Synlett 2014; 25(18): 2591-2594
DOI: 10.1055/s-0034-1379026
letter
© Georg Thieme Verlag Stuttgart · New York

A Practical, Large-Scale Synthesis of Pyrene-2-Carboxylic Acid

Juan M. Casas-Solvas
,
Tiddo J. Mooibroek
,
Shugantan Sandramurthy
,
Joshua D. Howgego
,
Anthony P. Davis*
Further Information

Publication History

Received: 09 July 2014

Accepted: 06 August 2014

Publication Date:
02 October 2014 (online)


Abstract

Pyrene-2-carboxylic acid is a versatile intermediate for introducing the unusual 2-pyrenyl unit into functional organic molecules. A classical preparation for this molecule has been revised and improved to give a robust and efficient three-step process. The method has been applied on a multigram scale to give pyrene-2-carboxylic acid in >70% overall yield from pyrene.

Supporting Information

 
  • References and Notes

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  • 21 Preparation of 1-(o-Carboxybenzoyl)pyrene (2): AlCl3 (15.4 g, 116 mmol) was added to a suspension of pyrene (9.4 g, 46 mmol) and phthalic anhydride (6.9 g, 46 mmol) in anhyd CH2Cl2 (280 mL) under N2 atmosphere. The mixture was heated under reflux for 3 h. The solvent was then evaporated and the residue was cooled to 0 °C and suspended in H2O (500 mL). The pH of the solution was adjusted to 0–1 by adding concd aq HCl (20 mL), and the solid was isolated by filtration, washed with ice water (2 × 150 mL) and dried by addition–evaporation of toluene. The solid was suspended in glacial AcOH (500 mL) and heated at 130 °C for 5 min, after which the insoluble material was removed by hot filtration and washing with hot glacial AcOH (3 × 50 mL). The filtrate was poured into ice water (1 L) and the resulting solid was isolated by filtration, washed with ice water (2 × 100 mL) and dried by addition–evaporation of toluene to give 2 (15.96 g, 45.6 mmol, 98%) as a bright yellow powder; mp 224–225 °C (Lit.9 mp 225–226 °C); Rf = 0.35 (CH2Cl2–MeOH, 10:1). FTIR (ATR): 3039, 2910, 2786, 2617, 2546, 2492, 1714, 1591, 1578, 1234, 941, 838, 708 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 13.01 (br s, 1 H, COOH), 9.18 (d, 3 J = 9.2 Hz, 1 H, H-10), 8.41 (d, 3 J = 9.2 Hz, 1 H, H-9), 8.40 (br d, J = 7.6 Hz, 2 H, H-6, H-8), 8.32 (d, 3 J = 9.1 Hz, 1 H, H-5), 8.21 (d, 3 J = 8.1 Hz, 1 H, H-3), 8.18 (d, 3 J = 9.1 Hz, 1 H, H-4), 8.15 (t, 3 J = 7.6 Hz, 1 H, H-7), 7.99 (br d, J = 7.6 Hz, 1 H, H-6′), 7.83 (d, 3 J = 8.1 Hz, 1 H, H-2), 7.77 (ddd, J = 7.6, 7.2, 1.2 Hz, 1 H, H-4′), 7.71 (ddd, J = 7.6, 7.2, 1.2 Hz, 1 H, H-5′), 7.63 (br d, J = 7.2 Hz, 1 H, H-3′). 13C NMR (125 MHz, DMSO-d 6): δ = 198.7 (CO), 167.5 (COOH), 142.9 (C-2′), 133.5 (C-3a), 132.1 (C-4′), 131.1 (C-1), 130.8 (C-1′), 130.6 (C-5a), 130.3 (C-5′), 130.0 (C-8a), 129.9 (C-5), 129.8 (C-10a), 129.7 (C-6′), 129.5 (C-9), 128.9 (C-2), 128.5 (C-3′), 127.2 (C-4), 126.8 (C-7), 126.7 (C-6), 126.3 (C-8), 125.1 (C-10), 124.1 (C-3a1), 123.9 (C-3), 123.3 (C-5a1). HRMS (ESI): m/z [M – H] calcd for C24H13O3: 349.0870; found: 349.0881.
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  • 23 Preparation of 1,2-Phthaloylpyrene (3): 1-(o-Carboxy-benzoyl)pyrene (2; 16.0 g, 45.7 mmol) was suspended in chlorobenzene (300 mL) under N2 atmosphere, and PCl5 (14.44 g, 69.3 mmol) and AlCl3 (9.58 g, 71.9 mmol) were added. The resulting dark green mixture was heated under reflux for 2.5 h. The solvent was removed by evaporation and the residue was cooled to 0 °C and suspended in H2O (450 mL). The dark red precipitate was collected by filtration, washed with H2O (4 × 100 mL), toluene was added and evaporated (3 × 200 mL), and the resulting solid was further dried in vacuo (overnight) to give 3 (15.5 g, ca. quantitative). This material appeared pure by 1H NMR and was used directly in the next step. Trace amounts of a highly coloured contaminant were removed by flash chromatog-raphy (CH2Cl2–hexane, 1:1 → CH2Cl2–MeOH, 10:1) to give a sample for characterisation; mp 255–256 °C (Lit.9 254 °C); Rf = 0.51 (EtOAc–hexane, 1:4). FTIR (ATR): 3119, 3024, 2804, 1716, 1661, 1615, 1443, 1392, 620 cm–1. 