Synthesis and reactivity of polydisulfonimides

Article abstract of DOI:10.1021/ja002465v

The first synthesis of alkyl disulfonimide oligomers is presented. In the process of synthesizing these oligomers, previously unreported reactivity of the N-substituted disulfonimide functional group was discovered. Under basic conditions, unexpected lengthening of the oligomers occurs through a "transdisulfonimidation" reaction, whereby new disulfonimides are synthesized from existing ones by reaction with sulfonamide anion. This process appears to proceed via formation of a sulfene intermediate. Support for the E1cB_Rev mechanism includes isotope scrambling, substituent effects, and sulfene trapping.

Full text of DOI:10.1021/ja002465v

VOLUME 123, NUMBER 13
APRIL 4, 2001
© Copyright 2001 by the
American Chemical Society
Synthesis and Reactivity of Polydisulfonimides
Benjamin T. Burlingham and Theodore S. Widlanski*,†
Contribution from the Department of Chemistry, Indiana UniVersity, Bloomington Indiana 47405
ReceiVed July 6, 2000
Abstract: The first synthesis of alkyl disulfonimide oligomers is presented. In the process of synthesizing
these oligomers, previously unreported reactivity of the N-substituted disulfonimide functional group was
discovered. Under basic conditions, unexpected lengthening of the oligomers occurs through a “transdisul-
fonimidation” reaction, whereby new disulfonimides are synthesized from existing ones by reaction with
sulfonamide anion. This process appears to proceed via formation of a sulfene intermediate. Support for the
E1cBRev mechanism includes isotope scrambling, substituent effects, and sulfene trapping.
Introduction
Polyanionic macromolecules are ubiquitous in biological
systems. Both homogeneous polyanions, such as the phosphate
backbone of nucleic acids, and heterogeneous polyanions,
represented by the heavily sulfated and carboxylated glycosami-
noglycans, participate in a variety of vital biochemical processes.
Many of these polyanions interact with specific proteins,
particularly enzymes. It is therefore surprising that there have
been relatively few attempts to develop new types of polyanionic
materials with useful biological properties. In this paper, we
report on the synthesis and reactivity of oligomeric disufonim-
ides, molecules that may be useful for mimicking biological
polyanions. Disulfonimides possess many features that may
make them a suitable functional group for mimicking various
charged groups found in biological anions. They contain an
acidic proton with a pKa of approximately 1, and therefore exist
in a largely anionic state at physiological pH1 (Figure 1).Dis-
ulfonimides contain five atoms over which the charge may
possibly be delocalized, which may give the functional group
an ability to mimic various charged groups, such as phosphates,
Figure 1. The disulfonimide functional group is fully deprotonated at
physiological pH.
sulfates, and carboxylates. The disulfonimide may also engage
in multidentate metal ligation, further expanding the ability of
this functional group to mimic biological polyanions. Despite
these potentially useful properties, little is known about the
chemistry of this underutilized functional group. We therefore
undertook a study of this functionalities’ synthesis and chemical
reactivity.
Crystal structures of both N-substituted and monoacidic
disulfonimides exist. Cotton and Stokely report a structure of
both the protonated and deprotonated forms of diphenyldisul-
fonimide.2 In these two structures, the only statistically relevant
bond length changes upon deprotonation are the S-N bonds.
The sodium salt has a sulfur-nitrogen bond length significantly
shorter than that of the protonated compound. Furthermore,
Cotton and Stokely’s structures show that the deprotonated
disulfonimide places the aryl groups syn to one another so that
the sodium cation may have the best possible interactions
† Email: twidlans@indiana.edu. Fax: 812-855-8300. Phone: 812-855-
6863.
(1) King, J. In The Chemistry of Sulphonic Acids, Esters and their
DeriVatiVes; Patai, S., Rappaport, Z., Eds.; John Wiley & Sons: Chichester,
UK, 1991, Chapter 6.
(2) Cotton, F.; Stockely, P. J. Am. Chem. Soc. 1970, 92, 294-302.
10.1021/ja002465v CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/13/2001

2938 J. Am. Chem. Soc., Vol. 123, No. 13, 2001
Burlingham and Widlanski
Results and Discussion
Synthetic Strategy. The strategy for the synthesis of the
tetramer (7) and hexamer (11) required the preparation of a
series of disulfonimide-containing molecules. A review of the
literature indicated that the most frequent and highest yielding
syntheses of disulfonimides utilize the reaction of a sulfonyl
chloride with a deprotonated sulfonamide,14 although other
means for this bond construction have been employed.15 We
therefore chose sulfonyl chlorides and sulfonamides as building
blocks for the polydisulfonimide. In considering the structure
of our target molecules, we opted for a strategy of multiple bond
disconnections (Scheme 1). The two major options involved
either forming many bonds simultaneously in an oligomerization
process or constructing bonds one at a time in a stepwise
manner. We reasoned that a stepwise synthesis would permit
better evaluation of the structure and purity of the compounds
produced, as well as allowing us the opportunity of studying
the chemistry of the disulfonimide functionality. Having chosen
a stepwise approach to construct the molecule, a convergent
synthesis rather than a linear one was then implemented.
Taking advantage of the molecule’s symmetry led to the
adoption of an “outside-in” approach. Scheme 1 outlines the
retrosynthesis of hexamer (11). By making disconnections at
two disulfonimide functionalities near the center of the molecule,
the hexameric molecule was quickly reduced to two much
simpler compounds. Disulfonamide 5 could be easily made from
hexane-1,6-disulfonyl chloride (3). The terminal sulfonyl chlo-
ride 9, which contained two internal disulfonimide functional
groups, could be broken down into hexane-1,6-disulfonyl
chloride (3) and a simpler sulfonamide (8). This terminal
sulfonamide, containing only one internal disulfonimide, could
be made from hexane-1,6-disulfonyl chloride (3) and N-benzyl
methylsulfonamide (1). In this approach, hexane-1,6-disulfonyl
chloride serves as the main carbon source for the target
molecule. This material could be conveniently synthesized in
two steps from 1,6-dibromohexane. Tetramer 7 was constructed
using an analogous strategy.
Scheme 2 depicts the synthesis of the tetrameric alkyldisul-
fonimide. One equivalent of N-benzyl methylsulfonamide (1)
was deprotonated with sodium hydride and then treated with 1
equiv of the disulfonyl chloride 3. This reaction yielded 30%
of product 4 on the basis of the initial amount of sulfonamide,
or 60% of the desired product on the basis of the statistical
mixture obtained in a putative unselective reaction. One-third
of an equivalent of disulfonyl chloride 3 was also recovered
from this reaction. Attempts were made to increase this yield
by adding excess disulfonyl chloride, but separation of the
product from the excess disulfonyl chloride by silica gel
chromatography then became difficult. Two equivalents of the
terminal sulfonyl chloride 4 were next treated with 1 equiv of
doubly deprotonated disulfonamide 5 to form two new disul-
fonimide linkages, thus completing the construction of the
N-benzylated tetramer 6. Finally, the protected tetramer 6 was
hydrogenolyzed, in quantitative yield, to give the tetrameric
sulfonimide 7. The MALDI mass spectrum of the material
contained five mass peaks corresponding to five distinct sodium
adducts. The masses are consistent with the sodium adduct of
the neutral molecule as well as the sodium adducts of the mono-,
di-, tri-, and tetraanionic molecules.
