A novel solid-phase synthesis of 2H-chromenes

Article abstract of DOI:10.3987/COM-15-13402

A method for synthesizing substituted 2H-chromenes using TMSOTf-catalyzed polystyrene-supported succinimidyl selenide-induced intramolecular seleno-arylation of tethered alkenes as a key step has been developed. The catalytic process provides an efficient

Full text of DOI:10.3987/COM-15-13402

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HETEROCYCLES, Vol. 92, No. 4, 2016
HETEROCYCLES, Vol. 92, No. 4, 2016, pp. 708 - 719. © 2016 The Japan Institute of Heterocyclic Chemistry
Received, 30th December, 2015, Accepted, 29th January, 2016, Published online, 16th February, 2016
DOI: 10.3987/COM-15-13402
A NOVEL SOLID-PHASE SYNTHESIS OF 2H-CHROMENES
E Tang,1,2,* Yinjiao Zhao,3 Meng Zhang,2 Xin Dai,2 Weilin Wang,2 and
Deshou Mao3,*
1Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan
University), Ministry of Education, P. R. China. 2School of Chemical Science and
Technology, Yunnan University, No 2 Green Lake North Road, Kunming 650091,
3
P. R. of China. Research Center of China Tobacco Yunnan Industrial Co., Ltd,
No.181 Hongjing Road, Kunming 650000, P. R. China
e-mail: tange@ynu.edu.cn
Abstract – A method for synthesizing substituted 2H-chromenes using
TMSOTf-catalyzed polystyrene-supported succinimidyl selenide-induced
intramolecular seleno-arylation of tethered alkenes as a key step has been
developed. The catalytic process provides an efficient method for the
stereoselective and regioselective synthesis of 3,4-dihydro-2H-chromenes
possessing a seleno-functionality, followed by syn-elimination of selenoxides to
provide 2H-chromenes in good yields and with high purities.
The regioselective and stereoselective solid-phase synthesis of heterocycles and its application to the
generation of drug-like molecules has attracted widespread attention.1 2H-Chromenes display a broad
spectrum of biological activities2 such as anticancer, antioxidant, anti-inflammatory, antitubercular,
antiviral, antitumor, antibacterial/antimicrobial, antidiabetic, anticoagulant, antianaphylatic, diuretic,
fungicidal, and anti-HIV activity; additionally, the 2H-chromene substructure is an important structural
motif present in a variety of medicines, natural products,3 and materials showing unique photophysical
properties.4 Hence, the structural importance of the benzopyran moiety has elicited a great deal of interest
in the field of organic synthesis and chemical biology to develop new and improved synthesis of these
molecular skeletons. The synthesis of 2H-chromenes is structured around the three main approaches
applied in catalytic 2H-chromene synthesis: (i) catalysis with (transition) metals,5 (ii) metal-free Brønsted
and Lewis acid/base catalysis, which includes examples of nonenantioselective organocatalysis,6 and (iii)
enantioselective organo-catalysis.7 Despite such synthetic advances, the original method of Iwai and Ide8
remains as a very useful method as it can provide the simplest 2H-chromene ring from an easily

HETEROCYCLES, Vol. 92, No. 4, 2016
709
accessible phenol in just two steps. However, the post reaction workup is quite tedious, and it produces
significant amount of environmentally unfriendly waste besides the poor yield. A method for the
solid-phase synthesis of 2H-chromenes in good yields has been developed by Nicolaou et al.9 This
approach was based on an electrophilic cyclization reaction via forming a carbon-heteroatom bond and
using the resin-bounded selenenyl bromide.9 However, to the best of our knowledge, the solid-phase
synthesis of 2H-chromenes via the selenium-induced and a carbon-carbon bond forming cyclization
reaction has not been reported. In recent years, we have been keen to study the solid-phase synthesis of
heterocyclic compounds,10 using organoselenium as a linker and the reagent since organoselenium
compounds can be utilized as synthetic intermediates11 and selenium-carbon bond can be easily broken by
various methods.12 Herein, we report an efficient solid-phase synthesis of 2H-chromenes via Lewis
acid-catalyzed, polymer-supported selenium-mediated, and intramolecular carbon-carbon bond forming
reaction, as well as the subsequent oxidative cleavage of selenium resins. Advantages of this method are
easy post reaction workup operations, odorlessness, easy preparation of the substrates, and good yield of
the product.
