Electrochemical oxidation of N-p-toluenesulfinamides

Article abstract of DOI:10.1021/ol0258381

Matrix presented Contrasting and interesting electrochemical behavior is observed in anodic oxidation of N-substituted p-toluenesulfinamides under controlled current conditions. For sulfinamides derived from secondary alkylamines and primary arylamines, the N-sulfinyl group is removed and the corresponding amines are formed; for sulfinamides derived from primary alkylamines, sulfur oxidation yields the corresponding sulfonamides in good yields.

Full text of DOI:10.1021/ol0258381

ORGANIC
LETTERS
2002
Vol. 4, No. 10
1763-1766
Electrochemical Oxidation of
N-p-Toluenesulfinamides
Marcelo G. Montes D’Oca,* Dennis Russowsky, Karen Canto,
Tanara Gressler, and Reinaldo S. Gonc¸alves
Instituto de Qu´ımica, UniVersidade Federal do Rio Grande do Sul,
Porto Alegre, RS 91501-970, Brazil
doca@iq.ufrgs.br
Received March 7, 2002
ABSTRACT
Contrasting and interesting electrochemical behavior is observed in anodic oxidation of N-substituted p-toluenesulfinamides under controlled
current conditions. For sulfinamides derived from secondary alkylamines and primary arylamines, the N-sulfinyl group is removed and the
corresponding amines are formed; for sulfinamides derived from primary alkylamines, sulfur oxidation yields the corresponding sulfonamides
in good yields.
In organic synthesis, electrochemical processes may offer
advantages over conventional methods, such as milder
reaction conditions, higher selectivity, and easier isolation
of products.1 An illustrative example is provided by the
electrochemical oxidation of amides and carbamates, a highly
efficient and general electrochemical reaction.2 Sulfoxides
and derivatives are routinely employed in organic synthesis3
and are particularly useful in asymmetric transformations.
However, the electrochemical behavior of sulfur compounds
has been studied to a limited extent.4
Electrochemical oxidation of organic sulfides in mixed
media of water, methanol, acetic acid, and aprotic solvents
has been reported to yield the corresponding sulfoxides,
sulfones, and sulfonic acids.5 Anodic oxidation of 2-phenyl-
1,2-benzisothiazol-3(2H)-ones in acetonitrile also yields the
corresponding sulfoxide.6 Shono7 and Ross8 reported that
anodic oxidation of N-sulfonamides in alcohols and acetic
acid afforded R-alkoxy and R-acetoxy N-sulfonamides,
respectively.
N-Sulfinamides are important synthons in organic syn-
thesis,9,10 but so far their electrochemical oxidation behavior
is unknown. Herein we report the first study of the anodic
oxidation of sulfinamides and discuss the contrasting and
interesting behavior observed for N-sulfinamides derived
from primary and secondary alkylamines and aniline.
(1) (a) Shono, T. Topics in Current Chemistry, Eletrochemistry III;
Steckhan, E., Ed.; Springer-Verlag: Berlin, Heidelberg, 1988; Vol. 148, p
131. (b) Baizer, M. M. In Organic Electrochemistry; Lund, H., Baizer, M.
M., Eds.; Marcel Dekker Inc.: New York, 1991. (c) Kyriakou, D. Modern
Electroorganic Chemistry; Springer-Verlag: Berlin, Heidelberg, 1994. (d)
Utley, J. Chem. Soc. ReV. 1997, 26, 157.
(2) (a) Shono, T.; Hamaguchi, H.; Matsumura, Y. J. Am. Chem. Soc.
1975, 97, 4264. (b) Yoshida, J.; Suga, S.; Suzuki, S.; Kinomura, N.;
Yamamoto, A.; Fujiwara, K. J. Am. Chem. Soc. 1999, 121, 9546. (c) D’Oca,
M. G. M.; Pilli, R. A.; Vencato, I. Tetrahedron Lett. 2000, 41, 9709. (d)
D’Oca, M. G. M.; Pilli, R. A.; Pardini, V. L.; Curi, D.; Comninos, F. C.
M. J. Braz. Chem. Soc. 2001, 12, 507. (e) Suga, S.; Okajima, M.; Yoshida,
J. Tetrahedron Lett. 2001, 42, 2173. (f) Suga, S.; Suzuki, S.; Yoshida, J. J.
Am. Chem. Soc. 2002, 124, 30.
(4) Simonet, J. In The Chemistry of Sulfones and Sulfoxides; Patai, S.,
Rappoport, Z., Stirling, C. J. M., Eds.; John Wiley & Sons Ltd. :New York,
1988; Chapter 23, pp 1001-1045.
(5) Uneyama, K.; Torii, S. J. Org. Chem. 1972, 37, 367 and references
therein
(6) Mu¨ller, R.; Dakova, B.; Lamberts, L.; Evers, M. Electrochim. Acta
1994, 39, 1961.
(7) Shono, T.; Matsumura, Y.; Tsubata, K.; Uchida, K.; Kanazawa, T.;
Tsuda, K. J. Org. Chem. 1948, 49, 3711.
(3) Solladie´, G. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 6, p 133.
(8) Ross, S. D.; Finkelstein, M.; Rudd, E. J. Org. Chem. 1972, 37, 2387.
10.1021/ol0258381 CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/17/2002

