On the oxidation of different iminic bonds by excess of 3-chloroperbenzoic acid

Article abstract of DOI:10.1055/s-0032-1317760

In the present work the behavior of different substituted iminic bonds toward the oxidative action of 3-chloroperbenzoic acid is reported. The C=N bond was or was not oxidized to oxaziridines, amides, oximes, nitroso-, nitro-, and azodioxy compounds depending on the substituents at the iminic group and on the imine/MCPBA stoichiometric ratio.

Full text of DOI:10.1055/s-0032-1317760

LETTER
▌53
letter
On the Oxidation of Different Iminic Bonds by Excess of 3-Chloroperbenzoic
Acid
Oxidation of Different Iminic Bonds
Luigino Troisi,*a Marina M. Carrozzo,a Cinzia Citti,a Aurelia Falcicchio,b Rosmara Mansueto,a Francesca Rosato,a
Giuseppe Cannazzac
a
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via Prov. le Lecce-Monteroni, 73100 Lecce, Italy
Fax +39(0832)298732; E-mail: luigino.troisi@unisalento.it
b
Istituto di Cristallografia (IC-CNR) , Via Amendola 122/o, 70125 Bari, Italy
c
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, via Campi 183, 41125 Modena, Italy
Received: 19.10.2012; Accepted after revision: 15.11.2012
Moreover, the azodioxy dimer 3c was obtained in quanti-
Abstract: In the present work the behavior of different substituted
tative yield by reaction of 1.1 mmol MCPBA with the iso-
iminic bonds toward the oxidative action of 3-chloroperbenzoic
lated oxaziridine 3a.
acid is reported. The C=N bond was or was not oxidized to oxaziri-
dines, amides, oximes, nitroso-, nitro-, and azodioxy compounds
depending on the substituents at the iminic group and on the
imine/MCPBA stoichiometric ratio.
The same result was obtained on oxidizing the cyclic im-
ine 3,4-dihydro-2H-pyrrole 4 with 1.1 mmol of MCPBA;
the condensed oxaziridine 4a (yield 98%) was obtained in
this case. Product 4a was subsequently oxidized into ni-
Key words: imines, oxidation, oxaziridines, C-nitroso compound,
oximes
troso compound 4b that rapidly dimerized to azoxydimer
4c when a further 1.1 mmol of MCPBA were added. Fur-
thermore, on heating 4c in toluene (80 °C), 4d was ob-
Although the reduction1 and hydrolysis2 of imines has
been largely studied, only a few publications report its be-
havior toward oxidizing agents. It has been reported that
benzylidene alkylamines lead to the corresponding oxa-
ziridines by stoichiometric oxidation with peracids,3 urea
hydrogen peroxide,4 and cobalt-mediated molecular
oxygen5 (Scheme 1).
tained (yield 80%, Scheme 3).12
Continuing our studies on the oxidation of imines with
MCPBA we have discovered outcomes strongly depen-
dent on the C=N bond substituents. Due to the lower
basicity of the nitrogen in 5–7 with respect to compounds
1–4, the second oxygen transfer on oxaziridines 5a–7a,
formed on initial oxidation, did not take place. Instead,
N,N-diarylamides 8–10 were obtained both with 1.1 mmol
or 2.2 mmol of peracid, after a carbon–nitrogen migration
of the aryl group (Scheme 4). Amides were also obtained
in reactions of imines with sodium perborate13 or with
MCPBA and BF3·OEt2.14
O
H
H
[O]
N
N
R
Ar
R
Ar
[O] = MCPBA, urea-hydrogen peroxide, Co/O2
Scheme 1 Synthetic methodology for oxaziridine generation
A further decrease of basicity of the imine nitrogen as in
oximes 11, isoxazolines 12, benzothiadiazines 13, and
osazones 14 (Figure 1), due to the presence of a heteroat-
om on the nitrogen atom, diminished the reactivity
towards C=N oxidation, and starting materials were re-
covered even using 5.0 mmol of MCPBA. Instead the osa-
A number of thermally stable oxaziridines, obtained by
oxidation of benzylidene alkylamines,6 have been em-
ployed both as oxygenating and/or aminating agents of
nucleophilic species7 and as reagents in cycloaddition re-
actions with heterocumulenes,8 alkenes,9 alkynes,10 and
nitriles.11 Reports of reactions of imines with excess
MCPBA are scarce. Previously, we have reported that the
oxidation of benzylidene alkylamines 1–3 by 1.1 mmol of
MCPBA in CH2Cl2 solution led to oxaziridines 1a–3a in
good yields (>90%),12 while nitroso compounds 1b–3b
rapidly dimerized to azodioxy compounds 1c–3c and
were obtained employing 2.2 mmol of MCPBA (Scheme
2). Furthermore compounds 2b, 3b, 2c, and 3c, having a
hydrogen at the α position of R1, undergo isomerization
into oximes 2d and 3d by heating in toluene solution.
