Synthesis of 3-thiophenchromone by stille cross-coupling palladium on charcoal-catalyzed ligand-free

Article abstract of DOI:10.1002/jhet.2035

A new concise, facile, and efficient method for synthesis of 3-thiophenchromone was accomplished in more than over 80% yield starting from formation of the substituted 3-iodochromones and tetrathiophentins by Stille cross-coupling reaction in the presence of palladium on charcoal-catalyzed ligand-free under mild conditions.

Full text of DOI:10.1002/jhet.2035

310
Synthesis of 3-Thiophenchromone by Stille Cross-coupling Palladium on
Vol 52
Charcoal-Catalyzed Ligand-Free
a
Qian Yang,a,b Zunting Zhang, and Bo Liang
*
aKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National
Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, and School of
Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062, China
bSchool of Sciences, Xi’an University of Technology, Xi’an 710054, China
*
E-mail: zhangzt@snnu.edu.cn
Received January 4, 2013
DOI 10.1002/jhet.2035
Published online 20 May 2014 in Wiley Online Library (wileyonlinelibrary.com).
O
S
O
R2
I
S
0.5 mol% Pd/C, 4eq NaOAc (aq)
EtOH, refluxing, 4 h
1
4
R2
Sn
R1
R1
4
O
O
2
3
1
R1=H, 6-F,6-Br,7-CH3O, 7-i-Pro,
6-Cl, 7-CH3, 6-CH3
R2=H, 2-CH3
A new concise, facile, and efficient method for synthesis of 3-thiophenchromone was accomplished in
more than over 80% yield starting from formation of the substituted 3-iodochromones and tetrathiophentins
by Stille cross-coupling reaction in the presence of palladium on charcoal-catalyzed ligand-free under
mild conditions.
J. Heterocyclic Chem., 52, 310 (2015).
INTRODUCTION
report here an efficient protocol for the ligand-free, Pd/
C-catalyzed Stille reaction under atmospheric conditions
to give corresponding 3-thiophenchromones (Scheme 2).
Heteroarylchromones as the derivatives of arylchromones
show the activities of antifungal [1], pesticidal [2] and
Gastroprotective agents [3]. Yokoe, I. etal. [4] reported the
synthesis of 3-thiophenchromones by the Suzuki cross-
coupling of thiophen-2-ylboronic acid and 3-(thiophen-
2-yl)-4H-chromen-4-one (Scheme 1). Stille reaction [5],
a palladium-catalyzed cross-coupling between organotin
compounds and aryl halides, has been widely used as a syn-
thetic method for functional and bioactive materials includ-
ing natural products, agrochemicals, pharmaceuticals, and
organic electroluminescent polymers [6]. Organostannanes
are air-stable and moisture stable and tolerate a wide variety
of functional groups [7]. Stille coupling reaction was gener-
ally catalyzed by homogenous palladium catalysts together
with expensive phosphine ligands. For example, Fu and
Littke developed a powerful method for the cross-coupling
between aryl chlorides and aryl or alkenyltributyltin com-
pounds using Pd2(dba)3 and P(n-Bu) [8] as catalysts. Using
homogeneous palladium catalysts unfortunately and fre-
quently causes a contamination of the residual metal in the
desired product due to the difficulty of its removal [9]. Palla-
dium on charcoal (Pd/C), which has been employed as a com-
mon heterogeneous catalyst for hydrogenations, is attracting
the interests of organic chemists as a practical catalyst for a
variety of bond forming reactions [10] due to the air-stability
and non-residual properties. On the basis of our previous
cross-coupling of stannanes Ph4Sn, Ph3SnCl, Ph2SnCl2, and
PhSnCl3 with aryl iodides promoted by TBAF/H2O [11], this
inspired us to apply the Stille reaction in the synthesis of
3-thiophenchromone by tetrathiophen-2-ylstannane. We
RESULTS AND DISCUSSION
As an initial experiment, 3-iodo-4H-chromen-4-one 1a
(0.5 mmol) [12] reacting with tetrathiophen-2-ylstannane
2a (0.15 mmol) in toluene by TBAF (1 M/THF solution
containing 5% of water) as base with Pd2(dba)3 catalyst
was tried. Unfortunately, no product 3a was obtained
(Table 1, entry 1). Then, the reaction was carried out in
the presence of NaOAc in THF with Pd(PPh3)4 catalyst
by refluxing, 33% of 3a was obtained (Table 1, entry 2).
