Synlett 2013; 24(19): 2609-2613
DOI: 10.1055/s-0033-1339879
letter
© Georg Thieme Verlag Stuttgart · New York

Transfer Reagents 4: Retro-Diels–Alder Routes to 3,6-Di(2-pyridyl)pyridazinonorbornadiene, a Test Bed for the Relative Dienofugacity of Isobenzofuran, Isoindole, and Anthracene

Davor Margetić*
a  Laboratory for Physical-organic Chemistry, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia   Fax: +385(1)4561008   Email: margetid@irb.hr
,
Douglas N. Butler
b  Centre for Molecular Architecture, Central Queensland University, Rockhampton, Queensland 4702, Australia
,
Ronald N. Warrener
b  Centre for Molecular Architecture, Central Queensland University, Rockhampton, Queensland 4702, Australia
› Author Affiliations
Further Information

Publication History

Received: 04 July 2013

Accepted after revision: 02 September 2013

Publication Date:
16 October 2013 (online)


Abstract

Norbornadiene cycloadducts reacted with 3,6-di(2-pyridyl)-s-tetrazine to produce pyridazines (diene-protected alkenes), following dehydrogenation (by DDQ) of the intermediate dihydropyridazines. The title 3,6-di(2-pyridyl)-pyridazinonorbornadiene was produced under flash vacuum pyrolysis conditions by ejection of anthracene (590 °C), isobenzofuran (630 °C) or isoindole (580 °C) from the corresponding pyridazines, establishing the following dienofugacity order: isoindole > anthracene > isobenzofuran. Calculations of the respective retro-Diels–alder activation energies at the B3LYP/6-31G* level of theory correctly predicted the experimentally found isobenzofuran > anthracene > isoindole order. Cavity bis-3,6-di(2-pyridyl)-pyridazine (dppn) and chevron-shaped bis-dppn ligands were prepared from the title compound by coupling at the norbornene π-bond.

Supporting Information

 
  • References and Notes

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  • 19 The NMR spectra were recorded in CDCl3 solutions containing TMS as internal standard on a Bruker AMX-300 or a Bruker Avance DPX-400 NMR spectrometer fitted with a gradient quattro nucleus probe. Melting points were determined using a Gallenkamp digital melting point apparatus and are uncorrected. The high-resolution mass spectra were recorded on a Micromass Platform II single quadrupole AutoSpec instrument (ESMS, electrospray mass spectrometry in CH2Cl2). Radial chromatography was carried out with a chromatotron, model No. 79245T, using 1 mm plates with silica gel 60F254 as the stationary phase. FVP experiments were conducted under vacuum (0.001 mbar) in an 600 × 10 mm Pyrex tube packed with broken glass and heated by a horizontally mounted ‘Thermolyne’ model 21100 tube furnace. Products were collected at the end of the furnace on the cooler part of the tube. Volatile products were condensed in a liquid nitrogen trap. New compounds were isolated by radial chromatography and gave satisfactory spectroscopic and analytical data (accurate mass). Compound 9 was prepared by a previously published procedure14 by reaction of anthracene and norbornadiene. Compounds 10 and 11 were prepared by a procedure analogous for the benzo crown ether derivative of 10.18,19 1α,2β,3β,6β,7β,8α-15-Oxatetracyclo[6.6.1.13,6.02,7.09,14]-hexadeca-4,9,11,13-tetraene (10) A solution of 1,4-dihydro-1,4-epoxynaphthalene (1.0 g, 6.94 mmol) and cyclopentadiene (2.00 g, 30.3 mmol) in CHCl3 (5 mL) was heated at 70 °C for 14 h in a glass high-pressure vessel. The solvent was removed under vacuum, and cyclopentadiene excess was removed under high vacuum to afford 10 as a yellow-colored oil (1.30 g, 89.2%). 1H NMR (300 MHz, CDCl3): δ = 1.37 (d, J = 8.0 Hz, 1 H, CH2), 1.54 (dt, J = 8.0, 1.8 Hz, 1 H, CH2), 2.37 (t, J = 1.8 Hz, 2 H, H endo ), 2.92 (q, J = 1.8 Hz, 1 H, Hbridgehead-C), 4.96 (s, 2 H, Hbridgehead-O), 6.13 (t, J = 1.5 Hz, 2 H, =CH), 7.09 (dd, J = 5.5, 3.1 Hz, 2 H, HAr), 7.17 (dd, J = 5.5, 3.1 Hz, 2 H, HAr). 13C NMR (75 MHz, CDCl3): δ = 44.4 (C endo ), 49.3 (Cbridgehead-C), 53.7 (CH2), 80.2 (Cbridgehead-O), 119.0 (=CH), 126.7 (CArH), 134.7 (CArH), 148.7 (CArq). ESI-HRMS: m/z calcd for C15H14O1 [M]+: 210.1045; found: 210.1046. 1α,2β,3β,6β,7β,8α-15-Azatetracyclo[6.6.1.13,6.02,7. 09,14]-hexadeca-4,9,11,13-tetraene (11) A solution of 1,4-dihydro-1,4-iminonaphthalene (2.0 g, 13.9 mmol) and freshly distilled cyclopentadiene (5.00 g, 75.6 mmol) in CHCl3 (10 mL) was heated at 70 °C overnight in a glass high-pressure vessel. The solvent was removed under vacuum and cyclopentadiene excess under high vacuum to afford 11 as a black-colored oil (2.10 g, 72.3%). 1H NMR (300 MHz, CDCl3): δ = 1.40 (d, J = 8.0 Hz, 1 H, CH2), 1.57 (d, J = 8.0 Hz, 1 H, CH2), 2.37 (s, 2 H, H endo ), 2.92 (s, 2 H, Hbridgehead-C), 3.68 (br s, 1 H, NH), 4.23 (s, 2 H, Hbridgehead-N), 6.25 (s, 2 H, =CH), 7.02–7.06 (m, 2 H, HAr), 7.13–7.16 (m, 2 H, HAr). 13C NMR (75 MHz, CDCl3): δ = 43.0 (C endo ), 49.1 (Cbridgehead-C), 55.1 (CH2), 63.0 (Cbridgehead-N), 119.3 (=CH), 125.8 (CArH), 136.2 (CArH), 153.1 (CArq). ESI-HRMS: m/z calcd for C15H15N1 [M]+: 209.1204; found: 209.1195. 5,8-Di(2-pyridyl)-6,7-diaza-1α,2β,3α,10α,11β,12α-octacyclo[10.6.6.13,10.02,11.04,9.013,18.019,24]pentacosa-4,6,8,13,15,17,19,21,23-nonaene (14) A solution of alkene 9 (300 mg, 1.11 mmol) in CHCl3 (10 mL) was treated with s-tetrazine (260 mg, 1.11 mmol) and refluxed overnight. To this mixture, DDQ (480 mg, 2.11 mmol) was added and refluxed overnight. Insoluble material was removed by filtration, and the residual liquid was washed with 3 M NaOH (3×), then with H2O, dried (MgSO4), and the solvent was removed under vacuum to afford 14 as a brown-colored powder (303 mg, 58.8%, mp 270–272 °C). 