C₃-Symmetric Pyridine and Bipyridine Derivatives: Simple Preparation by Cyclocondensation and 2D Self-Assembly at a Solution–Graphite Interface

Dedicated to Prof. K. Peter C. Vollhardt

Abstract

The efficient preparation of four C₃-symmetric (star-shaped) pyridine and bipyridine derivatives is reported. The key steps are Suzuki couplings of 4-pyridyl nonaflates with 4-acetyl-phenylboronic acid followed by an acid-promoted cyclocondensation reaction converting the methyl ketone moiety into the central benzene ring of the target compounds. Based on STM studies at a graphite–solution interface the two-dimensional arrangements of the compounds are discussed, showing the influence of the pyridine substitution pattern.

Key words

allenes - heterocycles - cyclization - coupling - self-assembly - scanning tunneling microscopy - highly oriented pyrolytic graphite

• References and Notes

• 1 Current address: University of Oxford, Department of Chemistry, South Parks Road, Oxford, OX1 3TA, UK.
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• 17 We expect order-disorder transitions to occur at elevated temperatures, but their study goes beyond the scope of the present work.Typical and Representative Experimental Procedures Typical Procedure A for Suzuki Coupling Reactions To a degassed solution of the corresponding nonaflate 5 (1 equiv), 4-acetylphenyl boronic acid (1.2 equiv), and K₂CO₃ (1.0 equiv) in DMF (5 mL/mmol) were added Pd(OAc)₂ (5 mol%) and Ph₃P (20 mol%). The resulting mixture was heated to 70 °C for 8 h. After cooling to room temperature and addition of water, the mixture was extracted with diethyl ether. The combined organic layers were washed with water and brine, dried with Na₂SO₄, filtered, and concentrated to dryness. The residue was purified by chromatography on silica gel (hexanes–ethyl acetate) to give the desired Suzuki coupling product 6. Typical Procedure B for Cyclocondensation Reactions To a stirred solution of the aryl methyl ketone derivative 6 in ethanol–toluene mixture (5:1, 6 mL) was added SiCl₄ (1.5 or 15 equiv) at 0 °C. After complete addition, the mixture was allowed to warm to room temperature and was then heated to 55 °C for 16 h. After cooling to room temperature sat. aq NH₄Cl solution and CH₂Cl₂ were added, the phases were separated, and the aqueous phase was extracted with CH₂Cl₂ and washed with brine. The combined organic layers were dried with Na₂SO₄ and concentrated to dryness to give product 7. Preparation of 1-{4-[3-Methoxy-2-octyl-6-(trifluoromethyl)pyridin-4-yl]phenyl}ethanone (6b) According to general procedure A, nonaflate 5b (587 mg, 1.00 mmol), 4-acetylphenyl boronic acid (197 mg, 1.20 mmol), K₂CO₃ (135 mg, 1.00 mmol), Pd(OAc)₂ (11 mg, 0.05 mmol), and Ph₃P (52 mg, 0.20 mmol) in DMF (5 mL) gave compound 6b (330 mg, 81%) as viscous oil after purification on silica gel (hexanes–ethyl acetate = 5:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.86 (t, J = 7.1 Hz, 3 H, Me), 1.24–1.36 (m, 8 H, CH₂), 1.72–1.77 (m, 2 H, CH₂), 2.64 (s, 3 H, Me), 2.91 (m_c, 2 H, CH₂), 3.42 (s, 3 H, OMe), 7.48 (s, 1 H, Py), 7.71 (d^*, J = 8.4 Hz, 2 H, Ar), 8.05 (d^*, J = 8.4 Hz, 2 H, Ar) ppm; * only the largest coupling constant of the AA′XX′ system is given. ¹³C NMR (125.8 MHz, CDCl₃): δ = 14.1, 22.7, 26.7, 29.0, 29.3, 29.5, 29.7, 31.9, 32.7 (Me, CH₂), 61.0 (OMe), 119.9 (Ar), 121.6 (q, ¹ J _CF = 273.5 Hz, CF₃), 128.8, 129.0, 137.3, 140.1, 140.9 (Ar), 142.9 (q, ² J _CF = 34.6 Hz, C-6), 153.7, 159.1 (Ar), 197.5 (C=O) ppm. IR (neat): ν = 3000 (=C–H), 2950–2860 (C–H), 1690, 1600 (C=C), 1460, 1370 cm^–1. HRMS (80 eV): m/z calcd for C₂₃H₂₈F₃NO₂: 407.2067; found: 407.2063. Preparation of Compound 7b According to general procedure B, aryl methyl ketone 6b (106 mg, 0.26 mmol) and SiCl₄ (0.45 mL, 3.90 mmol) gave compound 7b (72 mg, 71%) as yellow wax after purification on silica gel (hexanes–ethyl acetate = 3:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.89 (t, J = 6.9 Hz, 9 H, Me), 1.22–1.50 (m, 30 H, CH₂), 1.77–1.83 (m, 6 H, CH₂), 2.91 (m_c, 6 H, CH₂), 3.53 (s, 9 H, OMe), 7.57 (s, 3 H, Ar), 7.78 (d*, J = 8.4 Hz, 6 H, Ar), 7.87 (d*, J = 8.4 Hz, 6 H, Ar), 7.94 (s, 3 H, Ar) ppm; * only the largest coupling constant of the AA′XX′ system is given. ¹³C NMR (125.8 MHz, CDCl₃): δ = 14.2, 22.7, 29.2, 29.3, 29.5, 29.8, 32.0, 32.8 (Me, CH₂), 60.9 (OMe), 120.1 (Ar), 121.8 (q, ¹ J _CF = 273.0 Hz, CF₃), 125.6, 127.8, 129.3, 135.0, 141.48, 141.50, 141.8 (Ar), 142.9 (q, ² J _CF = 34.2 Hz, C-6), 153.8, 158.9 (Ar) ppm. IR (neat): ν = 3030 (=C–H), 2950–2855 (C–H), 1600 (C=C), 1540, 1520, 1460 cm^–1. HRMS (80 eV): m/z calcd for C₆₉H₇₈F₉N₃O₃: 1167.5894; found: 1167.5894.