One-Pot Four-Component Assembling for Selenoureas

Article abstract of DOI:10.1021/acs.joc.0c02179

An efficient and practical method for the straightforward construction of unsymmetrical selenoureas and cycloselenoureas via the combination of selenium powder, chloroform, and two different amines was comprehensively achieved in one-pot with only the assistance of a base under mild conditions. Thirty-three new structures of unsymmetrical selenoureas including three chiral examples and eight cycloselenoureas were achieved. 1,1-Dimethyl-3-phenylselenourea II, which shows good fungicidal activity, was practically synthesized through this protocol in gram-scale. Isoselenocyanate was further confirmed as a key intermediate by control experiment.

Full text of DOI:10.1021/acs.joc.0c02179

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One-Pot Four-Component Assembling for Selenoureas
Lai Li, Jiaqi Wu, Linsha Wei, Jianmei Lu,* and Xuefeng Jiang*
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ABSTRACT: An efficient and practical method for the straightforward construction of unsymmetrical selenoureas and
cycloselenoureas via the combination of selenium powder, chloroform, and two different amines was comprehensively achieved
in one-pot with only the assistance of a base under mild conditions. Thirty-three new structures of unsymmetrical selenoureas
including three chiral examples and eight cycloselenoureas were achieved. 1,1-Dimethyl-3-phenylselenourea II, which shows good
fungicidal activity, was practically synthesized through this protocol in gram-scale. Isoselenocyanate was further confirmed as a key
intermediate by control experiment.
INTRODUCTION
■
Selenoureas are a prevalent motif in the fields of bioorganic
and pharmaceutical chemistry.1,2 Recent studies demonstrated
that selenoureas were excellent antioxidant agents in vitro
showing relevant activities in the scavenging of free radicals
and peroxides such as phenolic selenourea I.1c 1,1-Dimethyl-3-
phenylselenourea II shows fungicidal activity against most
fungi.1d Meanwhile, piperidine-1-carboselenoamide III exhibits
inhibitory effects on tyrosinase activity.1f Selenoureas IV and V
possess jack bean urease inhibition.1g Furthermore, selenoureas
can be used as ligands for biologically active metal complexes3
such as complex VI displaying superior antitumor effect
(Figure 1).3b In addition, they are widely applied for the
Figure 1. Representative selenoureas.
synthesis of selenium-containing heterocycles4 such as
selenazole4a and selenazine,4d essential for drug discovery.
in the presence of a base.11 Although sulfur and selenium are in
The general synthesis of selenoureas is the reaction of
the same group in the periodic table, selenourea has never been
isoselenocyanates with amines.5 However, the formation of
achieved by this method. Compared to nonmetallic element
isoselenocyanates needs the utility of highly toxic and
sulfur, selenium is a semimetallic element. Due to its lower
electronegativity (Se: 2.55 vs S: 2.58),12 larger atomic radius
environmentally unfriendly triphosgene or potassium seleno-
(Se: 1.17 Å vs S: 1.02 Å),13 and higher polarizability (Se: 3.8 Å
cyanate (Scheme 1, route 1). Other methods scarcely avoid the
employment of unstable LiAlHSeH,6 toxic and smelly
vs S: 2.9 Å),14 the bond dissociation enthalpies of CSe is
isocyanide,7 high tempertature,8 and so on.9 Therefore,
development of an efficient and environmentally benign
approach for the synthesis of selenoureas is of great
Received: September 9, 2020
significance. With our continuing effort on the organosulfur
chemistry with ecofriendly concept,10 we have developed an
efficient and practical methodology for the synthesis of
thiocarbamides and oxazolidinethiones under mild conditions
by the combination of sulfur powder, chloroform, and amines
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Scheme 1. Synthesis of Selenoureas and Differences
Table 1. Optimization for the Reaction Conditions
between S and Se
a
b
entry
base
tBuOK
solvent
yield (%)
1
tBuOH/1,4-dioxane
tBuOH/1,4-dioxane
tBuOH/1,4-dioxane
tBuOH/1,4-dioxane
tBuOH/1,4-dioxane
tBuOH/1,4-dioxane
tBuOH/1,4-dioxane
EtOH/1,4-dioxane
nPrOH/1,4-dioxane
nBuOH/1,4-dioxane
iPrOH/1,4-dioxane
tBuOH/THF
63
33
NR
25
NR
35
16
42
48
47
61
51
33
39
61
32
74
2
KOH
3
K2CO3
NaOH
LiOH· H2O
tBuONa
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
4
5
6
7
8
9
10
11
12
13
14
1,4-dioxane
tBuOH
tBuOH/1,4-dioxane
tBuOH/1,4-dioxane
tBuOH/1,4-dioxane
c
15
d
16
e
17
a
Otherwise specified, all reactions were first carried out under N2
using 1a (1.2 mmol), CHCl3 (6.0 mmol), and a base (3.6 mmol) in
the mixture solvent (1.2/1.2 mL) or single solvent (2.4 mL) at 50 °C
for 3 h, and then 2a (0.6 mmol), Se (1.8 mmol), and the same base
(1.2 mmol) were added, and the mixture was further stirred under N2
about 20 kcal/mol lower than that of CS (Scheme 1, route
2).15 Therefore, selenoureas are less stable and more difficult
to synthesize than thiocarbamides. Moreover, in comparison to
other selenium sources, selenium powder is hypotoxic and
readily available, which makes it an ideal source to construct
selenoureas. Herein, we report an efficient method for the
synthesis of selenoureas by one-pot, four-component reactions
using selenium powder, chloroform, and amines under mild
conditions.
b
c
d
at 50 °C for 8 h. Isolated yields. Se (2.4 mmol). Se (1.2 mmol).
e
The second step was performed for 5 h.
presence of other solvents such as the combination of ethanol/
1,4-dioxane, propanol/1,4-dioxane, butanol/1,4-dioxane, and
tert-butyl alcohol/tetrahydrofuran, moderate yields were
afforded (Table 1, entries 8−10 and 12). Somewhat lower
yields were obtained when the combination of methanol/1,4-
dioxane or single 1,4-dioxane and tert-butyl alcohol were
applied (Table 1, entries 7, 13, and 14). Elevating the amount
of selenium powder to 4.0 equiv almost did not affect the
reaction (Table 1, entries 1 vs 15), while when that of selenium
powder decreased to 2.0 equiv, the yield dramatically declined
to 32% (Table 1, entries 1 vs 16). Further studies showed that
properly reducing the reaction time of the second step is
beneficial to the reaction to some extent, and the best yield was
achieved when the reaction time was reduced to 5 h (Table 1,
entry 17). Finally, it was found that both steps carried out at 50
°C were required to achieve satisfactory results. Either the one
step was carried out at 50 °C and another at room
temperature, or both steps were performed at room temper-
ature, the yields dramatically decreased to 28−44%.
Once the optimal conditions were established, the synthesis
of selenoureas by this methodology using morpholine as one of
the reaction partners was examined. As shown in Table 2, all
reactions took place smoothly to furnish the desired
selenoureas 3 in moderate to good yields. Substituents on
the phenyl rings of anilines 1 have some effect on the reactions.
