Photochemistry of N-Arylsulfonimides: An Easily Available Class of Nonionic Photoacid Generators (PAGs)

Article abstract of DOI:10.1002/chem.201603522

The photochemical behavior of differently substituted N-arylsulfonimides was investigated. Homolysis of the S?N bond took place as the exclusive path from the singlet state to afford both N-arylsulfonamides and photo-Fries adducts, the amount of which depended on reaction conditions and aromatic substituents. Sulfinic and sulfonic acids were released upon irradiation under deaerated and oxygenated conditions, respectively. The nature of the excited states and intermediates involved were proved by laser flash photolysis and EPR experiments. These results highlighted the potential of such compounds as nonionic photoacid generators able to photorelease up to two equivalents of a strong acid for each mole of substrate.

Full text of DOI:10.1002/chem.201603522

DOI: 10.1002/chem.201603522
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Reaction Mechanisms |Hot Paper|
Photochemistry of N-Arylsulfonimides: An Easily Available Class
of Nonionic Photoacid Generators (PAGs)
Edoardo Torti,[a] Stefano Protti,[a] Daniele Merli,[b] Daniele Dondi,[b] and Maurizio Fagnoni*[a]
Abstract: The photochemical behavior of differently substi-
tuted N-arylsulfonimides was investigated. Homolysis of the
SÀN bond took place as the exclusive path from the singlet
state to afford both N-arylsulfonamides and photo-Fries ad-
ducts, the amount of which depended on reaction condi-
tions and aromatic substituents. Sulfinic and sulfonic acids
were released upon irradiation under deaerated and oxygen-
ated conditions, respectively. The nature of the excited
states and intermediates involved were proved by laser flash
photolysis and EPR experiments. These results highlighted
the potential of such compounds as nonionic photoacid
generators able to photorelease up to two equivalents of
a strong acid for each mole of substrate.
Introduction
The photorelease of acids (especially strong sulfonic acids) is
widely recognized as an important tool in materials science
and micro-/nanoelectronics.[1] Aromatic iodonium or sulfonium
salts are known to be excellent photoacid generators (PAGs),[2]
but their thermal stability is, in some cases, counterbalanced
by their limited solubility in polymer matrices,[3] which makes
the development of nonionic PAGs desirable. Likewise, a deep
understanding of the mechanism involved in the release of the
acidic moiety from these substrates is fundamental for devel-
oping new and more efficient PAGs.
Scheme 1. Possible mechanisms of photorelease of sulfonic acids from non-
ionic PAGs.
The mechanism of photorelease of sulfonic acids in (com-
mercially available) nonionic PAGs may follow different path-
ways, as summarized in Scheme 1.[4] The homolytic cleavage of
the OÀN bond in iminosulfonates A[5] or imidosulfonates B[6,7]
lent of acid, through either multi-[10] or one-photon process-
es,[11] have been reported.
C
generates a sulfonyloxy radical (C ), which, upon hydrogen ab-
straction, gives the desired sulfonic acid. Recently, we discov-
ered that the photoheterolytic cleavage of the ArÀO bond in
electron-rich aryl mesylates and triflates (D) released the same
strong acids.[8] However, photolysis of other sulfonates, such as
aryl tosylates D’ (R=Ar’), takes place through homolysis of the
We report herein a new class of potential nonionic PAGs
able to release one (or more) equivalent(s) of strong sulfonic
acids smoothly, namely, N-arylsulfonimides 1a–j. Compounds
belonging to this class were recently investigated as potential
inhibitors of tryptophan-2,3-dioxygenase in cancer therapy,[12]
as hepatitis C virus inhibitors,[13] and as herbicides.[14] In the
field of organic synthesis, the sulfonyl group is currently adopt-
ed to protect the amino group.[15] However, to the best of our
knowledge, the potential of sulfonimides as PAGs was prelimi-
nary investigated only by Sasaki and Kawamura, who reported
the release of variable amounts of sulfonic and sulfinic acids
(depending on the reaction conditions) from both alkyl- and
phenyl-substituted sulfonimides.[16]
ArOÀS bond,[9] and the thus-formed sulfonyl radical (E ) gives
C
a sulfonic acid through the addition of oxygen present in solu-
tion (Scheme 1). In all of the abovementioned cases, one
equivalent of acid is released per equivalent of PAG. In a few
cases, however, PAGs able to generate more than one equiva-
[a] E. Torti, Dr. S. Protti, Prof. M. Fagnoni
Department of Chemistry, PhotoGreen Lab
University of Pavia, V.Le Taramelli 10, 27100 Pavia (Italy)
E-mail: fagnoni@unipv.it
N-Arylmethanesulfonimides with different aromatic substitu-
ents (1a–g) were initially tested, along with trimethylphenyl
derivative 1h, N-(4-acetylphenyl)-N-(p-tolylsulfonyl)-p-toluene-
sulfonamide (1i), and N-(4-acetylphenyl)-1,1,1-trifluoro-N-[(tri-
fluoromethyl)sulfonyl]methanesulfonamide (1j).
