Tunable synthesis of 3-acyl-2-naphthols and 3-substituted isocoumarins via jones reagent promoted cascade reactions of 2-(4-hydroxy-but-1-ynyl) benzaldehydes

Article abstract of DOI:10.1021/jo401502k

Novel and efficient synthesis of 3-acyl-2-naphthols and 3-substituted isocoumarins via the tunable cascade reactions of 2-(4-hydroxy-but-1-ynyl) benzaldehydes have been developed. Treatment of 2-(4-hydroxy-but-1-ynyl) benzaldehydes with 0.7 equiv of Jones

Full text of DOI:10.1021/jo401502k

Article
pubs.acs.org/joc
Tunable Synthesis of 3‑Acyl-2-naphthols and 3‑Substituted
Isocoumarins via Jones Reagent Promoted Cascade Reactions of
2‑(4-Hydroxy-but-1-ynyl)benzaldehydes
Yan He,†,‡ Xinying Zhang,‡ Nana Shen,‡ and Xuesen Fan*,†,‡
†School of Environment, Key Laboratory for Yellow River and Huai River Water Environment and Pollution Control, Ministry of
Education, Henan Normal University, Xinxiang, Henan 453007, PR China
‡School of Chemistry and Chemical Engineering, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education,
Henan Normal University, Xinxiang, Henan 453007, PR China
S
* Supporting Information
ABSTRACT: Novel and efficient synthesis of 3-acyl-2-
naphthols and 3-substituted isocoumarins via the tunable
cascade reactions of 2-(4-hydroxy-but-1-ynyl)benzaldehydes
have been developed. Treatment of 2-(4-hydroxy-but-1-
ynyl)benzaldehydes with 0.7 equiv of Jones reagent in
CH3CN and subsequent purification through column
chromatography on silica gel pre-eluted with Et3N afforded
3-acyl-2-naphthols with high efficiency. When the same
substrates were treated with 3 equiv of Jones reagents in acetone, on the other hand, 3-substituted isocoumarins could be
obtained in good yields.
strategies are not applicable for the synthesis of 3-acyl-2-
naphthols, mainly because of selectivity and/or reactivity
problems. For example, Hashimoto et al. observed that efficient
benzoylation of 2-naphthol needed 10 equiv of benzoyl chloride
in neat TfOH, and the reaction mainly gave 1-benzoyl-2-
naphthol rather than 3-benzoyl-2-naphthol (Scheme 3).7 It was
also found that the Fries rearrangement of 2-naphthyl benzoate,
another likely route leading to 3-benzoyl-2-naphthol, did not
take place at all under the catalysis of TfOH.7 Park et al. observed
that the reaction of 2-methoxynaphthalene with benzoyl chloride
in the presence of AlCl3 gave 1-benzoyl-2-naphthol in 77% yield,
but no 3-benzoyl-2-naphthol was obtained.8 To solve these
problems, Kozlowski et al. developed a pathway toward 3-aroyl-
2-naphthol in which 2-methoxynaphthalene was first ortho-
lithiated and then treated with a Weinreb amide to give 3-
benzoyl-2-methoxynaphthalene. Subsequent demethylation of 3-
benzoyl-2-methoxynaphthalene with BCl3 afforded the desired
3-benzoyl-2-naphthol (Scheme 3).5 While this elegant strategy is
reliable, the usage of powerful base and naphthalene precursors
may dent its application scope and substrate generality. On the
other hand, it is well-known that isocoumarins are ubiquitous
structural units in a plethora of natural products with remarkable
biological interests and the majority of the naturally occurring
isocoumarins that are of polyketide origin possess a C-3
substituent.9−11 As a result, developing practical and convenient
synthetic protocols for isocoumarins has always been a hot topic
in the synthetic community.12 On the basis of the above facts, the
INTRODUCTION
■
During our recent study on functionalized allenes, we have been
trying to prepare a 1,2-allenic ketone derivative, 2-(4-oxo-4-
phenylbuta-1,2-dienyl)benzaldehyde (A), based on an envi-
sioned synthetic pathway as shown in Scheme 1.
The synthetic work started with the coupling reaction of 1-
phenylbut-3-yn-1-ol (1a) with 2-bromobenzaldehyde (2a)
under standard conditions,1 which afforded 2-(4-hydroxy-4-
phenylbut-1-ynyl)benzaldehyde (3a) in 90% yield (Scheme 2).
Following oxidation of 3a with Jones reagent, however, did not
give the expected allenic ketone A.2 Instead, 2-(4-oxo-4-
phenylbut-1-ynyl)benzaldehyde (4a) was formed together with
3-benzoyl-2-naphthol (5a) and 3-(2-oxo-2-phenylethyl)-1H-
isochromen-1-one (6a). Moreover, it was observed that 4a
could be cleanly converted into 3-benzoyl-2-naphthol (5a) upon
purification via column chromatography on silica gel pre-eluted
with Et3N (Scheme 2).
Although the envisioned 1,2-allenic ketone was not obtained
from the reaction of 3a, we realized that the unexpected
formation of 5a and 6a might be more rewarding. First, (o-
hydroxyaryl)(aryl)methanones are the basic scaffolds of a
plethora of compounds with remarkable biological activities.3
In particular, 3-acyl-2-naphthols like 5a and their derivatives have
been used as building blocks of compounds with valuable
applications in chemical, medicinal as well as material fields.4−6
Notwithstanding their importance, efficient synthetic methods
toward 3-acyl-2-naphthols are surprisingly limited. While
Friedel−Crafts acylation of phenols or Fries-type rearrangement
of suitable aryl esters are the most frequently used methods to
prepare (o-hydroxyaryl)(aryl)methanone derivatives, these
Received: July 22, 2013
© XXXX American Chemical Society
A
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Scheme 1. Envisioned Synthetic Pathway toward 1,2-Allenic Ketone A
Scheme 2. Unexpected Formation of 5a and 6a from the Reaction of 3a
Scheme 3. Literature Synthetic Pathways toward 3-Benzoyl-2-naphthol (5a)
a
Table 1. Optimization Study for the Synthesis of 5a and 6a from 3a
b
yield (%)
entry
amount of oxidant (equiv)
solvent
T (°C)
t (min)
5a
42
6a
1
1.2
1.8
2.4
3
acetone
acetone
acetone
acetone
acetone
acetone
acetone
acetone
CH3CN
CH2Cl2
THF
0
0
10
10
10
10
10
10
20
10
10
30
30
33
43
50
68
69
42
15
9
2
21
10
3
0
4
0
trace
trace
31
5
3
−10
reflux
0
6
3
7
0.7
0.7
0.7
0.7
0.7
50
8
reflux
60
62
9
75
trace
8
10
11
reflux
60
35
48
7
a
b
Reaction conditions: 3a (0.5 mmol), solvent (5 mL). Isolated yield after column chromatography on silica gel pre-eluted with Et3N.
formation of 5a and 6a from readily obtainable 3a under mild
conditions validates its potentiality as alternative protocols for
the synthesis of 3-acyl-2-naphthols and 3-substituted isocoumar-
ins and deserves further exploration.
RESULTS AND DISCUSSION
■
On the basis of the above facts, optimization studies to make the
reaction of 3a proceed in a more selective manner to give either
5a or 6a as the main product were carried out. Thus, 3a was
B
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a
Table 2. Synthesis of 3-Acyl-2-naphthols 5a−5w
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Table 2. continued
a
b
c
3 (1 mmol), Jones reagent (0.7 mmol), CH3CN (10 mL), 60 °C, 10 min. Isolated yield. Confirmed by X-ray diffraction analysis.
treated with varied amounts of oxidant under different reaction
temperatures (Table 1). First, we observed that with Jones
reagent more than 1.2 equiv, the yield of 6a increased while that
of 5a decreased accordingly (entries 2−4). When 3a was treated
with 3 equiv of Jones reagent in acetone at 0 °C for 10 min, 6a
could be obtained in 68% yield (entry 4). With the same amount
of oxidant, lower temperature (−10 °C) resulted in similar yield
of 6a as that of 0 °C (entry 5). On the other hand, higher
temperature (in refluxing acetone) gave decreased yield of 6a but
increased yield of 5a (entry 6). Next, the reaction of 3a was tried
with Jones reagent in an amount less than 1.2 equiv. We found
that after 3a was treated with 0.7 equiv of Jones reagent in
acetone at 0 °C for 20 min, 5a and 6a were obtained in yields of
50 and 15%, respectively (entry 7). Further optimization showed
that higher temperature facilitated the transformation of 3a
toward 5a (entry 8). Finally, different solvents were also tried as
possible media (entries 9−11). It turned out that 5a could be
obtained in a yield of 75% by treating 3a with Jones reagent in
CH3CN at 60 °C for 10 min (entry 9). Under similar conditions,
using CH2Cl2 and THF as the solvent gave lower yields of 5a
(entries 10 and 11).
naphthyl (entry 20), thienyl (entry 21) or alkyl groups (entries
22 and 23) to afford the corresponding 3-acyl-2-naphthols 5b−
5w with yields ranging from 65 to 76% without showing obvious
electronic and steric effects.
Moreover, it was demonstrated that the aldehyde moiety of 3
with R2 as methyl or fluoro group is also suitable for the 3-acyl-
naphthols synthesis to give 5x−5cc in yields ranging from 65 to
74% (Table 3). These results suggest that the newly developed 3-
acyl-2-naphthols synthesis will find a broad range of applications.
In the next stage, the generality and scope for the synthesis of
3-substituted isocoumarins (6) from the tandem reaction of 3
was studied. As shown in Table 4, the reaction is compatible with
an array of 2-(4-hydroxy-but-1-ynyl)benzaldehydes bearing
either electron-withdrawing or electron-donating substituents
attached on the ortho, meta, or para positions (entries 1−18), and
all the substrates participated in this tandem reaction efficiently
to give the corresponding 3-substituted isocoumarins 6a−6r in
reasonably good yields.
On the basis of the above observations, plausible pathways to
account for the formation of 5a and 6a from 3a were proposed as
shown in Scheme 4. Initially, oxidation of 3a by Jones reagent
gives 3-yn-1-one 4a. In the presence of an excess amount of Jones
reagent, 4a is further oxidized to give 2-(4-oxo-4-phenylbut-1-
ynyl)benzoic acid (I). Under the reaction conditions, the
carboxyl group in I is protonated to initiate an intramolecular
Michael-type (6-endo) cyclization to give isocoumarin 6a.13 On
the other hand, in the presence of only 0.7 equiv of Jones reagent,
With the optimized conditions in hand, we first screened a
range of 2-(4-hydroxy-but-1-ynyl)benzaldehydes (3) to probe
the scope of the new synthetic strategy toward 3-acyl-2-
naphthols 5 (Table 2). It turns out that the R1 unit of 3 can be
either electron-rich (Table 2, entries 2, 6, 10, 11 and 19) or
electron-deficient (entries 3−5, 7−9, 12−16 and 18) phenyl,
D
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a
Table 3. Synthesis of 3-Acyl-2-naphthols 5x−5cc
a
b
Reaction conditions: 3 (1 mmol), Jones reagent (0.7 mmol), CH3CN (10 mL), 60 °C, 10 min. Isolated yield.
the oxidation mainly gives 4a. Isomerization of 4a affords its
allenic ketone counterpart (A),14 which then undergoes a
nucleophilic hydration to give an enol intermediate (II).
Following intramolecular Knoevenagel condensation of II results
in a cyclic enone (III). Aromatization of III affords 5a as the final
product.