In order to obtain a good to high yield, we first optimized
the palladium catalytic system with Pd(PPh3)4, Pd/C,
PdCl2(PPh3)2, and Pd(OAc)2 (Table 1, entries 2–5). It
can be seen that 10% Pd(0)/C was the most effective cata-
lyst for the reaction (Table 1, entry 3). Further reaction in
different solvents such as THF (Table 1, entry 3), DMF,
CH3CN, and EtOH (Table 1, entries 6–8) revealed EOH
as the solvent that yields 92% of 3a (Table 1, entry 8).
And EtOH was an ideal environmentally friendly ‘green’
synthesis solvent. Third, base NaOAc, Na2CO3, NaOH,
K2CO3, NaHCO3 were tested, and the result indicated that
NaOAc was the most effective base for the coupling reac-
tion (Table 1, entries 8–12). Finally, the investigation with
different NaOAc equivalents revealed that 16.0 equiv of
NaOAc is the most suitable to obtain a high yield (Table 1,
entries 13–16). It is interesting to note that the yield is not a
significant change that reacted in the air (Table 1, entry
17), although the argon shield could facilitate the yield.
© 2014 HeteroCorporation

January 2015
Synthesis of 3-Thiophenchromone by Stille Cross-coupling Palladium on Charcoal-
Catalyzed Ligand-Free
311
Scheme 1. Synthesis of 3-thiophenchromone by Suzuki cross-coupling reaction.
Scheme 2. Steps for synthesis of 3-thiophenchromones from 1-(2-hydroxyphenyl)ethanones.
Table 1
Optimization of coupling reaction of 3-iodo-4H-chromen-4-one 1a with tetrathiophen-2-ylstannane 2a.a
Entry
Solvent
Base
Catalytic
Molar ratios 1a:2a:base
Yieldb (%)
1
2
3
4
5
6
7
8
Toluene
THF
THF
THF
THF
DMF
CH3CN
EtOHc
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
TBAF
Pd2(dba)3
Pd(PPh3)4
Pd/C
PdCl2(PPh3)2
Pd(OAc)2
Pd/C
Pd/C
Pd/C
Pd/C
Pd/C
Pd/C
Pd/C
Pd/C
Pd/C
Pd/C
Pd/C
Pd/C
4:1.2:7
NR
33
85
72
82
71
90
92
82
N.R.
84
74
75
82
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
Na2CO3
NaOH
K2CO3
NaHCO3
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
4:1.2:20
4:1.2:20
4:1.2:20
4:1.2:20
4:1.2:20
4:1.2:20
4:1.2:20
4:1.2:20
4:1.2:20
4:1.2:20
4:1.2:20
4:1.2:4
9
10
11
12
13
14
15
16
17
4:1.2:12
4:1.2:16
4:1.2:28
4:1.2:16
96
86
94d
Reaction conditions:
aUnless specified, couplings were performed on 0.5 mmol scale of 1a, 0.15 mmol of 2a (1a:2a = 4:1.2), with 10% equiv (Pd/1a) Pd catalyst in 10 mL
solvent, toluene and DMF at 100 ꢀC, others solvent refluxing, argon shield.
bIsolated yield after silica chromatography.
cThe coupling were performed also at 60ꢀC, 40ꢀC and rt, 78%, 53%, and 0%.
dThe coupling were performed in the air.
So, all our subsequent studies could be carried out in the air
with undistilled solvents and rendered the method excep-
tionally practicable.
Moreover, the influence of quantity Pd/C and response
time was tested. The results indicated that 0.5–10 mol%
Pd/C of 1a can obtain high yield of 3a in 0.5–4 h (Table 2,
entries 1–4). The reaction can also be performed under
0.1 mol% Pd/C of 1a as catalyst in 15 h, but the yield of
3a is 68% (Table 2, entry 5). In Table 2, the response time
of coupling reactions and the quantity of Pd/C is inversely
proportional. Considering the value of Pd/C and yield of
3a, 0.5 mol% Pd/C of 1a as the appropriate catalyst was
chosen for this reaction (Table 2, entry 4).
