Iodine-Catalyzed Methylthiolative Annulation of 2-Alkynyl Biaryls with DMSO: A Metal-Free Approach to 9-Sulfenylphenanthrenes

Article abstract of DOI:10.1021/acs.joc.1c00861

An iodine-catalyzed sustainable, cost-effective, and atom-economic synthetic methodology is developed to synthesize a wide variety of valuable sulfenylphenanthrenes and polycyclic heteroaromatics in moderate to high yield through electrophilic thiolative annulation of 2-alkynyl biaryls (6-endo-dig cyclization) using methyl sulfoxides such as dimethyl sulfoxide (DMSO) as the sulfur source under transition-metal-free conditions. The transformation requires only iodine in a catalytic amount and trifluoroacetic anhydride. Notably, DMSO played multiple roles such as methylthiolating reagent, oxidant, and solvent in this reaction.

Full text of DOI:10.1021/acs.joc.1c00861

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Iodine-Catalyzed Methylthiolative Annulation of 2‑Alkynyl Biaryls
with DMSO: A Metal-Free Approach to 9-Sulfenylphenanthrenes
Nilanjana Mukherjee and Tanmay Chatterjee*
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ABSTRACT: An iodine-catalyzed sustainable, cost-effective, and
atom-economic synthetic methodology is developed to synthesize
a wide variety of valuable sulfenylphenanthrenes and polycyclic
heteroaromatics in moderate to high yield through electrophilic
thiolative annulation of 2-alkynyl biaryls (6-endo-dig cyclization)
using methyl sulfoxides such as dimethyl sulfoxide (DMSO) as the
sulfur source under transition-metal-free conditions. The trans-
formation requires only iodine in a catalytic amount and
trifluoroacetic anhydride. Notably, DMSO played multiple roles
such as methylthiolating reagent, oxidant, and solvent in this
reaction.
Scheme 1. General Synthetic Strategies to 9-
Sulfenylphenanthrenes
henanthrenes, one of the important classes of polycyclic
aromatic hydrocarbons, are ubiquitous in numerous
P
biologically active compounds including natural products1
and exhibit a broad spectrum of biological activities such as
antiviral,2 antimicrobial,3 anticancer,4 antitumor,5 and anti-
HIV6 activity. Moreover, phenanthrene derivatives also exhibit
interesting electronic7 and optical8 properties and are utilized
in various useful materials, such as organic field-effect
transistors9 and solar cells.10 Consequently, several synthetic
strategies have been developed so far for the synthesis of
phenanthrenes.11,12 Among them, two synthetic strategies, i.e.,
transition-metal (TM) (Pd, Ir, Rh, and Fe)-catalyzed or
visible-light photocatalyzed [4 + 2]-benzannulation of 2-
functionalized 1,1′-biaryls with alkynes13 and transition-metal
(Pt, Au, Ga, Ir, Ru, Fe, and Sn)-catalyzed/mediated intra-
molecular carbocyclization or electrophilic annulation of 2-
alkynyl biaryls (6-endo-dig cyclization) are widely employed,
perhaps because of their high atom-economical feature and the
requirement of relatively less prefunctionalized starting
materials.14 Despite significant advancement, the above-
mentioned synthetic methods suffer from at least one of the
following severe limitations, such as the requirement of (a)
expensive and toxic transition-metal salts or complexes in
catalytic or (sub)stoichiometric amounts, (b) expensive and
hazardous ligand and reagents, (c) harsh or critical reaction
conditions, and (d) limited substrate scope. In 2005, Larock et
al. disclosed a transition-metal-free, electrophilic 6-endo-dig
cyclization of 2-alkynyl biaryls with ICl, N-bromosuccinimide
(NBS), and p-O2NC6H4SCl to synthesize 9-halo (I and Br)-
and 9-(4-nitrophenyl)sulfenylphenanthrenes, respectively
(Scheme 1 A).15
Received: April 14, 2021
Published: May 24, 2021
However, the requirement of a highly electrophilic
arylsulfenyl chloride, p-O2NC6H4SCl, and its commercial
https://doi.org/10.1021/acs.joc.1c00861
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© 2021 American Chemical Society
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Note
a
nonavailability eventually limited this method’s scope to access
9-sulfenylphenanthrenes. In 2014, Qian and Zhang et al.
reported a Pd-catalyzed general synthetic strategy for
synthesizing 9-sulfenylphenanthrenes through electrophilic
annulation of 2-alkynyl biaryls with diphenyl disulfides in the
presence of 2 equiv of iodine (Scheme 1 B).16 Despite broad
substrate scope to access 9-sulfenylphenanthrenes, this method
also suffered from several limitations such as the requirement
of expensive, toxic, and rare transition-metal (Pd) catalysts in
substoichiometric amounts (10 mol %), super stoichiometric
(2 equiv) iodine, and relatively lower atom-economy of the
reaction as only 0.5 equiv of the disulfide was utilized in the
reaction. Herein, we designed and developed a TM-free,
sustainable, cost-effective, and atom-economical synthetic
strategy for the methylthiolative or phenylthiolative annulation
of 2-alkynyl biaryls by using inexpensive and commercially
available methyl sulfoxides such as DMSO as the source of
thiomethyl group (−SMe), iodine (I2) as the catalyst, and
TFAA as a reagent to synthesize a wide variety of 9-
sulfenylphenanthrenes and polycyclic heteroaromatics, i.e.,
naphthothiophenes (Scheme 1 C). We hypothesized that in
the presence of iodine an electrophilic species, i.e., methyl
sufenyl iodide (MeSI), could be generated through the in situ
decomposition of DMSO by an electrophilic reagent such as
TFAA into formaldehyde and thiomethanol.16,17 Subsequently,
the electrophilic methylthiolative annulation of 2-alkynyl
biaryls with MeSI would furnish the desired product, 9-
sulfenylphenanthrenes, via the formation of intermediate A.16
During the reaction, HI is formed, which will be oxidized by
DMSO under the reaction conditions to regenerate iodine in
the catalytic cycle.18 The unique feature of this protocol is the
cost-effective, atom-economic, and sustainable synthetic
approach to a wide variety of 9-sulfenylphenanthrenes and
polycyclic heteroaromatics from readily available 2-alkynyl
biaryls and DMSO, which played multiple roles such as
methylthiolating reagent, oxidant, and solvent in the reaction.
In recent times, DMSO has been utilized as the source of a
thiomethyl (−SMe) group in developing a few transition-
metal-catalyzed C−H methylthiolation reactions19 and radical
coupling reactions under TM-free conditions.20
Table 1. Optimization of the Reaction Conditions
b
yield (%)
entry
variation in conditions from scheme
3aa
4a
1.
2.
3.
4.
5.
6.
7.
none
10 mol % of I2
20 mol % of TBAI was used instead of I2
4 equiv of TFAA was used
4 equiv of Ac2O was used instead of TFAA
4 equiv of CF3SO2Cl was used instead of TFAA
91
50
65
90
0
trace
trace
trace
8
0
60
20
4 equiv of ρ-NO2C6H4SO2Cl was used instead of
TFAA
trace
8.
9.
2 equiv of TFAA was used
reaction was conducted at 100 °C
55
30
0
trace
trace
0
10. reaction was conducted at room temperature
(25 °C)
11. 5 equiv of DMSO was used
12. 3 equiv of Na2CO3 was used
13. 3 equiv of K3PO4 was used
14. 3 equiv of Et3N was used
15. reaction was conducted without I2 (blank
experiment)
16. reaction was conducted without TFAA (blank
experiment)
17. reaction was conducted under Ar atmosphere
40
7
trace
trace
0
0
trace
trace
trace
0
0
0
trace
91
60
trace
trace
trace
18. reaction was conducted for 1.5 h (conditions A)
19. reaction was conducted in toluene (0.4 M) using 2
equiv of DMSO for 22 h
20. reaction was conducted in toluene (0.4 M) using
92
60
trace
15
3 equiv of DMSO for 22 h (conditions B)
21. reaction was conducted in m-xylene (0.4 M) using
3 equiv of DMSO for 22 h
22. reaction was conducted in DMF (0.4 M) using 3
equiv of DMSO for 22 h
trace
trace
a
b
All of the reactions were conducted on a 0.1 mmol scale. Yield of
the products was determined by 1H NMR of the crude reaction
mixture using 1,3,5-trimethoxybenzene as the internal standard.