CONCLUSION
■
In summary, we have developed a tunable synthesis of 3-acyl-2-
naphthols and 3-substituted isocoumarins via Jones reagent
promoted cascade reactions of the readily obtainable 2-(4-
hydroxy-but-1-ynyl)benzaldehydes. Treatment of 2-(4-hydroxy-
but-1-ynyl)benzaldehydes with 0.7 equiv of Jones reagent
initiated a tandem process including oxidation, isomerization,
hydration, intramolecular Knovengel condensation and aromati-
zation to afford 3-acyl-2-naphthols in good yields. By using this
strategy, an alternative synthetic pathway toward the pharma-
ceutically attractive 1,3-dihydroxy-12H-benzo[b]xanthen-12-
one was developed. On the other hand, when 2-(4-hydroxy-
but-1-ynyl)benzaldehydes were treated with excess amount of
Jones reagent, another version of cascade process took place, and
the biologically and synthetically interesting 3-substituted
isocoumarin could be obtained with good efficiency. Compared
with literature procedures toward 3-acyl-2-naphthols and 3-
substituted isocoumarin, the strategies developed herein showed
advantages such as readily available starting materials and more
practical reaction conditions.
Recently, Wang et al. revealed that 1,3-dihydroxy-12H-
benzo[b]xanthen-12-one (7, Scheme 5) was capable of inhibiting
yeast’s α-glucosidase 17-fold more strongly than its xanthone
counterpart that has smaller conjugated π-system.15 Moreover,
Na et al. found the bisepoxyl derivative of 7 showed significant
cancer cell growth inhibition against the HT29 and DU145 cell
lines.16 We noticed that in the aforementioned two studies,
compound 7 was prepared through the condensation of 3-
hydroxy-2-naphthoic acid with phloroglucinol in the presence of
anhydrous zinc chloride in refluxing phosphoryl chloride.15,16 To
circumvent the usage of naphthalene precursor and harsh and
strictly anhydrous conditions employed in the above-mentioned
processes, we tried to prepare 7 with an alternative procedure
based on the synthetic strategy developed herein. Thus, 2-(4-(2-
bromo-4,6-dimethoxyphenyl)-4-hydroxybut-1-ynyl)benz-
aldehyde (3hh) was treated with Jones reagent to give (2-bromo-
4,6-dimethoxyphenyl)(3-hydroxynaphthalen-2-yl)methanone
(5dd), which was then transformed into 5ee upon treatment
with BBr3. Subsequent base-promoted intramolecular O-arylation
of 5ee afforded 7 with high efficiency (Scheme 5).
EXPERIMENTAL SECTION
■
General Methods. 2-(4-Hydroxy-but-1-ynyl)benzaldehydes (3)
were prepared through coupling of but-3-yn-1-ols (1) with 2-
bromobenzaldehydes (2) based on literature method.1 Melting points
were recorded with a micromelting point apparatus and uncorrected. 1H
E
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a
Table 4. Synthesis of 3-Substituted Isocoumarins 6a−6r
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Table 4. continued
a
b
Reaction conditions: 3 (1 mmol), Jones reagent (3 mmol), acetone (10 mL), 0 °C, 10 min. Isolated yield.
Scheme 4. Plausible Mechanism for the Formation of 5a and 6a from 3a
Scheme 5. Alternative Synthetic Pathway toward Compound 7
and 13C NMR spectra were recorded at 400 and 100 MHz, respectively.
Chemical shifts were reported in ppm from tetramethylsilane (TMS) as
internal standard in CDCl3 solutions. Multiplicity was indicated as
follows: s (singlet); d (doublet); t (triplet); m (multiplet); dd (doublet
of doublets); td (triplet of doublets); br s (broad singlet), etc. Coupling
constants are given in Hz. High-resolution mass spectra (HRMS) were
obtained by using a MicroTOF mass spectrometer. All reactions were
monitored by thin-layer chromatography (TLC) using silica gel plates
(silica gel 60 F254 0.25 mm).
Typical Procedure for the Synthesis of 3a and Spectroscopic
Data of 3a−3hh. To a flask containing 1-phenylbut-3-yn-1-ol (1a, 2
mmol) and 2-bromobenzaldehyde (2a, 2.4 mmol) in Et3N (8 mL) were
added Pd(PPh3)2Cl2 (0.04 mmol) and CuI (0.02 mmol). After the
mixture was stirred at 50 °C under N2 atmosphere for 2 h, the reaction
was quenched with aqueous NH4Cl and extracted with ethyl acetate (10
G
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mL × 3). The combined organic layers were washed with water and
brine and then dried over anhydrous Na2SO4. The solvent was
evaporated under a vacuum, and the crude product was purified by
chromatography on silica gel by using petroleum ether−ethyl acetate
(5:1) as the eluent to afford 3a. 3b−3hh were prepared in a similar
manner.
2-(4-Hydroxy-4-phenylbut-1-ynyl)benzaldehyde (3a). Eluent,
petroleum ether−ethyl acetate (5:1). Yellow liquid (450 mg, 90%): 1H
NMR (400 MHz, CDCl3) δ 2.89−2.94 (m, 2H), 3.50 (s, 1H), 4.97 (t, J =
6.4 Hz, 1H), 7.26−7.50 (m, 8H), 7.80 (d, J = 8.0 Hz, 1H), 10.21 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 30.5, 72.5, 79.0, 94.0, 125.9, 126.6,
71.7, 79.5, 93.3, 124.0, 126.10, 126.15, 128.1, 128.4, 128.6, 129.8, 133.5,
133.8, 134.4, 136.0, 144.9, 192.0; MS m/z 285 [MH]+; HRMS (ESI)
calcd for C17H14ClO2 285.0682 [M + H], found 285.0681.
2-(4-(3-Bromophenyl)-4-hydroxybut-1-ynyl)benzaldehyde
(3i). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (590
mg, 90%): 1H NMR (400 MHz, CDCl3) δ 2.90 (d, J = 6.8 Hz, 2H), 3.46
(s, 1H), 4.95 (t, J = 6.2 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.33−7.51 (m,
5H), 7.60 (s, 1H), 7.82 (d, J = 7.6 Hz, 1H), 10.24 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 30.7, 71.7, 79.6, 93.2, 122.6, 124.5, 126.0, 128.4,
128.7, 129.0, 130.1, 131.0, 133.5, 133.8, 136.0, 145.0, 192.1; MS m/z 329
[MH]+; HRMS (ESI) calcd for C17H14BrO2 329.0177 [M + H], found
329.0178.
2-(4-Hydroxy-4-(4-methoxyphenyl)but-1-ynyl)benz-
aldehyde (3j). Eluent, petroleum ether−ethyl acetate (5:1). Yellow
liquid (515 mg, 92%): 1H NMR (400 MHz, CDCl3) δ 2.90 (t, J = 6.4 Hz,
2H), 3.32 (s, 1H), 3.77 (s, 3H), 4.91 (d, J = 5.2 Hz, 1H), 6.87 (d, J = 9.2
Hz, 2H), 7.31−7.47 (m, 5H), 7.80 (d, J = 7.6 Hz, 1H), 10.21 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 30.5, 55.3, 72.2, 78.8, 94.1, 113.9, 126.7,
127.1, 127.9, 128.2, 133.4, 133.7, 135.0, 136.0, 159.3, 192.2; MS m/z 281
[MH]+; HRMS (ESI) calcd for C18H17O3 281.1178 [M + H], found
281.1175.
2-(4-Hydroxy-4-p-tolylbut-1-ynyl)benzaldehyde (3k). Eluent,
petroleum ether−ethyl acetate (5:1). Yellow liquid (475 mg, 90%): 1H
NMR (400 MHz, CDCl3) δ 2.35 (s, 3H), 2.91−2.93 (m, 2H), 3.05 (s,
1H), 4.95 (d, J = 5.6 Hz, 1H), 7.17 (d, J = 6.4 Hz, 2H), 7.30−7.49 (m,
5H), 7.82 (d, J = 7.6 Hz, 1H), 10.24−10.25 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 21.1, 30.5, 72.4, 78.9, 94.0, 125.7, 126.6, 128.0, 128.2,
129.2, 133.4, 133.6, 136.1, 137.8, 139.7, 192.1; MS m/z 265 [MH]+;
HRMS (ESI) calcd for C18H17O2 265.1229 [M + H], found 265.1233.
2-(4-(4-Fluorophenyl)-4-hydroxybut-1-ynyl)benzaldehyde
(3l). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (482
mg, 90%): 1H NMR (400 MHz, CDCl3) δ 2.79−2.90 (m, 2H), 4.26 (s,
1H), 4.90 (t, J = 6.6 Hz, 1H), 6.95 (t, J = 8.8 Hz, 2H), 7.24−7.40 (m,
5H), 7.70 (d, J = 7.6 Hz, 1H), 10.16 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 30.5, 71.7, 78.9, 94.0, 115.1, 115.3, 126.6, 127.6, 127.7, 127.9,
128.2, 133.4, 133.8, 135.9, 138.79, 138.82, 161.1, 163.5, 192.3; MS m/z
269 [MH]+; HRMS (ESI) calcd for C17H14FO2 269.0978 [M + H],
found 269.0982.
2-(4-(4-Chlorophenyl)-4-hydroxybut-1-ynyl)benzaldehyde
(3m). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (506
mg, 89%): 1H NMR (400 MHz, CDCl3) δ 2.89 (d, J = 6.4 Hz, 2H), 4.96
(t, J = 6.2 Hz, 1H), 7.27−7.51 (m, 7H), 7.81 (d, J = 8.0 Hz, 1H), 10.26 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 30.7, 71.8, 79.5, 93.3, 126.0, 127.2,
128.4, 128.6, 128.8, 133.5, 133.7, 133.8, 136.0, 141.2, 192.1; MS m/z 285
[MH]+; HRMS (ESI) calcd for C17H14ClO2 285.0682 [M + H], found
285.0677.
2-(4-(4-Bromophenyl)-4-hydroxybut-1-ynyl)benzaldehyde
(3n). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (597
mg, 91%): 1H NMR (400 MHz, CDCl3) δ 2.89 (d, J = 6.0 Hz, 2H), 3.39
(s, 1H), 4.94 (t, J = 5.6 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.41−7.52 (m,
5H), 7.82−7.84 (m, 1H), 10.27 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
30.7, 71.8, 79.5, 93.2, 121.8, 126.0, 127.6, 128.4, 128.9, 131.6, 133.5,
133.8, 136.0, 141.7, 192.1; MS m/z 329 [MH]+; HRMS (ESI) calcd for
C17H14BrO2 329.0177 [M + H], found 329.0182.
4-(4-(2-Formylphenyl)-1-hydroxybut-3-ynyl)benzonitrile
(3o). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (468
mg, 85%): 1H NMR (400 MHz, CDCl3) δ 2.90−2.94 (m, 2H), 5.07 (t, J
= 6.0 Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.52−7.57 (m, 3H), 7.65 (d, J =
8.0 Hz, 2H), 7.83 (d, J = 8.0 Hz, 1H), 10.24 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 30.7, 71.6, 111.6, 118.8, 126.6, 128.6, 132.3, 132.4,
133.5, 133.9, 136.0, 147.9, 192.0; MS m/z 276 [MH]+; HRMS (ESI)
calcd for C18H14NO2 276.1025 [M + H], found 276.1026.
2-(4-Hydroxy-4-(4-(trifluoromethyl)phenyl)but-1-ynyl)-
benzaldehyde (3p). Eluent, petroleum ether−ethyl acetate (5:1).
Yellow liquid (547 mg, 86%): 1H NMR (400 MHz, CDCl3) δ 2.91−2.94
(m, 3H), 5.07 (t, J = 5.8 Hz, 1H), 7.41−7.63 (m, 7H), 7.83 (d, J = 7.6 Hz,
1H), 10.26 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 30.8, 71.8, 79.9,
92.8, 125.4, 125.45, 125.52, 126.1, 128.4, 129.4, 133.5, 133.8, 135.9,
146.5, 192.0; MS m/z 319 [MH]+; HRMS (ESI) calcd for
C18H13F3NaO2 341.0765 [M + Na], found 341.0762.
128.0, 128.2, 128.5, 133.4, 133.8, 136.0, 142.8, 192.3; MS m/z 251
[MH]+; HRMS (ESI) calcd for C17H15O2 251.1072 [M + H], found
251.1066.
2-(4-Hydroxy-4-(2-methoxyphenyl)but-1-ynyl)benz-
aldehyde (3b). Eluent, petroleum ether−ethyl acetate (5:1). Yellow
liquid (515 mg, 92%): 1H NMR (400 MHz, CDCl3) δ 2.92−3.09 (m,
2H), 3.26 (s, 1H), 3.87 (s, 3H), 5.20 (t, J = 5.6 Hz, 1H), 6.91 (d, J = 8.4
Hz, 1H), 7.00 (t, J = 7.4 Hz, 1H), 7.26−7.50 (m, 6H), 7.84 (d, J = 7.6 Hz,
1H), 10.29 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 28.6, 55.3, 69.2,
78.6, 94.5, 110.4, 120.8, 127.0, 127.7, 128.1, 128.9, 130.3, 133.4, 133.7,
136.0, 156.2, 192.3; MS m/z 281 [MH]; HRMS (ESI) calcd for
C18H17O3 281.1177 [M + H], found 281.1182.
2-(4-(2-Fluorophenyl)-4-hydroxybut-1-ynyl)benzaldehyde
(3c). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (477
mg, 89%): 1H NMR (400 MHz, CDCl3) δ 2.92−3.07 (m, 2H), 5.32−
5.35 (m, 1H), 7.04−7.62 (m, 7H), 7.85 (d, J = 6.8 Hz, 1H), 10.26 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 29.5, 66.61, 66.63, 79.5, 93.1,
115.2, 115.5, 124.37, 124.41, 126.1, 127.2, 127.3, 128.3, 128.8, 129.4,
129.5, 129.7, 133.5, 133.7, 136.1, 158.4, 160.9, 192.1; MS m/z 269
[MH]+; HRMS (ESI) calcd for C17H14FO2 269.0978 [M + H], found
269.0980.
2-(4-(2-Chlorophenyl)-4-hydroxybut-1-ynyl)benzaldehyde
(3d). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (511
mg, 90%): 1H NMR (400 MHz, CDCl3) δ 2.84−3.10 (m, 3H), 5.41 (t, J
= 5.0 Hz, 1H), 7.22−7.52 (m, 6H), 7.68 (d, J = 7.6 Hz, 1H), 7.83 (d, J =
7.2 Hz, 1H), 10.28 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 28.8, 68.8,
79.4, 93.3, 126.1, 127.12, 127.15, 128.3, 128.8, 129.0, 129.4, 131.6, 133.5,
133.8, 136.0, 139.9, 192.2; MS m/z 285 [MH]+; HRMS (ESI) calcd for
C17H14ClO2 285.0682 [M + H], found 285.0677.
2-(4-(2-Bromophenyl)-4-hydroxybut-1-ynyl)benzaldehyde
(3e). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (577
mg, 88%): 1H NMR (400 MHz, CDCl3) δ 2.83−3.11 (m, 3H), 5.36 (t, J
= 5.6 Hz, 1H), 7.17 (t, J = 7.2 Hz, 1H), 7.34−7.54 (m, 5H), 7.68 (d, J =
8.0 Hz, 1H), 7.84 (d, J = 7.6 Hz, 1H), 10.29 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 28.9, 71.0, 79.4, 93.3, 121.7, 126.1, 127.4, 127.7, 128.3,
128.8, 129.3, 132.6, 133.5, 133.8, 136.0, 141.4, 192.2; MS m/z 329
[MH]+; HRMS (ESI) calcd for C17H14BrO2 329.0177 [M + H], found
329.0179.
2-(4-Hydroxy-4-m-tolylbut-1-ynyl)benzaldehyde (3f). Eluent,
petroleum ether−ethyl acetate (5:1). Yellow liquid (480 mg, 91%): 1H
NMR (400 MHz, CDCl3) δ 2.37 (s, 3H), 2.94 (d, J = 6.8 Hz, 3H), 4.97
(d, J = 2.4 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 7.22−7.51 (m, 6H), 7.84 (d,
J = 8.0 Hz, 1H), 10.27 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 21.5,
30.6, 72.6, 79.0, 93.9, 122.9, 126.50, 126.53, 128.2, 128.3, 128.5, 128.9,
133.4, 133.7, 136.1, 138.3, 142.6, 192.1; MS m/z 265 [MH]+; HRMS
(ESI) calcd for C18H17O2 265.1229 [M + H], found 265.1226.
2-(4-(3-Fluorophenyl)-4-hydroxybut-1-ynyl)benzaldehyde
(3g). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (466
mg, 87%): 1H NMR (400 MHz, CDCl3) δ 2.92−2.94 (m, 2H), 5.02 (t, J
= 6.0 Hz, 1H), 6.99−7.54 (m, 7H), 7.85 (d, J = 7.2 Hz, 1H), 10.27 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 30.7, 71.8, 79.7, 93.1, 112.7, 112.9,
114.8, 115.0, 121.40, 121.43, 125.9, 128.4, 129.0, 130.06, 130.14, 133.5,
133.8, 136.1, 145.2, 145.3, 161.7, 164.2, 192.0; MS m/z 269 [MH]+;
HRMS (ESI) calcd for C17H14FO2 269.0978 [M + H], found 269.0989.
2-(4-(3-Chlorophenyl)-4-hydroxybut-1-ynyl)benzaldehyde
(3h). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (494
1
mg, 87%): H NMR (400 MHz, CDCl3) δ 2.90 (d, J = 6.8 Hz, 2H),
3.71−3.72 (m, 1H), 4.96 (t, J = 6.6 Hz, 1H), 7.21−7.53 (m, 7H), 7.82
(d, J = 8.0 Hz, 1H), 10.26 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 30.7,
H
dx.doi.org/10.1021/jo401502k | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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2-(4-(2-Bromo-4-methylphenyl)-4-hydroxybut-1-ynyl)-
benzaldehyde (3q). Eluent, petroleum ether−ethyl acetate (5:1).
Yellow liquid (595 mg, 87%): 1H NMR (400 MHz, CDCl3) δ 2.31 (t, J =
2.8 Hz, 3H), 2.84−3.08 (m, 2H), 3.27 (s, 1H), 5.29−5.32 (m, 1H), 7.15
(d, J = 5.6 Hz, 1H), 7.35−7.56 (m, 5H), 7.83 (d, J = 5.6 Hz, 1H), 10.29
(t, J = 2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.8, 29.0, 71.0, 79.3,
93.5, 121.5, 126.3, 127.1, 128.3, 128.6, 133.1, 133.5, 133.8, 136.1, 138.4,
139.5, 192.2; MS m/z 343 [MH]+; HRMS (ESI) calcd for C18H16BrO2
343.0334 [M + H], found 343.0334.
2-(4-(2-Bromo-4-fluorophenyl)-4-hydroxybut-1-ynyl)benz-
aldehyde (3r). Eluent, petroleum ether−ethyl acetate (5:1). Yellow
liquid (588 mg, 85%): 1H NMR (400 MHz, CDCl3) δ 2.78−3.07 (m,
2H), 3.56 (s, 1H), 5.31 (s, 1H), 7.04−7.09 (m, 1H), 7.25−7.28 (m, 1H),
7.40−7.52 (m, 3H), 7.64−7.68 (m, 1H), 7.83 (d, J = 6.4 Hz, 1H), 10.30
(d, J = 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 29.1, 70.6, 79.7,
93.1, 114.8, 115.0, 119.7, 119.9, 121.5, 121.6, 125.8, 128.4, 128.5, 128.6,
129.2, 133.5, 133.8, 136.0, 137.5, 160.5, 163.0, 192.2; MS m/z 347
[MH]+; HRMS (ESI) calcd for C17H13BrFO2 347.0083 [M + H], found
347.0088.
2-(4-(3,4-Dimethoxyphenyl)-4-hydroxybut-1-ynyl)benz-
aldehyde (3s). Eluent, petroleum ether−ethyl acetate (3:1). Yellow
liquid (577 mg, 93%): 1H NMR (400 MHz, CDCl3) δ 2.72−2.83 (m,
2H), 3.66 (s, 3H), 3.67 (s, 3H), 3.98 (s, 1H), 4.78 (t, J = 6.0 Hz, 1H),
6.66 (d, J = 8.0 Hz, 1H), 6.78 (d, J = 8.4 Hz, 1H), 6.86 (s, 1H), 7.18 (t, J =
7.0 Hz, 1H), 7.26−7.32 (m, 2H), 7.62 (d, J = 8.0 Hz, 1H), 10.11 (s, 1H).
13NMR (100 MHz, CDCl3) δ 30.5, 55.7, 55.8, 72.1, 78.6, 94.4, 108.9,
110.9, 118.1, 126.7, 127.6, 128.0, 133.2, 133.7, 135.7, 135.9, 148.4, 148.8,
192.2; MS m/z 311 [MH]+; HRMS (ESI) calcd for C19H19O4 311.1283
[M + H], found 311.1286.
129.3, 132.7, 133.9, 134.0, 141.5, 144.9, 191.9; MS m/z 343 [MH]+;
HRMS (ESI) calcd for C18H16BrO2 343.0334 [M + H], found 343.0335.
2-(4-(2-Bromophenyl)-4-hydroxybut-1-ynyl)-4-fluorobenzal-
dehyde (3y). Eluent, petroleum ether−ethyl acetate (5:1). Yellow
liquid (630 mg, 91%): 1H NMR (400 MHz, CDCl3) δ 2.85−3.10 (m,
2H), 3.26 (s, 1H), 5.37 (d, J = 3.2 Hz, 1H), 7.07−7.19 (m, 3H), 7.34−
7.38 (m, 1H), 7.52−7.87 (m, 3H), 10.21 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 28.8, 71.0, 78.2, 94.9, 116.1, 116.3, 120.0, 120.3, 121.7, 127.4,
127.8, 128.9, 129.5, 131.2, 131.3, 132.7, 132.78, 132.81, 141.4, 164.3,
166.9, 190.6; MS m/z 347 [MH]+; HRMS (ESI) calcd for C17H13BrFO2
347.0083 [M + H], found 347.0085.
2-(4-(2-Bromo-4-methylphenyl)-4-hydroxybut-1-ynyl)-4-
methylbenzaldehyde (3z). Eluent, petroleum ether−ethyl acetate
(5:1). Yellow liquid (655 mg, 92%): 1H NMR (400 MHz, CDCl3) δ 2.31
(s, 3H), 2.37 (s, 3H), 2.81−3.18 (m, 3H), 5.31 (t, J = 3.6 Hz, 1H), 7.14−
7.21 (m, 2H), 7.30 (s, 1H), 7.35 (s, 1H), 7.52−7.54 (m, 1H), 7.72−7.75
(m, 1H), 10.22 (t, J = 2.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.8,
21.6, 29.0, 71.0, 79.5, 92.9, 121.5, 126.1, 127.1, 128.6, 128.9, 129.3,
133.1, 133.9, 134.0, 138.4, 139.5, 144.8, 191.9; MS m/z 357 [MH]+;
HRMS (ESI) calcd for C19H18BrO2 357.0490 [M + H], found 357.0488.