[b] Dr. D. Merli, Dr. D. Dondi
Department of Chemistry, University of Pavia
V. Le Taramelli 10, 27100 Pavia (Italy)
Supporting information for this article and ORCID(s) of the author(s) are
available on the WWW under http://dx.doi.org/10.1002/chem.201603522.
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compounds 1a–j showed two absorption maxima in the UV
region at lꢀ250–300 and 210–240 nm, with the exception of
1g and 1i, which exhibited single absorption bands at l=260
and 240 nm, respectively (Figures S1–S10 in the Supporting In-
formation). All of the sulfonimides tested showed a low (FF <
0.02) or negligible fluorescence emission, except for cyano de-
rivative 1e (FF ꢀ0.1). In view of the satisfactory F value ob-
À1
tained for 1b, photochemical experiments on 1a–j were car-
ried out in deaerated acetonitrile. As depicted in Table 2, a com-
plex mixture of desulfonylated derivatives 2 and 5 and Fries
adducts 3, 4 and 6 resulted, along with sulfonyl anilines 7. All
of the p-substituted derivatives 1a–g were consumed, with
a disappearance quantum yield FÀ1 >0.1; amino and acetyl
derivatives 1a and 1 f were the most reactive in the series
Results
(F ca. 0.3), whereas 1g was an exception (almost photosta-
À1
ble).
Photochemical experiments on 1a–j
Potentiometric titration and ionic chromatography analyses
were also carried out on the resulting solutions (Figures S13–
S31 in the Supporting Information). Sulfinic acids were the
only acid formed and their amount was comparable to that of
desulfonylated products 2, 4, and 5. To hamper the formation
of Fries adducts and to increase the release of acids, we tested
methanesulfonimide 1h, in which the ortho and para positions
had methyl groups. As expected, no ArÀS bonds were formed
in the reaction and only compounds 2h and 5h were ob-
tained, along with 71% yield of CH3SO2H (Table 2). We then
The examined sulfonimides were easily prepared from the cor-
responding anilines (see the Supporting Information for further
details). Preliminary irradiation experiments (l=254 nm, 2 h)
were carried out on compound 1b in medium to polar sol-
vents under deaerated conditions (Table 1). Good photoreactiv-
ity for such a substrate was observed in THF, ethyl acetate, and
acetonitrile (F in the 0.1–0.2 range). The presence of protic
À1
solvents (MeOH or water) did not increase the consumption of
1b, which was photostable in acetone. The product distribu-
tion is quite complex and all of the compounds formed arose
from the cleavage of the NÀS bond, as in the case of desulfo-
nylated derivatives 2b and 5b, or from a photo-Fries rear-
rangement (products 3b, 4b, and 6b). The presence of
a protic medium, however, increased the amounts of desulfo-
nylated adducts (Table 1).
tested compounds 1i and 1j. In both cases, the F value was
À1
in the same order as that observed for 1 f (ca. 0.25). The pho-
tochemical behavior of 1i was very similar to that of 1 f (and
included ipso-substituted adduct 7i) and a significant amount
of p-toluenesulfinic acid (along with traces of acetic acid) was
detected by chromatographic analyses. In contrast, no Fries re-
arrangement was observed in the case of compound 1j, and
a mixture of weak acids (H2SO3 and HF) was released in place
of expected CF3SO2H (Table 2). Gaseous fluoroform (CHF3) and
hexafluoroethane were also revealed in this photo-
lyzed solution by means of IR and GC-MS analyses
(see Figures S11 and S12 in the Supporting Informa-
tion).[8]
With these positive results in hand, we extended our investi-
gation to other sulfonimides. For the photophysical properties
(see Table S1 in the Supporting Information for further details),
Table 1. Irradiation of sulfonimide 1b in neat solvents.[a]
Photolysis of compounds 1a–j was then repeated
under oxygenated conditions (Table 3). As it is appar-
ent from comparing the results in Tables 2 and 3, the
presence of oxygen did not affect the F value. The
À1
scenario dramatically changed, however, upon ana-
lyzing the amount and nature of the acids released.
Methanesulfonic acid (up to two equivalents) was
formed from compounds 1a–h and, similarly, a quan-
titative amount of p-toluenesulfonic acid was re-
leased from 1i. In the case of 1 f, the result in air-
equilibrated solution is very similar to that observed
under oxygenated conditions. Compound 1j gave
the same acids formed in deaerated conditions,
albeit in a higher amount.
[b]
Solvent
F
Products, yield[c] [%]
Desulf./Fries[d]
À1
AcOEt
THF
MeCN
MeCN/MeOH (1:1)
MeCN/H2O (1:1)
acetone
0.14
0.08
0.21
0.16
0.10
2b, 25; 3b, 26; 5b, 9; 6b, 16
2b, 29; 3b, 5; 5b, 10; 6b, 16.
