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Table 2
In spite of the water as the byproduct of dehydration of oximes,
many of previously reported catalytic dehydrations of oximes have
required anhydrous solvents, and in some cases the molecular sieve
has been used as the additive.7b Therefore, it is worthy of noting that
the current catalysis shows moderate tolerance toward water and
the use of 11% wet acetonitrile as the solvent afforded a slightly re-
duced isolated yield (Table 1, entry 13). Although other organic sol-
vents, such as toluene, THF, ethyl acetate, and some ionic liquids,
including [bmim]Cl, [bmim]PF6, and [bmim]BF4, were tested under
identical condition, very low conversions (less than 10% after 2 h)
were observed under ambient and ultrasound irradiation
conditions.
Ultrasound-promoted Cu(OAc)2-catalyzed dehydration of oximes into nitriles under
ambient conditionsa
Entry
1
Oximes
Product
Yieldb (%)
90
NOH
CN
NOH
NOH
2
83
CN
CN
3c
4
91
88
73
83
NOH
NOH
MeO
O2N
CN
CN
MeO
O2N
Subsequently, the ultrasound-promoted catalysis11,12 dehy-
drated variousaromatic, allylic, and aliphaticaldoximesinto nitriles,
as summarized in Table 2. It is clear that all aromatic aldoximes with
electron-rich, electron-neutral, or electron-poor substitutes were
selectively converted into nitriles in high yields (Table 2, entries
1–5). It has to be pointed out that the dehydration of benzaldoxime
in a larger scale (10 mmol scale) afforded a paralleled isolated yield
(Table 2, entry 3).
In addition, heteroaromatic aldoximes were compatible with the
employed catalysis. For example, 2-pyridinealdoxime, 2-thiophen
ealdoxime, and 2-furanealdoxime were smoothly converted into
the corresponding nitriles in good yields (Table 2, entries 6-8).
trans-Cinnamonitrile was also conveniently obtained with the intact
double bond (Table 2, entry 9). However, the aliphatic aldoximes
such as 3-phenylpropanaldoxime and cyclohexanecarboxaldoxime
were less reactive and an increased catalyst loading (10 mol %)
was needed to provide good isolated yield (Table 2, entries 10 and
11).
5d
6
NOH
NOH
NOH
NOH
CN
O
S
N
O
S
7
8
90
74
CN
CN
N
CN
9
82
61
75
10d,e
11d,e
NOH
NOH
CN
CN
a
1.0 mmol oxime and 5 mol % Cu(OAc)2 in 1.0 mL acetonitrile at ambient tem-
perature under ultrasound irradiation for 2 h.
b
Isolated yield by flash chromatography.
10.0 mmol oxime and 5 mol % Cu(OAc)2 in 10.0 mL acetonitrile at ambient
c
Due to the moderate water tolerance of the current catalysis,
one-pot synthesis of m-tolunitrile from m-tolualdehyde was estab-
lished through p-tolualdoxime,13 as shown in Scheme 2.14 m-Tolu-
aldoxime was first formed from the m-tolualdehyde by adding
50 wt % aqueous hydroxylamine and followed by 30 min sonica-
tion. After flushing with molecular oxygen for 1 min, 5 mol %
Cu(OAc)2 was added into the reaction mixture, which then under-
goes ultrasound-promoted dehydration of m-tolualdoxime under
ambient condition to afford m-tolunitrile in 73% isolated yield.
In conclusion, an efficient ultrasound-promoted dehydration of
various aldoximes into nitriles by using copper(II) acetate/acetoni-
trile system under ambient conditions was developed. Furthermore,
the current catalytic system is notably not deactivated by hetero-
atom-containing (S, N, and O) compounds and shows moderate tol-
erance toward water, which allows one-pot synthesis of m-
tolunitrile from m-tolualdehyde in good yield with minimal
purification.
temperature under ultrasound irradiation for 2 h.
d
Ultrasound irradiation for 3 h.