Furthermore, with the optimized reaction conditions in
hand, a variety of structurally divergent 3-iodochromones
(1) and tetrathiophentins (2) were studied to illustrate this
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

312
Q. Yang, Z. Zhang, and B. Liang
Vol 52
Table 2
The influence of quantity of catalyst and response time.a
Entry
Molar ratios of Pd/C:1a
Time (h)
Yieldb (%)
1
2
3
4
5
10%
5%
1%
0.5%
0.1%
0.5
2
3
4
15
94
92
91
86
68
Reaction conditions:
aAll reactions coupling were performed on 0.5 mmol scale of 1a, 0.15 mmol of 2a, with NaOAc (2 mmol) in 10 mL EtOH refluxing in the air and until
complete disappearance of 1a by TLC.
bIsolated yield after silica chromatography.
(d scale) are reported in ppm downfield from Me4Si which was used
as the internal standard for all NMR spectra. H-NMR spectra are
efficient synthesis of 3-thiophenchromones (3) (Table 3). It
was shown that all substrates smoothly reacted to give the
corresponding 3-thiophenchromones in 4 h to good yields.
Products 3 were characterized by IR, 1H-NMR, 13C-NMR,
and HRMS. When tetrathiophen-2-ylstannane(2a) is
coupled with 1a–1g, the yields of 3 are higher than that
of tetrakis(5-methylthiophen-3-yl)stannane (2b). For 3-
iodochromone substituted electron-donating groups such
as methoxyl, isopropoxide, methyl substituent, the yields
of 3 were higher than that of 3-iodochromone substrates
with electron-withdrawing groups such as fluorine, bro-
mine, and chloride substituent.
1
reported in order as follows: multiplicity and approximate coupling
constant (J-value) in hertz (Hz), number of protons; signals were char-
acterized as s (singlet), d (doublet), t (triplet), m (multiplet), and br
(broad signal). The 13C-NMR spectra were recorded at 75.00 MHz;
chemical shifts (d scale) are reported in ppm. The molecular weights
were performed with a Bruker MADI-TOF (Bruker, USA). A part
of the products are new compounds, but all of the products were
characterized by IR, 1H-NMR and 13C-NMR spectra, and MS.
3-Iodochromones were prepared by 1-(2-hydroxyphenyl)ethanones
and tetrathiophentins were synthesized by bromothiophene through
Grignard reaction[13]. All other commercially obtained reagents were
used as received. The silica gel used for the column chromatography
was purchased from Qingdao Hailang Chemistry Plant. TLC: silica
gel 60 GF254 plate; and the eluant of column chromatography is the
mixture of petroleum ether and ethyl acetate at volume ratio of 25:1.
Preparation of 3-iodochromonones 1 [12]. The corresponding
1-(2-hydroxyphenyl)ethanones (2 mmol) and DMF-DMA (8 mmol)
were refluxed in DMF (20 mL) at 80ꢀC for 1 h. After completion of
the reaction, the mixture was poured into water (40 mL), an orange
precipitate appeared, filtered and dried, corresponding 3-
dimethylamino-1-(2-hydroxyphenyl)propenones were obtained.
Then, 3-dimethylamino-1-(2-hydroxyphenyl)propenones and iodine
(4 mmol) were stirred in CHCl3 at room temperature for 2 h. All
reactions were monitored by TLC. The solution of 5% NaHSO3
was poured into the reaction mixture to quench I2, stirred until color
of the solution turned to be yellow. After extracted by CHCl3, dried
by MgSO4, concentrated by rotary evaporator, and recrystallized by
10 mL ethanol, the pure product corresponding 3-iodochromonones
1 were obtained. The yield of 1a–1g was 89%, 90%, 87%, 88%,
86%, 87%, and 89%.
CONCLUSIONS
In conclusion, we have developed a Pd/C-catalyzed free li-
gand method for synthesis of 3-thiophenchromone from
substituted 1-(2-hydroxyphenyl)ethanone and tetrathiophentins.
This process has the following significant features: (1) atom-
efficient coupling as 4 equiv of 3-iodo-4H-chromen-4-one
reacted with 1 equiv of tetrathiophentins provides a high
yield of the cross-coupling products; (2) performed in envi-
ronmentally friendly media EtOH without argon protection;
and (3) catalyzed with simple Pd/C in the absence of
additional free ligand. The coupling reaction of synthesis of
3-thiophenchromone can greatly reduce the production cost,
easy for industrial production.
Preparation of tetrathiophentins 2 [13]. 2-Bromothiophene
(0.14 mol) and magnesium turnings (0.28 mol) were added into an
oven dried round-bottom flask, along with dry THF (200 mL).
