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DOI: 10.1055/s-2008-1078499
An Easy and Multigram Scale Synthesis of Anthracene-1,8-ditriflate
Publikationsverlauf
Publikationsdatum:
19. Juni 2008 (online)
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Abstract
1,8-Ditriflated anthracene was prepared by an easy and straightforward approach that enables its reproducible synthesis on a 10 gram scale. Its symmetric/unsymmetric diethynylations by using the Sonogashira cross-coupling reactions were also demonstrated.
Key words
anthracene - anthraquinone - zinc reduction - unsymmetric substitution - Sonogashira cross-coupling
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References and Notes
Instead of pyridine, dichloromethane is also usable for the acetylation as solvent in combination with acetyl chloride and triethylamine for acid scavenging, affording a comparable yield of 2.
141,8-Diacetoxyanthraquinone (2) ¹² ¹H NMR (200 MHz, CDCl3): δ = 8.21 (dd, ³ J = 7.6 Hz, 4 J = 1.1 Hz, 2 H), 7.75 (dd, ³ J = 8.0, 7.6 Hz, 2 H), 7.39 (dd, ³ J = 8.0 Hz, 4 J = 1.1 Hz, 2 H), 2.44 (s, 6 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 181.9, 180.8, 169.4, 150.0, 134.6, 134.4, 130.2, 125.6, 125.4, 21.1. ESI-HRMS: m/z calcd for C18H12O6 [M + Na]+: 347.0526; found: 347.0527.
15The products were separated by preparative recycling gel permeation chromatography (Japan Analytical Industry Co. Ltd., LC 9101) equipped with a pump (Hitachi l-7110, flow rate 3.5 mL/min), a degasser (GASTORR-702), a RI detector (Jai RI-7), a UV detector (Jai UV-3702, λ = 254 nm), and two columns (Jaigel 2H and 2.5H, 20 × 600 mm for each) using CHCl3 as eluent at r.t.
16
1-Acetoxy-8-hydroxy-10(9
H
)-anthrone
¹H
NMR (200 MHz, CDCl3): δ = 8.27 (d,
³
J = 7.8
Hz, 1 H), 7.96 (d,
³
J = 8.4 Hz,
1 H), 7.50 (t,
³
J = 7.8 Hz,
1 H), 7.41-7.28 (m, 2 H), 7.03 (d,
³
J = 7.8 Hz,
1 H), 5.27 (br, 1 H), 4.02 (s, 2 H), 2.44 (s, 3 H). HRMS (EI): m/z calcd
for C6H12O4 [M]+:
268.0730; found: 268.0730.
1-Acetoxy-8-hydroxyanthracene
¹H
NMR (200 MHz, CDCl3): δ = 8.76 (s,
1 H), 8.39 (s, 1 H), 7.86 (d,
³
J = 8.4 Hz,
1 H), 7.57 (d,
³
J = 8.7 Hz,
1 H), 7.48-7.18 (m, 3 H), 6.75 (d,
³
J = 7.2 Hz,
1 H), 5.53 (br, 1 H), 2.54 (s, 3 H). HRMS (EI): m/z calcd
for C6H12O3 [M]+:
252.0781; found: 252.0778.
1-Acetoxy-8-hydroxy-9,10-dihydroanthracene
³¹
¹H
NMR (200 MHz, CDCl3): δ = 7.33-7.18
(m, 2 H), 7.09 (t,
³
J = 7.7 Hz,
1 H), 6.99 (dd,
³
J = 7.2 Hz,
4
J = 1.5
Hz, 1 H), 6.90 (d,
³
J = 7.7 Hz,
1 H), 6.67 (d,
³
J = 7.7 Hz,
1 H), 5.75 (br, 1 H), 4.04 (s, 2 H), 3.85 (s, 2 H), 2.46 (s, 3 H).
HRMS (EI): m/z calcd
for C6H14O3 [M]+:
254.0938; found: 254.0938.
1,8-Dihydroxyanthracene
8,9
¹H
NMR (200 MHz, DMSO-d
6): d = 10.34
(s, 2 H), 9.08 (s, 1 H), 8.37 (s, 1 H), 7.51 (d,
³
J = 8.4
Hz, 2 H), 7.32 (dd,
³
J = 8.4, 7.0
Hz, 2 H), 6.82 (d,
³
J = 7.0 Hz,
2 H). ¹³C NMR (50.3 MHz, DMSO-d
6): d = 154.4, 133.6,
127.1, 125.5, 124.4, 119.2, 116.7, 106.2. HRMS (EI): m/z calcd
for C14H10O2 [M]+:
210.0676; found: 210.0675.
1,8,10-Triacetoxyanthracene ²0 ¹H NMR (200 MHz, CDCl3): δ = 8.42 (s, 1 H), 7.82 (d, ³ J = 8.8 Hz, 2 H), 7.50 (dd, ³ J = 8.8, 7.3 Hz, 2 H), 7.31 (d, ³ J = 7.3 Hz, 2 H), 2.62 (s, 3 H), 2.51 (s, 6 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 169.2, 168.9, 146.8, 142.9, 126.0, 125.9, 125.3, 119.5, 117.7, 112.2 21.0, 20.7. HRMS (EI): m/z calcd for C20H16O6 [M]+: 352.0941; found: 352.0942.
191,8-Diacetoxy-9,10-dihydroanthracene (3′) ³¹ ¹H NMR (300 MHz, CDCl3): δ = 7.22-7.13 (m, 4 H), 6.96 (dd, ³ J = 7.8 Hz, 4 J = 1.1 Hz, 2 H), 4.02 (s, 2 H), 3.66 (s, 2 H), 2.36 (s, 6 H).
21
Synthesis of Compound
3 (from 2 to 3)
Compound 2 (20.0
g, 61.7 mmol) was mixed with AcOH (900 mL) and heated at 140 ˚C
with stirring under nitrogen with a reflux condenser until the mixture
became a clear solution. To this solution, ground zinc powder (13.0
g, 198 mmol) was added portion by portion with stirring but heating stopped
during the addition. The reaction mixture was then kept stirred
at 135 ˚C for 3 h. The first TLC analysis was carried
out with CH2Cl2-MeOH (40:1) as eluent.
Besides the remaining reactant 2 (R
f
= 0.74),
the TLC displayed several product spots including the following
two main ones; the higher spot (R
f
= 0.44)
from 1-acetoxy-8-hydroxyanthracene that exhibited characteristic
blue fluorescence under UV (λ = 366 nm), and the
lower one (R
f
= 0.33)
from 1-acetoxy-8-hydroxy-10 (9H)-anthrone.
Ground zinc powder (4.00 g, 61.2 mmol) was further added to the
mixture portion by portion with stirring but heating stopped during
the addition. The mixture was kept stirred at 135 ˚C
for further 3 h. The second TLC analysis indicated diminishment
of the anthrone intermediate as well as increased formation of the anthracene.
To the mixture was then added more ground zinc powder (4.00 g, 61.2
mmol) portion by portion with stirring but heating stopped during
the addition. The reaction mixture was kept stirred at 135 ˚C
for further 15 h, until the last TLC analysis confirmed disappearance
of the intermediate. The reaction mixture was then cooled to r.t. and
passed through a short SiO2 column with EtOAc to remove
the remaining zinc powder and zinc salts. The solvent was removed
by evaporation. The residue was mixed with pyridine (400 mL) and
cooled at 0 ˚C. Acetyl chloride (9.0 mL, 130 mmol)
was added there dropwise with stirring under nitrogen. The reaction
mixture was warmed to r.t. and kept stirred overnight. After the
solvent was removed by evaporation, the residue was subjected to
silica gel chromatography (CH2Cl2) to give 3 as mixture with 3′ (11.3 g,
molar ratio 1:0.08 determined by ¹H NMR). The
yield of 3 was calculated as 58%.
1,8-Diacetoxyanthracene (3) 9 ¹H NMR (300 MHz, CDCl3): δ = 8.48 (s, 1 H), 8.45 (s, 1 H), 7.89 (d, ³ J = 8.6 Hz, 2 H), 7.46 (dd, ³ J = 8.6, 7.2 Hz, 2 H), 7.28 (d, ³ J = 7.2 Hz, 2 H), 2.51 (s, 6 H). ¹³C NMR (50.3 MHz, CDCl3): δ = 169.0, 146.5, 132.6, 126.9, 126.1, 125.5, 124.9, 117.3, 113.6, 20.8. HRMS (EI): m/z calcd for C18H14O4 [M]+: 294.0887; found: 294.0889.
23
Synthesis of Compound
5 (from 3 to 5 via 4)
A mixture of 3 and 3′ (12.9 g, 44.9 mmol, molar ratio
1:0.13) was dissolved in MeOH-CH2Cl2 (555
mL, 1:2) and degassed by freeze-pump-thaw cycle three times. Methylamine
(27.5 mL, 224 mmol, 33 wt% in EtOH) was added dropwise
at 0 ˚C under nitrogen in dark. The mixture was
stirred at r.t. for 1 d. The mixture was kept in dark, evaporated,
and dried in vacuo. The crude product was suspended in degassed
dry CH2Cl2 (260 mL), followed by addition
of Et3N (49.0 mL, 352 mmol). The mixture was cooled to -13 ˚C,
followed by slow dropwise addition of trifluoromethanesulfonic anhydride
(24.4 mL, 145 mmol), diluted with dry CH2Cl2 (90
mL) with stirring under nitrogen in dark. The mixture was warmed
to r.t. and kept stirred for 3 d. After solvent removal by evaporation,
the residue was subjected to silica gel chromatography (hexane-CH2Cl2, 10:3)
to give 5 as mixture with 5′ (10.9
g, molar ratio 1:0.07, determined by ¹9F NMR).
The yield of 5 was calculated as 54%.
1,8-Di(trifluoromethanesulfonyl)oxyanthracene (5) 8 ¹H NMR (300 MHz, CDCl3): δ = 8.85 (s, 1 H), 8.51 (s, 1 H), 7.99 (d, J = 8.1 Hz, 2 H), 7.54 (dd, ³ J = 7.5 Hz, 4 J = 1.3 Hz, 2 H), 7.49 (dd, ³ J = 8.1, 7.5 Hz, 2 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 145.5, 132.9, 128.7, 127.7, 125.4, 125.2, 118.9 (q, ¹ J C,F = 320 Hz, CF3), 118.3, 114.0. HRMS (EI): m/z calcd for C16H8F6O6S2 [M]+: 473.9661; found: 473.9662.
251,8-Di(trifluoromethanesulfonyl)oxy-9,10-dihydroanthracene (5") ¹H NMR (300 MHz, CDCl3): δ = 7.32-7.17 (m, 6 H), 4.07 (s, 2 H), 4.03 (s, 2 H).
271,8-Di[(trimethylsilyl)ethynyl]anthracene (6) 8 ¹H NMR (200 MHz, CDCl3): δ = 9.30 (s, 1 H), 8.40 (s, 1 H), 7.96 (d, ³ J = 8.4 Hz, 2 H), 7.77 (d, ³ J = 7.0 Hz, 2 H), 7.40 (dd, ³ J = 8.4, 7.0 Hz, 2 H), 0.36 (s, 18 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 132.3, 131.3, 131.2, 129.2, 127.6, 124.9, 123.9, 121.3, 103.6, 99.8, 0.4. HRMS (EI): m/z calcd for C24H26Si2 [M]+: 370.1568; found: 370.1566.
28
Synthesis of Compound
8 (from 5 to 8 via 7)
A mixture of 5 and 5′ (15.1 g, 31.9 mmol, molar ratio
1:0.09) was suspended in dry Et3N-toluene (210
mL, 1:1) and degassed by freeze-pump-thaw cycle three times. Then, TMS-acetylene
(4.5 mL, 32 mmol), freshly prepared palladium tetrakis(triphenylphosphine)³² (0.76
g, 0.64 mmol), and CuI (61 mg, 0.32 mmol) were added. The vessel was
filled with nitrogen and sealed. The reaction was performed at 60 ˚C
with stirring for 2 d. The reaction mixture was then cooled to r.t.
and passed through a short silica gel column with CH2Cl2 to
remove the catalysts and triethylammonium triflate. After removal
of the solvent by evaporation, the residue was subjected to silica
gel chromatography(hexane) to afford 9.83 g of 7 (79%)
as well as 1.17 g of 6 (11%).
Compound 7 (9.57 g, 22.7 mmol) was suspended in
dry Et3N-toluene (480 mL, 1:1) and degassed
by freeze-pump-thaw cycle three times. Then, TIPS-acetylene (6.1
mL, 27 mmol), freshly prepared palladium tetrakis(triphenyl-phosphine)
(0.54 g, 0.47 mmol), and CuI (44 mg, 0.23 mmol) were added. The
reaction was performed at 60 ˚C under nitrogen
with stirring for 6 d. The reaction mixture was then cooled to r.t.
and passed through a short silica gel column with CH2Cl2.
After removal of the solvent by evaporation, the residue was subjected
to silica gel chromatography (hexane-CH2Cl2,
20:1) to afford 8.95 g of 8 (87%).
1-(Trifluoromethanesulfonyl)oxy-8-(trimethylsilyl)ethy-nylanthracene (7)
¹H NMR
(300 MHz, CDCl3): d = 9.18 (s, 1 H), 8.47 (s,
1 H), 8.00 (d,
³
J = 7.5 Hz,
1 H), 7.97 (d,
³
J = 8.4 Hz,
1 H), 7.78 (d,
³
J = 7.0 Hz,
1 H), 7.51-7.41 (m, 3 H), 0.37 (s, 9 H). ¹³C NMR
(75.5 MHz, CDCl3):d = 146.1, 132.6, 131.8, 131.7, 131.7,
129.0, 128.7, 127.5, 125.8, 125.0, 124.2, 121.6, 119.1, 118.9 (q,
¹
J
C,F
= 321
Hz, CF3), 117.2, 102.0, 101.1,
-0.1.
HRMS (EI): m/z calcd
for C20H17F3O3SSi [M]+: 422.0614;
found: 422.0617.
1-(Triisopropylsilyl)ethynyl-8-(trimethylsilyl)ethynyl-anthracene (8) ¹H NMR (300 MHz, CDCl3): δ = 9.38 (s, 1 H), 8.26 (s, 1 H), 7.93-7.83 (m, 4 H), 7.47-7.38 (m, 2 H), 1.39 (s, 21 H), 0.53 (s, 9 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 132.9, 132.6, 131.2, 131.2, 131.1, 130.9, 129.2, 129.0, 127.6, 124.8, 124.7, 123.6, 121.6, 121.3, 105.8, 104.0, 99.6, 96.3, 19.0, 11.5, 0.3. HRMS (EI): m/z calcd for C30H38Si2 [M]+: 454.2507; found: 454.2505.