1.0 mol oxime and 10 mol % Cu(OAc)2 was used.
e
Cu(OTf)2, were tested as the catalyst. It is clear that Cu(OAc)2 gave
the best results (conversion 65% and isolated yield 56%) and Cu(a-
cac)2 showed no catalytic activity for the ultrasound-promoted
dehydration of p-tolualdoxime 1 (Table 1, entries 1–5). Further-
more, it has been reported that the sonochemical effects on the
chemical reactions can be enhanced when a solid acts as catalyst,10
therefore copper(II) hydroxide, Cu(OH)2, was also investigated for
aldoxime dehydration. However, only 35% conversion was ob-
served for Cu(OH)2 as the catalyst (Table 1, entry 6). In addition,
various transition-metal salt systems, including SnCl2,7a [RuCl2(p-
cymene)]2/molecular sieves (MS, 4 Å),7b Pd(OAc)2/PPh3,7c and
Ga(OTf)3,7d which have been reported to be effective catalysts for
the dehydration of oximes under heating condition, have also been
investigated and the results showed very low or no conversion of
p-tolualdoxime into p-tolunitrile under identical conditions (Table
1, entries 7–10). With Cu(OAc)2 showing optimum catalytic activ-
ity for ultrasound-promoted dehydration of p-tolualdoxime under
ambient condition, increasing the time of ultrasound irradiation to
2 h afforded excellent conversion and isolated yield (98% conver-
sion and 90% isolated yield, Table 1, entry 11). Furthermore, extre-
mely low conversion of p-tolualdoxime into p-tolunitrile was
observed under ambient condition without sonication irradiation
(6%, Table 1, entry 12), which confirmed that both ultrasound irra-
diation and Cu(OAc)2 are crucial for successful dehydration of p-
tolualdoxime under ambient condition.
Acknowledgment
This project was supported by the Georgia Institute of Technol-
ogy Focused Research Program.
References and notes
1. (a) Moruoka, K.; Yamamoto, H. In Comprehensive Organic Chemistry; Trost, B. M.,
Fleming, I., Winterfeld, E., Eds.; Pergamon Press: Oxford, 1991; Vol. 6, p 381; (b)
Fatiadi, A. J. In Preparation and Synthetic Applications of Cyano Compounds; Patai,
S., Rappaport, Z., Eds.; Wiley: New York, 1983; pp 1057–1061; (c) Miller, J. S.;
Manson, J. L. Acc. Chem. Res. 2001, 34, 563–570.
2. Bradamante, S.; Pagani, G. A. Adv. Carbanion Chem. 1996, 2, 189.
3. le Questel, J.-Y.; Berthelot, M.; Laurence, C. J. Phys. Org. Chem. 2000, 13, 347.
4. Comprehensive Organic Transformation, A Guide to Functional Group Preparation;
Larock, L. C., Ed.; VCH: New York, 1989.
1) 50 w% aq. NH2OH (1.0 equiv.)
MeCN, UI, rt, 30 min
5. (a) Denis, J. N.; Krief, A. Chem. Commun. 1980, 544; (b) Olah, G. A.; Vankar, Y. D.;
Garcia-Luna, A. Synthesis 1979, 227; (c) Carotti, A.; Campagna, F. Synthesis 1979,
56.
O
CN
2) 5 mol% Cu(OAc)2, UI, rt, 2 h
6. (a) Dulcere, J. P. Tetrahedron Lett. 1981, 22, 1599; (b) Konwar, D.; Boruah, R. C.;
Sandhu, J. S. Tetrahedron Lett. 1990, 31, 1063; (c) Fukuzawa, S.; Yamaishi, Y.;
Furuya, H.; Terao, K.; Iwasaki, F. Tetrahedron Lett. 1997, 38, 7203.
Yield: 73%
Scheme 2. One-pot synthesis of m-tolunitrile from m-tolualdehyde.