The result was an exothermic process and once vigorous reflux
had begun, additional dry THF (50 mL) was added, and the
mixture was heated at reflux for 3 h. Under an inert atmosphere,
the solution was transferred into another round-bottom flask
EXPERIMENTAL
Melting points were measured on X-5 micro melting point ap-
paratus (SanLi Instrument Corporation, Shenzhen, China), which
is uncorrected. IR spectra were recorded on FTIR (Nicolet, USA).
The H-NMR spectra were recorded at 300.00 MHz on Bruker
DRX-300 Advance spectrometer (Bruker, USA); chemical shifts
1
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DOI 10.1002/jhet

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Synthesis of 3-Thiophenchromone by Stille Cross-coupling Palladium on Charcoal-
Catalyzed Ligand-Free
313
Table 3
Synthesis of 3-thiophenchromones 3 by coupling of 3-iodochromones 1 with tetrathiophentins 2.
3-Iodochromones
1
Tetrathiophentins
2
3-thiophenchromones
3 Yieldb (%)
2a
2b
2a
2b
2a
2b
2a
2b
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

314
Q. Yang, Z. Zhang, and B. Liang
Vol 52
Table 3
(Continued)
3-Iodochromones
Tetrathiophentins
3-thiophenchromones
2a
2b
2a
2b
Reaction conditions:
aAll reactions were carried out in the indicated solvent (10 mL) using 3-iodo-4H-chromen-4-ones (1a–1g, 0.5 mmol), tetrathiophentins (2a, 2b,
0.15 mmol), 0.025 mmol 10% Pd(0)/C, and NaOAc (2 mmol).
bIsolated yield after silica chromatography.
containing a magnetic stirrer, leaving any unreacted magnesium
behind. The flask was cooled in an ice bath, and tin
tetrachloride (0.021 mol) was added drop-wise with rapid
stirring via a syringe. The mixture was refluxed for 12 h and
cooled. Hydrochloric acid (1 M, 50 mL) was added to the
mixture, suspension was appeared and filtered. The residue was
washed with methanol (50 mL), hydrochloric acid (1 M,
100 mL), and again with methanol (50 mL) to afford white
microcrystal tetrathiophentin 2a yield in 85%. Using the same
method to prepare 2b, the yield was 80%.
Preparation of 3-thiophenchromone 3. 3-Iodo-4H-chromen-4-
one 1a (0.5 mmol), tetrathiophen-2-ylstannane 2a (0.15 mmol),
NaOAc (2 mmol) and 10% Pd/C (0.025 mmol) were refluxed in
ethanol (10 mL) for 4 h. The reaction mixture was filtered, and the
mother liquid was acidified with 5% HCl/H2O to the neutral pH.
Evaporation of the solvent in vacuo and the residue was partitioned
(H2O/CH2Cl2). The organic layer was dried (MgSO4), evaporated,
and purified by silica gel column chromatography (petroleum ether-
ethyl acetate = 20:1) to the corresponding pure product 3a. 3b–3n
were obtained by the same method as 3a.
J=8.6, 1H,C5-H), 7.69 (t, J=7.5, 1H,C4`-H), 7.52–7.39 (m, 4H,C7-
H, C8-H, C3`-H, C5`-H), 7.11 (t, J=3.8, 1H, C6-H); 13C-NMR
[75 MHz, CDCl3/TMS, d (ppm)]: 175.1, 155.8, 151.5, 133.7,
132.4, 126.71, 126.6, 126.4, 125.4, 124.5, 123.9, 119.5, 118.1;
HRMS(ESI)[M + Na]+ for C13H8O2SNa, Calcd: 251.0143; found:
251.0140.
3-(5-Methylthiophen-3-yl)-4H-chromen-4-one (3b). White
solid; mp: 155.0–156.2ꢀC; IR (KBr), n (cmÀ1): 3133, 3067, 3042,
1632, 1616, 1468, 1365, 1219, 857, 751; 1H-NMR [300 MHz,
DMSO-d6/TMS, d (ppm)]: 8.79 (s, 1H,C2-H), 8.15 (d, J = 7.4,
1H,C5-H), 7.92 (s, 1H,C2`-H), 7.81 (t, J = 7.1, 1H, C7-H), 7.68
(d, J = 8.2, 1H, C8-H), 7.51 (t, J = 7.2, 1H, C6-H), 7.25 (s, 1H,
C4`-H), 2.48 (s, 3H, C5`-CH3); 13C-NMR [75MHz, DMSO-d6 /
TMS, d (ppm)]: 175.4, 155.7, 154.7, 139.0, 134.5, 131.8, 125.9,
125.2, 124.1, 122.4, 119.5, 118.8, 15.3; HRMS(ESI)[M + Na]+ for
C14H10O2SNa, Calcd: 265.0299; found: 265.0293.
