Multi-functionalized 2,2′:6′,2′′-Terpyridines

Abstract

In this contribution, Stille-type cross-coupling procedure is shown to be an easy and universal way to prepare a variety of functionalized terpyridines. They may be functionalized in one step with different substituents at the outer pyridine rings and at the 4′-position of the centered ring, leading to multi-functionalized compounds. The initially obtained methylester and ethylester groups may be simply converted into bromomethyl and hydroxymethyl groups, which allow further functionalization reactions.

terpyridine synthesis - Stille cross-coupling - functional groups - multidentate ligands - multifunctionality

References

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<A NAME="RG04102ST-11">11</A>

Dimethyl-2,2′:6′,2′′-terpyridines. Route 1: The methyl-2-tributylstannylpyridine 2a-c (3 g, 7.85 mmol), 2,6-dibromopyridine 1 (0.75 g, 3.17 mmol) and tetrakis-(triphenylphosphine)-palladium(0) (0.29 g, 6.0 mol%) are refluxed for 4 days in absolute toluene (50 mL). After removal of the solvent, the black residue is treated with aq HCl (6 M). The suspension is extracted with CH₂Cl₂ and the organic phase is washed again with HCl (6 M). The aq solution is added dropwise into cold aq ammonia (10%). The precipitate is filtered off, dissolved in CH₂Cl₂, dried over Na₂SO₄, the solvent is removed again and the residue is crystallized from ethyl acetate. Route 2: 2,6-Bis(trimethyl-stannyl)pyridine 6 (12.23 g, 7.66 mmol), the 2-bromo-methylpyridine 7a-c (3.29 g, 19.15 mmol) and tetrakis-(triphenylphosphine)-palladium(0) (0.6 g, 6 mol%) are refluxed in dry toluene (70 mL) for 72 h at 110 °C. The workup is identical to route 1. 3: White crystals. Mp 186 °C. ¹H NMR (CDCl₃): δ = 2.39 (s, 6 H, CH ₃ ), 7.17 (dd, J = 4.96 Hz, 0.77 Hz, 2 H, H^{5,5 ′′ )}, 7.94 (t, J = 8.01 Hz, 1 H, H^{4 ′}), 8.41 (s, 2 H, H^{3,3 ′′}), 8.42 (d, J = 8.01 Hz, 2 H, H^{3 ′ ,5 ′}), 8.56 (d, J = 4.95 Hz, 2 H, H^{6,6 ′′}). C₁₇H₁₅N₃ (261.32): Calcd C, 78.13; H, 5.79; N, 16.08. Found: C, 78.04; H, 6.00; N, 15.92. 4: White crystals (Lit. [15] 67%). Mp 173 °C (Lit. [15] 169-171 °C, Lit. [15] 174-175 °C). ¹H NMR (CDCl₃): δ = 2.39 (s, 6 H, CH ₃), 7.63 (dd, J = 8.01, 2.28 Hz, 2 H, H^{4,4 ′′}), 7.91 (t, J = 7.82 Hz, 1 H, H^{4 ′}), 8.38 (d, J = 7.62 Hz, 2 H, H^{3 ′ ,5 ′}), 8.49 (d, J = 8.40 Hz, 2 H, H^{3,3 ′′}), 8.50 (s, 2 H, H^{6,6 ′′}). C₁₇H₁₅N₃ (261.32): Calcd C, 78.13; H, 5.79; N, 16.08. Found: C, 77.92; H, 5.73; N, 16.07. 5: White crystals. Mp 171 °C (Lit. [16] >250 °C). ¹H NMR (CDCl₃): δ = 2.65 (s, 6 H, CH ₃ ), 7.18 (d, J = 7.63 Hz, 2 H, H^{5,5 ′′}), 7.73 (t, J = 7.63 Hz, 2 H, H^{4,4 ′′}), 7.93 (t, J = 8.01 Hz, 1 H, H^{4 ′}), 8.41 (d, J = 7.63 Hz, 2 H, H^{6,6 ′′}), 8.47 (d, J = 8.01 Hz, 2 H, H^{3 ′ ,5 ′}). C₁₇H₁₅N₃ (261.32): Calcd C, 78.13; H, 5.79; N, 16.08. Found: C, 78.42; H, 5.63; N, 16.16.

<A NAME="RG04102ST-12">12</A> Schubert US. Eschbaumer C. Org. Lett.  1999,  1:  1027 

<A NAME="RG04102ST-13">13</A> See also: Houghton MA. Bilyk A. Harding MM. Turner P. Hambley TW. J. Chem. Soc., Dalton Trans.  1997,  2725 

See also:

<A NAME="RG04102ST-14A">14a</A> Cardenas DJ. Sauvage J.-P. Synlett  1996,  9:  916 

<A NAME="RG04102ST-14B">14b</A> Schubert US. Eschbaumer C. Hochwimmer G. Polym. Mater. Sci. Eng.  1999,  80:  193 

<A NAME="RG04102ST-15">15</A> Constable EC. Baum G. Bill E. Dyson R. Eldik R. Fenske D. Kaderli S. Morris D. Neubrand A. Neuburger M. Smith DR. Wieghardt K. Zehnder M. Zuberbühler AD. Chem.-Eur. J.  1999,  5:  498 

<A NAME="RG04102ST-16A">16a</A> Fallahpour R.-A. Synthesis  2000,  8:  1138 

<A NAME="RG04102ST-16B">16b</A> Ulrich G. Bedel S. Picard C. Tisnes B. Tetrahedron Lett.  2001,  42:  6113 

<A NAME="RG04102ST-17">17</A> For a similar reaction see: Fallahpour R.-A. Synthesis  2000,  12:  1665 

<A NAME="RG04102ST-18">18</A>

5′,5′′-Bis(bromomethyl)-2,2′:6′,2′′-terpyridine-4′-ethylester 17 (0.5 g, 1.0 mmol) is dissolved in pure acetic acid (20 mL) and dry sodium acetate (82 mg, 1.0 mmol) is added. The mixture is heated under reflux for 1 h. After cooling, the solution is added dropwise to cold aq ammonia (10%). The oily product is extracted with CH₂Cl₂, washed with brine, dried and crystallized from ethyl acetate after removal of the solvent. Yield 0.31 g (71%). Mp 231 °C. ¹H NMR (CDCl₃): δ = 1.42 (t, J = 6.06 Hz, 3 H, OCH₂CH ₃), 2.10 (s, 6 H, OCOCH ₃), 4.45 (q, J = 7.06 Hz, 2 H, OCH ₂CH₃), 5.17 (s, 4 H, Ar-CH ₂ O), 7.83 (dd, J = 8.01, 2.20 Hz, 2 H, H^{4,4 ′′}), 8.50 (d, J = 8.02 Hz, 2 H, H^{3,3 ′′}), 8.57 (s, 2 H, H^{6,6 ′′}), 8.90 (s, 2 H, H^{3 ′ ,5 ′}). C₂₄H₂₃N₃O₆ (449.46): Calcd C, 64.13; H, 5.16; N, 9.35. Found: C, 64.55; H, 4.80; N, 9.01.