Reduction of 1,2-dicarbonyl compounds and of their N-phenylimine derivatives by sodium cyanide under aprotic conditions

Article abstract of DOI:10.1016/j.crci.2015.07.007

Some aromatic 1,2-dicarbonyl compounds, i.e. 9,10-phenanthrenequinone, acenaphthenequinone and benzil, and their corresponding N-phenyl monoimines, have been reduced, using dry acetonitrile as the solvent, in the presence of sodium cyanide as a reducing agent. Comparative potentiostatic preparative-scale electrolysis is described.

Full text of DOI:10.1016/j.crci.2015.07.007

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´
Full paper/Memoire
Reduction of 1,2-dicarbonyl compounds and of their
N-phenylimine derivatives by sodium cyanide under
aprotic conditions
a
a
Kaouthar Hamrouni b, Belen Batanero a, , Fructuoso Barba , Isidoro Barba ,
*
Khaled Boujlel b, Mohamed Lamine Benkhoud b
a
´
Department of Organic Chemistry, University of Alcala, 28871 Alcala de Henares, Madrid, Spain
b Laboratoire de chimie analytique et d’e´lectrochimie, faculte´ des sciences, universite´ Tunis El Manar, 2092 El Manar, Tunis, Tunisia
A R T I C L E I N F O
A B S T R A C T
Article history:
Some aromatic 1,2-dicarbonyl compounds, i.e. 9,10-phenanthrenequinone, acenaphthe-
nequinone and benzil, and their corresponding N-phenyl monoimines, have been reduced,
using dry acetonitrile as the solvent, in the presence of sodium cyanide as a reducing agent.
Comparative potentiostatic preparative-scale electrolysis is described.
Received 5 June 2015
Accepted after revision 7 July 2015
Available online xxx
ß 2015 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Keywords:
Homogeneous electron transfer
Radical anion
Cathode
Superoxide anion
Oxygen
1. Introduction
cellular proliferative disease [3] together with an anti-
proliferative agent, but also 1H-azepine-2,7-diones have
In 1971, it was published [1] that cyanide anions were
able to reduce electron acceptor molecules such as
fluorenone, anthraquinone or phenanthrenequinone
through the formation of the corresponding quinone anion
radical intermediates under aprotic polar solvents such as
DMF, DMSO or HMPA. The formation of these paramag-
netic anion radicals was proven by recording the ESR and
visible spectra of their strongly coloured solutions. More
recently, Roginsky et al. [2] described the similar one-
electron reduction of Ubiquinone-0 by ascorbate under
aerobic conditions. Nevertheless, the synthetic-scale way
has not yet been explored regarding these processes.
On the other hand, many imides, such as naphthalimi-
des, have been employed in the treatment of a host with a
demonstrated hypolipidemic and good hypotriglyceride-
mic activity [4].
The cathodic reduction of o-quinones and of other 1,2-
dicarbonyl compounds in aprotic organic solvents has
been studied in depth in our research group, both in the
absence and in the presence of arene diazonium salts. In
the absence of diazonium salts, o-quinones can be
transformed in good yield and only one pot to 1,3-dioxoles
when electrolysis is performed in dichloromethane as the
solvent. Other 1,2-dicarbonyl derivatives, such as benzil or
1,2-naphtoquinone, have been respectively converted into
methylenediesters [5] or lactones [6] by cathodic reduction
inthepresenceofoxygen. Whendiazoniumsaltsarepresent
in the catholyte, concomitant reduction of the latter and of
1,2-quinones produces coupling products with radicals
generated from the solvent. In this case, aryl radicals,
obtained in the diazonium salt discharge, led to cyanome-
thylated, alkylated or dimethylaminocarbonylated coupling
*
Corresponding author.
E-mail address: belen.batanero@uah.es (B. Batanero).
http://dx.doi.org/10.1016/j.crci.2015.07.007
1631-0748/ß 2015 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Hamrouni K, et al. Reduction of 1,2-dicarbonyl compounds and of their N-
phenylimine derivatives by sodium cyanide under aprotic conditions. C. R. Chimie (2015), http://dx.doi.org/10.1016/
j.crci.2015.07.007

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Ph
Ph
O
N
O
N
CN
CN
O2
+ O2
1b
E.T.
1 e-
E.T.
1b
O2
CN
Ph
N
O
O
O
O
H2O
N
O
O
O
N
Ph
+ 2H+
-H2O
O
N
Ph
Ph
CN
HO
2b
70%
3b
18%
Scheme 1. Proposed pathway for the reduction of 1b by the cyanide anion.
products with the anion radicals of different quinones, by
hydrogen atom abstraction from acetonitrile, dichloro-
ethane or DMF, respectively used as the solvent. This
reduction of 1,2-quinones in the presence of benzenedia-
zonium tetrafluorborate was extended to other solvents
such as dichloromethane, chloroform, ethyl acetate or
chloroacetonitrile. A very special case in this topic was the
electrosynthesis of 1,3,4-oxadiazol-2(3H)-ones and
dibenzo[c,e]azepines when N-methylformamide was
used as the solvent [7].
In the present paper, we describe the reduction of 1,2-
dicarbonyl compounds and their imine derivatives in
acetonitrile, but not only at the electrode: a comparison
between the electrochemical and a conventional electron
transfer process from cyanide anion to the quinone is
made. The subsequent formation, when oxygen is present
in solution, of superoxide anion provides an interesting
entry to 1H-azepine 2,7-diones.
(1e) or 1,2-diphenyl-2-(phenylimino)ethanone (1f) were
stirred for 24 h in the presence of a large excess of sodium
cyanide, a redox process was observed between them,
allowing one to get results similar to those obtained in the
corresponding preparative-scale electrochemical reduc-
tion of 1.
The expected cyanhydrins were obtained as side
products by direct attack of the nucleophile on the
carbonyl group.
The treatment of 1b with cyanide afforded 1-phenyl-
1H-azepine-2,7-dione (2b) as the main product (70% yield)
after an electron transfer reaction in solution from cyanide
to 1b, as indicated in Scheme 1. 9,10-Dihydro-9-hydroxy-
10-(phenylimino) phenanthrene-9-carbonitrile (3b) was
obtained in 18% yield.
In the reaction of 1a with cyanide, the higher stability of
the anion radical and of the dianion of 1a, related to that of
1b, is responsible for the lower conversion obtained in this
case, even after 48 h of stirring. Together with the
formation of the dicarboxylic acid and its anhydride (2a)
[8] as main products, lactone 3a was formed as a minor
product (12%) (see Scheme 2). A mechanism for the
formation of 3a has already been proposed [6] through a
Baeyer–Villiger/Dakin reaction involving oxygen.
2. Results and discussion
When 9,10-phenanthrenequinone (1a), 10-(phenylimi-
no)phenanthren-9(10H)-one (1b), acenaphthenequinone
(1c), 2-(phenylimino)acenaphthylen-1(2H)-one (1d), benzil
O
O
O
O
CN
CN
O2
+
O2
1a
E.T.
E.T.
1 e-
1a
+ O2
O
O
O
O
O
O
O
O
O
O
O
O
O
+ 2H+
-H2O
+
3a
12%
2a
50%
Scheme 2. Proposed pathway for the reduction of 1a by the cyanide anion.
Please cite this article in press as: Hamrouni K, et al. Reduction of 1,2-dicarbonyl compounds and of their N-
phenylimine derivatives by sodium cyanide under aprotic conditions. C. R. Chimie (2015), http://dx.doi.org/10.1016/
j.crci.2015.07.007

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3
-2e-
H2O
OHC-CHO + 2 NH3
NC-CN
O
2
CN
2
CN
H
N
O
O
O
O
+
NH3
2c
4c
Scheme 5. Proposed mechanism for the obtention of 4c from 1c.
.
_
+ 1e-/or CN-
Ar-CO-CO-Ar
Ar-CO-CO-Ar
1e
.
_
.
_
Ar-CO-CO-Ar
Fig. 1. (Colour online.) Cyclic voltammogram of 1b in dry acetonitrile/
LiClO4 at a platinum cathode. Reference electrode: Ag/AgCl. Scan rate:
100 mV/s.
1e + O2
+
O2
O- O-
.
_
.
_
2
Ar-COO-
Ar-CO-CO-Ar
+ O2
Ar
Ar
O
O
Preparative-scaled electrolysis of 10-(phenylimino)-
phenanthren-9(10H)-one (1b) in dry CH3CN (AN)/lithi-
um perchlorate at a mercury pool as the cathode
Scheme 6. Already published mechanism proposed for the cathodic
reduction of benzil (1e).
was carried out applying
a reduction potential of
–1.3 V (vs. Ag/AgCl) (see Fig. 1). As indicated in Scheme 3,
Ph
Ph
Ph
O
N
O
N
N
O
+ 2 e-
-1.3V
O2
+
O2
E.T.
1b
Ph
N
O
O
O
O
O
O
O
O
N
Ph
N
Ph
+H+
-H2O
2b (84%)
Scheme 3. Electrochemical reduction of 1b. Proposed pathway to explain the formation of the imide 2b.
O
O
O
O
CN
CN
O2
1c
+
O2
E.T.
E.T.
1 e-
1c
+ O2
O
CN
H2O
O
O
O
O
O
O
O
O
O
O
OH
O
+ 2H+
-H2O
CN
2c (75%)
3c (4%)
Scheme 4. Proposed pathway for the reduction of 1c by the cyanide anion.
Please cite this article in press as: Hamrouni K, et al. Reduction of 1,2-dicarbonyl compounds and of their N-
phenylimine derivatives by sodium cyanide under aprotic conditions. C. R. Chimie (2015), http://dx.doi.org/10.1016/
j.crci.2015.07.007

