The Journal of Organic Chemistry
Article
Synthesis of Compound C7. Compound C7 was prepared
according to the reported method.42 1H NMR (400 MHz, CDCl3) δ
= 7.25 (dd, J = 8.5, 1.8 Hz, 1H), 7.09 (d, J = 1.9 Hz, 1H), 6.88 (d, J =
8.4 Hz, 1H), 4.23−4.17 (m, 2H), 4.17−4.12 (m, 2H), 3.94−3.91 (m,
4H), 3.83−3.76 (m, 4H), 3.75−3.70 (m, 4H), 3.70−3.62 (m, 8H).
Synthesis of Compound 1. THF (200 mL) was added to a 500
mL round bottom flask, and then, triethylene glycol (20.00 g, 133.33
mmol) was added. The aqueous solution of NaOH was prepared by
dissolving NaOH (3.2 g, 80.0 mmol) in ionized water (50 mL) that
was added to the flask. The mixture was cooled to 0 °C in an ice water
bath. TsCl (12.73 g, 66.65 mmol) dissolved in THF (60 mL) was
added dropwise to the reaction solution. After addition, the reaction
mixture was kept at 0 °C and monitored by TLC. After TsCl was
consumed completely, most solvents were removed under reduced
pressure. Water (100 mL) was charged to the residue, and the mixture
was extracted by 2 × 100 mL DCM. Combined organic solution was
washed with brine at 100 mL and then was dried over Na2SO4.
Solvents were removed under reduced pressure to give a crude
product, and it was purified by a silicon column with DCM/EA (30/
1−30/8, v/v) as the eluent to yield compound 1 (11.6 g, 57%) as a
colorless oil. 1H NMR (400 MHz, CDCl3, 298 K) δ = 7.80 (d, J = 8.2
Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 4.22−4.14 (m, 2H), 3.73−3.69 (m,
4H), 3.61 (s, 4H), 3.60−3.55 (m, 2H), 2.45 (s, 3H); 13C {1H} NMR
(100 MHz, CDCl3, 298 K) δ = 145.0, 133.0, 130.0, 128.1, 72.6, 70.9,
70.4, 69.3, 68.8, 61.8, 21.8; HRMS (ESI) m/z (M + Na+) calcd for
C13H20O6SNa+: 327.0878, found: 327.0873.
Synthesis of Compound 3. Deoxygenated water (10 mL) was
added slowly to the mixture of the Se powder (0.37 g, 4.68 mmol)
and NaBH4 (0.54 g, 14.21 mmol) in an ice bath under a N2
atmosphere. The reaction mixture was stirred for 0.5 h and gradually
became clear to form NaHSe solution. Afterward, a solution of 1
(3.00 g, 9.83 mol) dissolved in 30 mL of deoxygenated THF was
added to the reaction solution by a syringe under N2 protection. The
temperature of the reaction mixture was kept at 50 °C in an oil bath
for 24 h. Then, it was cooled to room temperature and solvents were
removed under reduced pressure. Column chromatography was used
to purify the residue with DCM/MeOH = 500/1−50/1 (v/v) as the
eluent to yield compound 3 (1.33 g, 78%) as a colorless oil. 1H NMR
(400 MHz, CDCl3, 298 K) δ = 3.83−3.69 (m, 8H), 3.69−3.61 (m,
8H), 3.62−3.55 (m, 4H), 2.82 (t, J = 7.0 Hz, 4H); 13C {1H} NMR
(100 MHz, CDCl3, 298 K) δ = 72.7, 71.8, 70.3, 70.1, 61.6, 23.0;
HRMS (ESI) m/z (M + Na+) calcd for C12H26O6SeNa+: 369.0792,
found: 369.0799.
