In search of a new class of stable nitroxide: Synthesis and reactivity of a peri-substituted N,N-bissulfonylhydroxylamine

Article abstract of DOI:10.1039/c0ob00976h

Acyclic bissulfonylnitroxides have never been isolated, and degrade through fragmentation. In an approach to stabilising a bissulfonylnitroxide radical, the cyclic, peri-substituted N,N-bissulfonylhydroxylamine, 2-hydroxynaphtho[1,8- de][1,3,2]dithiazine 1,1,3,3-tetraoxide (1), has been prepared by formal nitrogen insertion into the sulfur-sulfur bond of a sulfinylsulfone, naphtho[1,8-cd][1,2]dithiole 1,1,2-trioxide. The heterocyclic ring of 1 is shown to adopt a sofa conformation by X-ray crystallography, with a pseudo-axial hydroxyl group. N,N-Bissulfonylhydroxylamine 1 displays high thermal, photochemical and hydrolytic stability compared to acyclic systems. EPR analysis reveals formation of the corresponding bissulfonylnitroxide 2 upon oxidation of 1 with the Ce(iv) salts CAN and CTAN. Although 2 does not undergo fragmentation, it cannot be isolated, since hydrogen atom abstraction to reform 1 occurs in situ. The stability and reactivity of 1 and 2 are compared with the known cyclic benzo-fused N,N-bissulfonylhydroxylamine, N-hydroxy-O- benzenedisulfonimide (6), for which the X-ray data, and EPR of the corresponding nitroxide 10, are also reported for the first time.

Full text of DOI:10.1039/c0ob00976h

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PAPER
In search of a new class of stable nitroxide: synthesis and reactivity of a
peri-substituted N,N-bissulfonylhydroxylamine†‡
Bhaven Patel,a Julie Carlisle,b Steven E. Bottle,c Graeme R. Hanson,d Benson M. Kariuki,§a Louise Male,a
John C. McMurtrie,c Neil Spencera and Richard S. Grainger*a
Received 3rd November 2010, Accepted 20th December 2010
DOI: 10.1039/c0ob00976h
Acyclic bissulfonylnitroxides have never been isolated, and degrade through fragmentation. In an
approach to stabilising a bissulfonylnitroxide radical, the cyclic, peri-substituted
N,N-bissulfonylhydroxylamine, 2-hydroxynaphtho[1,8-de][1,3,2]dithiazine 1,1,3,3-tetraoxide (1), has
been prepared by formal nitrogen insertion into the sulfur–sulfur bond of a sulfinylsulfone,
naphtho[1,8-cd][1,2]dithiole 1,1,2-trioxide. The heterocyclic ring of 1 is shown to adopt a sofa
conformation by X-ray crystallography, with a pseudo-axial hydroxyl group.
N,N-Bissulfonylhydroxylamine 1 displays high thermal, photochemical and hydrolytic stability
compared to acyclic systems. EPR analysis reveals formation of the corresponding bissulfonylnitroxide
2 upon oxidation of 1 with the Ce(IV) salts CAN and CTAN. Although 2 does not undergo
fragmentation, it cannot be isolated, since hydrogen atom abstraction to reform 1 occurs in situ. The
stability and reactivity of 1 and 2 are compared with the known cyclic benzo-fused
N,N-bissulfonylhydroxylamine, N-hydroxy-O-benzenedisulfonimide (6), for which the X-ray data, and
EPR of the corresponding nitroxide 10, are also reported for the first time.
nitroxides have not been isolated, and have been reported to readily
Introduction
∑
fragment through b-elimination to form sulfonyl radicals (RSO2 )
Although nitroxides are often regarded as long-lived “persistent”
and nitroso-species, which undergo further fragmentation and
radicals, their stability is highly dependent on the nature and
addition reactions to give N,N,O-trissulfonylhydroxylamines as
substitution on the atoms bonded to nitrogen.1 Fremy’s salt
(potassium nitrosodisulfonate), one of the earliest reported and
synthetically useful nitroxide radicals, contains a nitrogen attached
to two sulfonate anions, and is sufficiently stable for it to be com-
mercially available. In contrast, bis(organosulfonyl)-substituted
the major decomposition product (Scheme 1).2–4
aSchool of Chemistry, University of Birmingham, Edgbaston, Birmingham,
UK B15 2TT. E-mail: r.s.grainger@bham.ac.uk; Fax: +44 (0)121 4144403;
Tel: +44 (0)121 4144465
bDepartment of Chemistry, King’s College London, Strand, London, UK
WC2R 2LS
cARC Centre of Excellence for Free Radical Chemistry and Biotechnology,
Queensland University of Technology, Brisbane, Queensland, 4001, Australia
dCentre for Advanced Imaging, The University of Queensland, Brisbane,
Queensland, 4072, Australia
† Dedicated to the memory of Professor Athel Beckwith, pioneer in free
radical chemistry.
Scheme 1 Major decomposition pathway of acyclic bissulfonylnitroxides.
‡ Electronic supplementary information (ESI) available: 1H and 13C NMR
of all new compounds, X-ray experimental and additional information,
and EPR decay curves. X-ray data for 1·H2O, 1·EtOAc, 9, 12 and 6·H2O in
CIF format. The CIFs for these crystal structures have been deposited
with the CCDC, CCDC reference numbers 798806–798810. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c0ob00976h
We are interested in the use of peri-(1,8)-substituted naph-
thalenes for the generation and stabilisation of reactive sulfur
species,5,6 and as profluorescent nitroxide probes for polymer
degradation.7 In the present study, we report the synthesis of
the novel peri-substituted N,N-bissulfonylhydroxylamine 1, and
studies on its subsequent transformation to the nitroxide 2 (Fig. 1).
§ Present address: School of Chemistry, Cardiff University, Park Place,
Cardiff CF10 3AT, UK
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by slow recrystallisation from hot H2O (Fig. 2).¶ꢀ One molecule
of the solvent is present in the unit cell, hydrogen bonding to
the hydroxyl group of 1. The heterocyclic ring adopts a sofa
conformation, with the two peri-sulfur atoms essentially coplanar
˚
with the naphthalane ring and the nitrogen 0.60 A below the mean
plane of the naphthalene ring. The hydroxyl group resides in a
pseudo-axial orientation (O(5)–N(1)–S(1)–C(1) and O(5)–N(1)–
S(2)–C(10) torsion angles -60.0(2)◦ and 61.7(2)◦ respectively). In
this arrangement, the nitrogen lone-pair bisects (gauche) the two
sulfur–oxygen bonds on each adjacent sulfur. This conformation
is also seen to a lesser extent in the four known X-ray crystal
structures of acylic N-hydroxybissulfonamide derivatives found in
a search of the CCDC,11–13 and is commonly observed about the
S–N bond in sulfonamides.14 Selected bond lengths and angles are
reported in Table 1.