We commenced our investigation of methylthiolative
annulation of 2-(phenylethynyl)-1,1′-biphenyl 1a with 10
equiv DMSO 2a using iodine and TFAA at 120 °C under an
aerobic atmosphere. To our delight, when the reaction was
conducted using 20 mol % of I2 and 3 equiv of TFAA for 3 h,
91% of the desired product, methyl(10-phenylphenanthren-9-
yl)sulfane 3aa was formed along with a trace amount of 9-iodo-
10-phenylphenanthrene 4a (entry 1, Table 1). However, only
50% 3aa was formed using 10 mol % of I2 (entry 2, Table 1).
When 20 mol % of tetrabutylammonium iodide (TBAI) was
used instead of I2, 65% of 3aa was formed (entry 3, Table 1).
Among various electrophilic reagents such as TFAA, acetic
anhydride, CF3SO2Cl, and p-NO2C6H4SO2Cl, TFAA was
found to be the best (entries 5−7 vs entry 1, Table 1). The
use of 3 equiv of TFAA was found optimum for the reaction
(entries 4 and 8 vs entry 1, Table 1). Lowering of reaction
temperature from 120 °C had a negative impact on the
reaction outcome; no product was formed at room temper-
ature (entries 9 and 10 vs entry 1, Table 1). Lowering the
stoichiometry of DMSO also negatively impacted the reaction
outcome (entry 11, vs entry 1, Table 1). The use of inorganic
and organic bases such as Na2CO3, K3PO4, and Et3N also
harmed the reaction’s outcome (entries 12−14, Table 1). The
blank experiments revealed the essential roles of iodine and
TFAA in this reaction (entries 15 and 16, Table 1). Notably, a
trace amount of 3aa was formed when the reaction was
conducted under an argon atmosphere (entry 17, Table 1).
Thus, heating the reaction mixture of 1a with 10 equiv of
DMSO 2a in the presence of 20 mol % I2 and 3 equiv of TFAA
at 120 °C under aerobic atmosphere for 1.5 h (conditions A)
was found as the optimum conditions to furnish 3aa in 91%
yield (entry 18, Table 1).
To decrease the methyl sulfoxide loading, which would be
useful for the reactions with other methyl sulfoxides,
particularly the ones with a high melting point, we conducted
several experiments using another solvent and DMSO. Among
various solvents such as toluene, m-xylene, and DMF, toluene
was found to be the best (entries 19−22, Table 1), and by
using the same, the stoichiometry of DMSO could be lowered
to 3 equiv. The reaction of 1a with 3 equiv of 2a in the
presence of 20 mol % I2 and 3 equiv of TFAA in toluene (0.4
M) at 120 °C under aerobic atmosphere (conditions B)
furnished 3aa in 92% yield (entry 20, Table 1). The full
optimization table (Table S1) is given in the Supporting
Information (SI).
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Note
a−c
Scheme 2. Substrate Scope
a
b
Reaction conditions A: 1 (0.5 mmol), 2 (10 equiv), I2 (20 mol %), TFAA (3 equiv), 120 °C. Reaction conditions B: 1 (0.5 mmol), 2 (3 equiv),
c
I2 (20 mol %), TFAA (3 equiv), toluene (0.4 M), 120 °C. Yield of product was reported in parentheses.
Next, we explored the scope of 2-(arylethynyl)-1,1′-biaryls
for the methythiolative annulation reaction with DMSO under
conditions A or B (Scheme-2). Various electron-withdrawing
and -donating group substituted 2-(phenylethynyl)-1,1′-biaryls
participated in the reaction with DMSO smoothly under
conditions A to furnish 10-phenyl-9-sulfenylphenanthrenes
(3ba−3ha) in moderate to high yield. Notably, various
halogens (Br, Cl, and F) were found intact in the various
positions of phenanthrenes, which could further be utilized for
the products’ synthetic diversification via cross-coupling
reaction. Moreover, electron-donating and -withdrawing
group substituted 2-(arylethynyl)-1,1′-biphenyls also under-
went methythiolative annulation reaction with DMSO under
conditions A or B to furnish 10-aryl-9-sulfenylphenantheres
(3ia−3la) in moderate to high yield except 2-(4-cyanopheny-
lethynyl)-1,1′-biphenyl, which furnished the corresponding
product, 4-(10-(methylthio)phenanthren-9-yl)benzonitrile
(3la) in 31% yield. When 1-(2-(phenylethynyl)phenyl)-
naphthalene was subjected to reaction with DMSO under
conditions A, 6-phenyl-5-sulfenyl benzo[c]phenanthrene 3ma
was formed in low yield (35%). The 2-heteroaryl-substituted
phenylethynylbenzenes also participated in the reaction with
DMSO to furnish the corresponding polycyclic heteroaro-
matics such as naphthothiophenes (3na and 3oa).
Significantly, the methylthiolative annulation was found to
be highly regioselective since only one regioisomer, 5-
(methylthio)-4-phenylnaphtho[2,1-b]thiophene 3na was
formed from 3-(2-(phenylethynyl)phenyl)thiophene 1n,
which also supported the electrophilic annulation reaction.
The reaction of 2-(phenylethynyl)-1,1′-biphenyl 1a with
DMSO-d6 2b under conditions A furnished (methyl-d3)(10-
phenylphenanthren-9-yl)sulfane 3ab in 80% yield, which
further supported that the source of the thiomethyl group is
DMSO. When methyl phenyl sulfoxide 2c was subjected to
reaction with 1a under conditions B, 81% of phenyl(10-
phenylphenanthren-9-yl)sulfane 3ac was formed. The struc-
tures of 3ca, 3da, 3ea, 3fa, 3ha, and 3ab were confirmed by X-
ray crystallographic structure determination (see Figures S1−
S6 and Table S2). In all of the reactions, the corresponding 9-
iodophenanthrene was formed as the sole side product in 2−
15% yield. In the reactions which produced the desired
product in moderate yield, the corresponding starting material,
i.e., 2-alkynyl biaryl, was also recovered.
To shed light on the reaction mechanism, we carried out few
reactions, as outlined in Scheme 3. The reaction of 1a with
diphenyl sulfoxide did not furnish 3ac (Scheme 3 A), which
revealed the requirement of methyl sulfoxides to synthesize 9-
sulfenylphenanthrenes from 2-alkynyl biaryls. A couple of
radical quenching experiments of the model reaction in
between 1a and DMSO 2a in the presence of a radical
quencher such as galvinoxyl (Scheme 3 B) and butylated
hydroxytoluene (BHT) (Scheme 3 C) were conducted, and
3aa was formed in 91% and 89% yield, respectively, revealing
the noninvolvement of free-radicals in the reaction. To prove
the in situ decomposition of DMSO to MeSH and HCHO by
TFAA, we probed a reaction for the in situ detection of
formaldehyde, as outlined in Scheme 3D. The nucleophilic
addition of the enolate of 2-phenylacetophenone (5) to the in
situ formed formaldehyde from DMSO and TFAA furnished 3-
hydroxy-1,2-diphenylpropan-1-one in 60% yield. When the
mixture of DMSO and TFAA was treated with I2 and stirred at
room temperature for a while, MeSI was formed in situ, as
evident by the LC−MS analysis (base peak at m/z = 174) of
the reaction mixture (Figure S7). After 30 min, when 1a was
added to the reaction mixture and it was heated at 120 °C for
1.5 h, 3aa was produced in 82% yield (Scheme 3E), which
supported the fact that the intermediate MeSI is the active
electrophilic species for the methylthiolative annulation of 2-
alkynyl biaryls.
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Note
a
The in situ formed MeSH then immediately reacted with
iodine to form the active electrophilic species, MeSI, along
with the formation of HI. Finally, the electrophilic annulation
of 1a (6-endo-dig cyclization) with MeSI furnished 3aa along
with the formation of HI again, which was finally oxidized by
DMSO under acidic conditions to regenerate iodine in the
catalytic cycle.18
Scheme 3. Mechanistic Studies
The synthetic diversification of the product, 10-phenyl-9-
sulfenylphenanthrene 3aa was demonstrated through sustain-
able and selective oxidation reactions using oxone as the
oxidant to the corresponding sulfoxide and sulfone (Scheme
5). When 3aa was heated with 0.6 equiv of oxone in ethanol at
Scheme 5. Synthetic Diversification of Sythesized Product,
a
10-Phenyl-9-sulfenylphenanthrene 3aa
a
Reactions were performed on a 0.3 mmol scale.
