Synthesis of Aromatic Disulfonic Acids for Water-Soluble Dibenzothiophene Derivatives

Article abstract of DOI:10.1055/s-0036-1591969

There is a need for efficient methods for the synthesis of water-soluble dibenzothiophene (DBT) and dibenzothiophene S -oxide (DBTO) derivatives to allow for the study of atomic oxygen in biological applications. Attaining water-solubility of aromatic compounds is effectively achieved through functionalization with sulfonic acid groups. Three approaches for the synthesis were considered. An indirect approach was unsuccessful. A modular approach was found to be highly effective for one DBTO disulfonic acid derivative (>99% pure). The direct approach was the most straightforward and highest-yielding route. Additionally, a highly effective, scalable, and improved purification method was identified for disulfonic acid DBT and DBTO derivatives, allowing for the isolation of positional isomers and other modifications by using reverse-phase high-performance flash chromatography.

Full text of DOI:10.1055/s-0036-1591969

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–H
paper
A
en
S. M. Omlid et al.
Paper
Synthesis
Synthesis of Aromatic Disulfonic Acids for Water-Soluble Dibenzo-
thiophene Derivatives
Sara M. Omlid
Direct Approach
36% sulfoxide
(46% sulfide)
Ankita Isor
(2)
(3)
(1)
Kathryn L. Sulkowski
S. M. Chintala
+
+
+
O
O
SO3H
S
S
John T. Petroff II
Ryan D. McCulla*
0
0
0
0
0-
0
0
3
3-
3
8
1
8-
8
8
0
Br
Br
Modular Approach
Department of Chemistry, Saint Louis University,
3501 Laclede Ave., St. Louis, MO 63103, USA
ryan.mcculla@slu.edu
HO3S
SO3H
+
(2)
(1)
(3)
+
O
– R
RO3S
R = neopentyl
22% sulfoxide
(18% sulfide)
high purities (95–100%)
Received: 17.01.2018
Accepted after revision: 27.02.2018
Published online: 12.04.2018
Arylsulfonic acids are typically prepared via sulfona-
tion.8 A series of over ninety articles on aromatic sulfona-
tion reactions were published last century,14–26 and, yet,
there are still no reports that specifically address the issues
associated with the synthesis and subsequent purification
of multifunctional aryldisulfonic acids such as those in Fig-
ure 1.27 Sulfonation reactions can be severely restrictive to
the design of multistep syntheses due to harsh reaction
conditions (i.e., low pH, high temperatures) and a regio-
selectivity similar to other electrophilic aromatic substitu-
tion reactions.8,28 Additionally, further functionalization of
arylsulfonic acids can be challenging due to their poor solu-
bility in organic solvents, their hygroscopic properties, and
their purification, which is particularly arduous and can of-
ten be futile, since normal-phase chromatography is not
feasible.7,29
DOI: 10.1055/s-0036-1591969; Art ID: ss-2018-m0035-op
Abstract There is a need for efficient methods for the synthesis of wa-
ter-soluble dibenzothiophene (DBT) and dibenzothiophene S-oxide
(DBTO) derivatives to allow for the study of atomic oxygen in biological
applications. Attaining water-solubility of aromatic compounds is effec-
tively achieved through functionalization with sulfonic acid groups.
Three approaches for the synthesis were considered. An indirect ap-
proach was unsuccessful. A modular approach was found to be highly
effective for one DBTO disulfonic acid derivative (>99% pure). The direct
approach was the most straightforward and highest-yielding route. Ad-
ditionally, a highly effective, scalable, and improved purification meth-
od was identified for disulfonic acid DBT and DBTO derivatives, allowing
for the isolation of positional isomers and other modifications by using
reverse-phase high-performance flash chromatography.
Key words sulfonic acids, sulfonation, sulfoxides, sulfides, dibenzo-
thiophene, Suzuki coupling
O
S
S
Dibenzothiophene S-oxide (DBTO) has been suggested
as an adequate atomic oxygen [O(3P)] precursor and is of
particular interest for biological examination.1–3 Upon photo-
initiation, DBTO deoxygenates to form dibenzothiophene
(DBT) and, putatively, O(3P) in a variety of solvents.4 To al-
low for biological studies, we have taken an interest in pre-
paring water-soluble DBTO and DBT derivatives, particular-
ly through the addition of hydrophilic sulfonic acid groups
(–SO3H).
O
S
HO3S
SO3H
HO3S
SO3H
1a, 1b
3a
2a, 2b
HO3S
SO3H
Figure 1 DBT and DBTO disulfonic acid derivatives
Since they were first synthesized in 1825,5 arylsulfonic
acids and their salts (e.g. sodium sulfonate) have been use-
ful in improving the water-solubility of compounds found
in many industries, and today they are commonly found in
detergents, pharmaceuticals, polymers, fluorescent labels,
and dyes.6–13
Consequently, there is a need for better methods for the
synthesis and purification of multifunctional aryldisulfonic
acids. We sought to address this need through the develop-
ment of synthesis procedures for DBT derivatives 1a–3a
(Figure 1) and DBTO derivatives 1b and 2b (Scheme 1).
Herein, we evaluate three synthetic strategies for DBT and
DBTO disulfonic acid derivatives with the notion that our
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

B
S. M. Omlid et al.
Paper
Synthesis
evaluations might be more generally applicable to other
multifunctional aryldisulfonic acids. To gauge our success,
we compare our efforts to the previous synthesis of 1a and
1b (Scheme 1).3
O
S
mCPBA, CH2Cl2,
0 °C, 3 h
S
45–65%
Br
Br
Br
Br
6a
6b
O
DMDO,
MeOH,
H2O, –42 °C
ClSO3H,
CH2Cl2,
0 °C
Pd(PPh3)4,
Pd(dppf)Cl2,
PCy3, Na2CO3,
7, argon,
S
S
Pd(PPh3)4,
Pd2(dba)3,
Na2CO3,
7, argon,
50–65 °C, 7 h
RO3S
1a
23%
53%
20%
57%
HO3S
SO3H
50–65 °C, 7 h
1b
DBT
B(OH)2
Scheme 1 Previously reported synthesis of 1a and 1b3
7
O
S
S
Indirect Approach. With an aim to overcome purifica-
tion issues, we devised a synthetic strategy that would al-
low for normal-phase purification to easily separate consti-
tutional isomers. To synthesize the key disulfonyl ester in-
termediate (Scheme 2), we investigated a two-step protocol
that we previously implemented for the addition of a single
sulfonate ester group to a DBT derivative.30 However, when
we proceeded to add two sulfonyl chlorides to DBT, we
were unable to isolate the disulfonyl chloride product 5.
