LETTER
One-Pot Conversion of Aromatic Bromides and Aromatics into Aromatic Nitriles
1565
(6) (a) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am.
Chem. Soc. 2006, 128, 6790. (b) Jia, X.; Yang, D.; Zhang,
S.; Cheng, J. Org. Lett. 2009, 11, 4716.
1) n-BuLi
2) DMF
3) I2 aq. aq. NH3, r.t.
Ar
X
Ar
Ar
C
N
(7) (a) Gerhard, L. Chem. Ber. 1967, 100, 2719. (b) Lohaus, G.
X = Br, I, H
(– n-BuX)
n-BuLi
Org. Synth. 1970, 50, 52.
(– HI)
(8) For reviews, see: (a) Togo, H.; Iida, S. Synlett 2006, 2159.
(b) Togo, H. J. Synth. Org. Chem. 2008, 66, 652.
(9) (a) Mori, N.; Togo, H. Synlett 2004, 880. (b) Mori, N.;
Togo, H. Synlett 2005, 1456. (c) Mori, N.; Togo, H.
Tetrahedron 2005, 61, 5915. (d) Ishihara, M.; Togo, H.
Synlett 2006, 227. (e) Iida, S.; Togo, H. Synlett 2006, 2633.
(f) Ishihara, M.; Togo, H. Tetrahedron 2007, 63, 1474.
(g) Iida, S.; Togo, H. Tetrahedron 2007, 63, 8274. (h) Iida,
S.; Togo, H. Synlett 2007, 407. (i) Iida, S.; Togo, H. Synlett
2008, 1639. (j) Iida, S.; Ohmura, R.; Togo, H. Tetrahedron
2009, 65, 6257.
Ar:– + (a)
Li
I
C
N
DMF
H
(d)
H
Ar
NMe2
C
(– HI)
I2
O– Li+
(b)
Ar CH
NH
(c)
aq. NH3
NH3
(– NHMe2)
H
H
C
OH–
+
Ar
NMe2
C
Ar
NMe2
(10) (a) Misono, A.; Osa, T.; Koda, S. Bull. Chem. Soc. Jpn.
1966, 39, 854. (b) Talukdar, S.; Hsu, J.; Chou, T.; Fang, J.
Tetrahedron Lett. 2001, 42, 1103.
OH
Scheme 1 Possible reaction pathway for nitrile
(11) Ushijima, S.; Togo, H. Synlett 2010, 1067.
(12) Typical Experimental Procedure for the Conversion of
Aromatic Bromides into Aromatic Nitriles
Butyllithium (1.67 M solution in hexane, 3.3 mL, 5.5 mmol)
was added dropwise to a solution of 4-bromotoluene (855
mg, 5 mmol) in THF (5 mL) at –70 °C. After 30 min, the
resulting mixture was warmed and stirred for 5 min at 0 °C.
Then, DMF (0.43 mL, 5.5 mmol) was added to the mixture,
and the obtained mixture was stirred at 0 °C. After 1 h at the
same temperature, aq NH3 (10 mL, 150 mmol) and I2 (1396
mg, 5.5 mmol) were added, and the obtained mixture was
stirred for 2 h at r.t. The reaction mixture was quenched with
sat. aq Na2SO3 (15 mL) and was extracted with Et2O (3 × 20
mL). The organic layer was washed with brine and dried
over Na2SO4 to provide 4-methylbenzonitrile in 80% yield.
If necessary, the product was purified by a short column
chromatography on silica gel (hexane–EtOAc = 9:1) to give
pure 4-methylbenzonitrile as a colorless solid.
Most aromatic nitriles mentioned in this work are commer-
cially available and were identified by comparison with the
authentic samples.
Acknowledgment
Financial support in the form of a Grant-in-Aid for Scientific Re-
search (No. 20550033) from the Ministry of Education, Culture,
Sports, Science, and Technology in Japan, Iodine Research Project
in Chiba University, Academia Showcase Research Grant from the
Japan Chemical Innovation Institute (JCII), and Futaba Electronics
Memorial Foundation, is gratefully acknowledged.
References and Notes
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4-Methylbenzonitrile
Mp 26–28 °C (commercial, mp 26–28 °C). IR: 2227 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.41 (s, 3 H), 7.26 (d,
J = 8.1 Hz, 2 H), 7.52 (d, J = 8.1 Hz, 2 H).
3-Methylbenzonitrile
Oil (commercial). IR: 2229 cm–1. 1H NMR (500 MHz,
CDCl3): d = 2.38 (s, 3 H), 7.32–7.47 (m, 4 H).
2-Methylbenzonitrile
(4) (a) Sandmeyer, T. Chem. Ber. 1884, 17, 1633.
(b) Sandmeyer, T. Chem. Ber. 1884, 17, 2650.
Oil (commercial). IR: 2225 cm–1. 1H NMR (500 MHz,
CDCl3): d = 2.54 (s, 3 H), 7.26 (t, J = 7.6 Hz, 1 H), 7.31 (d,
J = 7.6 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 1 H), 7.58 (d, J = 7.6
Hz, 1 H).
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2,4-Dimethylbenzonitrile
Mp 23–24 °C (commercial, mp 23–25 °C). IR: 2221 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.36 (s, 3 H), 2.47 (s, 3 H),
7.05 (d, J = 8.0 Hz, 1 H), 7.10 (s, 1 H) 7.43 (d, J = 8.0 Hz, 1
H).
3,4-Dimethylbenzonitrile
Mp 63–64 °C (commercial, mp 64–67 °C). IR: 2224 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.29 (s, 3 H), 2.32 (s, 3 H),
7.21 (d, J = 7.8 Hz, 1 H), 7.39 (d, J = 7.8 Hz, 1 H), 7.41 (s,
1 H).
2,5-Dimethylbenzonitrile
Oil (commercial). IR: 2227 cm–1. 1H NMR (500 MHz,
CDCl3): d = 2.33 (s, 3 H), 2.48 (s, 3 H), 7.18 (d, J = 7.9 Hz,
1 H), 7.27 (d, J = 7.9 Hz, 1 H), 7.36 (s, 1 H).
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Synlett 2010, No. 10, 1562–1566 © Thieme Stuttgart · New York