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Electrochemical reduction of carbonimidoyl dichlorides. A new method for the preparation of isocyanides
0040.4039/92 $5.00 + Pergamon I’rcss Ltd
Tetrahedron Letters. Vol. 33. No. 33, pp. 4779-4182.1992 Printed in Great Brikin
ELECTROCHEMICAL
REDUCTION
METHOD
Antonio
FOR
THE
Guirado*,
OF
CARBONIMIDOYL
PREPARATION
Andrtk
Zapata,
OF
and
DICHLORIDES.
A NEW
ISOCYANIDES
Manuel
Fenor
Deparlamento de Quimica OrgAnica, Facultad de Quimica, Universidad de Murcia, Campus de Espinardo, E-30071, Murcia, Apartado 4021, Spain
Abstract:The reagent
cathodic
reduction
of carbonimidoyl
method for the preparation
The synthesis variety
of reactions
general
application
of isocyanides
of isocyanides leading
reviewed
were
reported
are fewer in number:
some those
reaction
cyanide salts, reaction of primary amines with dichlorocarbene monosubstituted chloride
formamides
or phosphorus
by treatment
oxychloride.
but it has the inconvenience devoted phosgene
to improving are foundz.
of isocyanides, polymers,
Advances
especially
The phosgene
as well as a recent
attention
time
agot.
arylsulfonyl
of isocyanides,
(1)
metal
of water from N-
chlorides,
cyanuric
to the isolation
t
metal
and synthesis
c’ 4779
+
2C1-
complexes,
of naturally
efforts
reagents
of the proved synthetic
compounds,
R-NC
numerous
using alternatives
because
of heterocyclic
2e
with heavy
literature
Cl \
a wide
to have the most
and the elimination
isocyanides3.
R-N=C’
Although
method gives by far the best results generally,
in this field are substantial
in the synthesis
yields.
that appear
In the subsequent
of synthesis
a new, mild and free-
of alkyl halides
with either phosgene,
of its high toxicity.
the methods
provides
in almost quantitative
was excellently
to isocyanides
in synthesis
dichlorides
to
utility and
occurring
4780
We herein report a new, efficient and simple method for the synthesis cathodic
reduction
of carbonimidoyl
dichlorides
isocyanates
and
isocyanides
(2) in almost quantitative
processes
N-monosubstituted
of other
gem-polyhalogenated
view6, the electrochemical In contrast the preparation
reductions
of isocyanides Therefore,
complex
reaction
difficult
because
mixture. the
However,
electrochemical
reaction
dimethylformamide
pronounced
reagents.
processes
to
present
can be avoided
This solution
mildness of the procedure by electrolysis
This would
concentrations7.
potential
glass frit (medium) platinum
diaphragm.
cooling.
cylindrical
A mercury
The reductions
50 mL and 20 mL of this solution respectively.
To prevent
anhydrous
sodium
dichlorides
(1) (5 mmol)
consumption
peak
up
after
the
generated
perchlorate
in a
and lithium
purposes.
The very
of non-electroactive
and work with them at very low
in a pure state, these are easily obtained
were
carried
pool (diameter
out
was magnetically
separated
by
a constant by a circular
stirred. The temperature
were carried out8 in DMF-LiCl04, in the cathodic
of electrogenerated
analyses
in the anode Solutions
cathodic
with capillary
isocyanides.
and a
was kept
at
0.2 M. Approximately
and the anodic
acid
under the appropriate
of the corresponding
under
5 cm) was used as the cathode
(39) was placed in this compartment.
were electrolyzed
a single
lithium
cell with two compartments
was 2 F . mot-1 for all cases. GUMS
showed
is “extremely
working
in the presence
isocyanides
Electrolyses
were placed
accumulation
carbonate
levels,
with ether.
plate as the anode. The catholyte
15 “C by external
solutions
are required
is frequently
feature of the method in order to enable
dichlorides
of labile
Procedure.