GC-MS and LC-MS analysis of the crude reaction mixture
did not reveal a peak corresponding to 5, and analysis of 1H
NMR did not reveal any peaks that could clearly be attribut-
ed to 5. In a previous study by another group, 5 was synthe-
sized in a similar fashion, but no NMR data were available
for 5.31 Therefore, we attempted to convert the crude prod-
uct from the synthesis of 5 into the disulfonyl ester by using
known procedures.30,32 However, we were again unable to
isolate or characterize the product. Similar results were ob-
served with the starting material 2,8-diphenyldibenzothio-
phene (4a). Despite the precedence, an indirect approach is
apparently not appropriate for the preparation of DBT di-
sulfonic acids derivatives.
O
O
O O
O
O
8a
8b
S
S
S
S
O
O
O O
O
O
NMe4Cl, DMF (anhydrous),
argon, 150 °C, 0.5–1 h
80%
63%
2a
2b
Scheme 3 Modular approach for 2a and 2b
The DBT synthon (2,8-dibromodibenzothiophene, 6a)
and the protected monosulfonic acid synthon [4-(neo-
pentyloxysulfonyl)phenylboronic acid, 7] were both com-
mercially available. Dibenzothiophene 6a was oxidized to
6b by using mCPBA and purified by using normal-phase
flash chromatography.33 Coupling of 6a or 6b and 7 was
achieved by using a Suzuki cross-coupling reaction,34 with
minor modifications to the standard protocol.30,35 Following
optimization, above average catalyst loading (9–12 mol%)
and molar ratios (>2:1) were found to be necessary to
achieve high conversions (>90%).
1) ClSO3H,
DABCO,
CH2Cl2, r.t.,
0.5 h
ROH, r.t.,
1 h
S
S
DBT
Coupling of 6a and 7 resulted in high yields of the 4-sul-
fonylester homocoupled product (9, identified by LC-MS,
Figure 2) relative to 8a, which could not be isolated with
column chromatography. Recrystallization of 8a and 9 re-
sulted in needle-like crystals of 8a; however, often a differ-
ent crystal type (polygonal crystals), primarily consisting of
9, was observed instead. Product 9 was also observed as an
SO3R
RO3S
SO2Cl
ClO2S
2) SOCl2,
DMF (cat.),
reflux, 24 h
5
R = iPr
Scheme 2 Proposed synthetic route for the disulfonyl ester intermedi-
ate
Modular Approach. An alternative, modular approach
was proposed as shown in Scheme 3. In this approach, a
DBT synthon and two protected monosulfonic acid syn-
thons are coupled, eliminating the need for the unattain-
able disulfonyl chloride intermediate. By protecting the sul-
fonic acid groups as non-polar sulfonate esters, positional
isomers and byproducts of further functionalization (in this
case, oxidation of the sulfide) can be removed through nor-
mal-phase column chromatography. For our purposes, this
approach was only feasible for target molecules 2a and 2b.
O
O
O
S
O
S
S
O
O
O
O
9
2c
HO3S
SO3H
Figure 2 Structure of the resulting homocoupling of 7 and the prod-
uct of overoxidation of 2a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

C
S. M. Omlid et al.
Paper
Synthesis
impurity in the synthesis of 8b, but to a much lesser extent
and was easily removed via normal-phase column chroma-
tography.
rification. This method was found to be successful in com-
pletely removing NMe4Cl from 2a and 2b in two sequential
columns. We also found that 2c could be completely re-
moved, and partial resolution of 2b and 2c was observed in
the HPFC-UV spectra. The result was surprising, since the
best baseline resolution obtained for 2b and 2c using a C18
analytical column (5 μm) was not quite one minute.
When a sample of crude 2b was loaded onto a C18 sam-
plet with water only, the sample dried as a thin layer on the
C18, and excellent separations were observed. Conversely,
when 90% methanol in water was used, there was virtually
no resolution between the peaks for 2b and 2c. The results
implied that dry loading was key to the success of this
method.
Although related purification methods have previously
been reported for many different aryldisulfonic acids,12,46,47
we are not aware of any that utilized dry loading, and, more
significantly, that have delivered the resolutions necessary
to separate water-soluble sulfoxides from sulfones (e.g., 2b
and 2c) on a medium scale (mg to g).
Direct Approach for Disulfonic DBT Derivatives. A di-
rect approach was previously used to synthesize 1a, but
with poor yields (20%).3 The better and more reliable purifi-
cation method presented in this report warranted the re-
evaluation of a direct method (Scheme 4).
Dibenzothiophenes 4a and 10a were synthesized by us-
ing previously reported methods with minor modifica-
tions.48,49 The Suzuki coupling of 6a and phenylboronic acid
resulted in 4a in high yields (79%). We primarily attributed
the higher yields of 4a relative to those of 8a (23%) and 8b
(53%) to easier purification of 4a and a high molar ratio of
boronic acid used relative to 6a (see the Supporting Infor-
mation, Table S2). However, it is also possible that the bulk-
iness of the neopentyl group of 7 played a role in the lower
yields observed for 8a and 8b.
Dibenzothiophene 6b and boronic acid 7 were coupled
to give 8b with no significant degradation of sulfoxide, sug-
gesting that diaryl sulfoxides are generally tolerated in
Suzuki coupling reactions at moderate temperatures (50–
70 °C). Additionally, no degradation or coupling at the sul-
fonyl ester was observed. We surmise that the choice of an
alkyl rather than an aryl protecting group was advanta-
geous here due to the slower rates of reductive elimination
for alkyl–aryl compared to aryl–aryl.36,37
Common reagents32 used to deprotect neopentyl sul-
fonate esters were unsuccessful for 8a or 8b; however, an
alternative method using NMe4Cl in DMF38 was successfully
employed and optimized (Scheme 3; optimizations shown
in the Supporting Information). For 8b, longer heating dura-
tions and/or the presence of air or water resulted in addi-
tional reactions that lead to the formation of the sulfone
(2c, identified by LC-MS; shown in Figure 2) and the sulfide
(2a). Sulfone 2c was not observed in the deprotection of 8a.
Thus, disproportionation and thermal deoxygenation
mechanisms could explain the formation of 2c and 2a ob-
served with 8b.
