Efficient synthesis of functionalized 6-substituted-thiosalicylates via microwave-promoted Suzuki cross-coupling reaction

Article abstract of DOI:10.1016/j.tet.2014.02.085

Functionalized 6-substituted-thiosalicylates are key intermediates for the synthesis of pyrimidinyl(thio)salicylic acids, a group of important herbicides targeting plant acetohydroxyacid synthase. Therefore, it is of great interest to develop an efficient method for the syntheses of 6-substituted-thiosalicylates. Herein, we have developed a direct and efficient method for the synthesis of functionalized 6-substituted-thiosalicylates (4) from aryl iodide (1) by using an improved microwave-assisted Suzuki cross-coupling reaction. Almost all the reactions proceeded smoothly and afforded moderate to excellent yields of products. Moreover, this protocol is obviously superior to the traditional available methods and could be utilized to synthesize pyrimidinyl(thio)salicylic acid and its derivatives.

Full text of DOI:10.1016/j.tet.2014.02.085

Tetrahedron 70 (2014) 2746e2752
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis of functionalized 6-substituted-thiosalicylates via
microwave-promoted Suzuki cross-coupling reaction
*
*
Yu-Chao Liu, Ren-Yu Qu, Qiong Chen , Qiong-You Wu, Guang-Fu Yang
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan,
Hubei 430079, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 January 2014
Received in revised form 20 February 2014
Accepted 27 February 2014
Available online 6 March 2014
Functionalized 6-substituted-thiosalicylates are key intermediates for the synthesis of pyrimidinyl(thio)
salicylic acids, a group of important herbicides targeting plant acetohydroxyacid synthase. Therefore, it is
of great interest to develop an efficient method for the syntheses of 6-substituted-thiosalicylates. Herein,
we have developed a direct and efficient method for the synthesis of functionalized 6-substituted-thi-
osalicylates (4) from aryl iodide (1) by using an improved microwave-assisted Suzuki cross-coupling
reaction. Almost all the reactions proceeded smoothly and afforded moderate to excellent yields of
products. Moreover, this protocol is obviously superior to the traditional available methods and could be
utilized to synthesize pyrimidinyl(thio)salicylic acid and its derivatives.
Keywords:
Pyrimidinyl(thio)salicylic acids
6-Substituted-thiosalicylates
Suzuki cross-coupling reactions
Microwave irradiation
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
reactions;4 The second method involved formal [3þ3]-cyclization
of 3-aryloxythio-1-trimethylsilyloxybuta-1,3-dienes with 3-
The pyrimidinyl(thio)salicylic acids are an important class of
commercial herbicides targeting acetohydroxyacid synthase.1 As
shown in Fig. 1, functionalized 6-substituted-thiosalicylates2 are
commonly found as a privileged structure in almost all the herbi-
cidal pyrimidinyl(thio)salicylic acids.
Traditionally, these compounds have been prepared by three
practical approaches. As shown in Fig. 2, the first pathway has re-
lied on transition-metal-catalyzed3 and metal-free CeS coupling
alkoxy-2-en-1-ones;5 The third synthetic methodology is based
on the carbanion-induced ring transformation of 2H-pyran-2-
ones.2i,6 Although these methods have provided useful access to
the substituted 6-substituted-thiosalicylates, there are still no-
ticeable drawbacks, such as relatively harsh reaction conditions,
inaccessible substrates, and low yields. Therefore, the development
of general and direct strategies for the preparation of functionalized
6-substituted-thiosalicylates would be highly interesting.
Fig. 1. Chemical structures of pyrimidinyl(thio)salicylic herbicides.
* Corresponding authors. Tel.: þ86 27 67867800; fax: þ86 27 67867141;
e-mail addresses: qchen@mail.ccnu.edu.cn (Q. Chen), gfyang@ccnu.edu.cn (G.-F. Yang).
Fig. 2. Three practical approaches for the synthesis of the thiosalicylates.
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.085

Y.-C. Liu et al. / Tetrahedron 70 (2014) 2746e2752
2747
Not long ago, our laboratory successfully employed microwave
irradiation7 to synthesize 6-arylsalicylates.8 However, application
of this strategy to prepare 6-substituted-thiosalicylates has been
surprisingly unsuccessful. As shown in Fig. 3, although the optimal
conditions have been used on the synthesis of 3a0 with excellent
yield, this methodology did not give similar results for the synthesis
of3a.
DME (3 mL), and H2O (0.6 mL). However, the transformation was
incomplete and the yield was only 26% (Table 1, entry 1). During
optimization, the stoichiometric ratio of the catalyst and the tem-
perature proved to be important parameters for this reaction (Table
1, entries 2e4). The yield was notably increased to 84% when the
reaction was carried out at 120 ꢀC, with 2 mol % of Pd(PPh3)4 (Table
1, entry 4). A survey of solvents revealed that toluene/H2O¼5:1 (v/
v) was optimal (Table 1, entries 4e8). Most surprisingly, we ob-
served no conversion of aryl halide into product 3s when the
phenylboronic acid was changed to furan-2-ylboronic acid (Table 1,
entry 9), indicating that this condition is not generally applicable
for different substrates. Therefore, the reaction conditions were
further adjusted. As shown in Table 1 (entries 10e12), when we
added a small amount of tetrabutyl ammonium bromide (TBAB)
into the reaction mixture, the yields of the product were improved
markedly. Maybe it is due to that TBAB can facilitate the migration
of a reactant from one phase into another phase where reaction
occurs. Furthermore, as compared with conventional heating
methods, microwave irradiation dramatically accelerated these
reactions and increased the reaction yields (Table 1, entry 13).
With the optimized conditions defined, we investigated the
scope of substrates by employing a variety of arylboronic acids
substituted with electron-donating and electron-withdrawing
groups. As shown in Table 2, significant structural variations in
the arylboronic acid components were well tolerated and afforded
the corresponding functionalized 6-substituted-thiosalicylates (3)
in moderate to good yields. Both electron-rich and electron-poor
arylboronic acids could be successfully utilized in this trans-
formation; methyl, methoxy, tert-butyl, nitro, trifluoromethyl, and
acetyl derivatives showed no significant effects on the trans-
formation and afforded good yields of products (Table 2, 3gel).
Even the potentially problematic bromo-substituted arylboronic
acid resulted in product 3e with acceptable yields. It should be
noted that incorporation of halogen-substituents at the ortho, meta
or para positions in arylboronic acids did not retard the reaction,
demonstrating that steric modification can be accomplished
without compromising the efficiency of the process (Table 2,
3bed).
Fig. 3. Synthesis of 2,2-dimethyl-5-phenyl-4H-benzo[d][1,3]oxathiin-4-one and 2,2-
dimethyl-5-phenyl-4H-benzo[d][1,3]dioxin-4-one.
Herein, as a continuation of our research on the synthesis of
structurally diverse heterocyclic compounds, we report the syn-
thesis of functionalized 6-substituted-thiosalicylates via an im-
proved Suzuki cross-coupling reaction under microwave
irradiation.
