Synthesis of Isoselenazoles and Isothiazoles from Demethoxylative Cycloaddition of Alkynyl Oxime Ethers

Article abstract of DOI:10.1021/acs.joc.0c02286

A general method for the synthesis of isoselenazoles and isothiazoles has been developed by the base-promoted demethoxylative cycloaddition of alkynyl oxime ethers using the cheap and inactive Se powder and Na2S as selenium and sulfur sources. This transformation features the direct construction of N-, Se-, and S-containing heterocycles through the formation of N-Se/S and C-Se/S bonds in one-pot reactions with excellent functional group tolerance.

Full text of DOI:10.1021/acs.joc.0c02286

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Article
Synthesis of Isoselenazoles and Isothiazoles from Demethoxylative
Cycloaddition of Alkynyl Oxime Ethers
Zhu-Zhu Zhang, Rong Chen, Xiao-Hong Zhang,* and Xing-Guo Zhang*
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ABSTRACT: A general method for the synthesis of isoselenazoles
and isothiazoles has been developed by the base-promoted
demethoxylative cycloaddition of alkynyl oxime ethers using the
cheap and inactive Se powder and Na2S as selenium and sulfur
sources. This transformation features the direct construction of N-,
Se-, and S-containing heterocycles through the formation of N−Se/S
and C−Se/S bonds in one-pot reactions with excellent functional group tolerance.
isothiazoles via the base-promoted demethoxylation and
cyclization of alkynyl oxime ethers with the cheap and readily
available Se powder and sodium sulfide (eq 7).
INTRODUCTION
■
Isoselenazoles and isothiazoles are important five-membered
heterocycles containing N and Se/S atoms.1 For example, 4,5-
diaryl isoselenazoles are the multiple target nonsteroidal anti-
inflammatory drugs and can also be used in Parkinson’s
disease, Alzheimer’s disease, and rheumatoid arthritis.2 Ebselen
bearing a isoselenazole moiety is identified as the cytopro-
tective, neuroprotective, and anti-inflammatory agents.3 More-
over, the isothiazole derivatives are widely utilized as antiviral,
antipsychotic, and antibacterial drugs, as well as antidiabetic,
antifungal, neuroprotective, antipoliovirus, and anticancer
agents.1,4 Consequently, the development of efficient and
convenient methods for the construction of isoselenazole and
isothiazole structural motifs has received great attention.1,2,5
The multistep reactions of alkynyl ketones with hydroxyl-
amine-O-sulfonic acid and K2Se or complicated diselenides
were early reported for the synthesis of isoselenazoles in low
yields (Scheme 1, eqs 1 and 2).5a,b The cycloaddition of aryl
ketones with KSeCN and NH4Cl provided another route to
4,5-diaryl substituted isoselenazoles, in which the hypertoxic
HCN was released (eq 3).2 For the synthesis of isothiazoles,
many cycloadditions and transannulations have been re-
ported,6 such as the condensation of β-keto dithioesters with
NH4OAc (eq 4),6d 1,4-cycloaddition of propynenitriles with
Na2S/ClNH2 (eq 5),6e and radical cyclization of α,β-
unsaturated N-sulfonylimines with K2S (eq 6).6f These
transformations provided various routes to isoselenazole and
isothiazole rings. However, the safe and general method for
their synthesis from readily available compounds is still highly
desirable.
RESULTS AND DISCUSSION
■
The model reaction of 1,3-diphenylprop-2-yn-1-one O-methyl
oxime 1aa9 with 1.5 equiv of Se powder was first conducted in
the presence of 2.0 equiv of K3PO4 and 4.0 equiv of H2O in
dimethylformamide (DMF) at 120 °C (Table 1). The target
3,5-diphenyl-1,2-selenazole 2a was obtained in 12% yield
(entry 1), and its structure was confirmed by X-ray single-
crystal diffraction analysis. After screening several bases
including K2CO3, Cs2CO3, 1,4-diazabicyclo[2.2.2]octane
(DABCO), 4-(dimethylamino)pyridine (DMAP), 1,5-
diazabicyclo[4.3.0]non-5-ene (DBN), and 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) (entries 2−7), we
were pleased to find that DBU could promote the
demethoxylative cycloaddition smoothly to furnish the desired
product 2a in 62% yield (entry 7). Encouraged by these results,
various solvents were investigated (entries 8−12) and N-
methyl-2-pyrrolidone (NMP) was the most suitable for this
reaction to afford product 2a in 78% yield (entry 11). Na2Se
was also found to be an effective selenium source, although
furnishing 2a in a lower yield (53%, entry 12). The reaction
yield was decreased when the loading of Se powder was
reduced to 1.2 equiv or when the reaction was carried out at
100 °C (entries 12 and 14).
With the optimized reaction conditions in hand, the
generality of demethoxylative cycloaddition was explored by
Alkynyl oxime ethers are versatile building blocks and often
used in demethylative cyclization for the preparation of
isoxazoles.7 Encouraged by our previous reports in the
chalcogen-containing compounds,8 we envision that deme-
thoxylative cyclization of alkynyl oxime ethers could occur in
the presence of proper selenium or sulfur nucleophiles. Herein,
we report the general synthesis of isoselenazoles and
Received: September 24, 2020
https://dx.doi.org/10.1021/acs.joc.0c02286
© XXXX American Chemical Society
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Scheme 1. Construction of Isoselenazole and Isothiazole Rings
a
Table 1. Optimization of the Reaction Conditions
entry
base
solvent
yield (%)
12
15
1
2
3
4
5
6
7
8
K3PO4
K2CO3
Cs2CO3
DABCO
NaHCO3
DMAP
DBN
DBU
DBU
DBU
DBU
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
toluene
DMAc
NMP
dioxane
NMP
28
NR
NR
NR
52
62
53
9
10
11
12
13
14
55
60
b
c
DBU
DBU
DBU
78, 53 , 55
54
62
d
a
Reaction conditions: 1aa (0.2 mmol), Se (0.3 mmol, 1.5 equiv), base (0.4 mmol, 2.0 equiv), H2O (4.0 equiv), solvent (2.0 mL), 120 °C, air, 12 h.
b
c
d
Na2Se. 1.2 equiv of Se. At 100 °C.
testing a variety of oxime ethers (Table 2). Initially, the R1
groups including aryl and alkyl on the alkynyl moiety were
investigated. Aryl acetylenes bearing both electron-donating
and electron-withdrawing substituents were well compatible
with the transformation. For instance, para-Me, t-Bu-, MeO-,
F-, Cl-, Br-, and CF3-substituted phenyl acetylenes provided
the corresponding isoselenazoles 2b−2h in 56−81% yield.
Ortho- and meta-Me groups did not affect the reactive
efficiency, leading products 2i and 2j in 85 and 83% yields,
respectively. Moreover, the demethoxylative cycloaddition is
amenable to scale-up and 75% yield of 2a was obtained when 5
mmol 1aa was used (56% for 45 mmol). Gratifyingly,
heteroaryl and aliphatic alkynyl oxime ethers, such as
pyridin-3-yl and 5-hexyl oxime ethers, are also suitable
substrates to deliver products 2k and 2l in 52 and 72% yields,
respectively. Subsequently, the scope of alkynyl oxime ethers
with different R2 substituents was examined. Me-, MeO-, F-,
Cl-, Br-, and CF3-substituted phenyl groups afforded the
products 2m−2u in 60−76% yields. Satisfyingly, polycyclic aryl
and heteroaryl oxime ethers showed good tolerance with the
reaction. For example, naphthalene-1-yl, naphthalene-2-yl and
thiophene-2-yl oxime ethers underwent the demethoxylative
cycloaddition smoothly to give products 2v−2x in 70−73%
yields. When R2 was a cyclohexyl group or H atom, the
reactions also worked well and products 2y and 2z were
isolated in 84 and 36% yields, respectively.
In our previously reported work,8f bisisothiazole-4-yl
disulfides were obtained when Se was replaced by S8 in the
DBU-promoted demethoxylative thioannulation. To acquire
the isothiazole derivatives, various sulfur sources were further
screened under different reaction conditions. It was found that
3,5-diphenylisothiazole 3a was obtained in 85% yields using
Na2S as the sulfur source in DMF at 90 °C (Table S2 in the
Supporting Information). Then, various isothiazole derivatives
were prepared by varying R1 and R2 substituents, including
aromatic or aliphatic alkynyl groups (Table 3). For example,
phenyl acetylenes with Me, t-Bu, MeO, F, Cl, Br, and NO2
furnished isothiazoles 3b−3j in moderate to excellent yields
(45−85%). The demethoxylative thioannulation is feasible to
scale-up to 5 mmol 1aa, leading product 3a in 83% yield. For
heteroaryl, aliphatic alkynyl, and polycyclic aryl groups, the 5-
pyridin-3-yl, 5-hexyl and 5-biphenyl isothiazoles 3k−3m were
obtained in good yields (61−83%). Finally, various R2
substituents of oxime ethers were tested. Me-, MeO-, F-, Cl-,
Br-, and CF3-phenyl-substituted oxime ethers underwent the
demethoxylative thioannulations successfully, leading products
3n−3v in 65−88% yields. Polycyclic naphthalene-1-yl and
heterocyclic thiophene-2-yl oxime ethers were also trans-
B
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a
Table 2. Scope with Respect to Alkynyl Oxime Ethers for the Synthesis of Isoselenazoles
a
Reaction conditions: 1 (0.2 mmol), Se (0.3 mmol, 1.5 equiv), base (0.4 mmol, 2.0 equiv), anhydrous NMP (2.0 mL), H2O (4.0 equiv), 120 °C,
b
c
air, 10−15 h. 1aa (5 mmol, 1.175 g). 1aa (45.0 mmol, 10.6 g).
formed into products 3w and 3x in 76 and 82% yields,
respectively. Moreover, oxime ethers bearing aliphatic moiety
gave 3-cyclohexyl isothiazole 3y in 86% yield.
which further attacks the carbon−carbon triple bond to furnish
dianion A. Dianion A abstracts the hydrogen atom from the
H2O to give intermediate B and its analogue B′, which follows
the intramolecular nucleophilic attack to furnish the target
product 2a with the loss of small molecule CH3OH. Moreover,
Na2S can directly release the S2− and undergo the similar
cycloaddition to give the product 3a.
To demonstrate the synthetic application of the obtained
isoselenazoles and isothiazoles, 3,5-diphenyl-1,2-isoselenazole
2a and 3,5-diphenyl-1,2-selenazole 3a were treated with
NBS.10 We were glad to find that the 3-brominated products
4 and 5 were obtained in excellent yields (eq 1, Scheme 2).
The reaction of product 2a with NIS furnished 3-iodinated
isoselenazole 6 in 90% yield.11 These 3-halogenated iso-
selenazoles and isothiazoles can be further modified through
the traditional transition-metal-catalyzed cross-coupling reac-
tions11,12 to synthesize a series of unknown isoselenazole- and
isothiazole-containing derivatives, which are potentially useful
in drug discovery.
To explore the possible mechanism, some control experi-
ments were conducted as shown in Scheme 3. When oxime
ether 1aa was treated with Se powder or Na2S using 2.0 equiv
of TEMPO, BHT, or 1,1-diphenylethylene as a radical
scavenger, the target isoselenazole 2a and isothiazole 3a were
still isolated in 63−78% yields (eq 1). These results suggested
that the demethoxylative cycloaddition might not be involved
in the radical pathway. Treatment of 1aa with Se or Na2S and
0.2 mL of D2O in anhydrous solvent under standard
conditions afforded the almost totally deuterated products D-
2a and D-3a in 62 and 76% yields, respectively, indicating that
the proton was derived from water (eq 2).
CONCLUSIONS
■
In summary, we have developed a facile strategy for the
construction of isoselenazole and isothiazole motifs from
readily available starting materials. A series of biologically
important 3,5-disubstituted isoselenazoles and isothiazoles
were prepared in moderate to good yields by the base-
promoted demethoxylative cycloaddition. These transforma-
tions are feasible to scale-up and possess the advantages of the
usage of cheap and stable selenium powder and Na2S as the Se
source and sulfur source, broad substrate scope, good
efficiency, and multibond formation in a one-pot reaction.
The obtained 3-halogenated isoselenazoles and isothiazoles
could be easily further transformed into potentially pharma-
ceutically active isoselenazole- and isothiazole-containing
derivatives.
EXPERIMENTAL SECTION
■
General Information. Chemicals were either purchased or
purified by standard techniques. 1H NMR and 13C{1H} NMR spectra
Based on the obtained experimental results and previous
literature,13 a plausible reaction pathway is proposed in
Scheme 4. First, the disproportionation reaction of Se with
−OH in the presence of DBU gives selenolate anion (Se2−),
1
were measured on a 500 MHz spectrometer (500 MHz for H and
125 MHz for 13C) or a 400 MHz spectrometer (400 MHz for H),
1
using CDCl3 as the solvent with tetramethylsilane (TMS) as an
internal standard at room temperature. Chemical shifts are given in δ
C
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a
Table 3. Scope with Respect to Alkynyl Oxime Ethers for the Synthesis of Isothiazole
a
Reaction conditions: 1 (0.2 mmol), Na2S (0.3 mmol, 1.5 equiv), NaHCO3 (0.4 mmol, 2.0 equiv), anhydrous DMF (2.0 mL), H2O (6.0 equiv), 90
b
°C, air, 10−15 h. 1aa (5 mmol, 1.175 g).
apparatus and uncorrected. Column chromatography was performed
using EM Silica gel 60 (300−400 mesh).
Scheme 2. Applications of Isoselenazole and Isothiazole as
the Building Blocks
General Procedure for the Synthesis of Isoselenazoles 1.9
An oven-dried 100 mL glass vial was charged with PdCl2(PPh3)2
(210.6 mg, 0.3 mmol), CuI (57.0 mg, 0.3 mmol), acid chloride (19.5
mmol), terminal alkyne (15.0 mmol), and anhydrous triethylamine
(50 mL). The vial was flushed with nitrogen and sealed with a
pressure relief cap. The reaction mixture was stirred at room
temperature, overnight, until the disappearance of starting material
was observed, as monitored by thin-layer chromatography. After the
reaction was finished, the mixture was poured into ethyl acetate,
which was washed with brine (2 × 15 mL). The combined organic
layers were dried over anhydrous MgSO4 and evaporated under
vacuum. The resulting residue was purified by flash column
chromatography on silica gel using petroleum ether/ethyl acetate
(30:1, v/v) as the eluent.
relative to TMS, the coupling constants J are given in hertz. High-
resolution mass spectra were recorded on electrospray ionization
quadrupole time-of-flight mass spectrometry (ESI-Q-TOF). All
reactions under air were conducted using standard Schlenk
techniques. Melting points were measured on an X4 melting point
An oven-dried 100 mL glass vial was charged with O-
methylhydroxylamine hydrochloride (1.68 g, 20.0 mmol), anhydrous
Scheme 3. Control Experiments
D
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Scheme 4. Possible Mechanism
Na2SO4 (2.84 g, 20.0 mmol), pyridine (5 mL), alkynone (10.0
mmol), and anhydrous methanol (20 mL). The reaction vial was
sealed with a pressure relief cap, and the mixture was stirred at room
temperature overnight. After the reaction was finished, the mixture
was poured into ethyl acetate, which was washed with brine (2 × 15
mL). The combined organic layers were dried over anhydrous MgSO4
and evaporated under vacuum. The residue was purified by flash
column chromatography using petroleum ether as the eluent to afford
the desired reagents 1.
General Procedure for the Synthesis of Isoselenazoles 2a−
2z. To a Schlenk tube with a magnetic stirring bar was charged with 1
(0.2 mmol), Se (0.3 mmol, 23.7 mg), DBU (0.4 mmol, 60.8 mg), and
H2O (0.8 mmol, 14.4 mg) in anhydrous NMP (2 mL) under air. The
reaction mixture was stirred at 120 °C in an oil bath for 10−15 h until
the starting material was consumed completely by thin-layer
chromatography (TLC). After the reaction was finished, the mixture
was poured into ethyl acetate, which was washed with brine (2 × 15
mL). The combined organic layers were dried over anhydrous MgSO4
and evaporated under vacuum. The residue was purified by flash
column chromatography using petroleum ether/ethyl acetate as the
eluent to afford the desired products 2a−2z.
General Procedure for the Synthesis of Isothiazoles 3a−3y.
To a Schlenk tube with a magnetic stirring bar was charged with 1aa
(0.2 mmol), Na2S (0.3 mmol, 23.4 mg), NaHCO3 (0.4 mmol, 33.6
mg), and H2O (1.2 mmol, 21.6 mg) in DMF (2 mL) under air. The
reaction mixture was stirred at 90 °C in an oil bath for 10−15 h until
the starting material was consumed completely by TLC. After the
reaction was finished, the mixture was poured into ethyl acetate,
which was washed with brine (2 × 15 mL). The combined organic
layers were dried over anhydrous MgSO4 and evaporated under
vacuum. The residue was purified by flash column chromatography
using petroleum ether/ethyl acetate as the eluent to afford the desired
products 3a−3y.
Procedure for the Scale Synthesis of 2a and 3a. To a Schlenk
tube with a magnetic stirring bar was charged with 1aa (5 mmol,
1.175 g), Se (7.5 mmol, 0.593 g)/Na2S (7.5 mmol, 0.176 g),
anhydrous DBU (10 mmol, 1.520 g)/NaHCO3 (10 mmol, 0.336 g),
and H2O (20 mmol, 0.360 g)/(30 mmol, 0.540 g) in anhydrous
NMP/DMF (10 mL) under air. The reaction mixture was stirred at
120/90 °C in an oil bath for 12 h. After the reaction was finished, the
mixture was poured into ethyl acetate, which was washed with brine
(2 × 30 mL). The combined organic layers were dried over
anhydrous MgSO4 and evaporated under vacuum. The residue was
purified by flash column chromatography using petroleum ether/ethyl
acetate (30:1, v/v) as the eluent to afford the desired scale products
2a (1.07 g, 75% yield) and 3a (0.98 g, 83% yield).