1H NMR (500 MHz, CDCl3): δ = 9.87 (d, 3 J = 9.8 Hz, 1 H, H-10), 8.90 (s, 1 H, H-3), 8.34 (dd, J = 7.6, 0.9 Hz, 1 H, H-3′), 8.28 (dd, J = 7.6, 0.9 Hz, 1 H, H-6′), 8.24 (d, 3 J = 9.8 Hz, 1 H, H-9), 8.21 (d, 3 J = 7.5 Hz, 1 H, H-8), 8.18 (d, 3 J = 7.5 Hz, 1 H, H-6), 8.13 (d, 3 J = 8.9 Hz, 1 H, H-5), 8.09 (d, 3 J = 8.9 Hz, 1 H, H-4), 8.02 (t, 3 J = 7.5 Hz, 1 H, H-7), 7.80 (dt, J = 7.5, 1.2 Hz, 1 H, H-4′), 7.75 (dt, J = 7.5, 1.2 Hz, 1 H, H-5′). 13C NMR (125 MHz, CDCl3): δ = 185.9 [C-1(CO)C-2′], 184.3 [C-2(CO)C-1′], 136.2 (C-2′), 135.0 (C-3a), 134.4 (C-4′), 133.5 (C-5′), 133.1 (C-1′), 132.0 (C-2), 131.9 (C-9), 131.8 (C-5a), 131.7 (C-10a), 131.2 (C-5), 131.0 (C-8a), 128.3 (C-4), 127.8 (C-7), 127.7 (C-3a1), 127.6 (C-3′), 127.5 (C-6), 127.1 (C-8), 126.8 (C-6′), 126.5 (C-10), 124.3 (C-1), 124.2 (C-3), 123.8 (C-5a1). HRMS (EI+): m/z [M]+ calcd for C24H12O2: 332.0837; found: 332.0842.
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  • 28 Preparation of Pyrene-2-carboxylic Acid (4): Crude 3 (10 g) was suspended in 1,2-dimethoxyethane (140 mL). H2O (3 equiv per carbonyl group, 3.3 mL, 180.6 mmol) was added, then potassium tert-butoxide (10 equiv per carbonyl group, 67.6 g, 602 mmol) was added portionwise with vigorous stirring to ensure that a fine suspension was maintained throughout the addition. The mixture was vigorously stirred under reflux for 7 h and the solvent was evaporated. The residue was cooled to 0 °C, suspended in H2O (1 L), and acidified to pH 1–2 with concd aq HCl. The resulting solid was removed by filtration, suspended in H2O (2 L), stirred overnight, collected by filtration, washed with H2O (2 × 250 mL) and dried in vacuo. The material was ground into a fine powder then slowly added to CH2Cl2–MeOH (1:1, 250 mL), forming a suspension. Silica (30 g) was then added and the mixture was concentrated to dryness. The resulting fine powder was carefully loaded (band height = 1.8 cm) on a short column (diameter = 6.5 cm, ca. 300 mL, silica gel, height = 5 cm) packed with CH2Cl2–hexane (1:1). Pyrene (1; 0.79 g, 3.9 mmol, 13% from 2) and starting diketone 3 (0.96 g, 2.9 mmol, 10% from 2) eluted with CH2Cl2–hexane (1:1, 500 mL) and CH2Cl2 (1.5 L), respectively. The polarity of the eluent was increased to 10% MeOH in CH2Cl2 (150 mL per 2.5% increment) and finally to CH2Cl2–MeOH–30% aq NH3 (90:9:1, 2 L) to elute the product. Elution of diketone 3 (bright yellow/orange fluorescence) and product 4 (dark purple fluorescence) could be monitored by irradiating the column with a 365 nm UV lamp. Pyrene-2-carboxylic acid (4; 5.46 g, 22.2 mmol, 75% from 2) was obtained as a light grey solid; mp 326 °C (Lit.9 326 °C); Rf = 0.33 (CH2Cl2–MeOH, 10:1). FTIR (ATR): 2596, 1685, 1305, 1247, 896, 840, 820, 704 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 13.31 (br s, 1 H, COOH), 8.86 (s, 2 H, H-1, H-3), 8.33 (d, 3 J = 7.6 Hz, 2 H, H-6, H-8), 8.31 (d, 3 J = 9.2 Hz, 2 H, H-4, H-10), 8.24 (d, 3 J = 9.2 Hz, 2 H, H-5, H-9), 8.13 (t, 3 J = 7.6 Hz, 1 H, H-7). 13C NMR (100 MHz, DMSO-d 6): δ = 167.8 (COOH), 131.2 (C-5a, C-8a), 130.5 (C-3a, C-10a), 128.1 (C-2), 128.0 (C-5, C-9), 127.7 (C-4, C-10), 127.3 (C-7), 125.8 (C-3a1), 125.5 (C-1, C-3, C-6, C-8), 123.3 (C-5a1). HRMS (ESI): m/z [M – H] calcd for C17H9O2: 245.0608; found: 245.0615.