Aminopyridinium iodide as a NH transferring agent for the synthesis of 2-aroyl-3-aryl aziridines

Article abstract of DOI:10.1007/s13738-015-0700-2

A new approach for the synthesis of N-H ketoaziridines is described. 1-aminopyridinium iodide as a NH transferring agent provides a straightforward access to the 2-aroyl-3-arylaziridines from the corresponding 1,3-diarylprop-2-en-1-one. A possible general mechanism involving the N-N ylide is proposed.

Full text of DOI:10.1007/s13738-015-0700-2

J IRAN CHEM SOC
DOI 10.1007/s13738-015-0700-2
ORIGINAL PAPER
Aminopyridinium iodide as a NH transferring agent for the
synthesis of 2‑aroyl‑3‑aryl aziridines
Heshmat A. Samimi1 · Ahmad R. Momeni1
Received: 6 February 2015 / Accepted: 12 July 2015
© Iranian Chemical Society 2015
Abstract A new approach for the synthesis of N–H
ketoaziridines is described. 1-aminopyridinium iodide as
a NH transferring agent provides a straightforward access
to the 2-aroyl-3-arylaziridines from the corresponding
1,3-diarylprop-2-en-1-one. A possible general mechanism
involving the N–N ylide is proposed.
by bromination of the related α,β-unsaturated carbonyl
compounds, followed with the reaction of ammonia solu-
tion [5–10].
Another synthetic pathway for the synthesis of aziridi-
nyl ketones involves formation of β-hydroxyamino deriva-
tives followed by treatment with either metal alcohol-
ates, or hydroxylamine hydrochloride and then potassium
hydroxide [11–14]. It has been reported the interaction of
unsaturated ketones with N-tosyliminoaryliodinanes in the
presence of mono-valent copper complexes produces the
related aziridinyl ketone [15, 16].
Keywords 1,3-diarylprop-2-en-1-one · Ketoaziridine ·
N–N ylide
Introduction
It was also reported that oximes could be converted into
N-unsubstituted aziridines by treatment with Grignard rea-
gents or by reduction with lithium aluminum hydride in
certain cases [17].
The aziridine moiety represents one of the most valuable
three-membered ring systems in organic chemistry that can
undergo various synthetically useful transformations and
are also an important part of many biologically active mol-
ecules. Numerous methods have been reported for the syn-
thesis and the reaction of differently substituted aziridines
containing alkoxy, acetoxy, chloro, bromo, fluoro, amino,
nitro, sulfonyl, and phosphoryl, in which the heteroatom is
directly attached to one or both carbon atoms of the ring
[1–4]. However, most of the methods produce N-substi-
tuted aziridines, such as N-arenesulfonyl, alkoxycarbonyl,
or aryl substituted aziridines. Only a few methods have
been reported for the direct preparation of N–H aziridines
until now.
3,3-Pentamethyleneoxaziridine can transfer its NH
group to electron-deficient olefins to give N-unsubstituted
aziridines in low yields [17, 18]. 2-ketoaziridine starting
materials were also prepared using 1,4-addition of meth-
oxyamine to α,β-unsaturated ketones followed by base-
promoted ring closure [19]. Ylides are another kind of
potential NH transfer agent. Free sulfimides HN = SR2,
sulfur–nitrogen ylide [20–24], are used for the direct syn-
thesis of N-unsubstituted aziridines. An one step synthesis
of aziridine by the type addition off free sulfimide has been
reported but yields are unsatisfactory and enaminoketones
are obtained as major byproducts in moderate yields.
On the other hand, an amineimide, as a type of nitrogen–
nitrogen ylide, is an effective NH source for direct N-unsub-
stituted aziridination of electron-deficient olefins. Recently,
a few method has been reported that tertiary amines such
as N-methylmorpholin [25], 1,4-diazabicyclo[2.2.2]octane
(DABCO) [26, 27]. Quinine chiral tertiary amine [28] and
Troger s base [29] can prepare amine imide which reacts
with chalcone to give desire aziridinyl ketones (Scheme 1).
The most common method for preparation of 2-arroyl-
3-arylaziridines is the one via Gabriel–Cromwell procedure
* Heshmat A. Samimi
samimi-h@sci.sku.ac.ir
1
Department of Chemistry, Faculty of Sciences, The
University of Shahrekord, P. O. Box 115, Shahrekord, Iran
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J IRAN CHEM SOC
NH2OSO3H
Na2CO3/H2O
HI/EtOH
-20OC
OMe
O
N
N
N
N
N
N
N
N
I
NH
NH2
OH
N
N
Quinine
Troger's Base
N-methylmorpholine
DABCO
Scheme 3 Synthesis of 1-aminopyridinium iodide (1)
Scheme 1 Some reported tertiary amines for preparation of amine
imide
Table 1 Optimization of the reaction conditions
H
H
O
N
N
N
I
NH2
O
Ph
Ph
O
conditions
LG-NH2
NR3
2a
3a
NR3
HN
OH
Ph
Yield (%)a,e
LG
Entry
Solvent
Base
Ph
1
THF
Et3N
Et3N
Et3N
Et3N
py
29
11
15
29
41
17
26
34
56
16
33
48
71
73
65
H2N
NR3
2
DMSO
O
H2N
NR3
3
Dioxane
CH3CN
THF
4
Ph
Ph
5
6
DMSO
Dioxane
CH3CN
THF
py
Scheme 2 Proposed mechanism for synthesis of aziridines from
N–N ylide
7
py
8
py
9
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
A general plausible mechanism of direct NH transfer
agent with tertiary amines in the reported aziridation of
chalcones is outlined in Scheme 2 which proposes that the
aziridination reaction occurs via in situ generation of N–N
ylides.
10
11
12
13b
14c
15d
DMSO
Dioxane
CH3CN
THF
THF
The search for the direct aziridination of olefins to
prepare N-unsubstituted aziridines is currently an attrac-
tive field of research [24–28]. Despite work reported on
the synthesis of ketoaziridines, novel and widely applica-
ble methods for the synthesis of them are still in demand.
Throughout our earlier studies on the ketoaziridines [30–
37], to further develop aziridination reaction, we have dis-
covered a simple and stereo-selective one-pot method for
the synthesis of ketoaziridines by the reaction of chalcones
with 1-aminopyridinium iodide via in situ formation of
N–N ylide. This method describes a novel method which
for the first time utilizes 1-aminopyridinium iodide for the
synthesis of aziridine in a one-pot reaction. According to
our knowledge, this method has not been reported in the
literature.
THF
Bold value indicates the best reaction conditions relative to others
a
Reactions were performed in a ratio of 1:1:2 for the aziridine/1/
base in refluxing solvent for 7 h
b
Ratio of 1:1.5:2 for the aziridine/1/base for 7 h, the optimal condi-
tions
c
Ratio of 1:3:2 for the aziridine/1/base for 7 h
d
Ratio of 1:1.5:3 for the aziridine/1/base for 7 h
e
Isolated yields
in the presence of potassium carbonate in refluxing condi-
tions, followed with the reaction of hydriodic acid. 1-ami-
nopyridinium iodide (1) was used for the preparation of
ketoaziridines (Scheme 3).
Our investigation started with the explore of a one-pot
process which involved the in situ generation of a N–N
ylide of 1-aminopyridinium iodide (l) and subsequent
aziridination of 1,3-diphenylprop-2-en-1-one (2a). When
a solution of 1-aminopyridinium iodide (1 equiv.) (l)
and 1,3-diphenylprop-2-en-1-one (2a) was heated under
Results and discussion
At the outset of this study, 1-aminopyridinium iodide (1)
was prepared via Gösl–Meuwsen procedure [38], by the
reaction of hydroxylamine-O-sulfonic acid with pyridine
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J IRAN CHEM SOC
Table 2 Synthesis of ketoaziridines (3) from 1,3-diarylprop-2-en-
1-one (2) and 1-aminopyridinium iodide (1)
electron-withdrawing and electron-donating groups were
compatible on the 1,3-diphenylprop-2-ene-1-one (2), gen-
erating the functionalized products in good yields. The
experimental results are given in Table 2. All the products
N
Ar2
I
1
were characterized by H, 13C NMR, and IR spectra. The
H
N
NH2
O
known aziridines were characterized by comparison of
their spectroscopic data (1H NMR, 13C NMR, and IR) and
melting point with literature values. The analytical data for
new compounds are also given.
Ar1
O
Ar1
THF/K2CO3
Reflux
2
Ar2
3
Entrya Ar1
Ar2
Yield (%)b Mp (°C)
In conclusion, we have developed a useful strategy for
the synthesis of N–H 2-aroyl-3-aryl aziridines from the cor-
responding 1,3-diarylprop-2-ene-1-one. In the presence of
K2CO3, the reaction of the 1,3-diphenylprop-2-ene-1-one
with 1-aminopyridinium iodide 1, as a NH transferring agent
provides a straightforward access to the 2-aroyl-3-aryl aziri-
dines. A possible general mechanism involving the N–N
ylide is proposed to satisfactorily elucidate the generation of
Ketoaziridines. A comparison of this procedure with previous
work [24–29] on the synthesis of N–H ketoaziridines shows
that simple one-pot, not expensive starting material and easy
workup are the advantage of this direct N–H insertion method.
a
b
c
d
e
f
C6H5
C6H5
71
66
64
72
61
71
69
52
60
74
67
100–101 [27]
3-NO2C6H4
4-MeOC6H4
2,4-Cl2C6H3
4-ClC6H4
4-MeOC6H4
C6H5
C6H5
97–99
C6H5
86–88 [27]
108–110
C6H5
C6H5
91–92 [27, 29]
98–100 [29]
75–78 [27, 28]
126–128 [29]
104–105
C6H5
g
h
i
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-BrC6H4
4-NO2C6H4
4-ClC6H4
2,4-Cl2C6H3
C6H5
j
130–132
k
101–103 [27]
General conditions: reactions were performed in CH3CN using a ratio
of 1:1.5:2 for aziridine/1/K2CO3 for 7 h
Experimental section
General
a
Reaction time for consuming all of the starting materials
b
Isolated yield
All yields refer to isolated products after purification by
column chromatography or distillation in vacuum. Products
were characterized by comparison with authentic samples
(IR and 1HNMR spectra, TLC, melting, and boiling points).
refluxing THF in the presence of Et3N (2 eq) for 7 h, com-
pound (3a) was obtained in 29 % yield (Table 1, entry 1).
Treating 1 (1.0 equiv) with 1,3-diphenylprop-2-ene-
1-one (2a) in the presence of Et3N (2.0 equiv) in some
other solvent such as DMSO, dioxane, and CH3CN at
refluxing conditions for 7 h gave the aziridine (3a) in low
yield (Table 1, entry 2–4). The similar examination was
performed in the presence of pyridine as base in solvents
such as DMSO, THF, dioxane, and CH3CN, but in all of
them unsatisfactory product was also obtained (entry 5–8).
When a mixture of 1 (1.0 equiv) with 1,3-diphenylprop-
2-ene-1-one (2a) in DMSO, CH3CN and/or, dioxane in the
presence of K2CO3 (2.0 equiv) was examined, low yields
of the product were obtained (entry 10–12), but a higher
yield of product was achieved using THF as solvent (entry
9). Varying the amount of K2CO3 and 1 (entries 9-12) in
THF improves the yield of the product (entry 13–15). The
reaction of 1,3-diphenylprop-2-ene-1-one with 1 (1.5 eq) in
refluxing THF in the presence of K2CO3 (1.0 equiv) gave
good yields (71 %) of the product (entry 13).
1
All HNMR spectra were recorded at 400 MHz (The Cen-
tral Laboratory of the University of Isfahan, Isfahan. Iran)
in CDCl3 relative to TMS, and IR spectra were recorded on
FT Infrared spectroscope JASCO, FT/IR-6300, The Cen-
tral Laboratory of the University of Isfahan, Isfahan, I.R.
Iran. All solvents used were dried and distilled according to
standard procedures.
General procedure for the synthesis of ketoaziridines
(3) from the reaction of 1,3‑Diarylprop‑2‑en‑1‑one (2)
and 1‑aminopyridinium iodide (1)
A mixture 1,3-diarylprop-2-en-1-one (2) (1 mmol) and
1-aminopyridinium iodide (1.5 mmol) in the presence of
K2CO3 (2 mmol) in THF (5 mL) was refluxed for 7 h. In all
of them, the completion of the reaction was confirmed by
TLC (EtOAc–Hexane: 1/4). After completion of the reac-
tion, evaporation of the solvent under reduced pressure and
subsequent purification of the residue by column chroma-
tography (silica gel, EtOAc–Hexane: 1/4) provided N–H
trans-2-Aroyl-3-aryl aziridines (3) (Table 1) as pure prod-
ucts in 52–74 % yields.
With the optimal conditions in hand (entry 13), we
examined the substrate scope of the reaction (Table 2).
Various 1,3-diphenylprop-2-ene-1-one containing phenyl
substituted were investigated for the synthesis of the cor-
responding ketoaziridines in the optimal conditions. Both
1 3

J IRAN CHEM SOC
2‑Benzoyl‑3‑phenyl aziridine (3a)
137.4, 137.1, 132.7, 130.8, 129.3, 128.8, 127.0, 127.5,
126.7, 41.7, 43.7.
Yellow solid, m.p. 98–100 IR (KBr): v (cm−1) = 3220,
3100, 1659, 1510, 756, 6901H NMR (400 MHz, CDCl3):
δ = 2.7 (s, 1H), 3.2 (d, J = 2.4 Hz, 1H), 3.5 (d, J = 2.4 Hz,
1H), 7.3-7.4 (m, 5H), 7.5 (m, 2H), 7.6 (t, J = 6.0 Hz, 1H),
8.0 (d, J = 6.0 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3)
(δ, ppm): 197.3, 139.9, 138.7, 137.5, 130.7, 129.4, 128.9,
128.7, 127.2, 44.1, 42.3.
Acknowledgments We are thankful to Research Council of Shahre-
kord University for supporting this work.
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