8446
R. X. Ren, W. Ou / Tetrahedron Letters 42 (2001) 8445–8446
Table 1. Formation of ketoximes using hydroxylamine and it salts in ionic liquids via Scheme 1
Entry
Substrate
Ionic liquid
Hydroxylamine source
Additive
Temp. (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cycloheptanone bmiPF6
Cycloheptanone bmiPF6
Cycloheptanone bmiPF6
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
bmiPF6
bmiPF6
bmiPF6
bmiPF6
bmiPF6
NH2OH·HCl
NH2OH·HCl
NH2OH·HCl
(NH2OH)2·H2SO4
NH2OH (aq.)
NH2OH·HCl
(NH2OH)2·H2SO4
NH2OH (aq.)
NH2OH·HCl
NH2OH (aq.)
NH2OH (aq.)
NH2OH·HCl
(NH2OH)2·H2SO4
NH2OH (aq.)
–
–
rt
40
40
20
20
20
20
20
20
40
40
40
0.5
0.5
0.5
NR
NR
90
90
85
85
85
80
NR
NR
NR
95
95
99
40
40
40
40
40
40
40
40
rt
1 equiv. NaOAc
1 equiv. NaOAc
5% CH3SO3H
1 equiv. NaOAc
1 equiv. NaOAc
5% CH3SO3H
1 equiv. NaOAc
5% CH3SO3H
5% CH3SO3H
–
9
bmiCl
bmiCl
bmiCl
bmiBF4
bmiBF4
bmiBF4
10
11
12
13
14
40
rt
rt
–
–
rt
All reactions were all carried out in sealed vials at 2 M concentration in 1 ml of ionic liquid, monitored via GC/MS; NR: no reaction.
the ketoxime formation reaction are currently under
investigation.
The same trend was observed for cycloheptanone sub-
strate (entries 6–8). It is possible that the initially
formed oxime may undergo fast hydrolysis in the pres-
ence of strong acid (HCl) and water, particularly in the
ionic liquid media. Neutralization of hydrogen chloride
by sodium acetate provided acetic acid, which could
have much lowered acidity. It is also possible that
bmiPF6 may decompose6 under the strongly acidic con-
dition (such as HCl) in the presence of hydroxylamine,
thus hampering the formation of cyclic ketoximes.
Acknowledgements
The authors would like to thank Wesleyan University
for a start-up fund.
References
However, the formation of oxime failed completely in
bmiCl7 using NH2OH·HCl, even when sodium acetate
was added (entry 9). When aqueous hydroxylamine was
used, no reaction occurred. Addition of acid catalyst
such as methanesulfonic acid did not help, even at
elevated temperature (entries 10 and 11).
1. For recent reviews on ionic liquids in green chemistry, see:
(a) Carlin, R. T.; Wilkes, J. S. In Advances in Nonaqueous
Chemistry; Mamantov, G.; Popov, A., Eds.; VCH: New
York, 1994; (b) Chauvin, Y.; Olivier, H. ChemTech 1995,
25, 26; (c) Seddon, K. R. J. Chem. Tech. Biotechnol. 1997,
68, 351; (d) Olivier, H. J. Mol. Cat. A: Chem. 1999, 146,
285; (e) Welton, T. Chem. Rev. 1999, 99, 2071; (f) Wasser-
scheid, P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39,
3772.
2. Gawly, R. E. Org. React. 1988, 35, 1 and references cited
therein.
3. Ren, R. X.; Zueva, L. D.; Ou, W. Tetrahedron Lett. 2001,
42, 8441.
4. Sahabari, J. J.; Russel, J. W. WO0032562, June 8, 2000.
5. Suarez, P. A. Z.; Dullius, J. E. L.; Einloft, S.; DeSouza, R.
F.; Dupont, J. Polyhedron 1996, 15, 1217–1219.
6. For a discussion of decomposition pathway of bmiPF6 in
high concentration of HNO3, see: Visser, A. E.; Swatloski,
R. P.; Reichert, W. M.; Griffin, S. T.; Rogers, R. D. Ind.
Eng. Chem. Res. 2000, 39, 3596.
7. bmiCl is prepared via alkylation of 1-methylimidazole
using n-chlorobutane. This ionic liquid has melting point
slightly above room temperature and hydrophilic. Addi-
tion of trace amount of water can render it liquid-like.
Surprisingly, bmiBF4 gave very different results. For all
the reactions carried out in bmiBF4 ionic liquids, for-
mation of oxime turned out to be very efficient, regard-
less of hydroxylamine sources (entries 12–14). The best
reaction condition was by using aqueous hydroxyl-
amine and bmiBF4 (entry 14). Upon addition of
aqueous hydroxylamine to a mixture of cyclohexanone
in bmiBF4, the oxime precipitated out of aqueous solu-
tion and the product was collected by simple filtration.
The bmiBF4 can be recycled via evaporation of water.
In conclusion, the preliminary results show that forma-
tion of cyclohexanone oxime from cyclohexanone can
be conducted using aqueous hydroxylamine in ionic
liquid bmiBF4 without any other additive. The ionic
liquid acts as the recyclable reaction media which facil-
itated such reaction under essentially neutral condition
at room temperature. The effects of counter-anions on