10.1002/ejoc.202000329
European Journal of Organic Chemistry
RESEARCH ARTICLE
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Lichter, J. D. Roberts J. Am. Chem. Soc. 1971, 93, 5218–5224; (c) J. D.
Baldeschwieler, E. W. Randall Proc. Chem. Soc. 1961, 303–304; (d) Z.
Dega-Szafran, M. Szafran, L. Stefaniak, C. Brevard, M. Bourdonneau
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Supporting Information. The NMR tube was sealed with a rubber
septum (wrapped around the outside with PTFE tape and then
Parafilm) under inert atmosphere, and brought to the NMR
spectrometer.
[4]
[5]
E. Haslinger, M. Schlederer, W. Robien, P. Wolschann Monatsh.Chem.
1984, 115, 1345–1351.
1H NMR (300 MHz, DMSO-d6) δ 9.40 (d, J = 6.3 Hz, 2H), 8.61 (t,
J = 7.8 Hz, 1H), 8.22 (t, J = 7.3 Hz, 2H), 4.45 (s, 3H).[39a]
(a) L. Pazderski, Magn. Reson. Chem. 2008, 46, S3–S15; (b) R. M.
Shanahan, A. Hickey, L. M. Bateman, M. E. Light, G. P. McGlacken J.
Org. Chem. 2020, 85, 2585–2596; (c) R. Kleinmaier, S. Arenz, A. Karim,
A;.-C. C. Carlsson, M. Erdélyi Magn. Reson. Chem. 2013, 51, 46 – 53;
(d) See reference 2c; (e) L. Pazderski, T, Pawlak, J. Sitkowski, L.
Kozerski, E. Szłyk Magn. Reson. Chem. 2010, 48, 417–426; (f) L.
Pazderski Annu. Rep. NMR Spectrosc. 2013, 80, 33–179.
(b) Pyridine N-oxide (4) (0.064 g, 0.67 mmol) was dissolved in
dry MeCN (5 ml) in a N2-filled Schlenk flask. Methyl triflate (0.111
g, 0.670 mmol) was subsequently added dropwise. After ca. 20
minutes, the MeCN was removed under vacuum – precise details
on how this was done are given in Procedure A in the General
Procedures section in the Supporting Information. The entirety of
the solid product was dissolved in DMSO (0.8 ml), and this
solution was transferred to a NMR tube under inert atmosphere
Full details of the protocol used for preparation of samples for
NMR spectroscopy under inert atmosphere are given in
Procedure B in the General Procedures section in the Supporting
Information. The NMR tube was sealed with a rubber septum
(wrapped around the outside with PTFE tape and then Parafilm)
under inert atmosphere, and brought to the NMR spectrometer.
1H and 1H-15N HMBC NMR spectra were recorded for the sample
using the solvent signal suppression protocol referred to above.
[6]
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B. Costisella, J. Schulz, H. Teichmann, C. Donaths, M. Meisels,
Phosphorus Sulfur Silicon Relat. Elem. 1990, 53, 367 – 371.
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Sitkowski, L. Stefaniak J. Org. Chem. 1998, 63, 2898 – 2908.
Approximate δN values for the N-alkylpyridinium salts produced by N-
alkylation of pyridines with bromoalkyl nitriles have also been reported.
Derived ∆(δN) values are of the order of −100 ppm, but as exact δN values
are not reported, precise ∆(δN) values cannot be determined: K. C,
Lethesh, K. Van Hecke, L. Van Meervelt, P. Nockemann, B. Kirchner, S.
Zahn, T. N. Parac-Vogt, W. Dehaen, K. Binnemans J. Phys. Chem. B
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E. Lukevics, E. Leipiņš, I. Segal, M. Fleisher, J. Organomet. Chem. 1991,
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[10] P. Cmoch, Magn. Reson. Chem. 2003, 41, 693 – 698.
[11] A. R. Katrizky, B. E-D. M. El-Gendy, B. Draghici, D. Fedseyenko, A.
1H NMR (600 MHz, DMSO) δ 9.41 (d, J = 6.3 Hz, 2H), 8.59 (t, J =
7.7 Hz, 1H), 8.21 (t, J = 7.2 Hz, 2H), 4.41 (s, 3H).[39a]
Fadli, E. Metais Magn. Reson. Chem. 2010, 48, 397–402.