2b, 22; 3b, 12; 5b, 11; 6b, 20
2b, 33; 3b, 6; 5b, 30; 6b, 14
2b, 30; 3b, 7; 5b, 16; 6b, 11
–
44/56
64/36
50/50
75/25
70/30
–
<0.01
[a] Conditions: A solution of 1b (10À2 m, nitrogen purged) in the chosen solvent was
irradiated for 2 h at l=254 nm (4ꢁ15 W Hg lamps). [b] Disappearance quantum yield
(FÀ1) measured on a N2-purged 10À2 m solution of 1b in the chosen solvent (l=
254 nm, 1ꢁ15 W Hg lamp). [c] Product yields calculated on the basis of the amount
of 1b consumed. In each case, compound 4b was detected in <1% yield. [d] Ratio
between the yields of desulfonylated compounds 2b and 5b versus photo-Fries ad-
ducts 3b, 4b, and 6b.
To gain a deeper insight into the mechanism, we
monitored the evolution of the photoproduct distri-
butions obtained from compound 1b under deaerat-
ed conditions after different irradiation times (see
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(FÀ1 =0.4). Again, the presence of oxygen did not
significantly affect the efficiency of consumption
(Table S3 in the Supporting Information). Irradiation
experiments were performed on nitrogen-saturated
solutions of sulfonamides 2a, 2b, and 2 f in MeCN.
Photolysis of 2a gave Fries-adduct 4a (91% yield) as
the only photoproduct (Scheme S1 in the Supporting
Information). An almost selective conversion of 2b to
anisidine 5b was observed, whereas in the case of 2 f
a mixture of Fries adduct 4 f and desulfonylated ani-
line 5 f, along with a minor amount of ipso-substitut-
ed product 7d, was obtained. Finally, irradiation of
Fries-adduct 3b gave exclusively compound 6b in
89% yield (Scheme 2).
Table 2. Irradiation of sulfonimides 1a–j in MeCN.[a]
[b]
1
F
Products, yield[c] [%]
H+ [%][d]
Acids, yield[e] [%]
À1
1a
1b
1c
1d
1e
1 f[f]
1 f
0.31
0.21
0.09
0.10
0.10
0.28
0.28
3a, 82; 6a, 10
<1
46
99
75
CH3SO2H, <1
CH3SO2H, 45
CH3SO2H, 96
CH3SO2H, 74
2b, 22; 3b, 12; 5b, 11; 6b, 20
2c, 21; 4c, 55; 5c, 12
2d, 32; 5d, 14; 7d, 9
2e, 17; 4e, 53; 5e, 22
2 f, 80; 4 f, 8; 5 f, 7
125
CH3SO2H, 116
[g]
[g]
2 f, 36; 4 f, 18; 5 f, 18; 7d, 4
98
<1
CH3SO2H, 93
[i]
[h]
1g
<0.01
Laser flash photolysis (LFP) and EPR experiments
Compounds 1b and 1 f were further examined by
means of time-resolved UV absorption spectroscopy.
LFP experiments at l=266 nm on a nitrogen-saturat-
ed solution of 1b (5ꢁ10À4 m) in acetonitrile revealed
the formation of two intense absorptions located at
l=300–340 and 440–460 nm (Figure 2a). The time
evolution of the transient spectrum revealed the
presence of different transient species, with the pre-
dominant contribution of a long-lived intermediate (t
ꢀ100 ms) in both absorption bands. However, two
short-lived intermediates characterized by lifetimes of
t=6 and 1.8 ms were also identified at l=300–340
and 440–460 nm, respectively (see inset in Figure 2a
and Figure S35 in the Supporting Information). Final-
ly, a residual absorption band located at 370–400 nm
can be observed about 50 ms after the laser pulse
(Figure 2b).
1h
0.13
2h, 56; 5h,9
72
CH3SO2H, 71
1i
1j
0.24
0.22
2i, 17; 4i, 38; 5 f, 28; 7i, 13
2j, 5; 5 f, 78
128
319
CH3C6H4SO2H, 116; CH3COOH, 11
H2SO3, 123; HF, 44
[a] Conditions: A solution of 1a–j (10À2 m, nitrogen purged) in MeCN was irradiated
for 2 h at l=254 nm. [b] Measured on a 10À2 m solution of 1a–j in nitrogen-purged
MeCN (l=254 nm). [c] Determined by HPLC or GC analyses. [d] Determined by poten-
tiometric titration. [e] Determined by HPLC ion chromatography analyses. [f] Irradia-
tion for 15 min. [g] Not determined. [h] No photoproducts detected. [i] No acid re-
leased.