Ar
N
R
O
N
OH
O
Ph
N
Ar
12a: Ar = 4-tolyl
12b: Ar = 1-naphthyl
11a: R = H
11b: R = Me
O2
S
Cl
N
N
N
Ph
N
R2
R1
13a: R1 = H; R2 = Me
13b: R1, R2 = (CH2)3
14
SYNLETT 2013, 24, 0053–0056
Advanced online publication: 11.12.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317760; Art ID: ST-2012-D0903-L
© Georg Thieme Verlag Stuttgart · New York
Figure 1

54
L. Troisi et al.
LETTER
R2
Ar
R2
Ar
R2
Ar
O
O
MCPBA (1.1 mmol)
CH2Cl2, 0 °C
O
MCPBA (1.1 mmol)
CH2Cl2, 0 °C
N
N
N
R1
R1
R1
1–3
1a–3a
1: R1 = t-Bu, R2 = H, Ar = Ph
2: R1 = n-Bu, R2 = H, Ar = Ph
3: R1 = n-Bu, R2 = Me, Ar = Ph
R2
Ar
OH
N
O
O
+
C
R1N
R
2d, 3d
1b–3b
R1
O
N
N
R1
O
1c–3c
Scheme 2 Oxidative action of the MCPBA toward N-alkyl imines
Other heterocycles with similar structure exhibit the same
behavior. When 16 was treated with 2.2 mmol of peracid,
16b was formed, which converted into the azoxydimeric
form 16c (yield 98%,16 Scheme 6). These results indicate
that the oxygen bound to the iminic carbon atom increases
reactivity toward oxidation reaction.
MCPBA
(1.1 mmol)
MCPBA
(1.1 mmol)
N
O
O
O
CH2Cl2, 0 °C
CH2Cl2, 0 °C
N
O
N
4
4a
Imidazoline 17, which contains a nitrogen atom connected
to the imine carbon was transformed (50%) into nitroso
compound 17b and subsequently into azoxydimer 17c
when treated with 1.1 mmol of MCPBA. It was not possi-
ble to isolate oxaziridine 17a and the intermediate form of
the second oxidation because of their high reactivity. In-
stead, 17 led to 17c (yield 99%) when treated with 2.2
mmol of peracid (Scheme 7).
O
N
N
OH
O
4d
4b
O
O
N
N
O
Only a 50% conversion of 2H-1,2,4-benzothiadiazine de-
rivatives 18 and 19,17 structurally similar to the imidazo-
lines, into nitroso compounds 18b–19b was observed on
reacting with 1.1 mmol of MCPBA, with azoxydimers
18c and 19c being isolated as final products. On the other
hand, when 2.2 mmol of peracid were employed the trans-
formation to the azoxydimers was complete (99%,
Scheme 8).