[12] R. Marek, O. Humpa, J. Dostál, J. Slavík, V. Sklená Magn. Reson. Chem.
1999 37, 195–202.
15N NMR (60.8 MHz, DMSO): δ 252.4.
[13] Some further examples involving isoquinolines and related but not
directly derived N-methylisoquinolinium ions also demonstrate this
principle qualitatively: (a) See reference 12; (b) A. Czyrski, U. Girreser,
T. Hermann J. Mol. Struct. 2013, 1036, 111–114; (c) See reference 2d.
(c) Pyridine N-oxide (4) (0.026 g, 0.27 mmol) was dissolved in
dry CH2Cl2 (0.8 ml) in a vial inside a glove box under an
atmosphere of dry N2. Methyl triflate (0.040 g, 0.24 mmol) was
added to the solution dropwise. The entire reaction mixture was
transferred to an NMR tube. The NMR tube was sealed with a
rubber septum (wrapped around the outside with PTFE tape and
then Parafilm) under inert atmosphere. After ca. 30 minutes, the
NMR tube was removed from the glove box, and the sample was
analysed by 1H and 1H-15N HMBC NMR spectroscopy (in CH2Cl2,
using the solvent signal suppression protocol referred to above).
Quantitative conversion to the product was observed based on
the 1H NMR spectrum (based on consumption of MeOTf, i.e. the
excess of 4 used remains).
[14]
(a) R. Marek, J. Brus, J.; J. ToušekL. Kovács, D. Hocková Magn. Reson.
Chem. 2002, 40, 353 – 360; (b) A.K. Bakkestuen, L.L. Gundersen, D.
Petersen, B.T. Utenova, A. Vik Org. Biomol. Chem. 2005, 3, 1025–1033;
(c) H. Roggen, L.L. Gundersen Eur. J. Org. Chem. 2008, 5099–5106; (d)
M. Hocek, R. Pohl, I. Císařová Eur. J. Org. Chem. 2005, 3026–3030.
[15] Z. Dega-Szafran, M. Szafran, J. Sitkowski, L. Stefaniak J. Phys. Org.
Chem. 1996, 9, 746 – 750.
[16] (a) K. A. Farley, P. B. Bowman, J. C. Brumfield, F. W. Crow, W. K.
Duholke, J. E. Guido, R. H. Robins, S. M. Sims, R. F. Smith, T. J.
Thamann, B. S. Vonderwell, G. E. Martin, Magn. Reson. Chem. 1998,
36, S11–S16; (b) G. E. Martin, C. E. Hadden, J. R. Blinn, M. H. M. Sharaf,
A. N. Tackie, P. L. Schiff Jr., Magn. Reson. Chem. 1999, 37, 1–6; (c) C.
E. Hadden, W. K. Duholke, J. E. Guido, R. H. Robins, G. E. Martin, M.
H. M. Sharaf, P. L. Schiff Jr., J. Heterocycl. Chem. 1999, 36, 525 – 531.
[17] The 15N NMR chemical shift values are referenced to liquid ammonia at
0 ppm (equivalent to referencing to nitromethane at 380.2 ppm) as per
the convention specified in reference 2a.
1H NMR (600 MHz, CH2Cl2) Signals of 13b: δ 9.18 (d, J = 6.7 Hz,
2H), 8.57 (td, J = 7.8, 0.8 Hz, 1H), 8.17 (t, J = 7.2 Hz, 2H), 4.47
(s, 3H).[39a] Signals of residual 4: δ 8.24 – 8.21 (m, 2H), 7.45 –
7.38 (m, 3H).
[18] See experimental details in the Supporting Information on pages S8 to
S22.
[19] Details of the conversion calculations are given in the Supporting
15N NMR (60.8 MHz, CH2Cl2): δ 251.0 (13b). No correlations for
signals of 4 were detected.
Information – see pages S8–S22 for experimental details.
[20] A. Dokalik, H. Kalchhauser, W. Mikenda, G. Schweng Magn. Reson.
Chem. 1999, 37, 895-902. In addition to 15N NMR spectral data for
diazines and other heterocycles in DMSO-d6 solvent, similar data in
CDCl3 is also given.
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[24] A detailed description of how inert NMR spectral analysis was carried
out is given on page S5 of the Supporting Information.
[25] Methylation of pyridine N-oxide (10) by MeI, for example, has been
shown to be reversible in MeCN (equilibrium favours starting materials):
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11
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