1H NMR (300 MHz, CDCl3): δ = 0.23 (d, J = 10.7 Hz, 1 H, CH2), 1.08 (d, J = 10.7 Hz, 1 H, CH2), 2.26 (s, 2 H, H endo ), 4.24 (s, 2 H, Hbridgehead-C), 4.46 (s, 2 H, Hbridgehead-2.2.2), 6.99–7.01 (m, 2 H, Ar), 7.19–7.22 (m, 2 H, HAr), 7.24–7.27 (m, 2 H, HAr), 7.34–7.39 (m, 4 H, HAr), 7.87 (dd, J = 6.4, 1.3 Hz, 2 H, HAr), 8.51 (dt, J = 7.1, 0.8 Hz, 2 H, HAr), 8.85 (d, J = 4.4 Hz, 2 H, HAr). 13C (NMR (75 MHz, CDCl3): δ = 41.2 (CH2), 46.1 (Cbridgehead-norb), 46.8 (C endo ), 48.8 (Cbridgehead-anthrac), 123.3, 123.9, 124.0, 125.2, 126.0, 126.8, 137.1, 142.7 (CArq), 145.4 (CArq), 149.6, 151.1 (CArq), 151.8 (CArq), 156.2 (CArq). ESI-HRMS: m/z calcd for C33H24N4 [M]+: 476.2001; found: 476.2001. 16,19-Di(2-pyridyl)-14-oxa-1β,2β,3α,10α,11β,12β-hexacyclo[10.6.1.13,10.02,11.04,9.015,20]icosa-4,6,8,15,17,19-hexaene (16) A solution of alkene 10 (430 mg, 2.05 mmol) in CHCl3 (5 mL) was treated with s-tetrazine (483 mg, 2.05 mmol) and refluxed overnight. To this mixture, DDQ (900 mg, 4.0 mmol) was added and refluxed overnight. Insoluble material was removed by filtration, and the residual liquid was washed with 3 M NaOH (3×), then with H2O, dried (MgSO4), and the solvent was removed under vacuum to afford a brown-colored oil, which was subjected to radial chromatography (CHCl3–MeOH = 10:1) to afford 16 as a colorless solid (331 mg, 38.8%, mp 202–205 °C). 1H NMR (300 MHz, CDCl3): δ = 1.81 (d, J = 9.3 Hz, 1 H, CH2), 1.93 (d, J = 9.3 Hz, 1 H, CH2), 2.86 (dd, J = 3.0, 1.6 Hz, 2 H, H endo ), 4.63 (d, J = 1.1 Hz, 2 H, Hbridgehead-C), 5.10 (s, 2 H, Hbridgehead-O), 7.04–7.07 (m, 2 H, HAr), 7.14–7.17 (m, 2 H, HAr), 7.38–7.41 (m, 2 H, HAr), 7.90 (dt, J = 9.0, 1.8 Hz, 2 H, HAr), 8.69 (d, J = 8.0 Hz, 2 H, Ar), 8.84 (dd, J = 4.7, 0.6 Hz, 2 H, Ar). 13C NMR (75 MHz, CDCl3): δ = 40.5, 50.1, 53.2 (CH2), 79.6 (Cbridgehead-O), 119.5, 112.8, 120.1, 123.4, 126.6, 139.0, 149.3, 149.6, 150.1, 155.4, 160.1. ESI-HRMS: m/z calcd for C27H20N4O1 [M]+: 416.1637; found: 416.1638. 16,19-Di(2-pyridyl)-14-aza-1β,2β,3α,10α,11β,12β-hexacyclo[10.6.1.13,10.02,11.04,9.015,20]icosa-4,6,8,15,17,19-hexaene (18) A solution of alkene 11 (870 mg, 4.16 mmol) in CHCl3 (5 mL) was treated with s-tetrazine (980 mg, 4.16 mmol) and refluxed overnight. To this mixture, DDQ (1.589 mg, 7.0 mmol) was added and refluxed overnight. Insoluble material was removed by filtration, and the residual liquid was washed with 3 M NaOH (3×), then with H2O, dried (MgSO4), and the solvent was removed under vacuum to afford a black-colored oily residue, which was subjected to radial chromatography (PE–EtOAc = 1:1, then the solvent polarity was gradually increased to EtOAc) to afford 18 as a black-colored solid (129 mg, 7.5%, mp 109–110 °C). 1H NMR (300 MHz, CDCl3): δ = 1.68 (br s, 1 H, NH), 1.80 (d, J = 9.2 Hz, 1 H, CH2), 1.96 (d, J = 9.2 Hz, 1 H, CH2), 2.69 (m, 2 H, H endo ), 4.22 (s, 2 H, Hbridgehead-C), 4.64 (s, 2 H, Hbridgehead-N), 6.99–7.01 (m, 2 H, HAr), 7.11–7.13 (m, 2 H, HAr), 7.39–7.43 (m, 2 H, HAr), 7.88–7.93 (m, 2 H, HAr), 8.63–8.77 (m, 4 H, HAr). 13C NMR (75 MHz, CDCl3): δ = 45.0 (C endo ), 48.6 (Cbridgehead-C), 53.0 (CH2), 61.8 (Cbridgehead-N), 119.5, 122.0, 123.8, 125.6, 137.0, 148.3, 149.4, 151.9, 152.9, 159.0. ESI-HRMS: m/z calcd for C27H21N5 [M]+: 415.1797; found: 415.1794. 3,6-Di(2-pyridyl)-4,5-diaza-1α,8α-tricyclo[6.2.1.02,7]-undeca-2,4,6,9-tetraene (3) Compound 14 (50 mg 0.108 mmol) was subjected to FVP at 590 °C to give two fractions, one colorless solid (anthracene) and 3 as a brown-colored solid (14 mg, 43.5%). 