Syntheses of 12H-benzo[a]xanthen-12-ones and benzo[a]acridin-12(7H)-ones through Au(i)-catalyzed Michael addition/6-endo-trig cyclization/aromatization cascade annulation

Article abstract of DOI:10.1039/C8OB01684D

A multifaceted gold(i)-catalyzed aromaticity-driven double 6-endo cascade cyclization strategy to synthesize both 12H-benzo[a]xanthen-12-ones and benzo[a]acridin-12(7H)-ones, whose core motifs xanthone and acridone both exist as important scaffolds in an

Full text of DOI:10.1039/C8OB01684D

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Organic &
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Zhang, Y. Li, X. Peng, J. Fu, J. Guo, C. Jiang, F. Xie, B. Lin, Y. Liu and M. Cheng, Org. Biomol. Chem., 2018,
DOI: 10.1039/C8OB01684D.
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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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DOI: 10.1039/C8OB01684D
Journal Name
ARTICLE
Syntheses of 12H-Benzo[a]xanthen-12-ones and Benzo[a]acridin-
2(7H)-ones through Au(I)-Catalyzed Michael Addition/6-Endo-
Trig Cyclization/Aromatization Cascade Annulation
1
Received 00th January 20xx,
Accepted 00th January 20xx
[
a,b]
[a,b,c]
[a,b,c]
[a,b]
[a,b,c]
DOI: 10.1039/x0xx00000x
Zhiling Xiong,
Xinhang Zhang,
Yangming Li,
Xiaoshi Peng,
Jiayue Fu,
and Maosheng Cheng*
Jiajia
[a,b]
[
a,b,c]
[a,b]
[a,b]
[a,b]
[a,b,c]
Guo,
Fukai Xie, Chongguo Jiang, Bin Lin, Yongxiang Liu,*
www.rsc.org/
A multifaced gold(I)-catalyzed aromaticity-drived double 6-endo cascade cyclization strategy to synthesize both 12H-
benzo[a]xanthen-12-ones and benzo[a]acridin-12(7H)-ones, whose core motifs xanthone and acridone both exist as
important scaffolds in immense number of bioactive compounds, was developed. The scopes of this strategy were
examined by using a batch of synthetic 1,3-diphenylprop-2-yn-1-one substrates. To probe the mechanism of this
cyclization a control experiment in capturing of intermediate was proceeded. Thus, a putative mechanism was given
according to this experiment and previous studies.
[3f]
Larock, where xanthones and acridones were generated in only
one methodology, and our proceeding work on gold(I)-catalyzed
cycloisomerization of 1,5-enynes with electron-rich alkenes to
synthesize benzene ring, a gold(I)-catalyzed Michael addition /6-
endo-trig cyclization/aromatization cascade strategy based on 1,3-
diphenylprop-2-yn-1-one substrates was proposed to synthesize
benzoxanthones and benzoacridones (Scheme 2). This strategy can
get access to both xanthone and acridone derivatives with ease.
Introduction
Xanthone and acridone derivatives, both natural and synthetic,
[
1]
[5]
[6]
[
2]
have shown multiple kinds of biological activities, including
[2g,h,l,m]
[2b,f,r,s]
[2i,j,n]
antitumor,
antimicrobial,
anti-inflammatory,
antioxidant
antimalarial,
and hepatoprotective,
[2o,p]
[2c,e,k,s]
[2a,d,q]
and
have attracted considerable attention in the community of
synthesis for their therapeutic usages and intriguing structures
(
Scheme 1).
[
3]
A number of classic synthetic strategies, e.g. Friedel-Crafts
[3b,d,e]
[3a,c]
[3f]
acylation,
dehydration
and dehydrohalogenation, were
developed and widely demonstrated. In recent years novel
[3f,4]
synthetic strategies were booming.
Larock group, using cascade
intermolecular nucleophilic coupling of the substituted benzoates
and fluoride ion-induced arynes, generated xanthones and
[
3f]
acridones.
Deng and co-workers synthesized acridones via
[4b]
copper-catalyzed intramolecular amination.
Studer group
[
4e]
developed oxidative coupling to synthesize xanthones. Gerbino
and colleagues applied copper-based strategy by using 2-
substituted benzaldehydes and phenols as starting materials in
synthesizing xanthones. Lei group developed a palladium/copper
co-catalyzed carbonylation strategy to acridones (Scheme 2). To Scheme 1. Bioactive compounds containing xanthone and acridone scaffolds.
[4f]
[4i]
date, most strategies are confined into Friedel-Crafts acylation,
oxidation and transition metal-meditated coupling, and cannot be
To test our idea, the 1,3-diphenylprop-2-yn-1-one
applied in the synthesis of both xanthones and acridones. Inspired
Results and discussion
[
7]
substrate
5
was prepared through the Sonogashira coupling
by the precedent literatures, especially the versatile work of
of 2-bromoaldehyde
1
and trimethylsilylacetylene followed by
a Wittig reaction, removal of the protective group, nucleophilic
addition and oxidation (Scheme 3). To our delight, when the
substrate
5
was
subjected
to
5
mol
%
[
bis(trifluoromethanesulfonyl)imidate] (triphenylphosphine)
[8]
gold(I) (Ph PAuNTf ) at 100 °C in toluene under the
3
2
microwave irradiation, 12H-benzo[a]xanthen-12-one
6 could
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Journal Name
be generated in 72% yield. With our design certified, our study optimization of the conditions in catalysts, temperatures and
View Article Online
DOI: 10.1039/C8OB01684D
catalyst loadings. The combination of chloro(triphenyl
was commenced with
phosphine)gold(I) (Ph PAuCl) and silver hexafluoroantimonate
3
[9]
(
AgSbF6) was found to be the optimal conditions among the
catalytic conditions screened (Table 1, entries 1-4). During the
study on temperatures, it is found that lowering the
temperature to 80 °C gave no compromise in yield; the yield
plunged when the temperature was switched to 50 °C (Table 1,
entries 4-6). Decreasing catalyst loading to 3 mol % or below
Scheme 3. The synthetic route to substrate 5.
gave poor yield, however increasing the loading to 10 mol %
gave no significant increasing in yield, therefore the optimal
catalyst loading was determined as 5 mol % (Table 1, entries 6,
9
-11). As for the screening of solvents, toluene and
tetrahydrofuran (THF) were found to be better than both
acetonitrile and 1,2-dicloroethane (DCE) in yield, however, the
toluene was chosen, due to THF causing high pressure at the
reaction temperature for its low boiling point (Table 1, entries
Scheme 2. Reported and our strategies to the xanthone and acridone scaffolds.
Table 1. Condition screening of the synthesis of 12H-benzo[a]xanthen-12-one
6
, 12-14). Thus, the optimal conditions were determined as to
a
6
.
b
entry
catalyst
Ph PAuNTf
additive
AgOTf
catalyst loading (mol %)
additive loading (mol %)
T (°C)
100
100
100
100
50
solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
acetonitrile
THF
yield (%)
1
2
3
4
5
6
7
8
9
3
2
5
5
72
0
Ph
Ph
Ph
Ph
3
3
3
3
PAuCl
PAuCl
PAuCl
PAuCl
PAuCl
5
5
5
5
5
81
94
38
95
0
AgSbF
6
6
5
AgSbF
5
Ph
3
AgSbF
6
5
80
AgSbF
6
5
100
80
HNTf
2
5
14
36
85
96
0
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
PAuCl
PAuCl
PAuCl
PAuCl
PAuCl
PAuCl
PAuCl
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
6
6
6
6
6
6
6
1
1
3
80
10
11
12
13
14
15
3
80
10
5
10
5
80
80
5
5
80
95
52
5
5
80
DCE
c
5
5
110
toluene
51
Note: [a] All these screening experiments were performed on a 0.1 mmol scale under microwave irradiation. [b] Isolated yields and the reactions were due in 60 min. [c]
Refluxed for 3 hours without microwave irradiation.
2
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stir the reaction at the catalysis of 5 mol % Ph PAuCl/5 mol %
3
View Article Online
DOI: 10.1039/C8OB01684D
AgSbF in toluene at 80 °C for 1 h under the irradiation of
6
microwave. Microwave irradiation was proved only to boost
the reaction and increase the yield by a control experiment
(Table 1, entry 15).
With the optimal conditions in hand, the substituent
tolerance was examined by a series of synthetic 1-(2-
hydroxyphenyl)-3-(2-(2-methoxyvinyl)phenyl)prop-2-yn-1-one
substrates 5a-5p. The substrates with electron-withdrawing
groups (EWG) on the methoxyvinyl phenyl ring gave higher
yields than these with electron-donating groups (EDG)
(
Scheme 4, 6a-6c). To test the influence of substituents on the
Scheme 5. Substrate scopes for the syntheses of benzo[a]acridin-12(7H)-ones.
phenol ring, substrates 5d-5p were synthesized in the same
way.When it was EDG, e.g. methyl and methoxyl, on the
phenol ring, substituents on the methoxyvinyl phenyl ring gave
minor influence on the yields, which were all above 90%
time (10 minutes), then the intermediate 5-3 was subjected to
standard conditions for another 10 minutes (Table 2, C1 and C2),
the desired product 6 was obtained. The control experiments
without the gold catalyst, gave neither 5-3 nor 6, suggesting that
the gold catalyst was indispensable in both cyclization steps (Table
(Scheme 4, 6d-6g, 6k-6p). However, the substrates with EWG
on the phenol ring gave poor yields, regardless of the
substitutions on the methoxyvinyl phenyl ring (Scheme 4, 6h-
6j).
2
, C1’ and C2’). To figure out the true catalytic species in the second
cyclization, 2,6-ditert-butylpyridine (5 mol %) was introduced as a
scavenger of the trace amount of acid, resulting the formation of
the product 6 in 85% yield, which implied that the second
cyclization was catalyzed by gold(I) catalyst.
Scheme 6. The proposed mechanism.
Scheme 4. Substrate scopes for the syntheses of 12H-benzo[a]xanthen-12-ones.
a
The optimized conditions were then applied to the synthesis of Table 2. Control experiments in probing the mechanism.
benzo[a]acridin-12(7H)-one, only by replacing the oxygen with the
nitrogen in the substrates. Therefore, the substrates 7a-7l were
synthesized and subjected to the optimal conditions. These tested
substrates all gave acceptable to excellent yields, higher than 80%.
But, it is worth mention that the substrates with EDG on the
methoxyvinyl benzene ring gave a little worse yield in comparison
condition
catalyst
additive
T (°C)
yield (%)
with the EWG substituent globally, which was similar to the
screened results in the synthesis of 12H-benzo[a]xanthen-12-ones.
To probe the mechanism, a set of control experiments were
C1
C1′
C2
C2′
Ph
3
PAuCl
AgSbF
6
50
50
80
80
98
0
b
Ph
3
PAuCl
AgSbF
6
93 (85)
0
proceeded. When the substrate 5 was subjected to Ph PAuCl (5
3
[
a] All these control reactions were performed in toluene as solvent and under
mol %)/AgSbF (5 mol %), the intermediate 5-3 was isolated by
6
microwave irradiation for 10 min. [b] 5 mol % 2,6-ditert-Butylpyridine was added.
lowering reaction temperature (50 °C) and shortening the reaction
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A putative mechanism of cyclization to 12H-benzo[a]xanthen- The crude materials were purified by
Journal Name
flash column
a
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[
5b]
1
2-ones, according to our previous studies and the isolation of chromatography (EtOAc/petroleum ether) oDnOsI:il1ic0a.10g3e9l/tCo8aOfBfo0r1d68t4hDe
intermediate 5-3 in the control experiments, was finally shown in
Scheme 6. The reactant 5 was activated by the gold(I)-catalyst in
forming 5-1 complex, which is then attacked by the hydroxyl group
products 2, 2a-2c.
Spectral data of 2, 2a-2c were consistent with those reported in
5a,10
the literatures.
in
a
6-endo-dig manner to give the intermediate 5-2.
Protodeauration of the intermediate 5-2 afforded 5-3, in which the
new formed enolether would attack the electron-rich methoxyl
vinyl ether under the activation of gold(I) species to give the final
product 6 after isomerization and aromatization by the release of a
General procedures for the preparation of 3, 3a-3c and
characterization data.
A magnetically stirred emulsion of (methoxymethyl)triphenylp-
hosphonium chloride (6 mmol, 2 g) in dry THF (30 mL) maintained
[10]
methanol from 5-4.
This mechanism can be applied to the
cycloisomerization of benzo[a]acridin-12(7H)-one by simply altering at –78 °C under a nitrogen atmosphere was treated with potassium
the nucleophile group of 6-endo-dig from the hydroxyl group into bis(trimethylsilyl)amide (1 M in THF, 6 mmol). The reaction was
amine group.
stirred for 0.5 h followed by the addition of 2, 2a-2c (3 mmol) in dry
THF (10 mL) dropwise. The resulting mixture was stirred at –78 °C
for 0.5 h and filtered through Celite. The filtrate was concentrated
in vacuo.
Conclusion
In summary,
a
unique Michael addition/6-endo cascade
To a solution of the residue obtained above in MeOH (40 mL) was
cyclization/aromatization strategy to yielding both benzoxanthone added anhydrous K CO (6 mmol, 829 mg). The resulting mixture
2
3
and benzoacridone derivatives was designed and applied in a series was stirred at room temperature for 20 min till TLC showed the
of substrates with acceptable to excellent yields. A predicted starting materials were completely consumed, which was then
mechanism based on the isolated intermediate and precedent concentrated under the reduced pressure. The reaction mixture
study was given. Further applications of this strategy to synthesizing was filtrated through Celite. The filtrate was concentrated and
compounds with more complexity and bioactivities are underway in purified by a flash column chromatography (EtOAc/petroleum ether)
our laboratory.
on alkaline aluminum oxide to afford the products 3, 3a-3c.
Spectral data of 3, 3a-3b were consistent with those reported in
1
2
the literatures.
Experimental section
General experiment methods
1
-Ethynyl-4-fluoro-2-(2-methoxyvinyl)benzene (3c).
Colorless oil (422 mg, 1:0.4 E/Z) in 80% yield (EtOAc/petroleum
Unless otherwise noted, reagents were obtained commercially
and used without further purification. Tetrahydrofuran (THF)
was distilled from sodium under a nitrogen atmosphere.
Dichloromethane (DCM) was distilled from calcium hydride
under a nitrogen atmosphere. Toluene was distilled from
sodium under a nitrogen atmosphere. TLC analysis of reaction
mixtures was performed on Dynamic Adsorbents silica gel F-
1
ether = 1:200): H NMR (600 MHz, DMSO-d ) δ 7.74 (dd, J = 11.3,
6
2
.7 Hz, 1H, Z), 7.52 (d, J = 12.9 Hz, 1H, E), 7.50 – 7.41 (m, 2H, E + 1H,
Z), 6.98 (td, J = 8.5, 2.7 Hz, 1H, Z), 6.95 (td, J = 8.5, 2.7 Hz, 1H, E),
.56 (d, J = 7.1 Hz, 1H, Z), 6.12 (dd, J = 12.9, 1.4 Hz, 1H, E), 5.66 (dd,
J = 7.1, 1.6 Hz, 1H, Z), 4.40 (s, 1H, Z), 4.39 (s, 1H, E), 3.83 (s, 3H, Z),
6
13
3
.68 (s, 3H, E); C NMR (150 MHz, DMSO-d ) δ 162.2 (d, J = 245.9
6
Hz, E), 161.7 (d, J = 245.3 Hz, Z), 152.8 (E), 152.0 (Z), 141.0 (d, J = 9.1
Hz, E), 139.8 (d, J = 9.6 Hz, Z), 134.8 (d, J = 9.3 Hz, E), 134.4 (d, J =
2
54 TLC plates. Flash chromatography was carried out on
1
13
Zeoprep 60 (200-300 mesh) silica gel. H and C NMR spectra
were recorded with Bruker Avance-III 600 spectrometers and
referenced to CDCl and DMSO-d . HR-ESI-MS was recorded on
9
=
.3 Hz, Z), 115.5 (d, J = 2.8 Hz, Z), 115.1 (d, J = 2.7 Hz, E), 114.2 (d, J
24.0 Hz, Z), 112.8 (d, J = 22.6 Hz, Z), 112.7 (d, J = 22.7 Hz, E), 109.7
3
6
(
8
3
d, J = 23.3 Hz, E), 101.8 (d, J = 2.5 Hz, E), 100.6 (d, J = 2.5 Hz, Z),
a Bruker micro-TOFQ-Q instrument. IR spectra were recorded
on a Bruker IFS 55 spectrometer. Melting points (mp) were
tested on Thomas Hoover capillary melting point apparatus.
Microwave reactions were performed using microwave oven
CEM Discover in sealed reaction vessels. The temperature was
monitored using an internal vertically focused IR temperature
sensor.
−
1
4.6 (E + Z), 81.3 (Z), 81.2 (E), 61.2 (Z), 56.9 (E); IR (thin film, cm )
+
864, 3672, 1734, 1705, 1685, 1549; HRMS (ESI) m/z [M+H] calcd
for C H FO 177.0710, found 177.0715.
11 10
General procedures for the preparation of 5, 5a-5p, 7a-7l and
characterization data.
To a stirring solution of 3, 3a-3c (2.1 mmol) in THF (11 mL) was
General procedures for the preparation of 2-alknyl benzald- added a solution of n-BuLi (1 M in THF, 2.1 mL) dropwise at –78 °C
ehydes 2, 2a-2c.
under a nitrogen atmosphere. The reaction was stirred at –78 °C for
1
h followed by the addition of 4, 4a-4g (1 mmol) dropwise. After
To a mixture of 2-bromobenzaldehyde 1, 1a-1c (10 mmol),
stirring at –78 °C for 1 h, the solution was warmed to 0 °C and stir
for another 1 h. The reaction mixture was quenched by the addition
of a saturated aqueous solution of NH Cl. The aqueous phase was
extracted with ethyl acetate. The combined organic portions were
washed with H O and brine, dried over anhydrous Na SO , filtered
(
Ph P) PdCl (0.2 mmol, 140 mg) and CuI (0.1 mmol, 19 mg) was
3 2 2
added degassed THF (50 mL) under a nitrogen atmosphere. Then
4
ethynyl trimethylsilane (20 mmol, 2.8 mL) and Et N (30 mmol, 4.2
3
mL) were added by syringe under a nitrogen atmosphere. The
solution was stirred at 25 °C for 5 h till the consumption of the
starting material. The reaction mixture was filtrated through Celite.
2
2
4
and concentrated in vacuo.
4
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To a solution of the residue obtained above in DCM (11 mL) was 182.1 (E), 163.01 (E), 162.98 (Z), 152.6 (E), 151.7 (Z), 142.6 (E), 141.1
View Article Online
DOI: 10.1039/C8OB01684D
added activated MnO (5 mmol, 434 mg). The mixture was stirred at (Z), 137.8 (E), 137.6 (Z), 137.3 (E), 137.2 (Z), 135.4 (E), 134.8 (Z),
2
room temperature for 3 h till TLC showed the consumption of the 133.0 (Z), 132.9 (E), 129.0 (Z), 126.1 (E), 126.0 (Z), 124.1 (E), 121.0
starting material. The reaction mixture was filtrated through Celite. (Z), 120.9 (E), 119.5 (Z), 119.4 (E), 118.4 (E), 118.3 (Z), 115.5 (Z),
The filtrate was concentrated and purified by a flash column 115.4 (E), 101.9 (E), 101.5 (Z), 94.5 (Z), 94.3 (E), 90.8 (E), 90.6 (Z),
−
1
chromatography (EtOAc/petroleum ether) on silica gel to afford the 61.6 (Z), 57.0 (E); IR (thin film, cm ) 3424, 2928, 2194, 1645, 1625,
+
products 5, 5a-5p, 7a-7l.
1341, 1226, 1155, 1014; HRMS (ESI) m/z [M+Na] calcd for
C H ClNaO 335.0445, found 335.0433.
18
13
3
1
-(2-Hydroxyphenyl)-3-(2-(2-methoxyvinyl)phenyl)prop-2-yn-1-one
(5).
3-(4-Fluoro-2-(2-methoxyvinyl)phenyl)-1-(2-hydroxyphenyl)prop-2-
Yellow solid (181 mg, 1:0.2 E/Z) in 65% yield (EtOAc/petroleum yn-1-one (5c).
1
ether = 1:70): mp 81.9 – 82.6 °C; H NMR (600 MHz, CDCl ) δ 11.83 Yellow solid (186 mg, 1:0.4 E/Z) in 63% yield (EtOAc/petroleum
3
1
(
s, 1H, Z), 11.82 (s, 1H, E), 8.16 (dd, J = 7.9, 1.6 Hz, 1H, E), 8.13 (dd, J ether = 1:70): mp 82.3 – 84.2 °C; H NMR (600 MHz, CDCl ) δ 11.79
3
=
7
1
2
8.0, 1.6 Hz, 1H, Z), 7.63 (dd, J = 7.7, 0.8 Hz, 1H, E + 1H, Z), 7.55 – (s, 1H, Z), 11.77 (s, 1H, E), 8.11 (dd, J = 7.9, 1.6 Hz, 1H, E), 8.08 (dd, J
.48 (m, 1H, E + 1H, Z), 7.43 – 7.31 (m, 2H, E + 2H, Z), 7.22 (d, J = = 7.9, 1.5 Hz, 1H, Z), 7.89 (dd, J = 11.1, 2.6 Hz, 1H, Z), 7.60 (dd, J =
2.9 Hz, 1H, E), 7.20 – 7.12 (m, 1H, E + 1H, Z), 7.04 – 6.88 (m, 2H, E + 8.6, 5.9 Hz, 1H, E + 1H, Z), 7.54 – 7.48 (m, 1H, E + 1H, Z), 7.21 (d, J =
H, Z), 6.34 (d, J = 7.1 Hz, 1H, Z), 6.30 (d, J = 12.9 Hz, 1H, E), 5.82 (d, 12.9 Hz, 1H, E), 7.08 (dd, J = 10.2, 2.5 Hz, 1H, E), 7.02 – 6.91 (m, 2H,
13
J = 7.1 Hz, 1H, Z), 3.83 (s, 3H, Z), 3.77 (s, 3H, E); C NMR (150 MHz, E + 2H, Z), 6.89 – 6.84 (m, 1H, E + 1H, Z), 6.38 (d, J = 7.1 Hz, 1H, Z),
CDCl ) δ 182.3 (Z), 182.2 (E), 162.9 (E), 162.8 (Z), 151.6 (E), 150.5 (Z), 6.25 (d, J = 12.9 Hz, 1H, E), 5.80 (dd, J = 7.1, 1.4 Hz, 1H, Z), 3.86 (s,
3
13
1
40.9 (E), 139.6 (Z), 137.1 (E), 137.0 (Z), 134.3 (E), 133.8 (Z), 133.01 3H, Z), 3.77 (s, 3H, E); C NMR (150 MHz, CDCl ) δ 182.2 (Z), 182.1
3
(
1
(
(
1
Z), 132.9 (E), 131.5 (E), 131.2 (Z), 129.0 (Z), 125.71 (E), 125.66 (Z), (E), 164.5 (d, J = 253.1 Hz, E), 164.3 (d, J = 251.8 Hz, Z), 163.0 (E),
24.0 (E), 121.0 (Z), 120.9 (E), 119.4 (Z), 119.3 (E), 118.25 (E), 118.17 162.9 (Z), 152.7 (E), 151.7 (Z), 143.8 (d, J = 9.4 Hz, E), 142.3 (d, J =
Z), 117.1 (Z), 116.9 (E), 102.6 (E), 102.4 (Z), 95.8 (Z), 95.6 (E), 90.2 10.4 Hz, Z), 137.2 (E), 137.1 (Z), 136.5 (d, J = 9.7 Hz, E), 135.8 (d, J =
−
1
E), 90.0 (Z), 61.2 (Z), 56.6 (E); IR (thin film, cm ) 3424, 2924, 2191, 9.6 Hz, Z), 133.0 (Z), 132.9 (E), 121.0 (Z), 120.9 (E), 119.5 (Z), 119.4
+
633, 1591, 1338, 1305, 1201, 1012; HRMS (ESI) m/z [M+Na] calcd (E), 118.4 (E), 118.3 (Z), 115.9 (d, J = 24.3 Hz, Z), 113.5 (d, J = 22.9 Hz,
for C H NaO 301.0835, found 301.0845.
E), 113.4 (d, J = 23.2 Hz, Z), 113.2 (d, J = 2.8 Hz, Z), 113.1 (d, J = 2.8
Hz, E), 110.7 (d, J = 23.2 Hz, E), 102.1 (d, J = 2.4 Hz, E), 101.9 (d, J =
18
14
3
1
-(2-Hydroxyphenyl)-3-(4-methoxy-2-(2-methoxyvinyl)phenyl)-
2
.4 Hz, Z), 94.9 (Z), 94.7 (E), 90.2 (E), 89.9 (Z), 61.5 (Z), 56.9 (E); IR
−
1
prop-2-yn-1-one (5a).
(
thin film, cm ) 3440, 2925, 2193, 1630, 1596, 1245, 1207, 1013;
+
Yellow solid (179 mg, 1:0.3 E/Z) in 58% yield (EtOAc/petroleum
HRMS (ESI) m/z [M+Na] calcd for C H FNaO 319.0741, found
18
13
3
1
ether = 1:70): mp 91.2 – 93.2 °C; H NMR (600 MHz, CDCl ) δ 11.91
3
319.0746.
(
s, 1H, Z), 11.89 (s, 1H, E), 8.15 (dd, J = 7.9, 1.7 Hz, 1H, E), 8.12 (dd, J
=
7.9, 1.6 Hz, 1H, Z), 7.72 (d, J = 2.6 Hz, 1H, Z), 7.59 (d, J = 8.6 Hz, 1H, 1-(2-Hydroxy-5-methylphenyl)-3-(2-(2-methoxyvinyl)-phenyl)prop-
E + 1H, Z), 7.53 – 7.46 (m, 1H, E + 1H, Z ), 7.23 (d, J = 12.9 Hz, 1H, E), 2-yn-1-one (5d).
7
8
.01 – 6.93 (m, 2H, E + 2H, Z), 6.90 (d, J = 2.5 Hz, 1H, E), 6.75 (dd, J = Yellow solid (196 mg, 1:0.1 E/Z) in 67% yield (EtOAc/petroleum
1
.6, 2.5 Hz, 1H, E + 1H, Z), 6.36 (d, J = 7.1 Hz, 1H, Z), 6.28 (d, J = 12.9 ether = 1:70): mp 91.7 – 93.2°C; H NMR (600 MHz, DMSO-d ) δ
6
Hz, 1H, E), 5.82 (d, J = 7.1 Hz, 1H, Z), 3.86 (s, 3H, Z), 3.86 (s, 3H, E), 11.27 (s, 1H, E), 11.24 (s, 1H, Z), 8.08 (d, J = 8.1 Hz, 1H, Z), 7.88 (s,
1
3
3
1
.85 (s, 3H, Z), 3.78 (s, 3H, E); C NMR (150 MHz, CDCl ) δ 182.4 (Z), 1H, E + 1H, Z), 7.72 (d, J = 7.7 Hz, 1H, E + 1H, Z), 7.66 (d, J = 8.0 Hz,
3
82.2 (E), 162.9 (E), 162.8 (Z), 162.3 (E), 162.1 (Z), 151.9 (E), 150.9 1H, E + 1H, Z), 7.55 – 7.41 (m, 3H, E + 2H, Z), 7.28 – 7.25 (m, 1H, E +
(
1
(
Z), 143.1 (E), 141.7 (Z), 136.84 (E), 136.79 (Z), 136.4 (E), 135.8 (Z), 1H, Z), 6.95 (d, J = 8.4 Hz, 1H, E), 6.62 (d, J = 7.1 Hz, 1H, Z), 6.27 (d, J
33.0 (Z), 132.9 (E), 121.1 (Z), 121.0 (E), 119.3 (Z), 119.2 (E), 118.3 = 12.8 Hz, 1H, E), 5.73 (d, J = 7.1 Hz, 1H, Z), 3.84 (s, 3H, Z), 3.72 (s,
E), 118.2 (Z), 114.1 (Z), 112.4 (Z), 112.3 (E), 109.6 (Z), 109.4 (E), 3H, E), 2.33 (s, 3H, Z), 2.31 (s, 3H, E); C NMR (150 MHz, DMSO-d6)
13
1
6
2
09.2 (E), 102.7 (E), 102.5 (Z), 97.3 (Z), 97.1 (E), 90.3 (E), 90.1 (Z), δ 180.5 (E), 180.3 (Z), 159.4 (E), 159.3 (Z), 152.8 (E), 151.8 (Z), 140.6
−
1
1.4 (Z), 56.7 (E), 55.5 (E), 55.4 (Z); IR (thin film, cm ) 3423, 2937, (E), 139.4 (Z), 138.4 (E), 138.4 (Z), 134.2 (E), 134.0 (Z), 132.0 (Z),
+
835, 2181, 1629, 1595, 1243, 1012; HRMS (ESI) m/z [M+Na] calcd 131.91 (E), 131.88 (E), 131.6 (Z), 129.6 (Z), 128.71 (Z), 128.68 (E),
for C H NaO 331.0941, found 331.0949.
128.4 (Z), 125.9 (E), 124.1 (E), 120.60 (Z), 120.56 (E), 117.82 (E),
19
16
4
1
9
17.79 (Z), 116.0 (Z), 115.6 (E), 102.2 (E), 100.8 (Z), 94.4 (E), 94.2 (Z),
0.5 (E), 90.4 (Z), 61.2 (Z), 57.0 (E), 20.00 (Z), 19.9 (E); IR (thin film,
3
-(4-Chloro-2-(2-methoxyvinyl)phenyl)-1-(2-hydroxyphenyl)prop-2-
−
1
yn-1-one (5b).
cm ) 3425, 2933, 2187, 1633, 1594, 1343, 1209, 1168, 1086; HRMS
+
Yellow solid (218 mg, 1:0.9 E/Z) in 70% yield (EtOAc/petroleum
ether = 1:70): mp 83.8 – 85.2 °C; H NMR (600 MHz, CDCl ) δ 11.76
(
ESI) m/z [M+Na] calcd for C H NaO 315.0992, found 315.0992.
19 16 3
1
3
(
s, 1H, Z), 11.74 (s, 1H, E), 8.17 (d, J = 2.1 Hz, 1H, Z), 8.12 (dd, J = 7.9, 1-(2-Hydroxy-5-methylphenyl)-3-(4-methoxy-2-(2-methoxyvinyl)-
1
2
7
.6 Hz, 1H, E), 8.09 (dd, J = 7.9, 1.6 Hz, 1H, Z), 7.59 – 7.51 (m, 2H, E + phenyl)prop-2-yn-1-one (5e).
H, Z), 7.41 (d, J = 2.0 Hz, 1H, E), 7.23 (d, J = 12.9 Hz, 1H, E), 7.18 – Yellow solid (200 mg, 1:0.3 E/Z) in 62% yield (EtOAc/petroleum
.13 (m, 1H, E + 1H, Z), 7.03 – 6.94 (m, 2H, E + 2H, Z), 6.39 (d, J = 7.1 ether = 1:70): mp 72.5 – 74.2 °C; H NMR (600 MHz, DMSO-d ) δ
1
6
Hz, 1H, Z), 6.24 (d, J = 12.9 Hz, 1H, E), 5.77 (d, J = 7.1 Hz, 1H, Z), 3.88 11.44 (s, 1H, E), 11.40 (s, 1H, Z), 7.81 (s, 1H, E + 1H, Z), 7.67 (d, J =
13
(
s, 3H, Z), 3.78 (s, 3H, E); C NMR (150 MHz, CDCl ) δ 182.2 (Z), 8.6 Hz, 1H, Z), 7.62 (d, J = 8.6 Hz, 1H, E + 1H, Z), 7.54 (d, J = 12.8 Hz,
3
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J. Name., 2013, 00, 1-3 | 5
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
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ARTICLE
Journal Name
1
H, E), 7.39 (dd, J = 8.4, 1.8 Hz, 1H, E + 1H, Z), 7.14 (d, J = 2.4 Hz, 1H, Hz, 1H, Z), 6.24 (d, J = 12.8 Hz, 1H, E), 5.74 (d, J = 7.0 Hz, 1H, Z), 3.83
View Article Online
DOI: 10.1039/C8OB01684D
13
E), 6.89 (d, J = 8.4 Hz, 1H, E + 1H, Z), 6.84 (dd, J = 8.6, 2.6 Hz, 1H, Z), (s, 3H, Z), 3.72 (s, 3H, E); C NMR (150 MHz, DMSO-d ) δ 178.3 (E),
6
6
1
.80 (dd, J = 8.6, 2.5 Hz, 1H, E), 6.60 (d, J = 7.1 Hz, 1H, Z), 6.21 (d, J = 178.0 (Z), 159.8 (E), 159.7 (Z), 152.7 (E), 151.7 (Z), 140.6 (E), 139.6
2.8 Hz, 1H, E), 5.68 (d, J = 7.1 Hz, 1H, Z), 3.84 (s, 3H, Z), 3.83 (s, 3H, (Z), 139.2 (E), 139.1 (Z), 134.3 (E), 134.0 (Z), 133.8 (Z), 133.7 (E),
13
E), 3.80 (s, 3H, Z), 3.72 (s, 3H, E), 2.30 (s, 3H, Z), 2.28 (s, 3H, E);
C
131.9 (E), 131.7 (Z), 128.5 (Z), 125.92 (Z), 125.86 (E), 123.9 (E), 123.2
NMR (150 MHz, DMSO-d ) δ 180.7 (E), 180.6 (Z), 162.1 (E), 161.8 (Z), (Z), 123.1 (E), 120.5 (E + Z), 116.0 (Z), 115.5 (E), 110.40 (E + Z), 101.8
6
1
59.5 (E), 159.4 (Z), 153.1 (E), 152.0 (Z), 142.9 (E), 141.4 (Z), 138.1 (E), 100.9 (Z), 94.6 (E), 94.4 (Z), 90.8 (E), 90.7 (Z), 61.2 (Z), 56.8 (E);
−
1
(
E), 138.0 (Z), 136.2 (E), 136.0 (Z), 131.9 (Z), 131.8 (E), 128.49 (Z), IR (thin film, cm ) 3425, 2924, 2853, 2183, 1631, 1548, 1160, 1012;
+
1
1
28.46 (E), 120.33 (Z), 120.28 (E), 117.7 (E), 117.6 (Z), 113.9 (Z), HRMS (ESI) m/z [M+Na] calcd for C H BrNaO 378.9940, found
18 13 3
12.91 (E), 112.0 (Z), 108.6 (E), 108.2 (Z), 107.8 (E), 102.2 (E), 100.9 378.9940.
(
5
1
Z), 96.4 (E), 96.1 (Z), 90.5 (E), 90.2 (Z), 61.2 (Z), 57.0 (E), 55.5 (E),
−
1
1
-(5-Bromo-2-hydroxyphenyl)-3-(4-fluoro-2-(2-methoxyvinyl)-
5.3 (Z), 20.0 (Z), 19.8 (E); IR (thin film, cm ) 3423, 2932, 2833,
+
phenyl)prop-2-yn-1-one (5i).
Yellow solid (206 mg, 1:1.5 E/Z) in 55% yield (EtOAc/petroleum
ether = 1:70): mp 92.5 – 94.5 °C; H NMR (600 MHz, DMSO-d ) δ
634, 1597, 1483, 1297, 1225, 1040; HRMS (ESI) m/z [M+Na] calcd
for C H NaO 345.1097, found 345.1095.
20
18
4
1
6
(
E)-3-(4-Chloro-2-(2-methoxyvinyl)phenyl)-1-(2-hydroxy-5-meth-
11.32 (s, 1H, E), 11.29 (s, 1H, Z), 8.05 (s, 1H, Z), 8.05 (s, 1H, E), 7.85 –
7.70 (m, 3H, E + 2H, Z), 7.65 (d, J = 12.7 Hz, 1H, Z), 7.56 (d, J = 10.5
ylphenyl)prop-2-yn-1-one (5f).
Yellow solid (209 mg) in 64% yield (EtOAc/petroleum ether = 1:70): Hz, 1H, E), 7.15 – 7.05 (m, 1H, E + 1H, Z), 7.01 (d, J = 8.7 Hz, 1H, E +
1
mp 76.5 – 78.4 °C; H NMR (600 MHz, CDCl ) δ 11.59 (s, 1H), 7.87 (s, 1H, Z), 6.68 (d, J = 6.8 Hz, 1H, Z), 6.20 (d, J = 12.7 Hz, 1H, E), 5.74 (d,
3
13
1
7
1
H), 7.55 (d, J = 8.3 Hz, 1H), 7.40 (s, 1H), 7.34 (dd, J = 8.4, 1.3 Hz, 1H), J = 6.7 Hz, 1H, Z), 3.87 (s, 3H, Z), 3.73 (s, 3H, E); C NMR (150 MHz,
.21 (d, J = 12.9 Hz, 1H), 7.16 (d, J = 8.2 Hz, 1H), 6.91 (d, J = 8.5 Hz, DMSO-d ) δ 178.0 (E), 177.6 (Z), 164.1 (d, J = 250.3 Hz, E), 163.6 (d, J
H), 6.25 (d, J = 12.9 Hz, 1H), 3.77 (s, 3H), 2.34 (s, 3H); C NMR (150 = 250.0 Hz, Z), 159.7 (E), 159.5 (Z), 154.2 (E), 153.2 (Z), 143.8 (d, J =
6
13
MHz, CDCl ) δ 182.0, 161.0, 152.7, 142.5, 138.5, 137.7, 135.3, 132.5, 10.0 Hz, E), 142.2 (d, J = 10.4 Hz, Z), 139.1 (E), 139.0 (Z), 136.9 (d, J =
3
1
2
1
3
28.7, 126.1, 124.2, 120.6, 118.2, 115.5, 102.2, 94.1, 90.9, 57.2, 9.9 Hz, E), 136.6 (d, J = 9.9 Hz, Z), 133.7 (Z), 133.6 (E), 123.3 (Z),
−
1
0.6; IR (thin film, cm ) 3424, 2924, 2189, 1632, 1588, 1478, 1348, 123.2 (E), 120.45 (E), 120.4 (Z), 114.7 (d, J = 24.2 Hz, E), 113.5 (d, J =
+
170, 1081; HRMS (ESI) m/z [M+Na] calcd for C H ClNaO
3
49.0602, found 349.0618.
23.0 Hz, Z), 113.5 (d, J = 23.2 Hz, Z), 112.4 (d, J = 2.1 Hz, Z), 112.0 (d,
J = 1.5 Hz, E), 110.39 (E), 110.35 (Z), 110.3 (d, J = 20.5 Hz, E), 101.2
19
15
(
E), 100.2 (Z), 93.5 (E), 93.1 (Z), 90.90 (E), 90.87 (Z), 61.5 (Z), 57.0 (E);
−
1
3
-(4-Fluoro-2-(2-methoxyvinyl)phenyl)-1-(2-hydroxy-5-methyl-
IR (thin film, cm ) 3426, 2927, 2184, 1627, 1587, 1462, 1180, 1097,
1
found 396.9840.
+
phenyl)prop-2-yn-1-one (5g).
Yellow solid (183 mg, 1:0.7 E/Z) in 59% yield (EtOAc/petroleum
ether = 1:70): mp 84.5 – 86.2 °C; H NMR (600 MHz, DMSO-d ) δ
013; HRMS (ESI) m/z [M+Na] calcd for C H BrFNaO 396.9846,
18 12 3
1
6
1
1.26 (s, 1H, E), 11.22 (s, 1H, Z), 7.89 – 7.75 (m, 2H, E + 3H, Z), 7.63 1-(5-Bromo-2-hydroxyphenyl)-3-(4-methoxy-2-(2-methoxyvinyl)-
(
d, J = 12.7 Hz, 1H, E), 7.55 (dd, J = 10.9, 2.1 Hz, 1H, E), 7.44 (d, J = phenyl)prop-2-yn-1-one (5j).
7
2
1
3
.4 Hz, 1H, E + 1H, Z), 7.13 (td, J = 8.5, 2.5 Hz, 1H, Z), 7.09 (td, J = 8.5, Yellow solid (197 mg, 1:0.3 E/Z) in 51% yield (EtOAc/petroleum
1
.3 Hz, 1H, E), 6.93 (d, J = 8.4 Hz, 1H, E + 1H, Z), 6.71 (d, J = 7.0 Hz, ether = 1:70): mp 86.5 – 88.3 °C; H NMR (600 MHz, CDCl ) δ 11.87
3
H, Z), 6.23 (d, J = 12.7 Hz, 1H, E), 5.74 (d, J = 6.9 Hz, 1H, Z), 3.88 (s, (s, 1H, E), 11.83 (s, 1H, Z), 8.26 (d, J = 2.3 Hz, 1H, Z), 8.20 (d, J = 2.3
13
H, Z), 3.73 (s, 3H, E), 2.32 (s, 3H, Z), 2.30 (s, 3H, E); C NMR (150 Hz, 1H, E), 7.68 (d, J = 2.3 Hz, 1H, Z), 7.60 (d, J = 8.6 Hz, 1H, E + 1H,
MHz, DMSO-d ) δ 180.4 (E), 180.2 (Z), 164.0 (d, J = 250.3 Hz, E), Z), 7.56 (dd, J = 8.8, 2.4 Hz, 1H, E + 1H, Z), 7.24 (d, J = 12.9 Hz, 1H, E),
6
1
1
1
1
63.6 (d, J = 249.8 Hz, Z), 159.4 (E), 159.3 (Z), 154.2 (E), 153.3 (Z), 6.93 – 6.87 (m, 2H, E + 1H, Z), 6.75 (dd, J = 8.6, 2.0 Hz, 1H, E + 1H, Z),
43.8 (d, J = 9.9 Hz, E), 142.1 (d, J = 10.6 Hz, Z), 138.4 (E), 138.3 (Z), 6.42 (d, J = 7.1 Hz, 1H, Z), 6.24 (d, J = 12.9 Hz, 1H, E), 5.80 (d, J = 7.1
36.9 (d, J = 10.0 Hz, E), 136.5 (d, J = 9.7 Hz, Z), 131.9 (Z), 131.8 (E), Hz, 1H, Z), 3.86 (s, 3H, E + 6H, Z), 3.81 (s, 3H, E); C NMR (150 MHz,
13
28.7 (Z), 128.6 (E), 120.5 (Z), 120.4 (E), 117.8 (E), 117.7 (Z), 114.7 CDCl ) δ 181.1 (Z), 181.0 (E), 162.5 (E), 162.4 (Z), 161.8 (E), 161.7 (Z),
3
(
1
d, J = 24.1 Hz, Z), 113.44 (d, J = 22.9 Hz, Z), 113.41 (d, J = 23.2 Hz, E), 152.1 (E), 151.1 (Z), 143.4 (E), 142.2 (Z), 139.4 (E), 139.2 (Z), 136.7
12.5 (d, J = 2.2 Hz, Z), 112.1 (d, J = 2.0 Hz, E), 110.4 (d, J = 23.4 Hz, (E), 136.1 (Z), 135.1 (Z), 134.7 (E), 122.3 (Z), 122.2 (E), 120.4 (E),
E), 101.6 (d, J = 1.6 Hz, E), 100.2 (d, J = 1.6 Hz, Z), 93.5 (E), 93.3 (Z), 120.3 (Z), 114.3 (Z), 113.2 (Z), 112.5 (Z), 112.4 (E), 110.8 (E), 109.23
0.5 (E), 90.3 (Z), 61.5 (Z), 57.2 (E), 20.0 (Z), 19.9 (E); IR (thin film, (Z), 109.19 (E), 109.0 (E), 102.5 (Z), 102.4 (E), 98.7 (Z), 98.4 (E), 90.2
9
−
1
−1
cm ) 3425, 2924, 2187, 1632, 1597, 1345, 1244, 1209, 1018; HRMS (E), 90.1 (Z), 61.4 (Z), 56.9 (E), 55.6 (E), 55.5 (Z); IR (thin film, cm )
(
+
ESI) m/z [M+Na] calcd for C H FNaO 333.0897, found 333.0896.
3431, 2933, 2178, 1637, 1585, 1466, 1231, 1013; HRMS (ESI) m/z
19
15
3
+
[
M+Na] calcd for C H BrNaO 409.0046, found 409.0059.
19 15 4
1
-(5-Bromo-2-hydroxyphenyl)-3-(2-(2-methoxyvinyl)phenyl)prop-2-
yn-1-one (5h).
1-(2-Hydroxy-3,5-dimethylphenyl)-3-(2-(2-methoxyvinyl)-
Yellow solid (189 mg, 1:0.3 E/Z) in 53% yield (EtOAc/petroleum phenyl)prop-2-yn-1-one (5k).
1
ether = 1:70): mp 72.7 – 74.6 °C; H NMR (600 MHz, DMSO-d ) δ Yellow solid (187 mg, 1:0.1 E/Z) in 61% yield (EtOAc/petroleum
6
1
1
1.33 (s, 1H, E), 11.29 (s, 1H, Z), 8.14 – 8.01 (m, 1H, E + 1H, Z), 7.79 ether = 1:70): mp 68.5 – 70.4 °C; H NMR (600 MHz, DMSO-d ) δ
6
–
7.61 (m, 3H, E + 3H, Z), 7.58 – 7.43 (m, 2H, E + 1H, Z), 7.32 – 7.21 11.74 (s, 1H, E), 11.71 (s, 1H, Z), 8.08 (d, J = 8.1 Hz, 1H, Z), 7.75 (s,
(
m, 1H, E + 1H, Z), 7.02 (d, J = 8.7 Hz, 1H, E + 1H, Z), 6.59 (d, J = 6.9 1H, E + 1H, Z), 7.72 (d, J = 7.5 Hz, 1H, E), 7.65 (d, J = 8.0 Hz, 1H, E),
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 7 of 14
O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
ARTICLE
7
1
5
.56 – 7.45 (m, 2H, E + 2H, Z), 7.37 (s, 1H, E + 1H, Z), 7.28 – 7.24 (m, Yellow solid (98 mg, 1:0.4 E/Z) in 32% yield (EtOAc/petroleum ether
View Article Online
DOI: 10.1039/C8OB01684D
1
H, E + 1H, Z), 6.62 (d, J = 7.1 Hz, 1H, Z), 6.25 (d, J = 12.8 Hz, 1H, E), = 1:70): mp 87.5 – 89.1 °C; H NMR (600 MHz, CDCl ) δ 12.30 (s, 1H,
3
.70 (d, J = 7.1 Hz, 1H, Z), 3.83 (s, 3H, Z), 3.72 (s, 3H, E), 2.30 (s, 3H, Z), 12.29 (s, 1H, E), 8.14 (d, J = 8.0 Hz, 1H, Z), 8.04 (d, J = 8.9 Hz, 1H,
13
Z), 2.27 (s, 3H, E), 2.17 (s, 3H, E + 3H, Z); C NMR (150 MHz, DMSO- E), 8.01 (d, J = 8.9 Hz, 1H, Z), 7.62 (d, J = 7.5 Hz, 1H, E + 1H, Z), 7.44 –
d6) δ 181.3 (E + Z), 158.31 (E), 158.26 (Z), 152.8 (E), 151.8 (Z), 140.6 7.34 (m, 2H, E + 1H, Z), 7.22 (d, J = 12.9 Hz, 1H, E), 7.20 – 7.15 (m,
(
1
(
(
6
3
E), 140.6 (Z), 139.5 (E), 139.4 (Z), 134.2 (E), 134.0 (Z), 131.9 (E), 1H, E + 1H, Z), 6.52 (dd, J = 9.0, 2.4 Hz, 1H, Z), 6.50 (dd, J = 8.9, 2.4
31.6 (Z), 129.7 (Z), 129.6 (E), 128.4 (Z), 128.1 (Z), 128.0 (E), 126.4 Hz, 1H, E), 6.45 – 6.44 (m, 1H, E + 1H, Z), 6.33 (d, J = 7.1 Hz, 1H, Z),
E), 126.3 (Z), 125.88 (Z), 125.86 (E), 124.1 (E), 119.4 (E + Z), 115.9 6.29 (d, J = 12.9 Hz, 1H, E), 5.82 (d, J = 7.1 Hz, 1H, Z), 3.87 (s, 3H, E +
13
Z), 115.5 (E), 102.1 (E), 100.8 (Z), 94.9 (E), 94.8 (Z), 90.2 (E), 89.9 (Z), 3H, Z), 3.84 (s, 3H, Z), 3.76 (s, 3H, E); C NMR (150 MHz, CDCl ) δ
3
−
1
1.2 (Z), 57.0 (E), 20.0 (Z), 19.9 (E), 14.9 (E + Z); IR (thin film, cm ) 180.4 (Z), 180.3 (E), 167.0 (E), 166.9 (Z), 165.83 (E), 165.77 (Z), 151.5
422, 2920, 2837, 2182, 1649, 1580, 1352, 1252, 1096; HRMS (ESI) (E), 150.4 (Z), 140.6 (E), 139.4 (Z), 134.7 (Z), 134.6 (E), 134.1 (E),
+
m/z [M+Na] calcd for C H NaO 329.1148, found 329.1149.
133.7 (Z), 131.2 (E), 130.9 (Z), 129.0 (Z), 125.71 (E), 125.66 (Z), 124.0
E), 117.4 (Z), 117.2 (E), 115.5 (Z), 115.4 (E), 108.5 (E + Z), 102.7 (E),
20
18
3
(
1
-(2-Hydroxy-3,5-dimethylphenyl)-3-(4-methoxy-2-(2-meth-
1
6
2
02.5 (Z), 100.70 (Z), 100.68 (E), 94.9 (Z), 94.7 (E), 90.1 (E), 89.9 (Z),
−
1
oxyvinyl)phenyl)prop-2-yn-1-one (5l).
Yellow solid (202 mg, 1:0.1 E/Z) in 60% yield (EtOAc/petroleum
ether = 1:70): mp 77.3 – 79.2 °C; H NMR (600 MHz, CDCl ) δ 12.02
(
1.2 (Z), 56.7 (E), 55.80 (E), 55.79 (Z); IR (thin film, cm ) 3421, 2932,
+
192, 1633, 1587, 1350, 1265, 1162, 1008; HRMS (ESI) m/z [M+Na]
1
3
calcd for C H NaO 331.0941, found 331.0950.
19 16 4
s, 1H, E), 12.02 (s, 1H, Z), 7.76 (s, 1H, E), 7.71 (d, J = 2.5 Hz, 1H, Z),
7
.59 (d, J = 8.6 Hz, 1H, E + 1H, Z), 7.22 – 7.20 (m, 2H, E + 1H, Z), 6.90 1-(2-Hydroxy-4-methoxyphenyl)-3-(4-methoxy-2-(2-methoxy-
(
6
d, J = 2.5 Hz, 1H, E + 1H, Z), 6.75 (dd, J = 8.6, 2.5 Hz, 1H, E + 1H, Z), vinyl)phenyl)prop-2-yn-1-one (5o).
.35 (d, J = 7.1 Hz, 1H, Z), 6.30 (d, J = 12.9 Hz, 1H, E), 5.86 (d, J = 7.1 Yellow solid (118 mg, 1:0.5 E/Z) in 35% yield (EtOAc/petroleum
1
Hz, 1H, Z), 3.86 (s, 3H, E + 3H, Z), 3.85 (s, 3H, Z), 3.76 (s, 3H, E), 2.32 ether = 1:70): mp 76.5 – 78.2 °C; H NMR (600 MHz, CDCl ) δ 12.38
(
3
13
s, 3H, Z), 2.30 (s, 3H, E), 2.25 (s, 3H, E + 3H, Z); C NMR (150 MHz, (s, 1H, Z), 12.36 (s, 1H, E), 8.03 (d, J = 8.9 Hz, 1H, E), 8.00 (d, J = 8.9
CDCl ) δ 182.43 (Z), 182.42 (E), 162.1 (E), 162.0 (Z), 159.43 (E), Hz, 1H, Z), 7.71 (d, J = 2.6 Hz, 1H, Z), 7.57 (d, J = 8.6 Hz, 1H, E + 1H,
3
1
(
1
(
59.35 (Z), 151.8 (E), 150.7 (Z), 142.9 (E), 141.6 (Z), 139.0 (E), 138.9 Z), 7.22 (d, J = 12.9 Hz, 1H, E), 6.90 (d, J = 2.4 Hz, 1H, E), 6.74 (dd, J =
Z), 136.3 (E), 135.7 (Z), 130.2 (Z), 130.1 (E), 127.8 (E), 127.7 (Z), 8.6, 2.3 Hz, 1H, E + 1H, Z), 6.52 (dd, J = 8.9, 2.4 Hz, 1H, Z), 6.49 (dd, J
27.1 (E), 127.0 (Z), 120.11 (Z), 120.06 (E), 114.2 (Z), 112.4 (Z), 112.3 = 8.9, 2.4 Hz, 1H, E), 6.44 – 6.43 (m, 1H, E + 1H, Z), 6.35 (d, J = 7.1 Hz,
E), 109.9 (Z), 109.7 (E), 109.3 (E), 103.1 (E), 102.8 (Z), 96.4 (E + Z), 1H, Z), 6.27 (d, J = 12.9 Hz, 1H, E), 5.82 (d, J = 7.1 Hz, 1H, Z), 3.86 (s,
0.6 (E), 90.4 (Z), 61.4 (Z), 57.0 (E), 55.6 (E), 55.5 (Z), 20.7 (Z), 20.6 3H, E + 3H, Z), 3.86 (s, 3H, E + 3H, Z), 3.85 (s, 3H, Z), 3.77 (s, 3H, E);
9
−
1
13
(
E), 15.4 (E + Z); IR (thin film, cm ) 3423, 2921, 2852, 2172, 1635,
C NMR (150 MHz, DMSO-d ) δ 179.20 (Z), 179.18 (E), 166.6 (E + Z),
6
+
1
598, 1347, 1217, 1076; HRMS (ESI) m/z [M+Na] calcd for 164.6 (Z), 164.5 (E), 162.0 (Z), 161.6 (E), 153.0 (Z), 152.2 (E), 142.7
(Z), 141.1 (E), 136.0 (Z), 135.9 (E), 134.4 (E), 134.3 (Z), 114.8 (E),
14.7 (Z), 113.9 (E), 112.9 (Z), 112.0 (E), 108.51 (Z), 108.48 (Z), 108.4
-(4-Fluoro-2-(2-methoxyvinyl)phenyl)-1-(2-hydroxy-3,5-
E), 108.3 (E), 108.0 (Z), 101.9 (Z), 100.9 (E), 100.84 (E), 100.76 (Z),
C H NaO 359.1254, found 359.1247.
21
20
4
1
(
3
dimethylphenyl)prop-2-yn-1-one (5m).
Yellow solid (188 mg, 1:0.8 E/Z) in 58% yield (EtOAc/petroleum
ether = 1:70): mp 75.9 – 77.2 °C; H NMR (600 MHz, DMSO-d ) δ
9
5
5.7 (Z), 95.5 (E), 89.9 (Z), 89.7 (E), 61.3 (Z), 56.7 (E), 56.0 (E + Z),
−
1
5.6 (Z), 55.3 (E); IR (thin film, cm ) 3422, 2924, 2169, 1631, 1384,
1
+
6
1271, 1115, 1009; HRMS (ESI) m/z [M+H] calcd for C H O
20 19 5
1
(
1.72 (s, 1H, E), 11.69 (s, 1H, Z), 7.85 – 7.74 (m, 1H, E + 2H, Z), 7.70
s, 1H, E + 1H, Z), 7.62 (d, J = 12.7 Hz, 1H, E), 7.54 (dd, J = 10.9, 2.5
Hz, 1H, E), 7.34 (s, 1H, E + 1H, Z), 7.12 (td, J = 8.4, 2.7 Hz, 1H, Z), 7.08 (E)-3-(4-Fluoro-2-(2-methoxyvinyl)phenyl)-1-(2-hydroxy-4-
td, J = 8.5, 2.5 Hz, 1H, E), 6.71 (d, J = 7.1 Hz, 1H, Z), 6.20 (d, J = 12.7 methoxyphenyl)prop-2-yn-1-one (5p).
Hz, 1H, E), 5.69 (dd, J = 7.0, 0.9 Hz, 1H, Z), 3.87 (s, 3H, Z), 3.73 (s, 3H, Yellow solid (107 mg) in 33% yield (EtOAc/petroleum ether = 1:70):
3
39.1227, found 339.1231.
(
13
1
E), 2.29 (s, 3H, Z), 2.26 (s, 3H, E), 2.16 (s, 3H, E + 3H, Z); C NMR mp 92.5 – 94.5 °C; H NMR (600 MHz, DMSO-d ) δ 11.99 (s, 1H),
6
(
150 MHz, DMSO-d ) δ 181.2 (E + Z), 164.1 (d, J = 250.4 Hz, E), 163.6 8.04 (d, J = 8.9 Hz, 1H), 7.79 (dd, J = 8.2, 6.3 Hz 1H), 7.66 (d, J = 12.8
6
(
(
1
1
1
d, J = 250.0 Hz, Z), 158.31 (E), 158.26 (Z), 154.3 (E), 153.4 (Z), 143.8 Hz, 1H), 7.57 (dd, J = 10.8, 1.6 Hz 1H), 7.11 (dt, J = 8.3, 1.8 Hz, 1H),
d, J = 10.0 Hz, E), 142.2 (d, J = 10.4 Hz, Z), 139.4 (E + Z), 136.9 (d, J = 6.63 (dd, J = 8.8, 1.7 Hz, 1H), 6.56 (d, J = 1.5 Hz, 1H), 6.20 (d, J = 12.8
13
0.0 Hz, E), 136.6 (d, J = 9.9 Hz, Z), 129.7 (Z), 129.6 (E), 128.1 (Z), Hz, 1H), 3.86 (s, 3H), 3.74 (s, 3H); C NMR (150 MHz, DMSO-d ) δ
6
28.0 (E), 126.4 (E), 126.3 (Z), 119.3 (E + Z), 114.7 (d, J = 24.2 Hz, Z), 178.9, 164.0 (d, J = 250.0 Hz), 154.2, 143.6 (d, J = 9.9 Hz), 136.7 (d, J
13.5 (d, J = 23.0 Hz, Z), 113.4 (d, J = 23.1 Hz, E), 112.3 (d, J = 2.5 Hz, = 9.9 Hz), 134.5, 131.5, 128.7, 114.8, 113.4 (d, J = 23.1 Hz), 112.1 (d,
Z), 112.0 (d, J = 2.3 Hz, E), 110.4 (d, J = 23.6 Hz, E), 101.5 (d, J = 2.2 J = 2.3 Hz), 110.3 (d, J = 23.6 Hz), 108.6, 101.3 (d, J = 2.2 Hz), 100.9,
−
1
Hz, E), 100.1 (d, J = 2.1 Hz, Z), 94.0 (E), 93.8 (Z), 90.2 (E), 89.9 (Z), 93.1, 89.9, 56.9, 56.1; IR (thin film, cm ) 3424, 2925, 2191, 2169,
−
1
-
6
3
1.5 (Z), 57.2 (E), 20.0 (Z), 19.9 (E), 14.9 (E + Z); IR (thin film, cm ) 1631, 1384, 1261, 1121, 1009; HRMS (ESI) m/z [M-H] calcd for
423, 2960, 2921, 2192, 1633, 1604, 1358, 1230, 1076; HRMS (ESI) C H FO 325.0882, found 325.0879.
19
14
4
+
m/z [M+Na] calcd for C H FNaO 347.1054, found 347.1063.
20
17
3
(
E)-1-(2-Aminophenyl)-3-(2-(2-methoxyvinyl)phenyl)prop-2-yn-1-
1
-(2-Hydroxy-4-methoxyphenyl)-3-(2-(2-methoxyvinyl)phen-
one (7a).
yl)prop-2-yn-1-one (5n).
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Page 8 of 14
ARTICLE
Journal Name
Yellow solid (158 mg) in 57% yield (EtOAc/petroleum ether = 1:50): (Z), 163.6 (d, J = 249.1 Hz, E), 163.1 (d, J = 248.5 Hz, Z), 153.7 (E),
View Article Online
1
DOI: 10.1039/C8OB01684D
mp 72.3 – 74.2 °C; H NMR (600 MHz, CDCl ) δ 8.24 (dd, J = 8.1, 1.4 153.0 (Z), 152.14 (E), 152.10 (Z), 143.0 (d, J = 9.7 Hz, E), 141.4 (d, J =
3
Hz, 1H), 7.62 (d, J = 7.7 Hz, 1H), 7.41 (d, J = 7.9 Hz, 1H), 7.36 – 7.30 10.2 Hz, Z), 136.2 (d, J = 9.5 Hz, E), 135.8 (d, J = 9.5 Hz, Z), 135.4 (E),
(
(
m, 2H), 7.22 (d, J = 13.0 Hz, 1H), 7.17 (t, J = 7.5 Hz, 1H), 6.71 – 6.67 135.3 (Z), 133.6 (Z), 133.5 (E), 117.21 (Z), 117.18 (E), 117.0 (E), 116.9
m, 2H), 6.33 (d, J = 13.0 Hz, 1H), 3.76 (s, 3H); C NMR (150 MHz, (Z), 115.1 (Z), 114.9 (E), 114.6 (d, J = 24.2 Hz, Z), 113.3 (d, J = 22.6 Hz,
13
DMSO-d ) δ 177.9, 152.25, 152.18, 139.9, 135.5, 133.7, 133.6, 131.1, E), 113.2 (d, J = 3.0 Hz, Z), 112.9 (d, J = 2.3 Hz, E), 110.22 (d, J = 23.5
6
1
25.8, 123.9, 117.3, 117.0, 116.5, 114.9, 102.1, 91.4, 90.5, 56.6; IR Hz, E), 110.18 (d, J = 21.1 Hz, Z), 101.4 (d, J = 2.2 Hz, E), 100.3 (d, J =
−
1
(
thin film, cm ) 3449, 3335, 3065, 2926, 2184, 1632, 1618, 1232, 1.8 Hz, Z), 91.3 (E), 91.1 (Z), 89.6 (E), 89.4 (Z), 61.4 (Z), 56.8 (E); IR
+
−1
1
3
159, 1003; HRMS (ESI) m/z [M+Na] calcd for C H NNaO
(thin film, cm ) 3401, 3303, 2928, 2192, 1638, 1618, 1243, 1159;
18
15
2
+
00.0995, found 300.1010.
HRMS (ESI) m/z [M+Na] calcd for C H FNNaO 318.0901, found
18
14
2
3
18.0902.
1
2
-(2-Aminophenyl)-3-(4-methoxy-2-(2-methoxyvinyl)phen-yl)prop-
-yn-1-one (7b).
1-(2-Amino-5-methylphenyl)-3-(2-(2-methoxyvinyl)phenyl)prop-2-
Yellow solid (187 mg, 1:0.2 E/Z) in 61% yield (EtOAc/petroleum yn-1-one (7e).
1
ether = 1:50): mp 63.5 – 65.5 °C; H NMR (600 MHz, DMSO-d ) δ Yellow solid (189 mg, 1:0.2 E/Z) in 65% yield (EtOAc/petroleum
6
1
8
.07 (dd, J = 8.1, 1.2 Hz, 1H, E), 8.04 (dd, J = 8.1, 1.2 Hz, 1H, Z), 7.63 ether = 1:50): mp 81.5 – 83.5 °C; H NMR (600 MHz, DMSO-d ) δ
6
(
d, J = 8.6 Hz, 1H, Z), 7.62 (d, J = 2.6 Hz, 1H, Z), 7.59 (d, J = 8.8 Hz, 1H, 8.07 (d, J = 8.0 Hz, 1H, Z), 7.85 (s, 1H, E + 1H, Z), 7.68 – 7.62 (m, 1H,
E), 7.57 (d, J = 13.1 Hz, 1H, E), 7.41 (s, 2H, E + 2H, Z), 7.34 – 7.29 (m, E + 1H, Z), 7.61 (d, J = 8.0 Hz, 1H, E), 7.49 – 7.45 (m, 1H, E + 1H, Z),
H, E + 1H, Z), 7.16 (d, J = 2.4 Hz, 1H, E), 6.85 (dd, J = 8.6, 2.6 Hz, 1H, 7.42 (t, J = 7.7 Hz, 1H, E), 7.33 (s, 2H, E + 2H, Z), 7.25 – 7.21 (m, 1H, E
Z), 6.82 – 6.81 (m, 2H, E + 1H, Z), 6.67 – 6.64 (m, 1H, Z), 6.63 – 6.59 + 1H, Z), 7.18 (dd, J = 8.5, 1.9 Hz, 1H, E + 1H, Z), 6.77 (d, J = 8.5 Hz,
1
(
m, 1H, E + 1H, Z), 6.21 (d, J = 12.8 Hz, 1H, E), 5.66 (d, J = 7.1 Hz, 1H, 1H, E + 1H, Z), 6.57 (d, J = 7.1 Hz, 1H, Z), 6.27 (d, J = 12.8 Hz, 1H, E),
13
Z), 3.83 (s, 3H, Z), 3.83 (s, 3H, E), 3.80 (s, 3H, Z), 3.73 (s, 3H, E);
NMR (150 MHz, DMSO-d ) δ 178.09 (Z), 178.07 (E), 161.4 (E), 161.0 Z), 2.21 (s, 3H, E); C NMR (150 MHz, DMSO-d ) δ 177.7 (E), 177.6
C
5.73 (d, J = 7.1 Hz, 1H, Z), 3.82 (s, 3H, Z), 3.71 (s, 3H, E), 2.23 (s, 3H,
13
6
6
(
Z), 152.6 (E + Z), 152.0 (E), 151.8 (Z), 142.1 (E), 140.6 (Z), 135.5 (E + (Z), 152.2 (E), 151.3 (Z), 150.32 (E), 150.27 (Z), 139.8 (E), 138.8 (Z),
Z), 135.2 (Z), 135.1 (E), 133.5 (Z), 133.4 (E), 117.4 (Z), 117.3 (E), 136.83 (E), 136.80 (Z), 133.6 (E), 133.3 (Z), 132.6 (Z), 132.5 (E), 130.9
16.91 (E), 116.86 (Z), 115.0 (Z), 114.8 (E), 113.9 (Z), 112.7 (E), 111.8 (E), 130.7 (Z), 128.4 (Z), 125.8 (Z), 125.7 (E), 124.0 (E), 123.34 (Z),
1
(
(
Z), 109.1 (Z), 108.8 (E), 108.5 (E), 102.1 (E), 101.0 (Z), 91.7 (E), 91.5 123.31 (E), 117.12 (Z), 117.10 (E), 117.08 (E), 117.06 (Z), 116.9 (Z),
Z), 91.2 (E), 90.9 (Z), 61.2 (Z), 56.5 (E), 55.4 (E), 55.2 (Z); IR (thin film, 116.6 (E), 102.4 (E), 101.1 (Z), 91.5 (E), 91.3 (Z), 90.4 (E), 90.3 (Z),
−
1
−1
cm ) 3434, 3315, 2925, 2853, 2178, 1619, 1539, 1233, 1159, 1001; 61.0 (Z), 56.9 (E), 20.0 (Z), 19.9 (E); IR (thin film, cm ) 3417, 3316,
HRMS (ESI) m/z [M+Na] calcd for C H NNaO 330.1101, found 2956, 2925, 2187, 1633, 1587, 1303, 1162, 1085; HRMS (ESI) m/z
3
+
19
17
3
+
30.1101.
[M+H] calcd for C H NO 292.1332, found 292.1344.
19
18
2
(
E)-1-(2-Aminophenyl)-3-(4-chloro-2-(2-methoxyvinyl)phen-
(E)-1-(2-Amino-5-methylphenyl)-3-(4-methoxy-2-(2-methoxy-
vinyl)phenyl)prop-2-yn-1-one (7f).
yl)prop-2-yn-1-one (7c).
Yellow solid (187 mg) in 60% yield (EtOAc/petroleum ether = 1:50): Yellow solid (189 mg) in 59% yield (EtOAc/petroleum ether = 1:50):
1
1
mp 83.5 – 85.5 °C; H NMR (600 MHz, CDCl ) δ 8.18 (d, J = 8.0 Hz, mp 75.5 – 77.5 °C; H NMR (600 MHz, DMSO-d ) δ 7.83 (d, J = 0.7 Hz,
3
6
1
H), 7.53 (d, J = 8.3 Hz, 1H), 7.38 (s, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.22 1H), 7.59 (d, J = 8.6 Hz, 1H), 7.56 (d, J = 12.8 Hz, 1H), 7.27 (s, 2H),
(
(
d, J = 12.9 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 6.70 – 6.68 (m, 2H), 6.37 7.18 – 7.16 (m, 2H), 6.82 (dd, J = 8.6, 2.5 Hz, 1H), 6.75 (d, J = 8.5 Hz,
13
s, 2H), 6.26 (d, J = 12.9 Hz, 1H), 3.76 (s, 3H); C NMR (150 MHz, 1H), 6.24 (d, J = 12.8 Hz, 1H), 3.84 (s, 3H), 3.72 (s, 3H), 2.21 (s, 3H);
13
DMSO-d ) δ 177.6, 153.8, 152.2, 141.9, 136.1, 135.5, 135.3, 133.5,
C NMR (150 MHz, DMSO-d ) δ 177.9, 161.4, 152.8, 150.1, 142.0,
6
6
1
25.7, 123.4, 117.1, 117.0, 115.2, 114.9, 101.1, 92.0, 89.2, 56.9; IR 136.6, 135.5, 132.5, 123.2, 117.12, 117.07, 112.8, 108.8, 108.6,
−
1
−1
(
thin film, cm ) 3415, 2924, 2853, 2192, 1632, 1583, 1384, 1229, 102.4, 91.6, 91.3, 57.0, 55.5, 19.9; IR (thin film, cm ) 3425, 2921,
+
+
1
3
160; HRMS (ESI) m/z [M+H] calcd for C H ClNO 312.0786, found 2839, 2186, 1689, 1594, 1298, 1108, 1020; HRMS (ESI) m/z [M+Na]
18
15
2
12.0791.
calcd for C H NNaO 344.1257, found 344.1260.
20 19 3
1
-(2-Aminophenyl)-3-(4-fluoro-2-(2-methoxyvinyl)phenyl)prop-2-
(E)-1-(2-Amino-5-methylphenyl)-3-(4-chloro-2-(2-methoxy-
vinyl)phenyl)prop-2-yn-1-one (7g).
yn-1-one (7d).
Yellow solid (183 mg, 1:0.3 E/Z) in 62% yield (EtOAc/petroleum Yellow solid (188 mg) in 58% yield (EtOAc/petroleum ether = 1:50):
1
1
ether = 1:50): mp 77.5 – 79.2 °C; H NMR (600 MHz, DMSO-d ) δ mp 72.5 – 74.5 °C; H NMR (600 MHz, DMSO-d ) δ 7.81 (s, 1H), 7.75
6
6
8
(
.06 (dd, J = 8.1, 1.4 Hz, 1H, E), 8.03 (dd, J = 8.1, 1.4 Hz, 1H, Z), 7.81 (d, J = 2.0 Hz, 1H), 7.66 (d, J = 8.3 Hz, 1H), 7.62 (d, J = 12.8 Hz, 1H),
dd, J = 11.3, 2.6 Hz, 1H, Z), 7.75 (dd, J = 8.5, 6.2 Hz, 1H, Z), 7.71 (dd, 7.33 (s, 2H), 7.26 (dd, J = 8.3, 2.1 Hz, 1H), 7.18 (dd, J = 8.5, 1.9 Hz,
J = 8.5, 6.2 Hz, 1H, E), 7.63 (d, J = 12.8 Hz, 1H, E), 7.53 (dd, J = 10.9, 1H), 6.76 (d, J = 8.5 Hz, 1H), 6.20 (d, J = 12.8 Hz, 1H), 3.72 (s, 3H),
13
2
7
7
.1 Hz, 1H, E), 7.46 (s, 2H, E + 2H, Z), 7.33 (m, 1H, E + 1H, Z), 7.11 – 2.20 (s, 3H); C NMR (150 MHz, DMSO-d ) δ 177.4, 153.9, 150.4,
6
.04 (m, 1H, E + 1H, Z), 6.82 (d, J = 8.4 Hz, 1H, E + 1H, Z), 6.69 (d, J = 141.9, 137.0, 136.0, 135.2, 132.4, 125.7, 123.5, 123.4, 117.1, 116.9,
−
1
.1 Hz, 1H, Z), 6.67 – 6.63 (m, 1H, Z), 6.61 (t, J = 7.5 Hz, 1H, E), 6.21 115.3, 101.4, 92.1, 89.2, 57.2, 19.9; IR (thin film, cm ) 3412, 2924,
+
(
d, J = 12.8 Hz, 1H, E), 5.69 (dd, J = 7.0, 1.4 Hz, 1H, Z), 3.86 (s, 3H, Z), 2182, 1630, 1585, 1384, 1234, 1112, 1015; HRMS (ESI) m/z [M+H]
13
3
.73 (s, 3H, E); C NMR (150 MHz, DMSO-d ) δ 177.78 (E), 177.75 calcd for C H ClNO 326.0942, found 326.0943.
6
19 17
2
8
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 9 of 14
O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
ARTICLE
1
-(2-Amino-5-methylphenyl)-3-(4-fluoro-2-(2-methoxyvinyl)-
114.0 (Z), 112.9 (E), 112.0 (Z), 109.5 (Z), 108.5 (E), 108.4 (E), 101.8
View Article Online
DOI: 10.1039/C8OB01684D
phenyl)prop-2-yn-1-one (7h).
(E), 100.9 (Z), 92.5 (E), 91.7 (Z), 90.7 (E), 90.4 (Z), 61.2 (Z), 56.7 (E),
−
1
Yellow solid (204 mg, 1:0.4 E/Z) in 66% yield (EtOAc/petroleum 55.5 (E), 55.3 (Z); IR (thin film, cm ) 3483, 3351, 2923, 2182, 1653,
ether = 1:50): mp 91.5 – 93.5°C; H NMR (600 MHz, DMSO-d ) δ 1575, 1295, 1216, 1095, 1005; HRMS (ESI) m/z [M+Na] calcd for
1
+
6
7
.84 – 7.79 (m, 1H, E + 2H, Z), 7.75 (dd, J = 8.6, 6.1 Hz, 1H, Z), 7.71 C H ClNNaO 364.0711, found 364.0715.
19 16 3
(
1
dd, J = 8.6, 6.1 Hz, 1H, E), 7.61 (d, J = 12.8 Hz, 1H, E), 7.53 (dd, J =
0.9, 2.6 Hz, 1H, E), 7.31 (s, 2H, E + 2H, Z), 7.19 – 7.17 (m, 1H, E + 1H,
1
-(2-Amino-5-chlorophenyl)-3-(4-chloro-2-(2-methoxyvinyl)-
phenyl)prop-2-yn-1-one (7k).
Yellow solid (214 mg, 1:0.4 E/Z) in 62% yield (EtOAc/petroleum
ether = 1:50): mp 75.3 – 77.2 °C; H NMR (600 MHz, DMSO-d ) δ
8
Z), 7.10 (td, J = 8.5, 2.7 Hz, 1H, Z), 7.07 (td, J = 8.5, 2.6 Hz, 1H, E),
.76 (d, J = 8.5 Hz, 1H, E + 1H, Z), 6.69 (d, J = 7.1 Hz, 1H, Z), 6.23 (dd,
J = 12.8, 1.1 Hz, 1H, E), 5.72 (dd, J = 7.1, 1.4 Hz, 1H, Z), 3.87 (s, 3H, Z),
6
1
6
13
.05 (s, 1H, Z), 7.96 – 7.94 (m, 1H, E + 1H, Z), 7.76 (s, 1H, E), 7.69 (d,
3
.72 (s, 3H, E), 2.23 (s, 3H, Z), 2.20 (s, 3H, E); C NMR (150 MHz,
J = 8.3 Hz, 1H, Z), 7.66 (s, 1H, E), 7.64 (d, J = 5.2 Hz, 1H, E), 7.60 (s,
DMSO-d ) δ 177.59 (E), 177.57 (Z), 163.5 (d, J = 249.0 Hz, E), 163.1
6
2
1
6
H, E + 2H, Z), 7.36 (d, J = 9.0 Hz, 1H, E + 1H, Z), 7.31 (d, J = 8.3 Hz,
H, Z), 7.27 (d, J = 8.3 Hz, 1H, E), 6.88 (d, J = 9.0 Hz, 1H, E + 1H, Z),
.66 (d, J = 7.1 Hz, 1H, Z), 6.15 (d, J = 12.8 Hz, 1H, E), 5.64 (d, J = 7.1
(
(
(
(
d, J = 248.6 Hz, Z), 153.9 (E), 152.9 (Z), 150.32 (E), 150.28 (Z), 143.0
d, J = 9.7 Hz, E), 141.4 (d, J = 10.1 Hz, Z), 136.9 (E), 136.8 (Z), 136.2
d, J = 9.7 Hz, E), 135.8 (d, J = 9.9 Hz, Z), 132.6 (Z), 132.5 (E), 123.4
Z), 123.3 (E), 117.11 (E), 117.08 (Z), 117.01 (Z), 116.99 (E), 114.6 (d,
13
Hz, 1H, Z), 3.87 (s, 3H, Z), 3.73 (s, 3H, E); C NMR (150 MHz, DMSO-
d6) δ 176.58 (E), 176.57 (Z), 153.9 (E), 152.9 (Z), 151.0 (E), 150.9 (Z),
J = 24.1 Hz, Z), 113.33 (d, J = 22.8 Hz, Z), 113.31 (d, J = 2.7 Hz, Z),
13.27 (d, J = 22.9 Hz, E), 112.96 (d, J = 2.3 Hz, E), 110.4 (d, J = 23.5
Hz, E), 101.7 (d, J = 2.2 Hz, E), 100.3 (d, J = 1.4 Hz, Z), 91.4 (E), 91.2
Z), 89.5 (E), 89.4 (Z), 61.4 (Z), 57.1 (E), 20.0 (Z), 19.9 (E); IR (thin film,
1
1
42.0 (E), 140.6 (Z), 136.4 (E), 135.9 (Z), 135.41 (E), 135.37 (E),
35.35 (Z), 135.0 (Z), 131.8 (Z), 131.6 (E), 127.7 (Z), 125.9 (Z), 125.8
1
(
E), 123.5 (E), 119.3 (E), 119.2 (Z), 118.0 (Z), 117.9 (E), 117.62 (Z),
(
−
1
1
9
2
17.56 (E), 115.3 (Z), 114.9 (E), 101.0 (E), 99.9 (Z), 91.6 (E), 91.4 (Z),
cm ) 3481, 3353, 2923, 2188, 1649, 1630, 1546, 1300, 1243, 1126,
1
found 332.1063.