O
4c
Scheme 3 Oxidative action of MCPBA toward cyclic imines
MCPBA
(1.1 or 2.2 mmol)
O
R
R
Ar
R
N
N
N
Ar
Ph
CH2Cl2, 0 °C
Ar
Ph
Ph
O
5–7
5a–7a
8–10
5, 8: R = H, Ar = Ph
6, 9: R = H, Ar = 4-ClC6H4
7, 10: R = Me, Ar = C6H5
Scheme 4 Oxidative action of MCPBA toward aryl imines
zone 14 was oxidized on the amine nitrogen, leading to a
mixture of different products.15
On the contrary, imines containing a heteroatom at the im-
ine carbon showed high reactivity towards oxidation. Ox-
azolines 15 reacted with 1.1 mmol of peracid leading to
the stable oxaziridines 15 after five hours. Further addi-
tion of 1.1 mmol of peracid to 15a led to an unstable N-
oxide intermediate which converted into 15b in equilibri-
um with the dimeric compound 15c (yield 98%) and/or
oxime 15d (R = H, Scheme 5).12
Figure 2 Projection of compound 18e at 298 K
Synlett 2013, 24, 53–56
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidation of Different Iminic Bonds
55
O
O
O
N
MCPBA (1.1 mmol)
CH2Cl2, 0 °C
MCPBA (1.1 mmol)
CH2Cl2, 0 °C
N
N
O
O
O
R
R
R
15
15a
R = H or Me
O
N
O
O
O
N
R
OH
15d
O
15b
R
O
O
O
O
N
N
O
O
R
Scheme 5 Oxidative action of the MCPBA toward O-activated cyclic imines
O
O
O
MCPBA (2.2 mmol)
CH2Cl2, 0 °C
O
O
O
N
N
N
N
O
O
O
16
16b
O
16c
Scheme 6 Oxidative action of the MCPBA toward O-activated cyclic imines
ent on the imine carbon make the imine double bond more
reactive; oxaziridines, amides, oximes, nitroso-, nitro-,
and azoxy compounds can be synthesized depending on
the imine/MCPBA stoichiometric ratio.
O
O
O
MCPBA
(1.1 mmol)
MCPBA
(1.1 mmol)
N
N
N
N
O
CH2Cl2, 0 °C, 1 h
CH2Cl2, 0 °C
O
N
N
O
17
17a
General Procedure
An excess of MCPBA (1.1 or 2.2 mmol) in CH2Cl2 (3 mL) was add-
ed to a solution of the requisite imine (1.0 mmol), dissolved in
CH2Cl2 (5 mL), with stirring and cooling (0–5 °C). When reaction
was complete (5–6 h), the excess of m-chloroperbenzoic acid, and
the benzoic acid formed was removed by filtration. The filtrate was
washed twice with a dilute solution of Na2SO3 (5%), then with a so-
lution of Na2CO3 (5%), and finally with H2O. After drying over an-
hyd MgSO4, the mixture was concentrated in vacuo, and the crude
product was purified by column chromatography (silica gel partly
deactivated with Et3N).
O
O
O
O
N
N
N
N
N
O
O
N
O
O
O
17b
17c
Scheme 7 Oxidative action of the MCPBA toward N-activated cyclic
imines
Furthermore, nitro compound 18e (90% yield) was isolat-
ed on treatment of 18 with 5.5 mmol of MCPBA. The
structure of 18e was characterized by X-ray crystallo-
graphic analysis (Figure 2).18
Acknowledgment
Thanks are due to the University of Salento and C.I.N.M.P.I.S.
(Consorzio Interuniversitario Nazionale Metodologie e Processi In-
novativi di Sintesi) for financial support. We would also like to
thank Giuseppe Chita (Istituto di Cristallografia (IC-CNR), Via
Amendola 122/o, 70125, Bari, Italy) for X-ray interpretation.