We also obtained the X-ray crystal structure of 1·EtOAc by
recrystallisation from hot EtOAc (Fig. S1, ESI‡).¶ꢀ The same
conformation is adopted in the solid state, and bond lengths and
angles are comparable to those in 1·H2O (Table 1).
Fig. 1 peri-Substituted bissulfonylhydroxylamine 1 and bissulfonylni-
troxide 2.
On the one hand the constrained cyclic system was anticipated to
stabilise the bissulfonylnitroxide moiety: the initial fragmentation
should be less entropically favourable, and because the sulfonyl
radical and nitroso species cannot diffuse apart, the reverse
reaction4 should be favoured as it is now an intramolecular
cyclisation. However, it was also recognized that fragmentation
to release nitric oxide might also be favoured due to the potential
reduction in the peri-interaction between the two sulfonyl groups
through S–S bond formation.5
We have previously reported release and in situ capture of the
reactive diatomic molecule sulfur monoxide upon thermolysis of
a peri-substituted trisulfide-2-oxide.5 We therefore undertook a
study on the thermal stability of 1, a potential source of nitroxyl
(HNO)15 or hydroxynitrene (HON).16 Solutions of 1 in DMSO
and D2O remained unchanged after 3 months. Heating 1 in
solvents at increasing temperatures (t-BuOH at 83 ◦C, DMSO
at 100 ◦C, toluene at 110 ◦C, chlorobenzene at 132 ◦C) over
extended periods quantitatively returned starting material in all
Results and discussion
Synthesis and analysis of 1,8-bissulfonylhydroxylamine 1
Peri-substituted bissulfonylhydroxylamine 1 was prepared in two
steps from the known thiosulfonate 3 (Scheme 2).6,8 Oxidation of 3
to the sulfinyl sulfone 4 has been previously carried out using basic
hydrogen peroxide,9 and we found that urea–hydrogen peroxide
(UHP) is equally effective in this respect, providing 4 in more
reproducible yields. Treatment of 4 under nitrosylating conditions
gave formal nitrogen insertion into the sulfur–sulfur bond. This
reaction is presumed to occur through the capture of nitrosonium
with the bissulfinic acid 5, present through the known equilibrium
with 4 in the acidic, aqueous media.10
¶ Crystallographic data:1·H2O: C10H7NO5S2·H2O, M = 303.30, mono-
˚
˚
clinic, space group P21/n◦, T = 120 K, a = 6.9698(2) A, b = 9.4671(3) A,
◦
◦
3
˚
˚
c = 17.7500(4) A, a = 90 , b = 94.399(2) , g = 90 , V = 1167.76(6) A ,
Z = 4, 16422 reflections measured, 2668 unique (Rint = 0.0898) which were
used in all calculations. Final R1 (I > 2s(I)) = 0.0552, wR2 (all data) =
0.1599, goodness of fit = 1.082 on F2.1·EtOAc: C10H7NO5S2, C4H8O2,M =
˚
373.39, monoclinic, space group P21/n, T = 296(2) K, a = 14.1894(3) A,
◦
◦
◦
˚
˚
b = 7.1236(2) A, c = 18.0588(4) A, a = 90 , b = 112.627(1) , g = 90 ,
3
˚
V = 1684.87(7) A , Z = 4, 10441 reflections measured, 3067 unique (Rint
=
0.0385) which were used in all calculations. Final R1 (I > 2s(I)) = 0.0388,
wR2 (all data) = 0.1083, goodness of fit = 1.040 on F2.9: C18H19N3O5S2, M =
˚
421.48, monoclinic, space group P21/c, T = 173(2) K, a =◦15.1983(◦15) A,
◦
˚
˚
b = 8.5889(7) A, c = 15.6813(15) A, a = 90 , b = 95.42(1) , g = 90 , V =
3
˚
2037.8(3) A , Z = 4, 14029 reflections measured, 4719 unique (Rint = 0.0522)
which were used in all calculations. Final R1 (I > 2s(I)) = 0.0476, wR2
(all data) = 0.1069, goodness of fit = 1.080 on F2.12: C14H15NO5S2·H2O,
¯
˚
M = 359.41, triclinic, space group P1, T = 120(2) K, a = ◦12.042(1) A, b◦=
◦
˚
˚
13.397(1) A, c = 21.306(3) A, a = 72.268(7) , b = 81.717 (4) , g = 74.535(7) ,
3
˚
V = 3148.0(6) A , Z = 8, 28727 reflections measured, 10075 unique (Rint
=
0.1065) which were used in all calculations. Final R1 (I > 2s(I)) = 0.1509,
wR2 (all data) = 0.3157, goodness of fit = 1.094 on F2. The structure
contains four crystallographically-independent nitroxide molecules. The
crystal was the best quality that could be obtained but in spite of this the
diffraction data were weak, especially at higher angles and the agreement
statistics are rather high. These facts can be at least partially attributed to
the substantial levels of disorder in the structure.6·H2O: C6H5NO5S2·H2O,
¯
˚
M = 253.25, triclinic, space group P1, T = 120(◦2) K, a = 7.2877(3) A,
◦
˚
˚
b = 8.1680(3) A, c = 8.3571(2) A, a = 93.740(2) , b = 107.823(2) , g =
◦
3
˚
92.785(2) , V = 471.35(3) A , Z = 2, 8728 reflections measured, 2171
unique (Rint = 0.0425) which were used in all calculations. Final R1 (I >
2s(I)) = 0.0391, wR2 (all data) = 0.0918, goodness of fit = 1.076 on F2.
Scheme 2 Synthesis of peri-substituted bissulfonylhydroxylamine 1 and
proposed mechanistic intermediates.
ꢀ There is evidence of p–p stacking between aromatic ring systems in the
solid state X-ray crystal structure of 1·H2O, 1·EtOAc, 9, 12 and 6·H2O
in the chemical shifts of the aromatic protons in the 1H NMR of 1
observed upon dilution between 0.1 M and 0.01 M may be related to
increased intermolecular aromatic-aromatic interactions in solution at
higher concentration (see experimental for details).
