Photochemical cleavage reactions of 8-quinolinyl sulfonates in aqueous solution

Article abstract of DOI:10.1248/cpb.57.1257

Photochemical cleavage reactions of 8-quinolinyl benzenesulfonate derivatives and related sulfonates in aqueous solutions are reported. The 8-quinolinyl benzenesulfonates undergo photolysis upon photoirradiation at 300-330 nm to give the corresponding 8-quinolinols and benzenesulfonic acids with the production of only negligible amounts of byproducts. The effects of substituent groups of the 8-quinolinyl moiety and the benzene ring on the photolysis reactions were examined. Based on steady-state mechanistic studies using a triplet sensitizer, a triplet quencher, and electron donors, it was suggested that the photolysis proceeds mainly via the homolytic cleavage of S-O bonds in the excited triplet state.

Full text of DOI:10.1248/cpb.57.1257

November 2009
Chem. Pharm. Bull. 57(11) 1257—1266 (2009)
1257
Photochemical Cleavage Reactions of 8-Quinolinyl Sulfonates in Aqueous
Solution
Yoshiyuki KAGEYAMA,a Ryosuke OHSHIMA,a Kazusa SAKURAMA,b Yoshihisa FUJIWARA,c
Yoshifumi TANIMOTO,c Yasuyuki YAMADA,a,d and Shin AOKI*,a,d
a Faculty of Pharmaceutical Sciences, Tokyo University of Science; d Center for Drug Delivery Research, Tokyo University
of Science; 2641 Yamazaki, Noda 278–8510, Japan: b CMC Research Center, Mitsubishi Tanabe Pharma Corporation;
3–16–89 Kashima, Yodogawa-ku, Osaka 532–8505, Japan: and c Graduate School of Science, Hiroshima University;
1–1–1 Kagamiyama, Higashi-Hiroshima 739–8524, Japan.
Received June 18, 2009; accepted July 17, 2009; published online August 18, 2009
Photochemical cleavage reactions of 8-quinolinyl benzenesulfonate derivatives and related sulfonates in
aqueous solutions are reported. The 8-quinolinyl benzenesulfonates undergo photolysis upon photoirradiation at
300—330 nm to give the corresponding 8-quinolinols and benzenesulfonic acids with the production of only neg-
ligible amounts of byproducts. The effects of substituent groups of the 8-quinolinyl moiety and the benzene ring
on the photolysis reactions were examined. Based on steady-state mechanistic studies using a triplet sensitizer, a
triplet quencher, and electron donors, it was suggested that the photolysis proceeds mainly via the homolytic
cleavage of S–O bonds in the excited triplet state.
Key words photolysis; sulfonate; 8-quinolinol; homolysis
Photochemical bond-cleavage reactions are potentially spectrum of 1 (5 mM) in the absence of Zn2ꢁ in 10 mM N-(2-hy-
useful in organic chemistry, biological chemistry and chemical droxyethyl)piperazine-Nꢃ-2-ethanesulfonic acid (HEPES) (pH
biology (e.g.; protection/deprotection in organic synthesis1—4) 7.4) with Iꢀ0.1 (NaNO3) at 25 °C (excitation at 338 nm) (the
and uncaging of chemically masked or caged molecules).5—13) emission spectra was obtained by rapid scanning (500—
To date, the photolysis of sulfonic esters,14—24) sulfon- 1000 nm/min)) and curve (b) shows a spectrum obtained
amides,25—32) and sulfones33,34) has been applied to photo- after Zn2ꢁ-promoted hydrolysis of 3 (via its Zn2ꢁ complex 4)
resist materials,15,26) protecting groups,8,19,20,27—32) and other for 3 h in the dark, as previously reported.39) On the other
chemical reactions.14,35—37) Based on the above findings, the hand, the photoirradiation of a mixture of 3 (5 mM) and Zn2ꢁ
development of new photocleavage reactions of sulfonic acid (5 mM) at 328 nm, gave curve (c) having an emission maxi-
derivatives and related mechanistic studies would be useful mum at 510 nm, which is in good agreement with curve (d)
in organic chemistry, bioorganic chemistry, analytical chem- for 2 (5 mM) (emission maximum at 512 nm). Based on the
istry, and material sciences.
observation in 1H-NMR (Figs. 2, 3) and UV spectral changes
We recently reported on the use of 5-N,N-dimethylaminosul- (Fig. 4), it was suggested that 3 and its Zn2ꢁ complex 4 were
fonyl-8-hydroxyquinolinyl-pendant cyclen (cyclenꢀ1,4,7,10-
tetraazacyclododecane) 1 (H2L1) as a Zn2ꢁ fluorophore. The
compound forms a very stable Zn2ꢁ complex 2 (Zn(Hꢂ1L1))
in aqueous solution (Kdꢀ8 fM at pH 7.4), resulting in a 17-
fold enhancement in the emission at 512 nm (excitation at
338 nm) (Chart 1).38) The caged derivative 3 (H2(BS-caged-
L1)), in which the 8-OH group of the quinolinol moiety is
protected by a benzenesulfonyl (BS) group, was recently
synthesized, in an attempt to improve the cell permeability
and Zn2ꢁ/Cd2ꢁ selectivity of 1. We were able to confirm that
the benzenesulfonyl ester of 3 is removed by a nucleophilic
attack of Zn2ꢁ-bound HOꢂ (in 4b) on sulfur atom in its Zn2ꢁ
complex 4 (Zn(BS-caged-L1)) to give 2.39,40)
During a study of the hydrolytic uncaging reaction of 4,
we found that 3 undergoes photolysis to yield 1, whose emis-
sion increased upon the addition of Zn2ꢁ. In this study, we re-
port on the photolysis of 3, 4, 8-quinolinyl sulfonate deriva-
tives that contain no metal chelating group (5—8), and re-
lated compounds in aqueous solution (Chart 2). Some mech-
anistic aspects of this photolysis reaction are also discussed.
Results
Finding of Photolysis of 3 During the fluorescent titra-
tion of 3 (H2(BS-caged-L1)) with Zn2ꢁ, an enhancement in
emission was observed. Curve (a) in Fig. 1 shows the emission
Chart 1
© 2009 Pharmaceutical Society of Japan
∗ To whom correspondence should be addressed. e-mail: shinaoki@rs.noda.tus.ac.jp

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Vol. 57, No. 11
Chart 2
Fig. 1. Change in Emission Spectra of 5 mM 3 (BS-Caged-L1) at pH 7.4
(10 mM HEPES with Iꢀ0.1 (NaNO3)) and 25 °C upon Photoirradiation
(a) Emission spectra of 5 mM 3 obtained by a rapid scanning of the emission wave-
length (excitation at 338 nm), (b) emission spectra of 5 mM 3 obtained 3 h after incuba-
tion in the presence of 5 mM Zn2ꢁ at 25 °C in the dark, (c) emission spectra of 5 mM 3
after photoirradiation at 328 nm for 3 h in the presence of 5 mM Zn2ꢁ (excitation wave-
length for emission spectra measurement was 338 nm), and (d) emission spectra of
5 mM 2 (Zn(Hꢂ1L1)). Arbitrary unit is a.u.
converted to 1 (H2L1) and 2 (Zn(Hꢂ1L1)), respectively, upon
photoirradiation.
Fig. 2. Photolysis of 3 (1 mM) in D2O at pD 7.4 (100 mM HEPES) and
25 °C Followed by 1H-NMR (Aromatic Region)
As shown in Fig. 5, 3 (50 mM) negligibly reacted in the ab-
sence of Zn2ꢁ in the dark (dashed curve (a)). Upon the addi-
tion of 1 equivalent of Zn2ꢁ, 4 was formed, which underwent
slow hydrolysis in the dark to afford 2 (Zn(Hꢂ1L1)) (plain
(a) 3 before photoirradiation, (b) after photoirradiation of 3 at 328 nm for 1 h, (c)
after photoirradiation of 3 at 328 nm for 3 h, (d)1 mM 1 (L1), (e) 1 mM benzenesulfonate
(PhSOꢂ3 ), and (f) 1 mM benzenesulfinate (PhSOꢂ2 ).
curve (b)). The photoirradiation of 4 at 328 nm then resulted the photohydrolysis of 3 and its Zn2ꢁ complex 4, some pho-
in a considerable enhancement in fluorescent emission, indi- toreactions of reference compounds that contain no cyclen
cating the formation of 2.
unit, 5a—d and 6—8, were examined (Chart 2). As shown in
Figure 6 shows the pH-rate profile for photoreactions of 3 spectra (a)—(c) in Fig. 7, 5a (1 mM) underwent photolysis
(open circles) and 4 (closed circles), exhibiting negligible upon irradiation at 328 nm in a 90/10 mixture of CD3CN and
pH-dependency ([3]ꢀ[4]ꢀ10 mM). These results were in D2O (10 mM HEPES at pD 7.4). Curves (d), (e), and (f) in
marked contrast to that for the pH-dependent hydrolysis of 4 Fig. 7 are H-NMR spectra of 9, benzenesulfonate (PhSOꢂ3 )
1
(open squares in Fig. 6), implying that the presence of Zn2ꢁ- 12a, and benzenesulfinate (PhSOꢂ2 ), respectively. A compari-
bound H2O (or HOꢂ) (shown in Chart 1) is not an important son of spectrum (c) in Fig. 7 with spectra (d), (e), and (f)
factor in the photoreaction of 4. The quantum yields (F) for strongly indicates that the photoproducts produced from 5a
the photolysis of 3 and 4 at pH 7.4 were calculated to be are 9 and 12a. The quantum yield for the photolysis of 5a
1.5ꢄ10ꢂ4 and 1.4ꢄ10ꢂ4, respectively.
was estimated to be (2.5ꢅ0.3)ꢄ10ꢂ4 (photoirradiation at
Photoreaction of Reference Compounds Having No Cy- 328 nm) and the value was independent of the irradiation
clen Unit In order to examine the mechanisms involved in wavelength (data not shown).41) An HPLC analysis of the

November 2009
1259
Fig. 6. pH–Quantum Yield Profile for the Photolysis of 3 (Open Circles)
and 4 (Closed Circles) by Photoirradiation at 328 nm ([3]ꢀ[4]ꢀ10 mM in
Good’s Buffer with Iꢀ0.1 (NaNO3) at 25 °C) in Comparison of pH–k1 Pro-
file Hydrolytic Uncaging of 4 (Open Squares) at [4]ꢀ50 mM
Fig. 3. Photolysis of 4 (1 mM) in D2O at pD 7.4 (100 mM HEPES) and
25 °C Followed by 1H-NMR (Aromatic Region)
(a) 4 before photoirradiation (15 min after mixing 1 mM 3 and 1 mM Zn2ꢁ), (b) after
photoirradiation of 4 at 328 nm for 1 h, (c) after photoirradiation of 4 at 328 nm for 3 h,
(d) 1 mM 2 (Zn(Hꢂ1L1)), and (e) 1 mM benzenesulfonate (PhSOꢂ3 ).
Fig. 4. Change in UV Absorption Spectra of 50 mM 4 (Formed in Situ by
Mixing 50 mM 3 and 50 mM Zn2ꢁ) upon Photoirradiation (at 328 nm) 10 mM
HEPES (pH 7.4) with Iꢀ0.1 (NaNO3) at 25 °C
Fig. 7. Photolysis of 5a (1 mM) in a Mixture of CD3CN and D2O (10 mM
HEPES at pD 7.4) (90/10) at 25 °C Followed by H-NMR (Aromatic Re-
gion)
1
(a) Before photoirradiation, (b) after photoirradiation for 20 min, (c) after photoirra-
diation for 40 min, (d) after photoirradiation after 1 h, and (e) UV spectra of 50 mM 2
(Zn(Hꢂ1L4)) in 10 mM HEPES (pH 7.4) with Iꢀ0.1 (NaNO3) at 25 °C.
(a) Before photoirradiation, (b) after photoirradiation at 328 nm for 0.5 h, (c) after
photoirradiation at 328 nm for 3 h (d) 9 in a mixture of CD3CN and D2O (10 mM
HEPES at pD 7.4) (90/10) at 25 °C, (e) benzenesulfonate (PhSOꢂ3 ) 12a and (f) benzene-
sulfinate (PhSOꢂ2 ) under the same conditions. Plain arrows in (b) and (c) indicate 1H
signals of 9 and bold arrows indicate 1H signals of 12a.
photolysis products derived from 5a also indicated that the
photoirradiation of 5a (50 mM) for 9 h (irradiated with weaker
UV light at 328 nm than those for the NMR study mentioned
above) gave 9 in 78(ꢅ3)% and unreacted 5a in 21(ꢅ3)%
with negligible byproduct formation (Fig. 8).
It was found that 5b—d also undergo photolysis to afford
9 and the corresponding sulfonates 12b—d, indicating that
this photolysis is common to an 8-quinolynyl ester of aryl or
alkylsulfonic acids. The quantum yields (Fs) for the photoly-
sis of 5b, 5c and 5d were found to be 2.4ꢂ2.5ꢄ10ꢂ4, almost
the same as that of 5a (2.5ꢄ10ꢂ4), implying that the sub-
stituent groups on the benzenesulfonyl moiety have negligi-
ble effect on this reaction (Table 1). It was also found that the
photolysis of 6 and 7 gave the corresponding quinolinols (10
or 11) and 12a with F values of 1.3ꢄ10ꢂ4 (photoirradiation
Fig. 5. Time Course for the Hydrolysis and Photolysis of 50 mM 4 at pH
7.4 (10 mM HEPES with Iꢀ0.1 (NaNO3)) and 25 °C
Uncaging yields were determined by UV absorption spectra. (a) 50 mM metal-free 3
in the dark (closed squares), (b) 50 mM 4 in the dark for 3 h, followed by photoirradia-
tion at 328 nm for 3 h (open circles).

1260
Vol. 57, No. 11
Chart 3
Fig. 8. HPLC Trace for the Photoreaction of 5a (50 mM)
(a) Before irradiation and (b) after irradiation for 9 h at 328 nm in a mixture of
CH3CN and HEPES (10 mM, pH 7.4) (90/10). For HPLC analysis, ODS-column was
used and the absorption at 220 nm was recorded (CH3CN–phosphate buffer (pH 6.0)
(1 : 1)).
Table 1. Quantum Yields for Photolysis of 8-Quinolinyl Sulfonates (5—8)
(Include ca. 10% Experimental Errors)
Chart 4
Irradiation
wavelength (nm)
Quantum yield for
photolysis (F)
Substrate
5a
5b
5c
5d
6
328
328
328
328
320
330
328
2.5ꢄ10ꢂ4
2.4ꢄ10ꢂ4
2.4ꢄ10ꢂ4
2.5ꢄ10ꢂ4
1.3ꢄ10ꢂ4
6.9ꢄ10ꢂ4
1.6ꢄ10ꢂ4
7
8
Chart 5
some unidentified byproducts.42) The photolysis of 16 af-
forded the corresponding 1-naphthol 17 and 12a with negli-
gible side reaction.42) The photocleavage of 18 was very slow
in the absence and presence of benzophenone or Et3N (see
below), and the photocleavage of 19, 20, and 21 resulted in a
formation of a complex mixture.43)
Discussion
Several reaction pathways for the photolysis of sulfonate
derivatives have been proposed to date. In 1975, Izawa and
Kuromiya reported that the photolysis of methyl benzenesul-
fonate 22 in methanol led to the production of benzene 23,
biphenyl 24, anisole 25, and other products (Chart 4).17) They
postulated that the photolysis proceeds via homolytic cleav-
age of the C (benzene)–S bond in the excited singlet state,
Fig. 9. Change in UV Absorption Spectra of 50 mM 5a upon UV Irradia-
tion at 328 nm in 10/90 CH3CN/10 mM CHES (pH 9.0 with Iꢀ0.1 (NaNO3))
at 25 °C
The inset shows the time course for the photolysis of 5a (closed circles) and 8
(closed squares).
at 320 nm) and 6.9ꢄ10ꢂ4 (photoirradiation at 330 nm), re- the lifetime of which was estimated to be in the order of
spectively, suggesting that the substituents of the quinolinyl nanoseconds.
moiety somehow affect the photoreactivity of the sulfonate
Zen’s group and Masanovi’s group reported on the photol-
substrates (Table 1). The methylsulfonate analogue 8 also un- ysis of tosylate derivatives (TsOR) such as the D-galactose
derwent photolysis (photoirradiation at 328 nm) to give 9 and derivative 26 under basic conditions. Masanovi et al. con-
methylsulfonate 13 in a somewhat smaller quantum yield cluded that this photoreaction requires electron donors such
than that of 5a (Fig. 9 and Table 1).
as hydroxide or DABCO (1,4-diazabicyclo[2,2,2]octane), as
For comparison, we also examined the photoreaction of shown in Chart 5.18,19) It was generally assumed that the S–O
.
.
other sulfonate derivatives 14, 16, and 18—21 (Chart 3). The bond of the radical anion 26 ꢂ ([Tol-SO2-OR] ꢂ), generated
photoirradiation of 14 gave 1-naphthol (15) and 12a with by electron transfer from electron donors, is cleaved to afford

November 2009
1261
.
the toluenesulfonyl radical 27 ([Tol-SO2] ) and an alkoxide photolysis and concluded that the photodissociated products
anion (ROꢂ), which is converted to alcohol 28. Unfortu- were formed as the result of the escape of a radical pair from
nately, the photoproducts derived from 27 were not fully the solvent cage.
characterized.
As described above, the photolysis of 3 (BS-caged-L1), 4
In 1977, Ogata’s group reported on the photo-Fries re- (Zn(BS-caged-L1)), and 5—8 proceeds even in the absence
arrangement of phenyl benzenesulfonate 29a (Chart 6).23) of a base such as methoxide and DABCO, to give the corre-
Based on the fact that the photoreaction of 29a was unaf- sponding 8-quinolinols and sulfonates via S–O bond cleav-
fected by a triplet quencher and triplet sensitizers, they con- age, and not via C–S bond fission. In addition, only negligi-
cluded that the reaction proceeds via the homolysis of the ble photo-Fries rearrangement products were detected. These
S–O bond in the lowest excited singlet state or in a triplet data suggest that mechanism involved in the photolysis of
manifold, the rate of which is under the exceeding diffusion 8-quinolinol sulfonates (5—8) in aqueous solution may be
control. Barcley and Scaiano’s group subsequently reported somewhat different from those for the photoreactions shown
that photolysis of 29b proceeds via a non-Fries type pathway in Charts 4—6.
to give phenol and p-toluenesulfonic acid as well as photo-
To investigate this further, we examined the mechanism
Fries rearrangement products (Chart 6).24) They observed for the photolysis of 8-quinolinyl sulfonates (5—8) using
transient spectra of a phenoxy radical by means of laser flash steady-state techniques. Our hypothesis for the mechanism of
this photolysis is summarized in Chart 7, as evidenced by the
following experimental data.
Triplet-Sensitizing Experiments for the Photolysis of 5a
in the Presence of Benzophenone We carried out the pho-
tolysis of 5a in the presence of benzophenone (BZ) (top part
of Chart 7). BZ is a well-known sensitizer that has a triplet-
state energy (ET) value of 69 kcal molꢂ1 and brings about the
triplet-state (T1) of the substrates by energy transfer from the
triplet state of BZ (BZ*(T1)).44—49) The ET value of 5a was
estimated to be 61 kcal molꢂ1 from its phosphorescence spec-
tra in a frozen MeCN/H2O. Upon photoirradiation of a mix-
ture of 1 mM of 5a and 10 mM of BZ in CD3CN/D2O (10 mM
HEPES at pD 7.4) (90/10) for 15 min at 355 nm, which is
Chart 6
absorbed only by BZ, photolysis of 5a proceeded in ca. 50%,
Chart 7

1262
Vol. 57, No. 11
Fig. 10. Stern–Volmer Plot for the Photolysis of 5a (50 mM) Irradiated at
328 nm with Potassium Sorbate (0—100 mM) in a Mixture of CH3CN and
10 mM HEPES (pH 7.4) (90/10) at 25 °C
F
0 is the quantum yield in the condition without potassium sorbate.
as evidenced by 1H-NMR experiments. In the absence of BZ,
negligible amounts of photoproducts were produced under
the same conditions.
The quantum yield for the BZ-sensitized photocleavage 5a
(1 mM) irradiated at 355 nm was estimated to be 7—8-fold
larger than that for the direct irradiation of 5a (328 nm exci-
tation). Assuming that the triplet–triplet energy exchange is
diffusion-controlled, the quantum yield of intersystem cross-
ing (fISC) from the excited singlet state to the excited triplet
state and the kinetics of escape from the T1 state (kesc) were
estimated to be 0.1 and 6ꢂ8ꢄ103 sꢂ1, respectively.50)
Effect of Triplet-Quencher (Sorbate) It was observed
that the photocleavage of 5a was efficiently inhibited by the
Fig. 11. (a) Transient Absorption Spectra Measured by the Photoexcita-
tion of 5a at 266 nm Laser Pulse in a 90/10 Mxture of CH3CN and Water
(10 mM HEPES at pH 7.4) and (b) Time Dependent Decrease in O.D. at
410 nm
presence of potassium sorbate (trans,trans-2,4-hexadienoate),
a
triplet quencher, whose ET is estimated to be about 60 kcal
molꢂ1 based on the reported ET value for methyl sorbate
(62 kcal molꢂ1)51) (right middle part in Chart 7). The Stern–
Volmer plot showed a linear correlation between sorbate con-
centration and the relative kinetics with a slope (KSV) of
ꢂ1
5.2ꢄ103 M (Fig. 10). According to the Eq. 1, in which KSV
is the Stern–Volmer constant (slope of Stern–Volmer plot), t
is the life time of an excited state, and kq is the quenching ki-
netics constant, the life time of an excited state (t) was esti-
mated to be 0.3 ms, assuming a diffusion-controlled quench
(kqꢀ1.7ꢄ1010 ꢂ1 sꢂ1).51) Consideration these results with
M
Fig. 12. Stern–Volmer Plot for the Photolysis of 5a (50 mM) with Et3N in
a Mixture of CH3CN and 10 mM HEPES (pH 7.4) (90/10) at 25 °C
the aforementioned BZ-sensitizing results led us to hypothe-
size that the photolysis of 5a proceeds via the excited triplet
state (5a*(T1)) rather than the singlet state (5a*(S1)).52)
We thus examined the kinetics of the photocleavage of 5a
(50 mM) in CH3CN/10 mM HEPES (pHꢀ7.4) (90/10) in the
presence of Et3N (0—10 mM), which serves as an external
KSVꢀtꢄkq
(1)
We also carried out the laser flash photolysis of 5a (excita- electron donor. Figure 12 shows the Stern–Volmer plot for
tion using the 266 nm laser pulse). The transient absorption the F0/F values (F0 is the quantum yield for the photoreac-
was observed with a lmax of 410 nm with a lifetime (t)ꢆ0.5 tion in the absence of Et3N) against the concentration of
ms, which might be assigned to T1 of 5a (Fig. 11).53)
Et3N. At [Et3N]ꢆ0.02 mM, the F0/F values decrease (the
Effect of Electron Donor (Et3N) Masanovi’s group and photoreaction is accelerated), indicating that Et3N accelerates
other groups reported that sulfonyl esters or sulfonamide de- the photolysis via the longer-lifetime excited state (T1) (bot-
rivatives undergo photolysis via intramolecular electron tom right part in Chart 7). In contrast, the F0/F values in-
transfer21,22,30) or intermolecular electron transfer.18—20,31) As creased (the photoreaction is decreased) at [Et3N]ꢇ0.02 mM
described above, the effect of substituent groups on the ben- with a gradual slope (KSVꢀ40 Mꢂ1 at [Et3N]ꢀ5—10 mM), in-
zenesulfonyl moiety on the kinetics of the photolysis of 5a— dicating that Et3N quenches the ns-lifetime excited state (S1)
d was negligible (Table 1), indicating that intramolecular (bottom left part in Chart 7).
photoinduced electron transfer between two aromatic rings of
It is generally assumed that hydrogen transfer from Et3N to
5a is a minor pathway.
the radical intermediate 31 formed by the homolysis of

November 2009
1263
Conclusion
In this report, we described the photolysis of our caged
Zn2ꢁ-fluorophore 3 (H2L1), its Zn2ꢁ complex 4 (Zn(Hꢂ1L1)),
8-quinolinyl sulfonates that have no Zn2ꢁ-chelation unit and
related compounds. It is noteworthy that the photolysis of
5—8 in aqueous solution is a very clean reaction, giving the
corresponding sulfonates and 8-quinolinols with the produc-
tion of only negligible amounts of byproducts, such as photo-
Fries rearrangement products. Based on steady-state experi-
ments and DFT calculations, we conclude that the photohy-
drolysis of 5a (as well as 3 and 4) proceeds via S–O bond ho-
molysis in the excited triplet state (Chart 7).
Because photolabile protecting groups for caging biomole-
cules are limited,58—69) these results may provide useful infor-
mation concerning the design and synthesis of sulfonate-
based photochemical protecting groups or reagents. Indeed,
we have recently reported on the photocleavable biotin linker
containing 8-quinolinyl sulfonate moiety for the isolation of
dopamine-antibody complex70) and photolabile liposome.71)
Moreover, 8-quinolinol derivatives have been reported as
potential platforms for the inhibitiors of metal enzymes (e.g.;
Zn2ꢁ enzymes),72) neuroprotective drugs,73—75) regulators of
gene expression,76) and building blocks of supramolecular
systems.77) Therefore, photochemical characteristics of pro-
tected 8-quinoline derivatives and their derivatives would be
useful in organic, bioorganic, and analytical chemistry and
Chart 8
Fig. 13. DFT Calculation (B3LYP/6-31ꢁG(d)) for (a) HOMO and (b)
LUMO of 5a
5a*(T1) prevents the recombination of the 30 and 31 radical related areas.
pair (Chart 7) resulting in an acceleration of the photolysis.
We assume that Et3N would donate its electron to 5a in the
Experimental
General Information All reagents and deuterated solvents were pur-
excited states 5a* at high concentrations of Et3N to form
chased at the highest commercial quality and were used without further pu-
rification. Solvents were purchased at the highest commercial quality and
were used after distillation. All aqueous solutions were prepared using
deionized and distilled water. Buffer solutions (CAPS, pH 10.0; CHES, pH
9.0; TAPS, pH 8.4 and 8.0; HEPES, pH 7.8, 7.6, 7.4, and 7.0; MES, pH 6.5)
were used and the ionic strengths were adjusted with NaNO3. The Good’s
buffer reagents (Dojindo) were commercially available: MES (2-morphololi-
noethanesulfonic acid, pKaꢀ6.2), HEPES (N-(2-hydroxyethyl)piperazine-
Nꢃ-2-ethanesulfonic acid, pKaꢀ7.5), TAPS (N-(tris(hydroxymethyl)methyl-
amino)-3-propanesulfonic acid, pKaꢀ8.4), CHES (2-(cyclohexylamino)-
ethanesulfonic acid, pKaꢀ9.5), CAPS (3-(cyclohexylamino)propanesulfonic
acid, pKaꢀ10.4). Melting points were measured on a Büchi 510 Melting
Point Apparatus and are uncorrected. UV spectra were recorded on a Hitachi
U-3500 spectrophotometer and JASCO UV/VIS spectrophotometer V-550,
and fluorescence (excitation and emission) spectra were recorded on a
JASCO FP-6500 spectrofluorometer at 25ꢅ0.1 °C. The quantum yield of
fluorescence (FF) was determined by comparison with the integrated
corrected emission spectrum of a quinine sulfate standard, whose quantum
yield in 0.1 M H2SO4 was assumed to be 0.55 (excitation at 366 nm). IR
spectra were recorded on a JASCO FTIR-410 spectrophotometer at room
temperature. 1H- (300 MHz) and 13C- (75 MHz) NMR spectra were recorded
on a JEOL Always 300 spectrometer. Tetramethylsilane was used as an inter-
nal reference for 1H- and 13C-NMR measurements in CDCl3 and CD3CN. 3-
(Trimethylsilyl)propionic-2,2,3,3-d4 acid (TSP) sodium salt was used as an
external reference for 1H- and 13C-NMR measurements in D2O. The pD val-
ues in D2O were corrected for deuterium isotope effects using pDꢀ(pH-
meter reading)ꢁ0.40. Elemental analyses were performed on a Perkin-Elmer
CHN 2400 analyzer. Thin-layer (TLC) and silica gel column chromatogra-
phies were performed using a Merck 5554 (silica gel) TLC plate and Fuji
Silysia Chemical FL-100D, respectively.
.
5a ꢂ, which would be converted to the ground state (S0), as a
consequence, thus suppressing photolysis.54,55)
The most plausible pathway for the photolysis of 5a based
on the aforementioned experimental results would be the ho-
molysis of an S–O bond in the excited triplet state (T1) to
give the corresponding radicals 30 and 31, which are then
converted to 12 (via auto-oxidation or similar paths)56) and 7,
respectively, as shown in Chart 7. The possibility that H2O
plays important roles (e.g. electron donor) cannot be com-
pletely excluded, because the photolysis of 5a in anhydrous
MeCN or in anhydrous 2-methyltetrahydrofuran affords, not
only 7 and 12a but also byproducts.
The difference in the reaction mechanism for the photoly-
sis of 5 from those of 22 (Chart 4), 26 (Chart 5), and 29
(Chart 6) can be explained by Chart 8. In the photolysis of 22
and 26, the arenesufonyl groups are excited.17—20) In addi-
tion, in the photolysis of 29, the arenesulfonyl and aryloxy
groups are excited.23,24) On the other hand, the photolysis of
our substrate 5—8 is triggered by excitation of the 8-quino-
linyl group, which may alter the reaction pathway.
Our hypothesis is consistent with a result of a density
functional theory (DFT) calculation study of 5a.57) As shown
in Fig. 13, the lowest unoccupied molecular orbital (LUMO)
includes an anti-bonding sigma orbital (s*) between S and O
(Fig. 13b), whereas the highest occupied molecular orbital
(HOMO) contains a bonding sigma orbital (s) (Fig. 13a). It
is likely that the homolytic fission of the S–O sigma bond is
triggered by the single electron excitation from HOMO to
LUMO. In fact, attempt at structural optimization of 5a*(T1)
induced the S–O bond cleavage to give 30 and 31 (data not
shown).
Material Preparation Quinolinol derivatives 9 and 11 were prepared
according to the method reported by Imperiali et al.78,79) The preparation of
8-quinolinol-pendant cyclen derivatives 1, 2, 3, and 4 were reported previ-
ously.38,40)
8-Benzenesulfonyloxy-5-N,N-dimethylaminosulfonylquinaldine (5a)38)
A solution of benzenesulfonyl chloride (164 ml, 1.28 mmol) in THF (10 ml)
was added dropwise to a solution of 5-N,N-dimethylaminosulfonyl-8-hy-
droxy-quinaldine (9) (256 mg, 1.00 mmol) and Et3N (210 ml, 1.5 mmol) in

1264
Vol. 57, No. 11
THF (10 ml). After stirring for 5 h at room temperature, the reaction mixture
was poured into water and the solution was extracted with CHCl3. The or-
ganic layer was washed with saturated NaHCO3 aq, 0.1 M aq. HCl, and brine.
The combined organic layer was dried over Na2SO4, filtered, and concen-
trated under reduced pressure. The resulting solid was recrystallized from
CH2Cl2/EtOH to give 5a (354 mg, 87% yield) as colorless crystals: mp
131.5—132.0 °C. IR (KBr) cmꢂ1: 3094, 2951, 1602, 1500, 1452, 1373,
1323, 1193, 1144, 1115, 1092, 1060, 957, 863, 834, 796, 756, 739, 726. 1H-
NMR (CDCl3) d: 2.53 (3H, s), 2.81 (6H, s), 7.36 (1H, d, Jꢀ9.0 Hz, ArH),
7.49 (2H, t, Jꢀ7.7 Hz, PhH), 7.62 (1H, t, Jꢀ7.5 Hz, PhH), 7.73 (1H, d, Jꢀ
8.2 Hz, ArH), 8.01 (2H, d, Jꢀ7.1 Hz, PhH), 8.11 (1H, d, Jꢀ8.2 Hz, ArH),
8.92 (1H, d, Jꢀ9.0 Hz, ArH). 13C-NMR (CDCl3) d: 25.1, 37.4, 121.3, 124.1,
124.7, 128.7, 128.8, 128.8, 131.8, 133.5, 134.1, 136.1, 141.3, 148.6, 160.5.
Anal. Calcd for C18H18N2O5S2: C, 53.19; H, 4.46; N, 6.89. Found: C, 52.73;
H, 4.00; N, 6.76.
5-N,N-Dimethylaminosulfonyl-8-(4-methoxybenzenesulfonyloxy)quinal-
dine (5b) A solution of 4-methoxybenzenesulfonyl chloride (186 mg, 0.90
mmol) in CH2Cl2 (3 ml) was added to a solution of 9 (200 mg, 0.75 mmol)
and Et3N (99 mg, 0.98 mmol) in CH2Cl2 (5 ml) at 0 °C. The reaction mixture
was stirred at 0 °C for 30 min and at room temperature for 1 h, to which H2O
(10 ml) was added and then the biphasic reaction mixture was vigorously
stirred for 30 min. The mixture was transferred to a separatory funnel and
extracted with CH2Cl2. The combined organic layer was washed with satu-
rated aq. K2CO3 and water, dried over K2CO3, filtrated, and concentrated
under reduced pressure. The residue was purified by silica gel column chro-
matography (1 : 3 hexanes/EtOAc) and recrystallization from AcOEt to
afford 5b (170 mg, 52% yield) as a colorless powder: mp 161.5—163.0 °C.
IR (KBr) cmꢂ1: 3087, 2914, 2847, 1597, 1498, 1464, 1351, 1321, 1264,
1188, 1141, 1115, 1094, 1060, 1027, 957, 864, 829, 810, 782, 729, 585. 1H-
NMR (CDCl3) d: 2.61 (3H, s), 2.81 (6H, s), 3.86 (3H, s), 6.92 (2H, d, Jꢀ
8.8 Hz), 7.37 (1H, d, Jꢀ9.0 Hz), 7.73 (1H, d, Jꢀ8.1 Hz), 7.92 (2H, d, Jꢀ
8.8 Hz), 8.09 (1H, d, Jꢀ8.1 Hz), 8.92 (1H, d Jꢀ9.0 Hz). 13C-NMR (CDCl3)
d: 25.1, 37.4, 55.7, 113.9, 121.2, 124.0, 124.7, 127.3, 128.9, 131.2, 131.6,
133.5, 141.4, 148.8, 160.4, 163.6, 164.1. Anal. Calcd for C19H20N2O6S2: C,
52.28; H, 4.62; N, 6.42. Found: C, 52.08; H, 4.32; N, 6.42.
s), 2.82 (6H, s), 2.91 (6H, s), 7.49 (1H, d, Jꢀ9.0 Hz, ArH), 7.62 (2H, t, Jꢀ
8.4 Hz, PhH), 7.74 (1H, t, Jꢀ8.4 Hz, PhH), 8.06 (2H, d, Jꢀ8.4 Hz, PhH),
8.53 (1H, s, ArH), 9.00 (1H, d, Jꢀ9.0 Hz, ArH). 13C-NMR (CDCl3) d: 24.8,
37.6, 37.6, 125.9 126.6, 128.1, 128.4, 128.8, 130.1, 132.2, 133.6, 133.8,
139.0, 142.2, 148.2, 161.5. Anal. Calcd for C20H23N3O7S3: C, 46.77; H,
4.51; N, 8.18. Found: C, 46.77; H, 4.18; N, 8.16.
5-N,N-Dimethylaminosulfonyl-8-methylsulfonyloxyquinaldine
(8)
Methanesulfonyl chloride (28 ml, 0.36 mmol) was added to a solution of 9
(80 mg, 0.30 mmol) and Et3N (28 ml, 0.39 mmol) in CH2Cl2 (2 ml) at 0 °C.
The reaction mixture was stirred at room temperature for 2 h, to which water
(0.5 ml) was added. After the whole was vigorously stirred for 30 min, the
reaction mixture was extracted with CH2Cl2. The combined organic layer
was washed with sat. aq. K2CO3 and sat. aq. NaCl, dried over K2CO3, fil-
tered, and concentrated under reduced pressure. The remaining residue was
purified by silica gel column chromatography (hexanes/AcOEt) to afford 8
as a colorless powder. After recrystallization from hexane/AcOEt, 8 was
obtained as colorless prisms (55 mg, 53% yield): mp 134—136 °C. IR (KBr)
1
cmꢂ1: 3092, 2918, 1499, 1464, 1358, 1342, 1180, 1151. H-NMR (CDCl3)
d: 2.79 (3H, s), 2.84 (6H, s), 3.56 (3H, s), 7.50 (1H, d, Jꢀ9.0 Hz, ArH), 7.73
(1H, d, Jꢀ8.0 Hz, ArH), 8.13 (1H, d, Jꢀ8.2 Hz, ArH), 9.03 (1H, d, Jꢀ
9.0 Hz, ArH). 13C-NMR (CDCl3) d: 25.3, 37.5, 39.7, 122.0, 124.3, 124.9,
129.1, 132.1, 134.1, 141.4, 148.9, 168.8. Anal. Calcd for C13H16N2O5S2: C,
45.34; H, 4.68; N, 8.13. Found: C, 45.41; H, 4.25; N: 8.00.
1-Benzenesulfonyloxynaphthalene (14)80) This sulfonate was obtained
as colorless fine cubic crystals (70% yield) from the reaction of 1-naphthol
(15) and benzenesulfonyl chloride in a manner similar to that described for
1
5a. H-NMR (CDCl3) d: 7.20 (1H, d, Jꢀ7.3 Hz), 7.30—7.46 (5H, m), 7.57
(1H, t, Jꢀ7.5 Hz), 7.71 (1H, d, Jꢀ7.7 Hz), 7.77 (1H, d, Jꢀ8.0 Hz), 7.85—
7.89 (3H, m). 13C-NMR (CDCl3) d: 118.4, 121.5, 125.0, 126.6, 127.1,
127.1, 127.6, 128.3, 129.1, 134.2, 134.6, 135.4, 145.6.
2,4,7-Tris(N,N-dimethylaminosulfonyl)-1-naphthol (17) A mixture of
1-naphthol (1.0 g, 6.9 mmol) and chlorosulfonic acid (10 ml) was stirred at
130 °C for 2 h and poured into ice (50 g). The insoluble residue was isolated
by filtration and dried under reduced pressure. The resulting solid was dis-
solved in CH2Cl2, to which a 2.0 M solution of Me2NH (20 mmol) in THF
(10 ml) was added, and the whole was stirred for 12 h at 25 °C. The solvent
was removed under reduced pressure and the remaining residue was recrys-
tallized from AcOEt to give 17 (1.2 g, 36% yield) as a colorless powder: mp
223—226 °C. IR (neat) cmꢂ1: 3244, 3021, 2970, 2893, 2815, 1616, 1563,
1500, 1459, 1342, 1262, 1189, 1163, 1073, 958, 763, 718, 604, 556, 425.
1H-NMR (CDCl3) d: 2.81 (6H, s), 2.86 (6H, s), 2.89 (6H, s), 8.09 (1H, dd,
Jꢀ9.0, 1.8 Hz), 8.37 (1H, s), 8.84 (1H, d, Jꢀ9.0 Hz), 8.94 (1H, d, Jꢀ1.8
Hz), 10.62 (1H, s). 13C-NMR (CDCl3) d: 37.3, 37.7, 37.9, 112.5 125.1, 125.4,
125.5, 126.8, 128.4, 130.9, 133.7, 135.1, 158.2. HR-FAB-MS m/z: 466.0776
(Calcd for C16H24N3O7S3:466.0776).
1-Benzenesulfonyloxy-2,4,7-tris(N,N-dimethylaminosulfonyl)naphtha-
lene (16) This sulfonate was isolated as a colorless powder (29% yield) from
the reaction of 17 and benzenesulfonyl chloride in a manner similar to that
described for 14. IR (neat) cmꢂ1: 3097, 3019, 2961, 1555, 1451, 1344,
1163, 1054, 960, 746, 719, 450. 1H-NMR (CDCl3) d: 2.63 (6H, s), 2.87 (6H,
s), 2.97 (6H, s), 7.66 (2H, t, Jꢀ8.1 Hz, PhH), 7.80 (1H, t, Jꢀ8.1 Hz, PhH),
8.12—8.18 (3H, m), 8.61 (1H, s, ArH), 8.97 (1H, d, Jꢀ9.0 Hz, ArH), 9.18
(1H, d, Jꢀ1.5 Hz, ArH). 13C-NMR (CDCl3) d: 37.5, 37.6, 38.0, 126.9,
126.9, 128.1, 128.3, 129.2, 129.3, 130.1, 130.8, 133.3, 133.8, 135.3, 136.4,
148.0. Anal. Calcd for C22H27N3O9S4: C, 43.62; H, 4.49; N, 6.94. Found: C,
43.48; H, 4.16; N, 6.59.
8-(4-Bromobenzenesulfonyloxy)-5-N,N-dimethylaminosulfonylquinal-
dine (5c) This sulfonate was prepared as colorless needles (60% yield)
from 9 and 4-bromobenzenesulfonyl chloride in a manner similar to that de-
scribed for 5b: mp 171.5—172.0 °C. IR (neat) cmꢂ1: 3097, 2912, 1599,
1575, 1496, 1377, 1343, 1189, 1150, 1092, 1059, 1011, 955, 796, 746, 720,
1
622, 437. H-NMR (CDCl3) d: 2.55 (3H, s), 2.82 (6H, s), 7.38 (1H, d Jꢀ
9.0 Hz, ArH), 7.63 (2H, d, Jꢀ8.7 Hz, BrArH), 7.75 (1H, d, Jꢀ8.1 Hz, ArH),
7.86 (2H, d, Jꢀ8.7 Hz, BrArH), 8.11 (1H, d, Jꢀ8.1 Hz, ArH), 8.93 (1H, d,
Jꢀ9.0 Hz, ArH). 13C-NMR (CDCl3) d: 25.1, 37.4, 121.6, 124.2, 124.7,
128.8, 129.5, 130.3, 132.1, 132.2, 133.4, 135.2, 141.2, 148.5, 160.6. Anal.
Calcd for C18H17BrN2O5S2: C, 44.54; H, 3.53; N, 5.77. Found: C, 44.46; H,
3.51; N, 5.81.
5-N,N-Dimethylaminosulfonyl-8-pentafluorobenzenesulfonyloxy-
quinaldine (5d) This sulfonate was prepared as a pale yellow powder
(78% yield) from 9 and pentafluorobenzenesulfonyl chloride in a manner
similar to that described for 5b: mp 163—166 °C. IR (KBr) cmꢂ1: 3095,
2975, 1648, 1602, 1523, 1507, 1395, 1345, 1194, 1148, 1102, 1055, 994,
1
962, 866, 854, 832, 817, 722, 625. H-NMR (CDCl3) d: 2.46 (3H, s), 2.83
(6H, s), 7.42 (1H, d, Jꢀ9.0 Hz, ArH), 7.80 (1H, d, Jꢀ8.1 Hz, ArH), 8.15
(1H, d, Jꢀ8.1 Hz, ArH), 8.99 (1H, d, Jꢀ9.0 Hz, ArH). 13C-NMR (CDCl3) d:
24.8, 37.4, 122.1, 124.4, 124.4, 124.9, 128.8, 129.8, 133.0, 133.9, 134.0,
140.8, 147.2, 148.3, 160.7. HR-FAB-MS m/z: 497.0263 (Calcd for C18H14F5-
N2O5S2: 497.0264).
2-Benzenesulfonyloxyanthraquinone (18) This sulfonate was obtained
as a brown solid (70% yield) from 2-hydroxyanthraquinone and benzenesul-
8-Benzenesulfonyloxyquinaldine (6)78) This sulfonate was prepared as
colorless needles (64% yield) from 8-hydroxyquinaldine (10) and benzene-
sulfonyl chloride in a manner similar to that for 5b: mp 116.0—117.5 °C.
1H-NMR (CDCl3) d: 2.50 (3H, s), 7.19 (1H, d, Jꢀ8.4 Hz), 7.40—7.47 (3H,
m), 7.57 (1H, tt, Jꢀ7.4, 1.3 Hz), 7.66 (2H, dt, Jꢀ8.8, 1.3 Hz), 7.95—8.00
(3H, m). 13C-NMR (CDCl3) d: 25.2, 122.6, 123.1, 125.1, 126.8, 127.8,
128.5, 128.8, 133.7, 135.7, 136.5, 140.8, 144.9, 159.6.
fonyl chloride in a manner similar to that described for 5b. IR (neat) cmꢂ1
:
1677, 1591, 1480, 1449, 1381, 1325, 1291, 1203, 1183, 1132, 1091, 984,
1
931, 866, 790, 742, 712, 687, 443. H-NMR (CDCl3) d: 7.50 (1H, dd, Jꢀ
8.4, 2.4 Hz), 7.58 (2H, t, Jꢀ7.5 Hz), 7.72 (1H, t, Jꢀ7.5 Hz), 7.80—7.85
(3H, m), 7.90 (2H, d, Jꢀ8.1 Hz), 8.27—8.32 (3H, m). 13C-NMR (CDCl3) d:
120.5, 127.4, 127.9, 128.5, 129.5, 129.7, 131.9, 133.2, 133.3, 134.3, 134.5,
134.8, 135.0, 135.3, 153.8, 181.8, 181.9. HR-FAB-MS m/z: 365.0484 (Calcd
for C20H13O5S: 365.0484).
8-Benzenesulfonyloxy-5,7-bis(N,N-dimethylaminosulfonyl)quinaldine
(7) A solution of 5,7-bis(N,N-dimethylaminosulfonyl)-8-quinolinol (11)78,79)
(430 mg, 1.1 mmol) and benzenesulfonyl chloride (190 ml, 1.4 mmol) and 4-
dimethylaminopyridine (28 mg, 0.24 mmol) in CH2Cl2 (5 ml) was stirred at
the reflux temperature for 24 h. The separation and purification were carried
out in a similar manner to that used for the preparation of 5b to obtain 7
(475 mg, 74% yield) as a colorless powder: mp 151.0—152.5 °C. IR (neat)
cmꢂ1: 3097, 3066, 2923, 1495, 1450, 1372, 1345, 1284, 1245, 1197, 1181,
1-Naphthalenesulfonic Acid Phenyl Ester (19)81) A solution of 1-
naphthalenesulfonyl chloride (226 mg, 2.0 mmol) in CHCl3 (5 ml) was added
to a solution of phenol (94 mg, 1.0 mmol) and Et3N (0.28 ml, 2.0 mmol) in
CHCl3 (3 ml) at 0 °C. After stirring for 5 h at room temperature, the reaction
mixture was washed with water, NH4Cl aq., Na2CO3 aq., and brine. The or-
ganic layer was dried over Na2SO4, filtrated, and concentrated under reduced
pressure. The remaining residue was purified by silica gel column chro-
matography (hexanes/CH2Cl2) to give 19 (248 mg, 87% yield) as a colorless
1
1165, 1144, 1075, 968, 797, 764, 718, 607. H-NMR (CDCl3) d: 2.40 (3H,

November 2009
1265
amorphous solid. IR (KBr) cmꢂ1: 1595, 1585, 1508, 1485, 1371, 1204,
1191, 1169, 1152, 1139, 855, 802, 786, 769, 729, 692, 587, 510. H-NMR
(CDCl3) d: 6.84—6.88 (2H, m), 7.14—7.26 (3H, m), 7.46 (1H, t, Jꢀ7.9
Hz), 7.68 (1H, t, Jꢀ7.4 Hz), 7.79 (1H, t, Jꢀ7.7 Hz), 8.08 (1H, d, Jꢀ7.4 Hz),
8.13 (1H, d, Jꢀ8.5 Hz), 8.83 (1H, d, Jꢀ8.5 Hz). 13C-NMR (CDCl3) d: 121.9,
123.8, 124.9, 127.0, 127.2, 128.4, 128.8, 128.9, 129.5, 130.6, 131.1, 131.1,
133.9, 35.6, 149.5.