(0.4 mmol, 60.8 mg)/NaHCO3 (0.3 mmol, 23.4 mg), H2O (0.8
mmol, 14.4 mg)/(1.2 mmol, 21.6 mg), and TEMPO (62.4 mg, 0.4
mmol) or BHT (88 mg, 0.4 mmol) or 1,1-diphenylethylene (72 mg,
0.4 mmol) in NMP/DMF (2 mL) under air. The reaction mixture
was stirred at 120/90 °C in an oil bath for 12 h. After the reaction was
finished, the mixture was poured into ethyl acetate, which was washed
with brine (2 × 15 mL). The combined organic layers were dried over
anhydrous MgSO4 and evaporated under vacuum. The residue was
purified by flash column chromatography using petroleum ether/ethyl
acetate (30:1, v/v) as the eluent to afford the desired products 2a and
3a.
Synthesis of 3-Brominated Isoselenazoles and Isothia-
zoles.10 To a Schlenk tube with a magnetic stirring bar was charged
with 2a/3a (0.60 mmol), N-bromosuccinimide (0.78 mmol, 139 mg)
and p-toluenesulfonic acid monohydrate (0.04 mmol, 8 mg) in DCM
(5 mL) under room temperature for 4 h. A further portion of N-
bromosuccinimide (0.78 mmol, 139 mg) and p-toluenesulfonic acid
monohydrate (0.04 mmol, 8 mg) was added, and the mixture was
stirred for 65 h. After the reaction was finished, the mixture was
poured into ethyl acetate, which was washed with brine (2 × 15 mL).
The combined organic layers were dried over anhydrous MgSO4 and
evaporated under vacuum. The residue was purified by flash column
chromatography using petroleum ether/ethyl acetate (30:1, v/v) as
the eluent to afford the desired products 4 (213.6 mg, 89% yield) and
5 (183.2 mg, 97% yield).
Synthesis of 3-Iodinated Isoselenazoles.11 To a Schlenk tube
with a magnetic stirring bar was charged with 2a (0.2 mmol), N-
iodosuccinimide (0.228 mmol, 51.3 mg), ammonium ceric nitrate
(0.022 mmol, 12.1 mg) in MeCN (2 mL) under air. The reaction
mixture was stirred at 82 °C in an oil bath for 16 h. After the reaction
was finished, the mixture was poured into ethyl acetate, which was
washed with brine (2 × 15 mL). The combined organic layers were
dried over anhydrous MgSO4 and evaporated under vacuum. The
residue was purified by flash column chromatography using petroleum
ether/ethyl acetate (3:1, v/v) as the eluent to afford the desired
products 6 (74.0 mg, 90% yield).
1,3-Diphenylprop-2-yn-1-one O-Methyl Oxime (1aa).8f Petro-
leum ether as the eluent; yellow oil (291.4 mg, 62% yield); 1H NMR
(400 MHz, CDCl3) δ 7.94−7.92 (m, 2H), 7.65−7.62 (m, 2H), 7.42−
7.39 (m, 6H), 4.16 (s, 3H).
1-Phenyl-3-(p-tolyl)prop-2-yn-1-one O-Methyl Oxime (1ab).8f
Petroleum ether as the eluent; yellow oil (333.7 mg, 67% yield);
1H NMR (400 MHz, CDCl3) δ 7.93−7.91 (m, 2H), 7.53−7.51 (m,
2H), 7.41−7.40 (m, 3H), 7.20−7.18 (m, 2H), 4.14 (s, 3H), 2.39 (s,
3H).
To a round-bottomed flask with a magnetic stirring bar was
charged with 1aa (45 mmol, 10.6 g), Se (67.5 mmol, 5.3 g),
anhydrous DBU (90 mmol, 13.7 g), and H2O (180 mmol, 3.2 g) in
anhydrous NMP (50 mL) under air. The reaction mixture was heated
to reflux at 120 °C in an oil bath for 12 h. After the reaction was
finished, the mixture was poured into ethyl acetate and washed with
brine (2 × 30 mL). The combined organic layers were dried over
anhydrous MgSO4 and evaporated by vacuum distillation. Crude
product 2a was obtained in 56% yield (7.2 g) by recrystallization from
the mixed petroleum ether/ethyl acetate.
3-(4-(tert-Butyl)phenyl)-1-phenylprop-2-yn-1-one O-Methyl
Oxime (1ac).8f Petroleum ether as the eluent; yellow oil (419.0 mg,
1
72% yield); H NMR (400 MHz, CDCl3) δ 7.94−7.91 (m, 2H),
7.57−7.55 (m, 2H), 7.42−7.40 (m, 5H), 4.15 (s, 3H), 1.34 (s, 9H).
3-(4-Methoxyphenyl)-1-phenylprop-2-yn-1-one O-Methyl Oxime
(1ad).8f Petroleum ether as the eluent; colorless oil (339.2 mg, 64%
1
yield); H NMR (400 MHz, CDCl3) δ 7.95−7.93 (m, 2H), 7.59−
7.57 (m, 2H), 7.42−7.41 (m, 3H), 6.92−6.90 (m, 2H), 4.16 (s, 3H),
3.83 (s, 3H).
3-(4-Fluorophenyl)-1-phenylprop-2-yn-1-one O-Methyl Oxime
(1ae).8f Petroleum ether as the eluent; yellow oil (273.2 mg, 54%
Control Experiments. To a flame-dried Schlenk tube with a
magnetic stirring bar was charged with 1aa (47.0 mg, 0.2 mmol), Se
(0.3 mmol, 23.7 mg)/Na2S (0.3 mmol, 23.4 mg), anhydrous DBU
1
yield); H NMR (400 MHz, CDCl3) δ 7.95−7.92 (m, 2H), 7.64−
7.60 (m, 2H), 7.43−7.42 (m, 3H), 7.11−7.07 (m, 2H), 4.17 (s, 3H).
E
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3-(4-Chlorophenyl)-1-phenylprop-2-yn-1-one O-Methyl Oxime
yield); H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H), 7.81−7.80 (m,
1H), 7.64−7.61 (m, 2H), 7.41−7.32 (m, 5H), 4.15 (s, 3H).
1-(Naphthalen-1-yl)-3-phenylprop-2-yn-1-one O-Methyl Oxime
(1av). Petroleum ether as the eluent; yellow oil (330.6 mg, 58%
(1af).8f Petroleum ether as the eluent; yellow oil (269.0 mg, 50%
1
yield); H NMR (400 MHz, CDCl3) δ 7.93−7.90 (m, 2H), 7.57−
7.55 (m, 2H), 7.43−7.41 (m, 3H), 7.38−7.36 (m, 2H), 4.16 (s, 3H).
3-(4-Bromophenyl)-1-phenylprop-2-yn-1-one O-Methyl Oxime
(1ag).14 Petroleum ether as the eluent; yellow oil (319.3 mg, 51%
yield); 1H NMR (500 MHz, CDCl3) δ 7.95−7.94 (m, 2H), 7.51 (dd,
J = 21.0, 8.5 Hz, 4H), 7.46−7.43 (m, 3H), 4.18 (s, 3H).
1
yield); H NMR (400 MHz, CDCl3) δ 8.63 (d, J = 8.4 Hz, 1H),
7.95−7.91 (m, 2H), 7.84 (d, J = 7.2 Hz, 1H), 7.62−7.53 (m, 5H),
7.39−7.34 (m, 3H), 4.25 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 140.6, 134.1, 132.3, 131.5, 131.0, 130.2, 129.6, 128.6, 128.5, 127.9,
126.9, 126.2, 125.7, 125.3, 121.9, 101.5, 81.5, 63.3; HRMS (ESI-
TOF) m/z: [M + Na]+ calcd for C20H15NNaO 308.1046; found
308.1050.
1-Phenyl-3-(4-(trifluoromethyl)phenyl)prop-2-yn-1-one O-Meth-
yl Oxime (1ah).8f Petroleum ether as the eluent; red oil (272.7 mg,
1
45% yield); H NMR (400 MHz, CDCl3) δ 7.91−7.89 (m, 2H),
7.74−7.72 (m, 2H), 7.66−7.64 (m, 2H), 7.43−7.41 (m, 3H), 4.16 (s,
3H).
1-(Naphthalen-2-yl)-3-phenylprop-2-yn-1-one O-Methyl Oxime
(1aw).8f Petroleum ether as the eluent; white oil (296.4 mg, 52%
1-Phenyl-3-(o-tolyl)prop-2-yn-1-one O-Methyl Oxime (1ai).8f
Petroleum ether as the eluent; yellow oil (288.8 mg, 58% yield);
1H NMR (400 MHz, CDCl3) δ 7.98−7.96 (m, 2H), 7.62−7.60 (m,
1H), 7.44−7.42 (m, 3H), 7.34−7.27 (m, 2H), 7.24−7.20 (m, 1H),
4.17 (s, 3H), 2.58 (s, 3H).
1
yield); H NMR (400 MHz, CDCl3) δ 8.37 (s, 1H), 8.11−8.08 (m,
1H), 7.94−7.92 (m, 1H), 7.87−7.85 (m, 2H), 7.71−7.68 (m, 2H),
7.53−7.51 (m, 2H), 7.44−7.42 (m, 3H), 4.21 (s, 3H).
3-Phenyl-1-(thiophen-2-yl)prop-2-yn-1-one O-Methyl Oxime
(1ax).8f Petroleum ether as the eluent; yellow oil (221.7 mg, 46%
1-Phenyl-3-(m-tolyl)prop-2-yn-1-one O-Methyl Oxime (1aj).8f
Petroleum ether as the eluent; yellow oil (323.7 mg, 65% yield);
1H NMR (400 MHz, CDCl3) δ 7.98−7.96 (m, 2H), 7.48−7.43 (m,
1
yield); H NMR (400 MHz, CDCl3) δ 7.62−7.61 (m, 2H), 7.52−
7.51 (m, 1H), 7.44−7.39 (m, 3H), 7.33−7.32 (m, 1H), 7.07−7.05
(m, 1H), 4.11 (s, 3H).
1-Cyclohexyl-3-phenylprop-2-yn-1-one O-Methyl Oxime (1ay).8f
5H), 7.32−7.28 (m, 1H), 7.25−7.23 (m, 1H), 4.18 (s, 3H), 2.39 (s,
3H).
1
Petroleum ether as the eluent; yellow oil (245.8 mg, 51% yield); H
1-Phenyl-3-(pyridin-3-yl)prop-2-yn-1-one O-Methyl Oxime
(1ak). Petroleum ether as the eluent; white oil (212.4 mg, 45%
yield); H NMR (500 MHz, CDCl3) δ 8.84 (m, 1H), 8.61 (m, 1H),
NMR (500 MHz, CDCl3) δ 7.54−7.51 (m, 2H), 7.37−7.33 (m, 3H),
3.96 (s, 3H), 2.44−2.38 (m, 1H), 1.90−1.78 (m, 4H), 1.71−1.69 (m,
1H), 1.56−1.46 (m, 2H), 1.38−1.28 (m, 2H), 1.26−1.20 (m, 1H).
3-Phenylpropiolaldehyde O-Methyl Oxime (1az).16 Petroleum
ether as the eluent; white oil (154.8 mg, 49% yield); H NMR (400
MHz, CDCl3) δ 7.53−7.51 (m, 2H), 7.34−7.32 (m, 3H), 6.90 (s,
1H), 4.03−3.95 (m, 3H).
3-(4-Nitrophenyl)-1-phenylprop-2-yn-1-one O-Methyl Oxime
(1ba). Petroleum ether as the eluent; yellow solid (202.9 mg, 43%
yield); mp 85−87 °C; 1H NMR (500 MHz, CDCl3) δ 8.25−8.24 (m,
2H), 7.89−7.87 (m, 2H), 7.77−7.75 (m, 2H), 7.43−7.41 (m, 3H),
4.16 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 148.0, 139.3,
133.1, 133.0, 130.1, 128.7, 128.6, 126.5, 123.8, 98.4, 83.8, 63.5;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H13N2O3 281.0921;
found 281.0917.
3-([1,1′-Biphenyl]-4-yl)-1-phenylprop-2-yn-1-one O-Methyl
Oxime (1bb).15 Petroleum ether as the eluent; white solid (342.1
mg, 55% yield); mp 95−97 °C; 1H NMR (400 MHz, CDCl3) δ 7.95−
7.94 (m, 2H), 7.71−7.69 (m, 2H), 7.64−7.62 (m, 4H), 7.49−7.39
(m, 6H), 4.17 (s, 3H).
1
7.91−7.88 (m, 3H), 7.41−7.39 (m, 3H), 7.33−7.30 (m, 1H), 4.15 (s,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 152.7, 149.8, 139.5, 139.1,
133.3, 130.0, 128.6, 126.5, 123.2, 119.2, 97.5, 82.5, 63.4; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C15H13N2O 237.1022; found
237.1029.
1
1-Phenylnon-2-yn-1-one O-Methyl Oxime (1al).15 Petroleum
ether as the eluent; white oil (232.4 mg, 50% yield); 1H NMR
(500 MHz, CDCl3) δ 7.88−7.87 (m, 2H), 7.37 (m, 3H), 4.10 (s,
3H), 2.56−2.54 (m, 2H), 1.67−1.34 (m, 8H), 0.93−0.92 (m, 3H).
3-Phenyl-1-(p-tolyl)prop-2-yn-1-one O-Methyl Oxime (1am).4
1
Petroleum ether as the eluent; white oil (363.5 mg, 73% yield); H
NMR (400 MHz, CDCl3) δ 7.85−7.83 (m, 2H), 7.65−7.63 (m, 2H),
7.42−7.37 (m, 3H), 7.24−7.22 (m, 2H), 4.15 (s, 3H), 2.40 (s, 3H).
1-(4-Methoxyphenyl)-3-phenylprop-2-yn-1-one O-Methyl Oxime
(1an).8f Petroleum ether as the eluent; white oil (371.0 mg, 70%
1
yield); H NMR (400 MHz, CDCl3) δ 7.88−7.84 (m, 2H), 7.63−
7.61 (m, 2H), 7.41−7.36 (m, 3H), 6.95−6.91 (m, 2H), 4.12 (s, 3H),
3.85 (s, 3H).
3,5-Diphenyl-1,2-Selenazole (2a). Petroleum ether/ethyl acetate
(30:1, v/v) as the eluent; yellow solid (44.5 mg, 78% yield); mp 88−
1-(4-Fluorophenyl)-3-phenylprop-2-yn-1-one O-Methyl Oxime
(1ao).8f Petroleum ether as the eluent; yellow oil (278.3 mg, 55%
1
90 °C; H NMR (400 MHz, CDCl3) δ 8.01−7.96 (m, 3H), 7.62−
1
yield); H NMR (400 MHz, CDCl3) δ 7.93−7.89 (m, 2H), 7.63−
7.59 (m, 2H), 7.50−7.40 (m, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ 173.6, 171.9, 137.0, 133.8, 129.7, 129.4, 129.3, 128.9, 127.2,
127.1, 120.7; 77Se NMR (114 MHz, CDCl3) δ 1066.9; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C15H12NSe 286.0130; found
286.0128.
7.61 (m, 2H), 7.42−7.37 (m, 3H), 7.12−7.07 (m, 2H), 4.14 (s, 3H).
1-(4-Chlorophenyl)-3-phenylprop-2-yn-1-one O-Methyl Oxime
(1ap).8f Petroleum ether as the eluent; white oil (263.6 mg, 49%
1
yield); H NMR (400 MHz, CDCl3) δ 7.87−7.85 (m, 2H), 7.63−
7.60 (m, 2H), 7.42−7.36 (m, 5H), 4.14 (s, 3H).
3-Phenyl-5-(p-tolyl)-1,2-Selenazole (2b). Petroleum ether/ethyl
1-(4-Bromophenyl)-3-phenylprop-2-yn-1-one O-Methyl Oxime
(1aq).8f Petroleum ether as the eluent; white oil (281.7 mg, 45%
acetate (30:1, v/v) as the eluent; yellow solid (102.0 mg, 81% yield);
1
1
mp 67−69 °C; H NMR (500 MHz, CDCl3) δ 8.00−7.98 (m, 2H),
yield); H NMR (400 MHz, CDCl3) δ 7.80−7.77 (m, 2H), 7.62−
7.93 (s, 1H), 7.50−7.43 (m, 5H), 7.24 (d, J = 8.0 Hz, 2H), 2.39 (s,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 173.6, 171.9, 139.9, 137.0,
131.0, 130.0, 129.2, 128.8, 127.2, 127.0, 120.2, 21.4; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C16H14NSe 300.0286; found
300.0290.
7.60 (m, 2H), 7.55−7.51 (m, 2H), 7.42−7.37 (m, 3H), 4.14 (s, 3H).
3-Phenyl-1-(4-(trifluoromethyl)phenyl)prop-2-yn-1-one O-Meth-
yl Oxime (1ar).8f Petroleum ether as the eluent; yellow oil (236.3 mg,
1
39% yield); H NMR (400 MHz, CDCl3) δ 8.04−8.02 (m, 2H),
7.67−7.61 (m, 4H), 7.43−7.38 (m, 3H), 4.17 (s, 3H).
3-Phenyl-1-(o-tolyl)prop-2-yn-1-one O-Methyl Oxime (1as).8f
Petroleum ether as the eluent; yellow oil (254.0 mg, 51% yield);
1H NMR (500 MHz, CDCl3) δ 7.46 (m, 3H), 7.29−7.15 (m, 6), 4.05
(s, 3H), 2.46 (s, 3H).
5-(4-(tert-Butyl)phenyl)-3-phenyl-1,2-selenazole (2c). Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; white solid (101.8 mg,
75% yield); mp 91−93 °C; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J
= 6.8 Hz, 2H), 7.95(s, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.50−7.43 (m,
5H), 1.37 (s, 9H); 13C{1H} NMR (125 MHz, CDCl3) δ 173.6, 171.9,
153.2, 137.1, 131.1, 129.2, 128.9, 127.3, 126.9, 126.3, 120.3, 35.0,
31.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C19H20NSe
342.0756; found 342.0755.