For example, the best yield was achieved when the methoxy
group was attached on the ortho-position (3e), followed by the
RESULTS AND DISCUSSION
■
At the outset of this investigation, the reactions were first
carried out using aniline 1a, chloroform, potassium tert-
butoxide in the mixture solvent of tert-butyl alcohol/1,4-
dioxane at 50 °C for 3 h, and then the extra potassium tert-
butoxide, selenium powder and morpholine 2a were added and
the mixture was further stirred at 50 °C for 8 h, selenourea 3a
was obtained in 63% yield (Table 1, entry 1). The structure of
3a was further confirmed through X-ray crystallographic
analysis.16 Inferior results were obtained when other bases
such as potassium hydroxide, sodium hydroxide, and sodium
tert-butoxide were used (Table 1, entries 2, 4, and 6). In
addition, no desired product can be detected when weak bases
such as potassium carbonate and lithium hydroxide were added
(Table 1, entries 3 and 5). When no extra potassium tert-
butoxide was added in the second step, the yield drastically
decreased from 63 to 39%, which indicated that the addition of
extra potassium tert-butoxide in the second step was beneficial.
Using potassium tert-butoxide as the base, a variety of solvents
were then tested (Table 1, entries 7−14). It was found that
solvents affected the reactions significantly. For instance, a
similar good yield was observed when the combination of
isopropanol/1,4-dioxane was used (Table 1, entry 11). In the
B
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Table 2. Synthesis of Selenoureas Using Various Aminesa
the limitation and scope of the methodology. Through the
reactions using various amines 1 and 2, the desired selenoureas
3 were also obtained in moderate-to-good yields in all cases.
The substrates examined showed that substituents on both
amines affected the reactions to some extent. For instance,
aniline 1 possessing an electron-rich group on the phenyl ring
gave inferior yield than that possessing electron-neutral one
(3s and 3t). In some cases, anilines 1 bearing both electron-
rich and -neutral groups on the phenyl rings gave similar
results (3o and 3v), while that having electron-poor group
gave the best yield (3ab). For the reactions of tryptamines,
sometimes, similar good yields can be achieved when an
electron-rich or -neutral group was attached on the phenyl ring
(3v and 3w), while in other cases, inferior yields were found
for the one having electron-rich group on the phenyl ring (3o
and 3p), or the opposite results were given (3y and 3z),
according to the other counterparts involved. When (S)-1-
phenylethan-1-amine was used as one of the reaction partners,
chiral selenoureas 3ad−3af were achieved, which may be
potential organocatalysts in asymmetric synthesis. All reactions
performed well to give the corresponding products in good
yields, with the ee values retained under such reaction
conditions (see the Supporting Information for the details).
The synthesis of cycloselenoureas 3 by the intramolecular
reaction was also performed. As shown in Table 3, the
corresponding five- and six-membered cycloselenoureas 3ag−
3an were obtained in moderate yields.
Table 3. Synthesis of Cycloselenoureas by Intramolecular
Reactiona
a
Under N2, all reactions were carried out using 1 (0.9 mmol), Se (2.7
a
t
i
Under N2, all reactions were carried out using 1 (1.2 mmol), CHCl3
mmol), and BuOK (4.05 mmol) in PrOH/1,4-dioxane (1.5/1.5
t
t
(6 mmol), and BuOK (3.6 mmol) in BuOH/1,4-dioxane (1.2/1.2
mL) at 50 °C for 3 h; then 2 (0.6 mmol), Se (1.8 mmol), and tBuOK
(1.2 mmol) were added, and the mixture was further stirred at 50 °C
for 5 h. Isolated yields.
mL); then CHCl3 (9 mmol) was added dropwise at 0 °C, and the
b
mixture was heated to 50 °C for 16 h. Isolated yields. 2-
Ethoxyethanol/1,4-dioxane (1.5/1.5 mL) was used as the solvent.
meta-substituted one (3d), and the lowest yield was observed
when the methoxy group was attached on the para-position
(3c). Sterically hindered substituents on the phenyl rings of
anilines also affected the reactions to some extent. For
instance, the best yield was given when 2,4-dimethylaniline
was used as the substrate (3j). Only 48% yield of the desired
product 3l was afforded when 2,6-di-isopropylaniline was used.
Compared to anilines, alkyl amine, such as 2-phenylethan-1-
amine, gave the desired product 3m in a somewhat lower yield.
Encouraged by the above results, a range of amines were
then subjected to the optimal conditions to further examine
As can be seen from Tables 1−3, comparted to their sulfur
analogues,11 relatively lower yields were observed for the
formation of selenoureas, implying the difficulty for the
synthesis of such compounds by this methodology. It should
be also noted here that the selenoureas are labile to decompose
in the reaction system, and they should be isolated by flash
column chromatography as soon as possible once the reaction
was completed.
Finally, 1,1-dimethyl-3-phenylselenourea II, which has good
fungicidal activity against most fungi, was efficiently synthe-
sized in an excellent yield of 82% (1.87 g) with aniline and a
C
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4.05 mmol, 4.5 equiv), Se (213.2 mg, 2.7 mmol, 3.0 equiv), and
iPrOH (or 2-ethoxyethanol)/1,4-dixoane (1.5/1.5 mL) were added
33% aqueous solution of dimethylamine as the starting
materials (Scheme 2).
into a Schlenk reaction tube at room temperature. Then, under 0 °C,
CHCl3 (0.72 mL, 9 mmol, 10.0 equiv) was added dropwise. The
mixture was stirred at 50 °C in a heating mantle for 16 h. After it was
cooled to room temperature, saturated aq. NH4Cl was added and the
mixture was extracted with ethyl acetate. The organic layer was dried
over anhydrous Na2SO4, and the solvent was removed under reduced
pressure. The residue was purified by column chromatography on
silica gel to give the pure products 3ag−3an.
Scheme 2. Gram-Scale Synthesis of 1,1-Dimethyl-3-phenyl
Selenourea II
General Procedure for the Synthesis of Phenyl Isoseleno-
cyanate. Under a N2 atmosphere, aniline 1a (109.5 μL, 1.2 mmol),
tBuOK (403.2 mg, 3.6 mmol, 3.0 equiv), CHCl3 (0.48 mL, 6 mmol,
To better understand this reaction process, aniline 1a,
chloroform, and potassium tert-butoxide were first stirred in
tert-butyl alcohol/1,4-dioxane at 50 °C for 3 h; then Se and
potassium tert-butoxide were added. Finally, phenylisoseleno-
cyanate 4, which is important material for selenoureas, was
obtained in 32% yield, demonstrating that isoselenocyanate
could be formed in the reaction (Scheme 3).
t
5.0 equiv), and BuOH/1,4-dixoane (1.2/1.2 mL) were added into a
Schlenk reaction tube. The mixture was stirred at 50 °C in a heating
mantle for 3 h. Then, also under a N2 atmosphere, Se (142.1 mg, 1.8
t
mmol, 1.5 equiv) and BuOK (134.4 mg, 1.2 mmol) were added to
the reaction mixture and it was stirred at the same temperature for
another 5 h. After it was cooled to room temperature, saturated aq.
NH4Cl was added and the mixture was extracted with ethyl acetate.
The organic layer was dried over anhydrous Na2SO4, and the solvent
was removed under reduced pressure. The residue was purified by
column chromatography on silica gel to give the pure products 4.