Figure 2. Oligodisulfonimide targets.
between the nitrogen and oxygen atoms of the entire disulfon-
imide functional group. Since this initial disulfonimide structure
report, a plethora of structures have been obtained with a variety
of neutral sulfonimides,3 sulfonimide salts,4 perfluoroalkyldis-
ulfonimides,5 and N-alkyl sulfonimides.6
Aside from the interest in their structure, the majority of
earlier studies of disulfonimides deal with the use of disulfon-
imides as leaving groups in substitution and elimination
reactions.7 While disulfonimides are leaving groups of moderate
reactivity, the elevated temperatures and long reactions times
necessary to effect substitution decrease the general utility of
this technique. The use of perfluorinated alkyl disulfonimides
ameliorates these problems and improves the utility of this
method. E2 eliminations have also been attempted with disul-
fonimide functional groups. They lead exclusively to Hofmann
products in some cases, making them more selective than even
ammonium leaving groups under similar conditions.8
Disulfonimide-containing compounds have found uses in
material science as industrial polishes9 and polymer curing
substances.10 Finally, one paper does report the use of a
disulfonimide as a replacement for tetrazole in Angiotensin II
receptor agonist, although this did not lead to a potent inhibitor.11
We found no reports of aliphatic oligodisulfonimides, however,
or their use in biochemical experiments. A few polymers
containing disulfonimides exist, but these are all either aryl- or
perflourinated polymers. Aryl polydisulfonimides were synthe-
sized and tested as water-soluble adhesives, powder coating
compounds, and photographic materials for printing plates.12
Perfluorinated alkylpolydisulfonimides have limited use as fuel
cell electrolytes.13
We sought to explore the synthesis, reactivity, and general
properties of the disulfonimide functional group in the context
of an oligomeric material. In designing these oligomers, we
opted to insert a hexamethylene unit between adjacent functional
groups, which would approximate the distance between charges
in nucleic acids and/or glycosaminoglycans. We chose tetrameric
(7) and hexameric (11) disulfonimide oligomers as our initial
synthetic targets (Figure 2).
(3) Attig, R.; Mootz, D. Acta Crystallogr. 1975, B31, 1212-1214.
(4) (a) Haas, A.; Klare, Ch.; Betz, P. Bruckmann, J.; Kruger, C.; Tsay,
Y.-H.; Aubke, F. Inorg. Chem. 1996, 35, 1918-1925. (b) Jones, P.; Moers,
O.; Blaschette, A. Acta Crystallogr. 1997, C53, 1811-1813.
(5) Xue, L.; DesMarteau, D.; Pennington, W. Angew. Chem., Int. Ed.
Engl. 1997, 36, 1331-1333.
(6) Jones, P.; Hamann, T.; Schaper, W.; Lange, I.; Blaschette, A.
Phosphorus, Sulfur Silicon Relat. Elem. 1995, 106, 91-104.
(7) Baumgarten, R. J. Chem. Educ. 1966, 43, 398.
(8) Bartsch, R.; Allaway, J.; Ingram, D.; Lee, J.-G. J. Am. Chem. Soc.
1975, 97, 6873.
(9) Chem. Abstr. 1968, 69, 51835h.
(10) Chem. Abstr. 1992, 116, 85874z.
(11) Perez, D.; et al. J. Med. Chem. 1995, 38, 2357-2377.
(12) (a) Chem. Abstr. 1988, 109, 240726d. (b) Chem. Abstr. 1992, 116,
85874z. (c) Chem. Abstr. 1980, 93, 150945w.
(13) Appleby, A.; Velev, O.; LeHelloco, J. Parthasarthy, A.; Srinivasan,
S.; DesMarteau, D.; Gillette, M.; Ghosh, J. J. Electrochem. Soc. 1993, 140,
109-110.
(14) DeChristopher, P.; Adamek, J. Lyon, G.; Klein, S.; Baumgarten,
R. J. Org. Chem. 1974, 39, 3525-3532.
(15) (a) Juschke, R.; Kockerling, M.; Sartori, P. Verlag Zeit. Natur. 1998,
135-144. (b) Kremlev, M.; Kharchencho, A.; Zyabrev, V.; Rudenko, E.
Z. Organich. Khimii 1989, 26, 1368-1369.

Synthesis and ReactiVity of Polysulfonimides
J. Am. Chem. Soc., Vol. 123, No. 13, 2001 2939
Scheme 1
Scheme 2
Scheme 3
The N-benzyl hexamer was constructed in an analogous
manner, including one additional monomer elongation step
(Scheme 3). After treating the sulfonyl chloride 4 with benzyl-
amine to obtain the corresponding terminal sulfonamide 8 in
high yield, sulfonamide 8 was deprotonated with sodium hydride
and then treated with 4 equiv of hexane-1,6-disulfonyl chloride
(3) to obtain the terminal sulfonyl chloride 9. The use of excess
hexane-1,6-disulfonyl chloride (3) minimized the undesired
reaction of the product monosulfonyl chloride with residual
sulfonamide anion. Isolated yields were significantly lower in
this reaction (36%), compared to the synthesis of terminal
sulfonyl chloride 4, due to problems with purification. Terminal
sulfonyl chloride 9 did not have good solubility in any applicable
silica gel chromatography eluents. Although the yield of this
reaction was relatively low, there was no difficulty in separating
the excess disulfonyl chloride 3 from the product, and 2.5 equiv
of the unreacted disulfonyl chloride was recovered.
Two equivalents of the terminal sulfonyl chloride (9), which
contains two internal disulfonimides, were next treated with 1
equiv of doubly deprotonated disulfonamide 5 to form two new
disulfonimide linkages, thus forming the hexamer 10. Workup
of the reaction included partitioning the crude material between
ethyl acetate and brine. A nonsoluble solid was filtered off, and
the soluble organic material was analyzed. 1H NMR of the crude,
soluble material, which amounted to approximately half of the
expected mass of the reaction, revealed what appeared to be a

2940 J. Am. Chem. Soc., Vol. 123, No. 13, 2001
Burlingham and Widlanski
mixture of product and two sulfonamide-containing compounds.
Purification by silica gel chromatography did not cleanly
separate pure product from sulfonamide-containing impurities.
The solid that had been filtered from the reaction mixture
also corresponded to about half of the expected mass of the
reaction. Characterization by NMR suggested that this solid was
pure oligodisulfonimide. The NMR spectrum of this material
appeared to support the proposed structure of 10 except that
the relative integrations did not correspond to the expected
values. Peaks for the methyl capping groups had a relatively
low integration value compared to those of the internal
methylene protons, indicating the presence of higher order
oligomers with a relatively higher number of internal protons
compared to the number of protons on the methyl capping group.
At first, this result seemed surprising because we had assumed
that the product disulfonimide would be unreactive and thus
only one product would be obtained under the reaction condi-
tions. To confirm the presence of higher order oligomers, the
oligomer sample was fractionally separated on a silica gel
column. NMR analysis revealed that the less polar fractions
eluted from the column were indeed shorter oligomers than the
more polar fractions, signifying that a continuum of molecular
weight oligomer lengths were produced under these reaction
conditions. Removal of the benzyl protecting groups in this
material has not yet been effected.
Scheme 4
In contrast, deprotected dimethyldisulfonimide (16) did not
react under similar conditions (Scheme 5B). An analogous
observation has been made in the chemistry of sulfonimides,
and this fact has been employed in “safety-catch” linkers for
solid support synthesis.20 N-Protonated sulfonimides are not
cleaved under basic conditions, whereas alkylated sulfonimides
are cleaved.
