Cerium(IV) ammonium nitrate promoted synthesis of O-phthalimide oximes from vinyl azides and N-hydroxyphthalimide

Article abstract of DOI:10.1016/j.tetlet.2020.152533

O-Phthalimide oximes with an N–O–N fragment were synthesized in high yields via the reaction of vinyl azides with phthalimide-N-oxyl radicals derived from N-hydroxyphthalimide under the action of cerium(IV) ammonium nitrate. The disclosed process is based on the radical transformation of vinyl azides with the elimination of nitrogen and the formation of iminyl N-radicals. The developed approach exploited the dual reactivity of imide-N-oxyl radicals. They act as O-components for oxidative C–O coupling with vinyl azides and participate in subsequent formation of the N–O bond via their recombination with intermediate iminyl radicals.

Full text of DOI:10.1016/j.tetlet.2020.152533

Journal Pre-proofs
Cerium(IV) ammonium nitrate promoted synthesis of O-phthalimide oximes
from vinyl azides and N-hydroxyphthalimide
Stanislav A. Paveliev, Liliya S. Alimkhanova, Anna V. Sergeeva, Alexander
O. Terent'ev
PII:
S0040-4039(20)31026-1
DOI:
Reference:
https://doi.org/10.1016/j.tetlet.2020.152533
TETL 152533
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
12 August 2020
23 September 2020
2 October 2020
Please cite this article as: Paveliev, S.A., Alimkhanova, L.S., Sergeeva, A.V., Terent'ev, A.O., Cerium(IV)
ammonium nitrate promoted synthesis of O-phthalimide oximes from vinyl azides and N-hydroxyphthalimide,
Tetrahedron Letters (2020), doi: https://doi.org/10.1016/j.tetlet.2020.152533
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Cerium(IV) ammonium nitrate promoted synthesis
of O-phthalimide oximes from vinyl azides and N-
hydroxyphthalimide
Leave this area blank for abstract info.
Stanislav A. Paveliev, Liliya S. Alimkhanova, Anna V. Sergeeva, Gennady I. Nikishin, Alexander O. Terent’ev
N3
O
O
O
N
O
CAN
MeOH
-N2
+
N
OH
N
R
O
O
N
R = H, Alk, Hal,
MeO, NO2, CF3
O
R
O
12 examples, 54-88% yield

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Cerium(IV) ammonium nitrate promoted synthesis of O-phthalimide oximes from
vinyl azides and N-hydroxyphthalimide
Stanislav A. Pavelieva, Liliya S. Alimkhanovaa,b, Anna V. Sergeevaa,b, and Alexander O. Terent’eva,b
a N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky prosp., Moscow 119991, Russian Federation
b D. I. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Square, Moscow 125047, Russian Federation
———
ARTICLE INFO
ABSTRACT
 Corresponding author. Tel.: +7-916-385-4080; e-mail: terentev@ioc.ac.ru (A.O. Terent’ev)
Article history:
Received
Received in revised form
Accepted
O-Phthalimide oximes with an N-O-N fragment were synthesized in high yields via the reaction
of vinyl azides with phthalimide-N-oxyl radicals derived from N-hydroxyphthalimide under the
action of cerium(IV) ammonium nitrate. The disclosed process is based on the radical
transformation of vinyl azides with the elimination of nitrogen and the formation of iminyl N-
radicals. The developed approach exploited the dual reactivity of imide-N-oxyl radicals. They
act as O-components for oxidative C-O coupling with vinyl azides and participate in subsequent
formation of the N-O bond via their recombination with intermediate iminyl radicals.
Available online
Keywords:
Free radicals;
Imide-N-oxyl radicals;
N-Hydroxyphthalimide;
Vinyl azides;
2020 Elsevier Ltd. All rights reserved.
Cerium(IV) ammonium nitrate
bifunctional
C-C,22, 23 C-N24, 25 and C-I26, 27 bonds were obtained. Recently, we
developed an approach for the selective radical
products
with
C-O,18-21
1. Introduction
The present work lies at the intersection of important areas of
organic chemistry, such as the chemistry of O-centered radicals,
oxidative transformations under the action of cerium(IV)
ammonium nitrate, and radical reactions involving C=C bonds.
difunctionalization of styrenes under the action of NHPI and
CAN.28
Vinyl azides possess a rich spectrum of reactivity, and have
therefore gained growing interest as versatile precursors for
Radicals with an unpaired electron localized on an N-O
fragment, namely, N-oxyl radicals are widely used in organic and
biological chemistry, the development of organic radical batteries
and material design.1 In organic synthesis, more stable nitroxyl
radicals are employed as free radical scavengers1 and catalysts
for the oxidation of alcohols.2-7 Less stable imide-N-oxyl radicals
have found application as mediators of hydrogen atom
organic synthesis.29-31 Reactions of ArSO2∙,32-34 CF3∙,35-39 SCN∙,40
41
NO2∙,34 ArC(O)∙34,
and various C-centered radicals42-44 with
vinyl azides have been reported. In general, such processes are
accompanied by the addition of a radical species to the terminal
atom of the C=C bond of vinyl azides with the release of nitrogen
and the formation of an iminyl radical. Depending on the reaction
conditions, the formation of ketones and enamines can occur. To
date, no intermolecular addition reactions of such iminyl radicals
have been reported.
abstraction for the subsequent formation of C-C, C-O, C-S, and
6, 8-13
C-N bonds.2,
Phthalimide-N-oxyl (PINO) generated from
inexpensive N-hydroxyphthalimide (NHPI) is widely employed
in the aerobic oxidation of bulk chemicals.8, 9, 14, 15
In the present work, the selective coupling of PINO radical
with vinyl azides, followed by recombination with iminyl
radicals was carried out to form O-substituted oximes containing
two phthalimide-N-oxyl fragments (Scheme 1).
The main approach for the generation of imide-N-oxyl
radicals is the oxidation of N-hydroxyimides under the action of
transition metal salts or hypervalent iodine compounds. Among
the metal-based reagents, cerium(IV) ammonium nitrate (CAN)
is widely used due to its commercial availability, ease of
handling, low toxicity and high solubility in organic solvents.
N3
N3
X
X
R
R
Present work:
Previous works:
O
N2
HAT
Using a combination of NHPI and CAN, a number of C-H
X
NH2
NH
O
16
functionalization12,
developed.
and oxidation17 processes have been
H2O
N
N
X =
N O
X
X
X
X
R
X
R
R
X
R
R
X = ArSO2, CF3, NO2, ArC(O)
O
In the last decade, the selective functionalization of alkenes
with N-oxyl radicals has become a prominent area of modern
organic chemistry. In the reactions of styrenes with NHPI,
Scheme 1. The present work in the context of the iminyl
radical mediated transformations of vinyl azides.

2
Tetrahedron
2. Results and Discussion
CAN/NHPI 2 molar ratios from 1 to 1.5 did not improved the
yield of the target product (Entry 8, 87%). The optimal reaction
time was 1 h, since carrying out the reaction for 30 min resulted
in decrease in the yield of the imide oxime 3a (Entry 9, 80%).
Prolonging the reaction time to 2 h reduced the yield of 3a (Entry
10, 84%).
In the present work we report the reaction of substituted vinyl
azides 1a-l and NHPI 2 under the action of CAN with the
formation of O-phthalimide oximes 3a-l (Scheme 2).
With the optimized conditions (Table 1, Entry 1) in hand, the
synthesis of O-phthalimide oximes 3a-l from various vinyl azides
1a-l was performed in order to study the scope of the discovered
process (Table 2).
O
O
N
O
O
N
O
N3
CAN
O
+
N OH
R
N
Table 2.
R
Scope of O-phthalimide oximes 3a-l synthesized from vinyl
O
2
O
3a-l
1a-l
azides 1a-l and NHPI 2.a
1a
1b
1c
1d
1e
: R = C6H5
1g
: R = 4-O2NC6H4
: R = 4-F3CC6H4
: R = 3-MeC6H4
: R = 3-MeOC6H4
: R = 2-MeC6H4
: R = 2-MeOC6H4
: R = 4-MeC6H4 1h
: R = 4-t-BuC6H4 1i
: R = 4-FC6H4
: R = 4-ClC6H4
O
O
1j
1k
N
O
O
N
N3
O
1f
: R = 4-MeOC6H4 1l
O
CAN
N
N
OH
+
Scheme 2. Reaction of vinyl azides 1a-l, NHPI 2 and CAN to
give O-phthalimide oximes 3a-l.
R
R
MeOH
rt, 1 h
O
O
1a-l
2
3a-l
An important feature of this work is that formation of the N-
O-N fragment proceeds through the recombination of N-centered
iminyl and O-centered PINO radicals.
O
O
O
O
O
O
N
O
N
O
N
O
N
N
N
O
O
O
O
O
O
N
N
N
t-Bu
O
O
O
Initially, we studied the model transformation of vinyl azide
1a under the action of NHPI 2 and CAN (Table 1).
3a (85)
3b (82)
3c (79)
Table 1.
O
O
O
N
O
O
N
O
N
O
Optimization of the CAN-mediated reaction of vinyl azide 1a
with NHPI 2.
O
N
O
N
N
O
O
O
O
O
O
N
N
N
F
Cl
MeO
O
O
O
3d (73)
3e (75)
3f (54)
O
O
N
O
N3
O
O
O
N
N
O
O
N
O
O
N
O
O
O
CAN
O
N
O
N
N
O
N
N
OH
+
O
O
O
Solvent
N
O
O
N
N
rt, 0.5-2 h
O
O
1a
2
3a
O
O2N
F3C
O
O
Molar
Time
(h)
Yield
3i (88)
3g (67)
3h (74)
Entrya ratio
Solvent
3a (%)b
1a:2:CAN
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:3:3
1:2:3
1
2
3
4
5
6
7
8
9
10
MeOH
CH3CN
1
1
1
1
1
1
1
1
88 (85)
74
70
76
78
81
85
87
80
O
O
N
O
O
N
O
O
N
O
N
O
N
O
Acetone
THF
CH2Cl2/H2O (3:2)
EtOAc/H2O (3:2)
MeOH
MeOH
MeOH
MeOH
O
N
O
O
O
N
O
N
O
N
O
OMe
O
O
OMe
3j (69)
3k (84)
3l (63)
a Reagents and conditions: CAN (1.0 mmol, 548 mg) was added to a mixture
of vinyl azide 1a-l (0.5 mmol, 73-107 mg) and NHPI 2 (1.0 mmol, 163 mg) in
MeOH (5 mL), and stirred at 20-25 °C for 1 h under an air atmosphere;
isolated yields.
1:2:2
1:2:2
0.5
2
84
a
Reagents and conditions: CAN (1.0-1.5 mmol) was added to a mixture of
vinyl azide 1a (0.5 mmol) and NHPI 2 (1.0 mmol) in solvent (5 mL), and
stirred at 20-25 °C for 0.5-2 h under an air atmosphere. For entries with a
mixture of solvents, the v/v ratio is in parentheses. NMR yields; isolated
yields are given in parentheses.
The reaction proceeded in high yields with vinyl azides
1b,c,i,k, containing weakly electron-donating alkyl substituents
on the aromatic ring (3b,c,i,k, 79-88%). The reactions with vinyl
azides 2d,e,h possessing moderately electron-withdrawing
groups (F, Cl, CF3) yielded O-phthalimide oximes 3d,e,h with
slightly diminished yields (73-75%). Vinyl azides bearing
strongly electron-donating (MeO) or -withdrawing (NO2)
substituents gave products 3f,g,j,l with the lowest yields of 54-
69%.
b
The effect of the solvent nature on the yield of O-phthalimide
oxime 3a was evaluated in Entries 1-6. In an initial experiment
using MeOH as the solvent, target product 3a was obtained in
88% yield. Carrying out the reaction in CH3CN, acetone or THF,
as well as in two-phase systems (CH2Cl2/H2O, EtOAc/H2O) led
to a decrease in the yield of 3a (Entries 2-6, 70-81%). Therefore,
MeOH proved to be the best solvent for the process under study,
and was chosen for further optimization.
Based on the literature data concerning the generation of
PINO radicals from NHPI under the action of CAN45 and the
addition of radical species to vinyl azides,29-31 we proposed a
Increasing the amount of NHPI 2 and CAN led to a slight
decrease in the yield of 3a (Entry 7, 85%). The increase in

3
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1
O
O
PINO
N3
Ph
N O
CAN
N
OPhth
A
N OH
Ph
2
O
O
N2
OPhth
OPhth
N
3
OPhth
B
Ph
Ph
Scheme 3. Proposed mechanism for the CAN-mediated
synthesis of O-phthalimide oxime 3 from vinyl azide 1 and
NHPI 2.
The reaction begins with the formation of PINO radical from
NHPI 2 under the action of CAN, followed by addition to the
terminal carbon atom of the C=C bond of vinyl azide 1. Nitrogen
elimination from the resulting radical A occurs with the
formation of iminyl radical B. At the last stage radical B is
intercepted by the PINO radical to form product 3.
3. Conclusion
In summary, we have disclosed the reaction between various
vinyl azides and N-hydroxyphthalimide resulting in the formation
of O-phthalimide oximes with an N-O-N fragment. The reaction
proceeds under the action of cerium(IV) ammonium nitrate
which acts as an oxidizing agent for the formation of the
phthalimide-N-oxyl radical from NHPI. The radical pathway
starts with the addition of the PINO radical to the C=C bond of
the vinyl azide which triggers
a
cascade of radical
transformations, including generation of the iminyl radical and its
recombination with the PINO radical. The developed approach
was successfully extended to various substituted vinyl azides. As
a result, a wide range of O-phthalimide oximes was obtained with
the yields ranging from 54-88%.
Acknowledgment
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Scientific Schools Development Program by Zelinsky Institute
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Supplementary data
Supplementary data (experimental procedures, spectroscopic
data for all of the synthesized compounds) associated with this
article can be found, in the online version, at
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Declaration of interests
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☒ The authors declare that they have no known
competing financial interests or personal
relationships that could have appeared to influence
the work reported in this paper.
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4
Tetrahedron
☐The authors declare the following financial
interests/personal relationships which may be
considered as potential competing interests:
N3
O
N
O
O
N OH
O
N
CAN
+
R
O
MeOH
-N2
O
O
N
R = H, Alk, Hal,
O
R
MeO, NO2, CF3
12 examples, 54-88% yield
 Cerium(IV) ammonium nitrate as a
reagent for radical oxidative
transformations.
 Preparative generation of imide-N-
oxyl radicals from N-
hydroxyphthalimide.
 Addition of O-centered imide-N-oxyl
radicals to double carbon-carbon
bonds.
 Reactions involving vinyl azides with
the formation of iminyl radicals.
 Formation of N-O bond through the
recombination of N- and O-centered
radicals.