Purification of Aryl Disulfonic Acids. Historically, pu-
rifications of aryldisulfonic acids are challenging. Purifica-
tion methods that have been employed include reverse-
phase HPLC techniques,12,39 ion-exchange chromatogra-
phy,40,41 column chromatography with resins,42 and recrys-
tallizations of sulfonate salts;41,43–45 however, such methods
were found to be impractical, too expensive or ineffective
for our purposes, or result in problematic inorganic impuri-
ties. Previously, 1b was purified by reverse-phase column
chromatography using an expensive preparative HPLC col-
umn (C18, 5 μm particles, N/m > 80,000). The method re-
quired multiple runs, was only practical on a milligram
scale, and was only somewhat effective.3
Traditional sulfonating reagents include sulfuric acid
(H2SO4), sulfur trioxide (SO3), and chlorosulfonic acid
(ClSO3H).8 Compared to H2SO4 and SO3 that often require
long reaction times, ClSO3H has the benefit of reacting very
quickly; however, there are drawbacks to these faster reac-
tion times. For example, we observed under- and over-sul-
fonation, as well as the formation of undesired disulfonic
acid isomers in the syntheses of 1a, 2a, and 3a.
Herein, we report a method involving reverse-phase
high-performance flash chromatography (HPFC) and a Bio-
tage SNAP C18 column (50 μm irregular silica, N/m > 3,000).
The solvent system 0.1% TFA in H2O/MeCN was found to be
superior to the more common H2O/MeOH.46 In a typical pu-
rification, a crude reaction mixture was dissolved in
H2O/MeOH and then pipetted onto a C18 samplet (small
cartridge for dry loading). Once the solvent evaporated, the
samplet was inserted into a pre-equilibrated column for pu-
The sulfonation of 10a resulted in two disulfonic acid
isomers and a monosulfonic acid (Scheme 5). 2D NMR was
used to differentiate and identify the two disulfonic acid
S
S
Pd(PPh3)4, K2CO3, phenylboronic acid,
toluene, MeOH, H2O, N2 (g), reflux, 3 h
ClSO3H, ClCH2CH2Cl,
40 °C, 2 h
6a
79%
59%
HO3S
SO3H
4a
2a
Scheme 4 Direct approach for 2a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

D
S. M. Omlid et al.
Paper
Synthesis
2
1
11
3
4
S
S
S
ClSO3H, CH2Cl2,
0–40 °C, 2 h
10
S
SO3H
9
8
5
6
7
SO3H
HO3S
HO3S
HO3S
10a
3a
3d
11a
(1.3 equiv ClSO3H, 22 °C, 3%)
(22 °C, 3%)
(0 °C, 7%)
Scheme 5 Direct approach for 3a, 3d, and 11a
constitutional isomers (see the Supporting Information).
purifications were more efficient due to modifications in
the sulfonation step, i.e. the identification of the optimal
temperature (≥r.t.) as well as the optimization of other re-
action conditions (see the Supporting Information for more
details), and the oxidation step, i.e. the use of the more se-
lective method resulted in less sulfone.
1
The 2D H–1H NOESY of one isomer revealed a cross peak
(8.96 and 8.79 ppm), indicating through-space coupling of
1
H-6 and H-7, observed as two singlet peaks in standard H
NMR; this supported the identification of the isomer as the
1
5,8-disulfonic acid 3a. The 2D H–1H NOESY of the other
isomer also displayed a cross peak (8.96 and 8.39 ppm), in-
dicating through-space coupling of H-6, a singlet, and H-7, a
doublet; this supported the identification of the isomer as
the 5,9-disulfonic acid (3d). The identification of monosul-
fonic acid 11a was also achieved by NMR (see the Support-
ing Information for details).
Overall yields for 2a and 2b were found to be higher
with the direct approach (46% and 36%) than with the mod-
ular approach (18% and 22%). However, the modular ap-
proach allowed for a higher purity (>99%) to be obtained for
2b. In the direct approach, the sulfone could not be com-
pletely removed from 1b or 2b, with purities of only 95–
99% after repeated purifications. Nonetheless, the utiliza-
tion of the modular approach is limited to target molecules
such as 2b, where a phenyl appendage can easily be added.
Consequently, target molecules such as 1a, 1b, or 3a are
limited to the purities that can be obtained with a direct
approach: after one to two columns, >97%, >95%, and >95%,
respectively.
Although previously sulfonation of DBT with ClSO3H
was performed at 0 °C,3,8 for DBT and 4a, conversions into
the desired disulfonic acids were highest at room tempera-
ture and above. For example, we observed a modest 10% in-
crease in the conversion of DBT into 1a at room tempera-
ture compared to 0 °C. No significant increase was observed
above ~40 °C. The thermodynamic sulfonation products for
DBT, 4a, and 10a were the desired products 1a, 2a, and 3a.
In general, temperature had the greatest effect on yield rel-
ative to other optimization parameters that were investi-
gated (for further details see the Supporting Information).
Direct Approach for Disulfonic DBTO Derivatives. Sul-
fides are easily over-oxidized to sulfones using traditional
methods for sulfoxide synthesis. Previously, dimethyldiox-
irane was used to oxidize 1a and resulted in 20–40% of the
sulfone (1c).3 In this work, we employed H2O2 and phospho-
nitrilic chloride trimer (TAPC), as oxidant and catalyst re-
spectively, to reduce the formation of sulfone50 (e.g., 2c in
Figure 2). Compared to the previous method (57% yield3),
H2O2/TAPC resulted in less sulfone (5–25%) and moderate
improvements in yield: 62% for 1b and 78% for 2b. These
improvements resulted in significantly easier purifications;
however, the sulfoxides could not be completely isolated
from their sulfone counterparts, which remained as a negli-
gible impurity (0.5–4% by HPLC and NMR), even after four
columns.