1H NMR (300 MHz, CDCl3): δ = 2.36 (td, J = 7.9, 1.5 Hz, 1 H, CH2), 2.41 (td, J = 7.9, 1.5 Hz, 1 H, CH2), 5.16–5.18 (m, 2 H, Hbridgehead), 6.99 (t, J = 1.9 Hz, 2 H, =CH), 7.35 (dd, J = 6.3, 1.3 Hz, 1 H, HAr), 7.38 (dd, J = 6.3, 1.3 Hz, 1 H, HAr), 7.88, (td, J = 8.7, 1.8 Hz, 2 H, HAr), 8.56 (td, J = 8.0, 0.9 Hz, 2 H, HAr), 8.76–8.79 (m, 2 H, HAr). These values are consistent with those reported in the literature.14 8,11-Di(2-pyridyl)-9,10-diazabicyclo[6.4.0]undeca-2,4,7,9,11-pentaene (8) Compound 24 (50 mg, 0.108 mmol) was subjected to FVP at 670 °C (in this experiment pyrolysis tube was not packed with broken glass) to give a black-colored oil, which was subjected to radial chromatography (CHCl3–MeOH = 10:1) to afford 8 as a brown-colored oil (9 mg, 30.6%). 1H NMR (300 MHz, CDCl3): δ = 3.12 (d, J = 5.8 Hz, CH2, 2 H), 6.10–6.18 (m, 1 H, =CH), 6.39 (dd, J = 7.9, 5.3 Hz, 1 H, =CH), 6.95 (dd, J = 10.5, 5.3 Hz, 1 H, =CH), 7.38–7.43 (m, 2 H, HAr), 7.72 (d, J = 11.6 Hz, 1 H, HAr), 7.86–7.91 (m, 2 H, HAr), 8.02 (d, J = 7.8 Hz, 1 H, =CH), 8.20 (d, J = 7.8 Hz, 1 H, HAr), 8.78 (d, J = 4.2 Hz, 2 H, HAr). 13C NMR (75 MHz, CDCl3): δ = 30.0 (CH2), 123.7, 125.1, 125.8, 127.3, 128.9, 126.1, 130.8, 132.7, 136.2, 137.6, 149.1, 149.2, 156.4, 156.8, 157.9. ESI-HRMS: m/z calcd for C19H12N4 [M]+: 298.1218; found: 298.1198. 3,14,18,29-Tetra(carbomethoxy)-7,10,22,5-tetra(2-pyridyl)-32,34-dioxa-8,9,23,24-tetraaza-1α,2β,4β,5α,12α, 13β,15β,16α,17β,19β,20α,27α,28β,30β-dodecacyclo-[14.14.1.13,14.15,12.118,29.120,27.02,15.04,13.06,11.017,30.019,28.021,26]-pentatriaconta-6,8,10,21,23,25-hexaene (21) A solution of alkene 3 (100 mg, 0.336 mmol) and bisepoxide 20 (68 mg, 0.167 mmol) in THF (2 mL) was heated overnight at 140 °C in a sealed high-pressure glass vessel. The solvent was removed under vacuum, and the residue was subjected to radial chromatography (PE–EtOAc = 1:1, then the solvent polarity was gradually increased to EtOAc), to afford 21 as a brown-colored solid (128 mg, 76%, mp >350 °C). 1H NMR (300 MHz, CDCl3): δ = 1.34 (d, J = 9.1 Hz, 2 H, CH2), 2.00 (s, 4 H, H endo ), 2.04 (s, 2 H, CH2), 2.22 (s, 2 H, Hbridgehead), 2.42 (s, 4 H, H endo ), 2.82 (d, J = 9.1 Hz, 2 H, CH2), 3.96 (s, 12 H, CO2Me), 4.36 (s, 4 H, Hbridgehead-C), 7.39–7.41 (m, 4 H, HAr), 7.92 (dt, J = 6.1, 0.7 Hz, 4 H, HAr), 8.58 (d, J = 6.1 Hz, 4 H, HAr), 8.71 (d, J = 5.6 Hz, 4 H, HAr). 13C NMR (75 MHz, CDCl3): δ = 28.7 (CH2), 41.2, 42.3 (CH2), 45.6, 52.6, 54.1, 56.6, 89.8 (Cbridgehead-O), 122.1, 123.3, 137.4, 149.3, 149.8, 152.3, 155.0, 169.2 (C=O). ESI-HRMS: m/z calcd for C57H48N8O10: 1004.3493 [M]+, 1027.3391 [M + Na]+, 1005.3557 [M + H]+; found: 1027.3352. 3,6,10,13-Tetra(2-pyridyl)-4,5,11,2-tetraaza-1α,8α-tetracyclo[6.6.1.02,7.09,14]pentadeca-2,4,6,9,11,13-hexaene (23) A solution of alkene 3 (55 mg, 0.125 mmol) in CHCl3 (2 mL) was treated with s-tetrazine (30 mg, 0.125 mmol) and refluxed overnight. To this mixture, DDQ (227 mg, 1.0 mmol) was added and refluxed overnight. The insoluble material was removed by filtration, and the residual liquid was washed with 3 M NaOH (3×), then with H2O, dried (MgSO4), and the solvent was removed under vacuum. The residue was subjected to radial chromatography (PE–EtOAc = 1:1), to afford 23 as a brown-colored solid (21 mg, 22.5%, mp 302–304 °C). 1H NMR (300 MHz, CDCl3): δ = 2.99 (s, 2 H, H endo ), 6.62 (s, 2 H, Hbridgehead), 7.30–7.34 (m, 4 H, HAr), 7.82 (dt, J = 6.1, 4.2 Hz, 4 H, HAr), 8.33–8.36 (m, 8 H, HAr). 13C NMR (75 MHz, CDCl3): δ = 49.3 (Cbridgehead-C), 67.9 (CH2), 123.4, 123.9, 137.0, 149.2, 151.5, 154.3, 155.7. ESI-HRMS: m/z calcd for C31H20N8 [M]+: 504.1811; found: 504.1815.