in a concentric
at low
are quantitatively
inorganic
out under
of the products from a
of purification
subsequent
Thus,
can be suppressed:
be used for most synthetic
is also a promising
isocyanides
Experimental
any
contains
could
even
isocyanides
of carbonimidoyl
addition of water and simple extraction
cathodic
since
permit the capture
If isolated
Typical
method
which additionally
exclusively.
and purification
vapours,
advantages.
which is carried
synthesis
of the usual techniques
isocyanide
by the
reaction
points of
unknown.
noteworthy
in isocyanide
and (ii) isolation
The application
solution
“in situ” synthesis
by a reagent-free
dehalogenation
from different
remained
shows valuable
two serious obstacles
exposure
distressing”1.
dichlorides
the corresponding
reductive
had been studied
of carbonimidoyl
is performed
(i) loss of yield due to secondary
salts,
compounds
via the
from isothiocyanates,
provide
While the electrochemical
with other methods this procedure
very mild conditions.
chloride
(1) which are easily available
formamides 4*5. These reactions yields.
of isocyanides,
Compartments,
compartment,
Of the carbonimidoyl
potential. column
High purity
The electricity of the catholyte products
were
4781
isolated
dropping
the catholyte
solution
mixture with ether, which was washed solid products
and those obtained
onto cold brine (200 mL) and filtrating with cold water and dried (Na2S04).
after removing
IR, MS and high field 1H NMR and f3C Entry numbers 3 and 4 correspond
Table 1. Preparation
ether under reduced
NMR spectra9.
The directly
pressure
the
collected
gave satisfactory
The results are summarized
in Table 1.
to new isocyanidesf0.
of isocianydes
carbonimidoyl
dichlorides
(2) by cathodic
reduction
of
(1).
Cathode R
Entry
or extracting
Potential Yield (%)a
(V y6 SCE)
1
Phenyl
- 1.90
91
2
4-Chlorophenyl
- 1.40
94
3
2-Chloro-4-Methylphenyl
- 1.45
82
4
2,4-Dichlorophenyl
- 1.25
95
5
Benzyl
- 1.75
96
6
Cyclohexyl
- 1.85
90
ayields in isolated products.
Acknowledgements: de Investigation REFERENCES 1.
We gratefully
Cientifica AND
the financial
H.; Murakami,
General
Chemistry; Ugi, I., Ed.:
1971.
Baldwin, J.E.; O’Neil, I.A. Synletf
M. Synthesis
K. Angew. Chem. Int. Ed. Engl. 1965,
D.; Hoffmann, P.; Ugi, I. lsonifrile
Press, New York, London,
See for example:
of the Direction
NOTES.
Ugi, I.; Fetzer, U.; Eholzer, U.; Knupfer, H.; Offermann,
Academic
support
y Tecnica (project number PB89-0442).
4, 472.; Gokel, G.; Marquarding,
2.
acknowledge
1990, 603.; Ito, Y; Ohnishi, A.; Ohsaki,
1988, 714.; Obrecht, R.; Herrmann,
FL; Ugi, I. Synthesis
1985, 400.; Baldwin, J.E.; Bottaro, J.C.; Riordan, P.D.; Derome, A.E. J. Chem. Sot., Chem. Commun.
1982, 942.; Beijer, B.; Hinrischs, E.; Ugi, I. Angew. Chem. Int. Ed. Engl. 1972,
4782
11, 929.; Baldwin, J.E.; Yamaguchi,
Y. Tetrahedron Lett. 1989, 30, 3335.; Hbfle, G.; Lange,
B.Angew. Chem. Int. Ed. Engl. 1976, 15, 113. 3.
See review: Edenborough,
4.
For general reviews, see: Kiihle, E.; Anders, B.; Zumach, G. Angew. Chem. Int. Ed. Engl.
M.S.; Herbert, R.B. Natural Product Reports, 1988, 229.
1967, 6, 649.; Kijhle, E. Angew. Chem. Int. Ed. Engl. 1962, 1, 647. 5.