All materials were purchased from Sigma-Aldrich or Fisher Scientific,
with the exception of 4-(neopentyloxysulfonyl)phenylboronic acid
(7), which was purchased from Combi-Blocks. 2,8-Dibromodiben-
zothiophene (6a) was prepared by using previously described meth-
ods33,51 or purchased from Bide Pharmatech. For sulfonation and oxi-
dation reactions, HPLC grade CH2Cl2 (without stabilizers) was used,
unless otherwise noted. The presence of stabilizers in CH2Cl2 severely
decreased yields in sulfonation reactions and resulted in an increase
in byproducts. NMR spectroscopy (i.e., 1H NMR, 13C NMR proton de-
coupled, and 2D NMR) was performed with a Bruker 400 MHz instru-
ment. HRMS was carried out on a JEOL MStation Mass Spectrometer
or Bruker 12 Tesla APEX – Qe FTICR-MS, and LC-MS was carried out
on a Shimadzu LCMS-2010 EV. IR was performed using a Shimadzu
IRAffinity-1S FTIR Spectrophotometer instrument with NaCl sample
preparations or through the use of ATR. UV-Vis analysis was per-
formed on a Shimadzu UV-1800 and a Thermo Scientific Nanodrop
2000c using a 10 mm quartz cuvette. Reverse-phase flash chromatog-
raphy was performed using a Biotage High Performance Flash Chro-
matography (HPFC) system, equipped with a Biotage Horizon detec-
tor and automated fraction collector, using reverse-phase solvent sys-
tems consisting of varying percentages of 0.1% TFA in H2O (solvent A)
and MeCN (solvent B). To construct these reverse-phase purifications
methods, first a method was developed on an Agilent 1200 series
HPLC fitted with a DAD and an Agilent Eclipse XDB-C18 column, and
then adapted for a larger scale. With minor modifications to previous-
ly described methods33 (i.e., using temperatures of ~0 °C and running
at 10× lower concentrations), 2,8-dibromodibenzothiophene 5-oxide
Overall, a direct approach proved to be the most suc-
cessful method relative to the other approaches for the di-
sulfonic acid derivatives. The overall yields for 1a and 1b
(65% and 40%) were significantly higher (previously, 20%
and 11%3), with the improvements attributed to the effi-
ciency of the new purification methodology. Furthermore,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

E
S. M. Omlid et al.
Paper
Synthesis
(6b) was produced in moderately higher yields (45–65% yields). Ben-
zo[b]naphtha[2,1-d]thiophene (10a) was prepared using a previously
described method.49
SNAP cartridge KP-C18-HS): (a) 0–1% B for 400 mL, (b) 0–15% B over
300 mL, and (c) 15–75% over 500 mL (2a eluted at ~1% B). We noted
that 2a could also be isolated from the deprotected product of 9 when
the deprotection reaction was run using 8a containing the impurity 9.
The solvent was removed under reduced pressure to yield pure 2a.
Dibenzothiophene-2,8-disulfonic Acid (1a)
Yield: 54 mg (80%); yellowish-white solid.
In a round-bottom flask, DBT (1011 mg, 5.48 mmol) was dissolved in
CH2Cl2 (178 mL); the flask was stoppered, stirred, and heated to 32 °C.
A ClSO3H stock solution was prepared by diluting ClSO3H (1 mL) with
CH2Cl2 (42 mL). Immediately following preparation, ClSO3H stock
solution (30 mL) was added to the round-bottom flask over a period
of about 2 min. After 1.7 h, H2O (200 mL) was added to quench the
reaction. The aqueous layer was washed once with CH2Cl2 (100 mL),
and then NaHCO3 (208 mg) was added to raise the pH to a manageable
level (pH > 2). The solvent was removed under heat and reduced pres-
sure. The crude product was redissolved in a minimal amount of H2O
and pipetted onto a Biotage 12 g C18 samplet. The samplet was al-
lowed to dry out thoroughly (resting in a fume hood, ~1 d). The prod-
uct was purified twice by HPFC using a C18 column (120 g, Biotage
SNAP cartridge KP-C18-HS): (a) 0–0% B for 3 L, (b) 0–1% B over 1.5 L,
and (c) 1–50% B over 2 L (1a eluted at 0% B). The solvent was removed
from pure fractions using heat and reduced pressure to give 1a.
Method 2 (Direct Approach): Dibenzothiophene 4a (494 mg, 1.48
mmol) was dissolved in DCM (66 mL) in a round-bottom flask and
stoppered. The solution was warmed to 40 °C. A stock solution of Cl-
SO3H (0.23 M) was prepared by diluting of ClSO3H (1 mL) with DCM
(65 mL). ClSO3H stock solution (13 mL) was slowly added to the reac-
tion mixture (over a period of about 2 min: the solution initially be-
came cloudy; after 3 mL, the solution became light blue; and then
slowly the solution color shifted to a dark green). The solution was al-
lowed to stir (with a stopper on top of the reaction flask) for 2 h. The
stopper was removed, and then H2O (2 mL) and MeOH (7 mL) were
added to the reaction mixture (slight fuming was observed and was
attributed to expulsion of HCl). The quenched solution was allowed to
stir for 30 min, and then the solvent was removed under reduced
pressure.
The crude product was redissolved in H2O (4 mL) and MeOH (1 mL)
and loaded onto a Biotage 12g C18 samplet cartridge. The samplet
was allowed to dry out thoroughly (resting in a fume hood, ~2 d). The
product was purified twice by HPFC using a C18 column (120 g, Bio-
tage SNAP cartridge KP-C18-HS): (a) 0–0% B for 100 mL, (b) 0–5% B
over 400 mL, and (c) 5–50% over 500 mL (2a eluted at ~1% B). The sol-
vent was removed under reduced pressure to yield pure 2a.
Yield: 1226 mg (65%); white, sticky solid.
1H NMR (400 MHz, CD3OD): δ = 8.73 (d, J = 0.7 Hz, 2 H), 8.01–7.96 (m,
4 H). Chemical shifts vary slightly from the previous report using
DMSO-d6 as the solvent.3
UV/Vis (H2O): λmax (log ε) = 244 nm (73100).
Other characterizations of 1a have been previously reported.3
Yield: 427 mg (59%); yellowish-white solid.
IR (NaCl): 3404, 2355, 1597, 1549, 1504, 1468, 1393, 1213, 1155,
5-Oxo-dibenzothiophene-2,8-disulfonic Acid (1b)
1128, 1036, 1003, 839, 808, 746, 718 cm–1
.
To a vial containing 1a (491 mg, 1.43 mmol), phosphonitrilic chloride
trimer (TAPC) (36 mg, 0.10 mmol), 30% (w/w) H2O2 (145 μL, 1.45
mmol), and H2O (1 mL) were added. The solution was allowed to stir
approximately 3 d at r.t., open to air. The solution was diluted with
H2O (2 mL) and was loaded onto a Biotage 12 g C18 samplet. The
product was purified twice by HPFC using a C18 column (120 g, Bio-
tage SNAP cartridge KP-C18-HS): (a) 0–0% B for 1.8 L, (b) 0–1% B over
1.2 L, and (c) 1–50% B over 2 L (1b eluted at 0% B). The solvent was
removed from pure fractions using low heat (≤50 °C) and reduced
pressure to give 1b.
1H NMR (400 MHz, CD3OD): δ = 8.65 (d, J = 1.0 Hz, 2 H), 7.98–7.94 (m,
6 H), 7.89–7.87 (m, 4 H), 7.79 (dd, J = 8.3, 1.4 Hz, 2 H).
13C NMR (100 MHz, CD3OD): δ = 144.41, 141.00, 138.26, 137.65,
128.34, 127.84, 127.46, 124.45, 121.57.