7-Methoxy-3-(thiophen-2-yl)-4H-chromen-4-one (3c). White
solid; mp: 170.6–172.3 ꢀC;IR (KBr), n (cmÀ1): 3267, 3257,
3218, 1635, 1598, 1499, 1445, 1321, 1276, 1231, 1219, 1025,
1
835, 708; H-NMR [300 MHz, DMSO-d6 /TMS, d (ppm)]: 8.94
3-(Thiophen-2-yl)-4H-chromen-4-one (3a). White solid; mp
126.6–127.8ꢀC; IR (KBr), n (cmÀ1): 3107, 3082, 3003, 1629,
1567, 1463, 1344, 1276, 1225, 834, 756, 726; 1H-NMR
[300 MHz, CDCl3/TMS, d (ppm)]: 8.36 (s, 1H, C2-H), 8.31 (d,
(s, 1H, C2-H), 8.07 (d, J = 8.9, 1H, C5-H), 7.72–7.53 (m, 2H, C6-
H, C8-H), 7.27–7.02 (m, 3H, C3`-H, C4`-H, C5`-H), 3.92 (s, 3H,
C7-OCH3); 13C-NMR [75 MHz, DMSO-d6 /TMS, d (ppm)]:
173.9, 164.5, 157.6, 153.2, 132.1, 127.5, 127.2, 126.7, 124.5,
Journal of Heterocyclic Chemistry
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Synthesis of 3-Thiophenchromone by Stille Cross-coupling Palladium on Charcoal-
Catalyzed Ligand-Free
315
118.4, 117.0, 115.6, 101.1, 56.6; HRMS(ESI)[M + Na]+ for
C14H10O3S Na, calcd: 281.0248; found: 281.0242.
116.4, 102.3, 71.0, 22.0; HRMS(ESI)[M+ Na]+ for
C16H14O3SNa, calcd: 309.0561; found: 309.0541.
7-Methoxy-3-(5-methylthiophen-3-yl)-4H-chromen-4-one (3d).
White solid; mp: 175.8–176.2ꢀC; IR (KBr), n (cmÀ1): 3171, 3147,
3022, 2975, 2834, 1629, 1594, 1435, 1338, 1275, 1239, 1168,
7-Isopropoxy-3-(5-methylthiophen-3-yl)-4H-chromen-4-one(3j).
White solid; mp: 119.6–120.7ꢀC; IR (KBr),n (cmÀ1): 3177, 3106,
2977, 1632, 1601, 1573, 1441, 1238, 1201, 824, 782; 1H-NMR
[300 MHz, DMSO-d6/TMS, d (ppm)]: 8.69 (s, 1H C2-H), 8.03
(d, J=8.8, 1H, C5-H), 7.90 (s, 1H, C8-H), 7.24 (s, 1H, C2`-H), 7.15
(s, 1H, C4`-H), 7.05 (d, J=8.7, 1H, C6-H), 4.97–4.75 (m, 1H, C7-
OCH), 2.48 (s, 3H, C5`-CH3), 1.33 (d, J=5.7, 6H, C7-OCH(CH3)
2); 13C-NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 174.8, 162.4,
157.7, 154.7, 139.3, 132.35, 128.0, 125.1, 122.8, 119.5, 118.2,
115.8, 102.2, 70.7, 22.0, 15.3; HRMS(ESI)[M + Na]+ for
C17H16O3SNa, calcd: 323.0718; found: 323.0701.
1097, 838, 789; 1H-NMR [300 MHz, DMSO-d6 /TMS,
d
(ppm)]:8.71 (s, 1H, C2-H), 8.05 (d, J=8.8, 1H, C5-H), 7.91 (s, 1H,
C2`-H), 7.24 (s, 1H, C8-H), 7.17 (s, 1H, C4`-H), 7.09 (d, J=8.8,
1H, C6-H), 3.91 (s, 3H, C7-OCH3), 2.48 (s, 3H, C5`-CH3); 13C-
NMR [75 MHz, DMSO-d6 /TMS, d (ppm)]: 174.9, 164.3, 157.4,
154.4, 139.2, 131.9, 127.3, 125.4, 122.3, 119.4, 118.2, 115.3,
101.3, 56.5, 15.3; HRMS(ESI)[M + Na]+ for C15H12O3SNa, calcd:
295.0405; found: 295.0394.