60 °C, 91% of the corresponding sulfoxide 11 was formed
selectively.21 However, when 3 equiv of oxone was used in
ethanol, 83% of the corresponding sulfone 12 was formed (see
the optimization of the reaction conditions to synthesize 12
selectively in Table S3).
In conclusion, we have developed an iodine-catalyzed
sustainable, cost-effective, and atom-economic synthetic
methodology for the methylthiolative annulation of 2-alkynyl
biaryls with DMSO to synthesize a wide variety of sulfenyl-
phenanthrenes and polycyclic heteroaromatics, i.e., naphtho-
thiophenes (15 new molecules) in moderate to good yields
under transition-metal-free, aerobic, and simple reaction
conditions. The mechanistic studies revealed that the reaction
proceeded through the in situ decomposition of DMSO by
TFAA to formaldehyde and MeSH, facilitated under the in situ
formed acid catalytic conditions. Notably, DMSO played
multiple roles in the methylthiolative annulation reaction, such
as the methylthiolating reagent, oxidant, and solvent. The
synthetic utility of the synthesized product, 10-phenyl-9-
sulfenylphenanthrene 3aa, was demonstrated by preparing
other new but potential molecules, 9-(methylsulfinyl)-10-
phenylphenanthrene and 9-(methylsulfonyl)-10-phenylphe-
nanthrene through selective and sustainable oxidation of 3aa
by using oxone. To the best of our knowledge, this is the first
report of iodine catalyzed methylthiolative annulation reaction
using DMSO as the sulfur source. We believe this cost-
effective, sustainable, atom-economic, and simple strategy will
be further explored in synthesizing various potential classes of
organic molecules.
a
Yield was determined by 1H NMR using 1,3,5-trimethoxybenzene as
the internal standard.
Based on the mechanistic studies and the previous literature
reports,16 we proposed a plausible mechanism for the
methylthiolative annulation reaction of 2-alkynyl biaryls with
DMSO as outlined in Scheme 4. Nucleophilic acyl substitution
Scheme 4. Plausible Reaction Mechanism
EXPERIMENTAL SECTION
■
of TFAA by DMSO followed by deprotonation produced a
sulfur ylide 7 along with the formation of trifluoroacetic acid
(TFA). A rearrangement of the ylide (7) through the
intramolecular migration of the trifluoroacetate group from
the S-center to the more electrophilic C-center furnished 8.
Next, in situ generated acid (TFA)-catalyzed nucleophilic acyl
substitution of 8 by another DMSO molecule (2a′)
reproduced the sulfur ylide 7 along with the formation of
MeSH and HCHO through C−O and C−S bond cleavage.
General Experimental Information. All reagents and solvents
including DMSO were purchased from Sigma-Aldrich and TCI
chemical companies. Flash column chromatography was performed
using silica gel (100−200 mesh). The starting materials such as 2-
(phenylethynyl)-1,1′-biaryls and products such as 9-sulfenylphenan-
threnes and naphthothiophenes were characterized by H, 13C, and
1
19F NMR. NMR spectra were recorded on a Bruker 400 MHz
instrument (400 MHz for 1H NMR, 100 MHz for 13C NMR, and 376
MHz for 19F NMR). Copies of 1H, 13C, and 19F NMR spectra can be
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1
found in the Supporting Information. 1H NMR experiments are
reported in units, parts per million (ppm) and were measured relative
to residual chloroform (7.26 ppm) in the deuterated solvent. 13C
NMR spectra are reported in ppm relative to deuterochloroform
and characterized by H and 13C NMR spectroscopy. The analytical
data of 1a matched with the reported literature.23
General Experimental Procedure for the Synthesis of 2-
(Phenylethynyl)-1,1′-biaryls (1c−1k and 1m−1o). Reperesentative
Experimental Procedure for the Synthesis of 4′-Chloro-2-(phenyl-
ethynyl)-1,1′-biphenyl (1c). Step 1:24 2-Iodoaniline (2.19 g, 10
mmol, 1 equiv), Pd(PPh3)2Cl2 (0.14 g, 0.4 mmol), CuI (0.076 g, 0.4
mmol), and Et3N (26 mL) were taken in a flame-dried two-neck RBF
in a standard Schlenk-line process under N2 atmosphere, and the
solution was stirred at room temperature for 5 min. Phenylacetylene
(1318 μL, 12 mmol, 1.2 equiv) was added to the RBF, and the
reaction mixture was stirred for 3 h at room temperature. After the
completion of the reaction, the solvent was evaporated. The crude
reaction mixture was diluted with ethyl acetate (100 mL) and washed
with water three times (3 × 10 mL). The crude product was purified
through silica gel column chromatography to provide 2-
(phenylethynyl)aniline (1.62 g, 8.4 mmol) in 84% yield as yellow
solid.
1
(77.00 ppm) and all were obtained with H decoupling. Coupling
constants are reported in hertz. Reactions were monitored by thin
1
layer chromatography (TLC) and H NMR of the crude reaction
mixture using 1,3,5-trimethoxybenzene as the internal standard. Mass
spectral data of unknown compounds were obtained from BITS-
Pilani, Pilani Campus, India, on a high resolution mass spectrometer,
HRMS (6545 Q-TOF LC/MS, Agilent). Melting points of unknown
compounds were recorded on a KRUSS Optronic M3000 apparatus.
The solvent system used for crystallization was the mixture of
dichloromethane and hexane (2:1). The crystals were grown by the
slow evaporation of the solvent from the solution. The single-crystal
XRD data collection and data reduction were performed using
CrysAlis PRO on a single-crystal Rigaku Oxford XtaLab Pro
diffractometer.
The product was characterized by the 1H and 13C NMR
spectroscopy, which matched with the reported literature.24
Step 2:25 2-(Phenylethynyl)aniline (1.55 g, 8 mmol) was added to
a solution of p-TsOH·H2O (4.57 g, 24 mmol) dissolved in MeCN (48
mL). The resulting suspension of ammonium salt was cooled to 0 °C
and was added gradually to a solution of NaNO2 (1.11 g, 16 mmol)
and KI (3.32 g, 20 mmol) in water (4.8 mL). The reaction mixture
was stirred for 10−15 min at 0 °C. After completion of the reaction,
saturated NaHCO3 and Na2S2O3 solution were added. The crude
reaction mixture was extracted with ethyl acetate (100 mL), washed
with water (30 × 3 mL) three times, and purified through silica gel
coloumn chromatography to provide 1-iodo-2-(phenylethynyl)-
benzene in 50% yield as yellow liquid.
General Experimental Procedure for the Synthesis of 2-
(Phenylethynyl)-1,1′-biaryls (1a and 1b). Representative Exper-
imental Procedure for the Synthesis of 5-Chloro-2-(phenylethynyl)-
1,1′-biphenyl (1b). Step 1:22 4-Chloro-2-iodoaniline (2.54 g, 10
mmol, 1 equiv), phenyl boronic acid (0.403 g, 10 mmol), Pd(PPh3)4
(0.578 g, 0.5 mmol), K2CO3 (8.3 g, 60 mmol), and solvent (320 mL,
PhMe/H2O/EtOH = 4.4:1:1) were taken in a 250 mL round-bottom
flask (RBF). The reaction mixture was refluxed in an oil bath, and the
progress of the reaction was monitored by TLC until the completion
of the reaction. The mixture was cooled to room temperature and
extracted with ethyl acetate (30 × 3 mL) three times. The combined
organic layer was further washed with brine (30 mL) and
subsequently dried over anhydrous Na2SO4. Finally, the solvent was
evaporated under reduced pressure to obtain the crude product which
was purified by flash column chromatography on silica gel to afford 4-
chloro-[1,1′-biphenyl]-2-amine (1.98 g, 9.7 mmol) in 97% yield.