˚
(average interplanar separations 3.3–3.6 A. Figs. S3–S7 ESI‡). Changes
The N,N-bissulfonylhydroxylamine 1 is a white crystalline solid,
and crystals suitable for X-ray diffraction analysis were obtained
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◦
˚
Table 1 Selected bond lengths (A) and angles ( ) for bissulfonylhydroxylamine derivatives from X-ray crystallographic data
Compound
1·H2O
1·EtOAc
9
12·H2Oa
6·H2O
14 (ref. 11) 15 (ref. 11) 16 (ref. 12) 17 (ref. 13)
Bond lengths
S–N
1.699(2)
1.718(2)
1.425(3)
1.703(2)
1.711(2)
1.423(2)
1.714(2)
1.719(2)
1.435(2)
1.66(1–3)
1.68(1–2)
1.41(1–7)
1.7215(19)
1.7411(19)
1.422(2)
1.71
1.72
1.41
1.73
1.75
1.42
1.71
1.71
1.33
1.75
1.72
1.42
N–O
Bond angles
S–N–S
O–N–S(1)
114.7(1)
106.2(1)
108.1(2)
329.0(1–2)
115.4(1)
107.3(1)
107.5(1)
330.2(1)
115.4(1)
105.2(1)
106.6(1)
327.2(1)
118(1–3)
100(1–3)
110(1–4)
328(1–4)
105.61(10)
106.77(13)
105.51(13)
317.89(10–13)
124.2
111.0
108.1
343.3
123.5
110.7
107.9
342.1
120.5
111.5
111.5
347.4
119.6
109.3
110.0
338.9
O–N–S(2)
ꢀ
Nb
Torsion angles
O–N–S–O
57.3(2)
54.0(2)
54.2(1)
61(1–4)
174(1–3)
53(1–4)
177(1–4)
-42.00(15)
-172.38(13)
39.85(15)
69.1
69.3
-31.6
97.1
50.4
100.0
-28.8
59.1
-175.9(1)
-53.4(2)
178.4(1)
-177.1(1)
-51.2(2)
-179.9(1)
-177.1(1)
-56.2(1)
176.6(1)
-163.4
-168.1
-41.0
-162.4
-167.9
-40.9
169.36(13)
178.5
-173.9
c,d
A ◊ ◊ ◊ napplane
S(1) ◊ ◊ ◊ napplane
S(2) ◊ ◊ ◊ napplane
N(1) ◊ ◊ ◊ napplane
0.17
0.09
0.60
0.15
0.03
0.64
0.05
0.04
0.70
0.1
0.3
0.6
0.08d
0.01d
0.62d
a Averages of parameters from the four crystallographically-independent molecules given. b Sum of bond angles at nitrogen. c Perpendicular distances
from mean plane through naphthalene. d For 6·H2O distances from mean plane through benzene given.
been reported to be thermally, base and water sensitive at room
temperature.2,17,18
The closely related cyclic, benzo-fused N,N-bissulfonyl-
hydroxylamine, N-hydroxy-O-benzenedisulfonimide (6), has been
reported to degrade upon prolonged standing at room temperature
and to slowly decompose in boiling water.19 This compound was
studied by Degani and Fochi et al. as an oxidising reagent for
organic synthesis.20 To further gauge the relative reactivity of 1
and 6, we ran a comparative sulfur oxidation under the conditions
reported for 6 (Scheme 3). Consistent with the literature,20 we
found that 6 effectively oxidises methyl phenyl sulfide to the
sulfoxide in 87% yield. In contrast, the naphthalene system 1 is
a less reactive oxidant, requiring 6 h to achieve a comparable 82%
yield of methyl phenyl sulfoxide. The novel sulfonic anhydride 7
was also isolated from this reaction, which presumably results from
hydrolysis of bissulfonamide 8, the expected product of oxygen
transfer from 1 to the sulfide.
Fig. 2 X-ray crystal structure of 1·H2O (hydrogen atoms and solvent
omitted for clarity).
The UV spectrum of N,N-bissulfonylhydroxylamine 1 shows an
absorbance at 298 nm (e 17700). However, 1 also proved stable to
irradiation in MeCN solution with a variety of light sources in
both quartz and Pyrex glassware (5 W low pressure and 125 W
medium pressure mercury arc lamps and a 500 W halogen lamp).
cases. Refluxing for 24 h in the presence of t-BuOK in t-BuOH,
or Et3N in dichloromethane, followed by reacidification again
returned starting material, suggesting 1 is stable to base. Finally,
1 proved to be hydrolytically stable in water, 1 M HCl and 1 M
NaOH over 24 h at reflux.
The high thermal and hydrolytic stability of 1 can be contrasted
with that of known N,N-bissulfonylhydroxylamines reported
in the literature. N,N-Bis(tolylsulfonyl)hydroxylamine has been
reported to be hydrolytically unstable, and breaks down slowly at
room temperature in CDCl3, accelerated in an oxygen atmosphere,
via the corresponding bissulfonylnitroxide radical.4 Other acyclic
N,N-bissulfonylhydroxylamines, both aryl and alkyl, have also
Nitroxide radical generation
The oxidation of hydroxylamines is a common method for
the synthesis of nitroxides, and has been successfully applied
in the study of acyclic N,N-bissulfonylhydroxylamines.2–4 How-
ever, TLC analysis of the reaction of hydroxylamine 1 with a
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Fig. 3 X-ray crystal structure of 9 (hydrogen atoms omitted for clarity).
Scheme 3 Comparative oxidation of methyl phenyl sulfide using cyclic
bissulfonylhydroxylamines.
substituent, similar to 1. Selected bond lengths and angles are
reported in Table 1.
wide variety of oxidants (Pd/C, PbO2,2,3,21 MnO2,22 Cu(OAc)2,23
Ce(NH4)4(SO4)4,4 Na2WO4·2H2O/H2O2,7 mCPBA) showed only
starting material, which could be reisolated in essentially quanti-
tative yield.
Notably, when the same conditions were applied to the benzo-
fused ring system 6, no compound analogous to 9 was isolated
and instead extensive decomposition of 6 occurred, again suggest-
ing that N,N-bissulfonylhydroxylamine 1 has a higher thermal
stability than 6.
In order to determine whether recovered starting material 1 in
these reactions was a consequence of a failure of the nitroxide 2
to form, or a result of in situ hydrogen atom abstraction by 2,
the reaction of 1 with excess CAN was monitored by EPR. A
three line spectrum was observed, consistent with formation of
nitroxide 2 (Fig. 4). Oxidation of 6 under the same conditions
gave a comparable aN value, which we assign to the novel nitroxide
10. The narrow spectral linewidths (DB1/2 = 0.32 G) enables
We also attempted formation of the nitroxide 2 through
radical-mediated hydrogen atom abstraction. Heating 1 with
benzoyl peroxide (benzene, reflux), di-tert-butoxydiazene (MeCN,
65 ◦C), or di-tert-butyl peroxydicarbonate (bromobenzene,
70 ◦C), or photoactivation of isoindoline nitroxide 1,1,3,3-
tetramethylisoindolin-2-yloxyl (TMIO) (benzene, 150 W medium
pressure Hg-arc lamp, pyrex, 7 h, rt)24 again did not show
formation of a new compound by TLC analysis. Use of Fenton
conditions (FeSO4·7H2O, DMSO, H2O2) to both generate the
nitroxide by hydrogen atom abstraction and trap it with methyl
radical also gave only starting material.