2. Result and discussion
The aryl iodide (1) was prepared by using a previously reported
synthetic strategy.8,9 To optimize the conditions for the palladium-
catalyzed Suzuki cross-coupling reaction, we selected the reaction
between aryl iodide (1) and phenylboronic acids (2a) as a model.
We initially studied the reaction with the optimal conditions pre-
viously established for the synthesis of functionalized 6-
arylsalicylates.8 As shown in Table 1, the reaction was carried out
at 110 ꢀC, with 1% of Pd(PPh3)4, 2 equiv of NaHCO3, in a solution of
Table 2
Table 1
The reaction with aryl iodide (1) and various arylboronic acids or alkenyl boronic
Optimization of the reaction conditionsa
acidsa
No Temp (ꢀC) Solvent (v/v)
Pd(PPh3)4 TBABb
Time (min) Yieldc
1
2
3
4
5
6
7
8
MW:110d DME/H2O¼5:1
MW:110 DME/H2O¼5:1
MW:110 DME/H2O¼5:1
MW:120 DME/H2O¼5:1
MW:120 DMF/H2O¼5:1
MW:120 THF/H2O¼1:1
1 mol %
2 mol %
5 mol %
2 mol %
2 mol %
2 mol %
0
0
0
0
0
0
0
0
0
17
6
6
3
4
4
6
6
6
6
6
26%
70%
62%
84%
35%
84%
37%
89%
0%
90%
91%
54%
75%
MW:120 1,4-Dioxane/H2O¼5:1 2 mol %
MW:120 Toluene/H2O¼5:1
2 mol %
2 mol %
2 mol % 0.3 equiv
2 mol % 0.5 equiv
2 mol % 0.5 equiv 13
2 mol % 0.5 equiv 480
9e MW:120 Toluene/H2O¼5:1
10 MW:120 Toluene/H2O¼5:1
11 MW:120 Toluene/H2O¼5:1
12e MW:120 Toluene/H2O¼5:1
13 120f
Toluene/H2O¼5:1
a
Unless otherwise noted, all the reactions were carried out at 0.5 mmol scale in
a solution of toluene (3 mL) and H2O (0.6 mL) with 2 mol % of Pd(PPh3)4, 2 equiv of
NaHCO3, 0.5 equiv TBAB, protected by N2.
b
TBAB¼tetrabutyl ammonium bromide.
c
Isolated yields.
d
Microwave irradiation.
The reaction between aryl iodide (1) and furan-2-ylboronic acid (2s).
Conventional heating method.
e
f

2748
Y.-C. Liu et al. / Tetrahedron 70 (2014) 2746e2752
Very promisingly, polysubstituted phenylboronic acids, furan-2-
7.26 ppm, DMSO: 2.50 ppm). Data are reported as follows: chemical
shift, multiplicity (s¼singlet, d¼doublet, t¼triplet, m¼multiplet,
q¼quaternary), coupling constants (Hertz) and integration. 13C
NMR spectra were recorded on 400/600 (100/150 MHz) spectro-
photometers (CDCl3: 77.0 ppm, DMSO: 39.5 ppm) with complete
proton decoupling. Mass spectra were measured on a Trace MS
spectrometer. Elemental analysis was determined on an elemen-
tary analysis instrument. Microwave irradiation reactions were
carried out with a Smith synthesizerÔ instrument.
ylboronic acid, and naphthalen-1-ylboronic acid also reacted with
aryl iodide (1) very well and gave moderate to excellent yields of
products (Table 2, 3mes).
In addition, we also extended the substrates to alkyl and alkenyl
boronic acids. Not surprisingly, the process showed good functional
group compatibility for the alkenyl reagents (Table 2, 3t). However,
alkyl reagents did not react with 5-iodo-2,2-dimethyl-4H-benzo[d]
[1,3]oxathiin-4-one (1) under the investigated conditions.
Finally, we removed the protecting groups of functionalized 6-
substituted-thiosalicylates (3) successfully to obtain the target
compounds 6-substituted-thiosalicylates (4). For almost all the
substrates 3 with different substituents, deprotection proceeded
very smoothly and afforded moderate to excellent yields of prod-
ucts (Table 3).
4.2. General procedure for the synthesis of compound 1
Table 3
The synthesis of functionalized 6-substituted-thiosalicylates (4) from functionalized
6-substituted-thiosalicylates (3)a
To a stirred solution of thiosalicylic acid (5.00 g, 32.5 mmol) in
TFA (25 mL) was added a solution of acetone (17 mL, 232 mmol) in
TFAA (18 mL) at 0 ꢀC and then stirred for 2 d at 5 ꢀC. After this time,
the mixture was concentrated, and the residue was redissolved
with EtOAc (30 mL) and washed with saturated aqueous NaHCO3.
The organic layer was dried over Na2SO4 and concentrated. Purifi-
cation of the residue by flash column chromatography (petroleum
ether/EtOAc¼5/1) gave 10 (2.33 g, 12.0 mmol) in 37% yield.
To a stirred solution of freshly prepared (TMP)2Mg$LiCl (0.42 M
in THF, 60 mL, 25.3 mmol) was added to a solution of 10 (1.60 g,
8.25 mmol) in THF at ꢁ20 ꢀC. After being stirred for 1 h at ꢁ20 ꢀC,
a solution of I2 (10.5 g, 41.3 mmol) in THF (42 mL) was added at 0 ꢀC.
The mixture was stirred for additional 4 h at room temperature. The
mixture was quenched with saturated aqueous NH4Cl, and
extracted with EtOAc. The organic layer was washed with saturated
aqueous Na2S2O3 and brine, dried over Na2SO4, and concentrated.
Purification of the residue by flash column chromatography (pe-
troleum ether/EtOAc¼10/1) gave 1 (1.06 g, 3.30 mmol) in 40% yield
as a yellow oil.
4.2.1. 2,2-Dimethyl-4H-benzo[d][1,3]oxathiin-4-one
solid, 2.33 g, 37% yield; mp: 85e86 ꢀC. 1H NMR (600 MHz, DMSO)
(10). Yellow
d
8.08 (dd, J¼7.8, 0.9 Hz, 1H), 7.64 (td, J¼7.8, 1.2 Hz, 1H), 7.48
(d, J¼7.8 Hz, 1H), 7.41 (t, J¼7.8 Hz, 1H), 1.79 (s, 6H). 13C NMR
(100 MHz, CDCl3)
d 163.24, 136.70, 133.73, 131.87, 127.71, 126.12,
123.26, 85.95, 28.91. EI-MS: m/z¼194.17 (Mþ). Anal. Calcd for
(C10H10O2S): C, 61.83; H, 5.19; S, 16.51. Found: C, 61.79; H, 5.20; S,
16.62.
3. Conclusion
In summary, we have developed a direct and efficient method
for the synthesis of functionalized 6-substituted-thiosalicylates (4)
from aryl iodide (1) by using an improved microwave-assisted
Suzuki cross-coupling reaction. Moreover, this protocol is notably
superior to the traditionally available methods and could be de-
veloped as a general method to synthesize pyrimidinyl(thio)
salicylic acid and its derivatives.
4.2.2. 5-Iodo-2,2-dimethyl-4H-benzo[d][1,3]oxathiin-4-one
(1). Yellow oil, 1.06 g, 40% yield. 1H NMR (600 MHz, CDCl3)
d
7.95
(d, J¼7.8 Hz, 1H), 7.30 (d, J¼7.8 Hz, 1H), 7.05 (t, J¼7.8 Hz, 1H), 1.81
(s, 6H). 13C NMR (100 MHz, CDCl3)
d 161.33, 140.70, 138.33, 133.03,
128.45, 126.39, 97.70, 85.51, 28.54. EI-MS: m/z¼320.05 (Mþ). Anal.
Calcd for (C10H9IO2S): C, 37.52; H, 2.83; S, 10.02. Found: C, 37.43; H,
2.78; S, 10.14.
4. Experimental section
4.1. General information
4.3. General procedure for the synthesis of compounds 3aet
Aryl iodide 1 (160 mg, 0.5 mmol) and 2a (61 mg, 0.5 mmol) were
dissolved in toluene (3 mL) and H2O (0.6 mL) in a microwave vial
under a nitrogen atmosphere. Pd(PPh3)4 (0.01 mmol, 11.56 mg),
sodium bicarbonate (84 mg, 1 mmol), and tetrabutyl ammonium
bromide (80.5 mg, 0.25 mmol) were added, and then the reaction
mixture was irradiated in a microwave apparatus at 120 ꢀC for
6e13 min. After the reaction mixture was cooled to ambient tem-
perature, the reaction mixture was concentrated, and the crude
residue was purified by silica gel column chromatography using
Unless otherwise noted, materials were purchased from com-
mercial suppliers and used without further purification. All the
solvents were treated according to general methods. Flash column
chromatography (FC) was performed using 200e300 mesh silica
gel.
1H NMR spectra were recorded on 400/600 (400/600 MHz)
spectrophotometers. Chemical shifts (d) are reported in parts per
million from the solvent resonance as the internal standard (CDCl3:

Y.-C. Liu et al. / Tetrahedron 70 (2014) 2746e2752
2749
petroleum ether/acetone (20/1 to 10/1) as eluent to give the title
compound 3a (123 mg) in 91% yield.
MS: m/z¼284.23 (Mþ). Anal. Calcd for (C17H16O2S): C, 71.80; H, 5.67;
S, 11.28. Found: C, 71.91; H, 5.69; S, 11.36.
4.3.1. 2,2-Dimethyl-5-phenyl-4H-benzo[d][1,3]oxathiin-4-one
4.3.8. 5-(4-Methoxyphenyl)-2,2-dimethyl-4H-benzo[d][1,3]oxathiin-
(3a). Yellow solid, 123 mg, 91% yield; mp: 109e110 ꢀC. 1H NMR
4-one (3h). White solid, 118 mg, 79% yield; mp: 166e167 ꢀC. 1H
(600 MHz, CDCl3)
(d, J¼7.2 Hz, 1H), 7.29 (d, J¼7.2 Hz, 3H), 7.23 (d, J¼7.8 Hz, 1H), 1.92
(s, 6H). 13C NMR (100 MHz, CDCl3)
162.25, 146.57, 141.08, 137.93,
d
7.46 (t, J¼7.8 Hz, 1H), 7.41 (t, J¼7.2 Hz, 2H), 7.37
NMR (600 MHz, CDCl3)
d
7.43 (t, J¼7.8 Hz, 1H), 7.24e7.19 (m, 4H),
6.94 (d, J¼7.8 Hz, 2H), 3.84 (s, 3H), 1.91 (s, 6H). 13C NMR (100 MHz,
d
CDCl3) d 162.42, 159.03, 146.08, 137.81, 133.29, 132.03, 129.57,
132.11, 129.71, 128.20, 128.09, 127.39, 126.97, 123.55, 85.78, 28.59.
EI-MS: m/z¼270.22 (Mþ). Anal. Calcd for (C16H14O2S): C, 71.08; H,
5.22; S, 11.86. Found: C, 71.23; H, 5.27; S, 11.89.
129.23, 126.48, 123.36, 113.70, 85.69, 55.10, 28.50. EI-MS: m/
z¼300.25 (Mþ). Anal. Calcd for (C17H16O3S): C, 67.98; H, 5.37; S,
10.68. Found: C, 67.92; H, 5.32; S, 10.74.
4.3.2. 5-(4-Chlorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]oxathiin-4-
4.3.9. 5-(4-(tert-Butyl)phenyl)-2,2-dimethyl-4H-benzo[d][1,3]ox-
one (3b). Yellow solid, 133 mg, 88% yield; mp: 134e135 ꢀC. 1H
athiin-4-one (3i). White solid, 152 mg, 93% yield; mp: 153e154 ꢀC.
NMR (600 MHz, CDCl3)
2H), 7.31 (d, J¼8.4 Hz, 1H), 7.21 (d, J¼7.8 Hz, 2H), 7.18 (d, J¼7.2 Hz,
1H), 1.91 (s, 6H). 13C NMR (100 MHz, CDCl3)
162.17, 145.40,
d
7.46 (t, J¼7.8 Hz, 1H), 7.37 (d, J¼7.8 Hz Hz,
1H NMR (600 MHz, CDCl3)
d
7.43 (m, 3H), 7.24 (m, 4H), 1.91 (s, 6H),
1.35 (s, 9H). 13C NMR (100 MHz, CDCl3)
d
162.33, 150.08, 146.42,
d
137.97, 137.74, 132.00, 129.64, 127.72, 126.61, 125.11, 123.46, 85.67,
34.39, 31.22, 28.49. EI-MS: m/z¼326.28 (Mþ). Anal. Calcd for
(C20H22O2S): C, 73.58; H, 6.79; S, 9.82. Found: C, 73.52; H, 6.85; S,
9.77.
139.63, 138.28, 133.54, 132.29, 129.58, 129.43, 128.45, 127.37,
123.36, 85.85, 28.62. EI-MS: m/z¼304.26 (Mþ). Anal. Calcd for
(C16H13ClO2S): C, 63.05; H, 4.30; S, 10.52. Found: C, 63.25; H, 4.24;
S, 10.70.
4.3.10. 2,2-Dimethyl-5-(4-(trifluoromethyl)phenyl)-4H-benzo[d][1,3]
oxathiin-4-one (3j). White solid, 137 mg, 81% yield; mp:
4.3.3. 5-(3-Chlorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]oxathiin-4-
one (3c). White solid, 127 mg, 84% yield; mp: 149e150 ꢀC. 1H NMR
160e161 ꢀC. 1H NMR (600 MHz, CDCl3)
d
7.65 (d, J¼7.8 Hz, 2H), 7.49
(600 MHz, CDCl3)
d
7.46 (t, J¼7.8 Hz, 1H), 7.35e7.29 (m, 3H), 7.27
(t, J¼7.8 Hz, 1H), 7.38 (d, J¼7.8 Hz, 2H), 7.34 (d, J¼7.8 Hz, 1H), 7.19
(s, 1H), 7.18 (d, J¼7.8 Hz, 1H), 7.14 (d, J¼6.6 Hz, 1H), 1.91 (s, 6H). 13
C
(d, J¼7.8 Hz, 1H), 1.92 (s, 6H). 13C NMR (100 MHz, CDCl3)
d 162.01,
NMR (100 MHz, CDCl3)
d
161.95, 145.06, 142.91, 138.21, 133.90,
145.12, 144.93, 138.40, 133.81, 132.38, 129.49, 129.09, 128.42, 127.73,
125.48, 125.09, 123.23, 122.78, 85.87, 28.51. EI-MS: m/z¼338.28
(Mþ). Anal. Calcd for (C17H13F3O2S): C, 60.35; H, 3.87; S, 9.48.
