Synthesis of Functionalized 1,4-Dihydro-9,10-anthraquinones and Anthraquinones by Ring Closing Metathesis Using Grubbs’ Catalyst

Abstract

A general and straightforward synthesis of anthraquinones was developed, in which diallylation of 1,4-naphthoquinones, followed by Ring Closing Metathesis (RCM) of the resulting diallylnaphthoquinones with Grubbs’ catalyst and subsequent dehydrogenation using Pd/C afforded the desired anthraquinones with regiocontrol of substituents and in good yields.

1,4-dihydro-9,10-anthraquinones - anthraquinones - Grubbs’ catalyst

References

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As a representative example, the synthesis of 2,3-diallyl-1,4-naphthoquinone 6d is described. To a solution of naphthoquinone 5d (0.22 g, 1.4 mmol) in MeCN (20 mL), 3-butenoic acid (0.36 g, 4.2 mmol, 3.0 equiv) was added at r.t., followed by the addition of a solution of AgNO₃ (0.16 g, 0.93 mmol, 0.65 equiv) in distilled H₂O (10 mL). The resulting mixture was heated to 75 °C and diammonium persulfate (1.31 g, 5.76 mmol, 4.00 equiv), dissolved in distilled H₂O (10 mL), was added slowly, followed by a stirring period of 2 h at 75 °C. Evaporation of the solvent, extraction of the residue with EtOAc (3 × 40 mL), drying (MgSO₄), filtration of the drying agent and removal of the solvent in vacuo afforded the crude naphthoquinone, which was purified by means of column chromatography (hexane-EtOAc 99:1) yielding 2,3-diallyl-1,4-naphthoquinone (6d) (0.22 g, 67%). Spectroscopic data of 2,3-diallyl-5,7-dimethoxy-1,4-naphthoquinone (6a, 62%). Yellow crystals, mp 111 °C. Flash chromatography R_f = 0.08 (hexane-EtOAc 4:1). ¹H NMR (270 MHz, CDCl₃): δ = 3.35-3.40 (4 H, m), 3.93 and 3.96 (6 H, 2 × s), 5.03-5.23 (4 H, m), 5.79-5.93 (2 H, m), 6.71 (1 H, d, J = 2.3 Hz), 7.26 (1 H, d, J = 2.3 Hz). ¹³C NMR (67.8 MHz, CDCl₃): δ = 30.60, 31.09, 55.90, 56.42, 102.93, 104.06, 116.62, 116.71, 133.99, 134.28, 136.06, 142.14, 147.04, 161.70, 164.40, 182.67, 184.90. IR (KBr): ν_C=O = 1651 cm^-1. MS (70 eV): m/z (%) = 299 (100) [M⁺ + 1]. All other new compounds were fully characterized by ¹H NMR, ¹³C NMR, IR and MS.

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<A NAME="RG17404ST-21">21</A>

As a representative example, the synthesis of 1,4-dihydro-9,10-anthraquinone 12d is described. To a solution of 2,3-diallyl-1,4-naphthoquinone (6d, 0.08 g, 0.330 mmol) in CH₂Cl₂ (35 mL), Grubbs’ catalyst was added [benzylidene-bis(tricyclohexylphosphine)dichlororuthenium, 0.02 g, 0.023 mmol, 0.07 equiv] at r.t. After heating under reflux for 12 h, the cooled reaction mixture was filtered over silica gel and washed with CH₂Cl₂ (3 × 50 mL). Removal of the solvent in vacuo afforded pure 1,4-dihydro-9,10-anthraquinone (12d, 0.06 g, 88%). Spectroscopic data of 1,4-dihydro-5,7-dimethoxy-9,10-anthraquinone (12a, 91%). Yellow crystals, mp 191 °C. ¹H NMR (270 MHz, CDCl₃): δ = 3.19 (4 H, s), 3.94 and 3.96 (6 H, 2 × s), 5.84 (2 H, s), 6.71 (1 H, d, J = 2.2 Hz), 7.25 (1 H, d, J = 2.2 Hz). ¹³C NMR (67.8 MHz, CDCl₃): δ = 24.15, 24.58, 55.89, 56.37, 102.97, 103.92, 114.43, 122.55, 123.09, 135.96, 138.78, 143.63, 161.71, 164.37, 182.75 and 184.60. IR (KBr): ν_C=O = 1652 cm^-1. MS (70 eV): m/z (%) = 271 (100) [M⁺ + 1], 269 (48). All other new compounds were fully characterized by ¹H NMR, ¹³C NMR, IR and MS.

<A NAME="RG17404ST-22">22</A>

As a representative example, the synthesis of 9,10-anthraquinone 13d is described. A solution of 1,4-dihydro-9,10-anthraquinone (12d, 50.70 mg, 0.238 mmol) and palladium on active carbon (10%) (25.3 mg, 0.024 mmol, 0.10 equiv) in dry toluene (10 mL) was refluxed for 12 h. The cooled reaction mixture was filtered over Celite^® and washed with CH₂Cl₂ (3 × 10 mL). Removal of the solvent in vacuo afforded the pure 9,10-anthraquinone 13d (46.50 mg, 94%). The anthraquinones 13 were recrystallized from EtOH. 1,3-Dimethoxy-9,10-anthraquinone (13a, 91%). The spectral data correspond well with those reported in the literature. [23] Yellow crystals, mp 159 °C (Lit.²³ mp 158-160 °C). ¹H NMR (270 MHz, CDCl₃): δ = 3.99 and 4.02 (6 H, 2 × s), 6.80 (1 H, d, J = 2.3 Hz), 7.47 (1 H, d, J = 2.3 Hz), 7.67-7.81 (2 H, m), 8.20-8.29 (2 H, m). ¹³C NMR (67.8 MHz, CDCl₃): δ = 56.44, 57.02, 103.81, 105.25, 116.60, 126.97, 127.69, 132.85, 133.30, 134.79, 135.63, 138.01, 163.09, 165.23, 181.76, 183.99. IR (KBr): ν_C=O = 1673 cm^-1. MS (70 eV): m/z (%) = 269 (100) [M⁺ + 1].

<A NAME="RG17404ST-23">23</A> Khanapure SP. Reddy RT. Biehl ER. J. Org. Chem.  1987,  52:  5685