2-(4-(2-Bromo-4-methylphenyl)-4-hydroxybut-1-ynyl)-4-flu-
orobenzaldehyde (3aa). Eluent, petroleum ether−ethyl acetate
1
(5:1). Yellow liquid (634 mg, 88%): H NMR (400 MHz, CDCl3) δ
2.31 (d, J = 1.6 Hz, 3H), 2.85−3.07 (m, 3H), 5.31−5.33 (m, 1H), 7.07−
7.16 (m, 3H), 7.35 (s, 1H), 7.51−7.54 (m, 1H), 7.83−7.86 (m, 1H),
10.21 (t, J = 2.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.8, 28.9,
70.8, 78.0, 95.0, 116.0, 116.3, 120.0, 120.2, 121.5, 127.1, 128.6, 129.1,
131.0, 131.1, 132.8, 133.1, 138.3, 139.7, 164.3, 166.9, 190.6; MS m/z 361
[MH]+; HRMS (ESI) calcd for C18H15BrFO2 361.0239 [M + H], found
361.0233.
2-(4-Hydroxy-4-(naphthalen-2-yl)but-1-ynyl)benzaldehyde
(3t). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (552
mg, 92%): 1H NMR (400 MHz, CDCl3) δ 3.04−3.22 (m, 2H), 5.79−
5.82 (m, 1H), 7.40−7.57 (m, 6H), 7.78−7.92 (m, 4H), 8.12 (d, J = 8.4
Hz, 1H), 10.31 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 29.9, 69.4, 79.6,
93.8, 122.8, 123.1, 125.5, 125.7, 126.3, 128.3, 128.58, 128.62, 129.1,
130.2, 133.5, 133.7, 133.8, 136.1, 138.0, 192.0; MS m/z 301 [MH]+;
HRMS (ESI) calcd for C21H17O2 301.1129 [M + H], found 301.1130.
2-(4-Hydroxy-4-(thiophen-2-yl)but-1-ynyl)benzaldehyde
(3u). Eluent, petroleum ether−ethyl acetate (5:1). Yellow liquid (461
mg, 90%): 1H NMR (400 MHz, CDCl3) δ 3.00 (d, J = 6.4 Hz, 2H), 3.85
(s, 1H), 5.21 (t, J = 6.4 Hz, 1H), 6.93−6.96 (m, 1H), 7.04 (d, J = 2.4 Hz,
1H), 7.22−7.24 (m, 1H), 7.32−7.35 (m, 1H), 7.45 (t, J = 2.4 Hz, 2H),
7.77−7.79 (m, 1H), 10.23 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 30.7,
68.6, 79.4, 93.4, 124.2, 125.0, 126.6, 126.7, 128.0, 128.3, 133.4, 133.8,
136.0, 146.6, 192.3; MS m/z 257 [MH]+; HRMS (ESI) calcd for
C15H13O2S 257.0636 [M + H], found 257.0629.
2-(4-(2-Bromo-4-fluorophenyl)-4-hydroxybut-1-ynyl)-4-
methylbenzaldehyde (3bb). Eluent, petroleum ether−ethyl acetate
(5:1). Yellow liquid (612 mg, 85%): 1H NMR (400 MHz, CDCl3) δ 2.36
(s, 3H), 2.78−3.06 (m, 2H), 3.70 (br s, 1H), 5.28−5.31 (m, 1H), 7.05−
7.08 (m, 1H), 7.20−7.29 (m, 3H), 7.64−7.72 (m, 2H), 10.22 (d, J = 2.4
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 21.6, 29.1, 70.6, 79.9, 92.5,
114.8, 115.0, 119.6, 119.8, 121.46, 121.54, 125.7, 128.56, 128.64, 129.4,
129.5, 133.8, 134.0, 137.6, 144.9, 160.5, 162.9, 191.9; MS m/z 361
[MH]+; HRMS (ESI) calcd for C18H15BrFO2 361.0239 [M + H], found
361.0246.
2-(4-(2-Bromo-4-fluorophenyl)-4-hydroxybut-1-ynyl)-4-fluo-
robenzaldehyde (3cc). Eluent, petroleum ether−ethyl acetate (5:1).
Yellow liquid (612 mg, 84%): 1H NMR (400 MHz, CDCl3) δ 2.80−3.06
(m, 2H), 3.48 (s, 1H), 5.30 (d, J = 10.0 Hz, 1H), 7.08−7.28 (m, 4H),
7.65 (t, J = 7.2 Hz, 1H), 7.83−7.87 (m, 1H), 10.24 (t, J = 4.0 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 29.0, 70.5, 78.4, 94.6, 114.9, 115.1,
116.1, 116.4, 119.7, 119.9, 120.1, 120.3, 121.5, 121.6, 128.5, 128.6, 128.7,
131.5, 131.6, 132.8, 137.4, 160.5, 163.0, 164.3, 190.6; MS m/z 365
[MH]+; HRMS (ESI) calcd for C17H12BrF2O2 364.9989 [M + H], found
364.9990.
2-(4-Hydroxy-5-phenylpent-1-ynyl)benzaldehyde (3v). Elu-
ent, petroleum ether−ethyl acetate (5:1). Yellow liquid (486 mg, 92%):
1H NMR (400 MHz, CDCl3) δ 2.61−2.74 (m, 2H), 2.89−3.00 (m, 3H),
4-Fluoro-2-(4-hydroxy-4-m-tolylbut-1-ynyl)benzaldehyde
(3dd). Eluent, petroleum ether−ethyl acetate (5:1). Yellow oil (508 mg,
90%): 1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3H), 2.89−2.91 (m, 2H),
3.75 (br s, 1H), 4.91 (t, J = 6.4 Hz, 1H), 6.98−7.10 (m, 3H), 7.18−7.25
(m, 3H), 7.76−7.80 (m, 1H), 10.11 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.4, 30.4, 72.4, 95.8, 115.9, 116.1, 119.8, 120.0, 122.9, 126.6,
128.4, 128.8, 129.4, 129.5, 130.4, 130.5, 132.8, 138.2, 142.8, 164.3, 166.9,
190.6; MS m/z 283 [MH]+; HRMS (ESI) calcd for C18H16FO2
283.1134 [M + H], found 283.1141.
2-(4-(3-Chlorophenyl)-4-hydroxybut-1-ynyl)-4-fluorobenzal-
dehyde (3ee). Eluent, petroleum ether−ethyl acetate (5:1). Yellow oil
(532 mg, 88%): 1H NMR (400 MHz, CDCl3) δ 2.88 (d, J = 6.0 Hz, 2H),
3.95 (br s, 1H), 4.92 (t, J = 6.0 Hz, 1H), 7.03−7.09 (m, 2H), 7.24 (s,
3H), 7.40 (s, 1H), 7.76−7.79 (m, 1H), 10.12 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 30.4, 71.7, 95.0, 116.1, 116.3, 119.9, 120.2, 124.0, 126.1,
128.1, 129.8, 130.8, 130.9, 132.7, 134.4, 144.8, 164.3, 166.9, 190.5; MS
m/z 303 [MH]+; HRMS (ESI) calcd for C17H13ClFO2 303.0588 [M +
H], found 303.0563.
4.12 (t, J = 6.2 Hz, 1H), 7.21−7.54 (m, 8H), 7.85 (d, J = 7.6 Hz, 1H),
10.46 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 27.6, 42.9, 71.1, 79.2,
94.2, 126.67, 126.70, 128.28, 128.30, 128.7, 129.5, 133.6, 133.8, 136.1,
137.9, 192.1; MS m/z 265 [MH]+; HRMS (ESI) calcd for C18H17O2
265.1229 [M + H], found 265.1228.
2-(4-Hydroxy-6-phenylhex-1-ynyl)benzaldehyde (3w). Elu-
ent, petroleum ether−ethyl acetate (5:1). Yellow liquid (500 mg,
90%): 1H NMR (400 MHz, CDCl3) δ 1.95−2.00 (m, 2H), 2.70−2.91
(m, 4H), 3.49 (s, 1H), 3.94 (t, J = 5.8 Hz, 1H), 7.18−7.38 (m, 6H),
7.47−7.50 (m, 2H), 7.84 (d, J = 7.2 Hz, 1H), 10.44 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 28.7, 32.0, 38.2, 69.4, 79.0, 94.4, 126.0, 126.7,
128.3, 128.4, 128.5, 133.6, 133.9, 136.0, 141.8, 192.2; MS m/z 279
[MH]+; HRMS (ESI) calcd for C19H19O2 279.1385 [M + H], found
279.1380.
2-(4-(2-Bromophenyl)-4-hydroxybut-1-ynyl)-4-methylben-
zaldehyde (3x). Eluent, petroleum ether−ethyl acetate (5:1). Yellow
1
liquid (616 mg, 90%): H NMR (400 MHz, CDCl3) δ 2.37 (s, 3H),
2.81−3.10 (m, 2H), 5.33−5.37 (m, 1H), 7.16−7.36 (m, 4H), 7.51−7.54
(m, 1H), 7.67−7.74 (m, 2H), 10.22 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.6, 29.0, 71.1, 79.7, 92.8, 121.7, 126.0, 127.5, 127.8, 129.2,
2-(4-Hydroxy-4-p-tolylbut-1-ynyl)-4-methylbenzaldehyde
(3ff). Eluent, petroleum ether−ethyl acetate (5:1). Yellow oil (512 mg,
92%): 1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3H), 2.34 (s, 3H), 2.89−
I
dx.doi.org/10.1021/jo401502k | J. Org. Chem. XXXX, XXX, XXX−XXX

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2.91 (m, 2H), 3.50 (br s, 1H), 4.93 (t, J = 6.4 Hz, 1H), 7.15−7.32 (m,
6H), 7.70 (d, J = 8.0 Hz, 1H), 10.16 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.2, 21.5, 30.5, 72.4, 79.0, 93.7, 125.8, 126.7, 128.1, 129.1,
129.2, 133.8, 133.9, 137.6, 139.9, 144.7, 191.9; MS m/z 279 [MH]+;
HRMS (ESI) calcd for C19H19O2 279.1385 [M + H], found 279.1386.
2-(4-(4-Chlorophenyl)-4-hydroxybut-1-ynyl)-4-methylben-
zaldehyde (3gg). Eluent, petroleum ether−ethyl acetate (5:1). Yellow
oil (530 mg, 89%): 1H NMR (400 MHz, CDCl3) δ 2.30 (s, 3H), 2.86 (d,
J = 6.4 Hz, 2H), 3.98 (s, 1H), 4.91 (t, J = 6.4 Hz, 1H), 7.12−7.33 (m,
6H), 7.65 (d, J = 7.6 Hz, 1H), 10.15 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.5, 30.6, 71.7, 79.5, 93.1, 126.3, 127.3, 128.5, 128.6, 129.3,
133.5, 133.8, 133.9, 141.5, 144.9, 191.8; MS m/z 299 [MH]+; HRMS
(ESI) calcd for C18H16ClO2 299.0839 [M + H], found 299.0848.
2-(4-(2-Bromo-4,6-dimethoxyphenyl)-4-hydroxybut-1-ynyl)-
benzaldehyde (3hh). Eluent, petroleum ether−ethyl acetate (3:1).
Yellow oil (675 mg, 87%): 1H NMR (400 MHz, CDCl3) δ 3.08 (d, J =
7.6 Hz, 2H), 3.81 (s, 3H), 3.86 (s, 3H), 5.41−5.43 (m, 1H), 6.46 (d, J =
1.2 Hz, 1H), 6.72 (d, J = 1.6 Hz, 1H), 7.34−7.47 (m, 3H), 7.82 (d, J = 8.0
Hz, 1H), 10.26 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 27.9, 55.6, 55.8,
72.5, 77.8, 94.3, 99.3, 109.6, 121.7, 124.3, 126.7, 127.6, 128.0, 133.3,
133.6, 136.1, 158.9, 160.2, 192.3; MS m/z 389 [MH]+; HRMS (ESI)
calcd for C19H18BrO4 389.0388 [M + H], found 389.0377.