The formation
of isocyanides
of phenyl and cyclohexyl in the presence
along with coupling
carbonimidoyl
of palladium catalyst
dichlorides
products was observed with Grignard
when the reaction
reagents
Ito, Y.; Inouye, M.; Murakami,
were carried out
M. Tetrahedron Lett.
1988, 29, 5379. 6.
See for example:
Peters, D.G. in Organic Electrochemistry; Lund, H.; Baizer, M.M. Eds.;
Marcel Dekker, Inc.: New York, 1991; Chap. 8. 7.
Some of these reactions
8.
DMF was taken from a freshly opened bottle and dried with molecular anhydrous.
9.
Both were purchased
Products of reduction with authentic
10.
are now in progress in our laboratory.
samples
from Fluka, and were used directly without
of phenyl and benzylcarbonimidoyl of phenyl and benzyl isocyanides
dichlorides
26), 116 (loo),
was
purification.
were compared
respectively.
Spectral data for 3: IR (nujol) 2126 cm- 1; MS 70 eV m/z (rel. intensity) 15l(M+,
sieve. LiCL04
153 (M+ + 2, 8)
89 (31), 63 (17) 50 (11); 1H NMR (CDC13) 6:.2.36 (s, 3H), 7.08 (d,
lH, 3J = 8.1 Hz) 7.27 (s, 1 H), 7.29 (d, 2H, 3J = 8.3 Hz), 13C NMR (CDC13) 6: 21.04, 122.77, 127. 44, 128.12, 130.19, 130.33, 141.07, 168.28.; spectral data for 4: IR (nujol) 2128 cm-l ; MS 70 eV m/z (rel. intensity)
173 (M+ + 2, 66), 171 (M+, loo),
136 (35), 100 (23); 1 H NMR
(CDC13) 6: 7.30 (dd, IH, 3J = 8,5 Hz, 4J = 1.8 Hz), 7.39 (d, lH, 3J = 8.5 Hz), 7.51 (d, 1t-L 4J = 1.8 Hz); 13C NMR (CDC13) 6: 124.02, 127.87, 128.49, 129.99, 131.66, 135.71, 170.67.
(Received in UK 27 May 1992)
Tetrahedron Letters. Vol. 33. No. 33, pp. 4779-4182.1992 Printed in Great Brikin
ELECTROCHEMICAL
REDUCTION
METHOD
Antonio
FOR
THE
Guirado*,
OF
CARBONIMIDOYL
PREPARATION
Andrtk
Zapata,
OF
and
DICHLORIDES.
A NEW
ISOCYANIDES
Manuel
Fenor
Deparlamento de Quimica OrgAnica, Facultad de Quimica, Universidad de Murcia, Campus de Espinardo, E-30071, Murcia, Apartado 4021, Spain
Abstract:The reagent
cathodic
reduction
of carbonimidoyl
method for the preparation
The synthesis variety
of reactions
general
application
of isocyanides
of isocyanides leading
reviewed
were
reported
are fewer in number:
some those
reaction
cyanide salts, reaction of primary amines with dichlorocarbene monosubstituted chloride
formamides
or phosphorus
by treatment
oxychloride.
but it has the inconvenience devoted phosgene
to improving are foundz.
of isocyanides, polymers,
Advances
especially
The phosgene
as well as a recent
attention
time
agot.
arylsulfonyl
of isocyanides,
(1)
metal
of water from N-
chlorides,
cyanuric
to the isolation
t
metal
and synthesis
c’ 4779
+
2C1-
complexes,
of naturally
efforts
reagents
of the proved synthetic
compounds,
R-NC
numerous
using alternatives
because
of heterocyclic
2e
with heavy
literature
Cl \
a wide
to have the most
and the elimination
isocyanides3.
