247719; E-mail: oki@chem.kitami-it.ac.jp
Received 15 July 2005
cyanide was favorable in affording higher yields of 2a
Abstract: Several b-dicarbonyl compounds were electrochemical-
(runs 5, 6). Excessive amounts of current passed de-
ly oxidized in a methanolic solution in the presence of sodium cya-
creased the yield of 2a (run 4). Within the temperature
nide and sodium methoxide to yield the corresponding a-cyano-b-
range of 5–50 °C, favorable results were obtained at a
dicarbonyl compounds in moderate to good yields. Presumably, a
two-electron transfer transforms the anion derived from the b-dicar- convenient reaction temperature of roughly 15 °C.
bonyl compounds into a cation, which then reacts with a cyanide ion
to afford the cyanation products.
Surprisingly, the presence of catalytic amounts halogen
ion source such as KI, KBr, or KCl did not function as
Key words: oxidation, ketones, esters, nitriles, cations
electron carriers for our electrooxidative reaction.
Table 1 Anodic Cyanation of Acetylacetonea
CN
The electrooxidative conversion of organic anions into the
corresponding radicals or cations has proven to be a
highly useful synthetic reaction.1 For example, it is well-
known that a b-dicarbonyl anion, one of the most common
organic anion, can readily undergo electrooxidation to
form a radical that can dimerize or add across a double
bond of an olefin to afford a coupled product.2 Further-
more, in addition to reports of direct cyanations of several
types of organic compounds via electrooxidation,3 we
have also established several valuable electrooxidative
procedures involving cyanation.4 In continuation of our
investigations on organic synthesis using the electro-
chemical method,5 we have carried out electrooxidation of
b-dicarbonyl compounds such as b-diketones and b-ke-
toesters in methanolic solution containing sodium cyanide
and sodium methoxide. Results show that such b-dicarbo-
nyl compounds successfully undergo cyanation at the
activated carbon of these substrates to afford the corre-
sponding cyano dicarbonyl compounds in moderate to
good yields.
–2e, –H+
CH3
C
O
CH2
C
O
CH3
CH3
C
O
CH
C
O
CH3
NaCN/MeOH
1a
2a
Run
NaCN
(mmol)
NaOMe
(mmol)
Current passed Yield of
(F/mol)
2a (%)b
1
2
3
4
5
6
30
0
0
2.2
23
75
1.0
30
75
0
2.2
54
75
0
3.0
44
75
15
30
2.2
57
75
2.2
65
a Reaction conditions: 1a (30 mmol), MeOH (80 mL), constant
current (0.5 A), temperature (ca. 15 °C).
b Yields were determined by GC analysis.
Using the optimal reaction conditions, which are based on
the yields as listed in Table 1, the anodic cyanations of
several b-dicarbonyl compounds (1a–h) were carried out,
and the results are shown in Table 2. In all cases, most of
the substrates were consumed after the passage of 2.0 F
mol–1 of electricity. Although a small portion of sodium
cyanide remained undissolved at the beginning of the re-
action, passage of the electrolytic current gradually dis-
solved the sodium cyanide into the methanolic solution.
During the course of the reaction, the initially colorless
methanolic solution became slightly yellow then muddy
brown at the final stages of the reaction. In the cases of 1a
and 1b, significant amounts of precipitates, presumably
the sodium salts of the corresponding cyanation products,
were observed in the electric cell after passage of about
1.5 F mol–1 of electricity. With the exception of 1g, the
cyanation products were obtained in moderate to good
yields after passage of 2.2 F mol–1 of electricity. In the
cases where the yields were low, such as 1g, the reaction
To establish the most favorable reaction conditions for the
electrooxidative cyanation of the b-dicarbonyl com-
pounds, electrooxidation using a model substrate (acetyl-
acetone, 1a), in the presence of varying amounts of
sodium cyanide and sodium methoxide, and under the dif-
fering amounts of current passed, were carried out. The
reaction conditions, along with the corresponding yields
of the product (2-acetyl-3-oxobutanenitrile, 2a) are listed
in Table 1. When an equimolar amount of sodium cyanide
relative to 1a was used as the lone supporting electrolyte,
the yield of 2a was merely 23% (run 1). However, increas-
ing the amount of sodium cyanide to 2.5 equivalents rela-
tive to 1a resulted in an increase of the yield to 54% (run
3). Furthermore, the addition of an equimolar amount of
sodium methoxide relative to 1a along with sodium
SYNLETT 2005, No. 16, pp 2507–2509
0
4
.1
0
.2
0
0
5
Advanced online publication: 21.09.2005
DOI: 10.1055/s-2005-872685; Art ID: U22905ST
© Georg Thieme Verlag Stuttgart · New York

2508
M. Okimoto et al.
LETTER
resulted in the formation of considerable amounts of tar- absence of 1a, however, the solution did not clearly dis-
like material that was insoluble in n-hexane and difficult charge unless the anode potential exceeded 1.2 V vs. SCE.
to purify (see experimental section). As a note, benzyl The results suggest that the cyanation involves a direct
ester 1d readily underwent transesterification during the two-electron oxidation of 1a to form the corresponding
electrooxidation resulting in the corresponding methyl cation, which immediately undergoes a nucleophilic at-
ester 2b (60% yield).
tack by a cyanide ion to afford the cyanation product, as
illustrated in Scheme 1. Presumably, the presence of the
methoxide anion facilitates the deprotonation of the
substrate in forming the anion. As a note, neither dicyan
(NC–CN) nor any dicyanation products were detected in
the reaction system.4c
Table 2 Anodic Cyanation of b-Dicarbonyl Compoundsa
CN
–2e, –H+
R1
C
O
CH2
C
O
R2
R1
C
O
CH
C
O
R2
NaCN/MeOH
2
1
R2
–
R1
Substrate
1
Isolated yield
of 2 (%)
+
R1
R2
CH2
CH
– H
C
C
O
C
O
C
O
O
base
1
R1
R2
–
CN
1a
1b
1c
1d
1e
1f
Me
Me
Me
Me
Me
i-Pr
Ph
Me
64
61
73
60b
60
73
41
80
CN
CH
+
CH
R2
R2
MeO
R1
R1
– 2e
C
C
O
C
C
t-BuO
BnO
Ph
O
O
O
2
Scheme 1 Proposed scheme of anodic cyanation
On the basis of their physical and spectral data, the prop-
erties of the compounds were in good agreement with
those from literature.6 Preparative scale electrooxidations
were carried out in a tall 100-mL beaker equipped with a
fine frit cup (porosity, ca. 100 mm) as the cathode com-
partment, an insert cylindrical platinum net (diameter, 32
mm; height, 35 mm; 55 mesh) as the anode, and a nickel
coil (diameter, 0.8 mm; length; 300 mm) as the cathode.
Oxidations of b-dicarbonyl compounds 1a–h were as fol-
low: a solution of substrate 1a–h (30 mmol), powdered
NaCN (3.68 g, 75 mmol), and NaOMe (30 mmol) in
MeOH (80 mL) was electrooxidized under a constant cur-
rent (0.5 A). During the course of the electrooxidation, the
anolyte was magnetically stirred while maintaining the
temperature of the cell at approximately 15 °C. Upon pas-
sage of 2.2 F mol–1 of electricity, the reaction mixture was
concentrated in vacuo at approximately 40 °C to remove
most of the methanol. The residue was treated with water
(ca. 30 mL), then washed with diethyl ether (2 × 30 mL)
to remove the ether soluble material. The aqueous layer
was acidified using 3 M HCl, then saturated with sodium
chloride. The resulting oily layer was extracted using di-
ethyl ether (3 × 60 mL), which were combined, washed
with brine, and dried over magnesium sulfate. Following
the removal of the solvent, the brownish viscous residue
was, in the cases of 2a–c, and 2f, purified by distillation
under reduce pressure. In the remainder of the cases, resi-
due was extracted with hot n-hexane (several times, total
volume of the n-hexane was ca. 60 mL), then cooled using
liquid nitrogen with vigorous stirring to afford white crys-
tals, which were collected by filtration then washed with
small portions of cold n-hexane (ca. –50 °C). Second crop
of the products was further obtained by concentration of
the mother liquid.
MeO
MeO
Ph
1g
1h
Ph
a Reaction conditions: 1 (30 mmol), NaCN (75 mmol), NaOMe (30
mmol), MeOH (80 mL), current passed (2.2 F mol–1), constant current
(0.5 A), temperature (ca. 15 °C).
b Transesterified methyl ester 2b was obtained instead of benzyl
ester 2d.
Figure 1 Cyclic voltammograms of NaCN/MeOH in the presence
and absence of 1a. Scan rate = 1.0 V/s; concentration of NaCN = 50
mM; concentration of 1a = 5 mM at Pt anode.
As shown by the results of the voltammetric experiments
(Figure 1), the methanolic solution of 1a containing sodi-
um cyanide was sufficiently oxidized at the platinum an-
ode, even with a potential of ca. 0.7 V vs. SCE. In the
Synlett 2005, No. 16, 2507–2509 © Thieme Stuttgart · New York

LETTER
Anodic Cyanation of b-Dicarbonyl Compounds
2509
Although these cyano diketones and cyano ketoesters are
known compounds, to the best of our knowledge, there
has yet to be a report that describes an electrochemical
technique for the umpolung of anions to cations in afford-
ing a-cyano b-dicarbonyl compounds. In general, cyana-
tions of such b-dicarbonyl compounds involve cyanogen
chloride, which is, not only an irritant, but highly poison-
ous.6 In contrast, our electrochemical method features
several advantages: a) very mild reaction conditions, b)
lack of harsh oxidizing agents, and c) convenience of a
one-pot reaction.
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Synlett 2005, No. 16, 2507–2509 © Thieme Stuttgart · New York