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K. Hamrouni et al. / C. R. Chimie xxx (2015) xxx–xxx
Ph
Ph
Ph
O
N
N
O
N
+ 2 NaCN
NC
CN CN
2f
1f
Scheme 7. Double cyanide nucleophilic addition to 1f explaining the formation of 2f.
1-phenyl-1H-azepine-2,7-dione (2b) was obtained as the
major product, together with the expected cyanhydrin:
9,10-dihydro-9-hydroxy-10-(phenylimino)phenanthrene-
9-carbonitrile (3b).
4. Experimental
4.1. General procedure
The reaction of acenaphthenequinone (1c) with sodium
cyanide produced, under the same experimental condi-
tions as those specified above, the expected dicarboxylic
acid and its anhydride (2c) as main products (75%) after
24 h of stirring (Scheme 4). The corresponding cyanhydrin:
1-hydroxy-2-oxo-acenaphthylene-1-carbonitrile (3c) was
formed as a minor product.
In this case, the azepine 4c was obtained as a trace
product. The formation of 4c has to be explained by the
presence of ammonia in the medium. The only source of
ammonia involves, however, a simultaneous oxidation of
the cyanide anion, as it is summarized in Scheme 5.
The reduction by cyanide of 2-(phenylimino)acenaph-
thylen-1(2H)-one (1d) afforded, almost quantitatively,
the N-phenylimide of naphthalene-1,8-dicarboxylic acid
(2d), through a pathway similar to that described in
Scheme 3.
The electron transfer reaction from the cyanide anion to
1,2-dicarbonyl compounds and their monoimine deriva-
tives 1a–f was performed under stirring conditions in dry
acetonitrile (40 mL) solutions where the substrate
(0,25 mmol) was maintained for 24 h (48 h for 1a and
1e) at room temperature and usual laboratory illumina-
tion conditions, in the presence of sodium cyanide
(10 mmol) over an open-air vessel. The reaction was
followed by TLC until complete disappearance of the
starting compound.
4.2. General electrochemical procedure
The electrochemical reduction of 1b was performed
under potentiostatic conditions in a concentric cell with
two compartments separated by a porous (D4) glass frit
diaphragm and equipped with a magnetic stirrer. A
mercury pool was used as the cathode (18 cm2), a
platinum plate as the anode (9 cm2) and an Ag/AgCl
electrode as the reference. The SSE was dry acetonitrile
(AN) containing 0.1 M lithium perchlorate.
Finally, the electron-transfer reaction from cyanide
anion to benzil (1e) was carried out, producing benzoic
acid and the expected cyanhydrin: 2-hydroxy-3-oxo-2,3-
diphenylpropanenitrile (2e) in 50% yield.
A solution of the electroactive substrate (1.0 mmol in
60 mL of SSE) was electrolyzed at a constant potential of
–1.3 V (vs. Ag/AgCl), corresponding to the only reduction
peak observed for this compound (see Fig. 1).
The mechanism proposed to explain the formation of
benzoic acid from cyanide and 1e is summarized in
Scheme 6. It has been discussed previously in a paper
reporting the electrochemical reduction of benzil in the
presence of oxygen [5].
The monoimine 1f afforded 2-phenyl-2-(phenylimi-
no)acetonitrile (2f) as the major product (72% yield)
together with the low yielded (10%) 2-hydroxy-2,3-
Once the reduction was finished, the solvent in the
reaction solution was removed under reduced pressure.
The residue was extracted with ether/water and the
organic phase dried over Na2SO4 and concentrated by
evaporation. The resulting solid was chromatographed on
silica gel (22 Â 3 cm) column, using PE/EtOAc (4:1) as an
eluent. The spectroscopic description of the obtained
compounds is given below. The aqueous phase was
acidified with HCl (5%) and further extracted with ether,
dried over Na2SO4 and concentrated by evaporation. From
the aqueous solutions were isolated, when formed,
carboxylic acids.
diphenyl-3-(phenylimino)propanenitrile
(cyanhydrin)
(3f). The formation of 2f could be rationalized through
the logical pathway proposed in Scheme 7, where a double
nucleophilic addition attack from cyanide to 1f can
produce a dianion intermediate that, similarly to benzoin
condensation, could evolve to 2f.
1-Phenyl-1H-azepine-2,7-dione (2b): (70% yield). Mp
195–197 8C. [Lit.[9] 197–198 8C]. MS m/e (relative intensi-
ty) EI: 299 (M+, 26), 254 (9), 206 (12), 180 (100), 152 (31),
76 (4).
9,10-Dihydro-9-hydroxy-10-(phenylimino)phenan-
threne-9-carbonitrile (3b): (18% yield). MS m/e (relative
intensity) EI: 311 (M+ + 1, 24), 310 (M+, 100), 309 (28), 281
(42), 267 (18), 254 (12), 190 (93), 180 (33), 165 (31), 152
(32), 77 (16).
3. Conclusion
The reactions here described involve an unexpected
electron transfer reaction in solution from the cyanide
anion to conjugated 1,2-dicarbonyl derivatives to give
interesting organic imides, such as 1H-azepine-2,7-diones.
The expected nucleophilic behaviour of the cyanide anion
to give the corresponding cyanhydrin has been minimized
under our employed experimental conditions.
Please cite this article in press as: Hamrouni K, et al. Reduction of 1,2-dicarbonyl compounds and of their N-
phenylimine derivatives by sodium cyanide under aprotic conditions. C. R. Chimie (2015), http://dx.doi.org/10.1016/
j.crci.2015.07.007