Compound 3a.17 Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (119.5 mg,
Scheme 3. Control Experiment
1
74%). mp 150.5 °C (decomposed). H NMR (500 MHz, CDCl3,
TMS) δ 7.35 (t, J = 7.5 Hz, 2H), 7.26 (s, 1H), 7.18 (d, J = 7.5 Hz,
1H), 7.14 (t, J = 7.5 Hz, 2H), 3.82 (t, J = 5.0 Hz, 4H), 3.73 (t, J = 5.0
Hz, 4H). 13C{1H} NMR (125 MHz, CDCl3) δ 184.0, 140.0, 129.4,
125.7, 122.8, 66.0, 52.1. IR (neat) 3386, 3041, 2852, 2226, 1738,
1525, 1330, 1221, 1109, 1023, 860, 751 cm−1. MS (ESI) 293 [M +
Na+]. HRMS (ESI) calcd for C11H14N2NaOSe [M + Na+] 293.0164;
found 293.0166.
CONCLUSIONS
■
In conclusion, an efficient and practical methodology for the
synthesis of selenoureas has been developed via a one-pot,
four-component reaction. By the combination of various
amines 1 and 2, a series of selenoureas were achieved in
moderate-to-good yields under a mild condition. In addition,
chiral selenoureas can also be achieved with the ee values kept
untouched through this method, which will thus display their
potential application in asymmetric catalysis. Further studies
on the application of such selenoureas are underway in this
laboratory.
Compound 3b. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as white solid (103.7 mg, 61%).
1
mp 163.1−163.4 °C. H NMR (500 MHz, CDCl3, TMS) δ 7.75 (s,
1H), 7.14 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 3.84 (s, 4H),
3.72 (t, J = 4.0 Hz, 4H), 2.33 (s, 3H). 13C{1H} NMR (125 MHz,
CDCl3) δ 183.9, 137.5, 135.8, 130.0, 123.3, 66.0, 51.9, 20.9. IR (neat)
3195, 3026, 2914, 2857, 1883, 1590, 1526, 1418, 1325, 1214, 1118,
1026, 940, 863, 806, 704 cm−1. MS (ESI) 285 [M + H+]. HRMS
(ESI) calcd for C12H17N2OSe [M + H+] 285.0501; found 285.0501.
Compound 3c. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (113.1 mg,
EXPERIMENTAL SECTION
■
1
63%). mp 221.3−221.8 °C. H NMR (400 MHz, CDCl3, TMS) δ
General Remarks. Melting points are uncorrected. NMR spectra
were recorded at 500 or 400 MHz (for 1H NMR) and 125 MHz (for
13C NMR), respectively. 1H and 13C NMR spectra recorded in CDCl3
or DMSO-d6 solutions were referenced to TMS (0.00 ppm) and the
residual solvent peak (77.0 ppm) or (39.5 ppm), respectively. J-values
are in Hz. Organic solvents used were dried by standard methods.
The mass analyzer type for the high-resolution mass spectra is Q-
TOF. Other commercially obtained reagents were used without
further purification. Flash column chromatography was performed on
silica gel.
7.69 (s, 1H), 7.07 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 3.86
(t, J = 4.4 Hz, 4H), 3.80 (s, 3H), 3.72 (t, J = 4.4 Hz, 4H). 13C{1H}
NMR (125 MHz, CDCl3) δ 184.0, 157.8, 133.1, 125.7, 114.5, 66.0,
55.4, 51.5. IR (neat) 3373, 3155, 3012, 2845, 1876, 1535, 1429, 1332,
1249, 1113, 1029, 936, 826 cm−1. MS (ESI) 301 [M + H+]. HRMS
(ESI) calcd for C12H17N2O2Se [M + H+] 301.0450; found 301.0443.
Compound 3d. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (127.5 mg,
1
71%). mp 146.2 °C (decomposed). H NMR (500 MHz, CDCl3,
TMS) δ 7.86 (s, 1H), 7.24 (t, J = 8.0 Hz, 1H), 6.72 (d, J = 8.0 Hz,
1H), 6.64 (d, J = 8.0 Hz, 1H), 6.62 (s, 1H), 3.83 (s, 4H), 3.79 (s,
3H), 3.71 (t, J = 4.5 Hz, 4H). 13C{1H} NMR (125 MHz, CDCl3) δ
183.9, 160.4, 141.0, 130.2, 114.7, 110.9, 108.5, 66.0, 55.4, 52.3. IR
(neat) 3223, 3052, 2932, 2828, 1586, 1533, 1467, 1412, 1309, 1219,
1112, 1024, 960, 859, 692 cm−1. MS (ESI) 301 [M + H+]. HRMS
(ESI) calcd for C12H17N2O2Se [M + H+] 301.0450; found 301.0441.
Compound 3e. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (140.0 mg,
General Procedure for the Synthesis of Selenoureas. Under
a N2 atmosphere, amine 1 (1.2 mmol, 2.0 equiv), BuOK (403.2 mg,
t
3.6 mmol, 6.0 equiv), CHCl3 (0.48 mL, 6 mmol, 10 equiv), and
tBuOH/1,4-dixoane (1.2/1.2 mL) were added into a Schlenk reaction
tube. The mixture was stirred at 50 °C in a heating mantle for 3 h.
Then, also under a N2 atmosphere, Se (142.1 mg, 1.8 mmol, 3.0
t
equiv), BuOK (134.4 mg, 1.2 mmol, 2.0 equiv), and amine 2 (0.6
mmol) were added to the reaction mixture and stirred at the same
temperature for 5 h. After the reaction was finished, saturated aq.
NH4Cl was added and the mixture was extracted with ethyl acetate.
The organic layer was dried over anhydrous Na2SO4, and the solvent
was removed under reduced pressure. The residue was purified by
column chromatography on silica gel to give the pure products 3a-3af.
General Procedure for the Synthesis of Cycloselenoureas.
1
78%). mp 219.9 °C (decomposed). H NMR (500 MHz, CDCl3,
TMS) δ 7.66 (s, 1H), 7.46 (dd, J = 10.0, 1.5 Hz, 1H), 7.13 (td, J =
10.0, 1.5 Hz, 1H), 6.97−6.90 (m, 2H), 3.90 (t, J = 6.0 Hz, 4H), 3.86
(s, 3H), 3.76 (t, J = 6.0 Hz, 4H). 13C{1H} NMR (125 MHz, CDCl3)
δ 183.3, 150.0, 128.7, 125.7, 122.7, 120.5, 111.0, 66.1, 55.7, 51.6. IR
(neat) 3244, 3149, 2918, 2853, 1602, 1526, 1453, 1334, 1322, 1223,
t
Under a N2 atmosphere, diamine 1 (0.9 mmol), BuOK (453.6 mg,
D
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1110, 1024, 937, 851, 749 cm−1. MS (ESI) 301 [M + H+]. HRMS
(ESI) calcd for C12H17N2O2Se [M + H+] 301.0450; found 301.0460.
Compound 3f. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as white solid (138.5 mg, 76%).
1120, 1027, 940, 805 cm−1. MS (ESI) 355 [M + H+]. HRMS (ESI)
calcd for C17H27N2OSe [M + H+] 355.1284; found 355.1291.
Compound 3m. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as white solid (82.1 mg, 46%).