When the same experiments were repeated in an
oxygen-saturated solution, a modification of the tran-
sient absorption profile was observed; both of the
Figure 1 and Table S2 in the Supporting Information). Com-
pounds 2b and 3b were initially formed, but their concentra-
tion settled to almost constant values during irradiation, with
the concomitant accumulation of anilines 5b and 6b
(Figure 1). Similar behavior was found for 1 f. In this case, sulfo-
namide 2 f was obtained in 80% yield after 15 min of irradia-
tion. Prolonged photolysis (2 h) caused the consumption of 2 f
in favor of the formation of anilines 4 f, 5 f, and 7d (Table 2).
Photochemical experiments on 2a–j and 3a,b
To determine the presence of secondary photochemical paths,
our investigation proceeded with the exploration of sulfona-
mides 2 and Fries adducts 3 in MeCN (Table S3 in the Support-
ing Information). Compounds 2b–j and 3a,b are slightly more
fluorescent than the corresponding sulfonimides 1b–j and the
Figure 1. Yields of photoproducts obtained from irradiation of 1b at differ-
ent times. Conditions: A solution of 1b (10À2 m, nitrogen purged) in acetoni-
trile at l=254 nm (4ꢁ15 W Hg lamps). Product yields calculated on the
basis of the initial concentration of 1b (see Table S3 in Supporting Informa-
tion for further details).
F
À1
values are, on average, lower than the corresponding sul-
fonimides, with notable exceptions for 2e (FÀ1 =0.2) and 2j
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Table 3. Irradiation of sulfonimides 1a–j in MeCN under oxygenated con-
ditions.[a]
[b]
F
À1
Conversion[c] H+[d] Acids, yield[e]
[%]
[%]
[%]
1a
1b
1c
1d
1e
1 f
1 f[f]
1g
1h
1i
0.29 100
72
149
172
157
190
199
195
<1
186
195
698
CH3SO3H, 66
0.21
0.08
0.08
0.10
92
74
70
80
CH3SO3H, 154
CH3SO3H, 178
CH3SO3H, 154
CH3SO3H, 182
CH3SO3H, 192
CH3SO3H, 185
–
CH3SO3H, 182
CH3C6H4SO3H, 200; CH3COOH, <1
H2SO3, 175; HF, 330
0.28 100
100
<0.01 <1
0.22 96
–
0.23 100
0.22 100
1j
[a] Conditions: Solutions of 1a–j (10À2 m, oxygen purged) in MeCN irradi-
ated for 2 h at l=254 nm. [b] Measured on a 10À2 m solution of 1a–j in
oxygen-purged MeCN (l=254 nm). [c] Determined by HPLC or GC analy-
ses. [d] Determined by potentiometric titration of the photolyzed solution
with aqueous NaOH. [e] Determined by HPLC ion chromatography analy-
ses. [f] Reaction carried out on an air-equilibrated solution.
Scheme 2. Irradiation of 2b, 2 f, and 3b (10À2 m, nitrogen purged) in MeCN.
Figure 2. Transient absorption spectra of a solution of 1b in nitrogen-
(black) and oxygen-saturated (gray) acetonitrile a) recorded 6 ms after a 7 ns
laser pulse (l=266 nm); inset: profile of the absorbance change observed
at 330 nm; and b) recorded 50 (upper curve) and 450 ms after a 7 ns laser
pulse (l=266 nm). c) Transient absorption spectra of a solution of 1i in ni-
trogen- (black) and oxygen-saturated (gray) acetonitrile recorded 6 ms after
a 7 ns laser pulse (l=266 nm); inset: profile of the absorbance change ob-
served at l=340 nm.
short-lived species were quenched (Figure 2a and Figures S32
and S33 in the Supporting Information), and a modest lower-
ing in the intensity of the remaining absorption bands resulted
(see Figure S33 in the Supporting Information). Analogous re-
sults were obtained in the case of acetyl derivative 1 f (5ꢁ
10À4 m in MeCN), for which again two absorption bands (lmax
=
300–340 and 450–480 nm) were detected under nitrogen-satu-
rated conditions. However, in this case, only two transient spe-
cies contributed to both bands, namely, a short- (t=1.8 ms)
and long-lived (t=100 ms) intermediate; the former was
quenched in the presence of oxygen (see Figures S37–S40 in
the Supporting Information).