1
The product was characterized by the H NMR spectroscopy and
matched with the reported literature.25
Step-3:26 1-Iodo-2-(phenylethynyl)benzene (0.913 g, 3 mmol),
phenyl boronic acid (0.403 g, 3.3 mmol), Pd(PPh3)4 (0.174 g, 0.15
mmol), K2CO3 (2.5 g, 18 mmol), and solvent (96 mL, PhMe/H2O/
EtOH = 4.4:1:1) were added subsequently in a 250 mL round-buttom
flask. The resulting mixture was refluxed in an oil bath, and the
progress of the reaction was monitored by thin layer chromatography
up to completion. The mixture was cooled to room temperature and
extracted with ethyl acetate. The combined organic layer was dried
over anhydrous Na2SO4. The solvent was evaporated under reduced
pressure to obtain the crude product, which was purified by flash
column chromatography on silica gel to afford 4′-chloro-2-(phenyl-
ethynyl)-1,1′-biphenyl 1c (0.704 g, 2.1 mmol) in 70% yield.
The product 1c was characterized by 1H and 13C NMR
spectroscopy, which matched with the reported literature.26
The other starting materials 1d,26 1e, 1f,26 1g,26 1h,29 1m,26 1n,
and 1o were also synthesized by following the above-mentioned
1
The product was characterized by H and 13C NMR spectroscopy,
and the corresponding analytical data is given, which also matched
with the reported literature:22 1H NMR (400 MHz, CDCl3) δ 7.50−
7.34 (m, 5H), 7.13−7.08 (m, 2H), 6.72−6.67 (m, 1H), 3.75 (s, 2H);
13C NMR (100 MHz, CDCl3) δ 142.13, 138.26, 129.95, 128.94,
128.89, 128.15, 127.64, 123.10, 116.63.
Step 2:22 4-Chloro-[1,1′-biphenyl]-2-amine (1.6 g, 8 mmol, 1
equiv) was added to a solution of aqueous HCl (4.16 mL in 13 mL of
H2O), cooled to 0 °C, and added gradually to an aqueous solution of
NaNO2(0.672 g in 13.28 mL H2O) and KI (2 g in 13.28 mL H2O) at
0 °C. The reaction mixture was stirred for 10−15 min at 0 °C, and
further stirring was continued at room temperature for 12 h. After the
completion of the reaction, saturated Na2S2O3 solution was added.
The crude reaction mixture was extracted with ethyl acetate (30 × 3
mL), washed with water (30 × 2 mL) twice, and purified through
silica gel coloumn chromatography to provide 5-chloro-2-iodo-1,1′-
biphenyl (1.58 g, 5 mmol) in 64% yield.
1
protocol and characterized fully by H and 13C NMR spectroscopy.
Reperesentative Experimental Procedure for the Synthesis of 2-
(m-Tolylethynyl)-1,1′-biphenyl (1j). Step 1:27 [1,1′-Biphenyl]-2-
amine (1.70 g, 10 mmol) was taken to aqueous HCl (5.2 mL, H2O
16.6 mL) solution. The reaction mixture was cooled to 0−5 °C. After
5 min, aqueous NaNO2 solution (0.84 g in 16.6 mL H2O) was added
dropwise at 0−5 °C. The resulting solution turned yellow after the
addition of aqueous KI solution (2.50 g in 16.6 mL H2O). The
reaction mixture was stirred vigorously for 18 h. After the completion
of the reaction, the solution was quenched by the addition of aqueous
Na2S2O3 solution. The resulting solution was extracted with ethyl
acetate (30 × 3 mL) and washed with water (30 mL). The combined
organic layer was dried over anhydrous Na2SO4. The solvent was
evaporated under reduced pressure to obtain the crude product which
was purified by flash column chromatography on silica gel to afford 2-
iodo-1,1′-biphenyl (2.38 g, 8.5 mmol) in 85% yield.
The product was characterized by the 1H and 13C NMR
spectroscopy which matched with the reported literature.22
Step 3:23 5-Chloro-2-iodo-1,1′-biphenyl (1.58 g, 5 mmol, 1 equiv),
Pd(PPh3)2Cl2 (0.07 g, 0.2 mmol), CuI (0.038 g, 0.2 mmol), and Et3N
(13 mL) were added in a flame-dried two neck RBF under N2
atmosphere in a standard Schlenk line process and stirred for 5 min at
room temperature. Then phenylacetylene (659 μL, 6 mmol, 1.2
equiv) was added to the reaction mixture under nitrogen atmosphere.
The reaction mixture was stirred for 3 h at room temperature. After
the completion of the reaction, the solvent was evaporated under
reduced pressure. The crude reaction mixture was diluted with ethyl
acetate (30 mL) and washed with water three times (3 × 10 mL). The
crude product was purified through silica gel column chromatography
to provide 2-chloro-5-(phenylethynyl)-1,1′-biphenyl 1b (1.275 g, 4.4
mmol) in 88.5% yield.
The product was characterized by the 1H and 13C NMR
spectroscopy which matched with the reported literature.27
The product was characterized by the 1H and 13C NMR
spectroscopy which matched with the reported literature.23
1a was also synthesized from commercially available [1,1′-
biphenyl]-2-amine by following steps 2 and 3 as mentioned above
Step 2:28 In a RBF, PdCl2(PPh3)2 (0.105 g, 0.15 mmol) and CuI
(0.028 g, 0.15 mmol) were added to a solution of 2-iodo-1,1′-
biphenyl (2.80 g, 3 mmol) in Et3N (9 mL) under nitrogen
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atmosphere in a standard Schlenk-line process. The reaction mixture
was stirred for 5 min. Then 1-ethynyl-3-methylbenzene (465 μL, 3.6
mmol, 1.2 equiv) was added to the RBF. The resulting mixture was
then heated in an oil bath under nitrogen atmosphere at 70 °C for 18
h. The reaction mixture was allowed to cool to room temperature.
Then the solvent was evaporated under reduced pressure. The crude
reaction mixture was extracted with ethyl acetate three times (3 × 30
mL). The combined organic layer was washed with water three times
(3 × 30 mL) and concentrated under reduced pressure to obtain the
crude product which was purified by column chromatography through
silica gel to afford 2-(m-tolylethynyl)-1,1′-biphenyl 1j (0.52 g, 1.94
mmol) in 63% yield.
added to the RBF, and the reaction mixture was stirred in an oil bath
at 120 °C under aerobic atmosphere. The progress of the reaction was
monitored by TLC. After completion of the reaction, the resulting
solution was extracted with ethyl acetate three times (3 × 10 mL),
and the combined organic layer was washed with water (3 × 10 mL).
The solvent was evaporated under reduced pressure to afford the
crude product which was purified by flash column chromatography
through silica gel to afford the product, (4,10-diphenylphenanthren-9-
yl)(methyl)sulfane 3ha (0.151 g, 0.401 mmol) in 80% yield.
Conditions B. To a solution of 2-(phenylethynyl)-1,1′-biphenyl 1a
(0.127 g, 0.5 mmol, 1 equiv) and (methylsulfinyl)benzene 2c (0.21 g,
1.5 mmol, 3 equiv) in toluene (1.25 mL, 0.4 M) was added I2 (0.0254
g, 0.1 mmol) in a flame-dried RBF. Then TFAA (0.212 mL, 1.5
mmol) was added to the RBF, and the reaction mixture was stirred in
an oil bath at 120 °C under aerobic atmosphere. The progress of the
reaction was monitored by TLC. After completion of the reaction, the
resulting solution was extracted with ethyl acetate three times (3 × 10
mL). The combined organic layer was washed with water (3 × 10
mL) and evaporated under reduced pressure. The crude product was
purified by flash column chromatography through silica gel to afford
pure phenyl(10-phenylphenanthren-9-yl)sulfane 3ac (0.147 g, 0.405
mmol) in 81% yield.
1 mmol Scale Detailed Experimental Procedure for the
Synthesis of (4,10-Diphenylphenanthren-9-yl)(methyl)sulfane 3ha
under Conditions A. To a solution of 2-(phenylethynyl)-1,1′:2′,1′′-
terphenyl 1h (0.33 g, 1 mmol, 1 equiv) in DMSO 2a (0.72 mL, 10
mmol, 1.4 M) was added I2 (0.0508 g, 0.2 mmol) in a flame-dried
RBF. Then TFAA (0.424 mL, 3 mmol) was added to the RBF, and
the reaction mixture was stirred in an oil bath at 120 °C under aerobic
atmosphere. The progress of the reaction was monitored by TLC.
After completion of the reaction, the resulting solution was extracted
with ethyl acetate three times (3 × 10 mL), and the combined organic
layer was washed with water (3 × 10 mL). The solvent was
evaporated under reduced pressure to afford the crude product which
was purified by flash column chromatography through silica gel to
afford the product, (4,10-diphenylphenanthren-9-yl)(methyl)sulfane
3ha (0.324 g, 0.74 mmol) in 74.5% yield.
Experimental Procedure for the Synthesis of 9-(Methylsulfinyl)-
10-phenylphenanthrene 11.21 Oxone (0.0553 g, 0.18 mmol) was
added to the solution of methyl(10-phenylphenanthren-9-yl)sulfane
3aa (0.0901 g, 0.3 mmol) dissolved in ethanol (1.5 mL). The reaction
mixture was stirred in an oil bath at 60 °C. The progress of the
reaction was monitored by TLC. After the completion of the reaction
the solvent was evaporated under reduced pressure. The crude
reaction mixture was extracted with ethyl acetate three times (3 × 10
mL). The combined organic layer was washed with water (3 × 10
mL) and evaporated under reduced pressure. The crude product was
purified by flash column chromatography through silica gel to afford
the 9-(methylsulfinyl)-10-phenylphenanthrene 11 in (0.0862 g, 0.273
mmol) in 91% yield.
Experimental Procedure for the Synthesis of 9-(Methylsulfonyl)-
10-phenylphenanthrene 12.21 Oxone (0.553 g, 1.8 mmol) was
added to the solution of methyl(10-phenylphenanthren-9-yl)sulfane
(0.91 g, 0.3 mmol) dissolved in ethanol (1.5 mL). The reaction
mixture was stirred in an oil bath at 60 °C. The progress of the
reaction was monitored by TLC until completion. After the
completion of the reaction the solvent was evaporated under reduced
pressure. The crude reaction mixture was extracted with ethyl acetate
three times (3 × 10 mL). The combined organic layer was washed
with water (3 × 10 mL) and evaporated under reduced pressure. The
crude product was purified by flash column chromatography through
silica gel to afford the 9-(methylsulfonyl)-10-phenylphenanthrene 12
in (0.083g, 0.25 mmol) 83% yield.
The product 1j was characterized by 1H and 13C NMR
spectroscopy, which matched with the reported literature.28
The other starting materials 1i and 1k were also synthesized by
following the above-mentioned protocol and characterized fully by 1H
and 13C NMR spectroscopy.
Experimental Procedure for the Synthesis of 4-([1,1′-Biphenyl]-
2-ylethynyl)benzonitrile (1l). Step-1:29 PdCl2(PPh3)2 (0.14 g, 0.4
mmol) and CuI (0.076 g, 0.4 mmol) were added to a solution of 2-
iodo-1,1′-biphenyl (2.80 g, 10 mmol) in Et3N (26 mL) under
nitrogen atmosphere in a standard Schlenk-line process. The reaction
mixture was stirred for 5 min. Then trimethylsilylacetylene (1709 μL,
12 mmol, 1.2 equiv) was added to the RBF. The resulting mixture was
heated in an oil bath under nitrogen atmosphere at 70 °C for 18 h.
The mixture was allowed to cool to room temperature. The solvent
was removed under reduced pressure. The crude reaction mixture was
extracted with ethyl acetate three times (3 × 30 mL). The combined
organic layer was washed with brine (30 mL) and concentrated under
reduced pressure. The crude product was purified by column
chromatography through silica gel to afford the corresponding
product, ([1,1′-biphenyl]-2-ylethynyl)trimethylsilane (1.0464 g, 4.2
mmol) in 42% yield.
The product was characterized by the 1H and 13C NMR
spectroscopy, which matched with the reported literature.29
Step 2:30 K2CO3 (1.104 g, 8 mmol) was added into the solution of
([1,1′-biphenyl]-2-ylethynyl)trimethylsilane (1.001 g, 4 mmol)
dissolved in MeOH (8.37 mL). The reaction mixture was stirred
for 3 h at room temperature. After the completion of the reaction,
solvent was evaporated under reduced pressure. The crude reaction
mixture was extracted with ethyl acetate three times (3 × 30 mL).
The combined organic layer was washed with brine (30 mL) and
concentrated under reduced pressure. The crude product was purified
by column chromatography to obtain pure 2-ethynyl-1,1′-biphenyl in
99% yield (0.704 g, 3.95 mmol).
The product was characterized by the 1H and 13C NMR
spectroscopy, which matched with the reported literature.30
Step-3:14e To a solution of 4-bromobenzonitrile (231 μL, 2 mmol,
1 equiv) in Et3N (20 mL) and DMF (6 mL) were added
PdCl2(PPh3)2 (0.070 g, 0.1 mmol) and CuI (0.019 g, 0.1 mmol)
under nitrogen atmosphere in a standard Schlenk-line process. The
reaction mixture was stirred for 5 min under N2 atmosphere. Then, 2-
ethynyl-1,1′-biphenyl (337 μL, 2 mmol, 1 equiv) was added to the
reaction mixture. The resulting mixture was then heated in an oil bath
under nitrogen atmosphere at 70 °C for 18 h. The mixture was
allowed to cool to room temperature. The solvent was removed under
reduced pressure. The crude reaction mixture was extracted with ethyl
acetate three times (3 × 30 mL). The combined organic layer was
washed with brine solution (30 mL) and concentrated under reduced
pressure. The crude product was purified by flash column
chromatography through silica gel to afford the product 4-([1,1′-
biphenyl]-2-ylethynyl)benzonitrile 1l (0.2 g, 0.72 mmol) in 36% yield.
1
The product was characterized by H and 13C NMR spectroscopy,
which matched with the reported literature.14e
4′-Bromo-2-(phenylethynyl)-1,1′-biphenyl (1e). White solid (2
mmol scale, 0.34 g, 51%); eluent hexane; mp = 64−66 °C; 1H NMR
(400 MHz, CDCl3) δ 7.67 (d, J = 7.4 Hz, 1H), 7.58 (q, J = 8.7 Hz,
4H), 7.44−7.29 (m, 8H); 13C{1H} NMR (100 MHz, CDCl3) δ 142.5,
139.4, 133.0, 131.3, 131.0, 129.3, 128.6, 128.32, 128.28, 127.4, 123.2,
121.8, 121.5, 92.6, 88.9 (overlapping peak present); HRMS (ESI), m/
z calcd for C20H13Br [M]: 332.0201; found: 332.0203.
General Experimental Procedure for the Synthesis of 10-
Aryl-9-sulfenylphenanthrenes or Naphthothiophenes (3aa−
3oa and 3ab−3ac). Conditions A. To a solution of 2-(phenyl-
ethynyl)-1,1′:2′,1′′-terphenyl 1h (0.165 g, 0.5 mmol, 1 equiv) in
DMSO 2a (0.36 mL, 5 mmol, 1.4 M) was added I2 (0.0254 g, 0.1
mmol) in a flame-dried RBF. Then TFAA (0.212 mL, 1.5 mmol) was
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2
2-((4-Propylphenyl)ethynyl)-1,1′-biphenyl (1i). Yellow viscous
liquid (2 mmol scale, 0.312 g, 52.6%); eluent hexane; 1H NMR
(400 MHz, CDCl3) δ 7.72−7.58 (m, 3H), 7.48−7.28 (m, 6H), 7.25−
7.23 (m, 2H), 7.09 (d, J = 8.2 Hz, 2H), 2.59−2.53 (t, 2H), 1.61 (m, J
= 7.5 Hz, 2H), 0.91 (t, J = 7.3 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 143.8, 143.0, 140.6, 132.8, 131.2, 129.4, 128.4, 128.3, 127.8,
127.4, 127.0, 121.8, 120.6, 92.5, 88.7, 37.9, 24.3, 13.7 (overlapping
peaks present); HRMS (ESI), m/z calcd for C23H20 [M]: 296.1565;
found: 296.1508.
3JC−F = 8.59 Hz), 122.7, 116.0 (d, JC−F = 23.63 Hz), 112.7, 19.9;
Anal. Calcd for C21H15FS: C, 79.22; H, 4.75; S, 10.07. Found: C,
79.74; H, 4.32; S, 10.32. The assignment is supported by an X-ray
crystallographic structure determination (CCDC 2041730).
(2-Bromo-10-phenylphenanthren-9-yl)(methyl)sulfane (3ea).
White crystalline solid (0.5 mmol scale, 0.127 g, 67%); eluent
hexane; mp = 202−204 °C; 1H NMR (400 MHz, CDCl3) δ 8.87 (dd,
J = 7.5, 1.9 Hz, 1H), 8.70 (d, J = 7.8 Hz, 1H), 8.58 (d, J = 8.9 Hz,
1H), 7.81−7.68 (m, 3H), 7.55 (dd, J = 6.8, 2.3 Hz, 4H), 7.32 (dd, J =
7.7, 1.7 Hz, 2H), 2.19 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
144.1, 139.9, 133.6, 133.2, 131.9, 130.5, 130.2, 129.8, 129.2, 128.3,
127.8, 127.6, 127.2, 124.3, 122.8, 120.9, 20.0. Anal. Calcd for
C21H15BrS: C, 66.50; H, 3.99; S, 8.45. Found: C, 66.66; H, 3.91; S,
7.86. The assignment is supported by an X-ray crystallographic
structure determination (CCDC 2033891).
2-((3-Nitrophenyl)ethynyl)-1,1′-biphenyl (1k). Yellow solid (2
mmol scale, 0.297 g, 49.7%); eluent hexane/EtOAc (16:1, v/v); mp =
68−70 °C; 1H NMR (400 MHz, CDCl3) δ 8.21−8.14 (m, 1H), 8.11
(ddd, J = 8.2, 2.3, 1.1 Hz, 1H), 7.70−7.65 (m, 3H), 7.60−7.56 (m,
1H), 7.52 (m, 2H), 7.49−7.45 (m, 3H), 7.44−7.35 (m, 2H); 13C{1H}
NMR (100 MHz, CDCl3) δ 148.0, 144.3, 140.2, 136.7, 132.8, 129.5,
129.23, 129.15, 127.9, 127.7, 127.1, 126.0, 125.1, 122.6, 120.5, 92.0,
89.6 (overlapping peak present). Anal Calcd for C20H13NO2: C,
80.25; H, 4.38; N, 4.68. Found: C, 80.75; H, 4.18; N, 5.08.
3-(2-(Phenylethynyl)phenyl)thiophene (1n). Colorless liquid (2
mmol scale, 0.397, 76.2%); eluent hexane; 1H NMR (400 MHz,
CDCl3) δ 7.71 (d, J = 2.9 Hz, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.55 (d, J
= 5.0 Hz, 1H), 7.51 (d, J = 7.1 Hz, 1H), 7.47−7.43 (m, 2H), 7.42−
7.37 (m, 2H), 7.37−7.28 (m, 5H); 13C{1H} NMR (100 MHz,
CDCl3) δ 141.0, 138.2, 133.2, 131.4, 129.0, 128.7, 128.6, 128.3, 128.2,
126.9, 124.7, 123.6, 123.4, 121.1, 92.6, 89.6. Anal. Calcd for C18H12S:
C, 83.04; H, 4.65; S, 12.31; found C, 83.25; H, 4.78; S, 12.01.
2-(2-(Phenylethynyl)phenyl)thiophene (1o). Colorless liquid (2
Methyl(10-phenyl-2-(trifluoromethyl)phenanthren-9-yl)sulfane
(3fa). Yellowish white crystalline solid (0.5 mmol scale, 0.128 g,
69.5%); eluent hexane; mp = 124−126 °C; H NMR (400 MHz,
1
CDCl3) δ 8.91 (d, J = 7.8 Hz, 1H), 8.84 (d, J = 8.9 Hz, 1H), 8.79 (d, J
= 8.0 Hz, 1H), 7.86−7.76 (m, 3H), 7.73 (d, J = 6.7 Hz, 1H), 7.60−
7.52 (m, 3H), 7.34 (d, J = 7.9 Hz, 2H), 2.20 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 144.9, 139.6, 133.5, 132.7, 132.5, 131.6, 130.0,
129.8, 129.6, 128.5, 128.3, 128.2, 127.9, 127.7, 127.3, 125.50, 125.46,
123.4, 122.9, 19.9; 19F NMR (376 MHz, CDCl3) δ −62.2. Anal.
Calcd for C22H15F3S: C, 71.72; H, 4.10; S, 8.70. Found: C, 71.48; H,
4.24; S, 8.10. The assignment is supported by an X-ray crystallo-
graphic structure determination (CCDC 2041729).
1
Methyl(4-methyl-10-phenylphenanthren-9-yl)sulfane (3ga).
White solid (0.5 mmol scale, 0.085 g, 54%); eluent hexane; mp =
75−78 °C; 1H NMR (400 MHz, CDCl3) δ 8.99 (d, J = 8.1 Hz, 1H),
8.91 (d, J = 7.9 Hz, 1H), 7.79−7.75 (m, 1H), 7.73−7.69 (m, 1H),
7.57−7.53 (m, 4H), 7.37−7.53 (m, 4H), 3.19 (s, 3H), 2.23 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 145.5, 141.5, 134.8, 133.6,
132.8, 131.9, 131.7, 131.5, 130.8, 129.9, 128.0, 127.9, 127.4, 127.1,
126.9, 126.7, 125.6, 125.4, 27.2, 19.9; HRMS (ESI) m/z: calcd for
C22H18S [M]: 314.1129; found: 314.1133.
mmol scale, 0.373 g, 71.6%); eluent hexane; H NMR (400 MHz,
CDCl3) δ 7.63 (ddd, J = 8.9, 8.0, 1.6 Hz, 3H), 7.54−7.49 (m, 2H),
7.36 (ddd, J = 6.5, 5.8, 1.2 Hz, 5H), 7.29 (td, J = 7.6, 1.3 Hz, 1H),
7.14 (dd, J = 5.1, 3.7 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
142.6, 136.0, 133.7, 131.4, 129.0, 128.6, 128.3, 127.14, 127.05, 126.8,
125.9, 123.4, 120.6, 93.7, 89.5 (Overlapping peak present); HRMS
(ESI) m/z: calcd for C18H12S [M]: 260.0660; found: 260.0607.
Methyl(10-phenylphenanthren-9-yl)sulfane (3aa).16 White solid
(0.5 mmol scale, 0.132 g, 88%); eluent hexane; 1H NMR (400 MHz,
CDCl3) δ 8.89 (dd, J = 7.5, 1.9 Hz, 1H), 8.81−8.74 (m, 2H), 7.78−
7.70 (m, 2H), 7.66 (m, 1H), 7.58−7.50 (m, 3H), 7.49−7.41 (m, 2H),
7.36 (dd, J = 7.9, 1.6 Hz, 2H), 2.20 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 145.2, 140.8, 132.1, 132.0, 131.6, 130.8, 130.5, 129.9,
128.4, 128.1, 127.7, 127.4, 127.3, 127.1, 126.9, 126.6, 123.0, 122.5,
20.0.
(4,10-Diphenylphenanthren-9-yl)(methyl)sulfane (3ha). White
crystalline solid (0.5 mmol scale, 0.151 g, 80.3%); eluent hexane;
mp = 143−145 °C; H NMR (400 MHz, CDCl3) δ 8.83 (d, J = 7.3
1
Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.59−7.37 (m, 14H), 7.14 (ddd, J
= 8.5, 6.9, 1.4 Hz, 1H), 2.22 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 145.4, 145.0, 141.2, 140.1, 133.6, 132.9, 132.1, 131.4, 130.8,
130.0, 129.2, 129.1, 128.1, 127.9, 127.3, 127.09, 127.05, 126.8, 125.6,
124.7, 20.0. Anal. Calcd for C27H20S: C, 86.13; H, 5.35; S, 8.51.
Found: C, 85.84; H, 5.43; S, 9.21. The assignment is supported by an
X-ray crystallographic structure determination (CCDC 2052186).