the Ministry of Education, Culture, Sports, Science and Technology
(MEXT) of Japan (No. 18390009 and 19659026) and High-Tech Research
Center Project for Private Universities (matching fund subsidy from
MEXT). S.A. is grateful to grants from the Mitsubishi Chemical Corpora-
tion Fund (Tokyo), the Terumo Life Science Foundation (Kanagawa), the
Mochida Memorial Foundation for Medical and Pharmaceutical Research
(Tokyo), the Novartis Foundation (Tokyo, Japan), the Naito Foundation
(Tokyo), and the Tokuyama Science Foundation (Tokyo).
1
5-(N,N-Dimethylamino)naphthalenesulfonyloxybenzene (20)82) A so-
lution of dansyl chloride (135 mg, 0.50 mmol) in CHCl3 (5 ml) was added to
a mixture of phenol (47 mg, 0.50 mmol) and Et3N (0.14 ml, 1.0 mmol) in
CHCl3 (1.5 ml) at 0 °C. After stirring for 5 h at room temperature, the reac-
tion mixture was washed with water, NH4Cl aq., Na2CO3 aq., and brine. The
organic layer was dried over Na2SO4, filtrated, and concentrated under re-
duced pressure. The remaining residue was purified by silica gel column
chromatography (hexanes/CH2Cl2) to give 20 (84 mg, 51% yield) as a pale
yellow oil. IR (KBr) cmꢂ1: 1587, 1572, 1487, 1456, 1410, 1369, 1310, 1234,
1204, 1191, 1172, 1144, 861, 784, 724, 689, 629, 573. 1H-NMR (CDCl3) d:
2.91 (6H, s), 6.87—6.91 (2H, m), 7.16—7.21 (3H, m), 7.25 (1H, d), 7.43
(1H, t, Jꢀ8.0 Hz), 7.68 (1H, t, Jꢀ8.2 Hz), 8.06 (1H, d, Jꢀ7.3 Hz), 8.48 (1H,
d, Jꢀ8.6 Hz), 8.59 (1H, d, Jꢀ8.4 Hz). 13C-NMR (CDCl3) d: 45.3, 115.5,
119.4, 122.0, 122.8, 126.9, 128.9, 129.5, 129.6, 130.0, 130.9, 131.1, 131.9,
149.6, 151.8.
References and Notes
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8-Quinolinesulfonic Acid Phenyl Ester (21) 8-Quinolinesulfonyl chlo-
ride (250 mg, 1,1 mmol) was added to a solution of phenol (104 mg, 1.1
mmol) and Et3N (220 mg, 2.2 mmol) in CH2Cl2 (6 ml) at 0 °C. The reaction
mixture was stirred for 2 h and concentrated under reduced pressure. The re-
sulting solid was recrystallized from AcOEt to give 21 (310 mg, 99% yield)
as a colorless powder. IR (neat) cmꢂ1: 1596, 1561, 1487, 1372, 1216, 1192,
1144, 861, 836, 788, 737, 693, 589, 448. 1H-NMR (CDCl3) d: 7.03 (2H, dd,
Jꢀ7.7, 2.0 Hz), 7.14—7.24 (3H, m), 7.59—7.63 (2H, m), 8.14 (1H, dd, Jꢀ
8.2, 1.3 Hz), 8.30 (1H, dd, Jꢀ8.2, 1.6 Hz), 8.38 (H, dd, Jꢀ7.4, 1.3 Hz), 9.27
(1H, dd, Jꢀ4.2, 1.6 Hz). 13C-NMR (CDCl3) d: 122.1, 122.5, 125.2, 126.9,
128.9, 129.5, 132.6, 134.0, 135.3, 136.6, 144.0, 149.9, 152.3. HR-FAB-MS
m/z: 286.0539 (Calcd for C15H12NO3S: 286.0538).
Photoreactions Followed by NMR and HPLC In a typical experiment,
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permeation liquid chromatography (GPLC).
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Determination of Quantum Yields of Photolysis Quantum yields for
the photocleavage of 5 were determined as follows: Method A: A 5—50 mM
solution of a given substrate in CH3CN and HEPES buffered water (10 mM,
pH 7.4) (9 : 1) was placed into 1ꢄ1 cm quartz cell, and irradiated with 150
W Xe lamp in a spectrofluorometer (JASCO FP-6500 with a band-width of
5 nm). The initial rate of the photolysis (vi) was determined by a UV–Vis
spectrometer and high performance liquid chromatography (HPLC, ODS-
column with a CH3CN–phosphate buffer (pH 6.0) (5 : 5) as the eluent). The
quantum yield was calculated using the equation FꢀviꢄV/{I0ꢄ(1—
10ꢂabs)}, where V is the volume of the reaction solution, I0 is the number of
photon per second at given wavelength, and abs is the initial absorbance
(cell lengthꢀ1 cm) of 5 (0.073 at 328 nm for 5a). The I0 value was deter-
mined by means of a ferroxalate actinometry.46) Method B: A 2.0 ml of 2.0
mM solution of a given substrate in CH3CN and HEPES buffered water (10
mM, pH 7.4) (9 : 1) was placed into 1ꢄ1 cm quartz cell, and irradiated with
150 W Xe lamp in a spectrofluorometer (JASCO FP-6200 with a band-width
of 20 nm). The initial absorbance (cell lengthꢀ1 cm) was ꢇ3. The numbers
of reacted molecules after irradiation was determined by HPLC (ODS-col-
umn with a MeOH–phosphate buffer (pH 6.0) (6 : 4 or 7 : 3) as the eluent).
The quantum yield was calculated using the equation Fꢀ(number of reacted
molecules)/(I0ꢄirradiation time). Quantum yields of photolysis for other
substrates were determined in a similar manner.
Quenching Examination The 50 mM solutions of substrates in CH3CN
and H2O (10 mM HEPES at pH 7.4) with given concentrations of potassium
sorbate or Et3N were placed in a 1ꢄ1 cm quartz cell and irradiated with a
150 W Xe lamp. The relative rates of photocleavage were determined by
UV–Vis spectrometry.
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Benzophenone Sensitizing Examination A mixture of 5a (1 mM) and
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the reaction mixture then analyzed by 1H-NMR spectroscopy.
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Acknowledgement This work was supported by the Grants-in-Aid from

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Vol. 57, No. 11
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photoirradiation. Even in the presence of O2, photoreaction rates and
photoproducts were identical to those in the absence (or at the low
concentration) of O2.
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