139.4, 157.3, 201.6; MS m/z 327 [MH]+; HRMS (ESI) calcd for
C17H12BrO2 327.0021 [M + H], found 327.0018.
(3-Hydroxynaphthalen-2-yl)(m-tolyl)methanone (5f). Eluent,
petroleum ether−ethyl acetate (10:1). Yellow solid (170 mg, 65%): mp
93−95 °C; 1H NMR (400 MHz, CDCl3) δ 2.47 (s, 3H), 7.30−7.59 (m,
7H), 7.73 (t, J = 7.8 Hz, 2H), 8.18 (s, 1H), 11.18 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 21.5, 112.3, 121.1, 124.1, 126.3, 126.7, 126.9, 128.3,
129.6, 129.8, 130.0, 133.1, 136.8, 137.9, 138.0, 138.6, 157.3, 202.1; MS
m/z 263 [MH]+; HRMS (ESI) calcd for C18H15O2 263.1072 [M + H],
found 263.1073.
(3-Fluorophenyl)(3-hydroxynaphthalen-2-yl)methanone
(5g). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (181
mg, 68%): mp 107−109 °C; 1H NMR (400 MHz, CDCl3) δ 7.30−7.37
(m, 3H), 7.46−7.53 (m, 4H), 7.69−7.74 (m, 2H), 8.14 (s, 1H), 11.00 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 112.6, 116.3, 116.6, 119.3, 119.5,
120.6, 124.3, 125.4, 126.3, 126.7, 129.6, 130.1, 130.2, 130.3, 136.6, 138.0,
139.8, 157.1, 161.2, 163.7, 200.2; MS m/z 267 [MH]+; HRMS (ESI)
calcd for C17H12FO2 267.0821 [M + H], found 267.0825.
(3-Chlorophenyl)(3-hydroxynaphthalen-2-yl)methanone
(5h). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (200
mg, 71%): mp 90−92 °C; 1H NMR (400 MHz, CDCl3) δ 7.33 (t, J = 7.6
Hz, 1H), 7.38 (s, 1H), 7.47−7.75 (m, 7H), 8.11 (s, 1H), 10.98 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 112.6, 120.7, 124.3, 126.4, 126.7, 127.7,
129.4, 129.7, 129.8, 130.1, 132.3, 134.8, 136.6, 138.1, 139.5, 157.2,
200.2; MS m/z 283 [MH]+; HRMS (ESI) calcd for C17H12ClO2
283.0526 [M + H], found 283.0528.
Typical Procedure for the Synthesis of (3-Hydroxynaphtha-
len-2-yl)(phenyl)methanone (5a). To a solution of 2-(4-hydroxy-4-
phenylbut-1-ynyl)benzaldehyde (3a, 1 mmol) in CH3CN (10 mL) was
added Jones reagent (0.7 mmol), and the resulting mixture was stirred at
60 °C for 10 min. The resulting mixture was quenched with isopropanol
and filtered, and the filtrate was concentrated under a vacuum. The
residue was purified by column chromatography on silica gel pre-eluted
with Et3N (0.2 mL) by using petroleum ether−ethyl acetate (10:1) as
the eluent to give (3-hydroxynaphthalen-2-yl)(phenyl)methanone (5a).
5b−5dd were obtained in a similar manner.
(3-Bromophenyl)(3-hydroxynaphthalen-2-yl)methanone
(5i). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (238
mg, 73%): mp 114−116 °C; 1H NMR (400 MHz, CDCl3) δ 7.31−7.45
(m, 3H), 7.55 (t, J = 7.4 Hz, 1H), 7.66−7.78 (m, 4H), 7.90 (d, J = 1.6 Hz.
1H), 8.11 (s, 1H), 10.98 (d, J = 2.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 112.6, 120.6, 122.8, 124.3, 126.4, 126.7, 128.1, 129.7, 130.07,
130.15, 132.3, 135.2, 136.6, 138.1, 139.7, 157.2, 200.1; MS m/z 327
[MH]+; HRMS (ESI) calcd for C17H12BrO2 327.0021 [M + H], found
327.0016.
(3-Hydroxynaphthalen-2-yl)(phenyl)methanone (5a).5 Elu-
ent, petroleum ether−ethyl acetate (10:1). Yellow solid (186 mg,
75%): mp 153−155 °C; 1H NMR (400 MHz, CDCl3) δ 7.31 (t, J = 7.6
Hz, 1H), 7.39 (s, 1H), 7.52−7.58 (m, 3H), 7.65−7.79 (m, 5H), 8.17 (s,
1H), 11.18 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 112.4, 121.0, 124.1,
126.3, 126.7, 128.5, 129.61, 129.63, 129.9, 132.4, 136.7, 137.9, 138.0,
157.4, 201.8; MS m/z 249 [MH]+.
(3-Hydroxynaphthalen-2-yl)(4-methoxyphenyl)methanone
(5j).5 Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (211
1
mg, 76%): mp 128−130 °C; H NMR (400 MHz, CDCl3) δ 3.93 (s,
3H), 7.04 (d, J = 8.8 Hz, 2H), 7.32 (t, J = 7.6 Hz, 1H), 7.37 (s, 1H), 7.53
(t, J = 7.2 Hz, 1H), 7.70−7.82 (m, 4H), 8.18 (s, 1H), 11.07 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 55.6, 112.3, 113.8, 121.4, 124.0, 126.3,
126.7, 129.5, 129.6, 130.4, 132.3, 136.0, 137.6, 157.2, 163.3, 200.1; MS
m/z 279 [MH]+.
(3-Hydroxynaphthalen-2-yl)(2-methoxyphenyl)methanone
(5b). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (200
1
mg, 72%): mp 113−115 °C; H NMR (400 MHz, CDCl3) δ 3.75 (s,
3H), 7.05−7.12 (m, 2H), 7.24−7.28 (m, 1H), 7.35−7.38 (m, 2H),
7.48−7.69 (m, 4H), 7.99 (s, 1H), 11.52 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 55.7, 111.6, 112.0, 120.6, 121.8, 123.9, 126.3, 126.9, 127.7,
129.2, 129.7, 129.9, 132.3, 137.2, 138.2, 156.8, 157.4, 202.5; MS m/z 279
[MH]+; HRMS (ESI) calcd for C18H15O3 279.1021 [M + H], found
279.1028.
(3-Hydroxynaphthalen-2-yl)(p-tolyl)methanone (5k). Eluent,
petroleum ether−ethyl acetate (10:1). Yellow solid (194 mg, 74%): mp
152−154 °C; 1H NMR (400 MHz, CDCl3) δ 2.50 (s, 3H), 7.30−7.38
(m, 4H), 7.51−7.55 (m, 1H), 7.69−7.74 (m, 4H), 8.19 (s, 1H), 11.15
(d, J = 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 21.7, 112.3, 121.2,
124.0, 126.3, 126.7, 129.2, 129.5, 129.6, 129.9, 135.2, 136.4, 137.8, 143.2,
157.3, 201.4; MS m/z 263 [MH]+; HRMS (ESI) calcd for C18H15O2
263.1072 [M + H], found 263.1078.
(4-Fluorophenyl)(3-hydroxynaphthalen-2-yl)methanone
(5l). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (176
mg, 66%): mp 134−136 °C; 1H NMR (400 MHz, CDCl3) δ 7.22−7.31
(m, 2H), 7.33 (t, J = 7.4 Hz, 1H), 7.38 (s, 1H), 7.52−7.56 (m, 1H),
7.70−7.83 (m, 4H), 8.13 (s, 1H), 10.99 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 112.5, 115.7, 115.9, 121.0, 124.2, 126.3, 126.7, 129.5, 129.9,
132.2, 132.3, 134.1, 134.2, 136.3, 137.9, 157.2, 164.1, 166.6, 200.1; MS
m/z 267 [MH]+; HRMS (ESI) calcd for C17H12FO2 267.0821 [M + H],
found 267.0828.
(4-Chlorophenyl)(3-hydroxynaphthalen-2-yl)methanone
(5m).5 Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (189
mg, 67%): mp 134−136 °C; 1H NMR (400 MHz, CDCl3) δ 7.33 (t, J =
7.6 Hz, 1H), 7.39 (s, 1H), 7.53−7.55 (m, 3H), 7.71−7.74 (m, 4H), 8.12
(s, 1H), 10.98 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 112.6, 120.9,
124.3, 126.4, 126.7, 128.9, 129.5, 130.0, 131.0, 136.3, 136.4, 138.0, 138.9,
157.2, 200.4; MS m/z 283 [MH]+.
(4-Bromophenyl)(3-hydroxynaphthalen-2-yl)methanone
(5n). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (248
mg, 76%): mp 115−117 °C; 1H NMR (400 MHz, CDCl3) δ 7.31−7.38
(2-Fluorophenyl)(3-hydroxynaphthalen-2-yl)methanone
(5c). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (181
mg, 68%): mp 161−163 °C; 1H NMR (400 MHz, CDCl3) δ 7.26−7.36
(m, 4H), 7.51−7.61 (m, 3H), 7.70 (d, J = 8.4 Hz, 2H), 8.03 (s, 1H),
11.20 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 112.3, 116.4, 116.6,
121.4, 124.2, 124.5, 126.3, 126.4, 126.9, 129.7, 130.2, 133.2, 133.3, 137.0,
138.3, 157.0, 160.6, 198.8; MS m/z 267 [MH]+; HRMS (ESI) calcd for
C17H12FO2 267.0821 [M + H], found 267.0830.
(2-Clorophenyl)(3-hydroxynaphthalen-2-yl)methanone (5d).
Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (212 mg,
75%): mp 141−142 °C; 1H NMR (400 MHz, CDCl3) δ 7.27 (t, J = 7.4
Hz, 1H), 7.37 (s, 1H), 7.42−7.54 (m, 5H), 7.63−7.69 (m, 2H), 7.89 (s,
1H), 11.29 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 112.5, 121.0, 124.2,
126.3, 126.88, 126.91, 128.9, 129.7, 130.3, 131.0, 131.6, 137.2, 137.4,
138.5, 157.2, 201.0; MS m/z 283 [MH]+; HRMS (ESI) calcd for
C17H12ClO2 283.0526 [M + H], found 283.0522.
(2-Bromophenyl)(3-hydroxynaphthalen-2-yl)methanone
(5e). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (238
mg, 73%): mp 119−121 °C; 1H NMR (400 MHz, CDCl3) δ 7.27 (t, J =
7.0 Hz, 1H), 7.37−7.53 (m, 5H), 7.64−7.72 (m, 3H), 7.86 (s, 1H),
11.25 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 112.5, 119.4, 120.7,
124.2, 126.4, 126.9, 127.4, 128.8, 129.8, 130.3, 131.6, 133.4, 137.3, 138.5,
J
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(m, 2H), 7.52−7.56 (m, 1H), 7.63−7.74 (m, 6H), 8.11 (s, 1H), 11.00
(d, J = 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 112.6, 120.8, 124.3,
126.4, 126.7, 127.4, 129.6, 130.0, 131.2, 131.9, 136.4, 136.6, 138.0, 157.1,
200.5; MS m/z 327 [MH]+; HRMS (ESI) calcd for C17H12BrO2
327.0021 [M + H], found 327.0018.
7.30−7.40 (m, 7H), 7.51−7.55 (m, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.83
(d, J = 8.4 Hz, 1H), 8.51 (s, 1H), 11.52 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 45.4, 112.5, 120.7, 124.1, 126.3, 126.8, 127.3, 128.9, 129.48,
129.52, 129.9, 133.4, 133.9, 138.2, 157.4, 204.2; MS m/z 263 [MH]+;
HRMS (ESI) calcd for C18H15O2 263.1072 [M + H], found 263.1070.