1
1
mp 148.0 °C (decomposed). H NMR (400 MHz, CDCl3, TMS) δ
mp 112.1 °C (decomposed). H NMR (400 MHz, CDCl3, TMS) δ
7.80 (s, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 3.87
(t, J = 4.8 Hz, 4H), 3.74 (t, J = 4.8 Hz, 4H). 13C{1H} NMR (125
MHz, CDCl3) δ 184.0, 138.5, 131.3, 129.4, 124.8, 66.0, 51.7. IR
(neat) 3183, 2854, 1880, 1593, 1528, 1491, 1421, 1318, 1209, 1114,
1025, 860, 817 cm−1. MS (ESI) 305 [M + H+]. HRMS (ESI) calcd for
C11H14ClN2OSe [M + H+] 304.9952; found 304.9950.
7.33 (t, J = 7.2 Hz, 2H), 7.25−7.22 (m, 3H), 5.68 (br, 1H), 4.07 (dd,
J = 12.0, 6.8 Hz, 2H), 3.77 (dd, J = 9.2, 4.0 Hz, 4H), 3.70 (dd, J = 8.4,
4.0 Hz, 4H), 3.00 (t, J = 6.8 Hz, 2H). 13C{1H} NMR (125 MHz,
CDCl3) δ 182.3, 138.5, 128.78, 128.75, 126.8, 66.0, 49.4, 49.0, 35.1.
IR (neat) 3328, 1553, 1455, 1334, 1236, 1118, 996, 877, 753 cm−1.
MS (ESI) 321 [M + Na+]. HRMS (ESI) calcd for C13H18N2NaOSe
[M + Na+] 321.0477; found 321.0472.
Compound 3g. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as white solid (110.3 mg, 64%).
Compound 3n. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as brownish solid (130.1 mg,
1
mp 170.9 °C (decomposed). H NMR (400 MHz, CDCl3, TMS) δ
1
7.67 (s, 1H), 7.13 (dd, J = 8.8, 4.8 Hz, 2H), 7.05 (t, J = 8.8 Hz, 2H),
3.89 (t, J = 4.0 Hz, 4H), 3.74 (t, J = 4.8 Hz, 4H). 13C{1H} NMR (125
MHz, CDCl3) δ 184.2, 160.6 (d, JC−F = 245.0 Hz), 136.1, 126.0 (d,
71%). mp 223.5 °C (decomposed). H NMR (500 MHz, CDCl3,
TMS) δ 8.17 (br, 1H), 7.40−7.28 (m, 7H), 6.94 (d, J = 7.5 Hz, 2H),
3.82 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6) δ 178.7, 157.0,
139.7, 132.4, 128.43, 128.38, 126.7, 125.0, 124.7, 124.6, 123.8, 115.0,
113.7. IR (neat) 3171, 3009, 1557, 1506, 1451, 1338, 1249, 1182,
1103, 1036, 932, 842, 753 cm−1. MS (ESI) 329 [M + Na+]. HRMS
(ESI) calcd for C14H14N2NaOSe [M + Na+] 329.0164; found
329.0171.
J
C−F = 8.75 Hz), 116.1 (d, JC−F = 22.5 Hz), 66.0, 51.4. IR (neat) 3076,
3025, 2909, 1881, 1641, 1552, 1470, 1362, 1199, 1112, 902, 834, 771
cm−1. MS (ESI) 289 [M + H+]. HRMS (ESI) calcd for
C11H14FN2OSe [M + H+] 289.0250; found 289.0248.
Compound 3h. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as white solid (94.8 mg, 55%).
Compound 3o. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as orange solid (154.0 mg,
75%). mp 221.9 °C (decomposed). 1H NMR (500 MHz, DMSO-d6)
δ 10.85 (s, 1H), 9.94 (s, 1H), 8.09 (s, 1H), 7.70 (d, J = 7.0 Hz, 1H),
7.36−7.31 (m, 3H), 7.23−7.17 (m, 4H), 7.07 (t, J = 7.0 Hz, 1H),
6.99 (t, J = 7.0 Hz, 1H), 3.84 (s, 2H), 3.00 (s, 2H). 13C{1H} NMR
(125 MHz, DMSO-d6) δ 178.2, 138.4, 136.2, 129.0, 127.2, 125.0,
123.9, 122.7, 120.9, 118.6, 118.2, 111.4, 111.3, 47.5, 24.6. IR (neat)
3393, 3337, 3145, 1711, 1539, 1455, 1293, 1233, 1158, 1074, 946,
831 cm−1. MS (ESI) 366 [M + Na+]. HRMS (ESI) calcd for
C17H17N3NaSe [M + Na+] 366.0480; found 366.0483.
1
mp 143.1 °C (decomposed). H NMR (500 MHz, CDCl3, TMS) δ
7.85 (s, 1H), 7.30 (dd, J = 15.0, 8.0 Hz, 1H), 6.90−6.81 (m, 3H),
3.86 (s, 4H), 3.74 (t, J = 5.0 Hz, 4H). 13C{1H} NMR (125 MHz,
CDCl3) δ 184.1, 163.1 (d, JC−F = 245.0 Hz), 141.3 (d, JC−F = 10.0
Hz), 130.6 (d, JC−F = 8.75 Hz), 118.1 (d, JC−F = 2.5 Hz), 112.4 (d,
JC−F = 21.25 Hz), 110.9 (d, JC−F = 23.75 Hz), 66.0, 52.2. IR (neat)
3404, 3147, 3005, 2951, 2840, 1613, 1465, 1433, 1361, 1150, 1067,
1021, 919, 784 cm−1. MS (ESI) 289 [M + H+]. HRMS (ESI) calcd for
C11H14FN2OSe [M + H+] 289.0250; found 289.0259.
Compound 3i. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (153.3 mg,
Compound 3p. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (149.7 mg,
1
74%). mp 297.4 °C (decomposed). H NMR (400 MHz, CDCl3,
1
TMS) δ 7.91 (s, 1H), 7.57−7.55 (m, 4H), 7.44 (t, J = 7.2 Hz, 2H),
7.35 (t, J = 7.2 Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 3.88 (t, J = 4.8 Hz,
4H), 3.74 (t, J = 4.8 Hz, 4H). 13C{1H} NMR (125 MHz, CDCl3) δ
183.8, 139.9, 139.1, 138.5, 128.8, 127.9, 127.4, 126.8, 123.1, 66.0,
52.0. IR (neat) 3284, 3051, 2939, 1573, 1509, 1404, 1344, 1253,
1183, 1102, 1006, 850 cm−1. MS (ESI) 347 [M + H+]. HRMS (ESI)
calcd for C17H19N2OSe [M + H+] 347.0658; found 347.0657.
Compound 3j. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (151.6 mg,
67%). mp 231.3−233.1 °C. H NMR (400 MHz, CDCl3, TMS) δ
8.18 (s, 1H), 7.97 (s, 1H), 7.26−7.20 (m, 4H), 7.07 (d, J = 2.0 Hz,
1H), 6.89−6.87 (m, 4H), 6.35 (s, 1H), 4.02 (dd, J = 12.0, 6.4 Hz,
2H), 3.84 (s, 3H), 3.06 (t, J = 6.4 Hz, 2H). 13C{1H} NMR (125
MHz, CDCl3) δ 178.6, 154.3, 135.4, 131.4, 130.1, 127.6, 127.5, 125.0,
122.8, 112.8, 112.0, 111.9, 100.5, 55.9, 48.3, 24.4. IR (neat) 3442,
1539, 1486, 1448, 1353, 1263, 1170, 1095, 1026, 926, 841, 795 cm−1.
MS (ESI) 396 [M + Na+]. HRMS (ESI) calcd for C18H19N3NaOSe
[M + Na+] 396.0586; found 396.0582.
1
85%). mp 156.3 °C (decomposed). H NMR (400 MHz, CDCl3,
Compound 3q. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (97.9 mg, 58%).
TMS) δ 7.40 (s, 1H), 7.04 (s, 1H), 7.00 (d, J = 8.4 Hz, 1H), 6.95 (d, J
= 8.4 Hz, 1H), 3.81 (t, J = 4.4 Hz, 4H), 3.71 (t, J = 4.4 Hz, 4H), 2.30
(s, 3H), 2.22 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 184.2,
136.7, 136.3, 132.4, 131.8, 127.6, 125.2, 66.0, 51.6, 20.9, 18.0. IR
(neat) 3202, 2962, 2924, 2852, 1730, 1675, 1525, 1460, 1378, 1321,
1205, 1115, 1025, 856, 807 cm−1. MS (ESI) 299 [M + H+]. HRMS
(ESI) calcd for C13H19N2OSe [M + H+] 299.0657; found 299.0659.
Compound 3k. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (125.8 mg,
1
mp 146.5 °C (decomposed). H NMR (500 MHz, CDCl3, TMS) δ
8.30 (s, 1H), 7.45 (t, J = 7.0 Hz, 2H), 7.33 (t, J = 7.0 Hz, 1H), 7.20
(d, J = 7.0 Hz, 2H), 6.14 (br, 1H), 4.35 (br, 1H), 2.10−2.08 (m, 2H),
1.67−1.60 (m, 3H), 1.44−1.37 (m, 2H), 1.15−1.13 (m, 3H).
13C{1H} NMR (125 MHz, CDCl3) δ 176.9, 135.7, 130.4, 127.6,
125.1, 56.8, 32.5, 25.3, 24.6. IR (neat) 3082, 2827, 2646, 2131, 1937,
1867, 1788, 1652, 1516, 1402, 1264, 1097, 982, 906, 823 cm−1. MS
(ESI) 305 [M + Na+]. HRMS (ESI) calcd for C13H18N2NaSe [M +
Na+] 305.0528; found 305.0537.
1
66%). mp 140.0 °C (decomposed). H NMR (500 MHz, CDCl3,
TMS) δ 7.42 (s, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.24 (s, 1H), 7.08 (d, J
= 8.0 Hz, 1H), 3.91 (s, 4H), 3.76 (t, J = 5.0 Hz, 4H), 2.33 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3) δ 183.9, 137.4, 134.3, 130.2,
128.1, 127.4, 126.1, 66.0, 51.3, 20.8. IR (neat) 3120, 2915, 2857,
1525, 1421, 1319, 1220, 1117, 1028, 937, 811 cm−1. MS (ESI) 319
[M + H+]. HRMS (ESI) calcd for C12H16ClN2OSe [M + H+]
319.0108; found 319.0099.
Compound 3l. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as white solid (101.8 mg, 48%).
mp 197.9 °C (decomposed). 1H NMR (500 MHz, DMSO-d6) δ 9.14
(s, 1H), 7.25 (t, J = 7.5 Hz, 1H), 7.13 (d, J = 7.5 Hz, 2H), 4.05 (s,
4H), 3.66 (s, 4H), 2.97 (hept, J = 6.5 Hz, 2H), 1.21 (d, J = 6.5 Hz,
6H), 1.12 (d, J = 6.5 Hz, 6H). 13C{1H} NMR (125 MHz, DMSO-d6)
δ 182.4, 146.0, 136.4, 127.4, 122.9, 65.9, 50.1, 28.0, 23.9, 23.1. IR
(neat) 3227, 2955, 2864, 1955, 1741, 1591, 1525, 1392, 1323, 1214,
Compound 3r. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (146.4 mg,
75%). mp 212.4 °C (decomposed). 1H NMR (500 MHz, DMSO-d6)
δ 9.81 (s, 1H), 8.05 (s, 1H), 7.35 (t, J = 7.5 Hz, 2H), 7.29 (d, J = 7.5
Hz, 2H), 7.17 (t, J = 7.5 Hz, 1H), 3.54−3.53 (m, 2H), 1.56−1.54 (m,
2H), 1.27 (s, 12H), 0.86 (t, J = 6.0 Hz, 3H). 13C{1H} NMR (125
MHz, DMSO-d6) δ 178.5, 138.6, 129.4, 128.8, 128.5, 124.9, 123.8,
46.7, 31.2, 28.8, 28.5, 26.2, 22.0, 13.8. IR (neat) 3209, 3048, 2923,
2855, 2139, 1630, 1583, 1493, 1312, 1235, 1069, 861 cm−1. MS (ESI)
349 [M + Na+]. HRMS (ESI) calcd for C16H26N2NaSe [M + Na+]
349.1154; found 349.1153.
Compound 3s. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (125.6 mg,
1
75%). mp 108.5−109.4 °C. H NMR (500 MHz, CDCl3, TMS) δ
8.59 (br, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.34−7.31 (m, 2H), 7.22 (d, J
E
https://dx.doi.org/10.1021/acs.joc.0c02179
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
= 7.5 Hz, 2H), 6.54 (br, 1H), 6.32 (s, 2H), 4.93 (d, J = 3.5 Hz, 2H).
13C{1H} NMR (125 MHz, CDCl3) δ 179.2, 149.7, 142.5, 135.6,
130.4, 127.8, 125.1, 110.5, 108.4, 100.0, 45.2. IR (neat) 3425, 3347,
3280, 3022, 2811, 1960, 1707, 1581, 1413, 1282, 1136, 1058, 938,
756 cm−1. MS (ESI) 303 [M + Na+]. HRMS (ESI) calcd for
C12H12N2NaOSe [M + Na+] 303.0007; found 303.0012.
119.6, 118.6, 112.3, 111.1, 48.2, 24.5, 21.0, 17.4. IR (neat) 3344,
3167, 1543, 1505, 1337, 1223, 1176, 1087, 933, 743 cm−1. MS (ESI)
394 [M + Na+]. HRMS (ESI) calcd for C19H21N3NaSe [M + Na+]
394.0794; found 394.0781.
Compound 3z. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (165.8 mg,
1
69%). mp 247.5 °C (decomposed). H NMR (500 MHz, CDCl3,
Compound 3t. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as pink solid (118.7 mg, 64%).
TMS) δ 7.94 (s, 1H), 7.74 (s, 1H), 7.23 (d, J = 8.5 Hz, 1H), 7.03 (s,
1H), 6.95 (s, 1H), 6.86−6.84 (m, 3H), 6.76 (d, J = 7.5 Hz, 1H), 5.92
(s, 1H), 3.97 (q, J = 6.5 Hz, 2H), 3.83 (s, 3H), 3.01 (t, J = 6.5 Hz,
2H), 2.28 (s, 3H), 2.03 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ
178.8, 154.1, 138.7, 135.2, 132.2, 131.3, 131.1, 128.0, 127.6, 126.9,
122.6, 112.7, 112.0, 11.8, 100.2, 55.8, 48.2, 24.5, 21.0, 17.4. IR (neat)
3362, 3221, 3134, 1732, 1560, 1479, 1405, 1256, 1201, 1160, 1012,
868, 809 cm−1. MS (ESI) 402 [M + H+]. HRMS (ESI) calcd for
C20H24N3OSe [M + H+] 402.1080; found 402.1086.
1
mp 126.1−128.1 °C. H NMR (500 MHz, CDCl3, TMS) δ 8.34 (s,
1H), 7.33 (s, 1H), 7.15 (d, J = 8.5 Hz, 2H), 6.93 (d, J = 8.5 Hz, 2H),
6.31−6.30 (m, 3H), 4.92 (d, J = 4.0 Hz, 2H), 3.82 (s, 3H). 13C{1H}
NMR (125 MHz, CDCl3) δ 179.6, 159.3, 149.9, 142.4, 127.9, 127.4,
115.5, 110.5, 108.3, 55.5, 45.1. IR (neat) 3321, 3159, 2364, 1607,
1547, 1511, 1354, 1308, 1244, 1147, 1069, 1019, 945, 828, 757 cm−1.
MS (ESI) 333 [M + Na+]. HRMS (ESI) calcd for C13H14N2O2Se [M
+ Na+] 333.0113; found 333.0108.
Compound 3aa. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as white solid (148.0 mg, 74%).
Compound 3u. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as pink solid (116.2 mg, 63%).
mp 128.3−128.5 °C. 1H NMR (500 MHz, CDCl3, TMS) δ 8.07 (br,
1H), 7.32 (s, 1H), 7.11 (s, 1H), 7.06 (s, 2H), 6.29 (d, J = 5.5 Hz,
2H), 6.10 (br, 1H), 4.91 (d, J = 4.0 Hz, 2H), 2.32 (s, 3H), 2.20 (s,
3H). 13C{1H} NMR (125 MHz, CDCl3) δ 179.6, 150.0, 142.4, 139.1,
135.4, 132.5, 131.2, 128.3, 127.1, 110.4, 108.2, 45.1, 21.0, 17.5. IR
(neat) 3129, 2960, 1541, 1505, 1416, 1284, 1227, 1185, 1103, 1010,
949, 839, 794, 738 cm−1. MS (ESI) 331 [M + Na+]. HRMS (ESI)
calcd for C14H16N2NaOSe [M + Na+] 331.0320; found 331.0323.
Compound 3v. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as red solid (169.8 mg, 76%).
mp 248.9 °C (decomposed). 1H NMR (400 MHz, DMSO-d6) δ
10.84 (s, 1H), 9.77 (s, 1H), 7.81 (s, 1H), 7.69 (d, J = 7.6 Hz, 1H),
7.34 (d, J = 8.0 Hz, 1H), 7.15 (s, 1H), 7.09−7.05 (m, 3H), 6.98 (t, J =
7.6 Hz, 1H), 6.89 (d, J = 8.4 Hz, 2H), 3.81−3.72 (m, 5H), 2.97 (t, J =
7.6 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d6) δ 178.2, 157.1,
136.2, 130.8, 127.2, 126.4, 122.7, 120.9, 118.6, 118.1, 114.3, 111.4,
111.3, 55.2, 47.5, 24.7. IR (neat) 3310, 3249, 1824, 1553, 1509, 1455,
1297, 1246, 1180, 1098, 1031, 905, 835, 741 cm−1. MS (ESI) 396 [M
+ Na+]. HRMS (ESI) calcd for C18H19N3NaOSe [M + Na+]
396.0586; found 396.0597.
Compound 3w. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as brown solid (176.3 mg,
73%). mp 241.5 °C (decomposed). 1H NMR (400 MHz, DMSO-d6)
δ 10.65 (s, 1H), 9.75 (s, 1H), 7.77 (br, 1H), 7.28 (br, 1H), 7.23 (d, J
= 8.4 Hz, 1H), 7.09 (s, 2H), 7.06 (s, 1H), 6.89 (d, J = 8.8 Hz, 2H),
6.72 (dd, J = 8.8, 2.4 Hz, 1H), 3.81−3.77 (m, 2H), 3.76 (s, 3H), 3.75
(s, 3H), 2.94 (t, J = 7.6 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-
d6) δ 178.2, 157.1, 152.9, 131.4, 130.8, 127.6, 126.4, 124.0, 123.3,
114.3, 111.9, 111.2, 100.7, 55.3, 55.2, 47.4, 24.8. IR (neat) 3159,
1546, 1511, 1442, 1385, 1303, 1249, 1171, 1026, 924, 846, 805 cm−1.
MS (ESI) 426 [M + Na+]. HRMS (ESI) calcd for C19H21N3NaO2Se
[M + Na+] 426.0692; found 426.0697.
1
mp 121.3 °C (decomposed). H NMR (500 MHz, CDCl3, TMS) δ
8.32 (s, 1H), 7.43−7.40 (m, 1H), 7.33 (t, J = 7.5 Hz, 2H), 7.28 (d, J =
8.0 Hz, 1H), 7.17 (t, J = 8.0 Hz, 1H), 7.00 (d, J = 7.5 Hz, 2H), 6.76
(d, J = 8.0 Hz, 1H), 6.71 (d, J = 7.5 Hz, 1H), 6.24 (s, 1H), 3.96 (q, J =
6.5 Hz, 2H), 3.77 (s, 3H), 2.91 (t, J = 6.5 Hz, 2H). 13C{1H} NMR
(125 MHz, CDCl3) δ 178.6, 159.9, 139.7, 135.4, 130.2, 129.8, 127.6,
125.7, 125.1, 120.9, 114.4, 112.1, 100.0, 55.1, 48.9, 34.8. IR (neat)
3350, 3167, 2939, 1583, 1529, 1480, 1289, 1238, 1152, 1012, 896,
790 cm−1. MS (ESI) 357 [M + Na+]. HRMS (ESI) calcd for
C16H18N2NaOSe [M + Na+] 357.0477; found 357.0480.
Compound 3ab. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (194.4 mg,
1
86%). mp 134.5 °C (decomposed). H NMR (400 MHz, CDCl3,
TMS) δ 8.43 (s, 1H), 8.13 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.38 (d, J
= 8.4 Hz, 1H), 7.22 (td, J = 8.0, 0.8 Hz, 1H), 7.12−7.08 (m, 3H),
6.93 (br, 1H), 6.76 (d, J = 8.4 Hz, 2H), 6.22 (br, 1H), 4.02 (q, J = 6.8
Hz, 2H), 3.08 (t, J = 6.8 Hz, 2H). 13C{1H} NMR (125 MHz, CDCl3)
δ 178.5, 136.3, 133.8, 133.0, 130.1, 127.0, 126.3, 122.5, 122.2, 199.9,
118.6, 112.1, 111.3, 48.3, 24.1. IR (neat) 3390, 3032, 1922, 1616,
1556, 1490, 1323, 1231, 1091, 1005, 818 cm−1. MS (ESI) 378 [M +
H+]. HRMS (ESI) calcd for C17H17ClN3Se [M + H+] 378.0271;
found 378.0272.
Compound 3ac. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as brown solid (127.9 mg,
1
60%). mp 251.4 °C (decomposed). H NMR (400 MHz, CDCl3,
TMS) δ 8.16 (s, 1H), 7.15 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.4 Hz,
2H), 6.04 (br, 1H), 3.83 (s, 3H), 3.67 (q, J = 6.4 Hz, 2H), 1.55 (t, J =
6.4 Hz, 2H), 1.26−1.24 (m, 12H), 0.88 (t, J = 6.8 Hz, 3H). 13C{1H}
NMR (125 MHz, CDCl3) δ 179.1, 159.2, 128.0, 127.6, 115.4, 55.5,
48.2, 31.8, 29.4, 29.14, 29.09, 28.9, 26.7, 22.6, 14.0. IR (neat) 3198,
2925, 2851, 1575, 1508, 1464, 1343, 1296, 1244, 1098, 1032, 835
cm−1. MS (ESI) 357 [M + H+]. HRMS (ESI) calcd for C17H29N2OSe
[M + H+] 357.1440; found 357.1464.