3-Phenyl-1-(m-tolyl)prop-2-yn-1-one O-Methyl Oxime (1at).8f
1
Petroleum ether as the eluent; yellow oil (299.8 mg, 60% yield); H
NMR (500 MHz, CDCl3) δ 7.72−7.70 (m, 2H), 7.62−7.60 (m, 2H),
7.39−7.35 (m, 3H), 7.30−7.27 (m, 1H), 7.22−7.19 (m, 1H), 4.13 (s,
3H), 2.39 (s, 3H).
5-(4-Methoxyphenyl)-3-phenyl-1,2-selenazole (2d). Petroleum
ether/ethyl acetate (15:1, v/v) as the eluent; white solid (94.9 mg,
1-(3-Chlorophenyl)-3-phenylprop-2-yn-1-one O-Methyl Oxime
(1au).8f Petroleum ether as the eluent; white oil (236.7 mg, 44%
70% yield); m.p. 111−113 °C; H NMR (400 MHz, CDCl3) δ 7.97
1
F
https://dx.doi.org/10.1021/acs.joc.0c02286
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(d, J = 6.8 Hz, 2H), 7.86 (s, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.49−7.42
(m, 3H), 6.94 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 173.3, 171.9, 160.9, 137.1, 129.2, 128.8, 128.5, 127.2,
126.5, 119.6, 114.7, 55.5; 77Se NMR (114 MHz, CDCl3) δ 1061.3;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H14NOSe 316.0236;
found 316.0232.
5-(4-Fluorophenyl)-3-phenyl-1,2-selenazole (2e). Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; white solid (79.3 mg,
61% yield); mp 77−79 °C; 1H NMR (400 MHz, CDCl3) δ 7.98−7.96
(m, 2H), 7.91 (s, 1H), 7.61−7.58 (m, 2H), 7.49−7.44 (m, 3H),
7.17−7.13 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 172.3,
172.0, 163.6 (d, JC‑F = 248.8 Hz), 137.0, 130.2, 129.4, 129.0, 128.9,
127.3, 121.0, 116.5 (d, JC‑F = 21.3 Hz); HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C15H11FNSe 304.0036; found 304.0035.
mp 82−84 °C; 1H NMR (500 MHz, CDCl3) δ 7.93 (s, 1H), 7.86 (d,
J = 8.0 Hz, 2H), 7.59−7.57 (m, 2H), 7.44−7.40 (m, 3H), 7.26−7.24
(m, 2H), 2.38 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 173.3,
172.0, 139.4, 134.4, 133.9, 129.7, 129.6, 129.4, 127.2, 120.7, 21.5; 77Se
NMR (114 MHz, CDCl3) δ 1063.3; HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C16H14NSe 300.0286; found 300.0288.
3-(4-Methoxyphenyl)-5-phenyl-1,2-selenazole (2n). Petroleum
ether/ethyl acetate (15:1, v/v) as the eluent; white solid (87.9 mg,
70% yield); mp 87−89 °C; 1H NMR (500 MHz, CDCl3) δ 7.94−7.91
(m, 3H), 7.59 (d, J = 7.0 Hz, 2H), 7.45−7.39 (m, 3H), 6.98 (d, J =
8.0 Hz, 2H), 3.85 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
173.1, 171.5, 160.5, 133.9, 130.1, 129.6, 129.3, 128.6, 127.1, 120.4,
114.2, 55.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C16H14NOSe 316.0236; found 316.0226.
5-(4-Chlorophenyl)-3-phenyl-1,2-selenazole (2f). Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; yellow solid (91.5 mg,
70% yield); mp 79−81 °C; 1H NMR (400 MHz, CDCl3) δ 7.97−7.95
(m, 2H), 7.91 (s, 1H), 7.51−7.43 (m, 5H), 7.41−7.39 (m, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 172.0, 171.9, 136.8, 135.6,
132.2, 129.5, 129.4, 128.9, 128.3, 127.2, 121.1; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C15H11ClNSe 319.9738; found 319.9749.
5-(4-Bromophenyl)-3-phenyl-1,2-selenazole (2g). Petroleum
ether/ethyl acetate (50:1, v/v) as the eluent; white solid (88.1 mg,
56% yield); mp 74−76 °C; 1H NMR (500 MHz, CDCl3) δ 7.97−7.94
(m, 3H), 7.57 (d, J = 8.0 Hz, 2H), 7.47−7.43 (m, 5H); 13C{1H}
NMR (125 MHz, CDCl3) δ 172.10, 172.07, 136. 0, 132.8, 132.6,
129.5, 129.0, 128.6, 127.3, 123.9, 121.2; HRMS (ESI-TOF) m/z: [M
+ Na]+ calcd for C15H10BrNNaSe 385.9051; found 385.9057.
3-Phenyl-5-(4-(trifluoromethyl)phenyl)-1,2-selenazole (2h). Pe-
troleum ether/ethyl acetate (50:1, v/v) as the eluent; yellow solid
(90.9 mg, 63% yield); mp 67−69 °C; 1H NMR (500 MHz, CDCl3) δ
8.01 (s, 1H), 7.97 (d, J = 7.0 Hz, 2H), 7.70 (m, 4H), 7.49−7.44 (m,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 172.1, 171.5, 137.1, 136.8,
131.5 (q, JC‑F = 33.75 Hz), 129.6, 129.0, 127.4, 127.3, 126.4, 124.0 (q,
3-(4-Fluorophenyl)-5-phenyl-1,2-selenazole (2o). Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; white solid (100.9 mg,
76% yield); mp 73−75 °C; 1H NMR (500 MHz, CDCl3) δ 7.97−7.91
(m, 3H), 7.59 (d, J = 7.0 Hz, 2H), 7.46−7.43 (m, 3H), 7.16−7.13 (m,
2H); 13C{1H} NMR (125 MHz, CDCl3) δ 173.9, 170.7, 163.5 (d, JC‑F
= 247.5 Hz), 133.7, 133.4, 129.8, 129.4, 129.1, 127.1, 120.5, 115.8 (d,
JC‑F = 22.5 Hz); 77Se NMR (114 MHz, CDCl3) δ 1067.4; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C15H11FNSe 304.0036; found
304.0045.
3-(4-Chlorophenyl)-5-phenyl-1,2-selenazole (2p). Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; white solid (95.6 mg,
75% yield); mp 89−91 °C; 1H NMR (500 MHz, CDCl3) δ 7.92−7.91
(m, 3H), 7.59−7.44 (m, 7H); 13C{1H} NMR (125 MHz, CDCl3) δ
174.1, 170.6, 135.4, 135.3, 133.6, 129.9, 129.4, 129.1, 128.5, 127.1,
120.4; 77Se NMR (114 MHz, CDCl3) δ 1070.0; HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C15H11ClNSe 319.9738; found 319.9742.
3-(4-Bromophenyl)-5-phenyl-1,2-selenazole (2q). Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; white solid (87.3 mg,
60% yield); mp 77−79 °C; 1H NMR (400 MHz, CDCl3) δ 7.92 (m,
1H), 7.86−7.83 (m, 2H), 7.61−7.58 (m, 4H), 7.45−7.44 (m, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 174.2, 170.7, 135.9, 133.6,
132.1, 129.9, 129.5, 128.8, 127.2, 123.7, 120.4; HRMS (ESI-TOF) m/
z: [M + Na]+ calcd for C15H10BrNNaSe 385.9051; found 385.9061.
5-Phenyl-3-(4-(trifluoromethyl)phenyl)-1,2-selenazole (2r). Pe-
troleum ether/ethyl acetate (30:1, v/v) as the eluent; white solid
(88.8 mg, 62% yield); mp 126−128 °C; 1H NMR (500 MHz, CDCl3)
δ 8.08 (d, J = 8.0 Hz, 2H), 7.98 (m, 1H), 7.72 (d, J = 8.0 Hz, 2H),
7.62−7.60 (m, 2H), 7.48−7.44 (m, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 174.7, 170.3, 140.0, 133.6, 131.0 (q, JC‑F = 32.5 Hz), 130.0,
129.5, 127.5, 127.2, 125.9, 124.2 (q, JC‑F = 271.3 Hz), 120.6; HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C16H10F3NNaSe 375.9823;
found 375.9821.
J
C‑F = 273.8 Hz), 122.0; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C16H10F3NNaSe 375.9823; found 375.9824.
3-Phenyl-5-(o-tolyl)-1,2-selenazole (2i). Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; yellow liquid (101.5 mg, 85%
1
yield); H NMR (500 MHz, CDCl3) δ 7.86−7.84 (m, 2H), 7.65 (s,
1H), 7.34−7.27 (m, 4H), 7.18−7.17 (m, 2H), 7.13−7.11 (m, 1H),
2.31 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 172.5, 170.8,
136.9, 135.2, 133.6, 131.1, 129.6, 129.2, 129.1, 128.8, 127.2, 126.2,
124.2, 21.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H14NSe
300.0286; found 300.0282.
3-Phenyl-5-(m-tolyl)-1,2-selenazole (2j). Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; yellow liquid (99.1 mg, 83% yield);
1H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 7.0 Hz, 2H), 7.82 (s, 1H),
7.35−7.26 (m, 5H), 7.20−7.17 (m, 1H), 7.09 (d, J = 7.5 Hz, 1H),
2.29 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 173.8, 171.9,
139.1, 137.1, 133.7, 130.5, 129.2, 128.9, 127.8, 127.2, 124.2, 120.6,
21.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H14NSe
300.0286; found 300.0278.