Turning to compound 1i (10À4 m in MeCN), an absorption
spectrum with a strong maximum located in the l=300–
340 nm region was observed, along with a weaker absorption
band at lꢀ440–470 nm (Figure 2c and Figures S42–S45 in the
Supporting Information). Kinetic analysis revealed the presence
of a long-lived intermediate (tꢀ100 ms) that was the main
contributor to both maxima. However, as in the case of 1b, we
also found the presence of two oxygen-sensitive species, char-
acterized by lifetimes of about 1.8 and 9.4 ms, respectively; the
former present in both maxima, whereas the latter only con-
tributed significantly to the absorption in the l=300–340 nm
region. A residual absorption with broad bands at l=300–340
and 420–480 nm has been detected for all of the compounds
examined, even 4000 ms after the laser pulse (Figures S36, S41,
and S46 in the Supporting Information). EPR analyses were
performed on solutions of 1 f, 1i, and 1j in deaerated benzoni-
trile. For compounds 1 f and 1i, two species with similar g
values (2.006Æ0.0005) were observed during irradiation of the
samples by a high-pressure Hg lamp (Figure 3 and Figure S47
in the Supporting Information). Analyses of 1 f carried out in
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the presence of the spin-trapping agent N-tert-butyl-a-phenyl-
nitrone (PBN) resulted in amplification of the generated spe-
cies, giving a signal with hyperfine coupling constants of 13
(aN) and (3Æ0.5) G (aH). In the case of 1j, a weak signal was
observed only upon irradiating the sample in the presence of
2-methyl-2-nitrosopropane (MNP) as a spin trap, although in
an amount below the limit of quantification (Figure S48 in the
Supporting Information).
the triplet state accessible; no alteration of the reaction mech-
C
C
anism was observed. Once generated, radicals I and II can
follow two competing pathways, namely, recombination to
yield Fries rearrangement products 3 or escape from the sol-
vent cage. In the former case, the formation of 3 (Scheme 3,
path d) proceeded via intermediate IV,[21] which was character-
ized by LFP experiments by the residual l=370 nm absorption
observed for 1b (see Figure 2b). In contrast, sulfonamide 2
C
arises from hydrogen abstraction by radical I from the reaction
medium (Scheme 3, path c). The competition between these
two pathways depends on the functional groups present in
the aryl moiety and reaction media. Compound 3 is formed
preferentially in less polar solvents (Table 1) and in the pres-
ence of electron-donating aromatic substituents (NMe2, OMe;
Table 2).
Figure 3. EPR spectra recorded during photolysis of 1 f in deaerated benzo-
nitrile.
Discussion
Photochemistry of compounds 1a–j
A tentative mechanism for the photoreactivity of N-arylsulfoni-
mides is shown in Scheme 3. Irradiation of 1a–j causes their
1
excitation to the singlet excited state, 1a–j. Then, homolytic
fragmentation of one of the NÀS bonds (Scheme 3, path a)
1
C
C
takes place from 1a–j to afford sulfamido (I ) and sulfonyl (II )
radicals. The presence of such species is strongly supported by
both time-resolved absorption and EPR spectroscopy tech-
niques. In particular, the long-lived transient spectrum with ab-
sorption maxima in the l=300–340 and 440–480 nm regions
C
was assigned to I , whereas methanesulfonyl and para-toluene-
C
sulfonyl radicals II were characterized as the short-lived (6 and
Scheme 3. Mechanism for the photochemical reactivity of N-arylsulfonimides
1a–j.
9.4 ms, respectively), oxygen-sensitive signals in the l=300–
340 nm region.[17] The presence of such sulfur-centered radicals
was further confirmed by EPR analyses on 1 f, for which the g
factor value obtained for the methanesulfonyl radical (2.006Æ
0.0005) was in accordance with literature data (Figure 3).[18]
The very short lived transient species at l=440–460 nm for
1b can be safely assigned to its triplet state, by comparison
with the absorption spectrum of the triplet state of anisi-
dine.[19] Similarly, the 2 ms long, oxygen-sensitive, signals at l=
As previously reported,[22,23] the obtained N-arylsulfonamides
are also photoactive, and both desulfonylation to the corre-
sponding anilines 5 (Scheme 3, path c’) and Fries rearrange-
ment products (4; Scheme 3, path c’’) can be observed. The
last pathway is favored for electron-rich sulfonamides, as in the
case of 2a, which gives Fries-adduct 4a exclusively upon irra-
diation. On the other hand, when irradiating nonsubstituted
1d, photo-Fries rearrangement from primary photoproduct 2d
results in the formation of either aniline 5d or p-substituted
compounds 7d (Scheme 3, path c’’’).
3
3
300–340 and 440–480 nm were assigned to 1 f and 1j (Fig-
ure S39).[20] However, the insensitivity of the photoreactions of
1a–j to oxygen (compare the similar F values reported in
À1
Tables 2 and 3), and the observed photostability of 1b in ace-
tone (a well-known triplet sensitizer), exclude fragmentation
from this state (Scheme 3, paths b and b’). Notably, despite the
presence of the acetyl substituent in derivatives 1 f, 1i and 1j
could increase the efficiency of intersystem crossing to make
Compounds 7 were also obtained as minor products from
acetyl derivatives 1 f and 1i. In the latter case, we suggest that
path c’’’ (Scheme 3) is still involved and an aromatic ipso sub-
stitution occurs with the subsequent release of acetic acid
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(Table 2). The radical-induced displacement of an acyl group
was previously observed for 2-acetylbenzothiazoles[24a] and
acylpyridines.[24b] Moreover, the photosubstitution of a chlorine
atom for a sulfonyl group has also been reported in the
photo-Fries rearrangement of N-chlorophenylsulfonamides, in
which a chlorine cation is supposed to be lost at the end of
the process.[23] The photoreactivity of photoproducts 3a and
b is instead limited to rearranged anilines 6a and b (Scheme 3,
path d’’), whereas desulfonylation to compounds 4 (Scheme 3,
path d’) seems to have no role.
