E. S. Kim et al. / Tetrahedron Letters 51 (2010) 1589–1591
1591
by the Ministry of Education, Science and Technology (2009-
0070633). Spectroscopic data was obtained from the Korea Basic
Science Institute, Gwangju branch.
InCl3 (5 mol%)
ArCN (1c, 5 mol%)
H
C
Ar
Ar
N-OH
Ar CONH2
toluene, reflux
3c
2c
References and notes
Ar
C
N
InCl3
1. (a) Thallaj, N. K.; Przybilla, J.; Welter, R.; Mandon, D. J. Am. Chem. Soc. 2008, 130,
2414–2415; (b) Larock, R. C. Comprehensive Organic Transformations, 2nd ed.;
Wiley-VCH: New York, 1999. p. 1988; (c) Kukushkin, V. Y.; Pombeiro, A. J. L.
Chem. Rev. 2002, 102, 1771–1802. and further references cited therein; (d)
Bokach, N. A.; Kukushkin, V. Y. Russ. Chem. Rev. 2005, 74, 153–170; (e)
Kukushkin, V. Y.; Pombeiro, A. J. L. Inorg. Chim. Acta 2005, 358, 1–21.
2. For the hydration of nitriles to amides catalyzed by acid or base, see: (a)
Moorthy, J. N.; Singhal, N. J. Org. Chem. 2005, 70, 1926–1929. and further
references cited therein; (b) Katritzky, A. R.; Pilarski, B.; Urogdi, L. Synthesis
1989, 949–950; (c) Kopylovich, M. N.; Kukushkin, V. Y.; Haukka, M.; Frausto da
Silva, J. J. R.; Pombeiro, A. J. L. Inorg. Chem. 2002, 41, 4798–4804; (d) Hall, J. H.;
Gisler, M. J. Org. Chem. 1976, 41, 3769–3770; (e) Sharghi, H.; Sarvari, M. H.
Synth. Commun. 2003, 33, 207–212; (f) Berrien, J.-F.; Royer, J.; Husson, H.-P. J.
Org. Chem. 1994, 59, 3769–3774; (g) McIsaac, J. E., Jr.; Ball, R. E.; Behrman, E. J. J.
Org. Chem. 1971, 36, 3048–3050; (h) Merchant, K. J. Tetrahedron Lett. 2000, 41,
3747–3749.
3. For the metal-assisted hydration of nitrile to amide, see: (a) Cadierno, V.;
Francos, J.; Gimeno, J. Chem. Eur. J. 2008, 14, 6601–6605; (b) Polshettiwar, V.;
Varma, R. S. Chem. Eur. J. 2009, 15, 1582–1586; (c) Yi, C. S.; Zeczycki, T. N.;
Lindeman, S. V. Organometallics 2008, 27, 2030–2035; (d) Leung, C. W.; Zheng,
W.; Zhou, Z.; Lin, Z.; Lau, C. P. Organometallics 2008, 27, 4957–4969; (e) Goto,
A.; Endo, K.; Saito, S. Angew. Chem., Int. Ed. 2008, 47, 3607–3609; (f) Mitsudome,
T.; Mikami, Y.; Mori, H.; Arita, S.; Mizugaki, T.; Jitsukawa, K.; Kaneda, K. Chem.
Commun. 2009, 3258–3260; (g) Crestani, M. G.; Arevalo, A.; Garcia, J. Adv. Synth.
Catal. 2006, 348, 732–742; Very recently, Chang and co-workers reported an
efficient Rh-catalyzed hydration of nitrile to amide with aldoxime as a water
surrogate as in our Pd-catalyzed hydration with acetaldoxime,4 see: (h) Lee, J.;
Kim, M.; Chang, S.; Lee, H.-Y. Org. Lett. 2009, 11, 5598–5601.
4. For our recent papers on Pd-catalyzed hydration of nitrile to amide, see: (a)
Kim, E. S.; Kim, H. S.; Kim, J. N. Tetrahedron Lett. 2009, 50, 2973–2975; (b) Kim,
E. S.; Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2009, 50, 6286–6289; For the Pd-
catalyzed dehydration of aldoxime to nitrile, see: (c) Kim, H. S.; Kim, S. H.; Kim,
J. N. Tetrahedron Lett. 2009, 50, 1717–1719.
5. For the examples of preferential activation of electrophiles in the presence of
aldoxime derivatives, see: (a) Yarovenko, V. N.; Taralashvili, V. K.; Zavarzin, I.
V.; Krayushkin, M. M. Tetrahedron 1990, 46, 3941–3952; (b) Nakama, K.; Seki,
S.; Kanemasa, S. Tetrahedron Lett. 2001, 42, 6719–6722; (c) Moustafa, A. H.
Synthesis 2003, 837–840.
6. Typical experimental procedure for the hydration of benzonitrile: A stirred
solution of 1a (103 mg, 1.0 mmol), acetaldoxime (177 mg, 3.0 mmol), and InCl3
(11 mg, 5 mol %) in toluene (1 mL) was heated to reflux for 3 h. After removal of
the solvent the residue was separated by column chromatographic purification
process (hexanes/EtOAc = 2:1) to afford benzamide, 119 mg (98%) as a white
solid. In addition, acetamide was isolated together, 34 mg (19% based on
acetaldoxime).