A number of plausible mechanisms may be proposed to
account for the trans-disulfonimidation reaction. Two such
mechanisms are shown in Scheme 6. The first mechanism (6A)
involves nucleophilic attack of the sulfonamide anion on one
of the sulfurs of the disulfonimide, yielding a new disulfonimide
and sulfonamide. An alternative mechanism (6B) posits an
elimination, in which the sulfonamide anion acts as a base to
generate a sulfene, which would later be trapped to form a new
disulfonimide.
Chemical Reactivity of the Disulfonimide Functional
Group. The formation of higher order disulfonimide oligomers
during a simple coupling reaction is unprecedented. Extant
literature on disulfonimide reactivity does not directly address
this unexpected result but does provide some salient facts.
Sulfonimides, such as saccharin, were first explored as activating
groups for the SN2 displacement of amines. However, the
nucleophile preferentially attacks the carbonyl group to cleave
the sulfonimide.16 Replacing the acyl group of the sulfonimide
with a second sulfonyl group, to give a disulfonimide, eliminates
some of these complications. N-(Alkyl)diaryl disulfonimides
undergo SN2 displacement in moderate yields when using
nucleophiles such as bromide, iodide, and aniline at elevated
temperatures and long reaction times.17 Alternately, S-N bond
cleavage occurs in these compounds with cyanide, hydroxide,
or mercaptide nucleophiles. Perfluorinated disulfonimides react
differently. Under mild conditions, di-triflated N-alkylamines
are susceptible to SN2 displacement by carbon nucleophiles such
as cyanide and diethyl malonate, with no evidence of S-N bond
cleavage.18 These examples clearly show that disulfonimides
may undergo sulfur-nitrogen bond cleavage. However, there
were no reports of new disulfonimides forming as a result of
these processes.
Mechanistic Investigations. The formation of oligomers
longer than hexamers requires that some type of “trans-
disulfonimidation” process takes place. To confirm the viability
of this unprecedented reaction, it was reproduced in a model
system (Scheme 4). Employing the same reaction conditions
as those used in the coupling reaction, diethyldisulfonimide (13)
was treated with the anion of propylsulfonamide (14). NMR
analysis of the reaction revealed the “trans-disulfonimidation”
reaction depicted in Scheme 5.19 Assuming that the equilibrium
ratio of the disulfonimides is equimolar, the half-life of this
reaction is about 6 h.
A simple experiment to aid in distinguishing between these
two mechanisms tests whether trans-disulfonimidation requires
the presence of a hydrogen R to the disulfonimide. N-(Benzyl)-
diphenyldisulfonimide (18) has no hydrogens in the R-position
and therefore cannot form a sulfene. Scheme 7 details this
experiment. When N-(benzyl)dimethyldisulfonimide (15) is
treated with deprotonated N-(benzyl)ethylsulfonamide (12), the
reaction yields trans-disulfonimidation products. On the other
hand, exposure of N-(benzyl)diphenyldisulfonimide (18) to the
same nucleophile yields only recovered starting materials. No
reaction can be detected by TLC or NMR.
If direct attack of a sulfonamide upon a sulfur center of the
disulfonimide were the mechanism of trans-disulfonimidation,
diphenyl disulfonimides should undergo this reaction as well
as alkyl disulfonimides. In fact, electronic effects would tend
to favor it as a substrate for the reaction due to the increased
nucleofugality of the sulfonamide leaving group. To obtain direct
evidence that trans-disulfonimidation proceeds through a sulfene
intermediate, sulfene trapping experiments were performed.
Numerous sulfene trapping reagents have been employed.
Nucleophiles such as water, alcohols, and amines have been
used to trap sulfenes, and cycloaddition reactions of sulfenes
with vinyl ethers, dienes, and imines have been reported.21 The
most commonly used substrates for cycloaddition to sulfenes,
however, are enamines.22 Sulfene intermediates formed during
(19) The benzylic protons of the starting material, propylsulfonamide,
and the product, ethylsulfonamide, are doublets near 4.3 ppm and may be
easily distinguished from one another. The protons of the disulfonimides,
in contrast, are difficult to distinguish due to overlap of their signals,
although it was assumed that the ethylpropyldisulfonimide and the dipro-
pyldisulfonimide were formed in the reaction. To validate this proposition,
we treated dimethyldisulfonimide with the same reaction conditions. The
benzylic protons of the starting materials, methylsulfonamide, methylpro-
pyldisulfonimide, and dipropyldisulfonimide were all easily distinguishable
by NMR in this case.
(16) DeChristopher, P.; Adamek, J.; Lyono, G.; Galante, J.; Haffner, H.;
Boggio, R.; Baumgarten, R. J. Am. Chem. Soc. 1969, 91, 2384-2385.
(17) Hendrickson, J.; Okano, S.; Bloom, R. J. Org. Chem. 1968, 34,
3434-3438.
(18) (a) Glass, R. Chem. Commun. 1971, 1546-1547. (b) Hendrickson,
J.; Bergeron, R.; Giga, A.; Sternbach, D. J. Am. Chem. Soc. 1973, 95, 3412-
3413.
(20) (a) Backes, B.; Virgilio, A.; Ellman, J. J. Am. Chem. Soc. 1996,
118, 3055-3056. (b) Kenner, G. W.; McDermott, J. R.; Sheppard, R. C. J.
Chem. Soc., Chem. Commun. 1971, 636-637.
(21) King, J.; Rathore, R. In The Chemistry of Sulphonic Acids, Esters
and their DeriVatiVes; Patai, S., Rappaport, Z., Eds.; John Wiley & Sons:
Chichester, UK, 1991, Chapter 17.
(22) Borowitz, I. J. Am. Chem. Soc. 1963, 86, 1146-1149.

Synthesis and ReactiVity of Polysulfonimides
J. Am. Chem. Soc., Vol. 123, No. 13, 2001 2941
Scheme 5
Scheme 6
Scheme 7
the trans-disulfonimidation reaction could, in principle, be
scavenged during the reaction by 1-morpholino-1-cyclohexene
via a 2 + 2 cycloaddition.
trapping experiment was 20%,24 a value consistent with similar
sulfene trapping experiments.25 This result confirms that elimi-
nation from the disulfonimide anion proceeds to give substantial
quantities of an intermediate sulfene.
Sulfene Studies. Sulfene formation is expected to occur by
one of three pathways. The reaction may involve a reversible
deprotonation followed by elimination of the leaving group
In a seminal paper concerning the cycloaddition of sulfenes,
Stork and Borowitz reported that treatment of methanesulfonyl
chloride with TEA in the presence of an enamine gives a cyclic
sulfone, presumably through a 2 + 2 cycloaddition. We
performed the analogous experiment to determine whether a
disulfonimide would undergo the same type of reaction (Scheme
8). Premixing 1-morpholino-1-cyclohexene and N-(benzyl)-
dimethyldisulfonimide (15) at -78 °C, followed by treatment
with butyllithium, resulted in the formation of a sulfone adduct
(22). This sulfone matches the characteristics of an authentic
sample synthesized as previously reported.23 The yield of the
(23) (a) Stork, G.; Borowitz, I. J. Am. Chem. Soc. 1962, 84, 3.
(24) After 1 h at -78 °C, the reaction was quenched with tosic acid.
NMR analysis of the mixture indicated that approximately 55% of the
disulfonimide 15 had broken down to sulfonamide 1, suggesting that as
much sulfene had been formed. Of this theoretical amount of sulfene formed,
20% was trapped as sulfone 22.