Found: C, 60.40; H, 3.82; S, 9.53.
132.28, 129.56, 129.32, 128.00, 127.50, 127.41, 126.49, 123.26, 85.82,
28.55. EI-MS: m/z¼304.18 (Mþ). Anal. Calcd for (C16H13ClO2S): C,
63.05; H, 4.30; S, 10.52. Found: C, 63.25; H, 4.39; S, 10.49.
4.3.4. 5-(2-Chlorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]oxathiin-4-
4.3.11. 2,2-Dimethyl-5-(4-nitrophenyl)-4H-benzo[d][1,3]oxathiin-4-
one (3d). White solid, 109 mg, 72% yield; mp: 154e155 ꢀC. 1H NMR
one (3k). Yellow solid, 131 mg, 83% yield; mp: 141e142 ꢀC. 1H NMR
(400 MHz, CDCl3)
(t, J¼7.2 Hz, 2H), 7.30 (dd, J¼11.6, 4.4 Hz, 2H), 7.12 (d, J¼7.6 Hz, 1H),
1.89 (s, 3H), 1.86 (s, 3H). 13C NMR (100 MHz, CDCl3)
161.63, 143.31,
d
7.49 (t, J¼7.6 Hz, 1H), 7.39 (d, J¼7.6 Hz, 1H), 7.35
(400 MHz, CDCl3)
d
8.35e8.17 (m, 2H), 7.51 (d, J¼7.6 Hz, 1H),
7.46e7.33 (m, 3H), 7.19 (d, J¼7.6 Hz, 1H), 1.93 (s, 6H). 13C NMR
d
(100 MHz, CDCl3) d 161.88, 148.10, 146.92, 144.26, 138.73, 132.55,
140.14, 137.29, 132.40, 131.34, 130.00, 129.77, 128.98, 128.64, 127.89,
126.86, 124.00, 85.67, 29.11, 28.36. EI-MS: m/z¼304.23 (Mþ). Anal.
Calcd for (C16H13ClO2S): C, 63.05; H, 4.30; S, 10.52. Found: C, 63.22;
H, 4.34; S, 10.32.
129.21, 128.98, 128.22, 123.37, 122.94, 85.94, 28.53. EI-MS: m/
z¼315.19 (Mþ). Anal. Calcd for (C16H13NO4S): C, 60.94; H, 4.16; N,
4.44; S, 10.17. Found: C, 60.81; H, 4.12; N, 4.49; S, 10.26.
4.3.12. 5-(4-Acetylphenyl)-2,2-dimethyl-4H-benzo[d][1,3]oxathiin-4-
4.3.5. 5-(4-Bromophenyl)-2,2-dimethyl-4H-benzo[d][1,3]oxathiin-4-
one (3l). White solid, 97 mg, 62% yield; mp: 149e150 ꢀC. 1H NMR
one (3e). White solid, 136 mg, 78% yield; mp: 150e151 ꢀC. 1H NMR
(600 MHz, CDCl3)
(d, J¼7.8 Hz, 2H), 7.34 (d, J¼7.8 Hz, 1H), 7.21 (d, J¼7.8 Hz, 1H), 2.63
(s, 3H), 1.92 (s, 6H). 13C NMR (100 MHz, CDCl3)
197.51, 162.03,
d
8.00 (d, J¼7.8 Hz, 2H), 7.48 (d, J¼7.8 Hz,1H), 7.38
(600 MHz, CDCl3)
d
7.53 (d, J¼6.6 Hz, 2H), 7.46 (s, 1H), 7.31
(d, J¼7.8 Hz, 1H), 7.20e7.12 (m, 3H), 1.91 (s, 6H). 13C NMR (100 MHz,
d
CDCl3)
d
162.09, 145.31, 140.07, 138.23, 132.28, 131.29, 129.71,
146.08, 145.44,138.36, 135.83, 132.35,129.39, 128.34, 128.27, 127.65,
123.26, 85.87, 28.58, 26.56. EI-MS: m/z¼312.22 (Mþ). Anal. Calcd for
(C18H16O3S): C, 69.21; H, 5.16; S, 10.26. Found: C, 69.33; H, 5.06; S,
10.11.
129.46, 127.35, 123.21, 121.66, 85.79, 28.56. EI-MS: m/z¼348.21
(Mþ). Anal. Calcd for (C16H13BrO2S): C, 55.03; H, 3.75; S, 9.18. Found:
C, 55.20; H, 3.74; S, 9.21.
4.3.6. 5-(4-Fluorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]oxathiin-4-
4.3.13. 5-(4-Fluoro-3-methylphenyl)-2,2-dimethyl-4H-benzo[d][1,3]
one (3f). White solid, 124 mg, 86% yield; mp: 158e159 ꢀC. 1H NMR
oxathiin-4-one (3m). White solid, 136 mg, 90% yield; mp:
(600 MHz, CDCl3)
(d, J¼4.2 Hz, 2H), 7.19 (d, J¼7.8 Hz, 1H), 7.09 (t, J¼7.8 Hz, 2H), 1.91
(s, 6H). 13C NMR (100 MHz, CDCl3)
163.48, 162.20, 161.03, 145.48,
d
7.46 (t, J¼7.8 Hz, 1H), 7.29 (d, J¼7.8 Hz, 1H), 7.24
133e134 ꢀC. 1H NMR (600 MHz, CDCl3)
d
7.44 (t, J¼7.8 Hz, 1H), 7.28
(d, J¼7.8 Hz, 1H), 7.18 (d, J¼7.8 Hz, 1H), 7.10 (d, J¼7.2 Hz, 1H),
d
7.07e6.95 (m, 2H), 2.31 (s, 3H), 1.91 (s, 6H). 13C NMR (100 MHz,
138.10, 137.09, 132.20, 129.74, 129.66, 127.15, 123.41, 115.28, 115.06,
85.78, 28.55. EI-MS: m/z¼288.23 (Mþ). Anal. Calcd for
(C16H13FO2S): C, 66.65; H, 4.54; S, 11.12. Found: C, 66.84; H, 4.39; S,
11.22.
CDCl3) d 162.28, 162.14, 159.70, 145.76, 138.02, 136.80, 132.13,
131.06, 131.01, 129.72, 127.19, 127.11, 127.02, 124.73, 124.55, 123.46,
114.92, 114.70, 85.80, 28.59, 14.68, 14.64. EI-MS: m/z¼302.19 (Mþ).
Anal. Calcd for (C17H15FO2S): C, 67.53; H, 5.00; S, 10.60. Found: C,
67.61; H, 5.09; S, 10.59.