N-Arylsulfonimides as PAGs
For the release of acid, under deaerated conditions, the corre-
sponding weak sulfinic acids are mainly released (Scheme 3,
path e). However, the presence of oxygen prevents any Fries
rearrangement from occurring and drives the process to the
C
Figure 4. Quartz tube containing a suspension of sodium alginate (2 wt%),
CaCO3 (0.015m) and 1i (0.030m) in water a) before irradiation, and b) after
6 h of irradiation at l=310 nm.
formation of radicals III , which are precursors of sulfonic acids
(Scheme 3, path f).[9] Thus, in the case of sulfonimides 1b–f, h,
and i, a strong acid is always photoreleased in high yields.
Paradigmatic is the case of compound 1i, for which almost
two equivalents of p-toluenesulfonic acid were obtained from
each mole of starting substrate.
erties and photochemical behavior could be simply tuned by
choosing suitable substituents.
Interestingly, no triflic acid was released upon irradiation of
triflimide 1j under oxygenated conditions. This is due to the
facile loss of SO2 (detected as H2SO3 by ion chromatography)
Experimental Section
[8]
C
from trifluoromethanesulfonyl radical II (Scheme 3, path g).
General
Secondary processes of the resulting trifluoromethyl radicals
1H NMR spectra were recorded with a 300 MHz spectrometer, and
13C NMR spectra were recorded with a 75 MHz spectrometer. As-
C
F3C lead to the formation of fluoroform, hexafluoroethane,
and the liberation of HF.[8] The presence of such radicals was
confirmed by EPR analyses on 1j. Indeed, the weak signal ob-
served during irradiation in the presence of the spin-trapping
1
signments were made on the basis of H and 13C NMR spectra, as
well as DEPT-135 experiments; chemical shifts are reported in ppm
downfield from tetramethylsilane (TMS).
C
agent MNP can be assigned to F3C species (Figure S48 in the
Supporting Information), according to data reported in the lit-
erature.[25]
The photochemical reactions were performed by using nitrogen-
or oxygen-saturated solutions in quartz tubes in a multilamp reac-
tor equipped with 4ꢁ15 W Hg lamps (emission centered at l=
254 nm) for irradiation. Quantum yields were measured at l=
254 nm (1 Hg lamp, 15 W). Solvents of HPLC-grade purity were em-
ployed for all photochemicals reactions. The reaction course was
followed by either GC (compounds 1c, 1d, and 1h) or HPLC analy-
ses (all other compounds) and the products formed were identified
and quantified by comparison with calibration curves of authentic
samples.
Ionic gelation of alginate polymer induced by 1i as a proof
of concept
To test the potential of the examined substrates as PAGs, light-
activated ionic gelation of alginate polymer[26] was promoted
by using sulfonimide 1i. Irradiation at l=310 nm of a fine dis-
persion of 2 wt% sodium alginate in water, CaCO3
(15 mmolLÀ1), and 1i (0.030m) resulted in the acid-induced re-
lease of soluble Ca2+ ions that were capable of inducing the
gelification of alginate to afford a gel capable of holding its
weight in the inverted tube, as illustrated in Figure 4 and Fig-
ure S47 in the Supporting Information.
GC analyses were carried out by using a chromatograph equipped
with a flame ionization detector (FID). A 30 mꢁ0.25 mmꢁ0.25 mm
capillary column was used for the separation of analytes with nitro-
gen as a carrier gas at 1 mLminÀ1. Injection into the GC system
was performed in split mode and the injector temperature was
2508C. The GC oven temperature was held at 1208C for 2 min, in-
creased to 2508C by a temperature ramp of 108CminÀ1, and held
for 10 min. HPLC analyses were carried out on a HPLC apparatus
equipped with two pumps and a UV detector (C-18 column: 300ꢁ
3.9 mm; eluent: MeCN/water 30/70, flux 0.5 mLminÀ1).
Conclusion
We presented herein a new class of nonionic PAGs able to re-
lease, upon irradiation, up to two equivalents of strong sulfon-
ic acids (methanesulfonic and p-toluenesulfonic acids) for each
mole of photoactive substrate. These compounds were effi-
ciently obtained in a straightforward way from the correspond-
ing commercially available anilines, and their absorption prop-
GC-MS analysis on an irradiated solution of compound 1i was car-
ried out by using a single quadrupole GC/MS system. A 30 mꢁ
0.25 mmꢁ0.25 mm capillary column was used for the separation of
analytes with helium as a carrier gas at 1 mLminÀ1. Injection into
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the GC system was performed in split mode and the injector tem-
perature was 2508C. The GC oven temperature was held at 1208C
chloride (2.28 g, 12 mmol) was added portionwise under stirring.