1-(3-Hydroxynaphthalen-2-yl)-3-phenylpropan-1-one (5w).
Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (199 mg,
72%): mp 92−95 °C; 1H NMR (400 MHz, CDCl3) δ 3.13 (t, J = 8.0 Hz,
2H), 3.44 (t, J = 7.4 Hz, 2H), 7.28−7.43 (m, 7H), 7.52 (t, J = 7.4 Hz,
1H), 7.65 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H), 8.24 (s, 1H),
11.71 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 30.0, 40.3, 112.3, 120.8,
124.1, 126.3, 126.5, 126.8, 128.6, 128.8, 129.4, 129.7, 132.6, 138.0, 140.8,
157.1, 205.6; MS m/z 277 [MH]+; HRMS (ESI) calcd for C19H17O2
277.1229 [M + H], found 277.1209.
4-(3-Hydroxy-2-naphthoyl)benzonitrile (5o).5 Eluent, petrole-
um ether−ethyl acetate (10:1). Orange solid (202 mg, 74%): mp 161−
163 °C; 1H NMR (400 MHz, CDCl3) δ 7.34 (t, J = 7.2 Hz, 1H), 7.39 (s,
1H), 7.54−7.58 (m, 1H), 7.71 (d, J = 9.2 Hz, 2H), 7.83−7.88 (m, 4H),
8.02 (s, 1H), 10.89 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 112.9,
115.7, 117.9, 120.4, 124.5, 126.4, 126.7, 129.6, 129.8, 130.4, 132.4, 136.6,
138.3, 141.6, 157.1, 200.0; MS m/z 274 [MH]+.
(3-Hydroxynaphthalen-2-yl)(4-(trifluoromethyl)phenyl)-
methanone (5p). Eluent, petroleum ether−ethyl acetate (10:1).
1
Yellow solid (231 mg, 73%): mp 155−157 °C; H NMR (400 MHz,
(2-Bromophenyl)(3-hydroxy-6-methylnaphthalen-2-yl)-
CDCl3) δ 7.32 (t, J = 6.8 Hz, 1H), 7.37 (s, 1H), 7.54 (t, J = 7.2 Hz, 1H),
7.71 (t, J = 7.6 Hz, 2H), 7.83−7.86 (m, 4H), 8.07 (s, 1H), 11.01 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 112.7, 120.5, 124.4, 125.50, 125.54,
methanone (5x). Eluent, petroleum ether−ethyl acetate (10:1).
1
Yellow solid (231 mg, 68%): mp 128−130 °C; H NMR (400 MHz,
CDCl3) δ 2.48 (d, J = 2.8 Hz, 3H), 7.12 (d, J = 8.4 Hz, 1H), 7.27 (s, 1H),
7.39−7.56 (m, 5H), 7.71−7.79 (m, 1H), 7.80 (s, 1H), 11.27 (d, J = 4.0
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 22.2, 111.7, 119.4, 120.0,
125.3, 126.8, 127.4, 128.8, 129.6, 131.5, 133.4, 137.0, 138.9, 139.6, 140.9,
157.6, 201.5; MS m/z 341 [MH]+; HRMS (ESI) calcd for C18H14BrO2
341.0177 [M + H], found 341.0179.
125.57, 125.61, 126.3, 126.7, 129.6, 129.7, 130.2, 136.7, 138.2, 141.0,
157.2, 200.6; MS m/z 317 [MH]+; HRMS (ESI) calcd for C18H12F3O2
317.0789 [M + H], found 317.0788.
(2-Bromo-4-methylphenyl)(3-hydroxynaphthalen-2-yl)-
methanone (5q). Eluent, petroleum ether−ethyl acetate (10:1).
1
Yellow solid (228 mg, 67%): mp 132−134 °C; H NMR (400 MHz,
(2-Bromophenyl)(6-fluoro-3-hydroxynaphthalen-2-yl)-
methanone (5y). Eluent, petroleum ether−ethyl acetate (10:1).
CDCl3) δ 2.44 (s, 3H), 7.26 (d, J = 7.2 Hz, 3H), 7.37 (s, 1H), 7.49−7.54
(m, 2H), 7.64−7.69 (m, 2H), 7.90 (s, 1H), 11.30 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 21.2, 112.4, 119.4, 120.9, 124.2, 126.4, 126.9,
128.1, 128.9, 129.8, 130.2, 133.9, 136.6, 137.3, 138.4, 142.4, 157.4,
201.8; MS m/z 341 [MH]+; HRMS (ESI) calcd for C18H14BrO2
341.0177 [M + H], found 341.0166.
1
Yellow solid (227 mg, 66%): mp 131−133 °C; H NMR (400 MHz,
CDCl3) δ 7.02 (t, J = 8.0 Hz, 1H), 7.05 (d, J = 2.0 Hz, 2H), 7.27−7.50
(m, 3H), 7.64−7.73 (m, 2H), 7.83 (s, 1H), 11.32 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 109.4, 109.6, 111.97, 112.03, 115.0, 115.2, 119.4,
120.09, 120.11, 124.0, 127.4, 128.8, 131.7, 132.6, 132.7, 133.4, 137.2,
139.3, 139.8, 139.9, 158.2, 162.4, 164.9, 201.4; MS m/z 345 [MH]+;
HRMS (ESI) calcd for C17H11BrFO2 344.9926 [M + H], found
344.9938.
(2-Bromo-4-fluorophenyl)(3-hydroxynaphthalen-2-yl)-
methanone (5r). Eluent, petroleum ether−ethyl acetate (10:1). Yellow
solid (248 mg, 72%): mp 139−141 °C; 1H NMR (400 MHz, CDCl3) δ
7.21−7.55 (m, 6H), 7.69 (d, J = 6.4 Hz, 2H), 7.85 (d, J = 2.8 Hz, 1H),
11.13−11.15 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 112.6, 114.8,
115.0, 120.4, 120.5, 120.7, 120.8, 121.1, 124.3, 126.4, 126.9, 129.7,
130.37, 130.41, 135.7, 137.1, 138.6, 157.2, 161.9, 164.4, 200.7; MS m/z
345 [MH]+; HRMS (ESI) calcd for C17H11BrFO2 344.9926 [M + H],
found 344.9936.
(2-Bromo-4-methylphenyl)(3-hydroxy-6-methylnaphthalen-
2-yl)methanone (5z). Eluent, petroleum ether−ethyl acetate (10:1).
1
Yellow solid (262 mg, 74%): mp 108−110 °C; H NMR (400 MHz,
CDCl3) δ 2.43−2.47 (m, 6H), 7.09−7.11 (m, 1H), 7.26 (s, 3H), 7.44 (s,
1H), 7.54 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 2.4 Hz, 1H), 11.34−11.35 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 21.2, 22.2, 111.7, 119.4, 120.2,
125.28, 125.30, 126.7, 128.1, 128.9, 129.6, 133.8, 136.7, 137.1, 138.8,
140.8, 142.3, 157.6, 201.7; MS m/z 355 [MH]+; HRMS (ESI) calcd for
C19H16BrO2 355.0333 [M + H], found 355.0334.
(3,4-Dimethoxyphenyl)(3-hydroxynaphthalen-2-yl)-
methanone (5s). Eluent, petroleum ether−ethyl acetate (10:1).
1
Yellow solid (219 mg, 71%): mp 119−121 °C; H NMR (400 MHz,
CDCl3) δ 3.94 (d, J = 4.0 Hz, 3H), 3.99 (d, J = 4.4 Hz, 3H), 6.94−6.96
(m, 1H), 7.30−7.39 (m, 4H), 7.51 (t, J = 7.6 Hz, 1H), 7.69−7.75 (m,
2H), 8.20 (s, 1H), 10.97 (d, J = 4.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 56.1, 56.2, 109.9, 112.1, 112.2, 121.4, 124.1, 125.0, 126.3,
126.7, 129.5, 129.6, 130.4, 136.0, 137.6, 149.1, 153.0, 157.1, 199.9; MS
m/z 309 [MH]+; HRMS (ESI) calcd for C19H17O4 309.1127 [M + H],
found 309.1116.
(3-Hydroxynaphthalen-2-yl)(naphthalen-1-yl)methanone
(5t). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (197
mg, 66%): mp 124−126 °C; 1H NMR (400 MHz, CDCl3) δ 7.23−7.26
(m, 1H), 7.43 (s, 1H), 7.50−7.62 (m, 6H), 7.72 (d, J = 8.8 Hz, 1H),
7.97−8.07 (m, 3H), 8.08 (d, J = 7.2 Hz, 1H), 11.58 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 112.4, 122.2, 124.1, 124.5, 125.3, 126.3, 126.79,
126.82, 127.1, 127.5, 128.6, 129.7, 130.1, 130.6, 131.3, 133.7, 135.7,
137.5, 138.4, 157.6, 204.0; MS m/z 299 [MH]+; HRMS (ESI) calcd for
C21H15O2 299.1072 [M + H], found 299.1076.
(3-Hydroxynaphthalen-2-yl)(thiophen-2-yl)methanone (5u).
Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (165 mg,
65%): mp 103−105 °C; 1H NMR (400 MHz, CDCl3) δ 7.24−7.27 (m,
1H), 7.36 (t, J = 8.2 Hz, 2H), 7.55 (t, J = 7.6 Hz, 1H), 7.72 (d, J = 8.4 Hz,
1H), 7.81−7.84 (m, 3H), 8.50 (s, 1H), 10.64 (d, J = 1.2 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 112.4, 121.7, 124.2, 126.4, 126.9, 128.2,
129.5, 129.7, 134.7, 135.3, 137.6, 142.5, 156.5, 191.3; MS m/z 255
[MH]+; HRMS (ESI) calcd for C15H11O2S 255.0480 [M + H], found
255.0477.
(2-Bromo-4-methylphenyl)(6-fluoro-3-hydroxynaphthalen-
2-yl)methanone (5aa). Eluent, petroleum ether−ethyl acetate (10:1).
1
Yellow solid (261 mg, 73%): mp 121−123 °C; H NMR (400 MHz,
CDCl3) δ 2.44 (s, 3H), 7.03−7.05 (m, 1H), 7.25−7.27 (m, 4H), 7.53 (s,
1H), 7.62−7.66 (m, 1H), 7.86 (s, 1H), 11.37 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 21.2, 109.3, 109.5, 111.86, 111.92, 114.9, 115.1, 119.3,
120.28, 120.30, 124.0, 128.1, 128.8, 132.6, 132.7, 133.9, 136.4, 137.2,
139.7, 139.8, 142.5, 158.3, 162.3, 164.8, 201.6; MS m/z 359 [MH]+;
HRMS (ESI) calcd for C18H13BrFO2 359.0083 [M + H], found
359.0099.
(2-Bromo-4-fluorophenyl)(3-hydroxy-6-methylnaphthalen-
2-yl)methanone (5bb). Eluent, petroleum ether−ethyl acetate (10:1).
1
Yellow solid (240 mg, 67%): mp 115−117 °C; H NMR (400 MHz,
CDCl3) δ 2.47 (s, 3H), 7.11−7.21 (m, 2H), 7.25 (s, 1H), 7.37−7.46 (m,
3H), 7.55−7.57 (m, 1H), 7.79 (s, 1H), 11.20 (d, J = 2.0 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 22.2, 111.8, 114.7, 114.9, 120.0, 120.4,
120.5, 120.8, 121.0, 125.30, 125.32, 126.9, 129.6, 130.4, 130.5, 135.80,
135.84, 136.9, 138.9, 141.0, 157.5, 161.8, 164.3, 200.5; MS m/z 359
[MH]+; HRMS (ESI) calcd for C18H13BrFO2 359.0083 [M + H], found
359.0086.