(25) Pregel, M.; Buncel, E. J. Chem. Soc., Perkin Trans. 2 1991, 307-
311.

2942 J. Am. Chem. Soc., Vol. 123, No. 13, 2001
Burlingham and Widlanski
Scheme 8
Dimethyldisulfonimide 15 was treated with 1 equiv of n-
butyllithium at -78 °C for 5 min, followed by quenching with
D4-methanol. Addition of tosic acid, followed by warming to
room temperature, afforded a mixture of deuterated starting
material and methyl sulfonamide. The recovered disulfonimide
starting material was mono-deuterated, showing full deproto-
nation by the butyllithium. Approximately 10% of the anion
had undergone elimination to give methyl sulfonamide.
This observation allows for a qualitative comparison of the
relative nucleofugality of sulfonamide anions vs alkoxides as
leaving groups. It has been suggested that sulfene formation
proceeds through a late transition state compared to alkene-
forming eliminations, and therefore the rate of reaction is rela-
tively dependent on the leaving group nucleofugality.29 The
disulfonimide anion formed was relatively unstable at even -78
°C, yielding a sulfonamide product consistent with a putative
sulfene intermediate. On the basis of the observation that sul-
fonate ester carbanions are stable to -40 °C,30 the sulfonamide
anion appears to be a better leaving group than an alkoxide ion.
Scheme 9
Conclusions
A novel, unnatural anionic oligomer joined by hexamethylene
linkers has been synthesized in a stepwise, convergent approach.
The reactivity of disulfonimides has been investigated, and
N-substituted disulfonimides should not be assumed to be base-
stable. The swapping of sulfonamide units in a disulfonimide
oligomer via a “trans-disulfonimidation” reaction occurs under
basic conditions. Isotope scrambling, substituent effects, and
sulfene trapping data are most consistent with a reaction
mechanism that includes an E1cBRev elimination to form a
sulfene intermediate. In sulfene-forming eliminations, the sul-
fonamide anion is a better leaving group than an alkoxide anion
but worse than activated phenoxide leaving groups. These
studies form the groundwork for an understanding of the
synthesis and reactivity of the disulfonimide functional group,
a moiety with potential utility as a mimic of biological anions.
(E1cBRev), an irreversible deprotonation followed by elimination
(E1cBIrrev), or a concerted deprotonation/elimination event (E2).
To investigate these possibilities, isotope effect experiments
were conducted.
Toward this end, (D6)-N-(benzyl)dimethyldisulfonimide (21)-
was synthesized as shown in Scheme 9. Treatment of D3-
methanesulfonyl chloride (19)26 with benzylamine gave the
sulfonamide 20. Deprotonation of sulfonamide 20 and treatment
with another equivalent of sulfonyl chloride 15 yielded the
deuterated product 21 with less than 5% hydrogen incorporation
detected by NMR.
The perdeuterated disulfonimide 21 was used to explore the
detailed mechanistic pathway of sulfene formation. A 50/50
mixture of (D6)-dimethyldisulfonimide (21) and (H6)-dimeth-
yldisulfonimide (15) was treated with a solution of deprotonated
propyl sulfonamide. Initially, a singlet at 3.05 ppm was observed
for the methyl groups of the disulfonimide, but as the reaction
progressed, peaks for mono- and dideuterated methyldisulfon-
imide were seen. This isotope scrambling is consistent with a
reversible deprotonation mechanism (Scheme 10). Similar results
have been invoked to support reversible E1cBRev elimination
to form a sulfene from sulfonate esters.27 Aryl sulfonate esters
may form sulfenes by either reversible or irreversible deproto-
nation, depending on the leaving group ability of the phenol.28
These results demonstrate that sulfonamides have a lower
nucleofugality than stable phenoxides in this reaction and that
the carbanion is a discrete intermediate.
Experimental Methods
General Information. Diethyl ether (Et2O) and tetrahydrofuran
(THF) were distilled under nitrogen from sodium-benzophenone ketyl.
Methylene chloride (CH2Cl2) was distilled from calcium hydride.
Pyridine (Pyr) was distilled from barium oxide. Commercial reagents
were used as received unless otherwise stated. All reactions were
conducted under an inert argon or nitrogen atmosphere. Previously
reported compounds are indicated by a footnote after the compound
number.
Chromatography. Analytical thin-layer chromatography (TLC) was
performed on precoated (0.25 mm thickness) glass plates (E. Merck,
silica gel 60 F-254). Components were visualized by UV light (254
nm) if possible and by staining plates with either an acidic solution of
(NH4)6Mo7O24‚H2O and ceric sulfate or an acidic ethanolic solution of
p-anisaldehyde, followed by heating. Column chromatography was
performed using Kieselgel-60 230-400 mesh silica gel (E. Merck).
Bulk solvent removal was carried out on a rotary evaporator at water
aspirator pressure. All nonvolatile compounds were routinely dried
under high vacuum.
Physical Data. Proton nuclear magnetic resonance spectra (1H NMR)
were recorded on a Varian 300 (300 MHz) and Varian-400 (400 MHz)
spectrometers. The chemical shifts are reported in parts per million (δ,
ppm) relative to an internal tetramethylsilane standard. Coupling
constants are reported in hertz (Hz), and the data are presented in the
The stability of the deprotonated disulfonimide was further
investigated by irreversibly deprotonating the disulfonimide.
(26) In the process of making disulfonimide 21, we sought a new
synthesis of (D3)-methanesulfonyl chloride (19). Many preparations of (D3)-
methanesulfonyl chloride (19) have been reported, but they are all either
low yielding, time-consuming, or very inconvenient. We found a more facile
procedure involves submitting (D3)-methyl iodide to the Strecker reaction
and treating the resultant sodium sulfonate salt with phosphorus pentachlo-
ride. This simple two-step procedure gives an overall yield of (D3)-methane-
sulfonyl chloride (19) of 59%, which is comparable to other procedures
but does not require the use of chlorine gas or extended reaction times.
(27) Pregel, M.; Buncel, E. J. Chem. Soc., Perkin Trans. 2 1991, 307-
311.
(28) (a) Davy, M.; Douglas, K.; Loran, J.; Steltner, A,; Williams, A. J.
Am. Chem. Soc. 1977, 99, 1196-1206. (b) King, J.; Beatson, R. Tetrahedron
Lett. 1975, 973-976.
(29) Stirling, C. Acc. Chem. Res. 1979, 12, 198-203.
(30) Truce, W.; Vrenour, D. J. Org. Chem. 1970, 35, 1226-1227.

Synthesis and ReactiVity of Polysulfonimides
J. Am. Chem. Soc., Vol. 123, No. 13, 2001 2943
Scheme 10
following form: chemical shift (multiplicity, number of protons,
coupling constants). Multiplicities are recorded by the following
abbreviations: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet;
br, broad; dd, doublet of doublets; J, coupling constant (Hz). Phosphorus-
31 nuclear magnetic resonance (31P NMR) spectra were recorded on a
Varian 300 spectrometer at 121.5 MHz. The chemical shifts are reported
in parts per million (δ, ppm) relative to an external neat H3PO4 standard
(δ ) 0 ppm). Carbon-13 nuclear magnetic resonance (13C NMR) spectra
were recorded on Varian-300 (75 MHz) and Varian-400 (101 MHz)
spectrometers. All spectra are reported with the corresponding solvent.
Infrared (IR) spectra (neat film or KBr pellet) were recorded on a
Mattson Galaxy 4020 FT-IR instrument. High-resolution mass spectra
(HRMS) and high-resolution FAB mass spectra (HRFABMS) were
recorded on a Kratos MS-80. Melting points were determined in a
Thomas capillary melting point apparatus and are uncorrected.