7. The reaction of acrylonitrile in the presence of CH3CH@NOH/InCl3 in aqueous
EtOH (80 °C, 4 h) showed the formation of some polymeric materials and
acrylamide was isolated in only 45%, whereas the reaction in the presence of
CH3CH@NOH/Pd(OAc)2/PPh3 in toluene (80 °C, 4 h) produced good yield (89%)
of acrylamide without the formation of polymeric materials.4a The results
stated that the formation of polymeric materials must be ascribed to the use of
indium catalyst.
8. (a) Barman, D. C.; Thakur, A. J.; Prajapati, D.; Sandhu, J. S. Chem. Lett. 2000,
1196–1197; (b) Ho, T.-L.; Wong, C. M. J. Org. Chem. 1973, 38, 2241–2242.
9. For the classical dehydration methods of amide to nitrile and conversion of
aldoxime to amide, see: (a) Larock, R. C. Comprehensive Organic
Transformations; Wiley-VCH: New York, 1989; (b) Smith, M. B.; March, J.
Advanced Organic Chemistry, 5th ed.; John Wiley & Sons: New York, 2001.
10. (a) Bose, D. S.; Jayalakshmi, B. J. Org. Chem. 1999, 64, 1713–1714; (b) Ishihara,
K.; Furuya, Y.; Yamamoto, H. Angew. Chem., Int. Ed. 2002, 41, 2983–2986.
11. For the conversion of aldoxime to amide, see: (a) Fujiwara, H.; Ogasawara, Y.;
Kotani, M.; Yamaguchi, K.; Mizuno, N. Chem. Asian J. 2008, 3, 1715–1721; (b)
Fujiwara, H.; Ogasawara, Y.; Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed.
2007, 46, 5202–5205; (c) Kim, M.; Lee, J.; Lee, H.-Y.; Chang, S. Adv. Synth. Catal.
2009, 351, 1807–1812; (d) Park, S.; Choi, Y.-a.; Han, H.; Yang, S. H.; Chang, S.
Chem. Commun. 2003, 1936–1937; (e) Owston, N. A.; Parker, A. J.; Williams, J.
M. J. Org. Lett. 2007, 9, 73–75; (f) Field, L.; Hughmark, P. B.; Shumaker, S. H.;
Marshall, W. S. J. Am. Chem. Soc. 1961, 83, 1983–1987.
12. Trace amounts of 1c remained and it was removed by column
chromatography. When we run the reaction of 3c in the presence of
acetonitrile (2–3 drops) instead of 1c, the reaction was sluggish and 2c was
isolated in 60% (40 h). Without acetonitrile or 1c, the reaction was very
sluggish to produce 2c in 35% (40 h). In addition, the reaction of 3c in the
presence of 1c (5%) afforded 10–15% of 2c even in o-dichlorobenzene (180 °C)
for 18 h without InCl3.
Ar is 4-methoxyphenyl
InCl3
Ar
C
N
H
InCl3
N
HO
N
H
HO
Ar
N
(regenerated)
Ar
Scheme 3.
Table 3
One-pot conversion of aldoximes to amides
Entry Aldoximea
Conditions
Amide (%)
InCl3
CH=NOH
CONH2
(5 mol %), 1c
(5 mol %)
toluene,
1
MeO
MeO
Cl
3c
2c (91)
reflux, 18 h
Cl
InCl3
CH=NOH
Cl
CONH2
(5 mol %), 1e
(5 mol %)
ODCB, reflux,
15 h
2
Cl
2e (94)
3e
Cl
Cl
InCl3
CH=NOH
CONH2
(5 mol %),
1m (5 mol %)
ODCB, reflux,
16 h
3
4
3m
2m (91)
InCl3
O2N
CH=NOH
O2N
CONH2
(5 mol %), 1n
(5 mol %)
ODCB, reflux,
16 h
2n (93)b
3n
The configuration of oxime is E (>95%).4c
Yield of 2n was 65% when toluene was used (24 h).
a
b
4-methoxybenzonitrile (1c, 5 mol %). Once the reaction started via
the similar mechanism involving a six-membered transition state
(Scheme 3), then 4-methoxybenzonitrile can be regenerated and
the catalytic cycle will go to completion. A similar concept was also
applied in the Rh-catalyzed conversion of amide to nitrile studied
by Chang and co-workers.11c Desired 4-methoxybenzamide (2c)
was isolated in 91% yield (entry 1 in Table 3).12 However, the reac-
tion of 2,6-dichlorobenzaldoxime (3e) in the presence of 2,6-
dichlorobenzonitrile (1e, 5 mol %) did not afford 2,6-dichlorobenz-
amide (2e) in toluene. Fortunately, 2e was obtained in 94% yield
when we heated the reaction mixture in o-dichlorobenzene
(ODCB) for 15 h. The results of one-pot conversion of aldoximes
into amides are summarized in Table 3.
In summary, we disclosed an efficient method for the hydration
of nitrile to amide catalyzed by InCl3 with the aid of acetaldoxime.
In addition, a one-pot conversion method of aldoxime to amide
was developed by using a similar concept.
Acknowledgment
This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded