Journal of the American Chemical Society
ARTICLE
gel layer. Evaporation of the filtrate produced the nitrile product in
analytically and spectroscopically pure form (see below).
(CDCl3, 25 °C), δ: 1.4 (t, 3J = 7.1 Hz, 3H, CH3), 4.4 (q, 3J = 7.1 Hz, 2H,
CH2), 7.7À7.8 (m, 2H, 3,5-H), 8.1À8.2 (m, 2H, 2,6-H). Calcd for
C10H9NO2: C, 68.6; H, 5.2; N, 8.0. Found: C, 68.8; H, 5.2; N, 7.9.
4-Chlorobenzonitrile was obtained and isolated in 95% yield
(0.523 g) from 4-bromochlorobenzene (0.766 g). The product
contained ca. 4 mol % of terephthalonitrile (NMR, GCÀMS). 1H
NMR (CDCl3, 25 °C), δ: 7.45À7.5 (m, 2H, 2,6-H), 7.55À7.65 (m, 2H,
3,5-H).
Benzonitrile. At full conversion, the yield was >99% (GCÀMS with
calibration).
2-Cyanonaphthalene was obtained and isolated in 99% yield
(0.605 g) from 2-bromonaphthaline (0.828 g). 1H NMR (CDCl3,
25 °C), δ: 7.55À7.7 (m, 3H, 3,6,7-H), 7.85À7.95 (m, 3H, 4,5,8-H),
8.2À8.3 (m, 1H, 1-H). Calcd for C11H7N: C, 86.3; H, 4.6; N, 9.1.
Found: C, 86.3; H, 4.8; N, 8.9.
4-Methylbenzonitrile was obtained and isolated in 93% yield
(0.436 g) from 4-bromotoluene (0.492 mL; 0.684 g). 1H NMR
(CDCl3, 25 °C), δ: 2.4 (s, 3H, CH3), 7.2À7.3 (m, 2H, 3,5-H),
7.45À7.6 (m, 2H, 2,6-H). Calcd for C8H7N: C, 82.0; H, 6.0; N, 12.0.
Found: C, 81.8; H, 6.1; N, 11.5.
3-Methylbenzonitrile was obtained and isolated in 97% yield
(0.453 g) from 3-bromotoluene (0.485 mL; 0.684 g). 1H NMR
(CDCl3, 25 °C), δ: 2.4 (s, 3H, Me), 7.3À7.5 (m, 4H, 2,4,5,6-H). Calcd
for C8H7N: C, 82.0; H, 6.0; N, 12.0. Found: C, 82.1; H, 6.2; N, 11.5.
2-Methylbenzonitrile was obtained and isolated in 94% yield
(0.438 g) from 2-bromotoluene (0.482 mL; 0.684 g). 1H NMR
(CDCl3, 25 °C), δ: 2.5 (s, 3H, Me), 7.2À7.35 (m, 2H, 3,5-H),
7.4À7.5 (m, 1H, 6-H), 7.5À7.6 (m, 1H, 4-H). Calcd for C8H7N: C,
82.0; H, 6.0; N, 12.0. Found: C, 81.5; H, 6.2; N, 11.6.
4-Fluorobenzonitrile was obtained and isolated in 97% yield
(0.468 g) from 4-bromofluorobenzene (0.439 mL; 0.700 g). To avoid
significant losses of this more volatile product, the reaction solvents were
carefully removed on a rotary evaporator at 500 mbar/80 °C. For the
same reason, care was exercised evaporating dichloromethane in the final
isolation step. The isolated product contained ca. 4 mol % of CH2Cl2
(NMR, GCÀMS). 1H NMR (CDCl3, 25 °C), δ: 7.1À7.25 (m, 2H, 3,5-
H), 7.65À7.75 (m, 2H, 2,6-H).
3-Cyanothiophene was obtained and isolated in 93% yield (0.568 g)
from 3-bromothiophene (0.525 mL; 0.913 g; 5.6 mmol) and NaCN
(0.291 g; 5.9 mmol) in 5.6 mL of acetonitrile with 1% of the catalyst. 1H
NMR (CDCl3, 25 °C), δ: 7.3 (dd, 3J4,5 = 5.1 Hz, 4J4,2 = 1.2 Hz, 1H, 4-H),
7.4 (dd, 3J5,4 = 5.1 Hz, 4J5,2 = 2.9 Hz, 1H, 5-H), 7.95 (dd, 4J2,4 = 1.2 Hz,
4J2,5 = 2.9 Hz, 1H, 2-H). The spectroscopically pure product was
additionally purified on a short silica gel column prior to elemental
analysis. Calcd for C5H3NS: C, 55.0; H, 2.8; N, 12.8; S, 29.4. Found: C,
55.4; H, 3.1; N, 12.7; S, 29.1.
3-Acetylbenzonitrile was obtained and isolated in 99% yield
(0.575 g) from 3-bromoacetophenone (0.534 mL; 0.796 g). 1H NMR
(CDCl3, 25 °C), δ: 2.6 (s, 3H, Me), 7.55À7.65 (m, 1H, 5-H), 7.8À7.9
(m, 1H, 6-H), 8.1À8.2 (m, 1H, 4-H), 8.2À8.25 (m, 1H, 2-H). Calcd for
C9H7NO: C, 74.5; H, 4.9; N, 9.7. Found: C, 74.6; H, 5.0; N, 9.4.
4-Acetylbenzonitrile was obtained and isolated in 99% yield
3-Trifluoromethylbenzonitrile was obtained and isolated in 88%
yield (0.602 g) from 3-bromobenzotrifluoride (0.559 mL; 0.900 g). 1H
NMR (CDCl3, 25 °C), δ: 7.6À7.7 (m, 1H, 5-H), 7.8À7.9 (m, 2H, 4,6-
H), 7.9À7.95 (m, 1H, 2-H). Calcd for C8H4F3N: C, 56.2; H, 2.4; N, 8.2.
Found: C, 56.6; H, 2.8; N, 8.0.
1
(0.575 g) from 4-bromoacetophenone (0.796 g). H NMR (CDCl3,
25 °C), δ: 2.6 (s, 3H, Me), 7.7À7.8 (m, 2H, 2,6-H), 8.0À8.1 (m, 2H,
3,5-H). Calcd for C9H7NO: C, 74.5; H, 4.9; N, 9.7. Found: C, 74.7; H,
4.9; N, 9.6.
’ ASSOCIATED CONTENT
Supporting Information. 1H NMR spectra of the iso-
4-Nitrobenzonitrile was obtained and isolated in 99% yield (0.586 g)
from of 4-bromonitrobenzene (0.808 g). 1H NMR (CDCl3, 25 °C), δ:
7.8À7.95 (m, 2H, 2,6-H), 8.3À8.4 (m, 2H, 3,5-H). Calcd for
C7H4N2O2: C, 56.8; H, 2.7; N, 18.9. Found: C, 57.2; H, 2.8; N, 18.6.
4-Methoxybenzonitrile was obtained and isolated in 99% yield
(0.530 g) from 4-bromoanisole (0.502 mL; 0.748 g). 1H NMR
(CDCl3, 25 °C), δ: 3.85 (s, 3H, Me), 6.9À7.0 (m, 2H, 3,5-H),
7.5À7.6 (m, 2H, 2,6-H). Calcd for C8H7NO: C, 72.2; H, 5.3; N, 10.5.
Found: C, 72.6; H, 5.4; N, 10.2.