In only one case was a new product observed, when 1 was
heated with an excess of AIBN. Formation of the unusual imidate
9 can be rationalized by addition of 1 to the ketenimine formed
by the combination of two isobutyronitrile radicals (Scheme 4).25
The structure of 9 was confirmed by X-ray diffraction analysis
(Fig. 3).¶ꢀ The location of the imino double bond is indicated by
˚
the N(2)–C(11) bond length (1.255(3) A). The heterocyclic ring
again adopts a sofa conformation with a pseudo-axial oxygen
Fig. 4 (a) EPR spectra of 2 at 298 K in PhBr u = 9.446851 GHz; (b)
simulated EPR spectra of 2; (c) EPR spectra of 10 at 298 K in PhBr u =
9.440798 GHz; (d) simulated EPR spectra of 10.
Scheme 4 Reaction of 1 with AIBN.
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the observation of hyperfine coupling to the 15N nucleus (0.36%
natural abundance) as seen in Fig. 4 (expanded resonances). The
aN values for the cyclic nitroxides 2 and 10 lie in the range of EPR
data reported for acyclic bis(arylsulfonyl)nitroxides (aN/gb = 10 –
12G).2,4,26
bubbling oxygen through the solution gave the butyl-substituted
naphthalene 12 (Scheme 6). When this reaction was carried out
in the absence of oxygen, no transformation to 12 occurred,
and the starting material was recovered after acidic work-up.
The formation of 12 may be rationalized as occurring through
a homolytic aromatic substitution reaction.33 If deprotonation of
1 is slow, formation of a butyl radical by oxidation of BuLi can
result. The nucleophilic butyl radical adds to the naphthalene ring,
ortho to the activating sulfonyl group, and the resulting delocalized
radical 13 regains aromaticity through oxidation.34 The structure
of 12 was confirmed by X-ray crystallography (Fig. S2, ESI‡ and
Table 1).¶ꢀ The same product 12 was observed when the reaction
was carried out at room temperature, suggesting deprotonation is
particularly slow in the case of 1. An analogous transformation
does not occur for the benzo-fused N,N-bissulfonylhydroxylamine
6, with starting material returned upon acidic work-up.
The conversion of 1 to 2 was estimated to be 10% by EPR after
a single scan using TMIO as an internal standard.** Nevertheless,
repetition of these conditions on a preparative scale with 10 equiv.
of CAN in PhBr or benzene over extended time periods and at
temperatures up to reflux did not reveal the formation of any new
compound, with hydroxylamine 1 recovered qualitatively.
CAN is essentially insoluble in PhBr and benzene, and hence
the EPR experiment was repeated using the more soluble ceric
tetra-n-butylammonium nitrate27 (CTAN) in CH2Cl2 as solvent.
The initial conversion of 1 to 2 increased to 24%,** but on a
preparative scale (2 equiv. CTAN in CH2Cl2 or MeCN, rt–reflux)
only starting material 1 was recovered. Application of the same
conditions to 6 showed an 85% initial conversion to nitroxide 10 by
EPR,** but again only starting material was obtained on scale-up.
The EPR signals for 2 and 10 decayed over time (Fig. S8, ESI‡),
more rapidly when using CTAN in CH2Cl2, presumably due to a
more facile hydrogen abstraction from solvent or ammonium salt.
No EPR signal for 2 is observed with CAN in PhBr at 100 ◦C.
The reversible homolytic fission of O-benzylic alkoxy amines
to nitroxides and benzylic radicals is a widely used technique
for initiation of living radical polymerization,28 and has also
been applied by Studer et al. in small molecule synthesis,29 both
methodologies based on exploitation of the persistent radical
effect.30 We therefore undertook a study on the O-alkylation of 1
with a range of electrophiles. The resulting systems were envisioned
as being potential precursors to nitroxide 2.
O-Alkylation of 1 proceeded readily in acetone at rt in the
presence of K2CO3 (Scheme 5). The O-styryl compound 11b and
the O-fluorenyl compound 11d were both investigated as a means
to synthesise the nitroxide 2, through heating in tert-butyl benzene
in the presence of oxygen,31 however only starting material was
observed. In situ generation of nitroxide 2 would be evidenced
by the formation of tandem homolytic fission–radical cyclisation–
nitroxide capture products28 in the thermolysis of 11e, however
again no change occurred even upon prolonged heating in a sealed
tube of a t-BuOH solution at 200 ◦C for 32 h.
Scheme 6 Homolytic aromatic substitution of 1.
This final intriguing result led us to determine the X-ray crystal
structure of 6 (Fig. 5).¶ꢀ The heterocyclic ring adopts an envelope
conformation, with the two sulfur atoms essentially coplanar with
the benzene ring and the nitrogen at the flap of the envelope.
The hydroxyl group is pseudo-axial on the 5-membered ring
(O(5)-N(1)-S(1)-C(1) and O(5)-N(1)-S(2)-C(6) torsion angles
74.55(14)◦ and -76.54(14)◦ respectively), with the nitrogen lone-
pair again bisecting the O–S–O dihedral angle (Table 1).
A selection of bond lengths and angles for the novel bissul-
fonylhydroxylamine derivatives reported herein, along with data
for literature compounds 14–17,11–13 are reported in Table 1.
The degree of pyramidalization at the bissulfonamide nitrogen
ꢀ
is reflected in the sum of the bond angles N. The nitrogen atom
of the bicyclic compounds, most notably 6, are significantly more
pyramidalized than the acyclic systems 14–17. The idealised O–N–
S–O torsion angles where the nitrogen lone-pair bisects (gauche)
the O–S–O system are 60◦ and 180◦. These are most closely
matched in the naphthalene-based systems.
Scheme 5 O-Alkylation of 1.
A final attempt to generate nitroxide 2 through oxidation of
the corresponding lithium alkoxide32 gave an unexpected result.
◦
Attempted deprotonation of 1 at -78 C with BuLi followed by
Discussion
** Data obtained after a single scan due to the nitroxide signal for 2 or 10
decaying over time. % conversion = A/B ¥ 100, where A = calculated double
integration of unknown radical 2 or 10 (obtained by subtracting TMIO
standard from spectrum containing both radicals), and B = calculated
double integration of total spectrum.
The data presented above suggests that although nitroxides 2 and
10 cannot be classified as stable radicals by the Ingold definition,35
they have sufficient lifetime to be characterized by EPR. The
major degradation pathway of 2 and 10 appears to be hydrogen
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there are notable differences in the chemistry of their precursor
hydroxylamines 1 and 6. Hydroxylamine 1 is notably more stable
(less reactive) than 6, as evidenced by the isolation of 9, and
the more facile O-transfer from 6. The only exception appears
to be reaction with butyllithium and oxygen, where in the case
of 1 butylation of the naphthalene ring is observed, whereas no
analogous reaction occurs with 6. Here, however, the recovery
of 6 may be rationalized in two ways. Deprotonation of 6 may
occur, and the resulting alkoxide is oxidised to the nitroxide,
which abstracts a hydrogen to return 6 (or if oxidation does
not occur, 6 is formed through protonation of the alkoxide on
work-up). Alternatively the reaction may proceed initially as for
1: deprotonation is again slow so that butyl radical formation
occurs, however intermolecular homolytic aromatic substitution
is less likelyfor6thanfor 1, duetotheeaseofbreakingnaphthalene
aromaticity compared with an isolated benzene ring. Our available
data do not allow us to distinguish between these pathways.