4.3.7. 2,2-Dimethyl-5-(p-tolyl)-4H-benzo[d][1,3]oxathiin-4-one
(3g). White solid, 125 mg, 88% yield; mp: 116e117 ꢀC. 1H NMR
4.3.14. 5-(3,5-Difluorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]ox-
athiin-4-one (3n). Yellow solid,138 mg, 90% yield; mp: 139e140 ꢀC.
(600 MHz, CDCl3)
d
7.44 (t, J¼7.8 Hz, 1H), 7.26 (s, 1H), 7.22
(d, J¼9.6 Hz, 3H), 7.18 (d, J¼7.2 Hz, 2H), 2.39 (s, 3H), 1.91 (s, 6H). 13
C
1H NMR (600 MHz, CDCl3)
d
7.48 (t, J¼7.8 Hz, 1H), 7.34 (d, J¼7.8 Hz,
1H), 7.17 (d, J¼7.8 Hz, 1H), 6.84e6.80 (m, 1H), 6.78 (d, J¼6.0 Hz, 2H),
1.91 (s, 6H). 13C NMR (100 MHz, CDCl3)
163.84, 163.72, 161.74,
NMR (100 MHz, CDCl3)
d 162.34, 146.52, 138.13, 137.83, 137.12,
132.07, 129.65, 128.98, 127.96, 126.71, 123.53, 85.73, 28.56, 21.17. EI-
d

2750
Y.-C. Liu et al. / Tetrahedron 70 (2014) 2746e2752
161.38, 144.26, 138.50, 132.40, 129.25, 127.91, 123.21, 111.43, 111.36,
111.18, 103.00, 102.75, 102.50, 85.91, 28.54. EI-MS: m/z¼306.18
(Mþ). Anal. Calcd for (C16H12F2O2S): C, 62.73; H, 3.95; S, 10.47.
Found: C, 62.68; H, 3.90; S, 10.41.
resulting mixture was stirred at 50 ꢀC for 1e10 h and then allowed
to cool to room temperature. The solvent was evaporated in vacuo.
The mixture was quenched with saturated aqueous NH4Cl and 1 N
aqueous HCl, and extracted with ethyl acetate. The organic layer
was dried over Na2SO4 and concentrated. Purification of the residue
by flash column chromatography (hexane/acetone¼5/1) gave 4a
(114 mg, 0.47 mmol) in 47% yield.
4.3.15. 5-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]
oxathiin-4-one (3o). White solid, 129 mg, 80% yield; mp:
147e148 ꢀC. 1H NMR (600 MHz, CDCl3)
d
7.46 (t, J¼7.8 Hz, 1H), 7.31
(t, J¼7.2 Hz, 2H), 7.16 (t, J¼7.8 Hz, 2H), 7.11 (s, 1H), 1.91 (s, 6H). 13
C
4.4.1. Methyl 3-mercapto-[1,10-biphenyl]-2-carboxylate (4a). Yellow
NMR (100 MHz, CDCl3)
d
161.97, 158.72, 156.24, 144.18, 138.38,
oil, 115 mg, 47% yield. 1H NMR (400 MHz, CDCl3)
d
7.45e7.29
(m, 6H), 7.27 (d, J¼13.6 Hz, 1H), 7.19 (d, J¼7.2 Hz, 1H), 3.94 (s, 1H),
3.57 (s, 3H). 13C NMR (100 MHz, CDCl3)
169.08, 141.81, 140.40,
138.28, 132.36, 130.02, 129.56, 128.09, 128.02, 127.66, 123.15, 120.71,
116.36, 116.15, 85.84, 28.54. EI-MS: m/z¼322.21 (Mþ). Anal. Calcd
for (C16H12ClFO2S): C, 59.54; H, 3.75; S, 9.93. Found: C, 59.67; H,
3.70; S, 10.02.
d
132.45, 130.30, 129.87, 129.75, 128.29, 127.95, 127.58, 127.45, 52.09.
EI-MS: m/z¼244.16 (Mþ). Anal. Calcd for (C14H12O2S): C, 68.83; H,
4.95; S, 13.12. Found: C, 68.79; H, 4.89; S, 13.26.
4.3.16. 5-(3,5-Dichlorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]ox-
athiin-4-one (3p). Yellow solid, 144 mg, 85% yield; mp: 160e161 ꢀC.
4.4.2. Methyl 40-chloro-3-mercapto-[1,10-biphenyl]-2-carboxylate
1H NMR (600 MHz, CDCl3)
d
7.47 (t, J¼7.8 Hz, 1H), 7.34 (dd, J¼7.8,
5.4 Hz, 2H), 7.15 (d, J¼7.8 Hz, 1H), 7.13 (d, J¼1.8 Hz, 2H), 1.91 (s, 6H).
13C NMR (100 MHz, CDCl3)
161.65, 144.11, 143.71, 138.47, 134.40,
(4b). Yellow oil, 225 mg, 81% yield. 1H NMR (600 MHz, CDCl3)
d
7.37 (dd, J¼7.8, 3.6 Hz, 3H), 7.32 (t, J¼7.8 Hz, 1H), 7.26 (d, J¼2.4 Hz,
d
2H), 7.15 (d, J¼7.8 Hz, 1H), 3.94 (s, 1H), 3.62 (s, 3H). 13C NMR
132.40, 129.36, 127.97, 127.28, 126.56, 122.91, 85.83, 28.50. EI-MS:
m/z¼338.16 (Mþ). Anal. Calcd for (C16H12Cl2O2S): C, 56.65; H,
3.57; S, 9.45. Found: C, 56.67; H, 3.61; S, 9.52.
(100 MHz, CDCl3) d 168.80, 140.51, 138.84, 133.74, 132.25, 130.67,
130.07, 129.97, 129.29, 128.49, 127.29, 52.22. EI-MS: m/z¼278.13
(Mþ). Anal. Calcd for (C14H11ClO2S): C, 60.32; H, 3.98; S, 11.50.
Found: C, 60.41; H, 3.97; S, 11.46.
4.3.17. 2,2-Dimethyl-5-(3,4,5-trimethoxyphenyl)-4H-benzo[d][1,3]
oxathiin-4-one (3q). Yellow solid, 117 mg, 65% yield; mp:
4.4.3. Methyl 30-chloro-3-mercapto-[1,10-biphenyl]-2-carboxylate
130e131 ꢀC. 1H NMR (400 MHz, CDCl3)
d
7.44 (t, J¼7.6 Hz, 1H), 7.26
(dd, J¼14.4, 8.4 Hz, 2H), 6.48 (s, 2H), 3.89 (s, 3H), 3.86 (s, 6H), 1.91
(s, 6H). 13C NMR (100 MHz, CDCl3)
162.15, 152.90, 146.43, 137.95,
(4c). Yellow oil, 239 mg, 86% yield. 1H NMR (400 MHz, CDCl3)
d
7.38 (d, J¼8.0 Hz, 1H), 7.36e7.28 (m, 4H), 7.24e7.18 (m, 1H), 7.17
d
(d, J¼7.6 Hz, 1H), 3.95 (s, 1H), 3.62 (s, 3H). 13C NMR (100 MHz,
137.56, 136.75, 132.04, 129.55, 126.97, 123.55, 105.53, 85.74, 60.82,
55.96, 28.52. EI-MS: m/z¼360.26 (Mþ). Anal. Calcd for (C19H20O5S):
C, 63.32; H, 5.59; S, 8.90. Found: C, 63.34; H, 5.61; S, 8.88.
CDCl3) d 168.60,142.10,140.26,134.11,132.10,130.80,130.20,129.95,
129.46, 128.02, 127.64, 127.19, 126.14, 52.12. EI-MS: m/z¼278.16
(Mþ). Anal. Calcd for (C14H11ClO2S): C, 60.32; H, 3.98; S, 11.50.
Found: C, 60.33; H, 4.07; S, 11.57.
4.3.18. 2,2-Dimethyl-5-(naphthalen-2-yl)-4H-benzo[d][1,3]oxathiin-
4-one (3r). Yellow solid, 144 mg, 90% yield; mp: 165e166 ꢀC. 1H
4.4.4. Methyl 20-chloro-3-mercapto-[1,10-biphenyl]-2-carboxylate
NMR (400 MHz, CDCl3)
7.49 (dd, J¼8.8, 6.4 Hz, 3H), 7.32 (dt, J¼13.2, 10.0 Hz, 3H), 1.95
(s, 6H). 13C NMR (100 MHz, CDCl3)
162.25, 146.49, 138.74, 138.02,
d
7.85 (dd, J¼10.0, 6.0 Hz, 3H), 7.80 (s, 1H),
(4d). Yellow oil, 245 mg, 88% yield. 1H NMR (600 MHz, CDCl3)
d
7.46e7.42 (m, 1H), 7.40 (d, J¼7.8 Hz, 1H), 7.33 (t, J¼7.8 Hz, 1H), 7.28
(dd, J¼7.2, 3.0 Hz, 2H), 7.22e7.19 (m, 1H), 7.12 (d, J¼7.8 Hz, 1H), 4.05
(s, 1H), 3.52 (s, 3H). 13C NMR (100 MHz, CDCl3)
167.88, 139.83,
d
133.28, 132.50, 132.23, 130.06, 128.08, 127.61, 127.50, 127.04, 126.86,
126.44, 126.06, 125.97, 123.45, 85.76, 28.58. EI-MS: m/z¼320.29
(Mþ). Anal. Calcd for (C20H16O2S): C, 74.97; H, 5.03; S, 10.01. Found:
C, 74.94; H, 5.11; S, 10.14.
d
139.33, 132.58, 132.09, 131.44, 130.37, 129.84, 129.22, 128.83, 127.98,
126.30, 119.27, 51.90. EI-MS: m/z¼278.14 (Mþ). Anal. Calcd for
(C14H11ClO2S): C, 60.32; H, 3.98; S, 11.50. Found: C, 60.36; H, 4.07; S,
11.64.
4.3.19. 5-(Furan-2-yl)-2,2-dimethyl-4H-benzo[d][1,3]oxathiin-4-one
(3s). White solid, 70 mg, 54% yield; mp: 69e70 ꢀC. 1H NMR
4.4.5. Methyl 40-bromo-3-mercapto-[1,10-biphenyl]-2-carboxylate
(600 MHz, CDCl3)
d
7.50 (s, 1H), 7.43 (dd, J¼15.0, 7.8 Hz, 2H), 7.26
(4e). Yellow oil, 268 mg, 83% yield. 1H NMR (600 MHz, CDCl3)
(d, J¼1.8 Hz, 1H), 6.64 (s, 1H), 6.50 (d, J¼1.8 Hz, 1H), 1.90 (s, 6H). 13
C
d
7.52 (d, J¼8.4 Hz, 2H), 7.37 (d, J¼7.8 Hz, 1H), 7.31 (t, J¼7.8 Hz, 1H),
7.20 (d, J¼8.4 Hz, 2H), 7.15 (d, J¼7.8 Hz, 1H), 3.94 (s, 1H), 3.62 (s, 3H).
13C NMR (100 MHz, CDCl3)
168.79, 140.54, 139.33, 132.19, 131.46,
NMR (150 MHz, CDCl3)
d 162.09, 152.43, 143.07, 138.09, 134.04,
132.25, 127.78, 127.20, 122.54, 111.46, 108.58, 86.02, 28.38. EI-MS:
m/z¼260.19 (Mþ). Anal. Calcd for (C14H12O3S): C, 64.60; H, 4.65; S,
12.32. Found: C, 64.76; H, 4.70; S, 12.34.
d
130.74, 130.11, 130.00, 129.62, 127.25, 121.96, 52.25. EI-MS: m/
z¼324.24 (Mþ). Anal. Calcd for (C14H11BrO2S): C, 52.03; H, 3.43; S,
9.92. Found: C, 52.07; H, 3.51; S, 9.76.
4.3.20. (E)-2,2-Dimethyl-5-styryl-4H-benzo[d][1,3]oxathiin-4-one
(3t). Yellow solid, 128 mg, 87% yield; mp: 106e107 ꢀC. 1H NMR
4.4.6. Methyl 40-fluoro-3-mercapto-[1,10-biphenyl]-2-carboxylate
(4f). Yellow oil, 234 mg, 92% yield. 1H NMR (600 MHz, CDCl3)
(400 MHz, CDCl3)
d
7.94 (d, J¼16.4 Hz, 1H), 7.58 (dd, J¼15.2, 7.6 Hz,
3H), 7.43 (t, J¼7.6 Hz, 1H), 7.36 (t, J¼7.6 Hz, 2H), 7.29 (d, J¼7.2 Hz,
d
7.37 (d, J¼7.8 Hz, 1H), 7.31 (ddd, J¼8.4, 7.8, 4.8 Hz, 3H), 7.16
1H), 7.22 (d, J¼7.6 Hz, 1H), 7.04 (d, J¼16.4 Hz, 1H), 1.83 (s, 6H). 13
C
(d, J¼7.8 Hz, 1H), 7.09 (t, J¼9.0 Hz, 2H), 3.92 (s, 1H), 3.61 (s, 3H). 13
C
NMR (100 MHz, CDCl3)
d
162.48, 142.42, 137.45, 136.93, 132.49,
NMR (100 MHz, CDCl3) d 168.91, 163.59, 161.14, 140.67, 136.38,
131.84, 128.49, 127.90, 127.60, 127.13, 126.90, 125.64, 121.97, 85.44,
28.58. EI-MS: m/z¼296.21 (Mþ). Anal. Calcd for (C18H16O2S): C,
72.94; H, 5.44; S, 10.82. Found: C, 72.85; H, 5.37; S, 10.90.
132.50, 130.42, 129.90, 129.70, 129.62, 127.40, 115.36, 115.15, 52.15.
EI-MS: m/z¼262.18 (Mþ). Anal. Calcd for (C14H11FO2S): C, 64.11; H,
4.23; S, 12.22. Found: C, 64.23; H, 4.20; S, 12.11.
4.4. General procedure for the synthesis of compounds 4aet
4.4.7. Methyl 3-mercapto-40-methyl-[1,10-biphenyl]-2-carboxylate
(4g). Yellow oil, 230 mg, 89% yield. 1H NMR (600 MHz, CDCl3)
To a stirred solution of 3a (270 mg, 1 mmol) in MeOH (10 mL)
was added NaOH (120 mg, 3.0 mmol) at room temperature. The
d
7.34 (d, J¼7.8 Hz, 1H), 7.32e7.26 (m, 1H), 7.23 (d, J¼8.4 Hz, 2H),
7.19 (dd, J¼7.8, 4.8 Hz, 3H), 3.91 (s, 1H), 3.61 (s, 3H), 2.38 (s, 3H). 13
C

Y.-C. Liu et al. / Tetrahedron 70 (2014) 2746e2752
2751
NMR (100 MHz, CDCl3)
d
169.12, 141.60, 137.35, 137.27, 132.47,
(d, J¼7.8 Hz, 1H), 6.87 (d, J¼6.0 Hz, 2H), 6.81 (t, J¼9.0 Hz, 1H), 3.96
(s, 1H), 3.67 (s, 3H). 13C NMR (100 MHz, CDCl3)
168.23, 163.85,
163.72, 161.37, 161.24, 143.55, 143.46, 139.33, 131.85, 131.12, 130.54,
129.98, 126.89, 111.15, 111.08, 110.97, 110.90, 103.12, 102.87, 102.62,
52.10. EI-MS: m/z¼280.16 (Mþ). Anal. Calcd for (C14H10F2O2S): C,
59.99; H, 3.60; S, 11.44. Found: C, 60.05; H, 3.55; S, 11.34.
129.98, 129.76, 129.50, 128.98, 127.76, 127.41, 52.03, 21.04. EI-MS:
m/z¼258.23 (Mþ). Anal. Calcd for (C15H14O2S): C, 69.74; H, 5.46;
S, 12.41. Found: C, 69.72; H, 5.32; S, 12.58.
d
4.4.8. Methyl 3-mercapto-40-methoxy-[1,10-biphenyl]-2-carboxylate
(4h). Yellow oil, 238 mg, 87% yield. 1H NMR (600 MHz, CDCl3)
d
7.33 (d, J¼7.8 Hz, 1H), 7.30 (d, J¼7.8 Hz, 1H), 7.26 (s, 2H), 7.18
(d, J¼7.8 Hz, 1H), 6.92 (d, J¼8.4 Hz, 2H), 3.89 (s, 1H), 3.84 (s, 3H),
3.63 (s, 3H). 13C NMR (100 MHz, CDCl3)
169.21, 159.11, 141.21,
4.4.15. Methyl 30-chloro-40-fluoro-3-mercapto-[1,10-biphenyl]-2-
carboxylate (4o). Yellow oil, 276 mg, 93% yield. 1H NMR
d
(600 MHz, CDCl3)
6.0 Hz, 1H), 7.21e7.07 (m, 3H), 3.94 (s, 1H), 3.64 (s, 3H). 13C NMR
(100 MHz, CDCl3) 168.46, 158.77, 156.29, 139.28, 137.43, 132.13,
d
7.37 (dd, J¼7.2, 5.4 Hz, 2H), 7.28 (dd, J¼13.8,
132.64, 132.51, 129.89, 129.75, 129.33, 129.06, 127.38, 113.72, 55.11,
52.09. EI-MS: m/z¼274.19 (Mþ). Anal. Calcd for (C15H14O3S): C,
65.67; H, 5.14; S, 11.69. Found: C, 65.79; H, 5.21; S, 11.53.
d
130.86, 130.27, 130.09, 129.95, 127.79, 127.72, 127.16, 120.88, 120.70,
116.43, 116.22, 52.15. EI-MS: m/z¼296.14 (Mþ). Anal. Calcd for
(C14H10ClFO2S): C, 56.66; H, 3.40; S, 10.81. Found: C, 56.77; H, 3.45;
S, 10.76.
4.4.9. Methyl 40-(tert-butyl)-3-mercapto-[1,10-biphenyl]-2-
carboxylate (4i). Yellow oil, 273 mg, 91% yield. 1H NMR (600 MHz,
CDCl3)
(t, J¼7.8 Hz, 1H), 7.28e7.25 (m, 2H), 7.20 (d, J¼7.8 Hz, 1H), 3.91
(s, 1H), 3.59 (s, 3H), 1.34 (s, 9H). 13C NMR (100 MHz, CDCl3)
169.12,
d
7.41 (d, J¼7.8 Hz, 2H), 7.34 (d, J¼7.8 Hz, 1H), 7.30
4.4.16. Methyl 30,50-dichloro-3-mercapto-[1,10-biphenyl]-2-
d
carboxylate (4p). Yellow oil, 253 mg, 81% yield. 1H NMR
150.41, 141.56, 137.29, 132.46, 129.99, 129.74, 129.45, 127.57, 127.36,
125.13, 51.91, 34.40, 31.19. EI-MS: m/z¼300.27 (Mþ). Anal. Calcd for
(C18H20O2S): C, 71.96; H, 6.71; S, 10.67. Found: C, 71.93; H, 6.64; S,
10.62.
(400 MHz, CDCl3)
(d, J¼7.6 Hz, 1H), 7.23 (d, J¼6.8 Hz, 2H), 7.14 (d, J¼7.6 Hz, 1H), 3.96
(s, 1H), 3.67 (s, 3H). 13C NMR (100 MHz, CDCl3)
168.28, 143.27,
139.07, 134.80, 131.92, 131.39, 130.75, 130.12, 127.65, 127.08, 126.52,
52.26. EI-MS: m/z¼312.11 (Mþ). Anal. Calcd for (C14H10Cl2O2S): C,
53.69; H, 3.22; S, 10.24. Found: C, 53.52; H, 3.24; S, 10.26.
d
7.41 (d, J¼7.6 Hz, 1H), 7.38e7.34 (m, 1H), 7.32
d
4.4.10. Methyl 3-mercapto-40-(trifluoromethyl)-[1,10-biphenyl]-2-
carboxylate (4j). Yellow oil, 265 mg, 85% yield. 1H NMR
(600 MHz, CDCl3)
(d, J¼7.8 Hz, 1H), 7.36 (d, J¼7.8 Hz, 1H), 7.18 (d, J¼7.8 Hz, 1H), 3.98
(s, 1H), 3.59 (s, 3H). 13C NMR (100 MHz, CDCl3)
168.62, 144.14,
d
7.66 (d, J¼7.8 Hz, 2H), 7.45 (d, J¼7.8 Hz, 2H), 7.41
4.4.17. Methyl 3-mercapto-30,40,50-trimethoxy-[1,10-biphenyl]-2-
carboxylate (4q). Yellow oil, 294 mg, 88% yield. 1H NMR
d
(600 MHz, CDCl3)
(d, J¼7.8 Hz, 1H), 6.57 (s, 2H), 3.88 (s, 3H), 3.86 (s, 6H), 3.66 (s, 3H).