−
1
+
0.1 (E), 89.9 (Z), 61.6 (Z), 56.9 (E); IR (thin film, cm ) 3443, 3330,
079; HRMS (ESI) m/z [M+Na] calcd for C H FNNaO 332.1057,
19 16 2
+
186, 1632, 1582, 1384, 1228, 1160, 1006; HRMS (ESI) m/z [M+H]
calcd for C H Cl NO 346.0396, found 346.0395.
18
14
2
2
1
-(2-Amino-5-chlorophenyl)-3-(2-(2-methoxyvinyl)phenyl)prop-2-
1
-(2-Amino-5-chlorophenyl)-3-(4-fluoro-2-(2-methoxyvinyl)phen-
yn-1-one (7i).
yl)prop-2-yn-1-one (7l).
Yellow solid (201 mg, 1:0.1 E/Z) in 61% yield (EtOAc/petroleum
ether = 1:50): mp 83.4 – 85.2 °C; H NMR (600 MHz, DMSO-d ) δ
Yellow solid (174 mg, 1:0.2 E/Z) in 56% yield (EtOAc/petroleum
ether = 1:50): mp 85.5 – 87.5 °C; H NMR (600 MHz, CDCl ) δ 8.19 (d,
J = 2.5 Hz, 1H, Z), 8.16 (d, J = 2.5 Hz, 1H, E), 8.11 (d, J = 8.0 Hz, 1H, Z),
1
3
1
6
7
2
.97 (d, J = 2.7 Hz, 1H, Z), 7.96 (d, J = 2.4 Hz, 1H, E), 7.80 (dd, J = 11.2,
.6 Hz, 1H, Z), 7.75 (dd, J = 8.6, 6.2 Hz, 1H, Z), 7.71 (dd, J = 8.6, 6.1
7
7
7
1
1
.63 (d, J = 7.7 Hz, 1H, E + 1H, Z), 7.42 (d, J = 7.9 Hz, 1H, E + 1H, Z),
.36 (t, J = 7.6 Hz, 1H, E), 7.27 – 7.22 (m, 2H, E + 1H, Z), 7.17 (t, J =
.5 Hz, 1H, E + 1H, Z), 6.64 (d, J = 8.8 Hz, 1H, E), 6.63 (d, J = 8.8 Hz,
H, Z), 6.40 (s, 2H, E + 2H, Z), 6.36 (d, J = 7.1 Hz, 1H, Z), 6.30 (d, J =
3.0 Hz, 1H, E), 5.84 (d, J = 7.1 Hz, 1H, Z), 3.83 (s, 3H, Z), 3.78 (s, 3H,
Hz, 1H, E), 7.64 (d, J = 12.8 Hz, 1H, E), 7.59 (s, 2H, E + 2H, Z), 7.54
dd, J = 10.9, 2.3 Hz, 1H, E), 7.36 (dd, J = 9.0, 2.5 Hz, 1H, E + 1H, Z),
.12 (td, J = 8.5, 2.6 Hz, 1H, Z), 7.08 (td, J = 8.5, 2.4 Hz, 1H, E), 6.88
d, J = 9.0 Hz, 1H, E + 1H, Z), 6.67 (d, J = 7.1 Hz, 1H, Z), 6.19 (d, J =
2.8 Hz, 1H, E), 5.68 (d, J = 7.0 Hz, 1H, Z), 3.87 (s, 3H, Z), 3.74 (s, 3H,
(
7
(
1
13
E); C NMR (150 MHz, CDCl ) δ 178.6 (Z), 178.5 (E), 151.5 (E), 150.4
3
(
1
(
1
Z), 149.7 (E), 149.6 (Z), 140.5 (E), 139.5 (Z), 135.3 (E), 135.2 (Z),
34.3 (E), 133.7 (Z), 133.3 (Z), 133.0 (E), 131.0 (E), 130.8 (Z), 129.0
Z), 125.73 (Z), 125.71 (E), 123.9 (E), 120.5 (Z), 120.4 (E), 119.7 (Z),
19.5 (E), 118.6 (E), 118.5 (Z), 117.7 (Z), 117.5 (E), 102.7 (Z), 102.5
E), 92.9 (Z), 92.7 (E), 91.2 (E), 91.0 (Z), 61.2 (Z), 56.7 (E); IR (thin film,
13
E); C NMR (150 MHz, DMSO-d ) δ 176.62 (E), 176.59 (Z), 163.70 (d,
J = 250.8 Hz, Z), 163.67 (d, J = 249.5 Hz, E), 153.9 (E), 153.0 (Z),
6
1
1
1
1
1
50.9 (E), 150.8 (Z), 143.1 (d, J = 9.8 Hz, E), 141.5 (d, J = 9.9 Hz, Z),
36.4 (d, J = 9.9 Hz, E), 135.9 (d, J = 9.2 Hz, Z), 135.24 (E), 135.21 (Z),
31.8 (Z), 131.6 (E), 119.20 (E), 119.16 (Z), 117.82 (Z), 117.78 (E),
17.6 (Z), 117.5 (E), 114.7 (d, J = 22.8 Hz, Z), 113.4 (d, J = 23.3 Hz, Z),
13.3 (d, J = 22.9 Hz, E), 112.6 (d, J = 1.8 Hz, Z), 112.5 (d, J = 2.4 Hz,
(
−
1
cm ) 3416, 3302, 2925, 2184, 1631, 1539, 1231, 1189, 1006; HRMS
+
(
ESI) m/z [M+H] calcd for C H ClNO 312.0786, found 312.0788.
18 15 2
1
-(2-Amino-5-chlorophenyl)-3-(4-methoxy-2-(2-methoxyvinyl)-
E), 110.3 (d, J = 23.6 Hz, E), 101.2 (d, J = 2.3 Hz, E), 100.2 (d, J = 4.0
Hz, Z), 90.8 (E), 90.5 (Z), 90.3 (E), 90.2 (Z), 61.5 (Z), 56.8 (E); IR (thin
phenyl)prop-2-yn-1-one (7j).
−
1
Yellow solid (198 mg, 1:0.2 E/Z) in 58% yield (EtOAc/petroleum film, cm ) 3431, 3316, 2925, 2185, 1637, 1618, 1467, 1241, 1201,
ether = 1:50): mp 86.5 – 88.2 °C; H NMR (600 MHz, DMSO-d ) δ 1007; HRMS (ESI) m/z [M+Na] calcd for C H ClFNNaO 352.0511,
1
+
6
18 13
2
7
2
2
.99 (d, J = 2.5 Hz, 1H, Z), 7.97 (d, J = 2.5 Hz, 1H, E), 7.63 – 7.61 (m, found 352.0509.
H, Z), 7.60 (d, J = 6.5 Hz, 1H, E), 7.58 (d, J = 2.2 Hz, 1H, E), 7.56 (s,
H, E + 2H, Z), 7.35 (dd, J = 9.0, 2.6 Hz, 1H, E + 1H, Z), 7.17 (d, J = 2.4
The procedure for the preparation of 5-3 and characterization
data.
Hz, 1H, E), 6.88 – 6.86 (m, 1H, E + 2H, Z), 6.83 (dd, J = 8.6, 2.5 Hz, 1H,
E), 6.59 (d, J = 7.1 Hz, 1H, Z), 6.19 (d, J = 12.8 Hz, 1H, E), 5.66 (d, J =
7
3
To a solution of the substrate 5 (0.5 mmol, 139 mg) in dry toluene
(
2 mL) was added the gold catalyst, which was generated by being
stirred for 30 min at room temperature after the mixture of
PPh AuCl (0.025 mmol, 12 mg) and AgSbF (0.025 mmol, 9 mg) in
.1 Hz, 1H, Z), 3.84 (s, 3H, Z), 3.84 (s, 3H, E), 3.81 (s, 3H, Z), 3.74 (s,
13
H, E); C NMR (150 MHz, DMSO-d ) δ 176.9 (E), 176.6 (Z), 161.6
6
(
1
(
E), 161.3 (Z), 152.9 (E), 151.8 (Z), 150.7 (E), 150.6 (Z), 142.2 (E),
40.8 (Z), 135.7 (E), 135.4 (Z), 135.02 (E), 134.97 (Z), 131.8 (Z), 131.5
E), 119.2 (E), 119.1 (Z), 117.75 (Z), 117.72 (E), 117.69 (E), 117.67 (Z),
3
6
dry toluene (2 mL) under a nitrogen atmosphere. The reaction
mixture was reacted under the irradiation of microwave at 50 °C for
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Page 10 of 14
ARTICLE
Journal Name
+
1
0 min. The solvent was removed in vacuo and the residue was 1468, 1384, 1271, 1185, 1096; HRMS (ESI) m/z [M+H] calcd for
View Article Online
DOI: 10.1039/C8OB01684D
purified by a flash column chromatography (EtOAc/petroleum ether C H ClO 281.0364, found 281.0378.
17
10
2
=
1:20) to afford the product 5-3 (137 mg, 1:0.2 E/Z) as a yellow
3
-Fluoro-7H-benzo[c]xanthen-7-one (6c).
solid with a yield of 98%: mp 45.2 – 47.2 °C.
White solid (119 mg) in 90% yield (EtOAc/petroleum ether = 1:50):
mp 122.5–124.5 °C; H NMR (600 MHz, CDCl ) δ 8.65 (dd, J = 9.1, 5.5
1
2
-(2-(2-Methoxyvinyl)phenyl)-4H-chromen-4-one (5-3).
3
1
H NMR (600 MHz, CDCl ) δ 8.27 – 8.22 (m, 1H, E + 1H, Z), 8.07 (d, J Hz, 1H), 8.39 (d, J = 7.9 Hz, 1H), 8.28 (d, J = 8.7 Hz, 1H), 7.80 – 7.75
3
=
+
8.0 Hz, 1H, Z), 7.72 – 7.63 (m, 1H, E + 1H, Z), 7.56 – 7.53 (m, 1H, E (m, 1H), 7.65 – 7.64 (m, 2H), 7.52 (dd, J = 9.4, 2.3 Hz, 1H), 7.46 –
1H, Z), 7.49 (d, J = 8.4 Hz, 1H, E + 1H, Z), 7.47 – 7.38 (m, 3H, E + 2H, 7.41 (m, 2H); C NMR (150 MHz, CDCl ) δ 176.7, 163.2 (d, J = 251.5
3
13
Z), 7.32 – 7.27 (m, 1H, E + 1H, Z), 6.99 (d, J = 12.8 Hz, 1H, E), 6.56 (s, Hz), 155.8, 153.7, 138.3 (d, J = 9.8 Hz), 134.6, 126.8, 125.9 (d, J = 9.6
1
1
H, E), 6.54 (s, 1H, Z), 6.18 (d, J = 7.2 Hz, 1H, Z), 5.99 (d, J = 12.8 Hz, Hz), 124.7, 123.4 (d, J = 4.4 Hz), 123.2, 122.5, 121.0 (d, J = 0.9 Hz),
13
H, E), 5.38 (d, J = 7.2 Hz, 1H, Z), 3.73 (s, 3H, Z), 3.61 (s, 3H, E);
C
118.1, 117.3, 117.0 (d, J = 24.9 Hz), 112.1 (d, J = 21.0 Hz); IR (thin
−
1
NMR (150 MHz, CDCl ) δ 178.3 (Z), 178.2 (E), 165.6 (Z), 165.4 (E), film, cm ) 3423, 2925, 1631, 1474, 1412, 1384, 1240, 1142, 1008;
1
3
+
56.74 (Z), 156.67 (E), 150.7 (E),149.4 (Z), 135.6 (E), 134.4 (Z), 133.9 HRMS (ESI) m/z [M+H] calcd for C H FO 265.0659, found
17
10
2
(
E), 133.8 (Z), 131.0 (E), 130.8 (Z), 130.6 (E), 130.5 (Z), 130.2 (Z), 265.0668.
1
1
29.5 (E), 129.1 (Z), 126.21 (E), 126.16 (E), 126.1 (Z), 125.84 (E),
25.77 (Z), 125.3 (E), 125.2 (Z), 124.0 (E), 123.9 (Z), 118.2 (Z), 118.1
9
-Methyl-7H-benzo[c]xanthen-7-one (6d).
White solid (120 mg) in 92% yield (EtOAc/petroleum ether = 1:50):
mp 162.5–164.5 °C; H NMR (600 MHz, CDCl ) δ 8.63 (d, J = 8.0 Hz,
1
–
(
(
E), 112.8 (Z), 112.7 (E), 103.0 (E), 102.4 (Z), 60.9 (Z), 56.8 (E); IR
thin film, cm ) 3424, 2930, 1631, 1463, 1383, 1222, 1127, 1010;
1
−
1
3
+
H), 8.26 (d, J = 8.7 Hz, 1H), 8.17 (s, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.73
7.64 (m, 3H), 7.559 (s, 1H), 7.557 (s, 1H), 2.49 (s, 3H); C NMR
HRMS (ESI) m/z [M+H] calcd for C H O 279.1016, found
2
18 15 3
1
3
79.1018.
(
150 MHz, CDCl ) δ 177.1, 154.1, 153.8, 136.6, 135.7, 134.4, 129.6,
3
The procedure for the preparation of 6 from the substrate 5-3 and
characterization data.
To a solution of the substrate 5-3 (0.4 mmol, 111 mg) in dry toluene 1085; HRMS (ESI) m/z [M+H] calcd for C H O 261.0910, found
128.2, 126.9, 126.0, 124.3, 123.9, 123.0, 122.2, 121.7, 117.9, 117.7,
−
1
21.1; IR (thin film, cm ) 3423, 2923, 1648, 1631, 1486, 1383, 1128,
+
18 13 2
(
2 mL) was added the gold catalyst, which was generated by being 261.0915.
stirred for 30 min at room temperature after the mixture of
PPh AuCl (0.020 mmol, 10 mg) and AgSbF (0.020 mmol, 7 mg) in
dry toluene (2 mL) under a nitrogen atmosphere. The reaction
mixture was reacted under the irradiation of microwave at 80 °C for
3
-Methoxy-9-methyl-7H-benzo[c]xanthen-7-one (6e).
3
6
Yellow solid (133 mg) in 92% yield (EtOAc/petroleum ether = 1:50):
mp 157.5–159.4 °C; H NMR (600 MHz, CDCl ) δ 8.52 (d, J = 9.1 Hz,
1
3
1
–
3
1
H), 8.22 (d, J = 8.7 Hz, 1H), 8.16 (s, 1H), 7.59 (d, J = 8.7 Hz, 1H), 7.57
7.50 (m, 2H), 7.28 (dd, J = 9.1, 2.5 Hz, 1H), 7.20 (d, J = 2.4 Hz, 1H),
1
0 min. The solvent was removed in vacuo and the residue was
purified by a flash column chromatography (EtOAc/petroleum ether
1:50) to afford the product 6 (92 mg) with a yield of 93%.
13
.97 (s, 3H), 2.49 (s, 3H); C NMR (150 MHz, CDCl ) δ 176.9, 160.7,
=
3
54.1, 154.0, 138.7, 135.5, 134.2, 126.0, 124.8, 123.0, 122.6, 122.2,
−
1
General procedures for the preparation of 6, 6a-6p, 8a-8l and 118.9, 118.8, 117.8, 116.3, 107.0, 55.6, 21.1; IR (thin film, cm )
characterization data. 3423, 2924, 1653, 1630, 1462, 1384, 1259, 1117, 1031; HRMS (ESI)
To a solution of the substrates 5, 5a-5p, 7a-7l (0.5 mmol) in dry m/z [M+H] calcd for C H O 291.1016, found 291.1019.
+
19 15 3
toluene (2 mL) was added the gold catalyst, which was generated
by being stirred for 30 min at room temperature after the mixture
of PPh AuCl (0.025 mmol, 12 mg) and AgSbF (0.025 mmol, 9 mg) in
dry toluene (2 mL) under a nitrogen atmosphere. The reaction
mixture was reacted under the irradiation of microwave at 80 °C for
3
-Chloro-9-methyl-7H-benzo[c]xanthen-7-one (6f).
Yellow solid (132 mg) in 90% yield (EtOAc/petroleum ether = 1:50):
mp 168.5–170.2 °C; H NMR (600 MHz, CDCl ) δ 8.50 (d, J = 8.9 Hz,
1
–
MHz, CDCl ) δ 176.7, 154.0, 153.5, 137.3, 135.9, 135.8, 134.6, 127.7,
1
IR (thin film, cm ) 3423, 2922, 1652, 1630, 1485, 1407, 1141, 1094;
HRMS (ESI) m/z [M+H] calcd for C H ClO 295.0520, found
3
6
1
3
H), 8.24 (d, J = 8.7 Hz, 1H), 8.12 (s, 1H), 7.84 (d, J = 1.8 Hz, 1H), 7.60
7.52 (m, 3H), 7.50 (d, J = 8.5 Hz, 1H), 2.48 (s, 3H); C NMR (150
13
6
0 min. The solvent was removed in vacuo and the residue was
purified by a flash column chromatography to afford the products 6,
3
27.1, 126.0, 124.7, 123.2, 122.9, 122.5, 122.1, 117.9, 117.7, 21.1;
6
a-6p, 8a-8l.
−
1
Spectral data of 6, 6a, 8a were consistent with those reported in
+
13
the literatures.
18 12
2
2
95.0529.
3
-Chloro-7H-benzo[c]xanthen-7-one (6b).
3
-Fluoro-9-methyl-7H-benzo[c]xanthen-7-one (6g).
White solid (126 mg) in 90% yield (EtOAc/petroleum ether = 1:50):
mp 132.5–134.4 °C; H NMR (600 MHz, CDCl ) δ 8.53 (d, J = 8.9 Hz,
1
Yellow solid (133 mg) in 96% yield (EtOAc/petroleum ether = 1:50):
mp 137.5–139.5 °C; H NMR (600 MHz, CDCl ) δ 8.59 (dd, J = 9.0, 5.6
Hz, 1H), 8.25 (d, J = 8.7 Hz, 1H), 8.13 (s, 1H), 7.60 (d, J = 8.7 Hz, 1H),
7
MHz, CDCl ) δ 176.7, 163.1 (d, J = 251.3 Hz), 154.0, 153.6, 138.1 (d, J
=
3
1
1
2
7
1
1
H), 8.37 (dd, J = 7.9, 1.6 Hz, 1H), 8.26 (d, J = 8.7 Hz, 1H), 7.86 (d, J =
.0 Hz, 1H), 7.76 (ddd, J = 8.6, 7.1, 1.7 Hz, 1H), 7.66 – 7.55 (m, 3H),
3
1
3
1
3
.56 – 7.44 (m, 3H), 7.42 – 7.35 (m, 1H), 2.48 (s, 3H); C NMR (150
.47 – 7.40 (m, 1H); C NMR (150 MHz, CDCl ) δ 176.6, 155.7, 153.5,
3
37.4, 136.0, 134.6, 127.8, 127.1, 126.7, 124.74, 124.66, 123.1 (2C),
22.5, 122.4, 118.1, 117.8; IR (thin film, cm ) 3423, 2924, 1631,
3
−
1
9.7 Hz), 135.8, 134.6, 126.0, 125.9 (d, J = 9.5 Hz), 123.20, 123.15
(
d, J = 4.3 Hz), 122.1, 121.0, 117.8, 117.2 (d, J = 1.8 Hz), 116.8 (d, J =
−
1
2
4.8 Hz), 112.0 (d, J = 21.1 Hz), 21.0; IR (thin film, cm ) 3423, 2923,
1
0 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 11 of 14
O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
ARTICLE
+
−1
1
648, 1631, 1486, 1383, 1230, 1128, 1085; HRMS (ESI) m/z [M+H]
film, cm ) 3423, 2922, 1655, 1630, 1483, 1426, 1366, 1255, 1024;
View Article Online
DOI: 10.1039/C8OB01684D
+
calcd for C H FO 279.0816, found 279.0809.
HRMS (ESI) m/z [M+H] calcd for C H O 305.1172, found 305.1167.
18
12
2
20 17 3
9
-Bromo-7H-benzo[c]xanthen-7-one (6h).
3-Fluoro-9,11-dimethyl-7H-benzo[c]xanthen-7-one (6m).
White solid (112 mg) in 69% yield (EtOAc/petroleum ether = 1:50): White solid (136 mg) in 93% yield (EtOAc/petroleum ether = 1:50):
1
1
mp 152.5–154.5 °C; H NMR (600 MHz, CDCl ) δ 8.62 (d, J = 8.2 Hz, mp 166.5–168.5 °C; H NMR (600 MHz, CDCl ) δ 8.49 (dd, J = 9.0, 5.5
3
3
1
H), 8.50 (d, J = 2.4 Hz, 1H), 8.23 (d, J = 8.7 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 8.21 (d, J = 8.7 Hz, 1H), 7.93 (s, 1H), 7.56 (d, J = 8.7 Hz, 1H),
Hz, 1H), 7.84 (dd, J = 8.8, 2.5 Hz, 1H), 7.76 – 7.67 (m, 3H), 7.57 (d, J = 7.45 (dd, J = 9.4, 2.3 Hz, 1H), 7.39 – 7.31 (m, 2H), 2.60 (s, 3H), 2.41 (s,
13
13
8
.8 Hz, 1H); C NMR (150 MHz, CDCl ) δ 175.8, 154.7, 153.8, 137.4, 3H); C NMR (150 MHz, DMSO-d ) δ 175.7, 162.5 (d, J = 248.7 Hz),
3 6
1
1
1
36.8, 130.0, 129.3, 128.3, 127.3, 124.6, 124.1, 123.9, 123.0, 121.5, 152.7, 151.8, 137.7 (d, J = 10.4 Hz), 137.0, 133.9, 127.3, 125.9 (d, J =
−
1
20.2, 117.8, 117.6; IR (thin film, cm ) 3423, 2962, 2169, 1654, 9.9 Hz), 123.5 (d, J = 4.2 Hz), 122.7, 122.4, 121.2, 120.7, 117.3 (d, J =
+
631, 1382, 1263, 1087, 1029; HRMS (ESI) m/z [M+H] calcd for 25.2 Hz), 116.3 (d, J = 1.2 Hz), 112.2 (d, J = 21.3 Hz), 20.5, 15.3; IR
−
1
C H BrO 324.9859, found 324.9869.
(thin film, cm ) 3423, 2920, 1651, 1631, 1480, 1418, 1209, 1151;
1
7
10
2
+
HRMS (ESI) m/z [M+H] calcd for C H FO 293.0972, found
19
14
2
9
-Bromo-3-fluoro-7H-benzo[c]xanthen-7-one (6i).
2
93.0977.
White solid (128 mg) in 75% yield (EtOAc/petroleum ether = 1:50):
mp 181.5–183.4 °C; H NMR (600 MHz, DMSO-d ) δ 8.76 (dd, J = 9.2, 10-Methoxy-7H-benzo[c]xanthen-7-one (6n).
1
6
5
.6 Hz, 1H), 8.28 (d, J = 2.5 Hz, 1H), 8.14 (d, J = 8.7 Hz, 1H), 8.09 (dd, Yellow solid (132 mg) in 96% yield (EtOAc/petroleum ether = 1:50):
1
J = 8.9, 2.5 Hz, 1H), 7.96 (dd, J = 10.0, 2.6 Hz, 1H), 7.91 (d, J = 8.8 Hz, mp 153.5–155.4 °C; H NMR (600 MHz, CDCl ) δ 8.62 (d, J = 8.0 Hz,
1
3
13
H), 7.90 (d, J = 8.6 Hz, 1H), 7.73 (td, J = 8.9, 2.6 Hz, 1H); C NMR 1H), 8.29 (d, J = 8.8 Hz, 1H), 8.26 (d, J = 8.7 Hz, 1H), 7.91 (d, J = 7.6
(
150 MHz, DMSO-d ) δ 174.5, 162.6 (d, J = 249.3 Hz), 154.2, 153.0, Hz, 1H), 7.74 – 7.63 (m, 3H), 7.05 (d, J = 2.3 Hz, 1H), 6.99 (dd, J = 8.8,
6
13
1
4
1
2
37.9 (d, J = 10.4 Hz), 137.7, 127.7, 126.2 (d, J = 9.9 Hz), 124.0 (d, J = 2.3 Hz, 1H), 3.97 (s, 3H); C NMR (150 MHz, CDCl ) δ 176.2, 164.9,
3
.3 Hz), 123.2, 122.2, 121.3, 120.4, 117.4 (d, J = 25.1 Hz), 117.2, 157.7, 153.7, 136.5, 129.4, 128.20, 128.17, 126.9, 124.1, 124.0,
−
1
−1
16.4 (d, J = 1.6 Hz), 112.2 (d, J = 21.4 Hz); IR (thin film, cm ) 3422, 122.8, 121.7, 117.8, 116.5, 113.9, 100.5, 56.0; IR (thin film, cm )
+
924, 2196, 1631, 1469, 1385, 1086, 1008; HRMS (ESI) m/z [M+H]
3423, 2936, 1631, 1500, 1440, 1384, 1281, 1119, 1027; HRMS (ESI)
+
calcd for C H BrFO 342.9764, found 342.9771.
m/z [M+H] calcd for C H O 277.0859, found 277.0866.
17
9
2
18 13 3
9
-Bromo-3-methoxy-7H-benzo[c]xanthen-7-one (6j).
3,10-Dimethoxy-7H-benzo[c]xanthen-7-one (6o).
White solid (106 mg) in 60% yield (EtOAc/petroleum ether = 1:50): Yellow solid (138 mg) in 90% yield (EtOAc/petroleum ether = 1:50):
1
1
mp 176.2–178.2 °C; H NMR (600 MHz, DMSO-d ) δ 8.63 (d, J = 9.1 mp 173.5–175.4 °C; H NMR (600 MHz, CDCl ) δ 8.53 (d, J = 9.1 Hz,
6
3
Hz, 1H), 8.30 (d, J = 2.5 Hz, 1H), 8.11 – 8.07 (m, 2H), 7.92 (d, J = 8.9 1H), 8.30 (d, J = 8.8 Hz, 1H), 8.23 (d, J = 8.7 Hz, 1H), 7.61 (d, J = 8.7
Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 2.5 Hz, 1H), 7.46 (dd, J = Hz, 1H), 7.29 (dd, J = 9.1, 2.5 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.05 (d,
1
3
9
1
1
3
.1, 2.5 Hz, 1H), 3.97 (s, 3H); C NMR (150 MHz, DMSO-d ) δ 174.4, J = 2.3 Hz, 1H), 7.00 (dd, J = 8.8, 2.4 Hz, 1H), 3.98 (s, 3H), 3.97 (s, 3H);
6
13
60.7, 154.3, 153.4, 138.6, 137.5, 127.7, 124.6, 123.8, 123.3, 121.5,
21.2, 119.4, 117.8, 117.0, 115.3, 107.6, 55.7; IR (thin film, cm ) 128.1, 124.6, 123.1, 122.6, 119.0, 118.7, 116.5, 116.3, 113.6, 106.9,
423, 2925, 2169, 1631, 1384, 1271, 1126, 1038, 1008; HRMS (ESI) 100.4, 56.0, 55.6; IR (thin film, cm ) 3422, 2924, 2169, 1630, 1476,
m/z [M+H] calcd for C H BrO 354.9964, found 354.9960.
C NMR (150 MHz, CDCl ) δ 176.1, 164.7, 160.6, 157.6, 153.9, 138.5,
3
−
1
−
1
+
+
1422, 1234, 1184, 1019; HRMS (ESI) m/z [M+H] calcd for C H O
18
12
3
19 15
4
3
07.0965, found 307.0957.
9
,11-Dimethyl-7H-benzo[c]xanthen-7-one (6k).
White solid (126 mg) in 92% yield (EtOAc/petroleum ether = 1:50): 3-Fluoro-10-methoxy-7H-benzo[c]xanthen-7-one (6p).
1
mp 142.8–144.4 °C; H NMR (600 MHz, CDCl ) δ 8.59 (d, J = 8.0 Hz, White solid (137 mg) in 93% yield (EtOAc/petroleum ether = 1:50):
3
1
1
H), 8.24 (d, J = 8.7 Hz, 1H), 8.00 (s, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.73 mp 148.5–150.5 °C; H NMR (600 MHz, CDCl ) δ 8.64 (dd, J = 9.1, 5.5
7.61 (m, 3H), 7.40 (s, 1H), 2.67 (s, 3H), 2.44 (s, 3H); C NMR (150 Hz, 1H), 8.30 (d, J = 8.8 Hz, 1H), 8.29 (d, J = 8.7 Hz, 1H), 7.66 (d, J =
3
13
–
MHz, CDCl ) δ 177.3, 153.4, 152.5, 136.7, 136.5, 133.8, 129.5, 128.2, 8.7 Hz, 1H), 7.54 (dd, J = 9.4, 2.5 Hz, 1H), 7.45 – 7.41 (m, 1H), 7.05 (d,
3
13
1
1
1
27.2, 126.9, 124.5, 123.8, 123.6, 122.9, 122.0, 121.7, 117.4, 21.0, J = 2.3 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 3.98 (s, 3H); C NMR
5.9; IR (thin film, cm ) 3423, 2919, 1642, 1614, 1475, 1384, 1264, (150 MHz, CDCl ) δ 176.0, 165.0, 163.0 (d, J = 251.2 Hz), 157.7,
211, 1024; HRMS (ESI) m/z [M+H] calcd for C H O 275.1067, 153.7, 138.1 (d, J = 9.7 Hz), 128.3, 125.7 (d, J = 9.4 Hz), 123.31 (d, J =
−
1
3
+
1
9 15 2
found 275.1070.
4.5 Hz), 123.26, 121.0, 117.4 (d, J = 2.0 Hz), 116.9 (d, J = 25.0 Hz),
−
1
1
3
16.4, 114.0, 112.0 (d, J = 21.0 Hz), 100.5, 56.1; IR (thin film, cm )
3
-Methoxy-9,11-dimethyl-7H-benzo[c]xanthen-7-one (6l).
423, 2925, 1631, 1412, 1384, 1270, 1120, 1026; HRMS (ESI) m/z
+
White solid (147 mg) in 97% yield (EtOAc/petroleum ether = 1:50):
mp 132.5–134.5 °C; H NMR (600 MHz, CDCl ) δ 8.45 (d, J = 9.1 Hz,
[
M+H] calcd for C H FO 295.0765, found 295.0767.
18
12
3
1
3
1
H), 8.20 (d, J = 8.7 Hz, 1H), 7.98 (s, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.38 3-Methoxybenzo[c]acridin-7(12H)-one (8b).
(
s, 1H), 7.26 (dd, J = 9.1, 2.5 Hz, 1H), 7.17 (d, J = 2.4 Hz, 1H), 3.96 (s, Yellow solid (110 mg) in 80% yield (MeOH/CH Cl = 1:50): mp
H), 2.64 (s, 3H), 2.43 (s, 3H); C NMR (150 MHz, DMSO-d ) δ 175.6, 183.5–185.4 °C; H NMR (600 MHz, CDCl ) δ 8.56 (dd, J = 7.9, 1.4 Hz,
6 3
60.4, 152.9, 151.8, 138.2, 136.7, 133.5, 129.6, 127.2, 124.3, 123.3, 1H), 8.10 (d, J = 7.3 Hz, 1H), 8.09 (d, J = 9.0 Hz, 1H), 7.88 (d, J = 8.7
22.6, 121.6, 119.3, 118.0, 115.1, 107.4, 55.6, 20.4, 15.3; IR (thin Hz, 1H), 7.73 – 7.65 (m, 1H), 7.50 (t, J = 7.4 Hz, 1H), 7.13 (s, 1H),
2
2
13
1
3
1
1
7
.07 (dd, J = 9.0, 2.5 Hz, 1H), 6.86 (d, J = 2.5 Hz, 1H), 6.73 (d, J = 7.7
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 11
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Page 12 of 14
ARTICLE
Journal Name
1
3
Hz, 1H), 3.89 (s, 3H); C NMR (150 MHz, CDCl ) δ 175.3, 162.1, Hz, 1H), 7.88 (d, J = 2.2 Hz, 1H), 7.69 (dd, J = 8.9, 2.1 Hz, 1H), 7.59
3
View Article Online
DOI: 10.1039/C8OB01684D
1
1
3
44.9, 137.8, 132.7, 131.9, 127.3, 127.03, 127.01, 125.7, 124.1, (dd, J = 8.8, 2.3 Hz, 1H), 7.22 (s, 1H), 7.03 (d, J = 7.8 Hz, 1H), 2.49 (s,
18.9, 117.7, 115.1, 111.9, 108.3, 102.3, 55.7; IR (thin film, cm ) 3H); C NMR (150 MHz, DMSO-d ) δ 173.9, 143.3, 136.3, 136.0,
423, 2925, 1631, 1594, 1414, 1352, 1239, 1124, 1009; HRMS (ESI) 135.6, 133.5, 132.4, 128.4, 127.6, 126.7, 126.6, 125.8, 125.0, 123.7,
−
1
13
6
+
−1
m/z [M+H] calcd for C H NO 276.1019, found 276.1025.
116.9, 110.0, 102.5, 20.5; IR (thin film, cm ) 3422, 2923, 2169, 1631,
591, 1384, 1269, 1127, 1076; HRMS (ESI) m/z [M+H] calcd for
C H ClNO 294.0680, found 294.0682.
8 13
1
8
14
2
+
1
3
-Chlorobenzo[c]acridin-7(12H)-one (8c).
Yellow solid (134 mg) in 96% yield (MeOH/CH Cl = 1:50): mp
94.5–196.5 °C; H NMR (600 MHz, DMSO-d ) δ 8.78 (d, J = 7.8 Hz, 3-Fluoro-9-methylbenzo[c]acridin-7(12H)-one (8h).
H), 8.51 (d, J = 8.9 Hz, 1H), 8.46 (d, J = 8.8 Hz, 1H), 8.34 (d, J = 7.8 Yellow solid (136 mg) in 98% yield (MeOH/CH Cl = 1:50): mp
Hz, 1H), 7.92 – 7.82 (m, 2H), 7.65 – 7.56 (m, 2H), 7.25 (s, 1H), 7.04 186.7–188.4 °C; H NMR (600 MHz, DMSO-d ) δ 8.71 (d, J = 7.8 Hz,
d, J = 7.7 Hz, 1H); C NMR (150 MHz, DMSO-d ) δ 174.0, 143.6, 1H), 8.51 (dd, J = 9.1, 5.3 Hz, 1H), 8.31 (d, J = 8.9 Hz, 1H), 8.08 (d, J =
6
1
2
2
1
1
1
6
2
2
1
6
13
(
1
1
1
37.9, 136.5, 132.4, 132.3, 128.5, 127.6, 126.8, 126.6, 125.9, 125.8, 0.7 Hz, 1H), 7.64 (dd, J = 8.8, 1.8 Hz, 1H), 7.55 (dd, J = 9.1, 2.6 Hz,
−
1
25.6, 123.7, 117.0, 110.1, 102.7; IR (thin film, cm ) 3423, 2962, 1H), 7.40 (td, J = 8.8, 2.6 Hz, 1H), 7.15 (s, 1H), 7.00 (d, J = 7.7 Hz, 1H),
+
13
631, 1542, 1384, 1261, 1097, 1030; HRMS (ESI) m/z [M+H] calcd 2.46 (s, 3H); C NMR (150 MHz, CDCl ) δ 175.5, 164.4 (d, J = 252.8
3
for C H ClNO 280.0524, found 280.0535.
Hz), 144.0, 136.3, 135.9, 133.6, 133.1 (d, J = 9.9 Hz), 127.9 (d, J = 9.2
Hz), 127.1, 126.5, 125.0, 122.2, 117.2 (d, J = 23.2 Hz), 115.2, 112.0
17 11
−
1
3
-Fluorobenzo[c]acridin-7(12H)-one (8d).
(
d, J = 21.8 Hz), 111.1 (d, J = 2.7 Hz), 103.1, 21.0; IR (thin film, cm )
Yellow solid (124 mg) in 94% yield (MeOH/CH Cl = 1:50): mp
2
2
3404, 2924, 2169, 1631, 1597, 1384, 1271, 1119; HRMS (ESI) m/z
1
+
1
1
95.7–197.4 °C; H NMR (600 MHz, DMSO-d ) δ 8.70 (d, J = 7.8 Hz,
6
[M+H] calcd for C H FNO 278.0976, found 278.0981.
1
8 13
H), 8.50 (dd, J = 9.0, 5.2 Hz, 1H), 8.39 (d, J = 8.8 Hz, 1H), 8.33 – 8.26
(
m, 1H), 7.81 (t, J = 7.3 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.51 (dd, J = 9-Chlorobenzo[c]acridin-7(12H)-one (8i).
9
7
2
9
.1, 2.4 Hz, 1H), 7.36 (td, J = 8.8, 2.5 Hz, 1H), 7.17 (s, 1H), 6.97 (d, J = Yellow solid (130 mg) in 93% yield (MeOH/CH Cl = 1:50): mp
2 2
13
1
.8 Hz, 1H); C NMR (150 MHz, DMSO-d ) δ 173.8, 163.6 (d, J = 193.5–195.2 °C; H NMR (600 MHz, DMSO-d ) δ 8.77 (d, J = 7.8 Hz,
6
6
50.3 Hz), 143.6, 137.7, 133.1 (d, J = 10.3 Hz), 132.1, 128.6 (d, J = 1H), 8.59 (d, J = 9.4 Hz, 1H), 8.56 (d, J = 8.3 Hz, 1H), 8.28 (d, J = 2.7
.4 Hz), 126.7, 126.3, 125.7, 125.6, 121.5 (d, J = 1.9 Hz), 116.8, 116.5 Hz, 1H), 7.93 (dd, J = 9.2, 2.7 Hz, 1H), 7.82 – 7.73 (m, 2H), 7.67 –
13
(
(
d, J = 23.2 Hz), 111.7 (d, J = 22.0 Hz), 110.4 (d, J = 2.7 Hz), 102.3; IR 7.60 (m, 1H), 7.35 (s, 1H), 7.15 (d, J = 7.8 Hz, 1H); C NMR (150 MHz,
thin film, cm ) 3404, 2923, 1631, 1602, 1383, 1269, 1121, 1051; DMSO-d ) δ 172.6, 144.6, 136.7, 132.0, 131.9, 130.8, 130.7, 128.8,
−
1
6
+
HRMS (ESI) m/z [M+H] calcd for C H FNO 264.0819, found 128.1, 126.9, 125.5, 125.2, 124.7, 124.5, 119.9, 111.8, 102.7; IR
2
17 11
−
1
64.0814.
(thin film, cm ) 3440, 2923, 1631, 1403, 1384, 1271, 1126, 1032,
+
1
2
010; HRMS (ESI) m/z [M+H] calcd. for C H ClNO 280.0524, found
17 11
9
-Methylbenzo[c]acridin-7(12H)-one (8e).
80.0528.
Yellow solid (124 mg) in 96% yield (MeOH/CH Cl = 1:50): mp
2
2
1
1
1
–
1
87.5–189.5 °C; H NMR (600 MHz, DMSO-d ) δ 8.69 (d, J = 7.6 Hz, 9-Chloro-3-methoxybenzo[c]acridin-7(12H)-one (8j).
6
H), 8.47 (d, J = 8.2 Hz, 1H), 8.35 (d, J = 8.8 Hz, 1H), 8.12 (s, 1H), 7.74 Yellow solid (127 mg) in 82% yield (MeOH/CH Cl = 1:50): mp
2
2
1
7.68 (m, 2H), 7.65 (d, J = 8.3 Hz, 1H), 7.59 (t, J = 7.3 Hz, 1H), 7.21 (s, 191.5–193.5 °C; H NMR (600 MHz, DMSO-d ) δ 8.75 (d, J = 7.9 Hz,
H), 7.04 (d, J = 7.6 Hz, 1H), 2.47 (s, 3H); C NMR (150 MHz, DMSO- 1H), 8.54 (d, J = 9.4 Hz, 1H), 8.47 (d, J = 9.2 Hz, 1H), 8.26 (d, J = 2.7
6
13
d6) δ 173.7, 143.9, 136.0, 135.4, 133.4, 131.6, 130.7, 128.6, 126.8, Hz, 1H), 7.89 (dd, J = 9.2, 2.7 Hz, 1H), 7.32 (d, J = 2.7 Hz, 1H), 7.24 –
1
3
1
25.3, 125.2, 125.0, 124.9, 118.8, 116.9, 111.2, 102.1, 20.5; IR (thin 7.17 (m, 2H), 7.09 (d, J = 7.8 Hz, 1H), 3.92 (s, 3H); C NMR (150 MHz,
−
1
film, cm ) 3408, 2962, 1631, 1596, 1384, 1261, 1097, 1028; HRMS DMSO-d ) δ 172.2, 162.0, 144.8, 136.5, 132.9, 131.7, 130.7, 128.1,
6
+
(
ESI) m/z [M+H] calcd for C H NO 260.1070, found 260.1075.
127.6, 125.7, 124.5, 119.6, 117.9, 117.6, 111.8, 108.6, 101.4, 55.7;
IR (thin film, cm ) 3422, 2923, 1631, 1402, 1387, 1287, 1265, 1010;
18 14
−
1
+
3
-Methoxy-9-methylbenzo[c]acridin-7(12H)-one (8f).
HRMS (ESI) m/z [M+H] calcd for C H ClNO 310.0629, found
18
13
2
Yellow solid (118 mg) in 82% yield (EtOAc/petroleum ether = 1:50):
mp 177.5–179.5 °C; H NMR (600 MHz, DMSO-d ) δ 8.67 (d, J = 7.7
3
10.0632.
1
6
Hz, 1H), 8.36 (d, J = 9.1 Hz, 1H), 8.30 (d, J = 8.9 Hz, 1H), 8.09 (s, 1H), 3,9-Dichlorobenzo[c]acridin-7(12H)-one (8k).
.62 (d, J = 8.3 Hz, 1H), 7.23 (d, J = 2.3 Hz, 1H), 7.14 (dd, J = 9.0, 2.4 Yellow solid (141 mg) in 90% yield (MeOH/CH Cl = 1:50): mp
7
2
2
1
Hz, 1H), 7.07 (s, 1H), 6.99 (d, J = 7.7 Hz, 1H), 3.89 (s, 3H), 2.46 (s, 3H); 185.5–187.4 °C; H NMR (600 MHz, DMSO-d ) δ 8.79 (d, J = 7.9 Hz,
6
13
C NMR (150 MHz, DMSO-d ) δ 173.4, 161.7, 144.1, 135.9, 135.2, 1H), 8.56 – 8.54 (m, 2H), 8.25 (d, J = 2.4 Hz, 1H), 7.96 – 7.84 (m, 2H),
33.1, 132.8, 127.3, 126.7, 125.7, 125.1, 118.1, 117.4, 116.7, 111.2, 7.62 (dd, J = 8.8, 1.6 Hz, 1H), 7.32 (s, 1H), 7.09 (d, J = 7.8 Hz, 1H); C
08.5, 100.9, 55.7, 20.5; IR (thin film, cm ) 3408, 2924, 2169, 1596, NMR (150 MHz, DMSO-d ) δ 172.7, 144.0, 136.7, 136.6, 132.4,
6
13
1
1
1
2
−
1
6
+
384, 1261, 1127, 1076; HRMS (ESI) m/z [M+H] calcd for C H NO
132.1, 130.9, 128.6, 128.1, 127.8, 126.7, 125.9, 124.5, 123.6, 119.9,
110.5, 103.0; IR (thin film, cm ) 3423, 2924, 1631, 1592, 1402, 1384,
269, 1008; HRMS (ESI) m/z [M+H] calcd for C H Cl NO 314.0134,
17 10 2
19
16
2
−
1
90.1176, found 290.1187.
+
1
3
-Chloro-9-methylbenzo[c]acridin-7(12H)-one (8g).
found 314.0141.
Yellow solid (144 mg) in 98% yield (MeOH/CH Cl = 1:50): mp
1
1
2
2
1
85.5–187.5 °C; H NMR (600 MHz, DMSO-d ) δ 8.77 (d, J = 7.9 Hz, 9-Chloro-3-fluorobenzo[c]acridin-7(12H)-one (8l).
6
H), 8.51 (d, J = 8.9 Hz, 1H), 8.37 (d, J = 9.0 Hz, 1H), 8.12 (d, J = 1.1
1
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 13 of 14
O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
Yellow solid (137 mg) in 92% yield (MeOH/CH Cl = 1:50): mp
ARTICLE
9
3, 295-306; g) P. Saha, S. Mandal, A. Das, P. CV.ieDwaAsrt,icSle.ODnlainse,
2
2
1
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1
1
2
1
91.5–193.3 °C; H NMR (600 MHz, DMSO-d ) δ 8.78 (d, J = 7.9 Hz,
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H), 8.62 (dd, J = 9.2, 5.2 Hz, 1H), 8.54 (d, J = 9.4 Hz, 1H), 8.25 (d, J =
.7 Hz, 1H), 7.91 (dd, J = 9.2, 2.7 Hz, 1H), 7.63 (dd, J = 9.1, 2.7 Hz,
H), 7.46 (td, J = 8.8, 2.7 Hz, 1H), 7.30 (s, 1H), 7.09 (d, J = 7.8 Hz, 1H);
1
3
C NMR (150 MHz, DMSO-d ) δ 172.6, 163.9 (d, J = 250.7 Hz), 144.1,
6
1
1
36.6, 133.3 (d, J = 10.4 Hz), 132.0, 130.9, 129.0 (d, J = 9.5 Hz),
28.0, 126.5, 124.5, 121.5 (d, J = 2.1 Hz), 119.8, 116.8 (d, J = 23.2
2
043; m) R. Satheeshkumar, W. Kaminsky, K. J. Rajendra Prasad,
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G. Cholewiński, K. Dzierzbicka, RSC Adv. 2017, 7, 15776-15804;
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Hz), 111.9 (d, J = 22.1 Hz), 111.0 (d, J = 2.8 Hz), 102.7; IR (thin film,
−
1
cm ) 3422, 2924, 1649, 1631, 1537, 1406, 1387, 1286, 1226; HRMS
+
(
ESI) m/z [M+H] calcd for C H ClFNO 298.0429, found 298.0434.
17 10
Acknowledgements
We were grateful to the National Natural Science Foundation of
China (Grants 21372157) and the Foundation of Liaoning Province
Education Administration of China (Grants 2017LQN08). We
acknowledged the program for innovative research team of the
Ministry of Education and the program for Liaoning innovative
research team in university and Career Development Support Plan
for Young and Middle-aged Teachers in Shenyang Pharmaceutical
University. The project is sponsored by “Liaoning BaiQianWan
Talents Program“.
80, 1187-1192.
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