At present we do not have a satisfactory explanation for the slow
deprotonation of 1 (and possibly 6) with butyllithium, although
the folded conformation of these molecules places the hydroxyl
group in the concave face of the molecule and hence deprotonation
may be kinetically disfavoured on steric grounds.
Fig. 5 X-ray crystal structure of 6·H2O (hydrogen atoms and solvent
omitted for clarity).
abstraction, as evidenced by the complete recovery of the precursor
hydroxylamines 1 and 6 under Ce(IV) oxidation conditions.
Fragmentation of the nitroxide to an N-sulfonylnitroso species
is either disfavoured or is rapidly reversible compared to hydrogen
abstraction, and so incorporation into a ring system does appear
to kinetically stabilise the nitroxide towards those degradation
pathways previously observed for this class of radical.2–4
Conclusions
The first study on the generation and stability of cyclic bis-
sulfonylnitroxides 2 and 10 has been reported. Use of a cyclic
system stabilises the radical towards fragmentation, the major de-
composition pathway for acyclic bissulfonylnitroxides. Hydrogen
atom abstraction by the radicals 2 and 10 is evidenced by the
complete recovery of the precursor hydroxylamines under Ce(IV)
oxidation conditions, where formation of the nitroxide has been
demonstrated by EPR. The high thermal, photochemical and
hydrolytic stability of N,N-bissulfonylhydroxylamine 1, its ease
of functionalisation, and the apparent reactivity of the nitroxides
2 and 10 towards hydrogen atom abstraction, may lead to new
applications in organic chemistry.
The lack of formation of nitroxide 2, or any products derived
thereof, from the attempted thermolysis of 11 reflects the high
C–O bond dissociation energy in these alkoxyamines. Since
other alkoxylamines undergo homolytic fission with the same
benzylic carbon substituents,28–30 nitroxide 2 must therefore be less
thermodynamically stable than a typical alkyl or aryl-substituted
nitroxide.
Nitroxide radicals are stabilised by the interaction of the
nitrogen lone pair with the SOMO of the oxygen centred radical,
which can be represented in the present case by the two resonance
forms A and B. Resonance form B is destabilised relative to A as
a result of the electron-withdrawing nature of the sulfonyl groups.
Previous studies on sulfonyl-substituted nitroxides have noted the
relatively largeaN values, also seen for 2 and 10, compared with acyl
nitroxides (aN 4–8). For resonance contributor B, delocalisation of
the unpaired electron into the sulfonyl group is negligible because
of poor orbital overlap. In contrast, with acyl nitroxides, the lone
pair of the nitrogen is conjugated with the carbonyl leading to
lower spin density on the nitrogen and hence smaller aN values.26,36
Experimental
General
1H and 13C NMR data were recorded on a Bruker AC300, Bruker
AVIII300, Bruker AV400 or a Bruker AMX400 spectrometer.
Spectra were recorded in CD2Cl2 referenced to residual CH2Cl2
(1H, 5.33 ppm), CD3CN referenced to residual CH3CN (1H,
1.92 ppm; 13C, 1.2 ppm), DMSO-d6 referenced to residual DMSO
(1H, 2.50 ppm) and CDCl3 referenced to residual CHCl3 (1H,
7.26 ppm; 13C, 77.0 ppm). Chemical shifts are reported in ppm
(d) and coupling constants (J) are reported in Hz. The following
abbreviations are used to describe multiplicity; s-singlet, d-
doublet, t-triplet, m-multiplet. Mass spectra were recorded on
either a LCT spectrometer or an Agilent QTOF LC/MS 6520
utilising electrospray ionisation (recorded in the positive mode)
with a methanol mobile phase, or electron impact ionisation,
and are reported as (m/z (%)). HRMS were recorded on a LCT
spectrometer using lock mass incorporated into the mobile phase.
IR spectra were recorded as KBr disks or neat on a Perkin
Elmer 1600 series FT-IR Perkin Elmer FT-IR Paragon 1000,
Nitroxides having electron-withdrawing groups on nitrogen,
particularly acyl nitroxides, are generally more reactive than
nitroxides flanked by alkyl groups. These systems have high spin
density on the nitroxide oxygen and high O–H bond dissociation
energies in the corresponding hydroxylamine, which has led to
their investigation as oxidants in organic chemistry through C–H
abstraction.37
Although both nitroxides 2 and 10 behave similarly in under-
going hydrogen atom abstraction in preference to fragmentation,
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◦
Perkin Elmer 100-series FT-IR or a Nicolet 870 Nexus FT-IR
spectrometer. UV/Vis spectra were recorded on a UV-3101PC
Shimadzu spectrophotometer. Melting points were determined
using open glass capillaries on a Gallenkamp melting point
apparatus and are uncorrected. Elemental analyses were carried
out by the University of Queensland Microanalytical Service.
Analytical TLC was carried out on Merck 60 F245 aluminium
backed silica gel plates. Short wave UV (245 nm), KMnO4 or
anisaldehyde were used to visualise components. Compounds
were purified by flash column chromatography using Merck silica
gel 60. Continuous wave X-band EPR spectra were recorded
with a Bruker Biospin Elexsys E580 EPR spectrometer fitted
with a super high Q cavity or a Bruker EMX-AR spectrometer
operating at X-band frequencies (ca 9.2–9.8 GHz) with 100
kHz field modulation. Magnetic field and microwave frequency
calibration were achieved with a Bruker ER 036M Teslameter
and a Bruker microwave frequency counter, respectively or a
Bruker ER 035M NMR gaussmeter and a Hewlett–Packard
5350B frequency counter respectively. Spectrometer tuning, signal
averaging and subsequent spectral comparisons were performed
with Bruker’s Xepr (version 2.6) software. Computer simulation
of the EPR spectra were performed using the XSophe-Sophe-
XeprView computer simulation software suite (v 1.1.4) running
on PC utilizing Mandriva 2009.1 as the Linux operating system.38
Naphthothiosulfonate 3 was prepared by oxidation of the
corresponding disulfide.6,39 (1-Bromohex-5-en-1-yl)benzene was
prepared by modification of a literature procedure.40 CTAN was
prepared by the literature procedure.27 All other compounds are
commercially available and were used as received. Reactions were
run in oven dried glassware under an argon atmosphere. Solvents
were purified and dried using standard methods.
