N-Hydroxy-o-benzenedisulfonimide: A misunderstood selective oxidizing agent

Article abstract of DOI:10.1021/jo961285u

N-Hydroxy-o-benzenedisulfonimide (now an easily accessible reagent) is a useful selective oxidizing agent; this is contrary to what was previously believed. The oxidation reactions of aldehydes to acids, benzyl alcohols to aldehydes, thiols to disulfides, and sulfides to sulfoxides were investigated (18 examples).

Full text of DOI:10.1021/jo961285u

8
762
J . Org. Chem. 1996, 61, 8762-8764
N-Hyd r oxy-o-ben zen ed isu lfon im id e: A Misu n d er stood Selective
Oxid izin g Agen t
Margherita Barbero, Iacopo Degani,* Rita Fochi,* and Paolo Perracino
Dipartimento di Chimica Generale ed Organica Applicata dell’Universit a` ,
C.so M. D’Azeglio 48, I-10125 Torino, Italy
Received J uly 8, 1996X
N-Hydroxy-o-benzenedisulfonimide (now an easily accessible reagent) is a useful selective oxidizing
agent; this is contrary to what was previously believed. The oxidation reactions of aldehydes to
acids, benzyl alcohols to aldehydes, thiols to disulfides, and sulfides to sulfoxides were investigated
(18 examples).
N-Hydroxy-o-benzenedisulfonimide (NHOBS, 1) was
Sch em e 1
first prepared in 1926 by Hurtley and Smiles by reduction
of o-benzenedisulfonyl chloride with sodium sulfite, fol-
1
lowed by nitrosation. More than 40 years later Hen-
drickson et al. reassessed 1, together with quite a few
other N-substituted derivatives of o-benzenedisulfonim-
2
ide, as synthetic tools. The possibility of NHOBS being
+
a potential source of OH, like a peracid, was particularly
investigated, but the results were negative, both as a
Baeyar-Villiger reagent and a valid oxidizing agent to
convert aldehydes to acids. It was probably these conclu-
sions that led to no further investigations into NHOBS
as an oxidizing agent. However, it was found2 that
N-chloro- and N-bromo-o-benzenedisulfonimide are very
+
+
active sources of ionic positive halogen, Cl or Br .
Furthermore other researchers have since demonstrated
that N-fluoro-o-benzenedisulfonimide acts as a selective
3
,4
electrophilic fluorinating agent.
On the basis of these results, and as we had available
a fairly efficient method (tiresome in the past) for the
preparation of the key intermediate, o-benzenedisulfonyl
5
chloride, for the synthesis of N-hydroxy-o-benzenedis-
ulfonimide and other N-substituted derivatives of o-
benzenedisulfonimide, we thought to further investigate
the explorative experiments of Hendrickson2 on the
oxidizing properties of NHOBS. We prepared this re-
agent by putting together known procedures, i.e. starting
from anthranilic acid and proceeding via 1,3-benzodithio-
6
,7
lium tetrafluoroborate, resulting in o-benzenedisulfonyl
chloride 5 that was then converted into NHOBS (1).8
We investigated the oxidation of aldehydes 2 to acids
3
6
, benzyl alcohols 4 to aldehydes 2, thiols 5 to disulfides
, and sulfides 7 to sulfoxides 8 (Scheme 1). Hendrick-
2
son’s attempts to convert aldehydes to acids were focused
on 4-anisaldehyde and on phenylacetaldehyde: these
were reacted with 1 (molar ratio ) 1:1) in THF, or in
acetonitrile, in the presence of catalytic amounts of
4
-toluenesulfonic acid or equimolar amounts of boron
trifluoride etherate for several hours at rt or at reflux.
In all cases the NHOBS (1) was largely consumed or
completely destroyed without substantial change in the
substrate to be oxidized. In fact in the case of pheny-
lacetaldehyde no oxidation took place and 50% of the
starting aldehyde was recovered whereas in the case of
4-anisaldehyde the result was 4-anisic acid, maximum
yield 13%, and the amount of aldehyde recovered was
X
Abstract published in Advance ACS Abstracts, November 1, 1996.
1) Hurtley, W. R. H.; Smiles, S. J . Chem. Soc. 1926, 1821.
3
4, 3434.
(3) Davis, F. A.; Han, W.; Murphy, C. K. J . Org. Chem. 1995, 60,
4
730.
6
0-81%. In our experiments we first investigated the
(4) Snieckus, V.; Beaulieu, F.; Mohri, K.; Han, W.; Murphy, C. K.;
Davis, F. A. Tetrahedron Lett. 1994, 35, 3465. de Silva, S. O.; Reed, J .
N.; Billedeau, R. J .; Wang, X.; Norris, D. J .; Snieckus, V. Tetrahedron.
oxidation of benzaldehyde (2a ). Under the best condi-
tions (entry 1), to a heated solution (60 °C) of 2a in acetic
acid we added, dropwise and in two portions, a solution
of 1 in acetonitrile (molar ratio 2a :1 ) 1:1.5). The
reaction lasted a total of 4 h. This led to a 75% yield of
benzoic acid (3a ), an aldehyde recovery of 19%, and also
o-benzenedisulfonimide (1: OH ) H) in an amount
1
992, 48, 4863. Davis, F. A.; Han, W. Tetrahedron Lett. 1992, 33, 1153.
Davis, F. A.; Han, W. Tetrahedron Lett. 1991, 32, 1631.
5) Barbero, M.; Degani, I.; Fochi, R.; Regondi, V. Gazz. Chim. Ital.
986, 116, 165.
(
1
(
(
(
6) Nakayama, J . Synthesis 1975, 38.
7) Degani, I.; Fochi, R. Synthesis 1976, 471.
8) Kice, J . L.; Liao, S. J . Org. Chem. 1981, 46, 2691.
S0022-3263(96)01285-6 CCC: $12.00 © 1996 American Chemical Society

N-Hydroxy-o-benzenedisulfonimide
J . Org. Chem., Vol. 61, No. 25, 1996 8763
almost corresponding to that of the NHOBS reagent.
With 4-tolualdehyde (2b), 4-chlorobenzaldehyde (2d ) and
NHOBS, one point in favor of the reagent is that it does
not involve metals as do most oxidizing agents.
4
-nitrobenzaldehyde (2e) almost identical results were
obtained (entries 2, 4, 5). On the contrary 4-anisaldehyde
2c; entry 3) gave the corresponding 4-anisic acid (3c),
Exp er im en ta l Section
(
maximum yield 22%, 69% of 2c being recovered unal-
tered, even with an excess of NHOBS (molar ratio 2c:1
Column chromatography and TLC were performed on Merck
silica gel 60 (70-230 mesh ASTM) and GF 254, respectively.
Petroleum ether refers to the fraction boiling in the range 40-
70 °C and is abbreviated as PE. Details for reactions 1-25
are listed in Table 1. Aldehydes 2, benzyl alcohols 4, thiols 5,
)
1:2.5) and extending the reaction time to 15 h. Thus
2
on comparing our results with those previously obtained
it can be concluded that the choice of the target reactions
was unfortunate and, as a consequence, the results were
misleading.
sulfides 7, glacial AcOH, and MeCN were of commercial origin
6,7
(
Aldrich). 1,3-Benzodithiolium tetrafluoroborate, o-benzene-
5
disulfonyl chloride, and N-hydroxy-o-benzenedisulfonimide
(NHOBS, 1) were prepared according to the literature meth-
8
To further evaluate the oxidizing properties of NHOBS
(
(
1) we investigated the oxidation of benzyl alcohols 4
entries 6-10) carrying out the reactions at 60 °C in
ods.