13C NMR (100 MHz, CDCl3)
169.18, 152.98, 141.45, 137.43, 135.86,
d
7.36 (d, J¼7.8 Hz, 1H), 7.31 (t, J¼7.8 Hz, 1H), 7.22
140.50, 132.15, 131.20, 130.51, 130.12, 129.61, 128.41, 127.33, 125.28,
122.72, 109.73, 52.21. EI-MS: m/z¼312.18 (Mþ). Anal. Calcd for
(C15H11F3O2S): C, 57.69; H, 3.55; S, 10.27. Found: C, 57.66; H, 3.60; S,
10.38.
d
132.63, 129.99, 129.77, 127.13, 105.16, 60.78, 55.98, 52.29. EI-MS: m/
z¼334.20 (Mþ). Anal. Calcd for (C17H18O5S): C, 61.06; H, 5.43; S,
9.59. Found: C, 60.91; H, 5.54; S, 9.55.
4.4.11. Methyl 3-mercapto-40-nitro-[1,10-biphenyl]-2-carboxylate
(4k). Yellow oil, 260 mg, 90% yield. 1H NMR (600 MHz, CDCl3)
4.4.18. Methyl
2-mercapto-6-(naphthalen-2-yl)benzoate
(4r).
7.86 (dd,
d
8.30e8.23 (m, 2H), 7.52e7.47 (m, 2H), 7.47e7.41 (m, 1H), 7.37
Yellow oil, 253 mg, 86% yield. 1H NMR (600 MHz, CDCl3)
d
(t, J¼7.8 Hz,1H), 7.21e7.16 (m,1H), 4.01 (s,1H), 3.61 (s, 3H). 13C NMR
J¼8.4, 4.2 Hz, 3H), 7.82 (s, 1H), 7.54e7.48 (m, 2H), 7.46 (d, J¼8.4 Hz,
(100 MHz, CDCl3)
d 168.24, 147.17, 139.70, 131.87, 131.62, 130.93,
1H), 7.40 (d, J¼7.8 Hz, 1H), 7.36 (t, J¼7.8 Hz, 1H), 7.30 (d, J¼7.2 Hz,
130.23, 128.91, 127.10, 125.18, 123.50, 52.28. EI-MS: m/z¼289.18
(Mþ). Anal. Calcd for (C14H11NO4S): C, 58.12; H, 3.83; N, 4.84; S,
11.08. Found: C, 58.23; H, 3.85; N, 4.80; S, 11.13.
1H), 3.98 (s, 1H), 3.52 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 169.13,
141.76, 137.87, 133.17, 132.52, 130.58, 129.95, 129.83, 128.08, 127.96,
127.78, 127.61, 126.89, 126.37, 126.19, 126.15, 52.17. EI-MS: m/
z¼294.19 (Mþ). Anal. Calcd for (C18H14O2S): C, 73.44; H, 4.79; S,
10.89. Found: C, 73.46; H, 4.71; S, 10.92.
4.4.12. Methyl 40-acetyl-3-mercapto-[1,10-biphenyl]-2-carboxylate
(4l). Yellow oil, 263 mg, 92% yield. 1H NMR (600 MHz, CDCl3)
d
8.00 (d, J¼7.8 Hz, 2H), 7.42 (dd, J¼15.0, 7.8 Hz, 3H), 7.35
(t, J¼7.8 Hz, 1H), 7.19 (d, J¼7.8 Hz, 1H), 3.98 (s, 1H), 3.59 (s, 3H),
2.64 (s, 3H). 13C NMR (100 MHz, CDCl3)
197.50, 168.60, 145.19,
4.4.19. Methyl 2-(furan-2-yl)-6-mercaptobenzoate (4s). Yellow oil,
210 mg, 90% yield. 1H NMR (600 MHz, CDCl3)
d
7.47 (s, 2H), 7.31 (dd,
J¼12.0, 7.8 Hz, 2H), 6.57 (d, J¼3.0 Hz, 1H), 6.47 (s, 1H), 3.89 (s, 3H),
3.80 (s, 1H). 13C NMR (100 MHz, CDCl3)
169.12, 151.44, 142.91,
d
140.70, 136.03, 131.91, 131.10, 130.36, 130.03, 128.31, 128.18, 127.18,
52.15, 26.55. EI-MS: m/z¼286.23 (Mþ). Anal. Calcd for
(C16H14O3S): C, 67.11; H, 4.93; S, 11.20. Found: C, 67.02; H, 4.86; S,
11.33.
d
130.58, 130.27, 129.77, 129.51, 129.38, 124.45, 111.68, 107.91, 52.53.
EI-MS: m/z¼234.13 (Mþ). Anal. Calcd for (C12H10O3S): C, 61.52; H,
4.30; S, 13.69. Found: C, 61.41; H, 4.25; S, 13.64.
4.4.13. Methyl 40-fluoro-3-mercapto-30-methyl-[1,10-biphenyl]-2-
carboxylate (4m). Yellow oil, 221 mg, 80% yield. 1H NMR
4.4.20. (E)-Methyl 2-mercapto-6-styrylbenzoate (4t). Yellow oil,
240 mg, 89% yield. 1H NMR (600 MHz, CDCl3)
d
7.50 (d, J¼6.6 Hz,
(600 MHz, CDCl3)
(d, J¼7.8 Hz, 2H), 7.10 (s, 1H), 7.01 (t, J¼9.0 Hz, 1H), 3.90 (s, 1H), 3.62
(s, 3H), 2.30 (s, 3H). 13C NMR (100 MHz, CDCl3)
168.94, 162.11,
d
7.35 (d, J¼7.8 Hz, 1H), 7.30 (t, J¼7.8 Hz, 1H), 7.16
1H), 7.47 (d, J¼7.8 Hz, 2H), 7.36 (t, J¼7.2 Hz, 2H), 7.29 (t, J¼8.4 Hz,
3H), 7.14 (d, J¼16.2 Hz, 1H), 7.03 (d, J¼16.2 Hz, 1H), 3.98 (s, 3H), 3.72
d
(s, 1H). 13C NMR (100 MHz, CDCl3)
d 168.58, 136.83, 136.67, 132.17,
159.67, 140.76, 136.06, 132.46, 131.09, 131.04, 130.20, 129.78, 129.71,
127.32, 126.88, 126.80, 124.83, 124.65, 114.90, 114.68, 52.04, 14.43.
EI-MS: m/z¼276.20 (Mþ). Anal. Calcd for (C15H13FO2S): C, 65.20; H,
4.74; S, 11.60. Found: C, 65.27; H, 4.79; S, 11.53.
132.00, 130.15, 129.98, 128.60, 128.05, 126.65, 125.26, 123.52, 52.33.
EI-MS: m/z¼270.21 (Mþ). Anal. Calcd for (C16H14O2S): C, 71.08; H,
5.22; S, 11.86. Found: C, 71.09; H, 5.30; S, 11.89.
Acknowledgements
4.4.14. Methyl 30,50-difluoro-3-mercapto-[1,10-biphenyl]-2-
carboxylate (4n). Yellow oil, 249 mg, 89% yield. 1H NMR
The research was supported in part by the National Key Tech-
nologies R&D Program (2011BAE06B05).
(600 MHz, CDCl3)
d
7.41 (d, J¼7.8 Hz, 1H), 7.33 (t, J¼7.8 Hz, 1H), 7.15

2752
Y.-C. Liu et al. / Tetrahedron 70 (2014) 2746e2752
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