Ruthenium Trichloride Catalyzed Highly Efficient Deoximation of Oximes to the Carbonyl Compounds and Nitriles without Acceptors

Article abstract of DOI:10.1002/cjoc.201500325

An acceptor-free catalysis protocol for the deoximation of ketoximes and aldoximes using RuCl₃ as the catalyst has been developed. Under the optimized conditions, various oximes were converted to ketones and nitriles with excellent isolated yields. An acceptor-free catalysis protocol for the deoximation of ketoximes and aldoximes using RuCl₃ as the catalyst has been developed. Under the optimized conditions, various oximes were converted to ketones and nitriles with excellent isolated yields.

Full text of DOI:10.1002/cjoc.201500325

COMMUNICATION
DOI: 10.1002/cjoc.201500325
Ruthenium Trichloride Catalyzed Highly Efficient Deoximation
of Oximes to the Carbonyl Compounds and
Nitriles without Acceptors
Yuxiao Liu, Na Yang, Changhu Chu, and Renhua Liu*
School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
An acceptor-free catalysis protocol for the deoximation of ketoximes and aldoximes using RuCl3 as the catalyst
has been developed. Under the optimized conditions, various oximes were converted to ketones and nitriles with
excellent isolated yields.
Keywords deoximation, ruthenium trichloride, hydrolysis, acceptor-free
Introduction
for conversion of oximes to the carbonyl compounds
without acceptors (Scheme 1d).
The conversion of oximes to the carbonyl com-
pounds is one of the most useful and fundamental proc-
esses in organic synthesis.[1] Interest in this area stems
from the practical application of oximes.[2-6] Oximes are
extensively used as a form of carbonyl protection[2] or to
purify, characterize[3-4] them as carbonyl derivatives.
Moreover, oximes not only are used as a kind of syn-
thetic precursor of amides[5] (via Beckmann rearrange-
ment) but also serve as an alternative strategy to prepare
Scheme 1 Synthetic methods for deoximation
Previous works
1.5 equiv. SnCl2
1.5 equiv. TiCl3
OH
R2
N
O
a)
R1
R1
R2
THF/H2O = 1:1, r.t.
OH
2H2O
2 equiv. CuCl2
N
O
+
Cu(NH2OH)Cl2
b)
MeCN/H2O = 4:1, 75 oC
aldehydes/ketones from noncarbonyl compounds.[6]
A
R1
R2
OH
R1
R2
variety of methods based on hydrolytic,[7] reductive,[8]
oxidative[9] and transoximation[10] reactions for conver-
sion of oximes into the carbonyl compounds have been
developed. However, these methods suffer from one or
more drawbacks, such as strong acidic conditions, use
of hazardous and/or expensive reagents, overreduction,
overoxidation and sacrificial use of hydroxylamine ac-
ceptors.
50% aq. CHOCOOH
r.t.
N
O
c)
R1
R2
R1
R2
This work
5-10 mol% RuCl3
60 mol% PTSA
O
NOH
R2
d)
R2
R1
R1
DMA/H2O = 20:1, 120 oC
Recently, there have been several reports describing
mild and efficient deoximation methods. Lin[11] and
Shi[12] research groups revealed facile deoximation with
the use of stoichiometric amounts of main or transition
metal salts, respectively (Scheme 1a and b). Chavan[13]
research group has reported the use of glyoxylic acid as
the hydroxylamine acceptor for the chemoselective de-
protection of oximes in an aqueous medium (Scheme
1c).
Despite the recent progress, there is still a strong
need for development of highly efficient catalytic sys-
tems for conversion of oximes to the corresponding ke-
tones or aldehydes. Here we described the discovery and
development of a convenient ruthenium catalyst system
Results and Discussion
The investigation began by initially attempting to
continue our research of acceptor-free dehydrogena-
tion:[14] dehydrogenation of cyclohexanon oximes to the
anilines. When cyclohexanone oxime was used as a
representative substrate with RuCl3 as the catalyst and
DMF as the solvent, we were surprised to find the reac-
tion product was cyclohexanone rather than aniline (Ta-
ble 1, Entry 1). This is an interesting finding and in-
spires us to systematically investigate the RuCl3-
catalyzed deoximation reaction. The results shown in
Table 1 gave the influence of solvent, temperature,
*
E-mail: liurh@ecust.edu.cn
Received April 22, 2015; accepted June 2, 2015; published online June 29, 2015.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201500325 or from the author.
Chin. J. Chem. 2015, 33, 1011—1014
© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1011

Liu et al.
COMMUNICATION
Table 1 Optimization of reaction conditionsa
OH
N
O
RuCl3, additive
solvent, T
Entry
1
RuCl3/mol%
Solvent
DMF
T/℃
120
120
120
80
Additive/mol%
Conv.b/%
68
Select.b/%
5
5
—
—
—
—
—
—
—
—
—
—
—
100
100
91
2
DMA
87
3
5
p-Xylene
Dioxane
43
4
5
33
84
5
5
Dichloroethane
CH3CN
80
31
100
100
100
100
93
6
5
80
30
7
5
DMA/H2O
DMA/H2O
DMA/H2O
DMA/H2O
DMA/H2O
DMA/H2O
DMA/H2O
DMA/H2O
DMA/H2O
DMA/H2O
120
100
140
120
120
120
120
120
120
120
89
8
5
71
9
5
89
10
11
12
13
14
15
16
2.5
10
5
52
84
90
100
76
K2CO3 (100)
NaOH (100)
PTSA (100)
PTSA (60)
79
5
58
50
5
100
100
31
93
5
94
0
PTSA (100)
100
a The reactions were carried out with cyclohexanone-oxime (1 mmol), RuCl3 (2.5－10 mol%), additive (0－100 mol%), solvent (2.1 mL,
DMA/H2O＝20∶1) at the appointed temperature under N2 (1 atm) for 8 h. bGC yield.
catalyst loading and additives on the deoximation. As
can be seen, the yield of cyclohexanone was moderate
when the reaction was performed in DMF (Table 1, En-
try 1).
ability to promote the deoximation reaction. Use of
potassium carbonate or sodium hydroxide as additive
gave lower conversion and selectivity of reaction (Table
1, Entries 12, 13). However, an increase of yield to 93%
was observed when using p-toluenesulfonic acid (PTSA)
as additive (Table 1, Entries 14, 15). The observations
could be rationalized due to the p-toluenesulfonic acid
protonation of the hydroxylamino groups, which is
conducive to the hydrolysis of hydroxylamino groups.
Notably, the reaction did not perform well in the
absence of RuCl3 (Table 2, Entry 16).
With the optimized protocol in hand, we next set out
to explore the scope of this new reaction. The results are
summarized in Table 2. As can be seen, the newly de-
veloped protocol was effective in the conversion of a
number of oximes to the carbonyl derivatives. The cy-
clic ketoximes are particularly effective for the protocol
(Table 2, Entries 1－4). A wide range of different func-
tional groups were tolerated under the optimized condi-
tions. For example, aromatic ketoximes containing elec-
tron-withdrawing or electron-donating groups afford the
desired products with excellent yields (Table 2, Entries
5 － 9). Substrates with electron-withdrawing bromo
substituent para on the benzene ring afforded corre-
sponding ketone in slightly lower yield (Table 2, Entry 6
vs. 5). Higher yield was found with the substrates whose
aromatic rings were para substituted with elec-
tron-donating methyl group (Table 2, Entry 7 vs. 5). The
position of different substituent on the aryl group was
also examined to determine the influence of steric hin-
The yield of cyclohexanone was increased to 87%
when DMA was used in place of DMF as solvent (Table
1, Entry 2). This result showed that solvents have sig-
nificant influence on the reaction. Further optimization
was therefore focused on screening different solvents
(Table 1, Entries 3－6). However, other screened sol-
vents did not result in any improvement in conversion
and selectivity compared with DMA. It is noteworthy
that the reaction could proceed under waterless and an-
aerobic conditions (Table 1, Entries 1－6). This result
suggests that the oxygen of the product carbonyl com-
pounds comes from the hydroxylamine group. A rea-
sonable speculation is proposed in Scheme 2(c). Further
enhancement of conversion was achieved by using di-
polar aprotic DMA with water (20∶1) as the solvent for
the reaction (Table 1, Entry 7). Although increasing
temperature from 100 ℃ to 120 ℃ led to reaction
rate increase (Entries 7, 8), raising the reaction tem-
perature to 140 ℃ did not increase the yield of cyclo-
hexanone, but decrease the selectivity of reaction (Table
1, Entries 7, 9). Increasing the catalyst loading from 2.5
mol% to 5 mol% dramatically improved both conver-
sion and selectivity of the reaction, however, the catalyst
increase from 5 mol% to 10 mol% did not obviously
increase the reaction yields (Table 1, Entries 7, 10 and
11). A variety of acids and bases were screened for their
1012
www.cjc.wiley-vch.de
© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2015, 33, 1011—1014

Deoximation of Oximes to the Carbonyl Compounds and Nitriles without Acceptors
drance on product yields. Slightly lower yields were
Continued
found with the ortho-hydroxy substrate than acetophe-
none oxime (Table 2, Entry 8 vs. 5). However, dramati-
cally lower yield was observed with the ortho-fluoro
substrate than acetophenone oxime (Table 2, Entry 9 vs.
5). Furthermore, the deoximation system tolerates a va-
riety of sterically hindered reactants (Table 2, Entries
10－12).
Entrya
7
Oxime
Product
RuCl3/mol%Yieldb/%
OH
O
N
10
90
81
OH
O
N
Having achieved the excellent results of catalytic
conversion of ketoximes to the ketones, we next exam-
ined deoximation of aldoximes under the same condi-
tions. Aldoximes could be hydrolyzed to the corre-
sponding aldehydes, which afforded primary amides in
strong acidic conditions (i.e., Beckmann rearrangement),
which converted to the amines through Hoffman reac-
tion in the presence of alkali hypochlorites, or dehy-
drated to the corresponding nitriles.[15] In this case, a
number of aldoximes were investigated under the opti-
mized deoximation conditions and the results showed
that these aldoximes were converted to nitriles rather
than aldehydes. Aromatic aldoximes containing elec-
tron-donating groups were tolerant, affording the de-
sired products with excellent yields (Table 2, Entries 14
－16). Unfortunately, despite extensive efforts, aromatic
aldoximes containing electron-withdrawing groups and
aliphatic aldoximes remained unreactive. However, it is
noteworthy that the position of the substituent on the
benzene ring did not diminish the efficiency of the reac-
tion.
8
9
10
OH
O
OH
OH
N
10
10
61
94
F
F
HO
O
N
10
OH
O
N
11
12
13
14
15
16
10
10
10
10
10
10
94
50
80
83
71
75
OH
O
N
OH
CN
Table 2 Scope of the RuCl3/PTSA deoximation system
N
N
Entrya
Oxime
Product
RuCl3/mol% Yieldb/%
HO
N
O
OH
CN
1
5
5
86
88
83
95
83
OMe
OMe
OMe
OMe
OH
N
O
OH
CN
2
3c
4c
5
N
OH
CN
OH
N
O
N
10
10
10
OH
OH
a The reactions were carried out with oxime (1 mmol), RuCl3 (5
or 10 mol%), PTSA (0.6 mmol), solvent (2.1 mL, DMA/H2O＝
20∶1) at 120 ℃ under N2 (1 atm) for 8 h. Isolated yield.
c Reaction for 14 h.
N
O
OH
b
OH
O
N
Mechanism
A plausible reaction mechanism for deoximation re-
action of ketoximes and aldoximes using RuCl3 as cata-
lyst has been proposed as shown in Scheme 2. The reac-
tions proceeded with initial coordination of hydroxyl-
amino groups to metal Ru(III) to form 1 or 4. Protona-
tion of 2 or 4 leads to 3 or 5. Dehydroxylamination of 3
OH
O
N
6
10
81
Br
Br
Chin. J. Chem. 2015, 33, 1011—1014
© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1013

Liu et al.
COMMUNICATION
generates ketones and dehydration of 5 generates ni-
triles. Although the reaction occurs at 120 ℃, the water
in the reaction solvent is difficult to be completely
evaporated, and considerable water would be captured
by DMA, staying in the reaction mixture.
Acknowledgement
Financial support from the National Natural Science
Foundation of China (No. 21072055) and the National
High Technology Research and Development Program
of China (863 Program) (No. 2008AA06Z306).
Scheme 2 Possible mechanism for deoximation reaction
References
RuCl3
Cl3Ru
Cl3Ru
a)
[1] (a) Corsaro, A.; Chiacchio, M. A.; Pistara, V. Curr. Org. Chem.
2009, 13, 482; (b) Sandler, S. R.; Karo, W. In Organic Functional
Group Preparations, Academic Press, London, 1989.
[2] (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Syn-
thesis, 3rd ed., John Wiley, New York, 1999; (b) Zhao, W. C.; Sha, Y.
W. Chin. J. Org. Chem. 1996, 16, 121.
[3] Shriner, R. L.; Fuson, R. C.; Curtin, D. Y.; Morrill, T. C. The Sys-
tematic Identification of Organic Compounds, 6th ed., John Wiley,
New York, 1980.
[4] (a) Kim, Y. H.; Jung, J. C.; Kim, K. S. Chem. Ind. 1992, 31; (b)
Shinada, T.; Yoshihara, K. Tetrahedron Lett. 1995, 36, 6701.
[5] (a) Ganboa, I.; Palomo, C. Synth. Commun. 1983, 13, 941; (b) Ghi-
aci, M.; Hassan, I. G. Synth. Commun. 1998, 28, 2275.
OH
R2
OH
R2
H2O
H
OH
OH
R2
N
H2+N
R1
HN
R1
R1
1
O
2
H
3
O
R2
R1
Ru(NH2OH)Cl3
b)
Cl3Ru
R1
Cl3Ru
R1
OH
H
H
+OH2
N
R1
N
CN
H
H2O
[6] (a) Shen, J. X.; Sun, J. K.; Qin, S. S.; Chu, C. H.; Liu, R. H. Chin. J.
Chem. 2014, 32, 405; (b) Wang, K.; Qian, X.; Cui, J. Tetrahedron
2009, 65, 10377; (c) Domingo, L. R.; Picher, M. T.; Arroyo, P.; Sez,
J. A. J. Org. Chem. 2006, 71, 9319; (d) Czekelius, C.; Carreira, E. M.
Angew. Chem., Int. Ed. 2005, 44, 612; (e) Kabalka, G. W.; Pace, R.
D.; Wadgaonkar, P. P. Synth. Commun. 1990, 20, 2453; (f) Baran, J.;
Mayr, H. J. Org. Chem. 1989, 54, 5012.
[7] (a) Lin, M. H.; Lin, L. Z.; Chuang, T. H.; Liu, H. J. Tetrahedron
2012, 68, 2630; (b) Li, J. T.; Meng, X. T.; Liu, L.; Chen, G. Chin. J.
Org. Chem. 2011, 31, 733; (c) Gogoi, P.; Hazarika, P.; Konwar, D. J.
Org. Chem. 2005, 70, 1934; (d) Bhar, S.; Guha, S. Synth. Commun.
2005, 35, 1183; (e) De, S. K. Tetrahedron Lett. 2003, 44, 9055; (f)
Shirini, F.; Zolfigol, M. A.; Safari, A.; Mirjalili, B. F. Tetrahedron
Lett. 2003, 44, 7463; (g) Shirini, F.; Zolfigol, M. A.; Mallakpour, B.;
Mallakpour, S. E.; Hajipour, A. R.; Baltork, I. M. Tetrahedron Lett.
2002, 43, 1555; (h) Lee, S. Y.; Lee, B. S.; Lee, C. W.; Oh, D. Y. J.
Org. Chem. 2000, 65, 256.
[8] (a) Majireck, M. M.; Witek, J. A.; Weinreb, S. M. Tetrahedron Lett.
2010, 51, 3555; (b) Martin, M.; Martinez, G.; Urpi, F.; Vilarrasa, J.
Tetrahedron Lett. 2004, 45, 5559; (c) Amold, J. N.; Hayes, P. Q.;
Kohaus, R. L.; Mohan, R. S. Tetrahedron Lett. 2003, 44, 9173; (d)
Lukin, K. A.; Narayanan, B. A. Tetrahedron 2002, 58, 215.
[9] (a) Zhang, G. F.; Wen, X.; Ding, C. R.; Cao, X. J. RSC Adv. 2013, 3,
22918; (b) Zhang, G. F.; Wen, X. J. Org. Chem. 2011, 76, 4665; (c)
Zhou, X. T.; Yuan, Q. L.; Ji, H. B. Tetrahedron Lett. 2010, 51, 613;
(d) Zhou, X. T.; Yuan, Q. L.; Ji, H. B. Tetrahedron Lett. 2010, 51,
613; (e) Shaabani, A.; Farhangi, E. Appl. Catal. 2009, 371, 148; (f)
Bahrami, K.; Khodaei, M. M.; Gorgin, U. Chin. J. Chem. 2009, 27,
384; (g) Gogoi, P.; Hazarika, P.; Konwar, D. J. Org. Chem. 2005, 70,
1934; (h) Kanta, D. S. Synth. Commun. 2004, 34, 4409.
4
5
H2N OH
+
H
H
c)
H2N OH2
H2N OH
RuCl3
N2
H2
H2N NHOH
HN=NH
H2O
Conclusions
In conclusion, we have developed an efficient meth-
od for the deoximation of ketoximes and aldoximes us-
ing RuCl3 as the catalyst and without any acceptors un-
der mild conditions. This procedure appears to be ad-
vantageous in terms of chemical yields, simple workup
and environmentally friendly reaction conditions, and
avoiding use of stoichiometric amounts of metal re-
agents. Possible mechanism for the deoximation reac-
tion has been proposed.
Experimental
Procedure for the catalytic deoximation
A mixture of oxime (1 mmol), RuCl3 (0.05 mmol or
0.1 mmol, 5.2 mg or 10.4 mg) and PTSA (0.6 mmol,
103 mg) in DMA/H2O (2.1 mL) was powerfully stirred
at 120 ℃ under N2 (1 atm). The mixture was con-
tinually and powerfully stirred for a certain period of
time, the conversion and selectivity of the product were
detected by GC. After completion of the reaction, H2O
(10 mL) and DCM (10 mL) were added, the organic
layer was separated and the aqueous layer extracted
with dichloromethane (10 mL×2). The combined or-
ganic extracts were dried over anhydrous sodium sulfate,
filtered, and concentrate under reduced pressure. The
residue was purified by silica gel column chromatog-
raphy (petroleum/EtOAc＝20/1) to give the correspond-
ing ketones or nitriles.
[10] (a) Li, D. M.; Deng, Y. Q. Tetrahedron Lett. 2004, 45, 265; (b)
Maynez, S. R.; Pelavin, L.; Erker, G. J. Org. Chem. 1975, 40, 3302;
(c) DePuy, C. H.; Ponder, B. W. J. Am. Chem. Soc., 1959, 81, 4629.
[11] Lin, M. H.; Liu, H. J.; Chang, C. Y.; Lin, W. C.; Chuang, T. H. Mol-
ecules 2012, 17, 2464.
[12] Na, Q.; Shi, X. X. Synlett 2011, 7, 1028.
[13] Chavan, S. P.; Soni, P. Tetrahedron Lett. 2004, 45, 3161.
[14] (a) Jin, X. K.; Liu, Y. X.; Lu, Q. Q.; Liu, R. H. Org. Biomol. Chem.
2013, 11, 3776; (b) Zhang, J. W.; Jiang, Q. Q.; Yang, D. J.; Zhao, X.
M.; Dong, Y. L.; Liu, R. H. Chem. Sci. 2015, DOI:
10.1039/C5SC01044F.
[15] Sandler, S. R. Organic Functional Group Preparations, Academic
Press, New York, 1968.
(Pan, B.; Qin, X.)
1014
www.cjc.wiley-vch.de
© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2015, 33, 1011—1014