Oxid a tion of Ald eh yd es 2 to Acid s 3: Rep r esen ta tive
P r oced u r e. Ben zoic Acid (3a ). In entry 1 (Table 1) a
solution of benzaldehyde (2a ; 1.06 g, 10 mmol) in glacial AcOH
acetonitrile. The reactions of entries 6, 7, and 10 gave
only the aldehydes 2a , 2b, and 2e in fair yields, without
the corresponding carboxylic acids. The reaction of entry
(20 mL) was heated at 60 °C. A solution of NHOBS (1; 2.35
g, 10 mmol) in MeCN (20 mL) was added dropwise during 30
min, and the resulting mixture was stirred at the same
temperature for an additional 1.5 h. Then a second portion
of 1 (1.18 g, 5 mmol) in MeCN (10 mL) was added dropwise
during 10 min, and heating at 60 °C was continued for a
further 2 h, until TLC analysis (PE-acetone, 9.5:0.5) showed
that the reaction stalled. The major product was the acid 3a ;
a minor amount of the starting compound 2a was also present.
Further additions of imide 1 did not change the 3a :2a ratio.
9
gave 4-chlorobenzaldehyde (2d ) in excellent yield
together with a small amount of 4-chlorobenzoic acid (3d ).
Attempts to oxidize 4-methoxybenzyl alcohol (4c) failed
(entry 8) and the starting compound was completely
destroyed.
Following this we investigated the oxidation of ben-
zenethiol (5a ) and octanethiol (5b), carrying out the
reactions in acetic acid-acetonitrile or only acetic acid:
thiol 5a gave diphenyl disulfide (6a ) in good yield (entries
After cooling, the reaction mixture was treated with H
O-
2
diethyl ether (1:1; 200 mL). The organic phase (A) was
1
1, 12); thiol 5b in acetic acid-acetonitrile gave rise to
separated and washed with H O (100 mL), and the aqueous
solutions were collected (B). Then the organic phase (A) was
dried over Na SO and concentrated under reduced pressure
2 4
to complete the elimination of AcOH. The residue was
dissolved again in diethyl ether (100 mL), which was washed
2
dioctyl disulfide (6b) in moderate yield, while with only
acetonitrile the disulfide yield was slightly better (entries
1
3, 14). In all cases the starting thiols were completely
consumed.
with 5% aqueous NaOH (2 × 50 mL) and successively H
2
O
Finally a study was made of the oxidation action of
NHOBS (1) on several representative sulfides 7a -f. The
reactions were carried out at 60 °C in acetic acid-
acetonitrile or only acetonitrile, working with an excess
of oxidant (7:1 ) 1:1.1-1.6). In all the considered cases,
the only exception being di-tert-butyl sulfide (7f), there
was the disappearance of the starting compound and the
formation of the corresponding sulfoxide 8 without sul-
fone. The yields in sulfoxide 8 were good for diphenyl
sulfide (7a ; entries 15, 16), thioanisole (7b; entries 17,
(
50 mL), dried, and evaporated as above to afford the starting
compound 2a in 19% yield (0.20 g). The collected aqueous
solutions were acidified with concd HCl and extracted with
diethyl ether (3 × 50 mL). The extracts were dried and
evaporated to afford the virtually pure (TLC, NMR) title
compound 3a in 75% yield (0.92 g). The aqueous solution (B)
was evaporated under reduced pressure to eliminate AcOH.
The residue was crude o-benzenedisulfonimide hydrate (1: OH
)
H) that was washed with pentane (20 mL) and then
dissolved in H
2
O (5 mL). The acid solution so obtained was
neutralized by addition of 10% aqueous NaOH and then passed
1
8), and dibutyl sulfide (7d ; entries 20, 21), modest for
through a 50 g column of Dowex 50 × 8 ion-exchange resin
(
2
Fluka), eluting with H O (50 mL). After evaporation of water,
di-sec-butyl sulfide (7e; entries 22, 23) and nil for di-tert-
butyl sulfide (7f; entries 24, 25). The oxidation of
p-(methylthio)benzaldehyde (7c) gave excellent yields of
the corresponding sulfoxide 8c with regioselective attack
at the sulfur atom, leaving the formyl group unchanged
virtually pure (NMR) o-benzenedisulfonimide hydrate was
3
obtained in 92% yield (3.02 g): mp 192-194 °C (toluene) (lit.