The resulting mixture was then allowed to warm to room tempera-
ture and stirred overnight. The reaction was quenched with a 6n
aqueous solution of NaOH (50 mL), and water was added to the re-
sulting mixture to dissolve the resultant salts. The layers were sep-
arated, the aqueous phase was washed with CH2Cl2 (3ꢁ40 mL),
cooled to 08C, and upon subsequent acidification to pH 2.0 (by
adding aqueous HCl 18%) a white solid precipitated. This solid was
separated by filtration on a sintered glass funnel and washed with
cold water to afford 2i as a white solid (87%) without need for fur-
ther purification.
for 2 min, increased to 2508C by
a temperature ramp of
108CminÀ1, and held for 10 min. The transfer line temperature was
2708C and the ion source temperature was 2508C. Mass spectral
analysis was carried out in full-scan mode.
The acidity liberated was determined on photolyzed solutions
(5 mL) by dilution with water (25 mL) and titration with a 0.1m
aqueous solution of NaOH. Titrations were followed by using an
Orion mod 250 potentiometer equipped with an Orion pH glass
combined electrode mod 91–56. Ion chromatography analyses
were performed by means of a Dionex GP40 instrument equipped
with a conductimetric detector (Dionex 20 CD20) and an electro-
chemical suppressor (ASRS Ultra II, 4 mm) by using the following
conditions: chromatographic column IONPAC AS23 (4 mmꢁ
250 mm), guard column IONPAC AG12 (4 mmꢁ50 mm), eluent:
NaHCO3 0.8 mm+Na2CO3 4.5 mm, flux: 1 mLminÀ1; current im-
posed at detector: 50 mA. Commercially available sodium metha-
nesulfinate, sodium p-toluenesulfinate, methanesulfonic acid, and
p-toluenesulfonic acid monohydrate were used as standards. The
presence of fluoroform and hexafluoroethane when irradiating 1j
was detected by IR[8] and GC-MS analyses (see Figures S11 and S12
in the Supporting Information).
Synthesis of 2j
Compound 2j was synthesized by adapting the procedure em-
ployed for the synthesis of N-alkyltrifluoromethanesulfonamides.[28]
Trifluoromethanesulfonic anhydride (1.8 mL, 11 mmol) was added
dropwise under stirring to a cooled solution (À788C) of 5 f (1.35 g,
10 mmol) and triethylamine (1.6 mL, 11 mmol) in dry CH2Cl2
(35 mL) under a nitrogen atmosphere. The mixture was stirred at
À788C for 2 h, allowed to warm to room temperature, transferred
to a separation funnel, and quenched with water (60 mL). The
aqueous layer was extracted with CH2Cl2 (2ꢁ25 mL), then the or-
ganic phases were combined and treated with a 6n aqueous solu-
tion of NaOH (50 mL) and water to dissolve the resultant salts. The
layers were separated, the aqueous phase was washed with CH2Cl2
(3ꢁ40 mL), cooled to 08C, and upon acidification to pH 2.0 (by
adding aqueous HCl (18%)) a white solid precipitated. This solid
was separated by filtration on a sintered glass funnel and washed
with cold water to afford 2j as a white solid (70%) without need
for further purification.
Microsecond transient absorption experiments were performed by
using a nanosecond LFP apparatus equipped with a 20 Hz Nd:YAG
laser (25 ns, 25 mJ at l=266 nm) and a 150 W Xe flash lamp as the
probe light. Samples were placed in a quartz cell (10ꢁ10 mm sec-
tion) at a concentration adjusted to obtain an optical density (OD)
value of 1.0 at l=266 nm.
EPR experiments were performed on a 0.01m solution of the
chosen compounds in freshly distilled benzonitrile. A Bruker EMX
10/12 spectrometer equipped with ER4102ST cavity was employed.
The lamp (a high pressure 500 W Hg lamp) was focused on the
window of the cavity by means of a crown glass lens (spot diame-
ter about 4 cm). When spin-trapping agents (PBN and MNP) were
present, a concentration of 10À1 m was used.
Synthesis of 1a–h
Compounds 1a–h were obtained from 2a–h by following a known
procedure.[29] Methanesulfonyl chloride (0.57 mL, 7.4 mmol) was
rapidly added to a solution of 2a–h (5.0 mmol) and NaOH
(5.2 mmol) in water (15 mL) under vigorous stirring. A white precip-
itate appeared instantaneously, then the resulting mixture was fur-
ther stirred for 30 min and extracted with CH2Cl2 (3ꢁ20 mL). The
organic phases were combined, washed with a 10% aqueous solu-
tion of NaOH (2ꢁ20 mL), dried over Na2SO4, and the solvent was
evaporated to give 1a–h as white solids.
