An Easy and Multigram Scale
Synthesis of Anthracene-1,8-ditriflate

Patrick Kissel; Fabian Weibel; Lukas Federer; Junji Sakamoto; A. Dieter Schlüter

doi:10.1055/s-2008-1078499

LETTER

An Easy and Multigram Scale Synthesis of Anthracene-1,8-ditriflate

Patrick Kissel, Fabian Weibel, Lukas Federer, Junji Sakamoto*, A. Dieter Schlüter*
Laboratory of Polymer Chemistry, Department of Materials, ETH Zurich, Wolfgang-Pauli-Strasse 10, HCI J541, 8093 Zurich, Switzerland
Fax: +41(44)6331395; e-Mail: sakamoto@mat.ethz.ch; e-Mail: schlueter@mat.ethz.ch;

Abstract

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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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Referenzen

References and Notes

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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.

1,8-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.

The 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.

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.

<A NAME="RG08908ST-17">17</A> Hadler HI. Raha CR. J. Org. Chem. 1957, 22: 433

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.

1,8-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).

<A NAME="RG08908ST-20">20</A> Brockmann H. Budde G. Chem. Ber. 1953, 86: 432

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.

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.

1,8-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).

<A NAME="RG08908ST-26">26</A> Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett. 1975, 16: 4467

1,8-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.

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.

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