and washed with brine (30 mL). After being dried over Na2SO4, the
organic solution was concentrated to remove the solvent under
reduced pressure, and the residue was purified by a silicon column
with DCM/MeOH = 500/1−500/7 (v/v) as the eluent to obtain
compound C7Se (0.38 g, 56%) as a yellow solid. Mp = 70−71 °C; IR
(KBr) = 2919, 2869, 2224 (−CN), 1596, 1518, 1451, 1422, 1360,
1332, 1276, 1238, 1138, 1094, 1084, 1053, 1029, 1010, 968, 947, 930,
879, 866, 808, 788; 1H NMR (400 MHz, CDCl3, 298 K) δ = 7.12 (d,
J = 1.9 Hz, 1H), 6.90 (d, J = 8.4 Hz, 1H), 4.23−4.14 (m, 4H), 3.92
(td, J = 6.2, 4.7 Hz, 4H), 3.84−3.72 (m, 8H), 3.70−3.63 (m, 4H),
2.83 (td, J = 6.4, 2.8 Hz, 4H); 13C {1H} NMR (100 MHz, CDCl3) δ =
153.0, 149.0, 126.9, 119.2, 117.2, 113.6, 104.2, 77.4, 77.2, 77.0, 76.7,
72.5, 72.4, 71.1, 71.0, 70.5, 70.4, 69.7, 69.5, 69.1, 23.1; 77Se NMR
(114 Hz, CDCl3) δ = 150.47; HRMS (ESI) m/z (M + Na+) calcd for
C19H27NO6SeNa+: 468.0901, found: 468.0882.
Synthesis of Compound 2. NaOH (0.62 g, 15.50 mmol)
dissolved in 10 mL of H2O was added to the solution of tetraethylene
glycol (10.0 g, 51.55 mmol) dissolved in THF (20 mL), and then, the
mixture was cooled to 0 °C in an ice water bath. The solution of TsCl
(2.46 g, 12.88 mmol) in THF (50 mL) was added dropwise to the
mixture at 0 °C, and the reaction was monitored by TLC. After TsCl
was consumed completely, most solvents were removed and 50 mL of
brine was charged. The reaction mixture was extracted by 3 × 50 mL
DCM. The combined organic solution was washed with brine at 100
mL and then was dried over Na2SO4. After solvents were removed
under reduced pressure, the residue was purified by a silicon column
with DCM/EA = 100/1−3/1 (v/v) as the eluent to yield compound
1
2 (3.1 g, 69%) as a colorless oil. H NMR (600 MHz, CDCl3) δ =
7.80 (d, J = 8.2, 2H), 7.35 (s, 2H), 4.17 (s, 2H), 3.70 (d, J = 4.9, 4H),
3.66 (s, 2H), 3.64 (s, 2H), 3.61 (d, J = 4.0, 6H), 2.45 (s, 3H); 13C
{1H} NMR (100 MHz, CDCl3, 298 K) δ = 145.0, 133.1, 130.0, 128.1,
72.6, 70.8, 70.7, 70.5, 70.4, 69.4, 68.8, 61.8, 21.8; HRMS (ESI) m/z
(M + Na+) calcd for C15H24O7SNa+: 371.1140, found: 327.1132.
Synthesis of Compounds 4 and 6. Deoxygenated water (10
mL) was added slowly to the mixture of the Se powder (0.32 g, 4.05
mmol) and NaBH4 (0.46 g, 12.11 mmol) in an ice bath under a N2
atmosphere. The reaction mixture was stirred for 0.5 h and gradually
became clear to yield NaHSe solution. Afterward, a solution of 2 (3.0
g, 8.61 mol) in deoxygenated THF (30 mL) was added to the
reaction solution by a syringe under N2 protection. The reaction
mixture was stirred at 50 °C in an oil bath for 24 h. After the reaction
mixture was cooled to room temperature, the mixture was
concentrated under reduced pressure. Then, DCM (50 mL) was
added to the residue and the mixture was filtered. The filtrate was
concentrated to give crude compound 4, which was used in the next
step without further purification. Crude compound 4 was dissolved in
THF (20 mL), and NaOH (0.86 g, 21.5 mmol) dissolved in H2O (10
mL) was added; the mixture was cooled to 0 °C in an ice water bath.