3-Phenyl-5-(pyridin-3-yl)-1,2-selenazole (2k). Petroleum ether/
ethyl acetate (10:1, v/v) as the eluent; white solid (66.8 mg, 52%
yield); mp 70−72 °C; 1H NMR (500 MHz, CDCl3) δ 8.85 (d, J = 2.0
Hz, 1H), 8.63−8.62 (m, 1H), 7.98−7.94 (m, 3H), 7.86−7.84 (m,
1H), 7.47−7.40 (m, 3H), 7.36 (dd, J = 5.0, 8.0 Hz, 1H); 13C{1H}
NMR (125 MHz, CDCl3) δ 172.0, 169.1, 150.5, 147.7, 136.6, 134.1,
129.9, 129.5, 128.9, 127.2, 124.0, 121.8; HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C14H11N2Se 287.0082; found 287.0089.
5-Hexyl-3-phenyl-1,2-selenazole (2l). Petroleum ether/ethyl ac-
etate (100:1, v/v) as the eluent; yellow liquid (77.1 mg, 72% yield);
1H NMR (500 MHz, CDCl3) δ 7.92 (d, J = 7.0 Hz, 2H), 7.55 (s, 1H),
7.45−7.39 (m, 3H), 3.02 (t, J = 7.5 Hz, 2H), 1.77−1.71 (m, 2H),
1.45−1.32 (m, 6H), 0.91 (t, J = 6.5 Hz, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 177.0, 171.1, 137.1, 129.0, 128.8, 127.2, 123.1, 32.1,
31.7, 31.6, 28.9, 22.6, 14.1; HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C15H20NSe 294.0756; found 294.0748.
5-Phenyl-3-(o-tolyl)-1,2-selenazole (2s). Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; yellow solid (95.4 mg, 74% yield);
1
mp 112−114 °C; H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.63
(d, J = 6.4 Hz, 2H), 7.57 (d, J = 7.2 Hz, 1H), 7.51−7.45 (m, 3H),
7.40−7.31 (m, 3H), 2.52 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 173.7, 172.7, 137.6, 136.3, 133.7, 131.0, 129.6, 129.34, 129.28,
128.8, 127.1, 125.8, 123.7, 20.7; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C16H14NSe 300.0286; found 300.0291.
5-Phenyl-3-(m-tolyl)-1,2-selenazole (2t). Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; yellow solid (91.4 mg, 75% yield);
1
mp 72−74 °C; H NMR (500 MHz, CDCl3) δ 7.98 (m, 1H), 7.84
(m, 1H), 7.77 (d, J = 7.5 Hz, 1H), 7.64−7.62 (m, 2H), 7.49−7.44 (m,
3H), 7.39−7.36 (m, 1H), 7.28 (m, 1H), 2.46 (s, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 173.4, 172.2, 138.6, 137.0, 133.9, 130.1, 129.7,
129.4, 128.8, 127.9, 127.2, 124.4, 120.9, 21.6; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C16H14NSe 300.0286; found 300.0293.
3-(3-Chlorophenyl)-5-phenyl-1,2-selenazole (2u). Petroleum
ether/ethyl acetate (50:1, v/v) as the eluent; white solid (90.5 mg,
71% yield); mp 72−74 °C; 1H NMR (500 MHz, CDCl3) δ 7.98−7.97
(m, 1H), 7.92 (m, 1H), 7.86−7.84 (m, 1H), 7.60−7.58 (m, 2H),
7.47−7.39 (m, 5H); 13C{1H} NMR (125 MHz, CDCl3) δ 174.3,
170.3, 138.5, 134.9, 133.6, 130.1, 129.9, 129.4, 129.3, 127.4, 127.1,
125.3, 120.5; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C15H11ClNSe 319.9738; found 319.9744.
5-Phenyl-3-(p-tolyl)-1,2-selenazole (2m). Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; yellow solid (87.5 mg, 73% yield);
G
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3-(Naphthalen-1-yl)-5-phenyl-1,2-selenazole (2v). Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; yellow liquid (96.1
mg, 70% yield); 1H NMR (500 MHz, CDCl3) δ 8.37−8.35 (m, 1H),
7.96−7.93 (m, 2H), 7.85 (m, 1H), 7.76−7.74 (m, 1H), 7.64−7.62
(m, 2H), 7.58−7.53 (m, 3H), 7.48−7.43 (m, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 173.0, 172.8, 135.6, 134.0, 133.7, 131.3, 129.7,
129.5, 129.4, 128.5, 127.3, 127.2, 126.8, 126.2, 125.9, 125.3, 124.5;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C19H14NSe 336.0287;
found 336.0291.
3-(Naphthalen-2-yl)-5-phenyl-1,2-selenazole (2w). Petroleum
ether/ethyl acetate (50:1, v/v) as the eluent; yellow solid (94.7 mg,
71% yield); mp 89−91 °C; 1H NMR (500 MHz, CDCl3) δ 8.42 (m,
1H), 8.19−8.17 (m, 1H), 8.10 (m, 1H), 7.96−7.93 (m, 2H), 7.88−
7.87 (m, 1H), 7.63 (d, J = 6.5 Hz, 2H), 7.54−7.52 (m, 2H), 7.48−
7.43 (m, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 173.5, 171.7,
134.3, 133.72, 133.71, 133.4, 129.7, 129.3, 128.7, 128.6, 127.8, 127.1,
126.8, 126.7, 126.6, 124.8, 120.8; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C19H14NSe 336.0287; found 336.0276.
2H), 7.70 (s, 1H), 7.65−7.62 (m, 2H), 7.50−7.43 (m, 3H), 7.18−
7.14 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 168.6, 167.3,
163.6 (d, JC‑F = 248.8 Hz), 135.0, 129.5, 129.0, 128.7, 127.5, 127.0,
117.9, 116.5 (d, JC‑F = 22.5 Hz); HRMS (ESI-TOF) m/z: [M + H]+
calcd for C15H11FNS 256.0591; found 256.0597.
5-(4-Chlorophenyl)-3-phenylisothiazole (3f).5d Petroleum ether/
ethyl acetate (30:1, v/v) as the eluent; white solid (86.7 mg, 76%
yield); mp 78−80 °C; 1H NMR (400 MHz, CDCl3) δ 7.99−7.97 (m,
2H), 7.72 (s, 1H), 7.59−7.57 (m, 2H), 7.50−7.41 (m, 5H); 13C{1H}
NMR (125 MHz, CDCl3) δ 168.6, 167.0, 135.7, 134.9, 129.7, 129.6,
129.5, 129.0, 128.0, 127.0, 118.0.
5-(4-Bromophenyl)-3-phenylisothiazole (3g). Petroleum ether/
ethyl acetate (15:1, v/v) as the eluent; white solid (114.1 mg, 80%
yield); mp 90−92 °C; 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 7.2
Hz, 2H), 7.73 (s, 1H), 7.61−7.59 (m, 2H), 7.53−7.41 (m, 5H);
13C{1H} NMR (125 MHz, CDCl3) δ 168.7, 167.1, 134.9, 132.6,
130.1, 129.5, 129.0, 128.2, 127.0, 123.9, 118.0; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C15H11BrNS 315.9790; found 315.9782.
5-(4-Nitrophenyl)-3-phenylisothiazole (3h). Petroleum ether/
ethyl acetate (50:1, v/v) as the eluent; yellow solid (50.6 mg, 45%
yield); mp 108−110 °C; 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J =
8.4 Hz, 2H), 8.00 (d, J = 6.8 Hz, 2H), 7.86−7.81 (m, 3H), 7.50−7.45
(m, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.0, 165.4, 148.3,
137.1, 134.5, 129.8, 129.1, 127.5, 127.1, 124.8, 119.4; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C15H11N2O2S 283.0536; found
283.0544.
5-Phenyl-3-(thiophen-2-yl)-1,2-selenazole (2x). Petroleum ether/
ethyl acetate (30:1, v/v) as the eluent; yellow solid (87.3 mg, 73%
yield); mp 80−82 °C; 1H NMR (500 MHz, CDCl3) δ 7.85−7.84 (m,
1H), 7.58−7.51 (m, 3H), 7.45−7.38 (m, 4H), 7.11−7.09 (m, 1H);
13C{1H} NMR (125 MHz, CDCl3) δ 173.5, 166.1, 141.5, 133.4,
129.8, 129.4, 127.7, 127.6, 127.1, 125.9, 119.9; HRMS (ESI-TOF) m/
z: [M + Na]+ calcd for C13H9NNaSSe 313.9513; found 313.9513.
3-Cyclohexyl-5-phenyl-1,2-selenazole (2y). Petroleum ether/ethyl
acetate (50:1, v/v) as the eluent; yellow liquid (49.0 mg, 84% yield);
1H NMR (500 MHz, CDCl3) δ 7.53−7.52 (m, 2H), 7.42−7.36 (m,
4H), 2.85−2.79 (m, 1H), 2.07−2.04 (m, 2H), 1.86−1.84 (m, 2H),
1.76−1.73 (m, 1H), 1.61−1.53 (m, 2H), 1.44−1.35 (m, 2H), 1.32−
1.24 (m, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 180.5, 172.2,
133.9, 129.3, 129.2, 127.0, 121.2, 45.3, 32.5, 26.4, 26.1; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C15H18NSe 292.0599; found
292.0599.