Firstly, the solid-phase cyclization of 1-methoxy-4-[[(2E)-3-phenyl-2-propen-1-yl]oxy]benzene (3a)13
with polystyrene-supported selenenyl bromide (1)14 (Br: 0.99 mmol/g) was explored at -78 °C to 40 °C in
dry CH2Cl2 for 48 h. But the selenium resin-bound annular intermediate 4a was not produced, since no
product 5a was obtained by treatment of the selenium resin-bound intermediate with 30% H2O2 at 0 °C to
room temperature. Inspired by Hajra’s work of Lewis acid-catalyzed intramolecular halo-arylation of
tethered alkenes,15 we had successfully developed convenient solid-phase syntheses of quinolines10f and
coumarins10e via TMSOTf-catalyzed intramolecular seleno-arylation of alkenes, using polystyrene-
supported succinimidyl selenide (PSSS) as a selenium source. PSSS resin was prepared from dark-red
polystyrene-supported selenenyl bromide (1)14 (Br: 0.99 mmol/g) sequentially via reduction reaction with
NaBH4, alkylation reaction with allyl bromide, and amidation reaction with N-chlorosuccinimide (NCS).
The reactions were monitored by FTIR (Scheme 1). With the help of Lewis acid, PSSS could react with
1) NaBH4, THF,
DMF, 40 oC
O
NCS
SeBr
Se
NSe
Cl
2) allyl bromide,
THF, rt
CH2Cl2, rt
O
PSSS
1
2
dark-red
pale-yellow
IR (KBr): υmax = 3019cm-1
flesh-coloured
1707 cm-1
Scheme 1. Synthesis of polystyrene-supported succinimidyl selenide (PSSS)

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HETEROCYCLES, Vol. 92, No. 4, 2016
3a to form seleniranium ion intermediate 6a which was subsequently attacked by the intramolecular
aromatic carbon-centered nucleophile from the anti-side to form a new carbon-carbon bond, and offer the
annular product 4a (Scheme 2). Considering PSSS is sensitive to moisture, a one-pot synthesis of
polymer-supported annular product 4 was employed. After completion of the reaction of the resin 2 with
NCS, PSSS was directly washed by dry CH2Cl2 under nitrogen atmosphere without being removed from
the reaction flask. PSSS was then treated with 10 mol% TMSOTf and 3a in dry CH2Cl2 at -78 °C for 2 h.
And then the reaction mixture was kept at -20 °C for 4 h to afford 3-polystyrene-supported
seleno-6-methoxy-4-phenyl-3,4-dihydro-2H-chromene (4a). The treatment of 4a with H2O2 in THF at
0 °C to room temperature gave 6-methoxy-4-phenyl-2H-chromene (5a) in 86% isolated yield and with
more than 90 % purity (Scheme 2).
O
O
O
30% H2O2
[PSSS], Catalyst
MeO
MeO
MeO
Se
THF, 0 oC~rt
CH2Cl2, -78 ~ -20 oC
3a
5a
4a
total yield: 86%
purity: > 90%
O
MeO
Se
6a
Scheme 2. Solid-phase synthesis of 2H-chromene 5a
Furthermore, a range of cyclization reaction conditions involving 3a and PSSS were explored. The results
are depicted in Table 1. This reaction was rather sluggish in the absence of catalyst, even under reflux
conditions (Table 1, entry 1). An investigation using a series of Lewis and Brønsted acids identified
TMSOTf as an active catalyst. Addition of double dose of TMSOTf and a prolonged reaction time did not
improve the yield of 5a (Table 1, entries 11 and 12 ); the yield and the purity of 5a decreased when 5
mol% of TMSOTf was employed (Table 1, entry 10); the employment of 10 mol% BF3·Et2O, AlCl3,
FeCl3, ZnCl2, TsOH, TFA, and HOAc afforded the product in very low yield when the cyclization
reaction was performed at -78 °C for 2 h and then -20 °C for 4 h in dry CH2Cl2 (Table 1, entries 5-8,
15-17); less than 5% yield of the annular product was obtained when the reaction was performed only at
-78 °C or at -20 °C (Table 1, entries 13 and 14); no product was obtained when other Lewis acids such as
TiCl4, Sm(OTf)3, and AgOTf were used (Table 1, entries 2-4).

HETEROCYCLES, Vol. 92, No. 4, 2016
711
Table 1. Optimization of solid-phase conditions of cyclization
Amount of catalyst
Reaction timec
Total yield of 5aa
Purity of 5ab
Entry
Lewis acid
(mol%)
-
(h)
6
(%)a
(%)b
1
2
none
TiCl4
nr
-
10
10
10
10
10
10
10
10
5
6
nr
-
3
Sm(OTf)3
AgOTf
BF3·Et2O
AlCl3
6
nr
-
4
6
nr
-
5
6
<5
<5
<5
<5
86
70
85
82
31
<5
<5
<5
<5
-
6
6
-
7
FeCl3
6
-
8
ZnCl2
6
-
9
TMSOTf
TMSOTf
TMSOTf
TMSOTf
TMSOTf
TMSOTf
TsOH
6
> 90
10
11
12
13
14
15
16
17
6
> 80
20
10
10
10
10
10
10
6
> 90
8d
6e
4f
6
> 90
-
-
-
-
-
TFA
6
HOAc
6
a Yields of the crude products based on the loading of polystyrene-supported selenenyl bromide (Br, 0.99
mmol/g); nr = no reaction.
b Determined by HPLC analysis.
c The cyclization reaction was performed at -78 °C for 2 h and then -20 °C for 4 h.
d The cyclization reaction was performed at -78 °C for 2 h and then -20 °C for 6 h.
e The cyclization reaction was performed at -78 °C for 6 h.
f The cyclization reaction was performed at -20 °C for 4 h.
Mechanistically, it appears that TMSOTf activates PSSS by chelating to the amide carbonyl group to
facilitate the formation of the seleniranium ion intermediate 6a from alkenes; the subsequent reaction
with arene led to the formation of annular products 4a and the regeneration of the TMSOTf catalyst
(Scheme 3).

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O
O
TMSOTf
O
MeO
Se
N
Se
N
O
O
PSSS
TMSOTf
3a
O
HN
O
TMSO
N
O
O
H
O
O
-
OTf
Se
Se
MeO
Se
MeO
MeO
-
OTf
4a
6a
Scheme 3. Mechanistic hypothesis for the intramolecular PSSS-promoted carboannulation reaction of
compound 3a
Then the polystyrene-supported selenium-mediated cyclization reactions of a series of olefins 3 in the
one-pot procedure were studied. The products 5 were obtained in good yields and with high purities via
intramolecular cyclization reaction and syn-elimination of selenoxides. The results are summarized in
Table 2. It is quite obvious that when R1, R2, R3, and R4 were H, bromo, electron-donating substituents
such as alkoxyl and alkyl, the carbon-based annulation reaction proceeded smoothly to give annular
compounds (Table 2, entries 1-15); good results were also obtained when R was alkyl, phenyl,
electron-donating group-substituted phenyl, and electron-withdrawing group-substituted phenyl (Table 2,
entries 1-9, 11-15); no annular products were obtained when R1, R2, R3, and R4 were
electron-withdrawing substituents such as formyl (Table 2, entry 16); besides the annular product 5k was
obtained in the yield of 60%, an unidentified by-product was found when R was H (Table 2, entry 10);
both 7-methoxy-4-phenyl-2H-chromene (5d) and 5-methoxy-4-phenyl-2H-chromene (5e) were obtained
from (E)-1-(cinnamyloxy)-3-methoxybenzene (3d) in the yields of 46% and 41% respectively (Table 2,
entry 4). It is interesting that the TMSOTf-catalyzed PSSS-mediated cyclization reaction of compounds 3
gave rise to the six-membered cyclic compounds 4 as a result of 6-endo-trig cyclization of compounds 3.
The five-membered cyclic compounds were not obtained.

HETEROCYCLES, Vol. 92, No. 4, 2016
713
Table 2. Solid-phase synthesis of 2H-chromenes 5 via PSSS-mediated cyclization reaction
R1
R4
R1
R1
[PSSS]
R2
R3
O
R
R2
R3
O
R
R2
R3
O
R
10 mol% TMSOTf
30% H2O2
THF, 0 oC~rt
o
CH2Cl2, -78 ~ -20 C
Se
R4
R4
5
3
4
Entry
R
R1
R2
R3
R4
Product
Total
Purity
yield (%)a (%)b
1
2
3
Ph
Ph
Ph
MeO
H
H
H
H
86
82
85
> 90
> 95
> 90
5a
5b
5c
H
MeO
H
H
H
MeO
MeO
Ph
Ph
H
H
MeO
H
H
H
H
MeO
5d
5e
87c
4
-
5
6
Ph
Ph
Ph
Ph
Ph
H
Me
H
Me
H
H
t-Bu
t-Bu
Me
H
Me
H
5f
5g
5h
5i
83
82
78
80
85
60d
82
75
79
80
83
0
> 95
> 95
> 90
> 90
> 95
-
7
t-Bu
t-Bu
i-Pr
H
H
H
8
H
H
9
H
Me
H
5j
10
11
12
13
14
15
16
H
MeO
Me
Me
Me
H
5k
5l
3’,5’-(MeO)2C6H3
4’-MeO-2’-NO2C6H3
4’-FC6H4
H
H
H
> 90
> 90
> 90
> 90
> 95
-
H
H
H
5m
5n
5o
5p
5q
H
H
H
4’- MeC6H4
Me
Br
MeO
H
H
H
MeO
H
H
Ph
CHO
H
H
a Yields of the crude products based on the loading of polystyrene-supported selenenyl bromide (Br, 0.99
mmol/g);
b
Determined by HPLC analysis; the products 5 with high purities were obtained because of water is the
only by-product in the oxidative cleavage of selenium resins with 30% H2O2 aqueous solution.
c Combined yield of 46% yield of 5d and 41% yield of 5e.
d An unidentified by-product was observed.
In conclusion, we have developed a highly regioselective selenium-mediated intramolecular
Friedel-Crafts alkylation of substituted 1-(allyloxy)benzene 3 using polymer-supported organoselenium
reagent as a selenium source. Among the catalysts investigated, TMSOTf was found to be the best one.
The target products were obtained in good yields and with good purities by the cleavage of the selenium

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HETEROCYCLES, Vol. 92, No. 4, 2016
linker. Furthermore, the easy workup procedure and easily prepared the substrates provide an approach
that is well-suited for building the parallel libraries upon the basis of further transformation of
polymer-supported seleno-3,4-dihydro-2H-chromene 4. The further modifications of resin 4 are currently
ongoing.