1
13
1
92-194 °C); H and C NMR spectra were identical to those
3
reported.
Entries 2-5 were also performed in the same way. Yields
(entry 19).
are reported in Table 1. The starting compounds 2b-e were
recovered in 23, 69, 16, and 21% yields, respectively, in entries
2, 3, 4, and 5.
The conclusion of this research is that not only does
N-hydroxy-o-benzenedisulfonimide (now an easily acces-
sible reagent) have outstanding oxidizing properties,
Oxid a tion of Ben zyl Alcoh ols 3 to Ald eh yd es 2: Rep -
r esen ta tive P r oced u r e. 4-Ch lor oben za ld eh yd e (2d ). In
entry 9 a solution of NHOBS (1; 2.82 g, 12 mmol) in MeCN
previously denied,2 but it also has high selectivity, a
particularly important feature for sulfide oxidation.9
Furthemore although the knowledge acquired till now
allows only a rough evaluation for or against the use of
(40 mL) was added dropwise during 60 min to a stirred
solution of 4-chlorobenzyl alcohol (3d ; 1.43 g) in the same
solvent (20 mL), previously heated at 60 °C. Stirring and
heating was maintained for a further 1.5 h, until NMR
analysis showed the disappearance of the starting compound
(9) Bosch, E.; Kochi, J . K. J . Org. Chem. 1995, 60, 3172. Uemura,
S. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon
Press: New York, 1991; Vol 7, pp 762-765. For review, see: Block, E.
In The Chemistry of Ethers, Crown Ethers, Hydroxyl Groups and Their
Sulphur Analogues; Patai, S., Ed.; Wiley & Sons, New York, 1980;
Supplement E, Part 1, Chapter 13.
3
d . The obtained solution was concentrated under reduced
pressure, and the residue was treated with H
O-diethyl ether
1:2; 150 mL). The organic phase (A) was separated and
2
(
2
washed with H O (50 mL), and the aqueous solutions were
(
(
10) Yiannios, C. N.; Karabinos, J . V. J . Org. Chem. 1963, 28, 3246.
11) Westlake, H. E.; Dougherty, G. J . Am. Chem. Soc. 1942, 64,
collected (B). Then the organic phase (A) was washed with
O (50 mL),
dried, and evaporated under reduced pressure: the virtually
pure (TLC, GC, NMR) title compound 2d was obtained in 91%
yield (1.28 g). The collected aqueous solutions were acidified
with concd HCl and extracted with diethyl ether (2 × 50 mL).
5
% aqueous NaOH (2 × 50 mL) and successively H
2
1
49.
(12) Drabowicz, J .; Mikolajczyk, M. Synth. Commun. 1981, 11, 1025.
13) Fringuelli, F.; Pellegrino, R.; Piermatti, O.; Pizzo, F. Synth.
(
Commun. 1994, 24, 2665.
14) Liu, K.-T.; Tong, Y.-C. J . Org. Chem. 1978, 43, 2717.
(

8
764 J . Org. Chem., Vol. 61, No. 25, 1996
Barbero et al.
Ta ble 1. Oxid a tion of Ald eh yd es 2 to Acid s 3, Alcoh ols 4 to Ald eh yd es 2, Th iols 5 to Disu lfid es 6, a n d Su lfid es 7 to
Su lfoxid es 8
starting
compd
entry 2, 4, 5, 7
molar ratio
2,4,5,7:1
reaction
solvent
timea product yieldb
chromatographic
solvent
mp (°C) (solvent) or
bp (°C)/mmHg
lit. mp (°C) or
bp (°C)/mmHg
(h)
3, 2, 6, 8
(%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
2a
2b
2c
2d
2e
4a
4b
4c
4d
4e
5a
1:1.5
1:1.5
1:2.5
1:2.0
1:2.0
1:1.5
1:1.25
1:1.2
1:1.2
1:2.0
1:0.5
1:0.5
1:0.9
1:0.75
1:1.5
1:1.5
1:1.2
1:1.2
1:1.1
1:1.6
1:1.6
1:1.5
1:1.5
1:1.5
1:1.5
AcOH-MeCN
AcOH-MeCN
4.0
4.5
3a
3b
3c
3d
3e
2a
2b
2c
2d
2e
6a
75
122-123 (H2O)
c
c
c
c
c
e
e
c
c
c
75
22
68
64
52
180-181 (EtOH-H2O)
183-184 (EtOH-H2O)
242-243 (EtOH-H2O)
240-241 (EtOH-H2O)
236-237 (PhNO2)
233-234 (PhNO2)
g
AcOH-MeCN 15.0
AcOH-MeCN
AcOH-MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
AcOH-MeCN
AcOH
AcOH-MeCN
MeCN
AcOH-MeCN
MeCN
AcOH-MeCN
MeCN
AcOH-MeCN
AcOH-MeCN
MeCN
5.5
8.0
5.0
5.0
6.0
2.5
7.0
1.0
1.5
8.0
7.5
3.0
4.0
0.5
1.0
4.5
6.0
9.0
6.0
7.0
7.0
7.0
d
57f
6
PE-MeCOMe (9:1)
91
45
89
87
40
59
80
84
87
76
87
70
70
48
31
h
47-48 (PE)
106-107 (C6H6-PE)
60-61 (PE)
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
PE-Et2O (9:1)
PE
1
0
61
5b
7a
7b
6b
8a
8b
PE
170-171/0.5
178-183/511
69-7112
PE-Et2O (3:2)
CHCl3
71-72 (C6H6-PE)
110-111/1
115/212
1
3
7c
7d
8c
8d
90-91 (CHCl3-PE)
109/1
92-93
12
CHCl3
CHCl3
32
72-74/114
7e
7f
AcOH-MeCN
MeCN
AcOH-MeCN
MeCN
8e
8f
80-81/0.5
h
a
Reaction time at 60 °C includes the dropping time of NHOBS. b Yields of pure isolated products. c Identical to that of an authentic
d
e
sample of commercial origin (Aldrich) and analytical purity. Yield of benzaldehyde 2,4-dinitrophenylhydrazone. Identical to that of an
f
g
+
authentic sample. Yield of 4-tolualdehyde 2,4-dinitrophenylhydrazone. MS: m/ z 136 (M ); structure was confirmed by comparison of
1
H NMR spectrum with that of an authentic sample. h The reaction failed.
the procedure described in entry 1 for the oxidation of
After evaporation, virtually pure (TLC, NMR) 4-chlorobenzoic
benzaldehyde, in entry 15 NHOBS (1) was added in two
acid (3d ) was obtained in 8.2% yield (0.13 g). According to
portions to the solution of diphenyl sulfide (7a ; 1.86 g, 10
mmol) in AcOH (20 mL), previously heated at 60 °C. The first
portion (2.82 g, 12 mmol, in 25 mL of MeCN) was added during
the procedure described above in entry 1, virtually pure (NMR)
o-benzenedisulfonimide hydrate was obtained in 91% yield
(2.39 g) from aqueous solution (B).
2
5-30 min and the second portion (0.7 g, 3 mmol) was added
Entries 6-8 and 10 were performed in the same way: in
in 10 min, after 2 h. Heating at 60 °C was continued for 30
min, until disappearance of the starting sulfide 7a (GC; TLC:
PE-diethyl ether, 3:2). The reaction mixture was worked up
as described above for diphenyl disulfide. The crude residue
was purified by chromatography on a short column, using PE-
diethyl ether (3:2), as eluent to afford the title compound 8a
in 80% yield (1.62 g). Virtually pure (NMR) o-benzenedisul-
fonimide hydrate was isolated in 100% yield (3.28 g).
all cases the only reaction products were the aldehydes 2. In
entries 6 and 7, pentane was used as solvent for the extraction
and was then evaporated at atmospheric pressure. From the
crude reaction residues, aldehydes 2a and 2b were isolated
as 2,4-dinitrophenylhydrazones.
Oxid a tion of Th iols 5 to Disu lfid es 6: Rep r esen ta tive
P r oced u r e. Dip h en yl Disu lfid e (6a ). In entry 11 a solution
of NHOBS (1; 1.18 g, 5 mmol) in MeCN (10 mL) was added
dropwise during 10 min to a stirred solution of benzenethiol
Entries 16-18, 20-25 were also performed in the same way.
In entries 17 and 18 the first portion of NHOBS was enough
to complete the reaction. Entries 16, 18, 21, 23, and 25 were
carried out in MeCN. Entries 24 and 25 failed.
(5a ; 1.10 g, 10 mmol) in AcOH (10 mL), previously heated at
6
0 °C. Stirring and heating was maintained for a further 50
min, until TLC (PE) and GC analyses showed the disappear-
ance of the starting compound 5a . After being cooled, the
4
-(Meth ylsu lfin yl)ben za ld eh yd e (8c). In entry 19 a
solution of NHOBS (1; 2.59 g, 11 mmol) in MeCN (40 mL) was
added dropwise during 2.5 h to a stirred solution of 4-(meth-
ylthio)benzaldehyde (7c; 1.52 g, 10 mmol) in glacial AcOH (14
mL), previously heated at 60 °C. After an additional 2 h the
reaction mixture was treated with H
mL). The organic phase (A) was separated and washed with
O (2 × 50 mL), and the aqueous solutions were collected
B). Then the organic phase (A) was washed with 5% aqueous
2
O-diethyl ether (1:2; 150
H
(
2
reaction was complete (TLC: CHCl
reaction mixture was treated with saturated aqueous NaCl
50 mL) and extracted with CH Cl
3
). After cooling, the
NaOH (4 × 50 mL) and successively H O (2 × 50 mL). The
2
crude residue obtained after the usual workup was chromato-
graphed on a short column with PE as eluent, to afford the
title compound 6a in 89% yield (0.97 g). As above, virtually
pure (NMR) o-benzenedisulfonimide hydrate was obtained in
(
2
2
(3 × 100 mL). The
collected organic extracts were worked up as described for the
oxidation of benzaldehyde. Pure title compound 8c was
obtained in 87% yield (1.47 g); no traces of 4-(methylthio)-
benzoic acid were isolated.
8
4% yield (0.92 g) from aqueous solution (B).
Entry 12 was performed in the same way carrying out the
reaction at 40 °C in AcOH as only solvent; in entry 14 AcOH
was replaced with the same amount of MeCN. In entries 13
and 14 the above procedure was slightly modified as follows:
NHOBS (1) was added in three portions, i.e. 5 mmol (1.18 g)
at the beginning, 1.5 mmol (0.35 g) after 2 h, and 2.5 (0.59 g)
or 1 mmol (0.23 g), respectively, in entry 13 or in entry 14,
after another 2 h.
Ack n ow led gm en t. This work was supported by the
National Research Council of Italy (CNR), Progetto
Strategico “Tecnologie Chimiche Innovative” and Pro-
getto Integrato CNR (I.Co.C.E.A., Bologna)/Universita`
(
Torino), and by Ministero dell’Universit a` e della Ricerca
Scientifica e Tecnologica (MURST).
Oxid a tion of Su lfid es 7 to Su lfoxid es 8: Rep r esen ta -
tive P r oced u r es. Dip h en yl Su lfoxid e (8a ). According to
J O961285U