TsCl (2.47 g, 12.93 mmol) dissolved in THF (20 mL) was added
dropwise to the reaction solution at 0 °C. After TsCl was consumed
completely, most solvents were removed and 50 mL of brine was
charged. The mixture was extracted by 3 × 50 mL DCM. All
combined organic solutions were washed with brine at 100 mL and
dried over Na2SO4. After removal of the solvents, the residue was
purified by silica gel column chromatography with DCM/EA = 100/
1−4/1 (v/v) as the eluent to yield a pure product (1.43 g, 44%) as a
slightly brown oil. IR (KBr) = 2867, 1597, 1451, 1351, 1292, 1248,
1173, 1095, 1011, 915, 816, 772, 663, 582, 554; 1H NMR (400 MHz,
CDCl3) δ = 7.80 (d, J = 8.3, 4H), 7.34 (d, J = 8.0, 4H), 4.16 (s, 4H),
3.69 (s, 8H), 3.61−3.59 (m, 16H), 2.75 (s, 4H), 2.45 (s, 6H); 13C
{1H} NMR (100 MHz, DMSO-d6) δ = 144.9, 132.4, 130.1, 127.6,
70.9, 70.0, 69.8, 69.8, 69.3, 67.9, 22.7, 21.1; HRMS (ESI) m/z (M +
Na+) calcd C30H46O12S2SeNa+: 765.1494, found: 765.1490.
Synthesis of Compound 5. Compound 3 (1.00 g, 2.90 mmol)
was dissolved in THF (20 mL), and then, NaOH (0.58 g, 14.50
mmol) dissolved in H2O (5 mL) was added to the solution. After
cooling the mixture to 0 °C in an ice water bath, TsCl (1.66 g, 8.69
mmol) dissolved in THF (15 mL) was added dropwise to the reaction
solution at 0 °C. After TsCl was consumed completely, most organic
solvents were removed and 50 mL of brine was charged. The mixture
was extracted by 2 × 50 mL DCM. All organic solutions were
combined and washed with brine at 100 mL and then were dried over
Na2SO4. Solvents were removed, and the residue was purified by silica
gel column chromatography with DCM/EA = 100/1−4/1 (v/v) as
1
the eluent to yield compound 5 (1.08 g, 57%) as a colorless oil. H
NMR (400 MHz, CDCl3, 298 K) δ = 7.80 (d, J = 8.3 Hz, 4H), 7.34
(d, J = 8.1 Hz, 4H), 4.17−4.14 (m, 4H), 3.74−3.62 (m, 8H), 3.62−
3.51 (m, 8H), 2.74 (t, J = 7.1 Hz, 4H), 2.45 (s, 6H); 13C {1H}NMR
(100 MHz, CDCl3, 298 K) δ = 145.0, 133.1, 130.0, 128.1, 71.8, 70.9,
70.2, 69.4, 68.9, 23.3, 21.8; HRMS (ESI) m/z (M + Na+) calcd for
C26H38O10S2SeNa+: 677.0969, found: 677.0969.
Synthesis of Compound C7Se. A suspension of K2CO3 (1.27 g,
9.20 mmol) and KBF4 (2.31 g, 18.33 mmol) in CH3CN (70 mL) was
heated to reflux in an oil bath under N2 protection. To the suspension,
a solution of the compound 5 (1.00 g, 1.53 mmol) and 3,4-dihydroxy-
nitrile (0.21 g, 1.55 mmol) in CH3CN (100 mL) was added dropwise.
The resulting reaction mixture was stirred for 24 h. After cooling the
mixture to room temperature, the suspension was filtered and the cake
was washed by DCM (30 mL). The filtrate was concentrated to
remove solvents. Then, the residue was redissolved in DCM (50 mL)
Synthesis of Compound C9Se. A suspension of K2CO3 (1.29 g,
9.35 mmol) and KBF4 (2.34 g, 18.57 mmol) in CH3CN (80 mL) was
heated to reflux in an oil bath under N2 protection. To the suspension,
a solution of the compound 6 (1.15 g, 1.55 mmol) and 3,4-
dihydroxybenzonitrile (210 mg, 1.55 mmol) in CH3CN (60 mL) was
added dropwise. The reaction mixture was stirred for 24 h. After
cooling the mixture to room temperature, the suspension was filtered
1434
J. Org. Chem. 2021, 86, 1430−1436