N-(Benzyl)methylsulfonamide (1).31 Benzylamine (10.7 g/100
mmol) was dissolved in 100 mL of dry THF, and the resulting solution
was cooled to 0 °C. Mesyl chloride (5.7 g/50 mmol) was added to the
reaction flask dropwise, and the mixture was permitted to stir for 3 h.
The solvent was removed, and the crude material was dissolved in ethyl
acetate and then washed three times with 30 mL of 2 N HCl. The
organic layer was dried with MgSO4, and the solvent was removed,
yielding 6.74 g of 1 (73%): 1H NMR (CDCl3) δ 2,83 (s, 3H); 4.30 (d,
2H, J ) 7.6 Hz); 4.98 (br. s, 1H); 7.35 (m, 5H) ppm; 13C NMR (CDCl3)
δ 41.2, 47.3, 128.1, 128.3, 129.1, 136.9 ppm; IR (KBr pellet) 3232,
3018, 2847, 1458, 1300, 1134 cm-1; HRFABMS (m/z) calcd for C8H11-
NO2S‚H+ 186.0588, found 186.0585.
evaporated. The crude material was purifed by column chromatography
(3:1 methylene chloride:hexane) and 1.29 g of the product (60% of
theoretical yield based on 1 was obtained): mp 70 °C; 1H NMR (CDCl3)
δ 1.45 (m, 4H); 1.76 (m, 2H); 2.01 (m, 2H); 2.97 (s, 3H); 3.30 (m,
2H); 3.65 (m, 2H); 4.90 (s,2H); 7.53,7.38 (m, 5H) ppm 13C NMR δ
22.47, 23.89, 26.79, 27.16, 43.76, 52.15, 56.20, 64.96, 128.64, 128.81,
129.35, 134.84 ppm; IR (KBr pellet) 3028, 2949, 1466, 1359, 1163,
1055 cm-1; HRFABMS (m/z) calcd for C14H22ClNO6S‚H+ 432.0376,
found 432.0368. Anal. Calcd for C14H22ClNO6S3: C, 38.93; H, 5.13;
N, 3.24. Found: C, 38.84; H, 5.15; N, 3.20.
Hexane-1,6-di-[N-(benzyl)sulfonamide] (5). Benzylamine (4.7 g/44
mmol) was dissolved in 20 mL dry THF and allowed to stir at 0 °C
for 15 min. The disulfonyl chloride 3 (3.1 g/11 mmol) was dissolved
in 10 mL of dry THF and was added dropwise to the reaction, which
was allowed to warm to room temperature and stir for 3 h. To the
reaction mixture was added 50 mL of ethyl acetate and 30 mL of 2 N
HCl. The organic layer was separated and washed with 30 mL of 2 N
HCl. The organic layer was separated, dried (MgSO4), and evaporated.
The crude product was recrystallized from THF/water. Recrystallization
yielded 4.26 g (91%): mp 171 °C; 1H NMR (DMSO) δ 1.20 (m, 4 H);
1.55 (m, 4 H); 2.84 (m, 4 H); 4.12 (d, 4 H, J ) 6.4 Hz); 7.35 (m, 10
H); 7.62 (t, 2H, J ) 6.4 Hz) ppm 13C NMR (DMSO) δ 22.8, 26.9,
45.8, 51.5, 127.1, 127.6, 128.3, 138.4 ppm; IR (KBr pellet) 3279, 3032,
2920, 2362, 1429, 1323, 1136 cm-1; HRFABMS (m/z) calcd for
C20H28N2O4S2‚H+ 425.1569, found 425.1567; Anal. Calcd for
C20H28N2O4S2: C, 56.58; H, 6.65; N, 6.60. Found: C, 56.44; H, 6.58;
N, 6.57.
Disodium Hexane-1,6-disulfonate (2).32 Sodium sulfite (63.02
g/0.500 mol) and 1,6-dibromohexane (48.79 g/0.200 mol) were boiled
under reflux in 100 mL of water for 72 h. The solvent was evaporated
under reduced pressure. The crude solid was recrystallized from a
minimum amount of water/methanol. Collection after two crops yielded
51.9 g (89%): 1H NMR (D2O) δ 1.32 (m, 4H); 1.61 (m, 4H); 2.78 (m,
4H) ppm; 13C NMR (D2O) δ 19.2, 22.7, 46.3 ppm; IR (KBr pellet)
6-[6-[6-[N-(Benzyl)methyldisulfonimidoylhexyl]-N-(benzyl)meth-
yldisulfonimidoylhexyl]-N-(benzyl)methyldisulfonimidoylhexyl]-N-
(benzyl)methyldisulfonimide (6). Sodium hydride (0.11 g, 2.8 mmol)
was washed with pentane and dried under nitrogen. Disulfonamide 5
(0.46 g, 1.1 mmol) was dissolved in 15 mL of dry THF and 1 mL of
DMSO. The solution was added into the base and stirred for 10 h. The
chloride 4 (0.93 g, 2.2 mmol) was dissolved in 5 mL of dry THF and
added to the reaction mixture to stir for 3 h. The solvent was evaporated
under vacuum, and the crude was taken up in 50 mL of methylene
chloride, filtering insoluble material. The organic layer was washed
three times with brine, dried over magnesium sulfate, and evaporated.
Silica gel column chromatography (1% MeOH/CH2Cl2) gave some
separation to yield 0.26 g (20%) of pure product and 0.45 g of partially
purified product. 1H NMR (CDCl3): δ 1.27 (m, 12H); 1.66 (m, 12H);
2.96 (s, 6H); 3.14 (m, 8H); 3.26 (m, 4H); 4.88 (s, 4H); 4.89 (s, 4H)
7.53, 7.37 (m, 20H) ppm. 13C (CDCl3): δ 22.39, 22.55, 27.22, 43.87,
52.26, 52.42, 56.42, 128.72, 128.84, 128.88, 129.47, 129.60, 134.99,
135.32 ppm.
3547, 2922, 2874, 2235, 2092, 1626, 1155 cm-1
.
Hexane-1,6-disulfonyl Chloride (3).33 The bis sulfonate sodium salt
2 was dried at 80 °C under reduced pressure to a constant weight of
13.8 g (47 mmol). Solid PCl5 (23.8 g/114 mmol) was mixed thoroughly
with 2. The reaction flask was fitted with a condenser and was heated
to 90 °C for 4 h. The reaction was quenched with ice water (30 mL),
which was then decanted. The crude solid was washed with water (2
× 30 mL) and then dissolved in ethyl acetate. The ethyl acetate was
dried (MgSO4) and evaporated under vacuum. The product was
recrystallized from a minimum amount of ethyl acetate/hexanes. Two
recrystallizations yielded 10.5 g (78%): 1H NMR (CDCl3) δ 1.58 (m,
4 H); 2.06 (m, 4 H); 3.67 (m, 4 H) ppm 13C NMR (CDCl3) δ 24.1,
27.0, 65.0 ppm; IR (KBr pellet) 2993, 2933, 2868, 1471, 1355, 1157,
6-(6-(6-(Methyldisulfonimidoylhexyl)methyldisulfonimidoylhexyl)-
methyldisulfonimidoylhexyl)methyldisulfonimide (7). The N-benzyl-
protected tetrakisdisulfonimide 6 (0.24 g) was dissolved in 30 mL of
THF, and about 50 mg of Pd-C was added. The flask was purged
with argon, and then hydrogen gas was added. The reaction was stirred
for 1 h, the vessel was purged with argon, and the solution was filtered
and evaporated under vacuum to give 0.168 g (100%) of product: 1H
NMR (D2O) δ 1.26 (m, 12H); 1.59 (m, 12H); 2.87 (s, 6H); 3.00 (m,
12H) ppm; 13C NMR (D2O) δ 23.02, 26.03, 42.43, 54.16, 54.44 ppm.