3-Phenyl-5-(o-tolyl)isothiazole (3i).17 Petroleum ether/ethyl ac-
etate (50:1, v/v) as the eluent; white liquid (51.9 mg, 82% yield); 1H
NMR (400 MHz, CDCl3) δ 8.02−8.00 (m, 2H), 7.61 (s, 1H), 7.50−
7.41 (m, 4H), 7.35−7.27 (m, 3H), 2.48 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 167.64, 167.55, 135.9, 135.1, 131.2, 131.0, 129.8,
129.4, 129.3, 129.0, 127.1, 126.4, 121.0, 21.2.
3-Phenyl-5-(m-tolyl)isothiazole (3j).17 Petroleum ether/ethyl
acetate (15:1, v/v) as the eluent; white liquid (42.7 mg, 85%
5-Phenyl-1,2-selenazole (2z).5a Petroleum ether/ethyl acetate
1
yield); H NMR (400 MHz, CDCl3) δ 8.06−8.04 (m, 2H), 8.78−
1
8.77 (m, 1H), 7.54−7.44 (m, 5H), 7.38−7.36 (m, 1H), 7.27 (d, J =
7.6 Hz, 1H), 2.46 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
168.6, 168.3, 139.1, 135.1, 131.0, 130.5, 129.3, 129.2, 128.9, 127.4,
127.0, 123.8, 117.6, 21.4.
(20:1, v/v) as the eluent; yellow liquid (30.2 mg, 36% yield); H
NMR (500 MHz, CDCl3) δ 7.46−7.39 (m, 6H), 5.88 (d, J = 17.0 Hz,
1H); 13C{1H} NMR (125 MHz, CDCl3) δ 150.7, 133.6, 131.3, 129.2,
127.5, 118.3, 96.5.
3,5-Diphenylisothiazole (3a).12 Petroleum ether/ethyl acetate
(30:1, v/v) as the eluent; yellow solid (40.1 mg, 85% yield); mp
83−85 °C; 1H NMR (400 MHz, CDCl3) δ 8.01−7.99 (m, 2H), 7.76
(s, 1H), 7.68−7.65 (m, 2H), 7.50−7.42 (m, 6H); 13C{1H} NMR
(125 MHz, CDCl3) δ 168.48, 168.45, 135.1, 131.2, 129.7, 129.39,
129.37, 129.0, 127.0, 126.8, 117.8.
3-Phenyl-5-(pyridin-3-yl)isothiazole (3k). Petroleum ether/ethyl
acetate (10:1, v/v) as the eluent; white solid (43.1 mg, 61% yield);
mp 91−93 °C; 1H NMR (500 MHz, CDCl3) δ 8.94 (s, 1H), 8.67 (s,
1H), 8.00−7.98 (m, 2H), 7.92 (d, J = 8.0 Hz, 1H), 7.79 (s, 1H),
7.50−7.41 (m, 4H); 13C{1H} NMR (125 MHz, CDCl3) δ 168.7,
164.4, 150.6, 147.5, 134.6, 133.9, 129.6, 129.0, 127.4, 127.0, 124.1,
118.6; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C14H10N2NaS
261.0457; found 261.0452.
5-Hexyl-3-phenylisothiazole (3l). Petroleum ether/ethyl acetate
(30:1, v/v) as the eluent; white liquid (68.2 mg, 70% yield); 1H NMR
(400 MHz, CDCl3) δ 7.95−7.92 (m, 2H), 7.46−7.33 (m, 4H), 2.95
(t, J = 7.6 Hz, 2H), 1.79−1.71 (m, 2H), 1.45−1.31 (m, 6H), 0.91 (t, J
= 6.8 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 170.5, 167.9,
135.3, 129.1, 128.9, 127.0, 119.8, 31.6, 31.1, 28.9, 28.2, 22.6, 14.2;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H20NS 246.1311;
found 246.1310.
3-Phenyl-5-(p-tolyl)isothiazole (3b).17 Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; white solid (81.3 mg, 81% yield);
1
mp 68−70 °C; H NMR (400 MHz, CDCl3) δ 8.01−7.99 (m, 2H),
7.72 (s, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.50−7.40 (m, 3H), 7.28−7.26
(m, 2H), 2.41 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 168.6,
168.4, 134.0, 135.2, 130.1, 129.3, 128.9, 128.4, 127.0, 126.6, 117.3,
21.5.
5-(4-(tert-Butyl)phenyl)-3-phenylisothiazole (3c). Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; yellow solid (97.7 mg,
85% yield); mp 91−93 °C; 1H NMR (500 MHz, CDCl3) δ 8.01 (d, J
= 7.5 Hz, 2H), 7.74 (s, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.50−7.41 (m,
5H), 1.38 (s, 9H); 13C{1H} NMR (125 MHz, CDCl3) δ 168.5, 168.4,
153.2, 135.2, 129.3, 128.9, 128.4, 127.0, 126.5, 126.3 117.4, 35.0,
31.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C19H20NS
294.1311; found 294.1305.
5-([1,1′-Biphenyl]-4-yl)-3-phenylisothiazole (3m). Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; white solid (103.9 mg,
1
83% yield); mp 111−113 °C; H NMR (400 MHz, CDCl3) δ 8.03−
8.01 (m, 2H), 7.80 (s, 1H), 7.75−7.68 (m, 4H), 7.66−7.64 (m, 2H),
7.51−7.39 (m, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 168.5,
168.0, 142.6, 140.2, 135.1, 130.1, 129.4, 129.1, 129.0, 128.0, 127.17,
127.16, 127.1, 117.7; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C21H16NS 314.0998; found 314.1002.
5-(4-Methoxyphenyl)-3-phenylisothiazole (3d).17 Petroleum
ether/ethyl acetate (50:1, v/v) as the eluent; white solid (38.1 mg,
71% yield); mp 95−97 °C; 1H NMR (400 MHz, CDCl3) δ 8.00−7.98
(m, 2H), 7.66 (s, 1H), 7.61−7.58 (m, 2H), 7.49−7.40 (m, 3H),
6.99−6.96 (m, 2H), 3.86 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 168.4, 168.3, 160.9, 135.2, 129.3, 128.9, 128.1, 127.0, 123.9, 116.8,
114.8, 55.5.
5-Phenyl-3-(p-tolyl)isothiazole (3n).17 Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; white solid (41.6 mg, 83% yield);
1
mp 61−63 °C; H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8.0 Hz,
2H), 7.73 (s, 1H), 7.65 (d, J = 7.2 Hz, 2H), 7.49−7.42 (m, 3H),
7.29−7.26 (m, 2H), 2.41 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 168.5, 168.2, 139.4, 132.4, 131.3, 129.7, 129.6, 129.4, 126.9, 126.8,
117.6, 21.5.
5-(4-Fluorophenyl)-3-phenylisothiazole (3e). Petroleum ether/
ethyl acetate (30:1, v/v) as the eluent; yellow solid (44.0 mg, 75%
yield); mp 90−92 °C; 1H NMR (400 MHz, CDCl3) δ 8.00−7.97 (m,
H
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3-(4-Methoxyphenyl)-5-phenylisothiazole (3o).17 Petroleum
ether/ethyl acetate (30:1, v/v) as the eluent; white solid (68.9 mg,
65% yield); mp 113−115 °C; 1H NMR (400 MHz, CDCl3) δ 7.94 (d,
J = 8.8 Hz, 2H), 7.68−7.63 (m, 3H), 7.47−7.41 (m, 3H), 6.99 (d, J =
8.8 Hz, 2H), 3.86 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
168.1, 160.6, 131.2, 129.6, 129.3, 128.4, 128.1, 126.7, 117.3, 114.3,
55.4.
13C{1H} NMR (125 MHz, CDCl3) δ 168.3, 162.8, 139.2, 130.8,
129.8, 129.3, 127.8, 127.2, 126.7, 125.9, 117.1; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C13H10NS2 244.0249; found 244.0244.
3-Cyclohexyl-5-phenylisothiazole (3y). Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; yellow liquid (94.5 mg, 86%
1
yield); H NMR (400 MHz, CDCl3) δ 7.58−7.57 (m, 2H), 7.43−
7.36 (m, 3H), 7.23 (s, 1H), 2.87−2.81 (m, 1H), 2.08−2.05 (m, 2H),
1.87−1.73 (m, 3H), 1.60−1.51 (m, 2H), 1.46−1.24 (m, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 177.1, 167.1, 131.4, 129.3,
129.2, 126.6, 118.2, 42.7, 32.7, 26.4, 26.1; HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C15H18NS 244.1154; found 244.1163.