(2-Bromo-4-fluorophenyl)(6-fluoro-3-hydroxynaphthalen-2-
yl)methanone (5cc). Eluent, petroleum ether−ethyl acetate (10:1).
1
Yellow solid (235 mg, 65%): mp 142−144 °C; H NMR (400 MHz,
CDCl3) δ 7.03−7.28 (m, 4H), 7.39−7.48 (m, 2H), 7.65−7.82 (m, 1H),
7.824 (s, 1H), 11.22−11.24 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
109.4, 109.6, 112.08, 112.13, 114.8, 115.06, 115.11, 115.4, 120.1, 120.35,
120.43, 120.9, 121.1, 124.0, 130.3, 130.4, 132.6, 132.7, 135.6, 137.0,
139.9, 140.0, 158.1, 161.9, 162.4, 164.4, 164.9, 200.5; MS m/z 363
1-(3-Hydroxynaphthalen-2-yl)-2-phenylethanone (5v). Elu-
ent, petroleum ether−ethyl acetate (10:1). Yellow solid (176 mg,
67%): mp 133−135 °C; 1H NMR (400 MHz, CDCl3) δ 4.49 (s, 2H),
K
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[MH]+; HRMS (ESI) calcd for C17H10BrF2O2 362.9832 [M + H], found
362.9833.
(100 MHz, CDCl3) δ 43.1, 106.8, 120.4, 123.3, 125.5, 127.1, 128.5,
129.7, 130.5, 131.5, 135.0, 136.7, 136.9, 137.7, 150.3, 162.4, 192.8; MS
m/z 343 [MH]+; HRMS (ESI) calcd for C17H12BrO3 342.9970 [M +
H], found 342.9978.
(2-Bromo-4,6-dimethoxyphenyl)(3-hydroxynaphthalen-2-
yl)methanone (5dd). Eluent, petroleum ether−ethyl acetate (5:1).
1
Yellow solid (251 mg, 65%): mp 175−177 °C; H NMR (400 MHz,
3-(2-(4-Methoxyphenyl)-2-oxoethyl)-1H-isochromen-1-one
CDCl3) δ 3.70 (s, 3H), 3.88 (s, 3H), 6.54 (d, J = 2.0 Hz, 1H), 6.81 (d, J =
2.0 Hz, 1H), 7.27 (t, J = 5.4 Hz, 1H), 7.34 (s, 1H), 7.50−7.52 (m, 1H),
7.67−7.70 (m, 2H), 7.90 (s, 1H), 11.29 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 55.8, 56.1, 98.3, 109.2, 112.1, 120.5, 121.8, 121.9, 123.9, 126.3,
127.2, 129.7, 129.9, 136.2, 138.5, 157.2, 158.6, 162.0, 200.7; MS m/z 387
[MH]+; HRMS (ESI) calcd for C19H16BrO4 387.0232 [M + H], found
387.0234.
(6g). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (206
1
mg, 70%): mp 149−150 °C; H NMR (400 MHz, CDCl3) δ 3.86 (s,
3H), 4.13 (s, 2H), 6.44 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 8.0
Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.66 (t, J = 7.6 Hz, 1H), 7.96−7.99 (m,
2H), 8.23 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 42.8, 55.6,
106.4, 114.0, 120.3, 125.5, 128.2, 129.1, 129.5, 130.9, 134.9, 137.1, 151.3,
162.6, 164.1, 192.5; MS m/z 295 [MH]+; HRMS (ESI) calcd for
C18H15O4 295.0970 [M + H], found 295.0973.
Typical Procedure for the Synthesis of 3-(2-Oxo-2-phenyl-
ethyl)-1H-isochromen-1-one (6a). To a solution of 2-(4-hydroxy-4-
phenylbut-1-ynyl)benzaldehyde (3a, 1 mmol) in acetone (10 mL) was
added Jones reagent (3 mmol), and the resulting mixture was stirred at 0
°C for 10 min. The resulting mixture was quenched with isopropanol
and filtered, and the filtrate was concentrated under a vacuum. The
residue was purified by column chromatography on silica gel by using
petroleum ether−ethyl acetate (10:1) as the eluent to give 6a. 6b−6r
were obtained in a similar manner.
3-(2-Oxo-2-p-tolylethyl)-1H-isochromen-1-one (6h). Eluent,
petroleum ether−ethyl acetate (10:1). Yellow solid (186 mg, 67%):
mp 124−126 °C; 1H NMR (400 MHz, CDCl3) δ 2.42 (s, 3H), 4.17 (s,
2H), 6.46 (s, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 7.6 Hz, 1H), 7.48
(t, J = 7.6 Hz, 1H), 7.68 (t, J = 7.6 Hz, 1H), 7.91 (d, J = 8.4 Hz, 2H), 8.26
(d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 21.7, 42.9, 106.4,
120.3, 125.4, 128.2, 128.6, 129.5, 133.6, 134.8, 137.0, 144.8, 151.1, 162.5,
193.6; MS m/z 279 [MH]+; HRMS (ESI) calcd for C18H15O3 279.1021
[M + H], found 279.1028.
3-(2-Oxo-2-phenylethyl)-1H-isochromen-1-one (6a). Eluent,
petroleum ether−ethyl acetate (10:1). White solid (180 mg, 68%): mp
104−106 °C; 1H NMR (400 MHz, CDCl3) δ 4.19 (s, 2H), 6.47 (s, 1H),
7.37 (d, J = 8.0 Hz, 1H), 7.46−7.51 (m, 3H), 7.59−7.68 (m, 2H), 8.00
(d, J = 8.0 Hz, 2H), 8.25 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 43.1, 106.6, 120.4, 125.5, 128.3, 128.5, 128.9, 129.6, 133.9,
134.9, 136.0, 137.0, 150.9, 162.5, 194.0; MS m/z 265 [MH]+; HRMS
(ESI) calcd for C17H13O3 265.0864 [M + H], found 265.0866.
3-(2-(2-Fluorophenyl)-2-oxoethyl)-1H-isochromen-1-one
(6b). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (147
3-(2-(4-Fluorophenyl)-2-oxoethyl)-1H-isochromen-1-one
(6i). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (169
1
mg, 60%): mp 154−156 °C; H NMR (400 MHz, CDCl3) δ 4.17 (s,
2H), 6.47 (s, 1H), 7.17 (t, J = 8.4 Hz, 2H), 7.38 (d, J = 7.6 Hz, 1H),
7.47−7.51 (m, 1H), 7.67−7.71 (m, 1H), 8.03−8.06 (m, 2H), 8.25 (d, J =
8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 43.0, 106.7, 116.0, 116.2,
120.3, 125.5, 128.4, 129.6, 131.2, 131.3, 135.0, 136.9, 150.7, 162.5, 164.9,
167.4, 192.5; MS m/z 283 [MH]+; HRMS (ESI) calcd for C17H12FO3
283.0770 [M + H], found 283.0761.
1
mg, 52%): mp 124−126 °C; H NMR (400 MHz, CDCl3) δ 4.20 (s,
3-(2-(4-Chlorophenyl)-2-oxoethyl)-1H-isochromen-1-one
(6j). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (182
2H), 6.46 (s, 1H), 7.14−7.27 (m, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.48 (t, J
= 7.4 Hz, 1H), 7.55−7.57 (m, 1H), 7.69 (t, J = 7.6 Hz, 1H), 7.89−7.93
(m, 1H), 8.25 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 47.6,
47.7, 106.7, 116.7, 116.9, 120.4, 124.81, 124.84, 125.5, 128.3, 129.6,
131.01, 131.03, 134.9, 135.5, 135.6, 137.0, 150.69, 150.71, 160.8, 162.6,
163.3, 192.17, 192.21; MS m/z 283 [MH]+; HRMS (ESI) calcd for
C17H12FO3 283.0770 [M + H], found 283.0775.
1
mg, 61%): mp 139−141 °C; H NMR (400 MHz, CDCl3) δ 4.17 (s,
2H), 6.47 (s, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.46−7.51 (m, 3H), 7.69 (t, J
= 7.6 Hz, 1H), 7.95 (d, J = 8.0 Hz, 2H), 8.26 (d, J = 8.0 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 43.1, 106.7, 120.4, 125.5, 128.4, 129.3,
129.6, 129.9, 134.3, 135.0, 136.9, 140.4, 150.5, 162.4, 192.9; MS m/z 299
[MH]+; HRMS (ESI) calcd for C17H12ClO3 299.0475 [M + H], found
299.0476.
3-(2-Oxo-2-m-tolylethyl)-1H-isochromen-1-one (6c). Eluent,
petroleum ether−ethyl acetate (10:1). Yellow solid (183 mg, 66%): mp
136−137 °C; 1H NMR (400 MHz, CDCl3) δ 2.41 (s, 3H), 4.18 (s, 2H),
6.45 (s, 1H), 7.36−7.42 (m, 3H), 7.47 (t, J = 7.6 Hz, 1H), 7.68 (t, J = 7.6
Hz, 1H), 7.79−7.81 (m, 2H), 8.25 (d, J = 8.0 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 21.4, 43.1, 106.5, 120.4, 125.5, 125.8, 128.2, 128.8,
129.0, 129.6, 134.6, 134.9, 136.1, 137.0, 138.8, 151.1, 162.5, 194.2; MS
m/z 279 [MH]+; HRMS (ESI) calcd for C18H15O3 279.1021 [M + H],
found 279.1012.
3-(2-(3,4-Dimethoxyphenyl)-2-oxoethyl)-1H-isochromen-1-
one (6k). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid
(243 mg, 75%): mp 171−173 °C; 1H NMR (400 MHz, CDCl3) δ 3.83
(s, 3H), 3.86 (s, 3H), 4.10 (s, 2H), 6.41 (s, 1H), 6.83−6.86 (m, 1H),
7.30 (d, J = 7.6 Hz, 1H), 7.38−7.42 (m, 1H), 7.48 (d, J = 1.6 Hz, 1H),
7.58−7.62 (m, 2H), 8.15 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 42.7, 56.0, 56.1, 106.4, 110.1, 110.2, 120.2, 123.5, 125.4, 128.2,
129.1, 129.4, 134.9, 137.0, 149.1, 151.3, 153.8, 162.5, 192.7; MS m/z 325
[MH]+; HRMS (ESI) calcd for C19H17O5 325.1076 [M + H], found
325.1077.
3-(2-(3-Fluorophenyl)-2-oxoethyl)-1H-isochromen-1-one
(6d). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (164
1
3-(2-(Naphthalen-1-yl)-2-oxoethyl)-1H-isochromen-1-one
mg, 58%): mp 125−127 °C; H NMR (400 MHz, CDCl3) δ 4.18 (s,
(6l). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (229
2H), 6.48 (s, 1H), 7.27−7.52 (m, 4H), 7.68−7.72 (m, 2H), 7.80 (d, J =
7.6 Hz, 1H), 8.26 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
43.2, 106.8, 115.1, 115.3, 120.4, 120.9, 121.1, 124.31, 124.34, 125.5,
128.4, 129.6, 130.6, 130.7, 135.0, 136.9, 138.0, 150.4, 162.5, 164.2,
192.9; MS m/z 283 [MH]+; HRMS (ESI) calcd for C17H12FO3
283.0770 [M + H], found 283.0786.
1
mg, 73%): mp 142−144 °C; H NMR (400 MHz, CDCl3) δ 4.27 (s,
2H), 6.49 (s, 1H), 7.34−7.65 (m, 7H), 7.86 (d, J = 7.2 Hz, 1H), 8.01 (d, J
= 7.2 Hz, 2H), 8.23 (d, J = 8.0 Hz, 1H), 8.74 (d, J = 8.4 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 46.1, 106.8, 120.3, 124.4, 125.5, 125.8,
126.8, 128.3, 128.5, 128.6, 128.9, 129.5, 130.3, 133.9, 134.00, 134.03,
134.9, 137.0, 151.1, 162.6, 197.4; MS m/z 315 [MH]+; HRMS (ESI)
calcd for C21H15O3 315.1021 [M + H], found 315.1018.
3-(2-(3-Chlorophenyl)-2-oxoethyl)-1H-isochromen-1-one
(6e). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (179
1
3-(2-Oxo-3-phenylpropyl)-1H-isochromen-1-one (6m). Elu-
ent, petroleum ether−ethyl acetate (10:1). Yellow solid (172 mg,
62%): mp 112−114 °C; 1H NMR (400 MHz, CDCl3) δ 3.63 (s, 2H),
3.84 (s, 2H), 6.35 (s, 1H), 7.21−7.36 (m, 6H), 7.48 (t, J = 7.6 Hz, 1H),
7.68 (t, J = 7.6 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 46.2, 50.1, 106.6, 120.3, 125.5, 127.4, 128.4, 128.9, 129.56,
129.60, 133.2, 134.9, 136.9, 150.4, 162.4, 202.1; MS m/z 279 [MH]+;
HRMS (ESI) calcd for C18H15O3 279.1021 [M + H], found 279.1016.
3-(2-Oxo-4-phenylbutyl)-1H-isochromen-1-one (6n). Eluent,
petroleum ether−ethyl acetate (10:1). Yellow solid (175 mg, 60%): mp
114−116 °C; 1H NMR (400 MHz, CDCl3) δ 2.92 (s, 4H), 3.58 (s, 2H),
mg, 60%): mp 156−158 °C; H NMR (400 MHz, CDCl3) δ 4.17 (s,
2H), 6.47 (s, 1H), 7.38−7.72 (m, 5 H), 7.89 (d, J = 7.6 Hz, 1H), 7.97 (s,
1H), 8.26 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 43.1,
106.8, 120.4, 125.5, 126.6, 128.4, 128.5, 129.6, 130.3, 133.8, 135.0, 135.3,
136.9, 137.5, 150.3, 162.4, 192.9; MS m/z 299 [MH]+; HRMS (ESI)
calcd for C17H12ClO3 299.0475 [M + H], found 299.0476.
3-(2-(3-Bromophenyl)-2-oxoethyl)-1H-isochromen-1-one
(6f). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (212
1
mg, 62%): mp 159−161 °C; H NMR (400 MHz, CDCl3) δ 4.17 (s,
2H), 6.47 (s, 1H), 7.37−7.52 (m, 3H), 7.68−7.75 (m, 2H), 7.94 (d, J =
7.2 Hz, 1H), 8.13 (d, J = 1.6 Hz, 1H), 8.27 (d, J = 8.0 Hz, 1H); 13C NMR
L
dx.doi.org/10.1021/jo401502k | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
6.34 (s, 1H), 7.17−7.37 (m, 5H), 7.36 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7,6
Hz, 1H), 7.70 (t, J = 7.6 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 29.5, 44.4, 47.3, 106.5, 120.3, 125.5, 126.3, 128.4,
128.6, 129.6, 135.0, 136.9, 140.5, 150.4, 162.4, 203.7; MS m/z 293
[MH]+; HRMS (ESI) calcd for C19H17O3 293.1177 [M + H], found
293.1180.
mixture was stirred at 80 °C for 2 h, the reaction was quenched with
aqueous solution of NH4Cl and extracted with ethyl acetate (5 mL × 3).
The combined organic layers were washed with H2O and brine, and then
dried over anhydrous Na2SO4 and concentrated under a vacuum. The
residue was purified by chromatography on silica gel by using petroleum
ether−ethyl acetate (3:1) as the eluent to afford 7.
1,3-Dihydroxy-12H-benzo[b]xanthen-12-one (7).15 Eluent,
petroleum ether−ethyl acetate (3:1). Yellow solid (51 mg, 91%): mp
270−272 °C (283−285 °C);15 1H NMR (400 MHz, acetone-d6) δ 6.25
(d, J = 2.0 Hz, 1H), 6.42 (d, J = 1.6 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.67
(t, J = 7.6 Hz, 1H), 7.93 (s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.4
Hz, 1H), 8.80 (s, 1H), 9.95 (s, 1H), 12.96 (s, 1H); 13C NMR (100 MHz,
acetone-d6) δ 94.18, 94.23, 97.68, 97.73, 113.2, 120.2, 125.8, 127.16,
127.23, 129.3, 129.6, 129.7, 136.9, 151.8, 158.4, 164.4, 166.1, 180.9; MS
m/z 279 [MH]+.
6-Fluoro-3-(2-oxo-2-m-tolylethyl)-1H-isochromen-1-one
(6o). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (198
1
mg, 67%): mp 136−138 °C; H NMR (400 MHz, CDCl3) δ 2.42 (s,
3H), 4.18 (s, 2H), 6.42 (s, 1H), 7.00−7.18 (m, 2H), 7.34−7.44 (m, 2H),
7.79 (d, J = 6.8 Hz, 2H), 8.24−8.28 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.4, 43.0, 106.1, 111.0, 111.3, 116.4, 116.6, 125.7, 127.3,
128.4, 128.8, 128.9, 132.9, 133.0, 134.7, 136.0, 138.8, 152.6, 161.6, 165.4,
168.0, 194.0; MS m/z 297 [MH]+; HRMS (ESI) calcd for C18H14FO3
297.0927 [M + H], found 297.0933.
3-(2-(3-Chlorophenyl)-2-oxoethyl)-6-fluoro-1H-isochromen-
1-one (6p). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid
(183 mg, 58%): mp 166−168 °C; 1H NMR (400 MHz, CDCl3) δ 4.17
(s, 2H), 6.43 (s, 1H), 7.05 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H), 7.20 (td, J1 =
8.4 Hz, J2 = 2.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H),
7.88 (d, J = 7.6 Hz, 1H), 7.96 (d, J = 1.6 Hz, 1H), 8.27−8.31 (m, 1H);
13C NMR (100 MHz, CDCl3) δ δ 43.1, 106.2, 106.3, 111.1, 111.4, 116.6,
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H and 13C NMR spectra, and the X-ray crystal
structure of 5l. This material is available free of charge via the
Internet at http://pubs.acs.org.
116.8, 116.89, 116.90, 126.6, 128.5, 130.3, 133.0, 133.1, 133.9, 135.4,
137.5, 139.6, 151.8, 161.4, 165.5, 168.0, 192.5; MS m/z 317 [MH]+;
HRMS (ESI) calcd for C17H11ClFO3 317.0381 [M + H], found
317.0379.
AUTHOR INFORMATION
Corresponding Author
*E-mail: xuesen.fan@htu.cn.
Notes
■
6-Methyl-3-(2-oxo-2-p-tolylethyl)-1H-isochromen-1-one
(6q). Eluent, petroleum ether−ethyl acetate (10:1). Yellow solid (193
1
mg, 66%): mp 118−120 °C; H NMR (400 MHz, CDCl3) δ 2.40 (s,
The authors declare no competing financial interest.
3H), 2.43 (s, 3H), 4.13 (s, 2H), 6.37 (s, 1H), 7.13 (s, 1H), 7.27 (d, J = 7.2
Hz, 3H), 7.89 (d, J = 8.0 Hz, 2H), 8.11 (d, J = 8.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 21.7, 21.9, 43.0, 106.4, 117.9, 125.5, 128.7, 129.1,
129.15, 129.24, 129.5, 129.6, 133.6, 137.2, 144.8, 146.0, 151.2, 162.6,
193.7; MS m/z 293 [MH]+; HRMS (ESI) calcd for C19H17O3 293.1177
[M + H], found 293.1181.
ACKNOWLEDGMENTS
■
We are grateful to the Natural Science Foundation of China
(21272058, 21172057), RFDP (20114104110005), PCSIRT
(IRT 1061), and 2012IRTSTHN006 for financial support.
3-(2-(4-Chlorophenyl)-2-oxoethyl)-6-methyl-1H-isochro-
men-1-one (6r). Eluent, petroleum ether−ethyl acetate (10:1). Yellow
solid (187 mg, 60%): mp 125−127 °C; 1H NMR (400 MHz, CDCl3) δ
2.44 (s, 3H), 4.13 (s, 2H), 6.38 (s, 1H), 7.14 (s, 1H), 7.26−7.29 (m,
1H), 7.44 (d, J = 7.6 Hz, 2H), 7.93 (d, J = 9.2 Hz, 2H), 8.11 (d, J = 8.0
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 22.0, 43.1, 106.6, 117.9, 125.5,
128.8, 129.2, 129.5, 129.7, 129.9, 131.0, 134.3, 137.0, 140.3, 146.1, 150.5,
162.5, 193.0; MS m/z 313 [MH]+; HRMS (ESI) calcd for C18H14ClO3
313.0631 [M + H], found 313.0626.
Typical Procedure for the Synthesis of (2-Bromo-4,6-
dihydroxyphenyl)(3-hydroxy naphthalen-2-yl)methanone
(5ee). To a dried round-bottom flask were added (2-bromo-4,6-
dimethoxyphenyl)(3-hydroxy naphthalen-2-yl)methanone (5dd, 0.5
mmol) and CH2Cl2 (5 mL). The flask was purged with nitrogen. BBr3
(0.75 mmol) in CH2Cl2 was then added dropwise to the mixture. The
mixture was allowed to stir at room temperature for 12 h. The reaction
was quenched with water and extracted with ethyl acetate (5 mL × 3).
The combined organic phases were dried, filtered, and concentrated
under reduced pressure. The residue was purified by chromatography on
silica gel by using petroleum ether−ethyl acetate (3:1) as the eluent to
afford 5ee.
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(2-Bromo-4,6-dihydroxyphenyl)(3-hydroxynaphthalen-2-yl)-
methanone (5ee). Eluent, petroleum ether−ethyl acetate (3:1).
1
Yellow solid (125 mg, 70%): mp 158−160 °C; H NMR (400 MHz,
acetone-d6) δ 6.59 (d, J = 1.6 Hz, 1H), 6.78 (d, J = 1.6 Hz, 1H), 7.29−
7.35 (m, 2H), 7.55 (t, J = 7.6 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.86 (d, J
= 8.4 Hz, 1H), 8.18 (s, 1H), 9.14 (s, 1H), 9.23 (s, 1H), 11.34 (s, 1H);
13C NMR (100 MHz, acetone-d6) δ 102.4, 111.3, 111.6, 119.8, 122.1,
(10) (a) Agata, N.; Nogi, H.; Milhollen, M.; Kharbanda, S.; Kufe, D.
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124.0, 126.1, 127.3, 129.7, 129.9, 136.4, 138.4, 156.6, 157.2, 160.1,
201.4; MS m/z 359 [MH]+; HRMS (ESI) calcd for C17H12BrO4
358.9919 [M + H], found 358.9926.
Typical Procedure for the Synthesis of 1,3-Dihydroxy-12H-
benzo[b]xanthen-12-one (7). To a flask containing (2-bromo-4,6-
dihydroxyphenyl)(3-hydroxynaphthalen-2-yl) methanone (5ee, 0.2
mmol) in CH3CN (2 mL) was added K2CO3 (0.4 mmol). After the
M
dx.doi.org/10.1021/jo401502k | J. Org. Chem. XXXX, XXX, XXX−XXX

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Article
̂
(12) (a) Cherry, K.; Parrain, J.-L.; Thibonnet, J.; Duchene, A.; Abarbri,
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