HRMS (ESI+): m/z [M + Na]+ calcd for C24H16O6S3Na+: 519.0001; found:
519.0001.
UV/Vis (MeOH): λmax (log ε) = 259 (61500), 291–292 nm (37900).
5-Oxo-dibenzothiophene-2,8-bis(phenyl-4-sulfonic Acid) (2b)
Yield: 316 mg (62%); yellow-white, sticky solid.
Method 1 (Modular Approach): Dibenzothiophene 8b (212 mg, 0.325
mmol), NMe4Cl (1162 mg, 10.61 mmol), and anhyd DMF (75 mL) were
added to a round-bottom flask. The solution was bubbled with N2(g)
for 10 min. The reaction flask was then fitted with a condenser and
placed in an argon atmosphere. An oil bath was pre-heated to 150 °C,
before the reaction flask was lowered into it. After stirring for 70 min,
the reaction flask was quickly removed from the heat by raising the
flask out of the oil bath. The solvent was removed under reduced
pressure. The crude product was redissolved in H2O and loaded onto a
Biotage 3 g C18 samplet cartridge. The samplet was allowed to dry
out thoroughly (resting in a fume hood, ~2 d). The product was puri-
fied twice by HPFC using a C18 column (30 g, Biotage SNAP cartridge
KP-C18-HS): (a) 0–0% B for 400 mL, (b) 0–5% B over 500 mL, and (c)
5–50% over 1 L (2b eluted at ~0% B). The solvent was removed under
reduced pressure to yield pure 2b.
1H NMR (400 MHz, DMSO-d6): δ = 8.16 (s, 2 H), 8.05 (d, J = 7.8 Hz, 2
H), 7.81 (dd, J = 7.9, 1.2 Hz, 2 H). The shifts match the previous re-
port.3
UV/Vis (H2O): λmax (log ε) = 237 (38500), 251 nm (43600).
Other characterizations of 1b have been previously reported.3
Dibenzothiophene-2,8-bis(phenyl-4-sulfonic Acid) (2a)
Method 1 (Modular Approach): Dibenzothiophene 8a (87 mg, 0.14
mmol) and NMe4Cl (508 mg, 4.64 mmol) were added to a round-bot-
tom flask, which was then stoppered. Anhyd DMF (30 mL) was added,
and then the solution was bubbled with N2 gas for 10 min. The reac-
tion flask was then fitted with a condenser and placed in an argon at-
mosphere. An oil bath was pre-heated to 150 °C, before the reaction
flask was lowered into it. After stirring for 1 h, the reaction flask was
immediately removed from the heat by raising the flask out of the oil
bath. The solvent was removed under reduced pressure. The crude
product was redissolved in H2O and loaded onto a Biotage 3 g C18
samplet cartridge and the solvent was allowed to evaporate. The
product was purified twice by HPFC using a C18 column (30 g, Biotage
Yield: 104 mg (63%); white solid.
Method 2 (Direct Approach): TAPC (27 mg, 0.077 mmol), 30% (w/w)
H2O2 (55 μL, 0.55 mmol), and H2O (0.6 mL) were added to a vial con-
taining 2a (248 mg, 0.499 mmol). The solution was stirred (open to
the air) for 30 h, and the reaction was monitored via HPLC. The solu-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

F
S. M. Omlid et al.
Paper
Synthesis
tion was diluted with H2O (4 mL) and loaded onto a Biotage 12 g C18
samplet. The samplet was allowed to dry out thoroughly (resting in a
fume hood, ~2 d). The product was purified twice by HPFC using a C18
column (120 g, Biotage SNAP cartridge KP-C18-HS): (a) 0–0% B for
300 mL, (b) 0–5% B over 1050 mL, and (c) 5–10% B over 1.2 L (2b elut-
ed at ~2% B). The solvent was removed from pure fractions using low
heat (≤50 °C) and reduced pressure to give 2b as a white-yellow,
sticky solid. The slight yellow hue observed was attributed to impuri-
ties of 2c, which was faintly observed in 1H NMR for 2b using the di-
rect approach (while the peaks were not observed using the modular
approach).
immediately added to the reaction mixture (stirring vigorously: a
rapid color change from colorless to purple to brown-yellow was ob-
served in the first few minutes). The stirring was continued until the
ice bath melted and the reaction solution reached r.t. The reaction
mixture was then quenched with MeOH (2 mL). The solvent was then
removed under reduced pressure. The crude product was redissolved
in a minimum amount of MeOH and loaded onto a 1 g Biotage sam-
plet cartridge. The product was purified twice using reverse-phase
chromatography with a C18 column (12 g, Biotage SNAP cartridge KP-
C18-HS) and reverse-phase solvents: (a) 0–0% for 100 mL, (b) 0–1% B
over 300 mL, and (c) 1–1% B over 300 mL (3d eluted at 1% B). The sol-
vent was removed from pure fractions (>99% by HPLC) using reduced
pressure to give 3d.
Yield (2b): 200 mg (78%); white-yellow, sticky solid.
IR (NaCl): 3428, 1597, 1557, 1470, 1383, 1190, 1128, 1040, 1003, 848,
Yield: 2 mg (7%); pale white solid.
818, 746, 710 cm–1
.
IR (NaCl): 3447, 3094, 2374, 1647, 1458, 1173, 1130, 1051, 1034, 874,
1H NMR (400 MHz, D2O): δ = 7.76 (d, J = 8.4 Hz, 4 H), 7.54 (d, J = 8.0
Hz, 2 H), 7.43 (d, J = 1.2 Hz, 2 H), 7.38 (d, J = 8.4 Hz, 4 H), 7.28 (dd, J =
8.1, 1.5 Hz, 2 H).
13C NMR (100 MHz, D2O): δ = 143.06, 142.31, 141.00, 140.04, 136.83,
128.21, 127.57, 127.01, 125.96, 119.56.
820, 750, 737, 692 cm–1
.
1H NMR (400 MHz, CD3OD): δ = 9.04–9.02 (m, 1 H), 8.96 (s, 1 H), 8.50
(s, 1 H), 8.39 (d, J = 8.5 Hz, 1 H), 8.24–8.22 (m, 1 H), 8.04 (d, J = 7.7 Hz,
1 H), 7.73–7.70 (m, 2 H).
13C NMR (100 MHz, CD3OD): δ = 142.81, 140.12, 139.32, 131.54,
130.67, 129.62, 129.47, 128.59, 128.56, 126.23, 125.75, 124.35,
122.79, 122.04, 120.96.