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5
1-Hydroxy-2-oxo-1-acenaphthylene-1-carbonitrile
(3c): (4% yield). MS m/e (relative intensity) EI: 209 (M+, 57),
181 (52), 164 (16), 155 (100), 138 (9), 127 (68).
Acknowledgements
The authors gratefully acknowledge the financial
support of the University of Alcala project
No. CCG2014/EXP-010. K. Hamrouni thanks the Tunisian
Ministry of Science that provided her a grant ‘‘bourse
d’alternance’’ as financial support of her stay in Spain.
1,8-Naphthalenedicarboximide (4c): Mp 298 8C.
[Lit.[10] 300–302 8C]. MS m/e (relative intensity) EI: 197
(M+, 100), 153 (78), 140 (6), 126 (40), 87 (9), 74 (9).
N-Phenyl 1,8-naphthalenedicarboximide (2d): (84%
yield). Mp 205–206 8C. [Lit.[11] 207–209 8C]. MS m/e
(relative intensity) EI: 273 (M+, 73), 272 (M+–1,100), 228
(26), 201 (7), 180 (20), 152 (11), 126 (18), 74 (4).
2-Hydroxy-3-oxo-2,3-diphenylpropanenitrile (2e):
–
References
(50% yield). 1H NMR (300 MHz, CDCl3)
7.42–7.48 (m, 5H), 8.04 (d, 2H, J = 7.8 Hz). 13C NMR
(75.4 MHz, CDCl3) : 63.5, 116.4, 127.9, 128.7, 129.3,
d: 6.7 (bs, 1H),
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yield) Mp 73–75 8C. [Lit.[12] 76 8C]. MS m/e (relative
intensity) EI: 206 (M+, 100), 205 (M+–1, 56), 180 (51), 129
(2), 103 (1), 77 (15).
2-Hydroxy-2,3-diphenyl-3-(phenylimino)propane-
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Please cite this article in press as: Hamrouni K, et al. Reduction of 1,2-dicarbonyl compounds and of their N-
phenylimine derivatives by sodium cyanide under aprotic conditions. C. R. Chimie (2015), http://dx.doi.org/10.1016/
j.crci.2015.07.007