Compound 3x. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (158.0 mg,
Compound 3ad. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as brown solid (173.0 mg,
76%). mp 127.4 °C (decomposed). 1H NMR (400 MHz, DMSO-d6)
δ 9.94 (s, 1H), 8.62 (br, 1H), 7.65 (t, J = 8.8 Hz, 4H), 7.47−7.33 (m,
9H), 7.26 (t, J = 7.2 Hz, 1H), 5.80 (br, 1H), 1.51 (d, J = 7.2 Hz, 3H).
13C{1H} NMR (125 MHz, CDCl3) δ 178.1, 141.6, 140.6, 139.6,
128.9, 128.8, 127.8, 126.9, 126.2, 125.3, 57.1, 21.1. IR (neat) 3360,
3022, 2122, 1884, 1519, 1483, 1312, 1235, 1110, 1007, 912, 832, 761
cm−1. MS (ESI) 403 [M + Na+]. HRMS (ESI) calcd for
C21H20N2NaSe [M + Na+] 403.0685; found 403.0686.
1
79%). mp 257.6 °C (decomposed). H NMR (400 MHz, CDCl3,
TMS) δ 8.19 (s, 1H), 7.27−7.21 (m, 3H), 7.12 (d, J = 6.4 Hz, 2H),
6.95 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 9.2 Hz, 2H), 6.03 (br, 1H), 3.93
(q, J = 6.8 Hz, 2H), 3.80 (s, 3H), 2.91 (t, J = 6.8 Hz, 2H). 13C{1H}
NMR (125 MHz, CDCl3) δ 179.0, 159.1, 138.2, 128.7, 128.7, 127.8,
127.5, 126.6, 115.3, 55.5, 48.8, 34.8. IR (neat) 3317, 3135, 1553,
1509, 1447, 1361, 1300, 1242, 1161, 1104, 1029, 941, 825, 781 cm−1.
MS (ESI) 357 [M + Na+]. HRMS (ESI) calcd for C16H18N2NaOSe
[M + Na+] 357.0477; found 357.0479.
Compound 3y. Purification on silica gel (petroleum ether/ethyl
Compound 3ae. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (143.8 mg,
79%). mp 84.6 °C (decomposed). 1H NMR (500 MHz, CDCl3,
TMS) δ 8.48 (br, 1H), 7.41−7.27 (m, 8H), 7.18 (d, J = 7.5 Hz, 2H),
6.45 (br, 1H), 5.84 (br, 1H), 1.57 (d, J = 7.0 Hz, 3H). 13C{1H} NMR
(125 MHz, CDCl3) δ 178.1, 141.6, 135.6, 132.7, 130.3, 128.8, 127.7,
126.2, 125.2, 57.1, 21.1. IR (neat) 3300, 1560, 1452, 1312, 1248,
1061, 936, 850, 752 cm−1. MS (ESI) 327 [M + Na+]. HRMS (ESI)
calcd for C15H16N2NaSe [M + Na+] 327.0371; found 327.0374.
acetate = 2:1) afforded the compound as yellow solid (137.8 mg,
1
62%). mp 221.2 °C (decomposed). H NMR (500 MHz, CDCl3,
TMS) δ 8.05 (s, 1H), 7.77 (s, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.35 (d, J
= 7.5 Hz, 1H), 7.19 (t, J = 7.5 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 6.96
(s, 1H), 6.88 (s, 1H), 6.84 (d, J = 7.5 Hz, 1H), 6.77 (d, J = 7.5 Hz,
1H), 5.91 (s, 1H), 3.99 (q, J = 6.0 Hz, 2H), 3.04 (t, J = 6.0, 2H), 2.28
(s, 3H), 2.04 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 178.8,
138.7, 136.3, 135.3, 132.2, 131.1, 128.0, 127.1, 127.0, 122.2, 122.0,
F
https://dx.doi.org/10.1021/acs.joc.0c02179
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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Article
Compound 3af. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as brown solid (134.0 mg,
67%). mp 106.5 °C (decomposed). H NMR (400 MHz, CDCl3,
Compound 3an. Purification on silica gel (petroleum ether/ethyl
acetate = 1:3) afforded the compound as pink solid (67.5 mg, 46%).
1
1
mp 96 °C (decomposed). H NMR (400 MHz, DMSO-d6) δ 8.23
(br, 2H), 3.09−3.06 (m, 4H), 1.74 (penta, J = 5.6 Hz, 2H). 13C{1H}
NMR (125 MHz, DMSO-d6) δ 168.6, 39.5, 18.2. IR (neat) 3197,
2968, 1559, 1422, 1314, 1199, 1067, 799, 746 cm−1. MS (ESI) 187
[M + Na+]. HRMS (ESI) calcd for C4H8N2NaSe [M + Na+]
186.9745; found 186.9739.
TMS) δ 8.18 (br, 1H), 7.35−7.27 (m, 5H), 7.12 (d, J = 8.4 Hz, 2H),
6.92 (d, J = 8.4 Hz, 2H), 6.23 (br, 1H), 5.82 (br, 1H), 3.81 (s, 3H),
1.54 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 178.6,
159.2, 141.8, 128.7, 127.6, 127.5, 126.2, 115.4, 56.9, 55.5, 21.2. IR
(neat) 3350, 3150, 2969, 1607, 1511, 1443, 1389, 1300, 1241, 1164,
1104, 1027, 950, 829, 787 cm−1. MS (ESI) 335 [M + H+]. HRMS
(ESI) calcd for C16H19N2OSe [M + H+] 335.0658; found 335.0658.
Compound 3ag. Purification on silica gel (petroleum ether/ethyl
acetate = 3:1) afforded the compound as yellow solid (76.3 mg, 43%).
mp 182.7 °C (decomposed). 1H NMR (400 MHz, DMSO-d6) δ
13.07 (br, 2H), 7.24−7.17 (m, 4H). 13C{1H} NMR (125 MHz,
DMSO-d6) δ 159.0, 132.9, 122.2, 109.4. IR (neat) 3147, 2988, 1508,
1461, 1262, 1169, 1050, 922, 739 cm−1. MS (ESI) 221 [M + Na+].
HRMS (ESI) calcd for C7H6N2NaSe [M + Na+] 220.9588; found
220.9597.
Compound 3ah. Purification on silica gel (petroleum ether/ethyl
acetate = 3:1) afforded the compound as yellow solid (89.3 mg, 47%).
mp 187.1 °C (decomposed). 1H NMR (500 MHz, DMSO-d6) δ
13.04 (br, 2H), 7.07−7.04 (m, 2H), 6.96 (d, J = 6.0 Hz, 1H), 2.41 (s,
3H). 13C{1H} NMR (125 MHz, DMSO-d6) δ 158.7, 133.3, 133.0,
123.5, 122.8, 120.4, 107.5, 16.3. IR (neat) 3087, 2985, 2902, 1501,
1379, 1183, 1067, 859, 735 cm−1. MS (ESI) 213 [M + H+]. HRMS
(ESI) calcd for C8H9N2Se [M + H+] 212.9926; found 212.9932.