HRMS (ESI+): m/z [M + H]+ calcd for C24H16O7S3H+: 513.0131; found:
513.0130.
UV/Vis (H2O): λmax (log ε) = 271 nm (75700).
HRMS (ESI+): m/z [M + Na]+ calcd for C16H10O6S3Na+: 416.9532; found:
416.9531.
Benzo[b]naphtho[2,1-d]thiophene-5,8-disulfonic Acid (3a)
UV/Vis (H2O–MeCN, 1:1): λmax (log ε) = 258–259 (63400), 280
(70900), 307 nm (27700).
Benzonaphthothiophene 10a (498 mg, 2.12 mmol) was dissolved in
CH2Cl2 (120 mL) in a round-bottom flask. The solution was chilled us-
ing an ice bath. A stock solution of ClSO3H was prepared by diluting
ClSO3H (0.5 mL) with CH2Cl2 (20 mL). ClSO3H stock solution (20 mL)
was added to the reaction flask over a period of 30 min by using an
addition funnel. The reaction mixture was stirred vigorously (a rapid
color change to deep brown was observed). The reaction mixture was
allowed to stir until the ice bath melted and the reaction solution
reached r.t.; then, the reaction was quenched with MeOH (5 mL). The
solvent was removed under reduced pressure. The crude product was
redissolved in a minimum amount of H2O and was loaded onto a 10 g
Biotage samplet cartridge. The product was purified twice by HPFC
using a C18 column (120 g, Biotage SNAP Cartridge KP-C18-HS): (a)
0–0% B for 325 mL, (b) 0–1% B over 325 mL, and (c) 1–2% B over 885
mL (3a eluted at ~1.5% B). The solvent was removed from pure frac-
tions of 3a (>96% by HPLC) using reduced pressure to give 3a.
2,8-Diphenyldibenzothiophene (4a)
Pd(PPh3)4 (2.08 g, 1.80 mmol), K2CO3 (9.39 g, 67.9 mmol) in H2O (65
mL), phenylboronic acid (5.83 g, 47.8 mmol) in EtOH (60 mL), and 6a
(4.04 g, 11.8 mmol) were added sequentially to toluene (360 mL) and
the mixture was bubbled with N2(g). The reaction mixture was stirred
vigorously and refluxed for 3 h. The organic layer was removed under
reduced pressure. The crude product was purified by chromatography
(silica gel, hexanes; Rf = 0.05), affording 4a.
Yield: 3.14 g (79%); white crystalline solid.
IR (ATR): 1599, 1547, 1497, 1466, 1454, 1441, 1422 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.42 (d, J = 1.5 Hz, 2 H), 7.94 (d, J = 8.3
Hz, 2 H), 7.75–7.72 (m, 6 H), 7.52 (m, 4 H), 7.41 (tt, J = 7.3, 1.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 141.35, 139.22, 138.24, 129.13,
Yield: 29 mg (3%); pale pinkish white solid.
127.62, 127.55, 126.55, 123.37, 120.31.
HRMS (EI): m/z [M]+ calcd for C24H16S: 336.097; found: 336.097.
IR (NaCl): 3399, 2524, 2361, 1684, 1647, 1449, 1202, 1177, 1051, 895,
816, 750, 739, 692 cm–1
.
1H NMR (400 MHz, CD3OD): δ = 9.04–8.96 (m, 2 H), 8.80 (s, 1 H), 8.22–
8.20 (m, 1 H), 8.11 (d, J = 8.4 Hz, 1 H), 8.00 (d, J = 8.4 Hz, 1 H), 7.72–
7.69 (m, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 145.52, 142.38, 138.55, 138.21,
135.45, 130.42, 129.12, 128.62, 128.29, 127.22, 126.58, 124.50,
124.09, 122.89, 118.25, 117.90.
UV/Vis (MeCN): λmax (log ε) = 257 (65300), 284–286 nm (33200).
Dineopentyl Dibenzothiophene-2,8-diylbis(benzene-4-sulfonate)
(8a)
Dibenzothiophene 6a (195 mg, 0.569 mmol) and Na2CO3 (466 mg,
4.40 mmol) were dissolved in H2O (8 mL), THF (60 mL), DME (25 mL),
and toluene (60 mL). The reaction mixture was placed under N2(g).
Boronic acid 7 (422 mg, 1.55 mmol), Pd(PPh3)4 (103 mg, 0.0891
mmol), PCy3 (23 mg, 0.082mmol), and Pd(dppf)Cl2 (21 mg, 0.029
mmol) were added to a vial and then dissolved in THF (20 mL), EtOH
(1 mL), and toluene (20 mL). Over a period of 4 h, the contents of the
vial were added to the reaction flask while the reaction flask was al-
lowed to stir at reflux (~65 °C). After an additional 3 h, the reaction
mixture was removed from heat, and EtOAc (100 mL) was added. The
organic layer was washed with H2O (3 × 25 mL), and dried with Mg-
SO4. After filtering off the drying agent, the solvent was removed un-
HRMS (ESI+): m/z [M + Na]+ calcd for C16H10O6S3Na+: 416.9532; found:
416.9532.
UV/Vis (H2O–MeCN, 1:1): λmax (log ε) = 257 (94600), 269 nm (88900).
Benzo[b]naphtho[2,1-d]thiophene-5,9-disulfonic Acid (3d)
Benzonaphthothiophene 10a (20 mg, 0.086 mmol) was dissolved in
CH2Cl2 (20 mL) in a round-bottom flask. The solution was chilled us-
ing an ice bath. A stock solution of ClSO3H was prepared by diluting
ClSO3H (1 mL) with CH2Cl2 (79 mL). ClSO3H stock solution (1 mL) was
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

G
S. M. Omlid et al.
Paper
Synthesis
der reduced pressure. Purification was achieved by column chroma-
tography [silica gel, pentane with increasing EtOAc percentage; Rf =
0.1 (EtOAc–hexanes, 1:9); 9 co-elutes with 8a], followed by recrystal-
lization (EtOAc/hexanes/pentane; in solution, crystals appeared nee-
dle-like and were dispersed throughout the solvent). (Note: another
crystal type was often observed, appearing as small polygonal crys-
tals and consisting primarily of the impurity 9.) The purification
yielded 8a.
aqueous layer were extracted with CH2Cl2 for maximum recovery. The
organic layers were combined, and the solvent was removed under
reduced pressure. The crude product was redissolved in a minimum
amount of CH2Cl2–MeOH (1:1) and loaded onto a Biotage 1 g samplet
cartridge. The product was purified by HPFC using a C18 column (120
g, Biotage SNAP cartridge KP-C18-HS): (a) 0–1% B for 480 mL, (b) 1–
5% B over 480 mL, and (c) 5–10% B over 480 mL (11a eluted at ~6% B).