6-Fluoro-3-(thiophen-2-yl)-4H-chromen-4-one (3e). Gray
solid; mp: 159.3–161.2ꢀC; IR (KBr),n (cmÀ1): 3200, 3071,
3032, 3108, 1633, 1625, 1574, 1475, 1425, 1325, 1264, 829,759,
698; 1H-NMR [300 MHz, DMSO-d6 /TMS, d (ppm)]: 9.06
(s, 1H, C2-H), 7.83 (dd, J = 8.1, 3.3, 1H, C5-H), 7.76(d, J = 3.0,
1H, C7-H), 7.73 (d, J = 8.7, 1H, C8-H), 7.67(d, J = 2.7, 1H, C3`-
H), 7.63 (d, J = 4.5, 1H, C5`-H), 7.16 (t, J = 3.9, 1H, C4`-H); 13C-
NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 173.8, 161.3, 157.9,
154.1, 152.3, 132.0, 127.8, 126.9, 124.7, 123.1, 122.8, 121.8, 121.7,
118.3, 110.6, 110.3; HRMS(ESI)[M + Na]+ for C13H7FO2SNa,
calcd: 269.0048; found: 269.0043.
6-Chloro-7-methyl-3-(thiophen-2-yl)-4H-chromen-4-one (3k).
White solid; mp: 186.6–189.2ꢀC; IR (KBr),n (cmÀ1): 3322, 3266,
3243, 1650, 1632, 1615, 1566, 1455, 1416, 1373, 1251, 1128,
1
844, 692; H-NMR [300 MHz, CDCl3/TMS, d (ppm)]: 8.30 (s,
1H, C2-H), 8.25 (s, 1H, C5-H), 7.50 (s, 1H, C8-H), 7.40 (d,
J = 5.0, 1H, C3`-H), 7.35 (d, J = 8.4, 1H, C5`-H), 7.11 (t, J = 3.8,
1H, C4`-H), 2.51(s, 3H, C7-CH3); 13C-NMR [75 MHz, CDCl3/
TMS, d (ppm)]: 173.3, 156.9, 153.6, 150.8, 142.7, 131.83, 126.2,
126.1, 125.5, 123.9, 122.3, 119.6, 118.9, 20.2; HRMS(ESI)
[M+ Na]+ for C14H9ClO2SNa, calcd: 299.9909; found: 298.9885.
6-Chloro-7-methyl-3-(5-methylthiophen-3-yl)-4H-chromen-
o
m
)
.
(
3
f
n
e
i
p
h
e
n
-
3
-
y
l
-
4
o
H
-
3
-
c
h
r
m
e
t h
y
l
Gray solid; mp: 164.9–166.3ꢀC; IR (KBr),n (cmÀ1): 3192,
4-one (3l).
White solid; mp: 193.3–194.9ꢀC; IR (KBr),n
3128, 3067, 1634, 1478, 1406, 1366, 1259, 1180, 1133, 817,
722; 1H-NMR [300 MHz, CDCl3/TMS, d (ppm)]:8.11 (s, 1H,
C2-H), 7.87 (d, J = 7.8, 1H, C5-H), 7.63 (s, 1H, C2`-H), 7.49(d,
J = 3.2, 1H, C7-H), 7.41 (d, J = 6.1, 1H, C8-H), 6.97 (s, 1H, C4`-
H), 2.45 (s, 3H, C5`-CH3); 13C-NMR [75 MHz, CDCl3/TMS, d
(ppm)]: 161.2, 152.4, 139.9, 130.9, 130.8, 128.7, 124.3, 122.4,
121.9, 121.5, 120.1, 120.0, 111.2, 110.9, 15.2; HRMS(ESI)
[M + Na]+ for C14H9FO2SNa, calcd: 283.0205; found: 283.0198.