R-N=C’
Although
method gives by far the best results generally,
in this field are substantial
in the synthesis
yields.
that appear
In the subsequent
of synthesis
a new, mild and free-
of alkyl halides
with either phosgene,
of its high toxicity.
the methods
provides
in almost quantitative
was excellently
to isocyanides
in synthesis
dichlorides
to
utility and
occurring
4780
We herein report a new, efficient and simple method for the synthesis cathodic
reduction
of carbonimidoyl
dichlorides
isocyanates
and
isocyanides
(2) in almost quantitative
processes
N-monosubstituted
of other
gem-polyhalogenated
view6, the electrochemical In contrast the preparation
reductions
of isocyanides Therefore,
complex
reaction
difficult
because
mixture. the
However,
electrochemical
reaction
dimethylformamide
pronounced
reagents.
processes
to
present
can be avoided
This solution
mildness of the procedure by electrolysis
This would
concentrations7.
potential
glass frit (medium) platinum
diaphragm.
cooling.
cylindrical
A mercury
The reductions
50 mL and 20 mL of this solution respectively.
To prevent
anhydrous
sodium
dichlorides
(1) (5 mmol)
consumption
peak
up
after
the
generated
perchlorate
in a
and lithium
purposes.
The very
of non-electroactive
and work with them at very low
in a pure state, these are easily obtained
were
carried
pool (diameter
out
was magnetically
separated
by
a constant by a circular
stirred. The temperature
were carried out8 in DMF-LiCl04, in the cathodic
of electrogenerated
analyses
in the anode Solutions
cathodic
with capillary
isocyanides.
and a
was kept
at
0.2 M. Approximately
and the anodic
acid
under the appropriate
of the corresponding
under
5 cm) was used as the cathode
(39) was placed in this compartment.
were electrolyzed
a single
lithium
cell with two compartments
was 2 F . mot-1 for all cases. GUMS
showed
is “extremely
working
in the presence
isocyanides
Electrolyses
were placed
accumulation
carbonate
levels,
with ether.
plate as the anode. The catholyte
15 “C by external
solutions
are required
is frequently
feature of the method in order to enable
dichlorides
of labile
Procedure.
in a concentric
at low
are quantitatively
inorganic
out under
of the products from a
of purification
subsequent
Thus,
can be suppressed:
be used for most synthetic
is also a promising
isocyanides
Experimental
any
contains
could
even
isocyanides
of carbonimidoyl
addition of water and simple extraction
cathodic
since
permit the capture
If isolated
Typical
method
which additionally
exclusively.
and purification
vapours,
advantages.
which is carried
synthesis
of the usual techniques
isocyanide
by the
reaction
points of
unknown.
noteworthy
in isocyanide
and (ii) isolation
The application
solution
“in situ” synthesis
by a reagent-free
dehalogenation
from different
remained
shows valuable
two serious obstacles
exposure
distressing”1.
dichlorides
the corresponding
reductive
had been studied
of carbonimidoyl
is performed
(i) loss of yield due to secondary
salts,
compounds
via the
from isothiocyanates,
provide
While the electrochemical
with other methods this procedure
very mild conditions.
chloride
(1) which are easily available
formamides 4*5. These reactions yields.
of isocyanides,
Compartments,
compartment,
Of the carbonimidoyl
potential. column
High purity
The electricity of the catholyte products
were
4781
isolated
dropping
the catholyte
solution
mixture with ether, which was washed solid products
and those obtained
onto cold brine (200 mL) and filtrating with cold water and dried (Na2S04).
after removing
IR, MS and high field 1H NMR and f3C Entry numbers 3 and 4 correspond
Table 1. Preparation
ether under reduced
NMR spectra9.
The directly
pressure
the
collected
gave satisfactory
The results are summarized
in Table 1.
to new isocyanidesf0.
of isocianydes
carbonimidoyl
dichlorides
(2) by cathodic
reduction
of
(1).
Cathode R
Entry
or extracting
Potential Yield (%)a
(V y6 SCE)
1
Phenyl
- 1.90
91
2
4-Chlorophenyl
- 1.40
94
3
2-Chloro-4-Methylphenyl
- 1.45
82
4
2,4-Dichlorophenyl
- 1.25
95
5
Benzyl
- 1.75
96
6
Cyclohexyl
- 1.85
90
ayields in isolated products.
Acknowledgements: de Investigation REFERENCES 1.
We gratefully
Cientifica AND
the financial
H.; Murakami,
General
Chemistry; Ugi, I., Ed.:
1971.
Baldwin, J.E.; O’Neil, I.A. Synletf
M. Synthesis
K. Angew. Chem. Int. Ed. Engl. 1965,
D.; Hoffmann, P.; Ugi, I. lsonifrile
Press, New York, London,
See for example:
of the Direction
NOTES.
Ugi, I.; Fetzer, U.; Eholzer, U.; Knupfer, H.; Offermann,
Academic
support
y Tecnica (project number PB89-0442).
4, 472.; Gokel, G.; Marquarding,
2.
acknowledge
1990, 603.; Ito, Y; Ohnishi, A.; Ohsaki,
1988, 714.; Obrecht, R.; Herrmann,
FL; Ugi, I. Synthesis
1985, 400.; Baldwin, J.E.; Bottaro, J.C.; Riordan, P.D.; Derome, A.E. J. Chem. Sot., Chem. Commun.
1982, 942.; Beijer, B.; Hinrischs, E.; Ugi, I. Angew. Chem. Int. Ed. Engl. 1972,
4782
11, 929.; Baldwin, J.E.; Yamaguchi,
Y. Tetrahedron Lett. 1989, 30, 3335.; Hbfle, G.; Lange,
B.Angew. Chem. Int. Ed. Engl. 1976, 15, 113. 3.
See review: Edenborough,
4.
For general reviews, see: Kiihle, E.; Anders, B.; Zumach, G. Angew. Chem. Int. Ed. Engl.
M.S.; Herbert, R.B. Natural Product Reports, 1988, 229.
1967, 6, 649.; Kijhle, E. Angew. Chem. Int. Ed. Engl. 1962, 1, 647. 5.
The formation
of isocyanides
of phenyl and cyclohexyl in the presence
along with coupling
carbonimidoyl
of palladium catalyst
dichlorides
products was observed with Grignard
when the reaction
reagents
Ito, Y.; Inouye, M.; Murakami,
were carried out
M. Tetrahedron Lett.
1988, 29, 5379. 6.
See for example:
Peters, D.G. in Organic Electrochemistry; Lund, H.; Baizer, M.M. Eds.;
Marcel Dekker, Inc.: New York, 1991; Chap. 8. 7.
Some of these reactions
8.
DMF was taken from a freshly opened bottle and dried with molecular anhydrous.
9.
Both were purchased
Products of reduction with authentic
10.
are now in progress in our laboratory.
samples
from Fluka, and were used directly without
of phenyl and benzylcarbonimidoyl of phenyl and benzyl isocyanides
dichlorides
26), 116 (loo),
was
purification.
were compared
respectively.
Spectral data for 3: IR (nujol) 2126 cm- 1; MS 70 eV m/z (rel. intensity) 15l(M+,
sieve. LiCL04
153 (M+ + 2, 8)
89 (31), 63 (17) 50 (11); 1H NMR (CDC13) 6:.2.36 (s, 3H), 7.08 (d,
lH, 3J = 8.1 Hz) 7.27 (s, 1 H), 7.29 (d, 2H, 3J = 8.3 Hz), 13C NMR (CDC13) 6: 21.04, 122.77, 127. 44, 128.12, 130.19, 130.33, 141.07, 168.28.; spectral data for 4: IR (nujol) 2128 cm-l ; MS 70 eV m/z (rel. intensity)
173 (M+ + 2, 66), 171 (M+, loo),
136 (35), 100 (23); 1 H NMR
(CDC13) 6: 7.30 (dd, IH, 3J = 8,5 Hz, 4J = 1.8 Hz), 7.39 (d, lH, 3J = 8.5 Hz), 7.51 (d, 1t-L 4J = 1.8 Hz); 13C NMR (CDC13) 6: 124.02, 127.87, 128.49, 129.99, 131.66, 135.71, 170.67.
(Received in UK 27 May 1992)