The solvent was removed from pure fractions of 11a (>95% by HPLC)
using heat and reduced pressure to give 11a.
Yield: 82 mg (23%); white fluffy solid.
Yield: 5 mg (3%), pale yellow-white solid.
IR (NaCl): 3501, 1647, 1638, 1188, 1057, 881, 843, 721 cm–1
.
IR (NaCl): 2959, 2870, 1595, 1472, 1356, 1179, 1099, 964, 937, 845,
818, 718 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.46 (d, J = 1.4 Hz, 2 H), 8.06–8.00 (m, 6
H), 7.91 (dt, J = 8.7, 2.0 Hz, 4 H), 7.78 (dd, J = 8.4, 1.8 Hz, 2 H), 3.77 (s, 4
H), 0.96 (s, 18 H).
1H NMR (400 MHz, CD3OD): δ = 9.10 (d, J = 8.1 Hz, 1 H), 8.86 (s, 1 H),
8.36 (d, J = 7.2 Hz, 1 H), 8.12 (d, J = 8.0 Hz, 1 H), 7.84 (d, J = 7.4 Hz, 1 H),
7.64–7.61 (m, 1 H), 7.57–7.52 (m, 1 H), 7.51–7.45 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 146.53, 140.75, 136.25, 136.22,
135.05, 128.80, 128.21, 126.71, 123.91, 120.64, 79.99, 31.97, 26.28.
HRMS (FAB): m/z [M + Na]+ calcd for C34H36O6S3Na: 659.157; found:
659.158.
13C NMR (100 MHz, CD3OD): δ = 143.32, 138.61, 136.76, 135.60,
133.36, 130.58, 129.86, 129.17, 127.72, 127.42, 126.39, 125.64,
124.21, 123.06, 122.81.
HRMS (ESI+): m/z [M + Na]+ calcd for C16H10O3S2Na+: 336.9964; found:
336.9963.
UV/Vis (MeCN): λmax (log ε) = 268 (54900), 299 nm (40000).
UV/Vis (MeCN): λmax (log ε) = 278 nm (97300).
Dineopentyl 5-Oxo-dibenzothiophene-2,8-diylbis(benzene-4-sul-
fonate) (8b)
Funding Information
Dibenzothiophene 6b (208 mg, 0.582 mmol) and Pd(PPh3)4 (24 mg,
0.020 mmol) were dissolved in THF (30 mL) and toluene (35 mL). The
reaction flask was placed under an argon atmosphere and heated to
50 °C. Two separate solutions were prepared: solution 1: Pd2(dba)3
(25 mg, 0.028 mmol), Pd(PPh3)4 [52 mg, 0.045 mmol], and 7 (566 mg,
2.08 mmol) in THF (45 mL) and toluene (14 mL); solution 2: Na2CO3
(279 mg, 2.63 mmol) in H2O (9 mL) and EtOH (2 mL). Over a period of
7 h, solutions 1 and 2 were slowly added to the reaction mixture, and
the temperature of the reaction mixture was allowed to warm up to
65 °C. The reaction mixture was diluted with EtOAc (100 mL) and
then washed with H2O (2 × 100 mL). The solvent was removed under
reduced pressure, and the crude solid was purified by column chro-
matography (silica gel, pentane–EtOAc, 1:1; Rf = 0.2). This afforded 8b.
This work was supported by grants CHE-1255270 from the National
Science Foundation and donors to the Herman Frasch Foundation.
N
oaitn
a
l
S
ecin
c
e
F
o
u
n
d
oaitn
C(
H
E-1
2
5
5
2
7
0)
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591969.
S
u
p
p
o
nrtogI
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
References
(1) Zhang, M.; Ravilious, G. E.; Hicks, L. M.; Jez, J. M.; McCulla, R. D.
J. Am. Chem. Soc. 2012, 134, 16979.
(2) Bourdillon, M. T.; Ford, B. A.; Knulty, A. T.; Gray, C. N.; Zhang,
M.; Ford, D. A.; McCulla, R. D. Photochem. Photobiol. 2014, 90,
386.
(3) Korang, J.; Emahi, I.; Grither, W. R.; Baumann, S. M.; Baum, D.
A.; McCulla, R. D. RSC Adv. 2013, 3, 12390.
(4) Gregory, D. D.; Wan, Z.; Jenks, W. S. J. Am. Chem. Soc. 1997, 119,
94.
Yield: 200 mg (53%); white solid.
IR (NaCl): 2963, 2905, 1595, 1476, 1400, 1356, 1180, 1099, 1078,
1036, 963, 937, 839, 822, 736, 704 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.16 (d, J = 8.0 Hz, 2 H), 8.11 (d, J = 1.1
Hz, 2 H), 8.06 (d, J = 8.5 Hz, 4 H), 7.86 (d, J = 8.5 Hz, 4 H), 7.79 (dd, J =
8.0, 1.5 Hz, 2 H), 3.77 (s, 4 H), 0.95 (s, 18 H).
13C NMR (100 MHz, CDCl3): δ = 145.97, 145.02, 144.24, 137.85,
136.42, 129.37, 128.91, 128.60, 128.38, 121.18, 80.14, 31.98, 26.26.
(5) Voss, J. J. Sulfur Chem. 2009, 30, 167.
HRMS (FAB): m/z [M + H]+ calcd for C34H37O7S3: 653.170; found:
(6) Cremlyn, R. J. W. Chlorosulfonic Acid: A Versatile Reagent; The
Royal Society of Chemistry: Cambridge UK, 2002.
(7) Jandera, P.; Fischer, J.; Stanck, V.; Kucerov, M.; Zvonieek, P.
J. Chromatogr. A 1996, 738, 201.
653.172.
UV/Vis (MeCN): λmax (log ε) = 271 nm (88100).
Benzo[b]naphtho[2,1-d]thiophene-5-sulfonic Acid (11a)
(8) El-Hiti, G. A. Sulfur Rep. 2001, 22, 217.
(9) Pouhov, S.; Jamieson, G.; Vajda, J.; Kruk, H.; McGinley, J. U.S.
Patent 20020022743A1, 2002.
(10) Elder, D. P.; Teasdale, A.; Lipczynski, A. M. J. Pharm. Biomed.
