1642
S. Iida, H. Togo
LETTER
B. J. Chem. Res., Synop. 1988, 168. (n) Nikishin, G. I.;
I2
RCH2X
RC
N
Troyanskii, E. I.; Joffe, V. A. Izv. Akad. Nauk. SSSR, Ser. Khim.
1982, 2758. (o) Kametani, T.; Takahashi, K.; Ohsawa, T.;
Ihara, M. Synthesis 1977, 245. (p)Capdevielle, P.;Lavigne, A.;
Maumy, M. Synthesis 1989, 453. (q) Capdevielle, P.; Lavigne,
A.; Sparfel, D.; Baranne-Lafont, J.; Nguyen, K. C.; Maumy, M.
Tetrahedron Lett. 1990, 31, 3305. (r) Maeda, Y.; Nishimura,
T.; Uemura, S. Bull. Chem. Soc. Jpn. 2003, 76, 2399. (s) Tang,
R.; Diamond, S. E.; Neary, N.; Mares, F. J. Chem. Soc., Chem.
Commun. 1978, 562. (t) Schroder, M.; Griffith, W. P.
J. Chem. Soc., Chem. Commun. 1979, 58. (u) Bailey, A. J.;
James, B. R. Chem. Commun. 1996, 2343. (v) Mori, K.;
Yamaguchi, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. Chem.
Commun. 2001, 461. (w) Yamaguchi, K.; Mizuno, N. Angew.
Chem. Int. Ed. 2003, 42, 1480. (x) Moriarty, R. M.; Vaid, R.
K.; Duncan, M. P.; Ochiai, M.; Inenaga, M.; Nagao, Y.
Tetrahedron Lett. 1988, 29, 6913. (y)Chen, F.;Kuang, Y.;Dai,
H.; Lu, L.; Huo, M. Synthesis 2003, 2629.
aq NH3
(SN2)
NH3
(–HX)
(– HI)
I
RC
H
(d)
N
RCH2NH2
(a)
I2
(– HX)
(– HX)
I2
H
RCHNH
(b)
RCH=NH
(c)
(– HI)
I
Scheme 1
In conclusion, benzylic halides and primary alkyl halides
could be easily and directly converted into the corre-
sponding nitriles without changing the number of carbon
atoms in good yields, using molecular iodine in aqueous
ammonia. As is well known, the advantages of molecular
iodine are operational simplicity, low cost, and low toxic-
ity, and therefore, the present reaction should be a useful
and environmentally benign method for the preparation of
nitriles from halides.
(6) (a) Mori, N.; Togo, H. Synlett 2004, 880. (b) Mori, N.; Togo,
H. Tetrahedron 2005, 61, 5915. (c) Ishihara, M.; Togo, H.
Synlett 2006, 227. (d) Ishihara, M.; Togo, H. Tetrahedron
2007, 63, 1474.
(7) (a) Mori, N.; Togo, H. Synlett 2005, 1456. (b) Iida, S.; Togo,
H. Synlett 2006, 2633. (c) Iida, S.; Togo, H. Tetrahedron 2007,
63, 8274.
(8) Typical Procedure for Oxidative Conversion of Benzyl
Halides into Nitriles with I2
Acknowledgment
To a mixture of 4-methylbenzyl chloride (140.6 mg, 1 mmol)
and aq NH3 (3.0 mL, 45 mmol) was added I2 (533.0 mg, 2.1
mmol) at r.t. under an empty balloon. The obtained mixture was
stirred at 60 °C. After 4 h at the same temperature, the reaction
mixture was quenched with H2O (10 mL) and sat. aq Na2SO3 (2
mL) at 0 °C and was extracted with Et2O (3 × 15 mL). The
organic layer was washed with brine and dried over Na2SO4 to
provide p-tolunitrile in 82% yield in an almost pure state. If
necessary, the product was purified by a column
Financial support in the form of a Grant-in-Aid for Scientific Re-
search (No. 16655012) from the Ministry of Education, Culture,
Sports, Science and Technology of Japan is gratefully acknowled-
ged.
References and Notes
chromatography (SiO2; hexane–EtOAc, 4:1) to give pure p-
tolunitrile as a colorless solid; mp 25 °C. IR (NaCl): 2230 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.55 (2 H, d, J = 7.9 Hz), 7.27
(2 H, d, J = 7.9 Hz), 2.42 (3 H, s).
(1) Review: Togo, H.; Iida, S. Synlett 2006, 2159.