In summary, in this work we have examined the influence
of substituents on the behavior of imines towards
MCPBA. Oxygen, nitrogen, or sulfur, attached to the ni-
trogen, render the substrates resistant to oxidation of the
π-bond. On the contrary, a heteroatom or carbon substitu-
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnuIpofoiprmntgirStanoIuifpog
r
t
iornat
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 53–56

56
L. Troisi et al.
LETTER
O
O2
S
O2
S
O2
S
Cl
R1
R2
R1
R2
Cl
Cl
[O] (2.2 mmol)
R2
[O] (1.1 mmol)
N
N
N
R1
N
N
N
O
O
18, 19
18a, 19a
18b, 19b
18: R1 = R2 = Me
19: R1–R2 = (CH2)3
O
O2
S
R2
NR1
Cl
O
O2
S
O
Cl
O
N
N
N
R1
NO2
O
NR1
R2
18e
S
Cl
O2
O
18c, 19c
Scheme 8 Oxidative action of the MCPBA toward S-activated cyclic imines
86.1, 170.3. FTIR (CHCl3): 2948, 2845, 1730, (C=O), 1270,
(NO), 1080 cm–1. ESI-HRMS: m/z calcd for C17H33N2O6 [M
+ H]+: 361.2333; found: 361.2330.
References and Notes
(1) (a) For a review, see: Harada, T. In The Chemistry of the
Carbon–Nitrogen Double Bond; Patai, S., Ed.; Interscience:
New York, 1970, 276–293. (b) Rylander, P. N. Best
Synthetic Methods: Hydrogenation Methods; Academic
Press: London, 1985, 193.
(2) Ranu, B. C.; Sarkar, D. C. J. Org. Chem. 1988, 53, 878.
(3) (a) Widmer, J.; Keller-Schierlein, W. Helv. Chem. Acta
1974, 57, 657. (b) Emmons, W. D. J. Am. Chem. Soc. 1956,
78, 6208.
(4) Lin, Y.; Miller, M. J. J. Org. Chem. 2001, 66, 8282.
(5) Damavandi, J. A.; Karami, B.; Zolfigol, M. A. Synlett 2002,
933.
(6) Troisi, L.; Rosato, F. Encyclopedia of Reagents for Organic
Synthesis; John Wiley and Sons: New York, 2011,; DOI:
10.1002/047084289X.rn01335.
(7) Blanc, S.; Bordogna, C. A. C.; Buckley, B. R.; Elsegood, M.
R. J.; Bulman Page, P. C. Eur. J. Org. Chem. 2010, 882; and
references cited therein.
(8) Davis, F. A.; Wei, J.; Sheppard, A. C.; Gubernick, S.
Tetrahedron Lett. 1987, 28, 5115.
(9) Fabio, M.; Ronzini, L.; Troisi, L. Tetrahedron 2007, 63,
12896.
(10) Fabio, M.; Ronzini, L.; Troisi, L. Tetrahedron 2008, 64,
4979.
(11) Troisi, L.; Ronzini, L.; Rosato, F.; Videtta, V. Synlett 2009,
1806.
(12) Perrone, S.; Pilati, T.; Rosato, F.; Salomone, A.; Videtta, V.;
Troisi, L. Tetrahedron 2011, 67, 2090.
(13) Nongkunsarn, P.; Ramsden, C. A. Tetrahedron 1997, 53,
3805.
(14) An, G.; Kim, M.; Kim, J. Y.; Rhee, H. Tetrahedron Lett.
2003, 44, 2183.
(15) (a) Gillis, B. T.; LaMontagne, M. P. J. Org. Chem. 1967, 32,
3318. (b) Witkop, B.; Kissman, H. M. J. Am. Chem. Soc.
1953, 75, 1975. (c) Lynch, B. M.; Pausacker, K. H. J. Chem.
Soc. 1953, 2517.
Z-Isomer: yield 89.7 mg, 49%, oil. 1H NMR (400.13 MHz,
CDCl3): δ = 1.04 (3 H, s, CCH3), 1.14 (3 H, s, CCH3), 1.20
(3 H, d, J = 6.1 Hz, CHCH3), 1.86 (3 H, s, COCH3), 2.15 (1
H, dd, J = 15.3, 3.1 Hz, CHaHbCH), 2.78 (1 H, dd, J = 15.3,
9.7 Hz, CHaHbCH), 4.84–4.92 (1 H, m, CHaHbCH). 13
C
NMR (100.62 MHz, CDCl3): δ = 20.5, 21.2, 21.9, 43.2, 67.3,
97.9, 170.5. FTIR (CHCl3): 2950, 2845, 1735, (C=O), 1270,
(NO), 1080 cm–1. ESI-HRMS: m/z calcd for C17H33N2O6 [M
+ H]+: 361.2333; found: 361.2330.
(17) Carrozzo, M. M.; Battisti, U. M.; Cannazza, G.; Citti, C.;
Parenti, C.; Troisi, L. Tetrahedron Lett. 2012, 53, 3023.
(18) (a) Crystal Data for Compound 18e
C9H9Cl1N2O5S1, Fw = 292.69, T = 298 K, monoclinic, space
group P21/n, a = 11.983(13), b = 7.370(6), c = 15.357(12) Å,
α = 90, β = 113.89(5), γ = 90, V = 1240.0 Å3, Z = 4, μ (Mo
Kα) = 0.491 mm–1; crystal dimensions 0.3 × 0.2 × 0.06 mm.
The X-ray experiments were carried out at r.t. by a Bruker-
Nonius KappaCCD diffractometer, using Mo Kα radiation
(λ = 0.71073 Å). Data collection was performed by
COLLECT (Nonius, 2002. COLLECT and EVAL. Nonius
BV, Delft, The Netherlands), cell refinement by DIRAX18b
and data reduction by EVAL (Nonius, 2002. COLLECT and
EVAL. Nonius BV, Delft, The Netherlands). Absorption
effects were corrected by SADABS.18c The crystal structure
was solved by SIR201118d and refined by SHELXL-97.18e
The H atoms were placed at calculated positions and refined
according to a riding model approximation. The software
used for preparing the material for publication: WinGX;18f
the software used for molecular graphics: Ortep-3.18g
Detailed crystallographic data were deposited as CCDC
884506 with the Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB2 1EZ, UK. (b) Duisenberg,
A. J. M. J. Appl. Crystallogr. 1992, 25, 92. (c) Sheldrick, G.
M. SADABS; University of Göttingen: Germany, 2002.
(d) Burla, M. C.; Caliandro, R.; Camalli, M.; Carrozzini, B.;
Cascarano, G. L.; De Caro, L.; Giacovazzo, C.; Polidori, G.;
Siliqi, D.; Spagna, R. J. Appl. Crystallogr. 2007, 40, 609;
the updated version of SIR2008 . (e) Sheldrick, G. M. Acta
Crystallogr., Sect. A: Found. Crystallogr. 2008, A64, 112.
(f) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837.
(g) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.
(16) Compound 16c: total yield 98%, 179.4 mg;
E-Isomer: yield 89.7 mg, 49%, oil; Rf = 0.33 (PE–EtOAc =
9:1). 1H NMR (400.13 MHz, CDCl3): δ = 1.23 (3 H, d, J =
6.5 Hz, CHCH3,), 1.57 (3H, s, CCH3), 1.59 (3 H, s, CCH3),
1.96 (3 H, s, COCH3), 1.97–2.07 (1 H, m, CHaHbCH), 2.47–
2.53 (1 H, m, CHaHbCH), 5.02–5.10 (1 H, m, CHCH3). 13
C
NMR (100.62 MHz, CDCl3): δ = 20.8, 24.5, 27.6, 45.7, 66.8,
Synlett 2013, 24, 53–56
© Georg Thieme Verlag Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.