6-Bromo-3-(thiophen-2-yl)-4H-chromen-4-one (3g). Gray
solid; mp: 189.3–190.7ꢀC; IR (KBr),n (cmÀ1): 3151, 3073, 3015,
1633, 1599, 1461, 1320, 1266, 847, 705; 1H-NMR [300 MHz,
CDCl3/TMS, d (ppm)]: 8.43 (s, 1H, C2-H), 8.33 (s, 1H, C5-H),
7.70 (d, J = 2.3, 1H, C7-H), 7.67 (d, J = 2.2, 1H, C8-H), 7.43
(d, J = 3.4, 1H, C3`-H), 7.34 (d, J = 4.6, 1H, C5`-H), 7.03
(t, J=3.7,1H, C4`-H); 13C-NMR [75 MHz, CDCl3/TMS, d (ppm)]:
173.2, 151.0, 136.6, 136.1, 128.5, 126.3, 126.2, 126.0, 124.5,
119.5, 119.3, 118.3; HRMS(ESI)[M + Na]+ for C13H7BrO2SNa,
calcd: 328.9248; found: 328.9218.
(cmÀ1): 3209, 3174, 3148, 2992, 2923, 2806, 1636, 1618,
1
1450, 1412, 1373, 1352, 1216, 1149, 1127, 897, 820, 632; H-
NMR [300 MHz, CDCl3/TMS, d (ppm)]:8.24 (s, 1H, C2-H),
8.12 (s, 1H, C5-H), 7.69 (s, 1H, C2`-H), 7.34 (s, 1H, C8-H),
7.02 (s, 1H, C4`-H), 2.51 (d, J = 6.5, 6H, C7-CH3, C5`-CH3);
13C-NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 174.8, 154.3,
153.6, 138.5, 135.3, 134.9, 131.5, 124.8, 124.4, 123.3, 123.1,
121.8, 119.2, 118.0, 20.4, 15.1; HRMS(ESI)[M + Na]+ for
C15H11ClO2S calcd: 313.0066; found: 313.0059.
6-Methyl-3-(thiophen-2-yl)-4H-chromen-4-one (3m). White
solid; mp: 169.2–170.5ꢀC; IR (KBr),n (cmÀ1): 3140, 3119,
3073, 2916, 1634, 1568, 1483, 1424, 1365, 1327, 1272, 1231,
844, 817, 686; 1H-NMR [300 MHz, CDCl3/TMS, d (ppm)]:
8.25 (s, 1H, C2-H), 8.02 (s, 1H, C5-H), 7.41 (dd, J = 6.36, 3.36,
2H, C7-H, C8-H), 7.32 (dd, J = 3.0, 1H, C3`-H), 7.27 (d, J = 9.1,
1H, C5`-H), 7.03 (t, J = 3.87, 1H, C4`-H), 2.47 (s, 3H, C6-CH3);
13C-NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 174.6, 159.4,
154.2, 153.4, 136.0, 135.8, 132.5, 127.3, 126.5, 125.2, 124.2,
123.2, 118.8, 20.9; HRMS(ESI)[M + Na]+ for C14H10O2SNa,
calcd: 265.0299; found: 265.0279.
6-Methyl-3-(5-methylthiophen-3-yl)-4H-chromen-4-one (3n).
White solid; mp: 138.6–139.4ꢀC; IR (KBr),n (cmÀ1):3215, 3280,
3119, 1633, 1614, 1548, 1485, 1354, 1268, 1224, 1173, 1150,
841, 813, 799, 717; 1H-NMR [300 MHz, CDCl3/TMS, d
(ppm)]: 8.11 (s, 1H,C2-H), 8.08(s, 1H, C5-H),7.69 (s, 1H, C2`-
H), 7.46 (d, J = 8.1, 1H, C7-H), 7.35 (d, J = 8.3, 1H, C8-H), 7.04
(s, 1H, C4`-H), 2.49 (d, J = 16.7, 6H, C6-CH3, C5`-CH3); 13C-
NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 175.3, 154.0, 153.5,
138.4, 135.0, 131.8, 124.6, 123.3, 121.8, 119.3, 118.9, 118.0,
20.46, 15.13; HRMS(ESI)[M + Na]+ for C15H12O2SNa, calcd:
279.0456; found: 279.0438.
6-Bromo-3-(5-methylthiophen-3-yl)-4H-chromen-4-one (3h).