Methyl(10-(4-propylphenyl)phenanthren-9-yl)sulfane (3ia). Off-
white crystalline solid (0.5 mmol scale, 0.121 g, 70.7%); eluent
hexane; mp = 134−136 °C; 1H NMR (400 MHz, CDCl3) δ 8.90 (dd,
J = 7.6, 1.9 Hz, 1H), 8.79 (dd, J = 7.7, 1.8 Hz, 1H), 8.76 (d, J = 8.6
Hz, 1H), 7.78−7.71 (m, 2H), 7.68−7.64 (m, 1H), 7.52−7.44 (m,
2H), 7.37 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 2.4 Hz, 2H), 2.82−2.70
(m, 2H), 2.21 (s, 3H), 1.85−1.79 (m, 2H), 1.08 (t, J = 7.3 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 145.3, 141.6, 137.9, 129.7,
128.5, 128.1, 127.7, 127.4, 127.1, 126.7, 126.6, 122.9, 122.4, 38.0,
24.5, 20.0, 14.03; HRMS (ESI) m/z calcd for C24H22S [M]:
342.1442; found: 342.1447.
(6-Chloro-10-phenylphenanthren-9-yl)(methyl)sulfane (3ba).
Yellow Solid (0.5 mmol scale, 0.101 g, 60.3%); eluent hexane; mp
1
= 92−95 °C; H NMR (400 MHz, CDCl3) δ 8.83 (d, J = 8.9 Hz,
1H), 8.73 (d, J = 2.1 Hz, 1H), 8.64 (d, J = 8.3 Hz, 1H), 7.71−7.64
(m, 2H), 7.58−7.43 (m, 5H), 7.35 (dd, J = 7.7, 1.6 Hz, 2H), 2.18 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.5, 140.4, 133.1, 132.5,
131.9, 131.2, 130.4, 129.8, 129.5, 129.4, 128.5, 128.1, 127.8, 127.4,
127.2, 122.6, 122.5, 20.0; HRMS (ESI) m/z: calcd for C21H15ClS
[M]: 334.0583; found: 334.0567.
(2-Chloro-10-phenylphenanthren-9-yl)(methyl)sulfane (3ca). Off
white crystalline solid (0.5 mmol scale, 0.116 g, 69%); eluent hexane;
mp = 185−187 °C; 1H NMR (400 MHz, CDCl3) δ 8.86 (dd, J = 7.6,
2.0 Hz, 1H), 8.73−8.68 (d, J = 8.9 Hz, 1H), 8.66 (d, J = 8.9 Hz, 1H),
7.80−7.69 (m, 2H), 7.62−7.49 (m, 4H), 7.39 (d, J = 2.2 Hz, 1H),
7.32 (dd, J = 7.8, 1.6 Hz, 2H), 2.19 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 144.2, 140.0, 133.3, 132.7, 131.9, 130.3, 129.8, 128.9,
128.3, 127.9, 127.7, 127.6, 127.4, 127.2, 124.2, 122.9, 20.0; Anal.
Calcd for C21H15ClS: C, 75.32; H, 4.52; S, 9.57. Found: C, 75.43; H,
4.55; S, 8.84. The assignment is supported by an X-ray crystallo-
graphic structure determination (CCDC 2052187).
Methyl(10-(m-tolyl)phenanthren-9-yl)sulfane (3ja). Yellowish
white crystalline solid (0.5 mmol scale, 0.128 g, 81.4%); eluent
hexane; mp = 205−207 °C; 1H NMR (400 MHz, CDCl3) δ 8.86 (dd,
J = 7.6, 1.9 Hz, 1H), 8.82−8.69 (m, 2H), 7.76−7.67 (m, 2H), 7.66−
7.59 (m, 1H), 7.46−7.38 (m, 3H), 7.33−7.29 (m, 1H), 7.15 (d, J =
0.6 Hz, 2H), 2.46 (s, 3H), 2.20 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 145.4, 140.8, 137.6, 132.2, 132.0, 131.4, 130.8, 130.5, 128.5,
128.0, 127.9, 127.7, 127.4, 127.1, 126.9, 126.8, 126.6, 123.0, 122.4,
21.6, 20.1. Anal. Calcd for C22H18S: C, 84.03; H, 5.77; S, 10.20.
Found: C, 83.83; H, 6.17; S, 9.82.
(2-Fluoro-10-phenylphenanthren-9-yl)(methyl)sulfane (3da).
White crystalline solid (0.5 mmol scale, 0.130 g, 82%); eluent
hexane; mp = 156−158 °C; 1H NMR (400 MHz, CDCl3) δ 8.91 (dd,
J = 7.6, 1.9 Hz, 1H), 8.74−8.65 (m, 2H), 7.80−7.70 (m, 2H), 7.58−
7.54 (m, 3H), 7.44−7.31 (m, 3H), 7.10 (dd, J = 10.8, 2.7 Hz, 1H),
2.22 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.1 (d, 1JC−F
=
Methyl(10-(3-nitrophenyl)phenanthren-9-yl)sulfane (3ka). Yel-
low viscous liquid (0.5 mmol scale, 0.107 g, 62%); eluent hexane/
EtOAc (12:1, v/v); 1H NMR (400 MHz, CDCl3) δ 8.85 (dd, J = 6.4,
245 Hz), 144.4, 144.3, 140.1, 133.4 (d, 3JC−F = 8.15 Hz), 133.1, 131.4,
130.4, 129.7, 128.2, 127.8, 127.5, 127.18, 127.15, 127.1, 124.8 (d,
7887
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Note
3.1 Hz, 1H), 8.81−8.77 (m, 2H), 8.39−8.36 (m, 1H), 8.25 (t, J = 1.7
Hz, 1H), 7.77 (dd, J = 6.3, 3.3 Hz, 2H), 7.73−7.67 (m, 3H), 7.51−
7.46 (m, 2H), 7.30 (dd, J = 8.3, 0.9 Hz, 1H), 2.19 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 148.2, 142.6, 142.4, 136.3, 132.3, 131.6,
131.3, 131.0, 130.7, 129.1, 127.7, 127.6, 127.5, 127.0, 125.0, 123.1,
122.8, 122.4, 20.0; HRMS (ESI) m/z: calcd for C21H15NO2S [M]:
345.0823; found: 345.0796.
9-(Methylsulfinyl)-10-phenylphenanthrene (11). White solid (0.3
mmol scale, 0.0862 g, 91%); eluent hexane/EtOAc (4:1, v/v); mp =
1
183−185 °C. H NMR (400 MHz, CDCl3) δ 9.55 (dd, J = 7.6, 2.0
Hz, 1H), 8.80 (d, J = 9.6 Hz, 1H), 8.73 (d, J = 8.3 Hz, 1H), 7.79−
7.67 (m, 3H), 7.60−7.39 (m, 6H), 7.12 (d, J = 6.5 Hz, 1H), 3.03 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.3, 136.8, 134.9, 131.4,
131.2, 130.6, 129.7, 129.6, 128.8, 128.7, 128.5, 128.1, 128.0, 127.4,
127.3, 127.0, 125.1, 123.4, 122.5, 38.7 (overlapping peaks present);
HRMS (ESI) m/z: calcd for C21H16OS [M]: 316.0922; found:
316.0893.
4-(10-(Methylthio)phenanthren-9-yl)benzonitrile (3la). Yellow
solid (0.5 mmol scale, 0.051 g, 31.3%); eluent hexane/EtOAc
1
(19:1, v/v); mp =155−157 °C; H NMR (400 MHz, CDCl3) δ 8.89
9-(Methylsulfonyl)-10-phenylphenanthrene (12). White solid
(0.3 mmol scale, 0.083 g, 83%); eluent hexane/EtOAc (8:1, v/v);
mp = 172−174 °C; 1H NMR (400 MHz, CDCl3) δ 9.10 (dd, J = 7.5,
2.2 Hz, 1H), 8.83 (dd, J = 7.5, 2.3 Hz, 1H), 8.76 (d, J = 8.3 Hz, 1H),
7.81−7.74 (m, 3H), 7.51 (ddd, J = 8.2, 5.4, 1.2 Hz, 4H), 7.42 (dd, J =
8.4, 1.0 Hz, 1H), 7.38−7.33 (m, 2H), 3.14 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 143.0, 137.9, 133.0, 132.0, 131.5, 131.1, 129.8,
129.6, 127.9, 127.82, 127.77, 127.6, 127.3, 126.8, 126.4, 123.3, 122.4,
46.0 (overlapping peaks present); HRMS (ESI) m/z: calcd for
C21H16O2S [M]: 332.0871; found: 332.0781.