solid. Rf 0.33 (7 : 3 Et2O–hexane); mp 167–169 C (EtOAc); lmax
(MeCN)/nm 298 (e/dm3 mol-1 cm-1 17 700); vmax (KBr)/cm-1 3535
(OH), 3092 (CH), 2862, 1497, 1380, 1361 (SO2N), 1220, 1191, 1174
(SO2N), 1156, 902, 846 (SO2) and 829; dH(300 MHz; CD3CN, 0.1
M) 7.91 (2 H, dd, J 8.3 and 7.5, SCCHCH), 8.44 (2 H, dd, J 8.5
and 1.0, SCCH), 8.49 (2 H, dd, J 7.4 and 1.1, SCCCCH) and 9.99
(1 H, s, NOH); dH(300 MHz; CD3CN, 0.01 M) 7.93 (2 H, dd, J
8.3 and 4.4, ArH), 8.47 (4H, dd, J 8.0 and 1.0, ArH), 8.50 (2 H,
dd, J 7.4 and 1.1, ArH) and 9.85 (1 H, s, NOH); dH(300 MHz;
CD2Cl2) 7.90 (2 H, t, J 7.8, ArH), 8.37 (2 H, d, J 8.4, ArH),
8.49 (2 H, d, J 7.4, ArH) and 8.60 (1 H, s, NOH); dH(300 MHz;
DMSO-d6) 8.62 (2 H, d, J 8.3, ArH), 8.60 (2 H, d, J 7.4, ArH)
and 8.02 (2 H, t, J 7.8, ArH); dC(100 MHz; CD3CN) 120.8 (SCC),
128.1 (SCCHCH), 129.7 (C), 130.9 (SCCCCH), 134.1 (C) and
136.9 (SCCH); m/z (ESI) 307.9669 ([M + Na]+, C10H7NO5S2Na
requires 307.9663), 308 (100%).
Oxidation of methyl phenyl sulfide with 1. Isolation of
3-oxa-1,3-dithiaphenalene 1,1,3,3-tetraoxide (7)
Thioanisole (8.57 mL, 0.073 mmol) was heated in acetic acid
(0.15 mL) at 60 ◦C. A solution of bissulfonylhydroxylamine 1
(20 mg, 0.070 mmol) in MeCN (0.15 mL) was added dropwise
◦
over a period of 30 min. The solution was heated at 60 C for a
2 h. Additional bissulfonylhydroxylamine 1 (5 mg, 0.017 mmol)
was added as a solid to the mixture and heating continued for
a further 4 h at 60 ◦C. The mixture was washed with water
(3 ¥ 3 mL), 5% NaOH solution (3 ¥ 3 mL) and extracted with
EtOAc (3 ¥ 5 mL). The combined organic phases were dried over
MgSO4 and concentrated under reduced pressure. Purification by
column chromatography (7 : 3 Et2O–hexane) yielded 3-oxa-1,3-
dithiaphenalene 1,1,3,3-tetroxide (7) (16 mg, 85%) as a white
solid. Further elution (Et2O) afforded methyl phenyl sulfoxide
(8 mg, 82%). 7: Rf 0.58 (7 : 3 Et2O–hexane); mp 211–213 ◦C;
vmax (KBr)/cm-1 3076, 1400, 1384, 1370, 1344, 1180 and 1147;
dH(300 MHz; CDCl3) 7.89 (2 H, dd, J 8.3 and 7.5, ArH) and 8.35 (2
H, dd, J 8.5 and 1.0, ArH) and 8.43 (2 H, dd, J 7.4 and 1.1, ArH);
dC(100 MHz; CDCl3) 119.9 (C), 127.0 (CH), 128.5 (CH), 130.5
(C), 133.1 (C), and 135.4 (CH); m/z (ESI) 292.9551 ([M + Na]+,
C10H6O5S2Na requires 292.9554), 292.8 (100%). Methyl phenyl
sulfoxide: Rf 0.10 (7 : 3 Et2O–hexane); mp 29–31 ◦C; dH(300 MHz;
CDCl3) 2.75 (3 H, s, CH3) and 7.54–7.70 (5 H, m); dC(75 MHz;
CDCl3) 45.9 (CH3), 127.4 (2 ¥CH), 128.9 (2 ¥ CH), 132.7 (CH)
and 143.2 (C).
Naphtho[1,8-c,d][1,2]dithiole 1,1,2-trioxide (4)
Thiosulfonate 3 (604 mg, 2.72 mmol) was dissolved in dioxane
(4.34 mL) and a solution of UHP (1.12 mL, 4.08 mmol) and NaOH
(331 mg, 8.28 mmol) in water (2.88 mL) was added. The mixture
was stirred for 15 min and evaporated to dryness. The resulting
disodium salt was dissolved in H2O (2.17 mL) and acidified slowly
with conc. HCl to pH<1. The resulting white solid was filtered and
recrystallised from hot CH2Cl2–hexane to give sulfinyl sulfone 4
(470 mg, 73%). Rf 0.61 (8 : 2 CH2Cl2–hexane); mp 148–150 ◦C
(CH2Cl2–hexane) (lit.,9 168–169 ◦C); vmax (KBr)/cm-1 3077, 1489,
1404, 1345, 1313 (SO2), 1182, 1152 (SO2), 1134 (SO2) and 1083
(SO); dH(300 MHz; CDCl3) 7.85–7.92 (2 H, m, ArH), 8.18 (1 H,
d, J 7.3, ArH) and 8.25–8.28 (3 H, m, ArH); dC(75 MHz; CDCl3)
123.9 (CH), 125.8 (C), 2 ¥ 128.6 (CH), 129.8 (CH), 132.4 (C), 132.9
(CH), 133.1 (CH), 135.5 (C) and 137.4 (C); m/z (ESI) 260.9651
([M + Na]+, C10H6NO3S2Na requires 260.9656), 260.9 (100%).
(Z)-1,1,3,3-Tetraoxidonaphtho[1,8-d,e][1,3,2]dithiazin-2-yl
N-(2-cyanopropan-2-yl)isobutyimidate (9)
A solution of AIBN (17 mg, 0.105 mmol) and bissulfonylhydrox-
ylamine 1 (10 mg, 0.035 mmol) in bromobenzene (1.06 mL) was
heated at reflux for 24 h. The solution was allowed to cool to
room temperature and was purified by column chromatography
(2 : 1 EtOAc–hexane) to afford 9 (12 mg, 81%) as a white solid.