(unreferenced); IR (KBr pellet) 3281, 2939, 1450, 1354, 1147, 877
cm-1. MALDI MS (dihydroxybenzoic acid matrix) (m/z) calcd for
C20H46N4O16S8‚Na 877.057, found 877.271; C20H45N4O16S8‚Na2 899.039,
found 899.282; C20H44N4O16S8‚Na3 921.021, found 921.274;
C20H43N4O16S8‚Na4 943.003, found 943.281; C20H42N4O16S8‚Na5 964.985,
found 965.297.
758 cm-1
.
1-[6-Hexylsulfonyl chloride]-N-(benzyl)methyldisulfonimide (4).
A 60% oil dispersion of sodium hydride (0.44 g/11 mmol) was washed
with pentane (2 × 8 mL) and dried under nitrogen. 1 (1.85 g/10 mmol)
was dissolved in 10 mL of dry THF and added dropwise to the sodium
hydride. An additional 20 mL of dry THF was added to the thick
suspension. The mixture was stirred for 1 h. 2.830 g (10 mmol) of
dichloride 3 was dissolved in 10 mL of dry THF, and the deprotonated
sulfonamide solution was added quickly to the dichloride. After 1 h,
the reaction was quenched with saturated ammonium chloride, the
solvent was removed, and the crude mixture was partitioned between
75 mL of ethyl acetate and distilled water. The organic layer was
washed with water, separated, dried over magnesium sulfate, and
(31) Breslow, D.; Edwards, E.; Lindsay, E. Omura, H. J. Am. Chem.
Soc. 1976, 98, 4268-4275.
(32) Stone, G. J. Am. Chem. Soc. 1936, 58, 488-489.
(33) Murahashi, S.; Takizawa, T. J. Soc. Chem. Ind. Jpn. 1944, 47, 784-
791.
1-[6-Hexyl-N-(benzyl)sulfonamide]-N-(benzyl)]methyldisulfonim-
ide (8). 4 (1.29 g, 3.0 mmol) was dissolved in 25 mL of THF and
cooled to 0 °C. Benzylamine (0.85 mL, 7.5 mmol) was added dropwise
to the reaction, which was stirred for 1.5 h. The THF was removed

2944 J. Am. Chem. Soc., Vol. 123, No. 13, 2001
Burlingham and Widlanski
under vacuum, and the crude material was partitioned between 50 mL
of ether and 50 mL of of 2 M HCl. The organic layer was separated,
washed with brine, dried over magnesium sulfate, and evaporated under
vacuum, leaving 1.387 g of product with no need for further purification
(92.4%): mp 118 °C; 1H NMR (CDCl3) δ 1.30 (m, 4H); 1.70 (m, 4H);
2.86 (m, 2H); 2.93 (s, 3H); 3.28 (m, 2H); 4.29 (d, 2H, J ) 6.4 Hz);
4.77 (t, 1H, J ) 6.4 Hz); 4.89 (s, 2H)7.55, 7.35 (m, 10H) ppm; 13C
NMR δ 22.52, 23.18, 27.28, 27.35, 43.85, 47.12, 52.26, 52.97, 56.35,
127.93, 128.06, 128.68, 128.85, 129.39, 134.89, 136.93 ppm; IR (KBr
pellet) 3250, 3032, 2941, 1462, 1358, 1151 cm-1; HRFABMS (m/z)
calcd for C21H30N2O6S3‚H+ 503.1344, found 503.1337. Anal. Calcd
for C21H30N2O6S3: C, 50.18; H, 6.02; N, 5.57. Found: C, 49.91; H,
5.82, N, 5.45.
1-[1-(6-Hexylsulfonyl chloride)-6-hexyl-N-(benzyl)hexyldisulfon-
imide]-N-benzyl)hexylmethyldisulfonimide (9). Sulfonamide 8 (1.36
g, 2.7 mmol) was dissolved in 30 mL of dry THF. The solution was
added into sodium hydride (0.12 g, 3.0 mmol) that had been washed
with 5 mL of pentane. The reaction was stirred for 2 h and grew mostly
clear. Dichloride 3 (3.06 g, 11 mmol) was dissolved in 10 mL of dry
THF. The deprotonated sulfonamide solution was added into the
dichloride slowly and stirred overnight. The reaction was quenched
with ammonium chloride, and the solvent was removed under vacuum.
The crude was partitioned between 100 mL of ethyl acetate and 50
mL of water. The organic layer was separated, washed with an
additional 50 mL of water and separated, dried with magnesium sulfate,
and evaporated under vacuum. The crude product was dissolved in 25
mL of methylene chloride, and 5 g of silica gel was added. The solvent
was removed to bind the crude product to the silica gel, and the mixture
was placed on top of a silica gel column (CH2Cl2) and chromatographed,
yielding 0.71 g of product (36% of theoretical yield based on 8): 1H
NMR (CDCl3) δ 1.28 (m, 4H); 1.42 (m, 4H), 1.68 (m, 6H); 2.00 (m,
2H); 2.96 (s, 3H); 3.17 (m, 4H), 3.26 (m, 2H); 3.63 (m, 2H); 4.88 (s,
2H), 4.89 (s, 2H); 7.55, 7.40 (m, 10H) ppm; 13C NMR 22.17, 22.27,
23.72, 26.55, 26.93, 26.99, 43.61, 51.96, 52.13, 56.06, 56.13, 64.81,
128.47, 128.65, 129.17, 129.32, 134.85, 135.14 ppm; IR (KBr pellet)
3040, 2949, 1466, 1369, 1151, 796 cm-1; HRFABMS (m/z) calcd for
C27H41ClN2O10S5‚H+ 771.09514, found 771.0939.
6-[6-[6-[6-[6-[N-(Benzyl)methyldisulfonimidoylhexyl]-N-(benzyl)-
methyldisulfonimidoylhexyl]-N-(benzyl)methyldisulfonimidoylhex-
yl]-N-(benzyl)methyldisulfonimidoylhexyl]-N-(benzyl)methyldisul-
fonimidoylhexyl]-N-(benzyl)methyldisulfonimide (10). Sodium hydride
(0.036 g, 0.9 mmol) was washed with 5 mL of pentane. The bis
sulfonamide 5 (0.15 g, 0.36 mmol) was dissolved in 5 mL of dry THF
and 0.3 mL of DMSO, and it was then added to the sodium hydride.
The thick slurry was stirred for 3 h. Sulfonyl chloride 9 (0.54 g, 0.72
mmol) was dissolved in 5 mL of dry THF and was added to the reaction
mixture quickly. THF (10 mL) was added to the reaction, which was
stirred for 20 h. The THF was removed, and the crude solid was
dissolved/suspended in 100 mL of ethyl acetate and 100 mL of 0.1 M
HCl. The remaining solid (0.350 g) was filtered, and the organic layer
was separated, dried with magnesium sulfate, and evaporated. Column
chromatography (1% MeOH/CH2Cl2) of the crude from the organic
layer gave 67 mg of product (10) plus an additional 170 mg of slightly
impure fractions of product. 1H NMR (CDCl3): δ 1.23 (m); 1.65 (m);
2.95 (s); 3.17 (m); 3.24 (m); 4.85 (s); 4.87 (s), 7.55-7.40 (m) ppm.
13C NMR (CDCl3): δ 22.34, 22.45, 27.18, 43.83, 52.21, 52.37, 56.38,
128.68, 128.80, 128.83, 129.42, 129.56, 134.97, 135.30 ppm.
N-(Benzyl)diethyldisulfonimide (13). Sodium hydride (0.22 g, 5.5
mmol) was washed with 5 mL of pentane. Sulfonamide 12 (0.99 g, 5
mmol) was dissolved in 10 mL of dry THF and added to the base.
After 0.5 h, the solution grew clear. Ethyl sulfonyl chloride (0.52 mL,
5 mmol) was added to the reaction which grew cloudy quickly. After
1 h, the solvent was evaporated and the crude was partitioned between
50 mL of ether and 50 mL of 2 M HCl. The ether phase was washed
with 50 mL of brine. The ether was separated, dried with magnesium
sulfate, and evaporated under reduced pressure. The crude was
chromatographed by silica gel chromatography (2:1 hexanes:ethyl
acetate) to give 1.27 g (87%) of solid product: mp 72-73 °C; 1H NMR
(CDCl3) δ 1.29 (t, 6H, J ) 7.2 Hz), 3.23 (q, 4H, J ) 7.2 Hz), 4.91 (s,
2H), 7-36-7.54 (m, 5H) ppm; 13C NMR (CDCl3) δ 7.44, 51.38, 52.62,
128.60, 128.78, 129.48 ppm; IR (KBr pellet) 3508, 3063, 2987, 1460,
1365, 1145 cm-1; HRFABMS (m/z) calcd for C11H17NO4S2‚H+
292.0677, found 292.0671. Anal. Calcd for C11H17NO4S2: C, 45.34;
H, 5.88; N, 4.81. Found: C, 45.52; H, 5.93; N, 4.82.
N-(Benzyl)propylsulfonamide (14).35 Propylsulfonyl chloride (5.6
mL, 50 mmol) was dissolved in 50 mL of ether at 0 °C. Benzylamine
(10.9 mL, 100 mmol) was added slowly to the reaction, which was
then allowed to warm to room temperature. Then 50 mL of 1 M HCl
was added to dissolve the benzylamine salt, and the ether layer was
washed with 0.2 M HCl (50 mL) and brine (50 mL). The ether was
dried with magnesium sulfate and evaporated under vacuum, yielding
a white solid (9.427 g, 89%): 1H NMR (CDCl3) δ 0.953 (t, 3H, J )
7.6 Hz), 1.75 (m, 2H), 2.86 (m, 2H), 4.27 (d, 2H, J ) 6.0 Hz), 4.94 (t,
1H, J ) 6.0 Hz), 7.35 (m, 5H) ppm; 13C NMR (CDCl3) δ 12.80, 17.23,
47.06, 54.93, 127.85, 127.91, 128.75, 137.03 ppm; IR (KBr pellet) 3285,
3036, 2926, 1431, 1325, 1132 cm-1; HRFABMS (m/z) calcd for C10H15-
NO2S‚H+ 214.0902, found 214.0905.
N-(Benzyl)dimethyldisulfonimide (15).36 Sodium hydride (0.24 g,
6.0 mmol) was washed with 5 mL of pentane. Sulfonamide 1 (0.926
g, 5 mmol) was dissolved in 10 mL of dry THF and added to the base.
After 0.5 h, methanesulfonyl chloride (0.43 mL, 5.5 mmol) was added
to the reaction. After 1 h, the solvent was evaporated and the crude
was partitioned between 100 mL of ether and 50 mL of 2 M HCl. The
ether was washed with 50 mL of brine. The ether was separated, dried
with magnesium sulfate, and evaporated under reduced pressure. The
crude was chromatographed by silica gel chromatography (2:1 hexanes:
ethyl acetate) to give a white solid (0.94 g, 71%): 1H NMR (CDCl3)
δ 3.07 (s, 6H), 4.92 (s, 2H), 7.37-7.54 (m, 5H) ppm; 13C NMR (CDCl3)
δ44.02, 51.96, 128.66, 128.89, 129.26, 134.70 ppm. IR (KBr pellet)
3050, 2359, 1628, 1365, 1273, 1103 cm-1
.
Dimethyldisulfonimide (16). The N-benzyl-protected disulfonimide
15 (0.58 g) was dissolved in 10 mL of THF, and 30 mg of Pd-C was
added. The flask was purged with argon, and then hydrogen gas was
added. The reaction was stirred for 1 h, the vessel was purged with
argon, and the solution was filtered and evaporated under vacuum to
give 0.384 g (100%) of product: 1H NMR (d6-acetone) δ 3.25 (s) ppm;
13C NMR (d6-acetone) δ 43.36 ppm.
N-(Benzyl)phenylsulfonamide (17).37 Phenylsulfonyl chloride (2.6
mL, 20 mmol) was dissolved in 100 mL of ether at 0 °C. Benzylamine
(4.4 mL, 40 mmol) was added dropwise, and the reaction was allowed
to warm to room temperature. Then 100 mL of 0.5 M HCl was added
to dissolve the benzylamine salt. The ether phase was washed with an
additional 100 mL of 0.5 M HCl. The ether was separated, dried with
magnesium sulfate, and evaporated under vacuum to reveal 4.57 g
(93%) of solid product: 1H NMR (CDCl3) δ 4.08 (d, 2H, J ) 6.0 Hz),
5.39 (t, 1H, J ) 6.0 Hz), 7.09-7.83 (m, 10H) ppm; 13C NMR (CDCl3)
δ 47.01, 126.91, 127.62, 127.70, 128.45, 128.95, 132.48, 136.20, 139.78
N-(Benzyl)ethylsulfonamide (12).34 Benzylamine (4.4 mL, 40
mmol) was dissolved in THF at 0 °C. Ethyl sulfonyl chloride (1.9 mL,
20 mmol) was added to the reaction, which was allowed to warm to
room temperature. The THF was evaporated under vacuum, and the
crude material was partitioned between 50 mL of ether and 50 mL of
1 M HCl. The ether phase was separated and washed with 50 mL of 1
M HCl. The ether layer was separated, dried with magnesium sulfate,
and evaporated under reduced pressure to yield a white solid (3.40 g,
85%): 1H NMR (CDCl3) δ 1.29 (t, 3H, J ) 7.2 Hz), 2.93 (q, 2H, J )
7.2 Hz), 4.28 (s, 2H), 4.82 (br s, 1H); 7.35 (m, 5H) ppm; 13C NMR
(CDCl3) 8.17, 47.11, 47.53, 127.84, 127.97, 128.78, 136.98 ppm; IR
(KBr pellet) 3288, 3035, 2976, 1453, 1313, 1138 cm-1; HRFABMS
(m/z) calcd for C9H13NO2S‚H+ 200.0745, found 200.0740.
ppm; IR (KBr pellet) 3331, 3063, 2930, 1445, 1325, 1151 cm-1
;
HRFABMS (m/z) calcd for C13H13NO2S 248.0745, found 248.0743.
N-(Benzyl)diphenyldisulfonimide (18).38 Sodium hydride (0.22 g,
5.5 mmol) was washed with 5 mL of pentane. Sulfonamide 17 (1.24
g, 5.0 mmol) was dissolved in 15 mL of dry THF and added to the
base. After stirring for 0.5 h, phenylsulfonyl chloride (0.64 mL, 5 mmol)
(35) Kataoka, T.; Iwana, T. Setta, T.; Takog, A. Synthesis 1998, 423.
(36) Dalluhm, J.; Prohl, H.; Henschel, D.; Blanschette, A.; Jones, P.
Phosphorus Sulfur, Silicon 1996, 114, 149-160.
(37) Hantzsch, A.; Voegelen, E. Ber. Dtsch. Chem. Ges. 1901, 34, 3142.
(38) Mueller, P.; Nguyen, T. Tetrahedron Lett. 1978, 4727-4730.
(34) Thompson, M. Synthesis 1988. 733-735.

Synthesis and ReactiVity of Polysulfonimides
J. Am. Chem. Soc., Vol. 123, No. 13, 2001 2945
was added to the reaction which grew thinner. After 2 h, the reaction
was quenched with ammonium chloride and the solvent was evaporated.
The crude material was partitioned between 50 mL of ether and 50
mL of 2 M HCl. The ether was washed with 50 mL of brine. The
ether layer was separated, dried with magnesium sulfate, and evaporated
under reduced pressure. The crude reaction mixture was chromato-
graphed by silica gel chromatography (1:1 hexanes:methylene chloride)
to give 1.496 g (77.3%) of solid product: 1H NMR (CDCl3) δ 4.94 (s,
2H), 7.1-7.8 (m, 15H) ppm; 13C NMR (CDCl3) δ 52.48, 128.07,
128.38, 128.76, 129.17, 133.54, 134.47, 140.08 ppm; IR (KBr pellet)
3063, 2962, 1446, 1373, 1167 cm-1; HRFABMS (m/z) calcd for C19H17-
NO4S2‚H+ 388.0677, found 388.0693.
5H) ppm; 13C NMR (CDCl3) δ 47.06, 127.84, 127.98, 128.80, 136.74
ppm; IR (KBr pellet) 3234, 3034, 1456, 1435, 1304, 1141 cm-1
.
HRFABMS (m/z) calcd for C8H8D3NO2S‚H+ 189.0773, found 189.0773.
Anal. Calcd for C8H8D3NO2S: C, 51.04; H+D as H, 5.89; N, 7.44.
Found: C, 51.13; H+D as H, 5.92; N, 7.40.
N-(Benzyl)dimethyldisulfonimide-d6 (21). Sulfonamide 28 was
dissolved in 50 mL of ether and washed with deuterium oxide (2 × 4
mL). The ether was dried with magnesium sulfate and evaporated.
Sodium hydride (0.26 g, 6.4 mmol) was washed with 5 mL of pentane.
The deuterated sulfonamide 20 was dissolved in 20 mL of dry THF
and added slowly to the base. An additional 20 mL of dry THF was
added to aid stirring for 2 h. Methanesulfonyl chloride-d3 was dissolved
in 10 mL of dry THF and added to the reaction, which grew thin and
milky quickly. After 15 min, TLC showed complete reaction. Deuterated
benzylamine was added to the reaction to scavenge any unreacted
sulfonyl chloride. Deuterium oxide (0.5 mL) was added to quench the
reaction. The THF was evaporated under reduced pressure, and the
crude was partitioned between 100 mL of ether and 40 mL of 1 M
HCl. The ether phase was separated and washed with 40 mL of 1 M
HCl. The ether was dried over magnesium sulfate, and the ether was
evaporated under reduced pressure. The crude solid was purified by
column chromatography (2:1 Hex:Ethyl acetate) to yield 1.39 g
(89%): mp 115 °C; 1H NMR (CDCl3) δ 3.03 (s, 0.12H), 4.91 (s, 2H),
7.3-7.4 (m, 5H) ppm; 13C NMR (CDCl3) δ 51.87, 128.59, 128.84,
129.21, 134.83 ppm; IR (KBr pellet) 3234, 3011, 2262, 1338, 1159
cm-1; HRFABMS (m/z) calcd for C9H7D6NO2S‚H+, 270.0734, found
270.0747. Anal. Calcd for C9H8D6NO2S: C, 40.13; H+D as H, 4.86;
N, 5.20. Found: C, 40.29; H+D as H, 4.88; N, 5.19.
Methanesulfonyl Chloride-d3 (19).39 Sodium sulfite (4.16 g, 33
mmol) was dissolved in 15 mL of water in a round-bottom flask sealed
with a septum. Iodomethane-d3 (5.0 g, 35 mmol) was added to the
flask and stirred for 3 h, until no longer biphasic. The solvent was
removed, and the crude white solid was dissolved in 12 mL of hot
water and added into 200 mL of hot acetone. The solution was cooled
overnight and the solid was then filtered. The solid was dried at 100
°C under vacuum for 2 h. PCl5 (3.44 g, 16.5 mmol) was mixed
thoroughly with 2.00 g (16.5 mmol) of the sodium salt and heated to
90 °C for 1 h under reflux. Dry ether (20 mL) was added to the flask,
and the contents were stirred for 10 min. The flask was cooled to 0
°C, and 30 mL of ether was added. To the reaction was added 40 mL
of 20% sodium bisulfite solution, and the reaction was stirred until no
solid remained. The organic layer was collected and washed twice with
40 mL of 20% sodium bisulfite solution. The aqueous fractions were
collected and back-extracted with 30 mL of ether. The ether fractions
were collected and washed with 40 mL of 20% sodium bisulfite. The
ether layer was dried over magnesium sulfate and evaporated to yield
1.15 g (59%) of a yellow tinted oil.
4-(7,7-Dioxido-7-thiabicyclo[4.2.0]oct-1-yl)morpholine (22).40 TEA
(0.70 mL/5.0 mmol) and 4-(1-cyclohexen-1-yl)morpholine (0.84 mL/
5.0 mmol) were dissolved in 5 mL of dry THF at room temperature
under nitrogen. Mesyl chloride (0.39 mL/5.0 mmol) was added to the
reaction flask dropwise. A white precipitate formed quickly. After
stirring for 16 h, 30 mL of distilled water was added to the crude
reaction, and the solution was shaken in a separatory funnel until a
white solid formed. Then 30 mL of ether was added, and the suspension
was shaken. The solid was filtered and dried under vacuum overnight
to yield 0.46 g (38%) of 21.
N-(Benzyl)methylsulfonamide-d3 (20). Deuterated benzylamine was
prepared by stirring with deuterium oxide and extraction with ether.
Methanesulfonyl chloride-d3 (19) (0.94 g, 8.0 mmol) was dissolved in
25 mL of dried ether at 0 °C. Benzylamine-d2 (2.2 mL, 20 mmol) was
added to the reaction vessel slowly and then stirred at room temperature
for 1.5 h. The creation was quenched with 25 mL of 2 M HCl. The
ether layer was separated and washed with 20 mL of 2 M HCl. The
ether layer was dried over magnesium sulfate and evaporated under
reduced pressure to yield 1.24 g (82%) of an off-white solid: mp 64
Acknowledgment. This work was supported by a Graduate
Assistantship in Areas of National Need Fellowship to B.T.B.
1
°C; H NMR (CDCl3) δ 4.30 (s, 2H), 5.05 (br s, 1H), 7.30-7.37 (m,
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G. Tetrahedron 1972, 28, 167-173. (d) King, J.; Lam, J,; Skonieczny, S.
J. Am. Chem. Soc. 1992, 114, 1743-1749.
JA002465V
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