3-(4-Fluorophenyl)-5-phenylisothiazole (3p). Petroleum ether/
ethyl acetate (30:1, v/v) as the eluent; white solid (87.8 mg, 78%
yield); mp 80−82 °C; 1H NMR (400 MHz, CDCl3) δ 7.99−7.96 (m,
2H), 7.69−7.63 (m, 3H), 7.48−7.41 (m, 3H), 7.17−7.13 (m, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 168.7, 167.3, 163.5 (d, JC‑F
=
4-Bromo-3,5-diphenyl-1,2-selenazole (4). Petroleum ether/ethyl
247.5 Hz), 131.4, 131.0, 129.8, 129.4, 128.5, 126.7, 117.4, 115.9 (d,
JC‑F = 22.5 Hz); HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C15H10FNNaS 278.0410; found 278.0419.
acetate (50:1, v/v) as the eluent; white solid (213.6 mg, 89% yield);
1
mp 88−90 °C; H NMR (400 MHz, CDCl3) δ 7.74−7.73 (m, 2H),
7.64−7.63 (m, 2H), 7.49 (m, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ 171.4, 167.4, 137.7, 133.3, 129.9, 129.5, 129.3, 129.2, 129.1,
128.3, 106.9; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C15H11BrNSe 363.9232; found 363.9237.
3-(4-Chlorophenyl)-5-phenylisothiazole (3q). Petroleum ether/
ethyl acetate (30:1, v/v) as the eluent; white solid (83.7 mg, 74%
yield); mp 89−91 °C; 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.8
Hz, 2H), 7.69 (s, 1H), 7.64−7.62 (m, 2H), 7.48−7.40 (m, 5H);
13C{1H} NMR (125 MHz, CDCl3) δ 168.8, 167.1, 135.3, 133.4,
130.9, 129.8, 129.4, 129.1, 128.2, 126.7, 117.4; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C15H11ClNS 272.0295; found 272.0306.
3-(4-Bromophenyl)-5-phenylisothiazole (3r).6f Petroleum ether/
ethyl acetate (30:1, v/v) as the eluent; white solid (41.4 mg, 65%
yield); mp 123−125 °C; 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J =
8.4 Hz, 2H), 7.71 (s, 1H), 7.64 (d, J = 7.6 Hz, 2H), 7.60 (d, J = 8.0
Hz, 2H), 7.49−7.41 (m, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
168.9, 167.2, 133.9, 132.2, 131.0, 129.9, 129.4, 128.5, 126.8, 123.7,
117.5.
4-Bromo-3,5-diphenylisothiazole (5).10 Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; white solid (183.2 mg, 97%
1
yield); mp 110−112 °C; H NMR (400 MHz, CDCl3) δ 7.86−7.85
(m, 2H), 7.68−7.67 (m, 2H), 7.52−7.49 (m, 6H); 13C{1H} NMR
(125 MHz, CDCl3) δ 167.3, 163.2, 135.0, 130.4, 130.1, 129.6, 129.3,
129.2, 129.1, 128.5, 106.3.
4-Iodo-3,5-diphenyl-1,2-selenazole (6). Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; yellow solid (74.0 mg, 90%
1
yield); mp 125−127 °C; H NMR (400 MHz, CDCl3) δ 7.69 (m,
2H), 7.58−7.49 (m, 8H); 13C{1H} NMR (125 MHz, CDCl3) δ 174.1,
171.3, 138.7, 134.9, 129.7, 129.5, 129.3, 129.1, 128.9, 128.1, 81.2;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H11INSe 411.9096;
found 411.9086.
5-Phenyl-3-(4-(trifluoromethyl)phenyl)isothiazole (3s).17 Petrole-
um ether/ethyl acetate (50:1, v/v) as the eluent; white solid (86.2 mg,
71% yield); mp 78−80 °C; 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J
= 8.4 Hz, 2H), 7.77 (s, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.67−7.64 (m,
2H), 7.50−7.44 (m, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.2,
166.8, 138.1, 131.1 (q, JC‑F = 32.5 Hz), 130.9, 130.0, 129.5, 127.3,
126.8, 125.9, 124.2 (q, JC‑F = 271.3 Hz), 117.8.
3,5-Diphenyl-1,2-selenazole-4-D (D-2a). Petroleum ether/ethyl
acetate (50:1, v/v) as the eluent; white solid (74.6 mg, 62% yield);
1
mp 75−77 °C; H NMR (500 MHz, CDCl3) δ 7.99−7.97 (m, 2H),
7.62−7.60 (m, 2H), 7.49−7.41 (m, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ 173.6, 172.0, 137.1, 133.8, 129.7, 129.4, 129.3, 128.9, 127.3,
127.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H11DNSe
287.0193; found 287.0193.
5-Phenyl-3-(o-tolyl)isothiazole (3t).17 Petroleum ether/ethyl
acetate (15:1, v/v) as the eluent; yellow solid (81.2 mg, 81%
yield); mp 78−80 °C; 1H NMR (400 MHz, CDCl3) δ 7.67−7.65 (m,
2H), 7.60−7.58 (m, 1H), 7.53 (s, 1H), 7.47−7.33 (m, 6H), 2.54 (s,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.8, 167.4, 136.5, 135.4,
131.1, 129.64, 129.60, 129.4, 128.9, 126.8, 126.0, 120.9, 21.0.
5-Phenyl-3-(m-tolyl)isothiazole (3u).17 Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; white solid (95.1 mg, 82% yield);
3,5-Diphenylisothiazole-4-D (D-3a). Petroleum ether/ethyl ac-
etate (30:1, v/v) as the eluent; white solid (36.4 mg, 76% yield); mp
75−77 °C; 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.0 Hz, 2H),
7.66 (d, J = 8.0 Hz, 2H), 7.50−7.41 (m, 6H); 13C{1H} NMR (125
MHz, CDCl3) δ 168.50, 168.45, 135.1, 131.2, 129.8, 129.3, 129.1,
127.1, 126.8; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C15H11DNS 239.0748; found 239.0752.
1
mp 76−78 °C; H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.81−
7.78 (m, 2H), 7.69 (d, J = 7.6 Hz, 2H), 7.51−7.38 (m, 4H), 7.29 (s,
1H), 2.47 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 168.7, 168.3,
138.7, 135.0, 131.2, 130.2, 129.7, 129.4, 128.9, 127.7, 126.8, 124.2,
117.8, 21.6.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02286.
3-(3-Chlorophenyl)-5-phenylisothiazole (3v). Petroleum ether/
ethyl acetate (30:1, v/v) as the eluent; white solid (100.6 mg, 88%
1
yield); mp 75−77 °C; H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H),
1
1
7.87−7.84 (m, 1H), 7.70 (s, 1H), 7.64−7.62 (m, 2H), 7.48−7.38 (m,
5H); 13C{1H} NMR (125 MHz, CDCl3) δ 168.9, 166.8, 136.6, 135.0,
130.9, 130.2, 129.9, 129.4, 129.3, 127.1, 126.7, 125.1, 117.6; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C15H11ClNS 272.0295; found
272.0291.
Copies of H NMR spectra for reagents 1; copies of H
and 13C NMR spectra products 2a−2z, 3a−3y, 4−6, D-
2a, and D-3a; copies of 77Se NMR spectra for
compounds 2a, 2d, 2m, 2o, and 2p and X-ray data for
compound 2a; optimization of H2O equivalent for the
synthesis of isoselenazole and optimization of the
reaction conditions for the synthesis of isothiazole
(PDF)
3-(Naphthalen-2-yl)-5-phenylisothiazole (3w). Petroleum ether/
ethyl acetate (30:1, v/v) as the eluent; white solid (87.2 mg, 76%
yield); mp 110−112 °C; 1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H),
8.19−8.17 (m, 1H), 7.96−7.93 (m, 2H), 7.88−7.87 (m, 2H), 7.70−
7.68 (m, 2H), 7.56−7.42 (m, 5H); 13C{1H} NMR (125 MHz,
CDCl3) δ 168.44, 168.35, 133.8, 133.5, 132.4, 131.1, 129.7, 129.4,
128.71, 128.68, 127.9, 126.8, 126.7, 126.6, 126.4, 124.6, 117.9; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C19H14NS 288.0841; found
288.0850.
5-Phenyl-3-(thiophen-2-yl)isothiazole (3x). Petroleum ether/ethyl
acetate (30:1, v/v) as the eluent; yellow liquid (79.6 mg, 82% yield);
1H NMR (400 MHz, CDCl3) δ 7.64−7.62 (m, 3H), 7.54−7.52 (m,
1H), 7.48−7.42 (m, 3H), 7.39−7.37 (m, 1H), 7.12−7.10 (m, 1H);
Accession Codes
CCDC 2009081 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
I
https://dx.doi.org/10.1021/acs.joc.0c02286
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
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AUTHOR INFORMATION
Corresponding Authors
■
Xiao-Hong Zhang − College of Chemistry and Materials
Engineering, Wenzhou University, Wenzhou 325035, China;
orcid.org/0000-0003-3243-5941; Email: kamenzxh@
wzu.edu.cn
Xing-Guo Zhang − College of Chemistry and Materials
Engineering, Wenzhou University, Wenzhou 325035, China;
Guangxi Key Laboratory of Calcium Carbonate Resources
Comprehensive Utilization, Hezhou University, Hezhou
542899, China; orcid.org/0000-0002-4539-7166;
Email: zxg@wzu.edu.cn
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Authors
Zhu-Zhu Zhang − College of Chemistry and Materials
Engineering, Wenzhou University, Wenzhou 325035, China
Rong Chen − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou 325035, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02286
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the Natural Science Foundation of Guangxi Province
(No. 2018GXNSFDA281011) for financial support.
■
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