Anal. 2008, 46, 1.
(11) Cui, J.; Van Koeverden, M. P.; Müllner, M.; Kempe, K.; Caruso, F.
Adv. Colloid Interface Sci. 2014, 207, 14.
(12) Toutchkine, A.; Nalbant, P.; Hahn, K. M. Bioconjugate Chem.
2002, 13, 387.
Benzonaphthothiophene 10a (120 mg, 0.510 mmol) was dissolved in
CH2Cl2 (64 mL) in a round-bottom flask. A stock solution of ClSO3H
was prepared by diluting ClSO3H (2 mL) with CH2Cl2 (57 mL). ClSO3H
stock solution (1 mL) was immediately added to the reaction mixture.
The reaction flask was partially sealed with a rubber septum with a
needle to vent. The reaction mixture was then stirred vigorously at r.t.
for 2 h (a rapid color change from colorless to light pink to light brown
was observed in the first few minutes). The reaction was then
quenched with MeOH. Di- and trisulfonic acid derivatives were re-
moved using extraction with H2O. Monosulfonated derivatives in the
(13) Waggoner, A. Curr. Opin. Chem. Biol. 2006, 10, 62.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

H
S. M. Omlid et al.
Paper
Synthesis
(14) Lambrechts, H. J. A.; Schaasberg-Nienhuis, Z. R. H.; Cerfontain,
H. J. Chem. Soc., Perkin Trans. 2 1985, 669.
(32) Miller, S. C. J. Org. Chem. 2010, 75, 4632.
(33) Nag, M.; Jenks, W. S. J. Org. Chem. 2004, 69, 8177.
(15) Cerfontain, H.; Schaasberg-Nienhuis, Z. R. H. J. Chem. Soc., Perkin
Trans. 2 1976, 1780.
(16) Cerfontain, H.; Lambrechts, H. J. A.; Schaasberg-Nienhuis, Z. R.
H. J. Chem. Soc., Perkin Trans. 2 1985, 659.
(34) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513.
(35) Page, P.; Jorand-Lebrun, C.; Quattropani, A.; Pomel, V.; Schwarz,
M.; Hamelin, E.; Thomas, R. J. Patent WO2003082278A1, 2003.
(36) Hartwig, J. F. Inorg. Chem. 2007, 46, 1936.
(17) Schaasberg-Nienhuis, Z. R. H.; Cerfontain, H.; Kortekaas, T. A.
J. Chem. Soc., Perkin Trans. 2 1979, 844.
(37) Chow, W. K.; Yuen, O. Y.; Choy, P. Y.; So, C. M.; Lau, C. P.; Wong,
W. T.; Kwong, F. Y. RSC Adv. 2013, 3, 12518.
(18) Cerfontain, H.; Schaasberg-Nienhuis, Z. R. H. J. Chem. Soc., Perkin
Trans. 2 1974, 989.
(38) Roberts, J. C.; Huai, G.; Gopalsamy, A.; Kongsjahju, A.; Patch, R. J.
Tetrahedron Lett. 1997, 38, 355.
(19) Cerfontain, H.; Schaasberg-Nienhuis, Z. R. H. J. Chem. Soc., Perkin
Trans. 2 1974, 536.
(39) Jandera, P.; Churacek, J.; Taraba, B. J. Chromatogr. 1983, 262, 121.
(40) Stehl, R. H. Anal. Chem. 1970, 42, 1802.
(20) Cerfontain, H.; Koeberg-Telder, A.; Lambrechts, H. J. A.; de Wit,
P. J. Org. Chem. 1984, 49, 4917.
(21) Ris, C.; Schaasberg-Nienhuis, Z. R. H.; Cerfontain, H. Tetrahedron
1973, 29, 3165.
(41) Jandera, P. J. Liq. Chromatogr. Relat. Technol. 2007, 30, 2349.
(42) Scoggins, M.; Miller, J. Anal. Chem. 1968, 40, 1155.
(43) Gilman, H.; Smith, E. W.; Oatfield, H. J. J. Am. Chem. Soc. 1934,
56, 1412.
(22) Kortekaas, T. A.; Cerfontain, H. J. Chem. Soc., Perkin Trans. 2
1977, 1560.
(23) Lammertsma, K.; Cerfontain, H. J. Chem. Soc., Perkin Trans. 2
1980, 28.
(44) Katash, I.; Luo, X.; Sukenik, C. N. Langmuir 2010, 26, 1765.
(45) Sias, R. C.; Woods, W. W. U.S. Patent 2899460, 1959.
(46) Mujumdar, R. B.; Ernst, L. A.; Mujumdar, S. R.; Lewis, C. J. Bio-
conjugate Chem. 1993, 4, 105.
(24) Kortekaas, T. A.; Cerfontain, H. J. Chem. Soc., Perkin Trans. 2
1979, 224.
(25) Kortekaas, T. A.; Cerfontain, H.; Gall, J. M. J. Chem. Soc., Perkin
Trans. 2 1978, 445.
(26) Bosscher, J. K.; Cerfontain, H. J. Chem. Soc. B 1968, 1524.
(27) Idzik, K. R.; Nödler, K.; Licha, T. Molecules 2015, 20, 6856.
(28) Mietrach, A.; Muesmann, T. W. T.; Christoffers, J.; Wickleder, M.
S. Eur. J. Inorg. Chem. 2009, 5328.
(47) Vyas, J. R.; Dhotre, H.; Sarma, N.; Patel, D. N.; Sangani, P.; Shah,
A. K.; Patel, B. R.; Wadia, D. Patent WO2017093866A2, 2013.
(48) Ma, B.; Wu, Y.; Lin, C.; Kwong, R. U.S. Patent 8367850B2, 2013.
(49) Zheng, X.; Baumann, S. M.; Chintala, S. M.; Galloway, K. D.;
Slaughter, J. B.; Mcculla, R. D. Photochem. Photobiol. Sci. 2016, 15,
791.
(50) Bahrami, K.; Khodaei, M. M.; Arabi, M. S. J. Org. Chem. 2010, 75,
6208.
(29) Jandera, P.; Churacek, J. J. Chromatogr. 1980, 197, 181.
(30) Petroff, J. T.; McCulla, R. D. Tetrahedron Lett. 2016, 57, 4723.
(31) Bassin, J. P.; Cremlyn, R. J.; Swinbourne, F. J. Phosphorus, Sulfur
Silicon Relat. Elem. 1992, 72, 157.
(51) Korang, J.; Grither, W. R.; Mcculla, R. D. J. Am. Chem. Soc. 2010,
132, 4466.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H