EXPERIMENTAL
Melting points were measured with an X-6 micro-melting apparatus and were uncorrected. 1H NMR (300
13
MHz) and C NMR (75 MHz) spectra were recorded on a Bruker Avance 300 spectrometer in CDCl3
with TMS as the internal standard; chemical shifts were quoted in ppm and J values were given in Hz. IR
spectra were recorded on a Thermo Nicolet Avatar 360 spectrometer. HRMS were performed on an
Agllent LC/Msd TOF instrument. HPLC were run on an Agilernt 1100 High performance liquid
chromatograph with a tunable UV detector. Dry CH2Cl2 and DMF were distilled from CaH2. Dry THF
was distilled from Na. Purities and yields of the products were determined by the crude products and
NMR, HRMS, and FTIR were determined by the purified products (the crude products were subjected to
TLC on silica gel with AcOEt and light petroleum as eluent to give the purified products. Allyl
polystyrene-supported selenide 210f and the substrates 313 were prepared according the literatures.
General procedure for the preparation of 3-polystyrene-supported seleno-3,4-dihydro-2H-
chromene (4): To a suspension of the swollen resin 2 (1.0 g) in dry CH2Cl2 (15 mL) was added NCS
(0.668 g, 5.0 mmol) at 0 °C. The mixture was stirred for 0.5 h at 0 °C and 2 h at room temperature. After
filtrating and washing with dry CH2Cl2 (15 mL×3), PSSS resin was suspended with dry CH2Cl2 (15 mL)
and cooled to -78 °C. Trimethylsilyl trifluoromethanesulfonate (0.022 g, 0.10 mmol) was added into the
reaction mixture. After stirring for 0.5 h at -78 °C, substituted 1-(allyloxy)benzene 3 (5.0 mmol) was
added into the reaction mixture under nitrogen atmosphere. The suspension was stirred for another 2 h at
-78 °C and then stored in a freezer at -20 °C for 4 h. Saturated NaHCO3 aqueous solution (5 mL) was
poured into the flask to quench the reaction. The resin 4 was collected by filtration, washed with THF (20
mL×2), Et2O (20 mL×2), THF/H2O (V/V = 3:1, 20 mL×2), H2O (20 mL×2), THF (20 mL×2), MeOH (20
mL×2), and CH2Cl2 (20 mL×2), and dried under vacuum.
General procedure for the preparation of 2H-chromenes 5: To a suspension of the swollen resin 4 in
THF (15 mL) was added 30% aqueous H2O2 (1.2 mL). After stirring for 1 h at 0 °C and for another 20
min at room temperature, the mixture was filtered and the resin was washed with CH2Cl2 (15 mL×2). The
filtrate was washed with H2O (30 mL×2), dried over MgSO4 and filtered. After removal of the solvents
under reduced pressure, the crude products 5 were obtained and then subjected to column
chromatography on silica gel (n-hexane/AcOEt (V/V) =10:1) to give the purified products 5.

HETEROCYCLES, Vol. 92, No. 4, 2016
715
6-Methoxy-4-phenyl-2H-chromene (5a)16: Light yellow solid, mp 66.3-68.6 °C; 1H NMR (300 MHz,
CDCl3): δ = 7.43-7.34 (m, 5H), 6.85 (d, J = 8.7 Hz, 1H), 6.72 (dd, J = 8.7 Hz, 3.0 Hz, 1H), 6.58 (d, J =
3.0 Hz, 1H), 5.85 (t, J = 3.9 Hz, 1H), 4.79 (d, J = 4.2 Hz, 2H), 3.67 (s, 3H); IR (KBr): υmax = 1655, 1618,
1507, 1484, 1254, 1202 cm–1; HRMS m/z: calcd for C16H14O2 [M]+ 238.0994; found 238.0999.
8-Methoxy-4-phenyl-2H-chromene (5b)17: Light yellow solid, mp 70.4-72.1 °C; 1H NMR (300 MHz,
CDCl3): δ = 7.39-7.30 (m, 5H), 6.84-6.76 (m, 2H), 6.65-6.61 (m, 1H), 5.79 (t, J = 3.9 Hz, 1H), 4.89 (d, J
= 3.9 Hz, 2H), 3.88 (s, 3H); IR (KBr): υmax = 1646, 1614, 1454, 1401, 1263, 1168 cm–1; HRMS m/z: calcd
for C16H14O2 [M]+ 238.0994; found 238.0983.
1
6,7-Dimethoxy-4-phenyl-2H-chromene (5c): Brown-orange oil; H NMR (300 MHz, CDCl3): δ =
7.42-7.31 (m, 5H), 6.58 (s, 1H), 6.54 (s, 1H), 5.68 (t, J = 3.9Hz, 1H), 4.76 (d, J = 3.9 Hz, 2H), 3.86 (s,
13
3H), 3.67 (s, 3H); C NMR (75 MHz, CDCl3): δ 149.8, 149.5, 143.3, 138.4, 137.2, 128.5, 128.4, 127.8,
117.3, 115.6, 109.6, 100.8, 65.3, 56.6, 56.0; IR (KBr): υmax = 1654, 1612, 1505, 1454, 1401, 1169 cm–1;
HRMS m/z: calcd for C17H16O3 [M]+ 268.1099; found 268.10990.
7-Methoxy-4-phenyl-2H-chromene (5d)18: Colorless oil; 1H NMR (300 MHz, CDCl3): δ = 7.36-7.18 (m,
6H), 6.93 (s, 1H), 6.46 (s, 1H), 5.61 (t, J = 3.9Hz, 1H), 4.78 (d, J = 3.9 Hz, 2H), 3.81 (s, 3H); IR (KBr):
υmax = 1655, 1613, 1596, 1479, 1444, 1381, 1319, 1266, 1140, 1032 cm–1; HRMS m/z: calcd for C16H14O2
[M]+ 238.0994; found 238.0993.
5-Methoxy-4-phenyl-2H-chromene (5e): Yellow oil; 1H NMR (300 MHz, CDCl3): δ = 7.27-7.24 (m,
5H), 6.84 (d, J = 8.4 Hz, 1H), 6.40 (d, J = 2.4 Hz, 1H), 6.32 (dd, J = 2.4 Hz, 8.4 Hz, 1H), 5.56 (t, J =
13
3.9Hz, 1H), 4.74 (d, J = 3.9 Hz, 2H), 3.69 (s, 3H); C NMR (75 MHz, CDCl3): δ = 160.6, 156.1, 138.5,
137.0, 128.6, 128.4, 127.7, 126.7, 117.0, 106.9, 102.0, 65.6, 55.4; IR (KBr): υmax = 1655, 1614, 1498,
1446, 1270, 1198, 1160, 1116, 1032 cm–1; HRMS m/z: calcd for C16H14O2 [M]+ 238.0994; found
238.0982.
5,7,8-Trimethyl-4-phenyl-2H-chromene (5f): Yellow oil; 1H NMR (300 MHz, CDCl3): δ = 7.35-7.19
(m, 5H), 6.57 (s, 1H), 5.88 (t, J = 4.8 Hz, 1H), 4.55 (d, J = 4.8 Hz, 2H), 2.24 (s, 3H), 2.17 (s, 3H), 1.68 (s,
3H); 13C NMR (75 MHz, CDCl3): δ = 154.3, 141.6, 139.1, 137.7, 132.3, 128.3, 127.6, 127.1, 125.9, 121.6,
121.5, 121.1, 64.4, 22.3, 20.0, 11.8; IR (KBr): υmax = 1664, 1601, 1449, 1112, 1061 cm–1; HRMS m/z:
calcd for C18H18O [M]+ 250.1358; found 250.1368.
6-(tert-Butyl)-4-phenyl-2H-chromene (5g): Yellow oil; 1H NMR (300 MHz, CDCl3): δ = 7.38-7.34 (m,
5H), 7.18 (d, J = 2.4 Hz, 8.4 Hz, 1H), 7.07 (d, J = 2.1 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1H), 5.78 (t, J = 3.9Hz,
13
1H), 4.79 (d, J = 3.9 Hz, 2H), 1.20 (s, 3H); C NMR (75 MHz, CDCl3): δ = 152.7, 143.9, 138.5, 137.6,
128.7, 128.5, 127.9, 127.1, 126.1, 123.0, 120.0, 115.7, 65.3, 34.3, 31.5; IR (KBr): υmax =1656, 1612, 1504,
1451, 1399 cm–1; HRMS m/z: calcd for C19H20O [M]+ 264.1514; found 264.1510.

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HETEROCYCLES, Vol. 92, No. 4, 2016
6,8-Di(tert-butyl)-4-phenyl-2H-chromene (5h): Yellow oil; 1H NMR (300 MHz, CDCl3): δ = 7.36 (s,
5H), 7.23 (s, 1H), 6.92 (s, 1H), 5.87 (t, J = 3.9 Hz, 1H), 4.73 (d, J = 3.9 Hz, 2H), 1.42 (s, 9H), 1.21 (s,
9H); 13C NMR (75 MHz, CDCl3): δ = 151.0, 142.7, 139.1, 138.3, 137.1, 128.7, 128.2, 127.6, 124.0, 123.7,
121.1, 119.6, 64.0, 34.8, 34.4, 31.5, 30.0; IR (KBr): υmax = 1654, 1611, 1503, 1449, 1400 cm–1; HRMS
m/z: calcd for C23H28O [M]+ 320.2140; found 320.2146.
1
8-(tert-Butyl)-6-methyl-4-phenyl-2H-chromene (5i): Yellow oil; H NMR (300 MHz, CDCl3): δ =
7.33-7.31 (m, 5H), 6.99(d, J = 1.8 Hz, 1H), 6.69(d, J = 1.5 Hz, 1H), 5.81 (t, J = 3.9Hz, 1H), 4.67 (d, J =
3.9 Hz, 2H), 2.17 (s, 3H), 1.40 (s, 9H); 13C NMR (75 MHz, CDCl3): δ = 151.2, 139.1. 138.1, 137.9, 129.6,
128.8, 128.6, 128.4, 127.7, 127.5, 124.9, 124.5, 120.1, 64.1, 34.6, 30.0, 21.2; IR (KBr): υmax = 1653, 1612,
1452, 1401 cm–1; HRMS m/z: calcd for C20H22O [M]+ 278.1671; found 278.1679.
1
8-Isopropyl-5-methyl-4-phenyl-2H-chromene (5j): Yellow oil; H NMR (300 MHz, CDCl3): δ =
7.30-7.20 (m, 5H), 7.05 (d, J = 7.8 Hz, 1H), 6.70 (d, J = 8.1 Hz, 1H), 5.93 (t, J = 4.5 Hz, 1H), 4.53 (d, J =
4.8 Hz, 2H), 3.36-3.23 (m, 1H), 1.71 (s, 3H), 1.25 (d, J = 6.9 Hz, 6H); 13C NMR (75 MHz, CDCl3): δ
=153.6, 141.6, 139.1, 133.9, 133.1, 128.4, 127.6, 127.2, 125.8, 124.5, 123.6, 122.6, 64.2, 27.2, 22.9, 22.5;
IR (KBr): υmax = 1654, 1613, 1453, 1401, 1168, 1083 cm–1; HRMS m/z: calcd for C19H20O [M]+
264.1514; found 264.1505.
19
1
6-Methoxy-2H-chromene (5k) : Colorless oil; H NMR (300 MHz, CDCl3): δ = 6.76-6.61 (m, 2H),
6.54 (d, J = 2.4 Hz, 1H), 6.40 (d, J = 9.3 Hz, 1H), 5.81 (dt, J = 9.3, 4.2 Hz, 1H), 4.76 (dd, J = 4.2, 2.4 Hz,
2H), 3.75 (s, 3H). IR (NaCl): υmax = 2981, 2826, 1474, 1265, 1210, 1150 cm–1; HRMS m/z: calcd for
C10H10O2 [M]+ 162.0681; found 162.0670.
20
1
4-(3’,5’-Dimethoxyphenyl)-6-methyl-2H-chromene (5l) : Yellow oil; H NMR (300 MHz, CDCl3):
δ = 6.85 (d, J = 8.2 Hz, 1H), 6.80 (s, 1H), 6.74 (d, J = 8.0 Hz, 1H), 6.41 (s, 3H), 5.71 (t, J = 3.9 Hz, 1H),
4.70 (d, J = 4.0 Hz, 2H), 3.71 (s, 6H), 2.11 (s, 3H); IR (neat): υmax = 1606, 1490, 1454, 1420, 1351, 1220,
1204, 1152 cm–1; HRMS (APCI) m/z: calcd for C18H19O3 [M+H]+ 283.1334; found 283.1325.
1
4-(4’-Methoxy-2’-nitrophenyl)-6-methyl-2H-chromene (5m)20: Brown oil; H NMR (300 MHz,
CDCl3): δ = 7.50 (d, J = 2.7 Hz, 1H), 7.27 (d, J = 8.7 Hz, 1H), 7.16 (dd, J = 8.6 Hz, 2.7 Hz, 1H), 6.93 (d,
J = 8.1 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.37 (s, 1H), 5.66 (t, J = 3.9 Hz, 1H), 4.81 (m, 2H), 3.90 (s, 3H),
2.11 (s, 3H); IR (neat): υmax = 1622, 1530, 1490, 1341, 1269, 1224, 1125 cm–1; HRMS (ESI) m/z: calcd
for C17H15NNaO4 [M+Na]+ 320.0899; found 320.0889.
1
4-(4-Fluorophenyl)-6-methyl-2H-chromene (5n)20: Yellow oil; H NMR (300 MHz, CDCl3): δ =
7.40-7.28 (m, 2H), 7.15-7.11 (t, J = 8.7 Hz, 2H), 7.03-6.70 (dd, J = 8.1, 1.8 Hz, 1H), 6.86-6.81 (d, J = 8.1
Hz, 1H), 6.76 (d, J = 1.8 Hz, 1H), 5.77 (t, J = 4.2 Hz, 1H), 4.80 (d, J = 4.2 Hz, 2H), 2.20 (s, 3H); IR
(neat): υmax = 2836, 1731, 1509, 1481, 1346, 1297, 1173 cm–1; HRMS (APCI) m/z: calcd for C16H14FO

HETEROCYCLES, Vol. 92, No. 4, 2016
717
[M+H]+ 241.1029; found 241.1021.
8-Bromo-7-methoxy-4-(p-tolyl)-2H-chromene (5o)20: Yellow oil; 1H NMR (300 MHz, CDCl3): δ = 7.30
(m, 4H), 6.90 (d, J = 8.6 Hz, 1H), 6.40 (d, J = 8.6 Hz, 1H), 5.64 (t, J = 3.9 Hz, 1H), 4.96 (d, J = 3.9 Hz,
2H), 3.86 (s, 3H), 2.37 (s, 3H); IR (neat): υmax = 2960, 2843, 1601, 1480, 1456, 1348, 1272 cm–1;
HRMS (APCI) m/z: calcd for C17H16BrO2 [M+H]+ 331.0334; found 331.0322.
6-Methoxy-4-methyl-2H-chromene (5p)20: Yellow oil; 1H NMR (300 MHz, CDCl3): δ = 6.79–6.67 (m,
3H), 5.61 (dd, J = 3.6, 1.8 Hz, 1H), 4.68 (dd, J = 3.6, 1.8 Hz, 2H), 3.76 (s, 3H), 2.00 (dd, J = 3.3, 1.8 Hz,
3H); IR (neat): υmax = 2830, 1581, 1493 cm−1; HRMS m/z: calcd for C11H12O2 [M ]+ 176.0837; found
176.0828.
ACKNOWLEDGEMENTS
This work was supported by the Program for Changjiang Scholars and Innovative Research Team in
University (IRT13095) and the Natural Science Foundation of China (NSFC 21162032).
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