Table 1. Anodic Oxidation of N-Substituted p-Toluenesulfinamides 1a-h
entry
sulfinamides
R1
-(CH2)4-
-(CH2)5-
PhCH2
i-Pr
Ph
R2
current (mA)
amines 2a -e
methyl sulfinate 3
sulfonamides 4f-h
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1e
1f
20
20
20
20
20
100
20
60
20
60
20
60
70%
72%
78%
n.d.
56%
30%
75%
76%
80%
80%
78%
70%
Me
Me
H
Ph
H
PhCH2
PhCH2
i-Pr
H
H
H
85%
80%
81%
79%
90%
85%
1f
tr
tr
1g
1g
1h
1h
10
11
12
i-Pr
H
t-Bu
t-Bu
H
H
The racemic N-p-toluenesulfinamides 1a-h were prepared
from their corresponding sodium p-toluenesulfinate. Reaction
of the sodium p-toluenesulfinate with SOCl2 followed by
addition of anhydrous ethanol afforded the ethyl p-toluene-
sulfinates in 85% yield. The cyclic (1a,b) and acyclic
(1e-h) (()-N-p-toluenesulfinamides were prepared in good
yields by the reaction of (()-ethyl p-toluenesulfinate with
lithium amides, which were prepared by treating the respec-
tive amines with n-BuLi (-78° C, THF).10 The N-p-toluenesul-
finamides 1c and 1d were prepared in high yield by
methylation (n-BuLi, MeI, -78° C, THF) of the correspond-
ing sulfinamides 1f and 1g.
toluenesulfinate 3 were isolated in good yields at time when
6 F mol-1 of electricity was passed (Table 1, entries 1 and
2). Amines 2a,b and methyl p-toluenesulfinate 3 were formed
by cleavage of the N-S bonds (Scheme 1).
Scheme 1
The electrochemical oxidation of N-substituted p-toluene-
sulfinamides 1a-h was carried out in an undivided cylindri-
cal cell equipped with reticulated vitreous carbon (RVC)
anode and platinum plate cathode electrodes using tetraethy-
lammonium p-toluenesulfonate (Et4NOTs) as the supporting
electrolyte and methanol as the solvent.
We then investigated the electrochemical behavior of the
acyclic N-p-toluenesulfinamides 1c-h derived from second-
ary and primary alkylamines and aniline (Scheme 2).
In general, three major reaction products were formed and
characterized (Table 1): the amines 2, methyl p-toluene-
sulfinate 3 (from cleavage of the N-S bond), and N-p-
toluenesulfonamides 4 (from sulfur oxidation).
Scheme 2
We first investigated the anodic oxidation of the cyclic
N-(alkyl)-p-toluenesulfinamides 1a,b in different but constant
electric currents using either RVC or Pt electrodes.11
Table 1 shows that best yields were observed when using
a constant current of 20 mA and RVC-anode and Pt-cathode
electrodes and that the amines 2a,b and the methyl p-
(9) (a) Moree, W. J.; van der Marel, G. A.; Liskamp, R. M. J. Tetrahedron
Lett. 1992, 33, 6389. (b) Moree, W. J.; van der Marel, G. A.; Liskamp, R.
M. J. J. Org. Chem. 1995, 60, 5157. (c) Gremmen, C.; Willemse, B.;
Wanner, M. J.; Koomen, G.-H Org. Lett. 2000, 2, 1955. (d) Davis, F. A.;
Lee, S.; Yan, H.; Titus, D. D. Org. Lett. 2001, 11, 1757.
(10) Garc´ıa-Ruano, J. L.; Alonso, R.; Zarzuelo, M. M.; Noheda, P.
Tetrahedron: Asymmetry 1995, 6, 1133.
(11) D’Oca, M. G. M.; Gonc¸alves, R. S.; Canto, K.; Russowsky, D. In
XII Simpo´sio Brasileiro de Eletroqu´ımica e Eletroanal´ıtica; Gramado, RS,
Brazil, 2001; p 606
In great contrast with the behavior of the cyclic amines
1a,b, the anodic oxidation of the N-(alkyl)-p-toluenesulfi-
1764
Org. Lett., Vol. 4, No. 10, 2002

namides 1f-h derived from primary amines under the same
electrochemical conditions (20 mA, MeOH) promotes sulfur
oxidation, thus affording the corresponding N-(alkyl)-p-
toluenesulfonamides 4f-h in good yields at time when 4 F
mol-1 of electricity was passed (Table 1, entries 7-12).
Monitoring by GC shows that electrochemical oxidation of
sulfinamides 1f-h at 60 mA gives identical results (Table
1, entries 8, 10, and 12) plus small amounts of sulfinate 3,
whereas the N-(phenyl)-p-toluenesulfinamide 1e afforded 2e
and 3 owing to N-S bond cleavage (Table 1, entries 5 and
6).
Scheme 3
To further confirm the contrasting behavior of sulfinamides
derived from secondary and primary amines, the acyclic
N-(alkyl)-p-toluenesulfinamides 1c,d (prepared by methyla-
tion of 1f,g) were also studied. As observed for the cyclic
sulfimanides 1a,b, the anodic oxidation of 1c,d (Scheme 2)
afforded the respective amines 2c,d and 3 (Table 1, entries
3 and 4) owing to N-sulfinyl group cleavage.
The contrasting electrochemical behavior of sulfinamides
derived from primary and secondary amines and aniline was
therefore confirmed. A mechanistic interpretation can be
rationalized: the different final products observed experi-
mentally suggest that the electron transfer takes place mainly
from nitrogen in the case of sulfinamides derived from
secondary alkylamines and aniline, whereas the electron
transfer take mainly from sulfur in the case of sulfinamides
derived from primary alkylamines.
In the case of the N-sulfinyl group cleavage (Scheme 3,
R1 ) R2 ) alkyl or R1 ) aryl and R2 ) H), the sulfinamides
1a-e derived from secondary alkylamines and aniline upon
surrendering one electron to the anode are transformed into
a N-radical cation A stabilized by the alkyl groups or
aromatic group, respectively. Because the electron-deficient
N-radical cation is a good leaving group, the attack of
methanol at the sulfur cleaves the N-S bond to give
N-radical B and methyl sulfinate 3. The formal reduction of
radical B by the cathodic process in galvanostatic conditions
followed of protonation gives amine 2.
In the sulfur oxidation case, for sulfinamides 1f-h derived
from primary alkylamines (Scheme 3, R1 ) alkyl and R2 )
H) the formation of the less stabilized N-radical cation may
be less operative because of lack of stabilization of this by
alkyl and hydrogen groups. In this case the sulfonamides 4
may be formed by a two-electron oxidation process, and it
could be rationalized by electron transfer taking place mainly
from sulfur to give the S-radical cation C. Two pathways
can be rationalized to explain the formation of sulfonamides
4 (sulfur oxidation products): In pathway a, the attack by
methanol at the S-radical cation C and elimination of a proton
gives the formal S-radical D, which undergoes further one-
electron oxidation. The attack by methanol followed by the
elimination of a proton afforded the dimethoxylated com-
pound. The dimethoxylated compound may be hydrolyzed
by water in the reaction media to give the sulfonamide 4. In
pathway b, the electrochemical nitrogen deprotonation of the
S-radical cation C by a cathodic process in the galvanostatic
conditions12 afforded the S-radical sulfoximine E. Further
one-electron oxidation followed by attack of the water in
the reaction media at sulfur of the E radical species gives
the sulfonamides 4.
To gain further insights into the mechanistic aspects and
different electrochemical behavior of N-p-toluenesulfina-
mides, the intrinsic gas-phase reactivity13 of ionized sulfi-
namides 1a-h with methanol is being currently investigated
by sequential mass spectrometry.
In conclusion, the anodic oxidation of N-p-toluenesulfi-
namides could be considered a new complementary alterna-
(12) Recently, the electrochemical deprotonation of N-H acids was
reported for oxazolidin-2-ones in galvanostatic conditions using a constant
current (16 or 25 mA) and C and Pt electrodes. (a) Feroci, M.; Inesi, A.;
Palombi, L.; Rossi, L.; Sotgiu, G. J. Org. Chem. 2001, 66, 6185. (b) Feroci,
M.; Inesi, A.; Palombi, L.; Rossi, L.; Sotgiu, G. J. Org. Chem. 2002, 67,
1719.
(13) (a) Eberlin, M. N. Mass Spectrom. ReV. 1997, 16, 113. (b) D’Oca,
M. G. M.; Moraes, L. A. B.; Pilli, R. A.; Eberlin, M. N. J. Org. Chem.
2001, 66, 3854. (c) Tomazela, D. M.; Moraes, L. A. B.; Pilli, R. A.; Eberlin,
M. N.; D’Oca, M. G. M. J. Org. Chem. 2002, accepted for publication.
Org. Lett., Vol. 4, No. 10, 2002
1765

tive to the existing chemical strategies to remove a N-sulfinyl
protecting group9,14 or oxidation of sulfinamides.15 The
important features of the electrochemical methodology are
the following: the reaction is operationally simple, is carried
out at room temperature, and uses neutral conditions, and
its products can be readily isolated. The extension of this
methodology to other N-sulfinamides is currently under
investigation.
Acknowledgment. The authors acknowledge the Con-
selho Nacional de Desenvolvimento Cient´ıfico e Tecno-
lo´gico-CNPq and the Fundac¸a˜o de Amparo a` Pesquisa do
Estado do Rio Grande do Sul-FAPERGS for the financial
support.
(14) Largeron, M.; Farrell, B.; Rousseau, J.-F.; Fleury, M.-B.; Potier,
P.; Dodd, R. H. Tetrahedron Lett. 2000, 41, 9403.
(15) (a) Gao, Y.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 7538.
(b) Backes, B. J.; Dragoli, D. R.; Ellman, J. A. J. Org. Chem. 1999, 64,
5472. (c) Dragoli, D. R.; Burdett, M. T.; Ellman, J. A. J. Am. Chem. Soc.
2001, 123, 10127. (d) Borg, G.; Chino, M.; Ellman, J. A. Tetrahedron Lett.
2001, 42, 1433.
Supporting Information Available: Experimental pro-
cedure of anodic oxidation. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL0258381
1766
Org. Lett., Vol. 4, No. 10, 2002