Gray solid; mp: 193.2–194.5ꢀC; IR (KBr),n (cmÀ1): 3169,
1
3064, 1605, 1557, 1438, 1275, 8151, 593; H- NMR [300 MHz,
CDCl3/TMS, d (ppm)]:8.42 (s, 1H, C2-H), 8.17 (s, 1H, C5-H),
7.75 (d, J = 8.7, 1H, C7-H), 7.70 (s, 1H, C2`-H), 7.37 (d, J = 8.9,
1H, C8-H), 7.02 (s, 1H, C4`-H), 2.52 (s, 3H, C5`-CH3); 13C-
NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 173.7, 154.5, 138.7,
136.6, 131.0, 128.63, 127.5, 125.1, 124.7, 122.2, 121.1, 119.3,
118.2, 14.9; HRMS(ESI)[M + Na]+ for C14H9BrO2SNa, calcd:
342.9404; found: 342.9387.
7-Isopropoxy-3-(thiophen-2-yl)-4H-chromen-4-one (3i).White
solid; mp: 123.4–124.5ꢀC; IR (KBr),n (cmÀ1): 3014, 2950, 2926,
1626, 1444, 1284, 1261, 1110, 847, 691; 1H-NMR [300 MHz,
DMSO-d6/TMS, d (ppm)]: 8.95 (s, 1H, C2-H), 8.05 (d, J = 8.8,
1H, C5-H), 7.71–7.51 (m, 2H, C3`-H, C5`-H), 7.20 (s, 1H, C8-H),
7.14 (t, J = 5.7, 1H C4`-H), 7.08 (d, J = 8.7, 1H, C6-H),4.87–4.82
(m, 1H, C7-OCH), 1.34 (d, J = 5.7, 6H,C7-OCH(CH3)2); 13C-
NMR [75MHz, DMSO-d6/TMS, d (ppm)]: 173.8, 162.6, 157.7,
153.1, 149.7, 132.5, 127.6, 127.5, 126.8, 124.3, 118.5, 117.0,
REFERENCES AND NOTES
[1] Wei, D. G.; Yang, G. F.; Wan, J.; Zhan, C. G. J Agric Food
Chem 2005, 53, 1604.
[2] Yang, G. F.; Jiang, X. H.; Yang, H. Z. Pest Manag Sci 2002,
58, 1063.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

316
Q. Yang, Z. Zhang, and B. Liang
Vol 52
[3] Jeffrey, J.; Ares, P. E.; Outt, J. L.; Randall, J. N. Bioorg Med Chem
Lett. 1996, 6, 995.
[4] Yokoe, I.; Sugita, Y.; Shirataki, Y. Chem Pharm Bull
1989, 37, 529.
[5] (a) Kosugi, M.; Sasazawa, K.; Shimizu, Y.; Migita, T. Chem. Lett.
1977, 301; (b) Kosugi, M.; Sasazawa, K.; Shimizu, Y.; Migita, T. Chem Lett
1977, 1423; (c) Milstein, D.; Stille, J. K. J Am Chem Soc 1978, 100, 3636;
(d) Milstein, D.; Stille, J. K. J Am Chem Soc 1979, 101, 4992.
[6] (a) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem.
Int. Ed. 2005, 44, 4442; (b) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz,
E.; Lemaire, M. Chem Rev 2002, 102, 1359; (c) Kotha, S.; Lahiri, K.;
Kashinath, D. Tetrahedron, 2002, 58, 9633.
[8] Littke, A. F.; Fu, G. C. Angew Chem Int Ed 1999,
38, 2411.
[9] Diederich, F., de Meijere, A., Eds. Metal-Catalyzed Cross-
Coupling Reactions, 2nd ed.; Wiley-VCH: Weinheim. 2004.
[10] (a) Seki, M. J. Synth. Org. Chem. Jpn. 2006, 64, 853; (b) Seki,
M. Synthesis 2006, 38, 2975; (c) Felpin, F. X.; Ayad, T.; Mitra, S. Eur
Org Chem 2006, 12, 2679.
[11] Zhang, Z. T.; Pitteloud, J. P.; Cabrera, L.; Liang, Y.; Toribio
M.; Wnuk, S. F. Org Lett 2010, 12, 816.
[12] Vasselin, D. A.; Westwell, A. D.; Matthews, C. S.; Bradshaw,
T. D.; Stevens, M. F. J Med Chem 2006, 49, 3973.
[13] Ng, M. C. C.; Craig, D. J.; Harper, J. B.; van - Eijck, L.; Stride,
J. A. Chem Eur 2009, 15, 6569.
[7] Stille, J. K. Angew Chem Int Ed Engl 1986, 25, 508.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet