Cerium (IV) ammonium nitrate (CAN) initiated O-alkylation of oximes with N-vinyl lactams

Article abstract of DOI:10.1016/j.cclet.2010.12.027

O-Alkylation of oximes with N-vinylpyrrolidin-2-one or N-methyl-N- vinylacetamide was efficiently initiated by a catalytic amount of cerium (IV) ammonium nitrate (CAN), giving the corresponding oxime ether derivatives in good yield.

Full text of DOI:10.1016/j.cclet.2010.12.027

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Chinese Chemical Letters 22 (2011) 655–658
www.elsevier.com/locate/cclet
Cerium (IV) ammonium nitrate (CAN) initiated
O-alkylation of oximes with N-vinyl lactams
Jian Tao Wang a, Xiao Dong Jia b, Li Jun Peng a, Long Min Wu a,
*
a State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
b College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China
Received 20 September 2010
Abstract
O-Alkylation of oximes with N-vinylpyrrolidin-2-one or N-methyl-N-vinylacetamide was efficiently initiated by a catalytic
amount of cerium (IV) ammonium nitrate (CAN), giving the corresponding oxime ether derivatives in good yield.
# 2010 Long Min Wu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Cerium (IV) ammonium nitrate; O-Alkylation; Oxime; N-Vinylpyrrolidin-2-one; N-Methyl-N-vinylacetamide
With a rather high reduction potential value of +1.61 V vs. NHE (normal hydrogen electrode), cerium (IV)
ammonium nitrate (CAN) has emerged as a powerful one-electron oxidant [1]. CAN offers several advantages like
easy handling, non-toxicity, and good solubility in organic solvents. It has been noted that more than 2 equiv. of CAN
are required inevitably in most CAN-mediated oxidations, whereas catalytically CAN-induced reactions have scarcely
been reported [2]. So making CAN catalytic performance should be a main focus of future on CAN chemistry.
Addition of organometallic reagents or radical species to oxime ethers have become an important protocol for many
chemical conversions [3,4]. In general, oxime ethers have been prepared either by the condensation of O-alkyl
hydroxylamine with a corresponding aldehyde or by the reaction of oximes with alkyl halides under basic conditions
[5]. Recently, new methods have been developed upon transition metal-catalyzed allylic substitution of oximes [6],
Michael addition [7], Cu-catalyzed cross-coupling reaction [8], and cation radical tris(aryl)aminium oxidation of O-
alkylation of oximes with N-vinyl lactams [9]. In the present work we will report CAN initiated O-alkylation of oximes
(1) with N-vinyl lactams, in which the corresponding oxime ethers (3 or 4) were produced in good yield.
We started with the addition reaction of (E)-4-chlorobenzaldehyde oxime (1e) to N-vinylpyrrolidin-2-one (2a,
Scheme 1). It was used to optimize the reaction conditions and found that 10 mol% of CAN resulted in the formation
of 3e in a yield of 95%. Although the reaction proceeded also readily in the presence of only 2 mol% of CAN, a slightly
lower yield was obtained and the reaction time was largely prolonged. It was still found that more than 10 mol% of
CAN lead to a dramatic decrease in the yield of adducts and promoted decomposition of products. In some cases, the
product of decomposition, 4-chlorobenzaldehyde, was detected. The solvent effects were then investigated using
10 mol% of CAN. Both of dichloromethane and acetonitrile were found to be the most favorable solvents.
* Corresponding author.
E-mail address: nlaoc@lzu.edu.cn (L.M. Wu).
1001-8417/$ – see front matter # 2010 Long Min Wu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.12.027

[()TD$FIG]
656
J.T. Wang et al. / Chinese Chemical Letters 22 (2011) 655–658
Scheme 1.
The substrate scope for aldoximes (entries 1–7, Table 1) was extended under the optimized conditions. It shows that
the reaction occurred satisfactorily in good yield and that an electron-withdrawing substituent bearing on the phenyl
ring of 1 led to a higher yield (entries 4–7, Table 1), whereas an electron-donating group (entries 1 and 3, Table 1)
resulted in a lower yield and a longer reaction time. This might be attributed to the lower oxidation potential of 1a and
1c, compared with those bearing an electron-withdrawing group [10], and partial decomposition of substrates.
Replacement of 2a by N-methyl-N-vinylacetamide 2b proved to be encouraging (entries 9 and 10, Table 1 and Scheme
2). Nevertheless, two rotamers exhibiting double sets of 1H NMR spectroscopy existed in the latter due to the restricted
rotation of the amide bond, as having been reported previously [9b]. The conformation of rotamer 4 (major) and 40
(minor) was deduced by NOE difference spectrum correlations. NOE enhancement of O–CH–N proton signals (q,
5.86) for 4 or NCH3 proton signals for 40 (q, 2.80) was observed on irradiation of NCOCH3 protons (s, 2.25–2.02). The
ratio of 4 to 40 was estimated to be ca. 3:1 (Table 1).
Addition of ketoximes (1i–1l) and 2-furaldehyde oxime (1m) to 2a also occurred under the same conditions, giving
the corresponding products 3 (entries 11–15, Table 1).
To identify the most possible reaction mechanism, some tests were carried out: (a) The reaction was performed both
in the absence of CAN and in the presence of cerium trichloride or cerium trinitrate. No reaction took place in the
former, and only a small amount of oximes converted to oxime ethers after 24 h in the latter; and (b) the aqueous
extraction from the acetonitrile reaction solution was subjected to a test of color fading of methyl orange solution,
which is characteristic of Ce4+. It failed to fade the color of methyl orange solution. These observations suggest: (a)
CAN most likely serves as a one-electron oxidant in the CAN initiated reaction. Because the oxidation potentials of 2a
(1.12 V vs. SCE [12]) and 2b (1.51 V vs. SCE [11]) are significantly lower than those of 1a–1g (1.45–2.14 V vs. Ag/
AgCl electrode) [10], enamide 2 will be preferentially oxidized by CAN, giving the corresponding cation radical 2+,
Table 1
CAN initiated addition of oximes 1 to N-vinyl lactams 2a or 2ba.
Entry
Oximes
Ar (R)
Lactam
Timeb (h)
Product
Yield of 3 or 4c (%)
R2
1
1a
1b
1c
1d
1e
1f
p-CH3OPh
Ph
H
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2a
2a
2a
2a
2a
3
3a
3b
73
87
85
89
95
91
88
83
72
88
82
85
90
84
85
2
H
1.5
3
3
p-CH3Ph
o-ClPh
p-ClPh
p-NO2Ph
m-NO2Ph
o-OHPh
p-CH3Ph
p-ClPh
Ph
H
3c
4
H
1
3dd
3e
5
H
1
6
H
1.5
2
3f
7
1g
1h
1c
1e
1i
H
3ge
8
H
2
3he
9
H
2
4c (3.2:1)d
10
11
12
13
14
15
H
2
4e (2.7:1)d
CH3
CH3
Ph
CH3
H
2
3i
1j
p-NO2Ph
Ph
2
3je
3ke
3le
3m
1k
1l
2
CH3
2.5
1.5
1m
2-Furyl
a
Reaction conditions: oximes (1.05 mmol), N-vinyl lactams (1 mmol), CAN (0.10 mmol), CH3CN (10 mL), r.t.
The reaction time.
b
c
d
e
Isolated yields of the products after column chromatography.
1
The ratio of 4 to 40 was evaluated using the characteristic H NMR peaks for O-CH-N at 5.86 (4) and 6.57 (40).
Five new compounds were characterized by 1H and 13C NMR spectroscopy, EI-MS, and HRMS.

[()TD$FIG]
J.T. Wang et al. / Chinese Chemical Letters 22 (2011) 655–658
657
O
1
1
1
R
R
R
mol% CAN
N
O
N
10
O
+
N
N
N
N
CH CN, r. t.
3
OH
O
O
4
1
4'
2b
Scheme 2.
[()TD$FIG]
Scheme 3.
and (b) Ce4+ was reduced to Ce3+ during the course of reaction, and a possible acid-induced process would be ruled
out, for no reduction of CAN would be detected if CAN acted as a Lewis acid catalyst [2b]. As such, a cation radical-
mediated O-alkylation of oximes as depicted in Scheme 3 is proposed to rationalize the reaction. [13]
In conclusion, we present herein a simple, novel, highly efficient method for O-alkylation of oximes with N-
vinylpyrrolidin-2-one or N-methyl-N-vinylacetamide by using CAN as an initiator. This entry offers several
advantages like short reaction time, good yields, ready availability of the initiator, and mild reaction conditions.
Acknowledgment
Project 20572040 was supported by National Natural Science Foundation of China.
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[13] General procedure: An anhydrous acetonitrile solution (10 mL) of 1 (1.05 mmol) and 2 (1 mmol) was dropwise added to an acetonitrile
solution (10 mL) of CAN (0.10 mmol) at ambient temperature under stirring. After the reaction was completed as monitored by TLC, it was
diluted with water and extracted with 3 ꢀ 10 mL of dichloromethane. The crude organic solution was then extracted three times with water to
remove inorganic salts. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced
pressure. The product was separated by silica gel column chromatography eluted with ethyl acetate/acetone (v/v 3:1) to afford the pure oxime
ether as a unique product. Selective data for 3g: Colorless oil; IR (KBr) n 2988, 2956, 1697, 1532, 1418, 1352, 1282, 1269, 1087, 958 cmꢁ1; 1H
NMR (400 MHz, CDCl3): d 8.30 (m, 1H), 8.17–8.20 (m, 1H), 8.11 (s, 1H), 7.95–7.97 (m, 1H), 7.53 (m, 1H), 6.16 (q, 1H, J = 6.0 Hz), 3.42–3.48
(m, 2H), 2.42–2.46 (m, 2H), 2.00–2.03 (m, 2H), 1.48 (d, 3H, J = 6.0 Hz); 13C NMR (100 MHz, CDCl3): d 175.7, 148.4, 147.2, 133.8, 132.3,
129.7, 124.4, 122.8, 80.9, 41.7, 31.6, 18.1, 16.9; MS-EI (70 eV): m/z (rel. int., %) = 277 (0.01), 166 (1.2), 113 (7.5), and 112 (100); HR-ESI-
MS: m/z calcd for C13H15N3O4 + H: 278.1135. Found: 278.1136.