Rf 0.50 (1 : 1 EtOAc–hexane); mp 170–172 ◦C (CH2Cl2); found:
C, 51.25; H, 4.4; N, 9.8; S, 15.35. C18H19N3O5S2 requires C, 51.3;
H, 4.5; N, 10.0; S, 15.2%; vmax (neat)/cm-1 2971, 2925, 2233, 1700,
1559, 1497, 1392, 1373, 1364, 1219, 1189, 1177, 1160, 1151, 1116
and 1076; dH(400 MHz; CDCl3) 8.48 (2 H, d, J 7.2, ArH), 8.34 (2
H, d, J 8.2, ArH), 7.87 (2 H, t, J 7.8, ArH), 3.35 (1 H, septet, J
2-Hydroxynaphtho[1,8-de][1,3,2]dithiazine 1,1,3,3-tetraoxide (1)
Naphtho[l,8-cd][l,2]dithiole l,l,2-trioxide (4) (258 mg, 1.08 mmol)
and NaNO2 (75.0 mg, 1.08 mmol) were dissolved in a mixture
of H2O (4.82 mL) and 1,4-dioxane (4.82 mL). Conc. HCl
(386 mL) was added dropwise at room temperature and the
solution was stirred overnight. The resulting precipitate was
filtered and recrystallised from hot EtOAc (~3 mL) yielding
bis(sulfonyl)hydroxylamine 1 (0.212 g, 69%) as a white, crystalline
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6.6, CH(CH3)2), 1.25 (6 H, d, J 6.6, CH(CH3)2) and 1.17 (6 H, s,
NCC(CH3)2); dC(100 MHz; CDCl3) 161.7 (C), 136.0 (CH), 133.3
(C), 130.2 (CH), 129.6 (C), 126.9 (CH), 121.3 (C), 120.5 (C), 47.9
(C), 29.7 (CH), 28.9 (CH3) and 20.4 (CH3); m/z (ESI) 444.0674
([M + Na]+, C18H19N3O5S2Na requires 444.0658), 444 (69%), 422
(100), 338 (34) and 282 (25).
Rf 0.52 (1 : 1 hexane–EtOAc); mp 232–234 ◦C; vmax (neat)/cm-1
3091, 1496, 1421, 1388, 1368, 1188, 1173 and 1147; dH(300 MHz;
CDCl3) 8.45 (2 H, dd, J 7.4 and 1.2, ArH), 8.29 (2 H, dd, J 8.4
and 1.1, ArH), 7.85 (1 H, d, J 7.5, ArH), 7.83 (1 H, d, J 7.5, ArH),
5.86–6.00 (1 H, m, CH2CH), 5.29–5.39 (2 H, m, OCH2) and 4.79
(2 H, dt, J 6.8 and 0.9, CH CH2); dC(100 MHz; CDCl3) 135.3
(CH), 133.2 (C), 130.5 (C), 130.1 (C), 129.6 (CH), 126.8 (CH),
122.3 (CH2), 120.4 (CH) and 81.2 (CH2); m/z (EI) 347.9980 ([M +
Na]+, C13H11NO5S2Na requires 347.9976), 488 (100%).
O-Alkylation of 1: General procedure
To a solution of 1 (1 eq) in acetone (0.05 M) was added potassium
carbonate (1.5 eq) followed by alkyl halide (10 eq) at room
temperature. After stirring for 16 h the solvent was removed
under reduced pressure. The residue was dissolved in EtOAc and
washed with water. The organic phase was dried over Na2SO4 and
concentrated under reduced pressure. The O-alkylated product 11
was purified by column chromatography.
2-((9H-Fluoren-9-yl)oxy)naphtho[1,8-de][1,3,2]dithiazine
1,1,3,3-tetraoxide (11d)
Following the general procedure, 1 (100 mg, 0.35 mmol), potas-
sium carbonate (73 mg, 0.53 mmol) and bromofluorene (860 mg,
0.35 mmol) in acetone (7 mL) afforded 11d (56 mg, 36%) as a
white solid after column chromatography (1 : 1 hexane–EtOAc).
Rf 0.48 (1 : 1 hexane–EtOAc); mp 224–226 ◦C; vmax (neat)/cm-1
3081, 1494, 1453, 1382, 1367, 1192, 1173 and 1155; dH(300 MHz;
CDCl3) 8.44 (2 H, dd, J 7.4 and 1.1, ArH), 8.24 (2 H, dd, J 8.4
and 0.9, ArH), 7.81 (1 H, d, J 7.6, ArH), 7.79 (1 H, d, J 7.7,
ArH), 7.72 (2 H, d, J 7.6, ArH), 7.56 (2 H, d, J 7.6, ArH), 7.37 (1
H, d, J 6.8, ArH), 7.35 (1 H, d, J 6.8, ArH), 7.23 (2 H, td, J 7.5
and 1.0, ArH) and 6.39 (1 H, s, CH); dC(100 MHz; CDCl3) 141.2
(C), 139.4 (C), 135.3 (CH), 133.2 (C), 131.7 (C), 130.2 (CH), 129.6
(CH), 127.5 (CH), 127.4 (CH), 126.8 (CH), 120.3 (C), 119.9 (CH)
and 89.3 (CH); m/z (ESI) 472.0293 ([M + Na]+, C23H15NO5S2Na
requires 472.0289), 472 (100%).
2-Methoxynaphtho[1,8-de][1,3,2]dithiazine 1,1,3,3-tetraoxide
(11a)
Following the general procedure, 1 (100 mg, 0.35 mmol), potas-
sium carbonate (73 mg, 0.53 mmol) and methyl iodide (0.22 mL,
3.50 mmol) in acetone (7 mL) afforded 11a (62 mg, 61%) as a
white solid after column chromatography (1 : 1 hexane–CH2Cl2).
Rf 0.78 (1 : 1 hexane–CH2Cl2); mp 178–180 ◦C; lmax (MeCN)/nm
298 (e/dm3 mol-1 cm-1 31 300); vmax (neat)/cm-1 3094, 1381, 1362,
1188, 1173 and 1153; dH(300 MHz; CDCl3) 8.46 (2 H, dd, J 7.5
and 1.7, ArH), 8.30 (2 H, dd, J 8.5 and 1.1, ArH), 7.86 (1 H, d,
J 7.5, ArH), 7.84 (1 H, d, J 7.5, ArH) and 4.09 (3 H, s, OCH3);
dC(100 MHz; CDCl3) 135.4 (CH), 133.20 (C), 130.0 (C), 129.7
(CH), 126.9 (CH), 120.5 (C) and 67.4 (CH3); m/z (EI) 298.9911
(M+, C11H9NO5S2 requires 298.9922), 299 (83%), 284 (41), 269
(100), 255 (28), 254 (42), 206 (92), 190 (48), 174 (86), 162 (63), 134
(61), 126 (27), 114 (40) and 102 (28).