Synthesis of 2a–h
Compounds 2a–h were prepared by following a known proce-
dure.[27] A solution of the chosen aniline 5a–h (10 mmol) and pyri-
dine (0.90 mL, 11 mmol) in dry dichloromethane (25 mL) was
cooled to 08C under a nitrogen atmosphere. Methanesulfonyl chlo-
ride (0.85 mL, 11 mmol) was added dropwise with stirring, then the
mixture was allowed to warm to room temperature and stirred
overnight. The reaction was quenched with a 6n aqueous solution
of NaOH (50 mL) and water was added to the resulting mixture to
dissolve the resultant salts. The layers were then separated: the
aqueous phase was washed with CH2Cl2 (3ꢁ40 mL) and cooled to
08C. Upon subsequent acidification to pH 2.0 (by adding aqueous
HCl (18%)) a white solid precipitated. The obtained product was
collected on a sintered glass funnel, washed repeatedly with cold
water, and then dried under vacuum; thus giving the desired com-
pounds without need for further purification.
Synthesis of 1i
Compound 1i was synthesized by adapting a known procedure for
the synthesis of N-aryl-p-toluenesulfonimides.[30] p-Toluenesulfonyl
chloride (4.0 g, 21 mmol) was added portionwise under stirring at
room temperature to a solution of aniline 5 f (1.35 g, 10 mmol) and
triethylamine (4.2 mL, 30 mmol) in CH2Cl2 (30 mL). After 24 h of stir-
ring, the mixture was quenched with water (30 mL) and extracted
with CH2Cl2 (3ꢁ30 mL). The organic layer was washed sequentially
with water (75 mL), a 10% aqueous solution of HCl (3ꢁ30 mL),
water (2ꢁ50 mL), a 10% aqueous solution of NaOH (2ꢁ30 mL),
and brine (2ꢁ30 mL) and dried with Na2SO4. The solvent was then
evaporated to afford the crude product. After purification by
column chromatography (eluent: cyclohexane/ethyl acetate, 9:1),
compound 1i was obtained as a white solid (77%).
Synthesis of 2i
Compound 2i was synthesized by adapting the procedure em-
Synthesis of 1j
ployed for the synthesis of N-arylmethanesulfonamides 2a–h.[27]
A
solution of aniline 5i (1.35 g, 10 mmol) and pyridine (1.50 mL,
19 mmol) in CH2Cl2 (35 mL) was cooled to 08C. p-Toluenesulfonyl
Compound 1j was synthesized by using a procedure employed for
the synthesis of N-(4-vinylphenyl)-1,1,1-trifluoro-N-[(trifluorome-
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thyl)sulfonyl]methanesulfonamide.[31] Trifluoromethanesulfonic an-
hydride (3.6 mL, 21 mmol) was added dropwise to a cooled solu-
tion (À788C) of 5 f (1.35 g, 10 mmol) and triethylamine (4.0 mL,
30 mmol) in dry CH2Cl2 (35 mL) under a nitrogen atmosphere. The
mixture was stirred at À788C for 1 h, allowed to warm to room
temperature, and then further stirred for another hour. The result-
ing mixture was diluted with dichloromethane (80 mL) and washed
with a saturated aqueous solution of NaHCO3 (3ꢁ30 mL) and brine
(3ꢁ30 mL). The organic layer was then dried over Na2SO4 and the
solvent was evaporated. The crude residue was thus purified by
column chromatography (eluent: hexane/ethyl acetate, 95:5) to
afford 1j as a white solid (83%).
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Preparative photochemical reactions were performed by using ni-
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tilamp reactor equipped with 4ꢁ15 W Hg lamps (emission cen-
tered at l=254 nm) for irradiation. Workup of the photolytes in-
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using a magnetic stirring bar and then sonicated for 45 min at
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We acknowledge Prof. A. Albini (University of Pavia) for fruitful
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zione Cariplo (grant no. 2012-0186).
Keywords: photochemistry · radicals · reaction mechanisms ·
sulfonic acids · sulfonimides
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Received: July 26, 2016
Published online on && &&, 0000
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FULL PAPER
&
Reaction Mechanisms
E. Torti, S. Protti, D. Merli, D. Dondi,
M. Fagnoni*
&& – &&
Photochemistry of N-Arylsulfonimides:
An Easily Available Class of Nonionic
Photoacid Generators (PAGs)
Two-for-one on acid generation: The
photochemical behavior of differently
substituted N-arylsulfonimides is de-
scribed. Homolysis of the SÀN bond
takes place as the exclusive pathway
from the singlet state to afford both N-
arylsulfonamides and photo-Fries ad-
ducts, the amount of which depends on
reaction conditions and aromatic sub-
stituents (see scheme). Sulfinic and sul-
fonic acids were likewise released under
deaerated and oxygenated conditions,
respectively.
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