(dd, J = 7.5, 1.9 Hz, 1H), 8.81−8.74 (m, 2H), 7.78−7.70 (m, 2H),
7.66 (ddd, J = 8.3, 6.4, 1.9 Hz, 1H), 7.58−7.50 (m, 3H), 7.49−7.41
(m, 2H), 7.36 (dd, J = 7.9, 1.6 Hz, 2H), 2.20 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 145.8, 143.3, 132.0, 131.7, 131.6, 131.2, 131.0,
130.9, 130.6, 127.7, 127.6, 127.5, 127.4, 127.0, 123.1, 122.8, 120.0,
111.3, 20.0; HRMS (ESI) m/z: calcd for C22H15NS [M]: 325.0925;
found: 325.099.
Methyl(6-phenylbenzo[c]phenanthren-5-yl)sulfane (3ma).
White solid (0.5 mmol scale, 0.062 g, 35.4%); eluent hexane; mp =
1
134−136 °C; H NMR (400 MHz, CDCl3) δ 9.08 (dd, J = 12.9, 8.2
Hz, 2H), 8.97 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.81−
7.71 (m, 3H), 7.71−7.61 (m, 2H), 7.59−7.52 (m, 3H), 7.39 (dd, J =
8.4, 6.9 Hz, 3H), 2.23 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
144.4, 140.8, 133.4, 133.1, 130.6, 130.3, 128.8, 128.7, 128.2, 128.1,
127.4 127.2, 127.0, 126.9, 126.4, 126.2, 126.1, 125.4, 20.1; HRMS
(ESI) m/z: calcd for C25H18S [M]: 350.1129; found: 350.1138.
5-(Methylthio)-4-phenylnaphtho[2,1-b]thiophene (3na). White
solid (0.5 mmol scale, 0.092 g, 60%); eluent hexane; mp = 109−111
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00861.
■
sı
FAIR data including the primary NMR FID files for
compounds 1a−1o, 3aa-3oa, 11 and 12 (ZIP)
1
Optimization of reaction conditions (full table), X-ray
crystal structure and selected crystal data of 3ca, 3da,
3ea, 3fa, 3ha, and 3ab, optimization of reaction
conditions for the synthesis of 11 and 12, mass spectrum
°C; H NMR (400 MHz, CDCl3) δ 8.90−8.83 (m, 1H), 8.44−8.36
(m, 1H), 8.04 (d, J = 5.5 Hz, 1H), 7.71−7.65 (m, 2H), 7.60 (d, J =
5.4 Hz, 1H), 7.54−7.49 (m, 5H), 2.19 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 142.2, 140.7, 138.3, 138.0, 131.6, 129.7, 129.2, 129.1,
128.1, 128.0, 127.4, 126.8, 126.7, 125.9, 124.6, 124.3, 20.2; HRMS
(ESI) m/z: calcd for C19H14S2 [M]: 306.0537; found: 306.0494.
5-(Methylthio)-4-phenyl-3H-1λ3-naphtho[1,2-b]thiophene (3oa).
of in-situ generated MeSI, copies of H and 13C NMR
1
spectra for all synthesized compounds (PDF)
1
Accession Codes
Colorless liquid (0.5 mmol scale, 0.038 g, 24.8%); eluent hexane; H
NMR (400 MHz, CDCl3) δ 8.84 (d, J = 7.7 Hz, 1H), 8.21 (d, J = 7.3
Hz, 1H), 7.65 (m, 2H), 7.55−7.47 (m, 3H), 7.44−7.37 (m, 3H), 6.99
(d, J = 5.4 Hz, 1H), 2.17 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 142.2, 140.7, 138.3, 138.0, 131.6, 129.7, 129.2, 129.1, 128.1, 128.0,
127.4, 126.8, 126.7, 125.9, 124.6, 124.3, 20.2; HRMS (ESI) m/z:
calcd for C19H14S2 [M]: 306.0537; found: 306.0535.
CCDC 2033891, 2041729−2041730, 2044602, and 2052186−
2052187 contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033.
(Methyl-d3)(10-phenylphenanthren-9-yl)sulfane (3ab). White
crystalline solid (0.5 mmol scale, 0.122 g, 80.4%); eluent hexane;
1
mp =178−180 °C; H NMR (400 MHz, CDCl3) δ 8.94 (d, J = 7.6
AUTHOR INFORMATION
Corresponding Author
Hz, 1H), 8.82−8.76 (m, 2H), 7.82−7.72 (m, 2H), 7.70−7.66 (m,
1H), 7.63−7.44 (m, 5H), 7.40 (d, J = 6.2 Hz, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ 145.2, 140.8, 132.1, 132.0, 130.7, 130.5, 129.9,
128.4, 128.0, 127.6, 127.4, 127.2, 127.1, 126.8, 126.6, 122.9, 122.4.
Anal. Calcd for C21H13D3S: C, 83.12; H, 6.31; S, 10.57. Found: C,
83.02; H, 6.55; S, 10.43. The assignment is supported by an X-ray
crystallographic structure determination (CCDC 2044602).
Phenyl(10-phenylphenanthren-9-yl)sulfane (3ac).16 Yellow solid
(0.5 mmol scale, 0.147 g, 81.2%); eluent hexane; 1H NMR (400
MHz, CDCl3) δ 8.80 (dd, J = 8.3, 3.9 Hz, 2H), 8.65 (d, J = 7.3 Hz,
1H), 7.76−7.67 (m, 2H), 7.60 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 7.54−
7.49 (m, 2H), 7.47−7.40 (m, 3H), 7.29−7.26 (m, 2H), 7.16−6.98
(m, 3H), 6.93 (dd, J = 8.3, 1.2 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 146.8, 140.2, 139.0, 134.2, 132.3, 132.1, 131.1, 130.9, 130.0,
129.5, 128.73, 128.65, 128.5, 128.3, 128.1, 128.0, 127.63, 127.59,
127.4, 127.13, 127.06, 126.7, 126.4, 124.7, 122.8, 122.6 (overlapping
peaks present).
■
Tanmay Chatterjee − Department of Chemistry, Birla
Institute of Technology and Science, Pilani (BITS Pilani),
Hyderabad 500078, Telangana, India; orcid.org/0000-
0001-6342-0166; Email: tanmay@hyderabad.bits-
pilani.ac.in
Author
Nilanjana Mukherjee − Department of Chemistry, Birla
Institute of Technology and Science, Pilani (BITS Pilani),
Hyderabad 500078, Telangana, India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00861
Notes
3-Hydroxy-1,2-diphenylpropan-1-one (6).31 White solid (0.5
The authors declare no competing financial interest.
1
mmol scale, 0.068 g, 60.1%); eluent hexane/EtOAc (10:1, v/v); H
NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 8.4, 1.3 Hz, 2H), 7.40 (ddd,
J = 6.8, 4.0, 1.3 Hz, 1H), 7.32−7.16 (m, 7H), 4.72 (dd, J = 8.4, 4.8
Hz, 1H), 4.20 (dd, J = 11.4, 8.4 Hz, 1H), 3.81 (dd, J = 11.4, 4.8 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 200.0, 136.2, 136.1, 133.2,
129.2, 128.9, 128.5, 128.4, 127.6, 65.2, 56.4.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the Additional Competitive
Research Grant (BITS/GAU/ACRG/2019/H602) of BITS-
Pilani, Hyderabad campus, for this study. The NMR, SCXRD,
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J. Org. Chem. 2021, 86, 7881−7890

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
F.; Castedo, L.; Fernandez, D.; Neo, A. G.; Romero, V.; Tojo, G.
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and LC-MS facilities at the Central Analytical Laboratory
(CAL) of BITS-Pilani, Hyderabad campus, and the HRMS
facility, funded by DST-FIST at BITS-Pilani, Pilani campus,
are also gratefully acknowledged.
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J. Org. Chem. 2021, 86, 7881−7890