2-((1-Phenylhex-5-en-1-yl)oxy)naphtho[1,8-de][1,3,2]dithiazine
1,1,3,3-tetraoxide (11e)
Following the general procedure, 1 (20 mg, 0.07 mmol), potas-
sium carbonate (14 mg, 0.11 mmol) and (1-bromohex-5-en-1-
yl)benzene (168 mg, 0.70 mmol) in acetone (1.4 mL) afforded
11e (28 mg, 90%) as a white solid after column chromatography
(1 : 1 hexane–EtOAc). Rf 0.50 (1 : 1 hexane–EtOAc); mp 144–146
◦C; vmax (neat)/cm-1 2929, 1496, 1391, 1372, 1221, 1191, 1175 and
1151; dH(300 MHz; CDCl3) 8.38–8.43 (2 H, m, ArH), 8.19 (2 H,
dd, J 8.3 and 0.8, ArH), 7.76 (2 H, t, J 7.7, ArH), 7.27–7.34
(5 H, m, ArH), 5.61–5.75 (1 H, m, CH2 CH), 5.29–5.34 (1 H,
m, OCH), 4.87–4.95 (2 H, m, CH CH2), 2.18–2.30 (1 H, m,
0.5 ¥ OCHCH2), 1.97–2.05 (2 H, m, CH2 CHCH2), 1.81–1.89
(1 H, m, 0.5 ¥ OCHCH2) and 1.12–1.31 (2 H, m, CH2CH2CH2);
dC(100 MHz; CDCl3) 138.1 (CH), 136.9 (C), 135.3 (CH), 133.1 (C),
130.4 (C), 129.4 (CH), 129.1 (CH), 128.9 (CH), 128.3 (CH), 126.7
(CH), 120.3 (C), 114.9 (CH2), 92.1 (CH), 33.4 (CH2), 32.5 (CH2)
and 24.7 (CH2); m/z (ESI) 466.0747 ([M + Na]+, C22H21NO5S2Na
requires 466.0759), 466 (100%).
2-(1-Phenylethoxy)naphtho[1,8-de][1,3,2]dithiazine
1,1,3,3-tetraoxide (11b)
Following the general procedure, 1 (50 mg, 0.18 mmol), potas-
sium carbonate (36 mg, 0.26 mmol) and 1-bromoethylbenzene
(0.24 mL, 1.75 mmol) in acetone (3.5 mL) afforded 11b (64 mg,
94%) as a white solid after column chromatography (1 : 1 hexane–
EtOAc). Rf 0.30 (1 : 1 hexane–EtOAc); mp 129–131 ◦C; vmax
(neat)/cm-1 2935, 1496, 1386, 1366, 1189, 1173 and 1149;
dH(300 MHz; CDCl3) 8.41 (2 H, d, J 6.7, ArH), 8.19 (2 H, dd, J
8.4 and 0.9, ArH), 7.76 (2 H, t, J 7.8, ArH), 7.27–7.37 (5 H, m,
ArH), 5.55 (1 H, q, J 6.6, OCH) and 1.77 (3 H, d, J 6.6, OCCH3);
dC(100 MHz; CDCl3) 138.2 (C), 135.20 (CH), 133.1 (C), 130.2
(C), 129.4 (CH), 128.9 (CH), 128.3 (CH), 128.0 (CH), 126.7 (CH),
120.3 (C), 87.7 (CH) and 19.2 (CH3); m/z (EI) 412.0295 ([M +
Na]+, C18H15NO5S2Na requires 412.0289), 482 (30%), 467 (12),
466 (100), 428 (18) and 412 (63).
4-Butyl-2-hydroxynaphtho[1,8-de][1,3,2]dithiazine
1,1,3,3-tetraoxide (12)
A solution of n-BuLi in hexanes (1.69 M, 0.04 mL, 0.07 mmol) was
added dropwise to a stirred solution of bissulfonylhydroxylamine
1 (20 mg, 0.07 mmol) in THF (0.7 mL) and pentane (0.7 mL)
2-(Allyloxy)naphtho[1,8-de][1,3,2]dithiazine 1,1,3,3-tetraoxide
(11c)
◦
Following the general procedure, 1 (50 mg, 0.18 mmol), potassium
carbonate (36 mg, 0.26 mmol) and allyl bromide (0.15 mL,
1.75 mmol) in acetone (3.5 mL) afforded 11c (47 mg, 83%) as
a white solid after column chromatography (1 : 1 hexane–EtOAc).
at -78 C. After stirring for 30 min at the same temperature, O2
was bubbled through the solution for 5 min. The mixture was
stirred under an oxygen atmosphere for 16 h, warming to room
temperature. The mixture was washed with water (3 ¥ 3 mL) and
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extracted with EtOAc (3 ¥ 5 mL). The combined organic phases
were dried over MgSO4 and concentrated under reduced pressure.
Purification by column chromatography afforded 12 (11 mg, 46%)
as a white solid. Rf 0.60 (7 : 3 EtOAc–hexane); mp 86–88 ◦C
(CH2Cl2); vmax (neat)/cm-1 3607, 3538, 2961, 2932, 2861, 1498,
1466, 1388, 1368, 1188, 1170, 1161 and 1105; dH(300 MHz; CDCl3)
8.44 (1 H, dd, J 7.4 and 1.2, ArH), 8.20 (1 H, dd, J 8.2 and 1.1,
ArH), 8.14 (1 H, d, J 8.5, ArH), 7.73 (1 H, t, J 7.8, ArH), 7.68
(1 H, d, J 8.5, ArH), 3.29–3.34 (2 H, m, CH2), 1.75–1.86 (2 H, m,
CH2), 1.53 (2 H, sextet, J 7.4, CH2) and 0.99 (3 H, t, J 7.4, CH3);
dC(75 MHz; CDCl3) 147.4 (C), 135.5 (CH), 134.1 (CH), 132.0 (C),
131.0 (CH), 130.0 (CH), 128.3 (C), 127.9 (C), 125.4 (CH), 121.8
(C), 35.1 (CH2), 33.4 (CH2), 22.9 (CH2) and 13.8 (CH3); m/z (EI)
364.0279 ([M + Na]+, C14H15NO5S2Na requires 364.0289), 364
(100%).
13 V. K. Brink and R. Mattes, Acta Crystallogr., Sect. C: Cryst. Struct.
Commun., 1986, 42, 1625–1627.
14 For discussion on possible stabilising effects see: (a) A. R. Modarresi-
Alam, H. A. Amirazizi, H. Bagheri, H.-R. Bijanzadeh and E. Klein-
peter, J. Org. Chem., 2009, 74, 4740–4746; (b) P. V. Bharatam, Armita,
A. Gupta and D. Kaur, Tetrahedron, 2002, 58, 1759–1764; (c) L. A.
Paquette, C. S. Ra, J. D. Schloss, S. M. Leit and C. Judith Gallucci,
J. Org. Chem., 2001, 66, 3564–3573.
15 K. M. Miranda, Coord. Chem. Rev., 2005, 249, 433–455.
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We thank the EPSRC (EP/C543122/1 Advanced Research Fel-
lowship 2005–2010 to RSG, EP/C543130/1 studentship and PhD
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of Excellence for Free Radical Chemistry and Biotechnology
(CEO 561607) for funding. We thank the UK National Crystal-
lography Service for X-ray diffraction data collection for 1.H2O,
12 and 6.H2O. The NMR spectrometers used in this research were
obtained through Birmingham Science City: Innovative Uses for
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2344 | Org. Biomol. Chem., 2011, 9, 2336–2344
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