FeCl3-Mediated One-Pot Domino Reactions for the Synthesis of 9-Aryl/9-Arylethynyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones from Propargylic Amines/Diaryl Amines and 1,3-Cyclohexanediones

Article abstract of DOI:10.1021/acs.joc.6b00001

An efficient, environmentally friendly and one-pot route to new 9-aryl/9-arylethynyl-2,3,4,9-tetrahydro-1H-xanthen-1-one derivatives from inexpensive starting materials has been developed. This method proceeded by a domino nucleophilic-substitution/intram

Full text of DOI:10.1021/acs.joc.6b00001

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Article
FeCl3-mediated One-pot Domino Reactions for the Synthesis of
9-Aryl/9-Arylethynyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones from
Propargylic amines/Diaryl Amines and 1,3-Cyclohexanediones
Xinwei He, Jiajia Tao, Xiaoqian Hu, Hui Wang, and Yongjia Shang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00001 • Publication Date (Web): 15 Feb 2016
Downloaded from http://pubs.acs.org on February 20, 2016
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FeCl3-mediated One-pot Domino Reactions for the Synthesis of
9-Aryl/9-Arylethynyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones
from Propargylic amines/Diaryl Amines and
1,3-Cyclohexanediones
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Xinwei He,§ Jiajia Tao,§ Xiaoqian Hu, Hui Wang, Yongjia Shang*
The Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui
Laboratory of MoleculeꢀBased Materials, College of Chemistry and Materials Science,
Anhui Normal University, Wuhu, Anhui 241000, P. R. China
Corresponding Author: Prof. Y.J. Shang
Email: shyj@mail.ahnu.edu.cn
Fax: +86ꢀ553ꢀ5910126
Abstract Graphic
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Abstract: An efficient, environmentally friendly and oneꢀpot route to new
9ꢀaryl/9ꢀarylethynylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone derivatives from inexpensive
starting materials has been developed. This method proceeded by a domino nucleophilic
ꢀsubstitution/intramolecular cyclization/dehydration sequence of propargylic amines/diaryl
amines and 1,3ꢀcyclohexanediones under the promotion of FeCl3, which involved the
formation of two new σ (C−C and C−O) bonds in a single operation for the construction of
novel tetrahydroxanthene skeletons in 68ꢀ95% yields.
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INTRODUCTION
Xanthenes and their derivatives have attracted substantial research interest due to their
various biological activities and antibacterial,1 antioxidant,2 anticancer,3 antimalarial,4 and
antiꢀinflammatory properties.5 Furthermore, some of these compounds have been widely
used as lecodyes6 and pHꢀsensitive fluorescent materials for visualization of biomolecules7
and are utilized in laser technologies due to their unique photochemical and photophysical
properties.8 In particular, 9ꢀsubstitutedꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone derivatives
have been identified as orally active neuropeptide Y Y5 and C CR1 receptor antagonists.9
Conventional methods to produce tetrahydroꢀ1Hꢀxanthenꢀ1ꢀones include the tandem
Knoevenagel–Michael reaction of salicylaldehydes with dimedone using CeCl3,10
pꢀtoluenesulfonic acid,11 triethylbenzylammonium chloride,12 tetraꢀnꢀbutylammonium
fluoride,13 Zn[(L)proline]2,14 and ZnO nanoparticles15 as catalysts and copper(I)ꢀcatalyzed
intramolecular Oꢀarylation.16 Over the years, only a few methods have been available for
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the efficient synthesis of 2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀones.17 Consequently, the
development of an efficient, operationally simple, ecoꢀfriendly and practical method for the
synthesis of 9ꢀsubstitutedꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone derivatives is in high
demand.
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In recent years, iron(III) chloride has emerged as an efficient, cheap and environmentally
benign Lewis acid for a variety of domino reactions.18 Previously, we developed an efficient
synthetic approach to coumarins and polysubstituted pyridines using FeCl3ꢀcatalyzed
oneꢀpot cascade and multicomponent reactions.19 On the other hand, propargylic amines,
which are products of the threeꢀcomponent reaction of aldehydes, amines and alkynes
(A3ꢀcoupling), are versatile building blocks for the synthesis of Nꢀcontaining biologically
active compounds and are key intermediates for the synthesis of many natural products.20
Our research group has been working on the synthesis of βꢀalkynyl ketones from
propargylic amines using FeCl3 as a catalyst.21 As a continuation of our work to explore the
synthetic utility of FeCl3, we herein report a simple and efficient synthesis of
9ꢀsubstitutedꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀones by FeCl3ꢀmediated oneꢀpot domino
reactions of propargylic amines or diarylamines and 1,3ꢀcyclohexanediones (Scheme 1).
O
O
O
R4
R4
Our previous work
R1
Ar
FeCl3 (50 mol%)
MeCN, 80oC, 24 h
Ar
O
O
O
Ar
O
N
R1
OH
n = 0, 1
O
R3
R2
O
This work
R3
R2
R1
1. FeCl3 (1.0 equiv.)
MeCN, 90 oC, 8 h
2. TsOH (1.0 equiv.), 1 h
n = 0, 1
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Scheme
1.
Synthesis
of
βꢀalkynyl
ketones
and
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9
9ꢀaryl/arylethynylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀones by FeCl3ꢀmediated domino
reactions of propargylic amines and 1,3ꢀdiketones.
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RESULTS AND DISCUSSION
Initially,
2ꢀ(3ꢀphenylꢀ1ꢀ(piperidinꢀ1ꢀyl)propꢀ2ꢀynꢀ1ꢀyl)phenol
(1a)
and
cyclohexaneꢀ1,3ꢀdione (2a) served as model substrates for the optimization of the domino
reaction conditions; the results are presented in Table 1. The domino reaction proceeded in a
oneꢀpot twoꢀstep fashion as follows: the first step was promoted by a Lewis acid, whereas
the second step was promoted by the addition of a Brønsted acid. Lewis acids such as FeCl3,
Sc(OTf)3, Cu(OAc)2, CuI, AgNO3, and Pd(OAc)2 were examined first (Table 1, entries 1ꢀ6).
Of these, FeCl3 (1.0 equiv.) was found to be the best promoter, giving 3a in 85% yield
(Table 1, entry 6). Neither reducing the catalyst loading nor increasing the catalyst loading
increased the yield further (Table 1, entries 7, 8). Particularly, when 2 equiv. of FeCl3 was
used, the reaction system became very viscous and the reaction hardly took place (Table 1,
entry 8). Further screening of the solvents showed that acetonitrile yielded the best result
compared with H2O, toluene, THF, DMF, 1,4ꢀdioxane, ethanol, and methanol as shown in
Table S1 in the Supporting Information (SI) (Table S1, entries 9ꢀ15). In addition, the effects
of temperature and reaction time were also investigated (Table 1, entries 10, 11 and 12ꢀ14).
It was found that neither decreasing nor increasing the reaction temperature or time could
improve the yield. Therefore, the optimum reaction conditions for the transformation were
established as 1.0 equiv. of FeCl3, 8 h at 90 °C for the first step, followed by the addition of
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TsOH (1.0 equiv.) and stirring for another 1 h at 90 °C in CH3CN.
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Table 1. Optimization of the reaction conditions.a
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Entry Lewis acid (1.0 equiv.)
Solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
toluene
MeCN
MeCN
MeCN
MeCN
MeCN
Temp. (ºC)
Time (h)
Yield (%)
75
1
2
Sc(OTf)3
Cu(OAc)2
CuI
90
90
90
90
90
90
90
90
90
rt
8
8
trace
35
3
8
4
AgNO3
Pd(OAc)2
FeCl3
8
65
5
8
78
6
8
85
7 b
8 c
9
FeCl3
8
45
FeCl3
8
trace
60
FeCl3
8
10
11
12
13
14
FeCl3
24
8
trace
67
FeCl3
60
90
90
90
FeCl3
2
20
FeCl3
5
55
FeCl3
10
80
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a Reaction conditions: 2ꢀ(3ꢀphenylꢀ1ꢀ(piperidinꢀ1ꢀyl)propꢀ2ꢀynꢀ1ꢀyl) phenol 1a (1.0 mmol),
cyclohexaneꢀ1,3ꢀdione 2a (1.0 mmol), Lewis acid, solvent (5 mL); then TsOH (1.0 equiv.)
9
b
c
was added and stirred for another 1 h. 0.5 equiv. of FeCl3 was used. 2.0 equiv. of FeCl3
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was used.
Having optimized the reaction conditions, the substrate scope was examined with various
aromatic propargylic amines 1 and 1,3ꢀcyclohexanediones 2. The results are summarized in
Table 2. In most cases, the desired 9ꢀarylethynylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀones
were smoothly generated in 75ꢀ87% yields. Among the various propargylic amines 1
examined, the reaction showed good tolerance of the substituents on the Ar group of the
alkyne moiety, and 75ꢀ83% yields were obtained regardless of their electronic nature (Table
2, entries 2ꢀ4, 6, 8, 11). For substituents on the benzene ring of the phenol moiety, substrates
with a moderately electronꢀwithdrawing R1 group (e.g., F, Cl, Br) or a moderately
electronꢀdonating R1 (e.g., CH3) (Table 2, entries 5ꢀ9, 11) gave the desired products in
82ꢀ87% yields. However, the reaction failed to occur in cases of substrate 1j bearing a
strongly electronꢀwithdrawing group (ꢀNO2) (Table 2, entry 10), substrate 1l bearing a
strongly electronꢀdonating group (ꢀOCH3) (Table 2, entry 12) and substrate 1m bearing two
sterically demanding tertꢀbutyl groups at the orthoꢀ and paraꢀ positions of the hydroxyl of
propargylic amines (Table 2, entry 13). Different 1,3ꢀcyclohexanediones 2 were then
examined (entries 15ꢀ24). Compared with 2a, the desired products were obtained in lower
yields when R2 was a methyl group (2c) or when R2 and R3 were both methyl groups (2b).
The structure of the product 3e was unambiguously confirmed by Xꢀray crystallographic
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analysis as shown in Figure S1 in the Supporting Information (SI).
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In
contrast
to
our
previously
result,21
the
reaction
between
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2ꢀ(3ꢀphenylꢀ1ꢀ(piperidinꢀ1ꢀyl)propꢀ2ꢀynꢀ1ꢀyl)phenol (1a) and acetylacetone in the
optimized conditions only gave one product 2ꢀ(5ꢀoxoꢀ1ꢀphenylhexꢀ1ꢀynꢀ3ꢀyl)phenyl acetate,
which was detected by TLC after 8h. No other product was detected by TLC by adding
TsOH (1.0 equiv.) and increasing the reaction time.
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Table 2. FeCl3ꢀmediated oneꢀpot domino reaction for the formation of
9ꢀarylethynylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀones. a
Ar
Ar
O
1. FeCl3 (1.0 equiv.)
O
R1
MeCN, 90 oC, 8 h
+
R1
N
R4
R3
2. TsOH (1.0 equiv.), 1 h
O
R4
R3
OH
2
O
R2
1
3
R2
Entry
R1, R2, Ar
R3, R4
Product 3
Yield (%)
1
2
3
4
5
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8
1a (H, H, C6H5)
1b (H, H, 4ꢀCH3C6H4)
R3 = R4 = H (2a)
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75
78
87
82
85
83
3a
3b
3c
3d
3e
3f
2a
2a
2a
2a
2a
2a
2a
1c (H, H, 4ꢀCH3OC6H4)
1d (H, H, 4ꢀClC6H4 )
1e (Br, H, C6H5)
1f (Br, H, 4ꢀCH3C6H4)
1g (Cl, H, C6H5)
3g
3h
1h (Cl, H, 4ꢀCH3C6H4)
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1i (F, H, C6H5)
87
NR c
81
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2a
3i
-
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1j (NO2, H, C6H5)
1j (CH3, H, 4ꢀCH3C6H4)
1l (H, OCH3, C6H5)
1m (tertꢀbutyl, tertꢀbutyl, C6H5)
1a (H, H, C6H5)
2a
3j
-
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NR b
NR b
70
2a
2a
-
R3 = R4 = CH3 (2b)
3k
3l
1b (H, H, 4ꢀCH3C6H4)
1e (Br, H, C6H5)
2b
68
73
2b
3m
3n
3o
3p
3q
3r
3s
3t
3u
1f (Br, H, 4ꢀCH3C6H4)
1g (Cl, H, C6H5)
2b
76
78
2b
1h (Cl, H, 4ꢀCH3C6H4)
1i (F, H, C6H5)
2b
78
80
2b
1j (CH3, H, 4ꢀCH3C6H4)
1k (H, H, 4ꢀFC6H4)
1a (H, H, C6H5)
2b
78
70
2b
R2 = CH3, R3 = H (2c)
80
1b (H, H, 4ꢀCH3C6H4)
2c
73
a Reaction conditions: aromatic propargylic amines 1 (1.0 mmol), cyclic 1,3ꢀdiketones 2 (1.0
mmol), FeCl3 (1.0 mmol), CH3CN (5 mL), 90 °C, 8 h; then, 1.0 equiv. TsOH was added and
stirred for another 1 h. b No reaction.
To expand the scope of the present approach, we next subjected
2ꢀ(aryl(piperidinꢀ1ꢀyl)methyl)phenols 4, which are easily available by the Petasis boronic
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Mannich reaction of salicylaldehydes, phenylboronic acid and piperidine, 22 to the otherwise
identical reaction conditions as above. Pleasingly, the corresponding products
9ꢀarylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀones 5 were obtained in 78ꢀ95% yields, and the
results are summarized in Table 3. Likewise, various moderately electronꢀwithdrawing or
electronꢀdonating groups on the benzene ring of phenols, such as Cl, Br, and CH3, are
wellꢀtolerated in the reaction to afford the desired products in high yields (Table 3, entries
4ꢀ6, 10ꢀ12). Notably, unlike in the case of substrate 1, substrates with strongly an
electronꢀdonating group (ꢀOCH3) in the orthoꢀ and paraꢀ position (Table 2, entries 2, 3) or a
strongly electronꢀwithdrawing group (ꢀNO2) in the paraꢀ position (Table 2, entry 8) the
hydroxyl of 2ꢀ(aryl(piperidinꢀ1ꢀyl)methyl)phenols were also tolerated in the reaction to give
78ꢀ87% yields. The structure of product 5b was unambiguously confirmed by Xꢀray
crystallographic analysis as shown in Figure S2 in the Supporting Information (SI).
Table 3. FeCl3ꢀmediated oneꢀpot domino reaction for the formation of
9ꢀarylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀones. a
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Entry
R1, R5, R2, Ar
4a (H, H, H, C6H5)
R3, R4
Product 5
Yield (%)
1
2
3
R3 = R4 = H (2a)
95
85
87
5a
5b
5c
4b (H, H, OCH3, C6H5)
4c (H, OCH3, H, C6H5)
2a
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4d (CH3, H, H, C6H5)
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2a
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5e
5f
4e (Cl, H, H, C6H5)
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4f (Br, H, H, C6H5)
2a
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4g (Br, H, Br, C6H5)
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5i
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4h (NO2, H, H, C6H5)
4i (H, H, H, 4ꢀCH3C6H4)
4j (CH3, H, H, 4ꢀCH3C6H4)
4k (Cl, H, H, 4ꢀCH3C6H4)
4l (Br, H, H, 4ꢀCH3C6H4)
4m (Br, H, Br, 4ꢀCH3C6H4)
4a (H, H, H, C6H5)
2a
9
2a
10
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12
13
14
15
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2a
5j
2a
5k
5l
2a
2a
5m
5n
5o
5p
R3 = R4 = CH3 (2b)
4c (H, OCH3, H, 4ꢀCH3C6H4)
4k (Cl, H, H, 4ꢀCH3C6H4)
2b
2b
a Reaction conditions: aromatic propargylic amines 4 (1.0 mmol), cyclic 1,3ꢀdiketones 2
(1.0 mmol), FeCl3 (1.0 mmol), CH3CN (5 mL), 90 °C, 8 h, then 1.0 equiv. TsOH was added
and stirred for another 1 h.
Some control experiments were then carried out to gain some insight into the mechanism
of this reaction (Scheme 2). Terminating the reaction of 1a with 2b after the first step of the
reaction produced an intermediate 3k' in 70% yield (Scheme 2, eq. (1)). Under the reaction
conditions in Table 3, 3k' underwent dehydrative cyclization to give the final product 3k in
75% yield (Scheme 2, eq. (4)). In contrast, in the absence of either FeCl3 or TsOH, the
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cyclization step proceeded very poorly under otherwise identical reaction conditions
(Scheme 2, eq. (2)ꢀ(3)).
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Scheme 2. Control Experiments.
To further demonstrate the versatility of the present method, other propargylic amine
such as 2ꢀ(1ꢀ(dimethylamino)ꢀ3ꢀphenylpropꢀ2ꢀynꢀ1ꢀyl)phenol and propargylic alcohol such
as 2ꢀ(1ꢀhydroxyꢀ3ꢀphenylpropꢀ2ꢀynꢀ1ꢀyl)phenol, were also used in the FeCl3ꢀmeidated
oneꢀpot domino reaction under standard reaction conditions, but no desired product was
obtained (Scheme S1).
22
On the basis of previous studies
and the experimental results described above, a
plausible mechanism is proposed in Scheme 3. First, the Lewis acid FeCl3 would promote
the nucleophilic substitution reaction between A, the enolate form of 1,3ꢀcyclohexanedione
2a, and propargylic amine 1a by coordination to the basic amine moiety. The resultant
intermediate B could be readily converted to intermediate C via an intramolecular
hemiketalization and elimination of a proton in the presence of the Lewis acid. Finally, after
the loss of one molecule of H2O, the intermediate C is transformed to the desired product 3
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in the presence of both pꢀtoluenesulfonic acid and FeCl3.
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Ar
O
N
Cl3Fe
R1
O
O
H
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O
A
Ar
R1
HO
Lewis Acid
1
R3
R2
R3
R2
O
R3
R2
OH
OH
2
FeCl3
B
N
H
FeCl3
Ar
Ar
Ar
O
O
O
H
R1
TsOH
-H2O
R1
R1
R3
R2
R3
R2
R3
R2
O
O
O
3
OH
O
H
C
FeCl3
Scheme 3. Proposed mechanism for the formation of 9ꢀarylethynylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀ
xanthenꢀ1ꢀones via the oneꢀpot domino reactions.
CONCLUSION
In conclusion, a simple and efficient method for the synthesis of substituted
9ꢀaryl/arylethynylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀones from easily accessible propargylic
amines/diaryl amines and 1,3ꢀcyclohexanediones as starting materials has been developed.
The present method yielded the desired products in good to excellent yields (68ꢀ95%) and
offers several notable advantages such as the use of an inexpensive and ecoꢀfriendly Lewis
acid, the base/ligandꢀfree conditions, and the simple operation under open air, which add to
the practicality of this method for potential applications in organic synthesis and medicinal
chemistry.
Experimental Section
General comments
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Unless otherwise specified, all reagents and starting materials were purchased from
commercial sources and used as received, and the solvents were purified and dried using
standard procedures. The chromatography solvents were technical grade and distilled prior
to use. Flash chromatography was performed using 200ꢀ300 mesh silica gel with the
indicated solvent system according to standard techniques. Element analyses were
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performed on an Elementar Vario El III. The H and C NMR data were recorded on 300
MHz NMR spectrometers, unless otherwise specified. Chemical shifts (δ) in parts per
1
million are reported relative to the residual signals of chloroform (7.26 ppm for H and
77.16 ppm for 13C), and all 13C NMR were recorded with proton broadband decoupling and
indicated as 13C{1H}NMR. Multiplicities are described as s (singlet), d (doublet), t (triplet),
q (quartet), or m (multiplet), and the coupling constants (J) are reported in Hertz. HRMS
analysis with a quadrupole timeꢀofꢀflight mass spectrometer yielded ion mass/charge (m/z)
ratios in atomic mass units. IR spectra were measured as dry films (KBr), and the peaks are
reported in terms of wave number (cmꢀ1).
General
procedure
for
the
synthesis
of
9-(phenylethynyl)-2,3,4,9-tetrahydro-1H-xanthen-1-one (3a).
Anhydrous FeCl3 (1.0 mmol, 81 mg) was added to a stirred solution of aromatic
propargylic amine 1a (1.0 mmol, 306 mg), 1,3ꢀcyclohexanedione 2a (1.0 mmol, 112 mg) in
acetonitrile (5 mL). The mixture was heated at 90 °C for 8 h in an oil bath. Then,
pꢀtoluenesulfonic acid (1.0 mmol, 172 mg) was added, and the reaction system was stirred
at 90 °C for another 1 h. Upon completion of the reaction, the mixture was cooled to room
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temperature, diluted with CH2Cl2 (3 × 20 mL), and washed with water. The organic layers
were combined, dried over Na2SO4, filtered, and then evaporated in vacuum. The residue
was purified by flash column chromatography on silica gel with ethyl acetate and petroleum
ether as the eluting solvent to produce product 3a at a yield of 85%.
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9ꢀ(Phenylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (3a). Petroleum ether/ethyl
1
acetate 16:1, White solid; Yield 85% (255 mg, 0.85 mmol), mp 120ꢀ122 °C; H NMR
(CDCl3, 300 MHz) δ 7.44 (d, J = 7.5 Hz, 1H), 7.31ꢀ7.35 (m, 2H), 7.13ꢀ7.27 (m, 5H), 7.03 (d,
J = 8.1 Hz, 1H), 5.02 (s, 1H), 2.54ꢀ2.74 (m, 3H), 2.37ꢀ2.48 (m, 1H), 2.05ꢀ2.15 (m, 2H) ppm;
13C NMR (75 MHz, CDCl3) δ 196.6, 166.6, 148.8, 131.7, 130.0, 128.4, 127.9, 127.7, 125.2,
123.3, 121.5, 116.6, 110.9, 91.1, 80.3, 36.8, 27.9, 24.4, 20.3 ppm; IR (KBr) ν 2955, 2928,
2887, 1639, 1584, 1489, 1445, 1371, 1234, 1172, 1132, 993, 850, 758, 694 cmꢀ1; HRMS
(ESI) calcd for [C21H16O2+H]+ 301.1223, found 301.1228.
9ꢀ(pꢀTolylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (3b). Petroleum ether/ethyl
acetate 16:1, White solid; Yield 85% (266 mg, 0.85 mmol), mp 172ꢀ174 °C; 1H NMR
(CDCl3, 300 MHz) δ 7.46 (d, J = 7.5 Hz, 1H), 7.12ꢀ7.26 (m, 4H), 7.00ꢀ7.05 (m, 3H), 5.01 (s,
1H), 2.53ꢀ2.75 (m, 3H), 2.35ꢀ2.48 (m, 1H), 2.28 (s, 3H), 2.04ꢀ2.16 (m, 2H) ppm; 13C NMR
(75 MHz, CDCl3) δ 196.6, 166.6, 148.8, 137.7, 131.6, 130.0, 128.7, 128.4, 125.2,121.7,
120.2, 116.6, 111.0, 90.3, 80.4, 36.8, 27.8, 24.4, 21.4, 20.3, ppm; IR (KBr) ν 2957, 2895,
2864, 1647, 1582, 1487, 1452, 1371, 1236, 1173, 999, 812, 764 cmꢀ1; HRMS (ESI) calcd
for [C22H18O2+H]+ 315.1380, found 315.1385.
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9ꢀ((4ꢀMethoxyphenyl)ethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (3c). Petroleum
ether/ethyl acetate 16:1, White solid; Yield 75% (247 mg, 0.75 mmol), mp 160ꢀ162 °C; 1H
NMR (CDCl3, 300 MHz) δ 7.45 (d, J = 7.5 Hz, 2H), 7.22ꢀ7.30 (m, 3H), 7.13ꢀ7.19 (m, 1H),
7.03ꢀ7.06 (m, 1H), 6.70ꢀ6.77 (m, 2H), 5.01 (s, 1H), 3.77 (s, 3H), 2.56ꢀ2.75 (m, 4H),
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2.39ꢀ2.49 (m, 1H), 2.09ꢀ2.17 (m, 2H) ppm; C NMR (125 MHz, CDCl3) δ 197.0, 166.9,
159.6, 149.2, 133.5, 130.4, 128.7, 125.6, 122.2, 117.0, 115.9, 114.0, 111.5, 90.0, 80.6, 55.6,
37.2, 28.3, 24.8, 20.7 ppm; IR (KBr) ν 2957, 2837, 1647, 1603, 1582, 1566, 1508, 1454,
1371, 1284, 1169, 1132, 1034, 999, 831 cmꢀ1; HRMS (ESI) calcd for [C22H18O3+H]+
331.1333, found 331.1329.
9ꢀ((4ꢀChlorophenyl)ethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3d).
Petroleum
ether/ethyl acetate 16:1, White solid; Yield 78% (277 mg, 0.78 mmol), mp 185ꢀ187 °C; 1H
NMR (CDCl3, 300 MHz) δ 7.42 (d, J = 7.5 Hz, 1H), 7.14ꢀ7.27 (m, 6H), 7.03 (d, J = 7.5 Hz,
1H), 5.01 (s, 1H), 2.54ꢀ2.74 (m, 4H), 2.38ꢀ2.48 (m, 1H), 2.08ꢀ2.12 (m, 2H) ppm; 13C NMR
(75 MHz, CDCl3) δ 195.6, 165.8, 147.5, 133.4, 131.9, 128.9, 127.5, 127.2, 124.2, 121.1,
120.2, 115.7, 91.0, 80.2, 35.8, 26.8, 23.3, 19.2 ppm; IR (KBr) ν 2961, 2891, 1649, 1582,
1487, 1454, 1373, 1236, 1001, 841 cmꢀ1; HRMS (ESI) calcd for [C21H15O2Cl+Na]+
357.0658, found 357.0653.
7ꢀBromoꢀ9ꢀ(phenylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3e).
Petroleum
ether/ethyl acetate 16:1, White solid; Yield 87% (348 mg, 0.87 mmol), mp 185ꢀ187 °C; 1H
NMR (CDCl3, 300 MHz) δ 7.56 (d, J = 6.8 Hz, 1H), 7.33ꢀ7.37 (m, 3H), 7.20ꢀ7.25 (m, 3H),
6.92 (d, J = 8.1 Hz, 1H), 4.97 (s, 1H), 2.53ꢀ2.73 (m, 3H), 2.37ꢀ2.48 (m, 1H), 2.06ꢀ2.15 (m,
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2H) ppm; C NMR (75 MHz, CDCl3) δ 195.4, 165.4, 147.1, 131.7, 130.9, 130.6, 127.1,
122.7, 122.1, 117.6, 116.6, 109.8, 89.4, 80.0, 35.9, 26.9, 23.4, 19.3 ppm; IR (KBr) ν 2949,
2889, 2876, 1645, 1576, 1479, 1371, 1234, 1167, 1138, 997, 883, 810 cmꢀ1; HRMS (ESI)
calcd for [C21H15BrO2+Na]+ 401.0153, found 401.0147. Anal. Calcd for C21H15BrO2: C,
66.51; H, 3.99. Found: C, 66.25; H, 3.65.
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7ꢀBromoꢀ9ꢀ(pꢀtolylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3f).
Petroleum
1
ether/ethyl acetate 16:1, White solid; Yield 82% (339 mg, 0.82 mmol), mp 175ꢀ177 °C; H
NMR (CDCl3, 300 MHz) δ 7.57 (s, 1H), 7.35 (d, J = 7.2 Hz, 1H), 7.23 (d, J = 7.8 Hz, 2H),
7.02 (d, J = 7.8 Hz, 2H), 6.91 (d, J = 8.4 Hz, 1H), 4.96 (s, 1H), 2.54ꢀ2.68 (m, 4H), 2.42ꢀ2.48
13
(m, 1H), 2.29 (s, 3H), 2.07ꢀ2.15 (m, 2H) ppm; C NMR (75 MHz, CDCl3) δ 195.3, 165.2,
146.9, 136.9, 131.5, 130.6, 130.4, 127.7, 122.7, 118.8, 117.4, 116.4, 109.7, 88.5, 79.9, 35.7,
26.7, 23.2, 20.4, 19.2 ppm; IR (KBr) ν 2949, 1645, 1574, 1477, 1371, 1337, 1233, 1173,
1134, 997, 822 cmꢀ1; HRMS (ESI) calcd for [C22H17O2Br+Na]+ 415.0308, found 415.0304.
7ꢀChloroꢀ9ꢀ(phenylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3g).
Petroleum
ether/ethyl acetate 16:1, White solid; Yield 85% (283 mg, 0.85 mmol), mp 178ꢀ180°C; 1H
NMR (CDCl3, 300 MHz) δ 7.42 (s, 1H), 7.34ꢀ7.36 (m, 2H), 7.19ꢀ7.23 (m, 4H), 6.98 (d, J =
8.7 Hz, 1H), 4.97 (s, 1H), 2.56ꢀ2.73 (m, 4H), 2.38ꢀ2.48 (m, 1H), 2.08ꢀ2.12 (m, 2H) ppm;
13C NMR (75 MHz, CDCl3) δ 195.3, 165.3, 146.4, 130.7, 129.0, 128.5, 127.6, 127.0, 126.9,
122.1, 121.9, 117.1, 109.5, 89.2, 79.8, 35.7, 26.7, 23.3, 19.2 ppm; IR (KBr) ν 2947, 2889,
1645, 1483, 1373, 1234, 1171, 1136, 999, 808, 761 cmꢀ1; HRMS (ESI) calcd for
[C21H15O2Cl+H]+ 335.0838, found 335.0833.
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7ꢀChloroꢀ9ꢀ(pꢀtolylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3h).
Petroleum
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ether/ethyl acetate 16:1, White solid; Yield 83% (288 mg, 0.83 mmol), mp 159ꢀ161 °C;
1H NMR (CDCl3, 300 MHz) δ 7.42 (s, 1H), 7.17ꢀ7.25 (m, 3H), 6.96ꢀ7.04 (m, 3H), 4.96 (s,
1H), 2.54ꢀ2.72 (m, 4H), 2.39ꢀ2.47 (m, 1H), 2.28 (s, 3H), 2.07ꢀ2.13 (m, 2H), ppm; 13C NMR
(75 MHz, CDCl3) δ 195.3, 165.2, 146.4, 136.9, 130.6, 128.9, 128.6, 127.7, 127.5, 122.2,
118.9, 117.0, 109.6, 88.5, 79.9, 35.7, 26.7, 23.3, 20.4, 19.2 ppm; IR (KBr) ν 2963, 1647,
1578, 1481, 1372, 1261, 1333, 1096, 1024, 802 cmꢀ1; HRMS (ESI) calcd for
[C22H17O2Cl+H]+ 349.0995, found 349.0990.
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7ꢀFluoroꢀ9ꢀ(phenylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3i).
Petroleum
ether/ethyl acetate 16:1, White solid; Yield 87% (276 mg, 0.87 mmol), mp 115ꢀ117 °C; 1H
NMR (CDCl3, 300 MHz) δ 7.36 (d, J = 6.3 Hz, 2H), 7.15ꢀ7.24 (m, 4H), 6.92ꢀ7.05 (m, 2H),
5.00 (s, 1H), 2.57ꢀ2.73 (m, 3H), 2.38ꢀ2.49 (m, 1H), 2.08ꢀ2.12 (m, 2H) ppm; 13C NMR (125
MHz, CDCl3) δ 196.8, 166.9, 160.9 (1JCF = 243.2 Hz), 145.4, 132.1, 128.4 (3JCF = 10.6 Hz),
123.5, 118.5 (3JCF = 8.0 Hz), 116.4 (2JCF = 23.6 Hz), 116.0 (2JCF = 23.8 Hz), 110.5, 90.7,
81.2, 37.2, 28.2, 25.1, 20.7 ppm; IR (KBr) ν 2938, 2872, 1645, 1489, 1371, 1194, 999, 831,
758 cmꢀ1; HRMS (ESI) calcd for [C21H15O2F+H]+ 319.1134, found 319.1129.
7ꢀMethylꢀ9ꢀ(pꢀtolylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3j).
Petroleum
ether/ethyl acetate 16:1, White solid; Yield 81% (265 mg, 0.81 mmol), mp 114ꢀ116 °C; 1H
NMR (CDCl3, 300 MHz) δ 7.23 (d, J = 8.1 Hz, 3H), 7.01 (d, J = 7.8 Hz, 3H), 6.92 (d, J =
8.1 Hz, 1H), 4.96 (s, 1H), 2.54ꢀ2.69 (m, 4H), 2.37ꢀ2.48 (m, 1H), 2.33 (s, 3H), 2.29 (s, 3H),
13
2.07ꢀ2.11 (m, 2H) ppm; C NMR (125 MHz, CDCl3) δ 197.0, 167.1, 147.2, 138.1, 135.2,
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132.0, 130.5, 129.5, 129.4, 129.1, 121.7, 120.7, 116.7, 111.4, 90.9, 80.7, 37.3, 28.3, 24.8,
21.7, 21.2, 20.7 ppm; IR (KBr) ν 2963, 2922, 1643, 1562, 1487, 1261, 1229, 1016, 804 cmꢀ1;
HRMS (ESI) calcd for [C23H20O2+H]+ 329.1538, found 329.1536.
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3,3ꢀDimethylꢀ9ꢀ(phenylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (3k). Petroleum
ether/ethyl acetate 16:1, yellow oil; Yield 70% (229 mg, 0.70 mmol), 1H NMR (CDCl3, 300
MHz) δ 7.47 (d, J = 9.0 Hz, 1H), 7.15ꢀ7.32 (m, 7H), 7.05 (d, J = 6.0 Hz, 1H), 5.01 (s, 1H),
13
2.44ꢀ2.58 (m, 2H), 2.30ꢀ2.39 (m, 2H), 1.17 (s, 3H), 1.13 (s, 3H) ppm; C NMR (75 MHz,
CDCl3) δ 196.4, 164.9, 149.0, 131.7, 130.0, 128.4, 127.9, 127.7, 125.2, 123.3, 121.5, 116.7,
109.8, 90.8, 80.5, 50.7, 41.5, 32.2, 28.9, 27.6, 24.3 ppm; IR (KBr) ν 2959, 2928, 2852, 1697,
1653, 1487, 1375, 1232, 1172, 1024, 755, 692, 535 cmꢀ1; HRMS (ESI) calcd for
[C23H20O2+H]+ 329.1536, found 329.1531.
3,3ꢀDimethylꢀ9ꢀ(pꢀtolylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (3l). Petroleum
ether/ethyl acetate 16:1, yellow oil; Yield 68% (232 mg, 0.68 mmol), 1H NMR (CDCl3, 300
MHz) δ 7.44 (d, J = 7.8 Hz, 1H), 7.12ꢀ7.27 (m, 4H), 6.99ꢀ7.05 (m, 3H), 5.00 (s, 1H),
2.44ꢀ2.58 (m, 2H), 2.30ꢀ2.43 (m, 2H), 1.17 (s, 3H), 2.28 (s, 3H), 1.13 (s, 3H) ppm; 13C
NMR (75 MHz, CDCl3) δ 195.5, 163.8, 147.9, 136.7, 130.5, 129.0, 128.0, 127.7, 127.4,
124.4, 124.2, 120.6, 119.2, 115.7, 108.8, 89.0, 79.6, 49.6, 40.5, 31.1, 27.9, 26.5, 23.2, 20.3
ppm; IR (KBr) ν 2957, 2868, 1672, 1643, 1487, 1464, 1319, 1229, 1159, 814, 756 cmꢀ1;
HRMS (ESI) calcd for [C24H22O2+H]+ 343.1698, found 343.1693.
7ꢀBromoꢀ3,3ꢀdimethylꢀ9ꢀ(phenylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3m).
Petroleum ether/ethyl acetate 16:1, White solid; Yield 73% (296 mg, 0.73 mmol), mp
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133ꢀ135 °C; H NMR (CDCl3, 300 MHz) δ 7.57 (s, 1H), 7.31ꢀ7.36 (m, 3H), 7.21ꢀ7.25 (m,
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3H), 6.94 (d, J = 8.4 Hz, 1H), 4.95 (s, 1H), 2.30ꢀ2.57 (m, 4H), 1.16 (s, 3H), 1.12 (s, 3H)
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ppm; C NMR (75 MHz, CDCl3) δ 195.3, 163.7, 147.2, 131.7, 130.9, 130.6, 127.1, 122.7,
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122.1, 117.7, 116.6, 108.6, 89.1, 80.2, 49.8, 40.5, 31.3, 28.1, 26.6, 23.3 ppm; IR (KBr) ν
2963, 1651, 1477, 1371, 1261, 1231, 1173, 1098, 1016, 802 cmꢀ1; HRMS (ESI) calcd for
[C23H19BrO2+H]+ 407.0641, found 407.0644.
7ꢀBromoꢀ3,3ꢀdimethylꢀ9ꢀ(pꢀtolylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3n).
Petroleum ether/ethyl acetate 16:1, White solid; Yield 76% (319 mg, 0.76 mmol),
mp156ꢀ158 °C; 1H NMR (CDCl3, 300 MHz) δ 7.57 (s, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.24 (d,
J = 7.5 Hz, 2H), 7.05 (d, J = 7.8 Hz, 2H), 6.94 (d, J = 8.7 Hz, 1H), 4.95 (s, 1H), 2.36ꢀ2.57
(m, 4H), 2.29 (s, 3H), 1.16 (s, 1H), 1.13 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ 196.5,
164.9, 148.5, 138.3, 133.0, 132.0, 131.8, 129.1, 129.0, 124.2, 120.4, 118.9, 117.9, 110.1,
89.7, 81.6, 51.1, 41.8, 32.6, 32.5, 29.3, 29.2, 27.9, 24.6, 21.8 ppm; IR (KBr) ν 2955, 2868,
1645, 1572, 1476, 1371, 1236, 1169, 1028, 829 cmꢀ1; HRMS (ESI) calcd for
[C24H21O2Br+H]+ 421.0802, found 421.0798.
7ꢀChloroꢀ3,3ꢀdimethylꢀ9ꢀ(phenylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3o).
Petroleum ether/ethyl acetate 16:1, White solid; Yield 78% (282 mg, 0.78 mmol), mp
141ꢀ143 °C; 1H NMR (CDCl3, 300 MHz) δ 7.43 (s, 1H), 7.31ꢀ7.34 (m, 2H), 7.18ꢀ7.25 (m,
4H), 6.97 (d, J = 9.0 Hz, 1H), 4.96 (s, 1H), 2.30ꢀ2.56 (m, 4H), 1.16 (s, 3H), 1.12 (s, 3H)
13
ppm; C NMR (75 MHz, CDCl3) δ 195.1, 163.6, 146.5, 130.7, 129.0, 128.5, 127.6, 127.0,
126.9, 122.1, 122.0, 117.1, 108.4, 89.0, 80.0, 49.6, 40.3, 31.1, 27.9, 26.4, 23.3 ppm; IR
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(KBr) ν 2963, 2866, 1651, 1481, 1371, 1233, 1177, 1028, 1016, 820, 764 cmꢀ1; HRMS (ESI)
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calcd for [C23H19O2Cl+H]+ 363.1148, found 363.1146.
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7ꢀChloroꢀ3,3ꢀdimethylꢀ9ꢀ(pꢀtolylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3p).
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Petroleum ether/ethyl acetate 16:1, White solid; Yield 78% (293mg, 0.78 mmol), mp
152ꢀ154 °C; 1HNMR (CDCl3, 300 MHz) δ 7.42 (s, 1H), 7.17ꢀ7.25 (m, 3H), 6.96ꢀ7.04 (m,
3H), 4.94 (s, 1H), 2.35ꢀ2.57 (m, 4H), 2.29 (s, 3H), 1.16 (s, 3H), 1.13 (s, 3H) ppm; 13CNMR
(75 MHz, CDCl3) δ 195.2, 163.5, 146.5, 136.9, 130.6, 128.9, 128.5, 127.7, 127.5, 122.2,
118.9, 117.1, 108.5, 88.2, 80.1, 49.6, 40.3, 31.1, 27.9, 26.5, 23.2, 20.4 ppm; IR (KBr) ν
2955, 2870, 1645, 1576, 1508, 1479, 1373, 1236, 1172, 1028, 876, 831 cmꢀ1; HRMS (ESI)
calcd for [C24H21ClO2+H]+ 377.1309, found 377.1303.
7ꢀFluoroꢀ3,3ꢀdimethylꢀ9ꢀ(phenylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3q).
Petroleum ether/ethyl acetate 16:1, White solid; Yield 80% (276 mg, 0.80 mmol), mp
174ꢀ176 °C; 1H NMR (CDCl3, 300 MHz) δ 7.34 (s, 1H), 7.23ꢀ7.26 (m, 3H), 7.15 (d, J = 8.4
Hz, 1H), 6.92ꢀ7.05 (m, 2H), 4.98 (s, 1H), 2.31ꢀ2.58 (m, 4H), 1.17 (s, 3H), 1.14 (s, 3H) ppm;
13C NMR (125 MHz, CDCl3) δ 196.6, 165.1, 160.8 (1JCF = 233.2 Hz), 145.5, 132.1, 128.4
(3JCF = 11.7 Hz), 123.5 (3JCF = 7.1 Hz), 118.5, 116.5 (2JCF = 23.5 Hz), 116.1 (2JCF = 24.0
Hz), 109.4, 90.4, 81.4, 51.1, 41.9, 32.6, 29.3, 27.9, 25.0 ppm; IR (KBr) ν 2957, 2868, 1647,
1491, 1373, 1260, 1211, 1196, 1030, 918, 822 cmꢀ1; HRMS (ESI) calcd for [C23H19O2F+H]+
347.1142, found 347.1147.
3,3,7ꢀTrimethylꢀ9ꢀ(pꢀtolylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (3r). Petroleum
ether/ethyl acetate 16:1, White oil; Yield 78% (277 mg, 0.78 mmol), mp 134ꢀ136 °C; 1H
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NMR (CDCl3, 300 MHz) δ 7.23 (d, J = 7.8 Hz, 3H), 7.02 (d, J = 7.5 Hz, 3H), 6.94 (d, J =
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8.1 Hz, 1H), 4.95 (s, 1H), 2.35ꢀ2.50 (m, 4H), 2.32 (s, 3H), 2.28 (s, 3H), 1.16 (s, 3H), 1.12 (s,
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3H) ppm; C NMR (75 MHz, CDCl3) δ 196.4, 165.0, 146.9, 137.7, 134.8, 131.6, 130.1,
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129.1, 128.7, 125.5, 121.2, 120.3, 116.4, 109.8, 90.2, 80.5, 50.7, 41.5, 32.1, 28.9, 27.8, 27.5,
24.3, 21.4, 20.8 ppm; IR (KBr) ν 2949, 2864, 1647, 1591, 1508, 1494, 1373, 1231, 1207,
1026, 820 cmꢀ1; HRMS (ESI) calcd for [C25H24O2+H]+ 357.1853, found 357.1849.
9ꢀ((4ꢀFluorophenyl)ethynyl)ꢀ3,3ꢀdimethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3s).
Petroleum ether/ethyl acetate 16:1, White solid; Yield 70% (257 mg, 0.70 mmol), mp
103ꢀ105 °C; 1H NMR (CDCl3, 300 MHz) δ 7.44 (d, J = 7.2 Hz, 1H), 7.24ꢀ7.33 (m, 3H),
7.15ꢀ7.20 (m, 1H), 7.04 (d, J = 8.1 Hz, 1H), 6.87ꢀ6.95 (m, 2H), 4.99 (s, 1H), 2.32ꢀ2.60 (m,
4H), 1.18 (s, 3H), 1.14 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ 196.8, 165.3, 163.5
(1JCF = 246.7 Hz), 149.3, 134.0 (3JCF = 7.8 Hz), 130.3, 128.9, 125.7, 119.8, 117.2, 115.7
(2JCF = 21.3 Hz), 110.1, 90.9, 79.9, 51.1, 41.9, 32.6, 29.3, 28.0, 24.7 ppm; IR (KBr) ν 2957,
2868, 1643, 1582, 1506, 1377, 1233, 1148, 1034, 1015, 835 cmꢀ1; HRMS (ESI) calcd for
[C23H19O2F+Na]+ 369.1266, found 369.1261.
3ꢀMethylꢀ9ꢀ(phenylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3t).
Petroleum
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ether/ethyl acetate 16:1, White solid; Yield 91% (285 mg, 0.91 mmol), mp 134ꢀ136 °C; H
NMR (CDCl3, 300 MHz) δ 7.47 (d, J = 7.5 Hz, 1H), 7.31ꢀ7.35 (m, 2H), 7.13ꢀ7.28 (m, 5H),
7.02ꢀ7.06 (m, 1H), 5.00 (s, 1H), 2.07ꢀ2.72 (m, 5H), 1.12 (t, J = 5.7 Hz, 3H) ppm; 13C NMR
(75 MHz, CDCl3) δ 196.6, 166.3, 165.6, 148.9, 148.8, 131.7, 130.0, 128.5, 128.4, 128.3,
128.0, 127.8, 125.3, 123.3, 121.6, 121.3, 116.7, 110.6, 110.3, 91.1, 80.4, 45.1, 35.9, 28.5,
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27.7, 24.5, 20.8 ppm; IR (KBr) ν 2957, 2897, 1638, 1582, 1487, 1456, 1379, 1231, 1165,
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1132, 1018, 754 cmꢀ1; HRMS (ESI) calcd for [C22H18O2+H]+ 315.1380, found 315.1385.
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3ꢀMethylꢀ9ꢀ(pꢀtolylethynyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(3u).
Petroleum
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ether/ethyl acetate 16:1, White solid; Yield 73% (289 mg, 0.73 mmol), mp 120ꢀ122 °C; 1H
NMR (CDCl3, 300 MHz) δ 7.47 (d, J = 7.5 Hz, 1H), 7.12ꢀ7.26 (m, 4H), 6.96ꢀ7.05 (m, 3H),
4.99 (s, 1H), 2.37ꢀ2.72 (m, 4H), 2.35 (s, 3H), 2.07ꢀ2.34 (m, 1H), 1.12 (t, J = 6.0 Hz, 3H)
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ppm; C NMR (75 MHz, CDCl3) δ 195.7, 165.4, 164.6, 148.0, 136.8, 130.7, 129.2, 128.2,
127.8, 127.5, 124.6, 124.3, 120.9, 120.6, 119.4, 115.8, 109.9, 109.5, 89.5, 79.6, 44.3, 35.1,
27.6, 26.8, 23.6, 20.5, 20.0 ppm; IR (KBr) ν 2949, 2918, 2870, 1668, 1651, 1580, 1487,
1456, 1342, 1234, 1171, 1018, 889, 812, 762 cmꢀ1; HRMS (ESI) calcd for [C23H20O2+H]+
329.1536, found 329.1535.
9ꢀPhenylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5a). Petroleum ether/ethyl acetate 8:1,
White solid; Yield 95% (262 mg, 0.95 mmol), mp 122ꢀ123 °C; 1H NMR (CDCl3, 300 MHz)
δ 7.02ꢀ7.25 (m, 9H), 5.06 (s, 1H), 2.59ꢀ2.76 (m, 2H), 2.29ꢀ2.47 (m, 2H), 1.97ꢀ2.10 (m, 2H)
ppm; 13C NMR (125 MHz, CDCl3) δ 197.4, 166.7, 148.8, 146.6, 130.5, 128.8, 128.3, 128.0,
126.8, 125.8, 125.5, 116.9, 115.1, 38.2, 37.4, 28.3, 20.8 ppm; IR (KBr) ν 2947, 2364, 1653,
1636, 1486, 1374, 1236, 1224, 1171, 991, 768, 712, 528, 482cmꢀ1; HRMS (ESI) calcd for
[C19H16O2+H]+ 277.1223, found 277.1220.
5ꢀMethoxyꢀ9ꢀphenylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5b). Petroleum ether/ethyl
acetate 8:1, White solid; Yield 85% (260mg, 0.85 mmol), mp 156ꢀ157 °C; 1H NMR (CDCl3,
300 MHz) δ 7.11ꢀ7.26 (m, 5H), 6.96 (t, J = 8.1 Hz, 1H), 6.76(d, J = 8.1 Hz,1H), 6.69(d, J =
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7.8 Hz, 1H), 5.04 (s, 1H), 3.92 (s, 3H), 2.64ꢀ2.87 (m, 2H), 2.35ꢀ2.45 (m, 2H), 2.00ꢀ2.06 (m,
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2H); C NMR (125 MHz, CDCl3) δ 197.4, 166.4, 148.2, 146.4,139.5, 128.8, 128.3, 126.8,
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126.8, 125.2, 121.9, 115.1, 110.2, 56.5, 38.2, 37.4, 28.3, 20.8 ppm; IR (KBr) ν 3007, 2944,
2891, 1637, 1610, 1581, 1484, 1385, 1327, 1276, 1227, 1186, 1097, 765, 731, 537cmꢀ1;
HRMS (ESI) calcd for [C20H18O3+H]+ 307.1329, found 307.1325. Anal. Calcd for C20H18O3:
C, 78.41; H, 5.92. Found: C, 78.74; H, 5.63.
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6ꢀMethoxyꢀ9ꢀphenylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5c). Petroleum ether/ethyl
acetate 8:1, White solid; Yield 87% (266mg, 0.87 mmol), mp 144ꢀ145 °C; 1H NMR (CDCl3,
300 MHz) δ 7.20ꢀ7.26 (m, 4H), 7.08ꢀ7.18 (m, 1H), 6.97ꢀ7.00 (m, 1H), 6.59ꢀ6.62 (m, 2H),
4.99 (s, 1H), 3.78 (s, 3H), 2.63ꢀ2.75 (m, 2H), 2.34ꢀ2.41 (m, 2H), 1.98ꢀ2.08 (m, 2H) ppm;
13C NMR (125 MHz, CDCl3) δ 197.4, 166.4, 159.4, 146.8, 131.0, 128.8, 128.2, 126.6, 117.9,
115.5, 112.1, 101.8, 55.9, 37.6, 37.4, 28.3, 20.8 ppm; IR (KBr) ν 2964, 2934, 1637, 1508,
1370, 1288, 1218, 1108, 1031, 995, 850, 794, 695, 540, 503 cmꢀ1; HRMS (ESI) calcd for
[C20H18O3+H]+ 307.1329, found 307.1326.
7ꢀMethylꢀ9ꢀphenylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5d). Petroleum ether/ethyl
acetate 8:1, Gray solid; Yield 92% (266 mg, 0.92 mmol), mp 141ꢀ142 °C; 1H NMR(CDCl3,
300MHz) δ 7.21ꢀ7.25 (m, 3H), 7.10ꢀ7.14 (m, 1H), 6.96 (s, 2H), 6.88 (s, 1H), 5.00 (s, 1H),
2.62ꢀ2.74 (m, 2H), 2.33ꢀ2.43 (m, 2H), 2.20 (s, 3H), 1.98ꢀ2.06 (m, 2H) ppm; 13C NMR (125
MHz, CDCl3) δ 197.3, 166.7, 147.9, 146.7, 135.0, 130.6, 128.8, 128.7, 128.3, 126.7, 125.4,
116.5, 115.1, 38.3, 37.4, 28.3, 21.1, 20.8 ppm; IR (KBr) ν 2886, 1642, 1588, 1494, 1455,
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1375, 1218, 1126, 997, 920, 813, 750, 717, 617, 528 cmꢀ1; HRMS (ESI) calcd for
[C20H18O2+H]+ 291.1380, found 291.1384.
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acetate 8:1, White solid; Yield 82% (254 mg, 0.82 mmol), mp 170ꢀ172 °C; H NMR
(CDCl3, 300 MHz) δ 7.15ꢀ7.24 (m, 5H), 7.00ꢀ7.12 (m, 3H), 5.00 (s, 1H), 2.63ꢀ2.72 (m, 2H),
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2.35ꢀ2.41 (m, 2H), 2.02ꢀ2.06 (m, 2H) ppm; C NMR (125 MHz, CDCl3) δ 197.1, 166.3,
148.4, 145.9, 130.2, 130.1, 129.0, 128.3, 128.2, 127.4, 127.1, 118.3, 114.7, 38.3, 37.3, 28.2,
20.7 ppm; IR (KBr) ν 3075, 2964, 2896, 1668, 1649, 1576, 1477, 1378, 1230, 1177, 1133,
999, 927, 845, 699, 593, 528 cmꢀ1; HRMS (ESI) calcd for [C19H15ClO2+H]+ 311.0833,
found 311.0830.
7ꢀBromoꢀ9ꢀphenylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5f). Petroleum ether/ethyl
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acetate 8:1, White solid; Yield 85% (300 mg, 0.85 mmol), mp 183ꢀ184 °C; H NMR
(CDCl3, 300 MHz) δ 7.15ꢀ7.29 (m, 7H), 6.96 (d, J = 8.7 Hz, 1H), 5.00 (s, 1H), 2.57ꢀ2.77 (m,
2H), 2.29ꢀ2.41 (m, 2H), 1.97ꢀ2.11 (m, 2H) ppm; 13C NMR (125 MHz, CDCl3) δ 197.1,
166.3, 148.9, 145.9, 133.1, 131.1, 129.0, 128.3, 127.9, 127.1, 118.7, 117.8, 114.8, 38.2, 37.3,
28.2, 20.7 ppm; IR (KBr) ν 3084, 2964, 2920, 2867, 1666, 1644, 1569, 1472, 1453, 1373,
1334, 1232, 1181, 1167, 1128, 1068, 997, 925, 886, 828, 693, 593, 525 cmꢀ1; HRMS (ESI)
calcd for [C19H15BrO2+H]+ 355.0328, found 355.0326. Anal. Calcd for C19H15BrO2: C,
64.14; H, 4.26. Found: C, 64.19; H, 4.38.
5,7ꢀDibromoꢀ9ꢀphenylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5g). Petroleum ether/ethyl
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acetate 8:1, White solid; Yield 83% (358 mg, 0.83 mmol), mp 173ꢀ174 °C; H NMR
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(CDCl3, 300 MHz) δ 7.55 (s, 1H), 7.17ꢀ7.26 (m, 6H), 5.00 (s, 1H), 2.70ꢀ2.85 (m, 2H),
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2.36ꢀ2.42 (m, 2H), 2.00ꢀ2.11 (m, 2H) ppm; C NMR (125 MHz, CDCl3) δ 196.9, 166.1,
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146.1, 145.3, 134.2, 132.2, 129.1, 128.2, 127.3, 117.6, 115.2, 112.0, 38.7, 37.3, 28.0, 20.7
ppm; IR (KBr) ν 3070, 2954, 1666, 1651, 1588, 1554, 1491, 1448, 1375, 1235, 1177, 1002,
862, 729, 678, 625, 537, 482 cmꢀ1; HRMS (ESI) calcd for [C19H14Br2O2+H]+ 432.9433,
found 432.9430.
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7ꢀNitroꢀ9ꢀphenylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5h). Petroleum ether/ethyl
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acetate 8:1, Yellow solid; Yield 78% (250 mg, 0.78 mmol), mp 242ꢀ243 °C; H NMR
(CDCl3, 300 MHz) δ 8.02ꢀ8.09 (m, 2H), 7.15ꢀ7.34 (m, 6H), 5.09 (s, 1H), 2.69ꢀ2.82 (m, 2H),
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2.38ꢀ2.49 (m, 2H), 2.03ꢀ2.14 (m, 2H) ppm; C NMR (125 MHz, CDCl3) δ 196.8, 165.6,
153.9, 145.2, 145.0, 129.2, 128.2, 127.5, 126.6, 123.9, 117.9, 114.9, 38.3, 37.3, 28.0, 20.7
ppm; IR (KBr) ν 3099, 3056, 2944, 1673, 1654, 1576, 1518, 1450, 1370, 1341, 1240, 1277,
1126, 997, 922, 842, 702, 530 cmꢀ1; HRMS (ESI) calcd for [C19H15NO4+H]+ 322.1074,
found 322.1072.
9ꢀ(pꢀTolyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5i). Petroleum ether/ethyl acetate 8:1,
1
Yellow solid; Yield 90% (261 mg, 0.90 mmol), mp 120ꢀ121 °C; H NMR (CDCl3, 300
MHz) δ 7.05ꢀ7.17 (m, 5H), 6.99ꢀ7.02 (m, 3H), 5.01 (s, 1H), 2.59ꢀ2.74 (m, 2H), 2.31ꢀ2.43
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(m, 2H), 2.24 (s, 3H), 1.96ꢀ2.07 (m, 2H) ppm; C NMR(125 MHz, CDCl3) δ 197.4, 166.5,
149.8, 143.8, 136.3, 130.4, 129.5, 128.2, 127.9, 126.0, 125.4, 116.8, 115.3, 37.8, 37.4, 28.3,
21.4, 20.8 ppm; IR (KBr) ν 2944, 2900, 2866, 1639, 1949, 1918, 1806, 1637, 1610, 1578,
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1508, 1487, 1455, 1378, 1336, 1252, 1240, 1179, 1128, 995, 867, 838, 825, 755, 637, 620,
598 cmꢀ1; HRMS (ESI) calcd for [C20H18O2+H]+ 291.1380, found 291.1385.
8
9
7ꢀMethylꢀ9ꢀ(pꢀtolyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5j). Petroleum ether/ethyl
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acetate 8:1, White solid; Yield 88% (267 mg, 0.88 mmol), mp 127ꢀ128 °C; H NMR
(CDCl3, 300 MHz) δ 7.02ꢀ7.13 (m, 4H), 6.95 (s, 2H), 6.88(s, 1H), 4.97 (s, 1H), 2.61ꢀ2.69
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(m, 2H), 2.33ꢀ2.38 (m, 2H), 2.25 (s, 3H), 2.20 (s, 3H), 2.00ꢀ2.04 (m, 2H) ppm; C NMR
(75 MHz, CDCl3) δ 197.5, 166.7, 147.8, 143.9, 136.2, 135.0, 130.6, 129.5, 128.6, 128.2,
125.6, 116.5, 115.2, 37.8, 37.4, 28.3, 21.4, 21.2, 20.8 ppm; IR (KBr) ν 2959, 2867, 1654,
1634, 1586, 1491, 1375, 1249, 1213, 1126, 995, 823, 779, 615, 520, 496 cmꢀ1; HRMS (ESI)
calcd for [C21H20O2+H]+ 305.1536, found 305.1531.
7ꢀChloroꢀ9ꢀ(pꢀtolyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5k). Petroleum ether/ethyl
1
acetate 8:1, White solid; Yield 80% (259 mg, 0.80 mmol), mp 172ꢀ173 °C; H NMR
(CDCl3, 300 MHz) δ 6.99ꢀ7.13 (m, 7H), 4.96 (s, 1H), 2.59ꢀ2.75 (m, 2H), 2.33ꢀ2.44 (m,
2H), 2.26 (s, 3H), 1.97ꢀ2.10 (m, 2H) ppm; 13C NMR (125 MHz, CDCl3) δ 197.2, 166.2,
148.3, 143.1, 136.7, 130.2, 130.1, 129.7, 128.1, 128.0, 127.7, 118.3, 114.8 , 37.9, 37.3, 28.2,
21.4, 20.7 ppm; IR (KBr) ν 2954, 1665, 1644, 1576, 1508, 1477, 1375, 1227, 1186, 1174,
1128, 999, 917, 840, 823, 726, 670, 615, 525, 508, 453 cmꢀ1; HRMS (ESI) calcd for
[C20H17ClO2+H]+ 325.0990, found 325.0989.
7ꢀBromoꢀ9ꢀ(pꢀtolyl)ꢀꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5l). Petroleum ether/ethyl
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acetate 8:1, White solid; Yield 80% (294 mg, 0.80 mmol), mp 184ꢀ186 °C; H NMR
(CDCl3, 300 MHz) δ 7.18ꢀ7.27 (m, 2H), 7.03ꢀ7.14 (m, 4H), 6.95 (d, J = 8.7 Hz, 1H), 4.96
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(s,1H), 2.62ꢀ2.70 (m, 2H), 2.32ꢀ2.40 (m, 2H), 2.26 (s, 3H), 1.96ꢀ2.07 (m, 2H) ppm; 13C
NMR (125 MHz, CDCl3) δ 197.2, 166.2, 148.3, 143.1, 136.7, 130.2, 130.1, 129.7, 128.1,
128.0, 127.7, 118.3, 114.8 , 37.9, 37.3, 28.2, 21.4, 20.7 ppm; IR (KBr) ν 2959, 2920, 1666,
1644, 1569, 1472, 1375, 1232, 1179, 1167, 1128, 999, 915, 830, 724, 605, 547, 528 cmꢀ1;
HRMS (ESI) calcd for [C20H17BrO2+H]+ 369.0485, found 369.0480.
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5,7ꢀDibromoꢀ9ꢀ(pꢀtolyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone
(5m).
Petroleum
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ether/ethyl acetate 8:1, White solid; Yield 78% (347 mg, 0.78 mmol), mp 148ꢀ149 °C; H
NMR (CDCl3, 300 MHz) δ 7.54 (s, 1H), 7.05ꢀ7.17 (m, 5H), 4.97 (s,1H), 2.70ꢀ2.85 (m, 2H),
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2.32ꢀ2.46 (m, 2H), 2.27 (s, 3H), 2.02ꢀ2.08 (m, 2H) ppm; C NMR (125 MHz, CDCl3) δ
196.9, 166.0, 146.1, 142.5, 137.0, 134.1, 132.2, 129.8, 129.4, 128.1, 117.6, 115.3 , 112.0,
38.3, 37.3, 28.0, 21.4, 20.7 ppm; IR (KBr) ν 3070, 2944, 2886, 1671, 1651, 1557, 1511,
1450, 1368, 1242, 1181, 999, 830, 811, 620, 532, 506 cmꢀ1; HRMS (ESI) calcd for
[C20H16Br2O2+H]+ 446.9590, found 446.9585.
3,3ꢀDimethylꢀ9ꢀphenyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5n). Petroleum ether/ethyl
acetate 8:1, White solid; Yield 92% (280 mg, 0.92 mmol), mp 141ꢀ142°C; 1H NMR(CDCl3,
300MHz) δ 7.05ꢀ7.25 (m, 9H), 5.03 (s,1H), 2.55 (s, 2H), 2.25 (m, 2H), 1.12 (s, 3H), 1.03 (s,
13
3H) ppm; C NMR (125 MHz, CDCl3) δ 197.2, 164.9, 149.8, 146.5, 130.5, 128.8, 128.2,
128.0, 126.7, 125.8, 125.4, 116.9 , 113.9, 51.2, 42.0, 38.3, 32.5, 30.0, 27.8ppm; IR (KBr) ν
2964, 2935, 1664, 1644, 1579, 1487, 1453, 1373, 1237, 1012, 765, 699, 542 cmꢀ1; HRMS
(ESI) calcd for [C21H20O2+H]+ 305.1536, found 305.1531.
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6ꢀMethoxyꢀ3,3ꢀdimethylꢀ9ꢀ(pꢀtolyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5o). Petroleum
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ether/ethyl acetate 8:1, White solid; Yield 82% (285 mg, 0.82 mmol), mp 132ꢀ133 °C; H
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NMR (CDCl3, 300MHz) δ 6.97ꢀ7.22 (m, 5H), 6.61 (m, 2H), 4.96 (s, 1H), 3.77 (s, 3H), 2.54
(s, 2H), 2.24 (m, 2H), 1.12 (s, 3H), 1.03 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ 197.2,
164.7, 159.4, 150.4, 146,7, 131.0, 128.7, 128.2, 126.6, 117.9, 114.2, 112.1 , 101.9, 55.8,
51.2, 42.0, 37.8, 32.5, 29.6, 27.8 ppm; IR (KBr) ν 2959, 1644, 1508, 1373, 1286, 1218,
1165, 1143, 1116, 1036, 867, 784, 697, 557, 525 cmꢀ1; HRMS (ESI) calcd for
[C23H24O3+H]+ 349.1798, found 349.1794.
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7ꢀChloroꢀ3,3ꢀdimethylꢀ9ꢀ(pꢀtolyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀxanthenꢀ1ꢀone (5p). Petroleum
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ether/ethyl acetate 8:1, White solid; Yield 80% (281 mg, 0.80 mmol), mp 146ꢀ147 °C; H
NMR (CDCl3, 300 MHz) δ 6.98ꢀ7.11 (m, 7H), 4.93 (s, 1H), 2.54 (s, 2H), 2.17ꢀ2.30 (m, 5H),
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1.12 (s, 3H), 1.03 (s, 3H) ppm; C NMR (125 MHz, CDCl3) δ 197.0, 164.5, 148.3, 143.0,
136.6, 130.2, 130.1, 129.7, 128.1, 128.0, 118.3, 113.5 , 51.2, 41.8, 38.0, 32.6, 29.7, 27.8,
21.4 ppm; IR (KBr) ν 2959, 1671, 1651, 1482, 1472, 1373, 1230, 1172, 1123, 1019, 881,
828, 724, 654, 593, 540, 518 cmꢀ1; HRMS (ESI) calcd for [C22H21ClO2+H]+ 353.1300,
found 353.1303.
2ꢀ(1ꢀ(2ꢀHydroxyphenyl)ꢀ3ꢀphenylpropꢀ2ꢀynꢀ1ꢀyl)ꢀ5,5ꢀdimethylcyclohexaneꢀ1,3ꢀdione
(3k'). Petroleum ether/ethyl acetate 8:1, Yellow oil, Yield 70% (242mg, 0.70 mmol), 1H
NMR (CDCl3, 300 MHz) δ 9.02 (s, 1H), 7.59ꢀ7.61 (m, 2H), 7.35ꢀ7.40 (m, 2H), 7.16ꢀ7.28
(m, 3H), 7.04ꢀ7.06 (m, 1H), 6.89ꢀ6.94 (m, 1H), 5.70 (d, J = 1.8 Hz, 1H), 5.30 (s, 1H), 2.61
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(s, 2H), 2.32 (s, 2H), 1.17 (s, 3H), 1.10 (s, 3H) ppm; C NMR (75 MHz, CDCl3) δ 196.6,
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175.6, 157.3, 155.2, 134.4, 130.4, 129.1, 129.0, 128.9, 128.1, 127.5, 122.2, 120.4, 118.3,
108.5, 50.6, 43.3, 35.1, 29.1, 29.0 ppm; IR (KBr) ν 3448, 2964, 1680, 1627, 1593, 1455,
1419, 1402, 1278, 1227, 1024, 884, 755, 690 cmꢀ1; HRMS (ESI) calcd for [C23H22O3+H]+
347.1642, found 347.1641.
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ASSOCIATED CONTENT
AUTHOR INFORMATION
Corresponding Author
*Tel:+86ꢀ553ꢀ5910129. Fax: +86ꢀ553ꢀ5910126. Eꢀmail: shyj@mail.ahnu.edu.cn
Author Contributions
§X. H. and J. T. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The work was partially supported by the National Natural Science Foundation of China (No.
21172001, 21372008), the Anhui Provincial Natural Science Foundation (No.
1308085QB39), and the Special and Excellent Research Fund of Anhui Normal University.
Supporting Information
Spectral data for all compounds and crystallographic data of compound 3e and 5b. This
material is available free of charge via the Internet at http://pubs.acs.org.
REFERENCES
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