S
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lated products. This material is available free of charge via the
’ AUTHOR INFORMATION
Corresponding Author
3-Methoxybenzonitrile was obtained and isolated in 99% yield
(0.528 g) from 3-bromoanisole (0.509 mL; 0.748 g). 1H NMR
(CDCl3, 25 °C), δ: 3.8 (s, 3H, Me), 7.1À7.15 (m, 2H) and 7.2À7.25
(m, 1H, 2,4,6-H), 7.3À7.4 (m, 1H, 5-H). Calcd for C8H7NO: C, 72.2;
H, 5.3; N, 10.5. Found: C, 72.5; H, 5.5; N, 10.3.
’ ACKNOWLEDGMENT
We thank Prof. Antonio M. Echavarren for a discussion. The
ICIQ Foundation and Consolider Ingenio 2010 (Grant
CSD2006-0003) are thankfully acknowledged for support.
2-Aminobenzonitrile was obtained and isolated in 99% yield (0.470 g)
from 2-bromoaniline (0.688 g). 1H NMR (CDCl3, 25 °C), δ: 4.0À4.7 (br
s, 2H, NH2), 6.65À6.8 (m, 2H, 3,5-H), 7.3À7.35 (m, 1H, 4-H), 7.35À7.45
(m, 1H, 6-H). Calcd for C7H6N2: C, 71.2; H, 5.1; N, 23.7. Found: C, 71.4;
H, 5.3; N, 22.2 (N content outside the range of the method).
4-Aminobenzonitrile was obtained and isolated in 99% yield
’ REFERENCES
(1) For recent reviews, see: (a) Anbarasan, P.; Schareina, T.; Beller,
M. Chem. Soc. Rev. 2011, Advance article, DOI: 10.1039/c1cs15004a.
(b) Sundermeier, M.; Zapf, A.; Beller, M. Eur. J. Inorg. Chem. 2003, 3513.
(c) Zapf, A.; Beller, M. Chem. Commun. 2005, 431. (d) Torborg, C.;
Beller, M. Adv. Synth. Catal. 2009, 351, 3027. (e) Jones, L. H.; Summerhill,
N. W.; Swain, N. A.; Mills, J. E. Med. Chem. Commun. 2010, 1, 309.
(f) Magano, J.; Dunetz, J. R. Chem. Rev. 2011, 111, 2177.
(2) Takagi, K.; Okamoto, T.; Sakakibara, Y.; Oka, S. Chem. Lett.
1973, 471.
(3) Independently and simultaneously, Cassar reported the first
Ni-catalyzed aromatic cyanation reaction. See: Cassar, L. J. Organomet.
Chem. 1973, 54, C57.
(4) Takagi, K.; Okamoto, T.; Sakakibara, Y.; Ohno, A.; Oka, S.;
Hayama, N. Bull. Chem. Soc. Jpn. 1975, 48, 3298.
1
(0.470 g) from 4-bromoaniline (0.688 g). H NMR (CDCl3, 25 °C),
δ: 3.9À4.4 (br s, 2H, NH2), 6.55À6.7 (m, 2H, 3,5-H), 7.35À7.45 (m,
2H, 2,6-H). Calcd for C7H6N2: C, 71.2; H, 5.1; N, 23.7. Found: C, 71.5;
H, 5.2; N, 23.1. (N content outside the range of the method).
4-(Dimethylamino)benzonitrile was obtained and isolated in 99%
yield (0.582 g) from 4-bromo-N,N-dimethylaniline (0.800 g). 1H NMR
(CDCl3, 25 °C), δ: 3.05 (s, 6H, NCH3), 6.6À6.7 (m, 2H, 3,5-H),
7.4À7.5 (m, 2H, 2,6-H). Calcd for C9H10N2: C, 73.9; H, 6.9; N, 19.2.
Found: C, 74.2; H, 6.7, N, 18.9.
Ethyl 4-cyanobenzoate was obtained and isolated in 99% yield
(0.696 g) from ethyl 4-bromobenzoate (0.640 mL; 0.916 g). 1H NMR
11004
dx.doi.org/10.1021/ja2042035 |J. Am. Chem. Soc. 2011, 133, 10999–11005