(2) (a) Friedrick, K.; Wallensfels, K. The Chemistry of the
Cyano Group; Rappoport, Z., Ed.; Wiley-Interscience: New
York, 1970. (b) North, M. Comprehensive Organic
(9) Typical Procedure for Oxidative Conversion of Alkyl
Halides into Nitriles with I2
Functional Group Transformation; Katritzky, A. R.; Meth-
Cohn, O.; Rees, C. W., Eds.; Pergamon: Oxford, 1995.
(c) Murahashi, S.-I. Synthesis from Nitriles with Retention of
the Cyano Group, In Science of Synthesis, Vol. 19; Thieme:
Stuttgart, 2004, 345–402. (d) Collier, S. J.; Langer, P.
Application of Nitriles as Reagents for Organic Synthesis
with Loss of the Nitrile Functionality, In Science of
A mixture of 3-phenylpropyl bromide (199.1 mg, 1 mmol) and
aq NH3 (5.0 mL, 75 mmol) in a screw-capped glass vial (10
mL) was stirred at 60 °C for 24 h. Then, aq NH3 (3.0 mL, 45
mmol) and I2 (761.4 mg, 3.0 mmol) were added. After 4 h at the
same temperature, the reaction mixture was quenched with H2O
(10 mL) and sat. aq Na2SO3 (2 mL) at 0 °C and was extracted
with Et2O (3 × 15 mL). The organic layer was washed with
brine and dried over Na2SO4 to provide 3-phenylpropionitrile in
73% yield in an almost pure state. If necessary, the product was
purified by column chromatography (SiO2; hexane–EtOAc,
4:1) to give pure 3-phenylpropionitrile as a colorless oil. IR
(NaCl): 2250 cm–1. 1H NMR (400 MHz, CDCl3): d = 7.34 (2 H,
t, J = 8.2 Hz), 7.28 (1 H, t, J = 8.2 Hz), 7.23 (2 H, d, J = 8.2 Hz),
2.96 (2 H, d, J = 7.9 Hz), 2.62 (2 H, d, J = 7.9 Hz).
All nitrile products mentioned in this work, except 10-
cyanodecanoic acid, were identified with commercially
available authentic samples.
Synthesis, Vol. 19; Thieme: Stuttgart, 2004, 403–425.
(3) Fabiani, M. E. Drug News Perspect. 1999, 12, 207.
(4) Comprehensive Organic Transformation; Larock, R. C.,
Ed.; VCH Publishers, Inc.: New York, 1989, 976–993.
(5) (a) Clarke, T. G.; Hampson, N. A.; Lee, J. B.; Morley, J. R.;
Scanlon, B. Tetrahedron Lett. 1968, 5685. (b) Vargha, L.;
Remenyi, M. J. Chem. Soc. 1951, 1068. (c) Cason, J. Org.
Synth., Coll. Vol. III; Wiley: New York, 1955, 3.
(d) Mihailovic, M. L.; Stojiljkovic, A.; Andrejevic, V.
Tetrahedron Lett. 1965, 461. (e) Stojiljkovic, A.; Andrejevic,
V.; Mihailovi, M. L. Tetrahedron 1967, 23, 721. (f) Below, J.
S.; Garza, C.; Mathieson, J. W. J. Chem. Soc., Chem. Commun.
1970, 634. (g) Troyanskii, E. I.; Svitanko, I. V.; Ioffe, V. A.;
Nikishin, G. I. Izv. Akad. Nauk. SSSR, Ser. Khim. 1982, 2180.
(h) Yamazaki, S.; Yamazaki, Y. Bull. Chem. Soc. Jpn. 1990, 63,
301. (i) Biondini, D.; Brinchi, L.; Germani, R.; Goracci, L.;
Savelli, G. Eur. J. Org. Chem. 2005, 3060. (j) Chen, E.; Peng,
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(k) Lee, G. A.; Freedman, H. H. Tetrahedron Lett. 1976, 1641.
(l) Yamazaki, S. Synth. Commun. 1997, 27, 3559. (m) Jursic,
10-Cyanodecanoic Acid
Mp 42–44 °C. IR (neat): 2243, 1690 cm–1. 1H NMR (400 MHz,
CDCl3): d = 2.35 (t, J = 7.4 Hz, 2 H), 7.34 (t, J = 7.2 Hz, 1 H),
1.64 (m, 4 H), 1.44 (br, 2 H) 1.32 (br, 9 H). 13C NMR (100
MHz, CDCl3): d = 179.7, 119.9, 34.0, 29.1, 29.0, 28.72, 28.66,
25.4, 24.7, 17.2. HRMS: m/z calcd for C11H19O2N: 198.1494;
found: 198.1484.
Synlett 2008, No. 11, 1639–1642 © Thieme Stuttgart · New York