Compound 3ai. Purification on silica gel (petroleum ether/ethyl
acetate = 3:1) afforded the compound as yellow solid (83.6 mg, 44%).
mp 149.3 °C (decomposed). 1H NMR (400 MHz, DMSO-d6) δ
12.96 (br, 2H), 7.12 (d, J = 8.0 Hz, 1H), 7.05 (s, 1H), 6.98 (d, J = 8.0
Hz, 1H), 2.34 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6) δ
158.9, 133.7, 132.2, 131.5, 123.8, 110.0, 109.6, 20.9. IR (neat) 3120,
2972, 2860, 1621, 1490, 1430, 1339, 1260, 1065, 970, 804, 713 cm−1.
MS (ESI) 213 [M + H+]. HRMS (ESI) calcd for C8H9N2Se [M + H+]
212.9926; found 212.9929.
Compound II.1d Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (1.87 g, 82%).
1H NMR (500 MHz, CDCl3, TMS) δ 7.48 (br, 1H), 7.35 (t, J = 7.5
Hz, 2H), 7.23−7.20 (m, 3H), 3.34 (s, 6H). 13C{1H} NMR (125
MHz, CDCl3) δ 182.4, 140.3, 128.9, 126.0, 125.2, 43.4.
Compound 4.18 Purification on silica gel (petroleum ether)
1
afforded the compound as yellow liquid (69.9 mg, 32%). H NMR
(500 MHz, CDCl3, TMS) δ 7.39−7.32 (m, 3H), 7.30−7.28 (m, 2H).
13C{1H} NMR (125 MHz, CDCl3) δ 129.6, 129.5, 128.1, 126.1.
Crystal Structure Determinations. Single crystal of compound
3a was obtained in ethanol. The intensity data was collected on a
Bruker APEX II CCD area detector using graphite-monochromated
Mo Kα radiation. Data were integrated using SAINT19 and a
semiempirical absorption correction applied using SADABS.20 The
structures were solved by direct methods (SHELXL-2018/3)21 and
2
refined by full-matrix least-squares techniques against Fo (SAINT;
Bruker, 2014). Molecular structures were prepared using SHELXTL
(Sheldrick, 2018). All hydrogen atoms were included at calculated
positions with fixed thermal parameters. Crystallographic data as well
as structure solution and refinement details are summarized in Table
S1 (see the Supporting Information).
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02179.
1
Copy of H and 13C NMR spectra of compounds 3 and
Compound 3aj. Purification on silica gel (petroleum ether/ethyl
acetate = 3:1) afforded the compound as yellow solid (97.3 mg, 48%).
mp 221.5 °C (decomposed). 1H NMR (500 MHz, DMSO-d6) δ
12.85 (br, 2H), 7.03 (s, 2H), 2.23 (s, 6H). 13C{1H} NMR (125 MHz,
DMSO-d6) δ 157.4, 132.0, 131.1, 110.5, 19.6. IR (neat) 3093, 2364,
1663, 1470, 1330, 1245, 1161, 1001, 848 cm−1. MS (ESI) 227 [M +
H+]. HRMS (ESI) calcd for C9H11N2Se [M + H+] 227.0082; found
227.0083.
4, HPLC spectra of compound 3ad, and X-ray data of
compound 3a (CCDC-2015425) (PDF)
Accession Codes
CCDC 2015425 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.
Compound 3ak. Purification on silica gel (petroleum ether/ethyl
acetate = 1:3) afforded the compound as brown solid (96.9 mg, 53%).
1
mp 172.8−174.6 °C. H NMR (400 MHz, DMSO-d6) δ 8.82 (br,
2H), 3.05−2.96 (m, 2H), 1.93 (d, J = 10.8 Hz, 2H), 1.68 (d, J = 8.4
Hz, 2H), 1.36−1.19 (m, 4H). 13C{1H} NMR (125 MHz, DMSO-d6)
δ 180.9, 64.1, 28.0, 23.0. IR (neat) 3213, 2943, 2867, 1504, 1450,
1353, 1212, 1096, 828, 658 cm−1. MS (ESI) 227 [M + Na+]. HRMS
(ESI) calcd for C7H12N2NaSe [M + Na+] 227.0058; found 227.0058.
Compound 3al. Purification on silica gel (petroleum ether/ethyl
acetate = 1:3) afforded the compound as yellow solid (64.6 mg, 44%).
AUTHOR INFORMATION
■
Corresponding Authors
Jianmei Lu − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou, Zhejiang Province 325035,
People’s Republic of China; orcid.org/0000-0002-6983-
9846; Email: ljm@wzu.edu.cn
Xuefeng Jiang − Shanghai Key Laboratory of Green Chemistry
and Chemical Process, School of Chemistry and Molecular
Engineering, East China Normal University, Shanghai
200062, P. R. China; orcid.org/0000-0002-1849-6572;
Email: xfjiang@chem.ecnu.edu.cn
1
mp 88.9−91.8 °C. H NMR (400 MHz, DMSO-d6) δ 8.63 (s, 1H),
8.43 (s, 1H), 3.94−3.87 (m, 1H), 3.61 (t, J = 10.0 Hz, 1H), 3.04 (dd,
J = 10.0, 7.6 Hz, 1H), 1.12 (d, J = 6.4 Hz, 3H). 13C{1H} NMR (125
MHz, DMSO-d6) δ 175.4, 52.4, 51.4, 20.0. IR (neat) 3212, 2972,
2862, 1525, 1496, 1368, 1301, 1274, 1197, 1006, 699 cm−1. MS (ESI)
187 [M + Na+]. HRMS (ESI) calcd for C4H8N2NaSe [M + Na+]
186.9745; found 186.9755.
Compound 3am. Purification on silica gel (petroleum ether/ethyl
acetate = 2:1) afforded the compound as yellow solid (127.3 mg,
67%). mp 200.5−201.5 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.70
(s, 1H), 9.06 (s, 1H), 7.17 (td, J = 8.0, 1.2 Hz, 1H), 7.07 (d, J = 7.2
Hz, 1H), 7.01−6.96 (m, 2H), 4.36 (s, 2H). 13C{1H} NMR (125
MHz, DMSO-d6) δ 170.8, 134.4, 128.1, 126.1, 123.4, 117.2, 114.1,
42.9. IR (neat) 3128, 3075, 3005, 1933, 1559, 1503, 1378, 1243,
1166, 1093, 920, 789 cm−1. MS (ESI) 213 [M + H+]. HRMS (ESI)
calcd for C8H9N2Se [M + H+] 212.9925; found 212.9926.
Authors
Lai Li − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou, Zhejiang Province 325035,
People’s Republic of China
Jiaqi Wu − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou, Zhejiang Province 325035,
People’s Republic of China
G
https://dx.doi.org/10.1021/acs.joc.0c02179
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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Article
Kawde, A.-N.; Zierkiewicz, W.; Ahmad, S.; Altuwaijri, S.; Isab, A. A.
Synthesis, X-ray structure, DFT calculations and anticancer activity of
a selenourea coordinated gold(I)-carbene complex. Polyhedron 2017,
137, 197−206.
Linsha Wei − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou, Zhejiang Province 325035,
People’s Republic of China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02179
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for financial support provided by NSFC (nos.
21471115, 21971065, 21722202, 21672069).
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