Oxidative addition of N-aminophthalimide to styryl-1,2,4-oxadiazoles

Article abstract of DOI:10.1134/S1070428010050143

The oxidation of N-aminophthalimide with lead tetraacetate in the presence of 5-[(E)-2-arylethenyl]-3-(4-methylphenyl)-1,2,4-oxadiazoles and 5-(4-methylphenyl)-3-[(E)-2-phenyl-ethenyl]-1,2,4-oxadiazole led to the formation of the corresponding (3-aryl-1-phthalimidoaziridin-2-yl)-(4- methylphenyl)-1,2,4-oxadiazoles. In the reaction with 3,5-distyryl-1,2,4- oxadiazole a mixture was obtained of two regioisomeric monoadducts and a diadduct in the ratio 80: 15: 5; at the use of 3 equiv of the aziridinating reagents only diadduct was isolated as a mixture of two diastereoisomers in the ～3: 2 ratio that were separated by recrystallization. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070428010050143

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 5, pp. 678−684. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © E.V. Beletskii, O.A. Ignatenko, M.A. Kuznetsov, S.I. Selivanov, 2010, published in Zhurnal Organicheskoi Khimii, 2010,
Vol. 46, No. 5, pp. 678−684.
OxidativeAddition of N-Aminophthalimide
to Styryl-1,2,4-oxadiazoles
E. V. Beletskii, O. A. Ignatenko, M. A. Kuznetsov, and S. I. Selivanov
St. Petersburg State University, St. Petersburg,198504 Russia
e-mail: mak@mail.wplus.net
Received August 26, 2009
Abstract—The oxidation of N-aminophthalimide with lead tetraacetate in the presence of 5-[(Ε)-2-arylethenyl]-3-
(4-methylphenyl)-1,2,4-oxadiazoles and 5-(4-methylphenyl)-3-[(Ε)-2-phenyl-ethenyl]-1,2,4-oxadiazole led to the
formation of the corresponding (3-aryl-1-phthalimidoaziridin-2-yl)-(4-methylphenyl)-1,2,4-oxadiazoles. In the
reaction with 3,5-distyryl-1,2,4-oxadiazole a mixture was obtained of two regioisomeric monoadducts and a diadduct
in the ratio 80 : 15 : 5; at the use of 3 equiv of the aziridinating reagents only diadduct was isolated as a mixture of
two diastereoisomers in the ~3 : 2 ratio that were separated by recrystallization.
DOI: 10.1134/S1070428010050143
of the trans-location of these protons in the course of the
cyclization. In their 13C NMR spectra the carbon atoms
of the heterocycle at δ 168–169 (C3) and ~175 ppm (C5)
are characteristic; they are shifted downfield by 5–10
ppm compared with the carbon atoms of the isomeric
1,3,4-oxadiasoles (cf. [2]).
The oxidative phthalimido-aziridination of alkenyl-
substituted pyrazoles and 1,3,4-oxadiazoles proceeds at
the exocyclic C=C bond and affords cleanly the
corresponding aziridinylazoles [1, 2]. In this connection
the evaluation of the applicability range and revealing the
regular trends of this reaction as a general method for
designing linearly connected polyheterocyclic systems
containing aziridine fragment is an urgent task. To this
end we selected styryl-substituted 1,2,4-oxadiazoles fairly
different from its isomers, symmetric 1,3,4-oxadiazoles.
The oxidative addition of the N-aminophthalimide to
styryloxadiazoles IIa–IIe was carried out by the standard
procedure adding in turns by small portions N- amino-
phthalimide and lead tetraacetate to the solution of the
unsaturated compound in dichloromethane [2]. We
established in the preliminary runs with IIa substrate (from
Initial unsaturated 1,2,4-oxadiazoles IIa–IIe were
obtained by procedure [3] through the thermal cyclization
of acylation products of amidoximes Ia, Id prepared from
p-tolunitrile or cinnamonitrile and hydroxylamine
(Scheme 1) [3].
The 1H NMR spectra of styryl-1,2,4-oxadiazoles IIa–
IIe in the region δ 7.0–8.0 ppm contain doublets of the
olefin protons with 3J 15–17 Hz indicating the retention
1
the H NMR spectra of the reaction mixtures) that at
cooling the solution from the room temperature to –10°C
the conversion of the initial compound considerably grew,
but further cooling practically did not affect the rate of
the process, therefore all subsequent reactions were
performed at–10°C. The composition of separated
Scheme 1.
NH2 O
NH2
N O
N
K2CO3
PhMe
Δ, PhMe
+ R2COCl
R1
R1
R2
R1
R2
_H2O
NOH
N
O
IIа_IIe, 40_75%
Iа, Id
R1 = C6H4Me-p, R2 = CH=CH–Ph (a), CH=CH–C6H4OMe-p (b), CH=CH–C6H4NO2-p (c); R1 = CH=CH–Ph, R2 = C6H4Me-p
(d), CH=CH–Ph (e).
678

OXIDATIVE ADDITION OF N-AMINOPHTHALIMIDE
679
Scheme 2.
the trans-location of the aziridine protons as is expectable
for the configuration of the double bond is always retained
at the oxidative aminoaziridination [4]. The ratio of
invertomers varied from ~5:1 to ~10 : 1; therewith in the
1H NMR spectra the signals of the aziridine protons
belonging to the main invertomer are located upfield with
respect to the minor invertomer, and the vicinal coupling
constant of the aziridine protons in the major invertomer
is always somewhat smaller than in the minor one. The
available data do not allow the reliable assignment of the
configuration of these invertomers to the syn or anti
structure, but however analogously to the aziridinyl-1,3,4-
oxadiazoles [2] it is presumable that the major invertomer
possesses the syn-orientation of the heterocycle and the
phthalimide residue.
The comparison of the 13C NMR spectra of adducts
IIIa–IIId and initial styryl-1,2,4-oxadiazoles IIa–IId
shows that the replacement of the styryl substituent by
the aziridinyl residue leads to the upfield shift of the
contiguous carbon atom of the oxadiazole molety by 2.5–
2.8 ppm, but practically does not affect the position of
the signal of the carbon atom attached to the para-tolyl
substituent.
N O
N
PiNNH2
IIа_IIc
R
п-MeC6H4
Pb(OAc)4
N
NPi
IIIа_IIIc
O
b
a
c
PiN_
=
.
N
O
N O
N
PiNNH2
IId
Ph
C6H4Me-p
Pb(OAc)4
N
PiN
IIId
R = Ph (a), C6H4OMe-p (b), C6H4NO2-p (c);
products was confirmed by elemental analyses, and their
structure, by H, 13C NMR and mass spectra.
1
From monostyryl-substituted oxadiazoles IIa–IId the
products of addition to the exocyclic C=C bonds were
obtained in 34–70% yield. These compounds are the first
representatives of the series of aziridinyl-1,2,4-oxadi-
azoles IIIa–IIId, a new class of linearly connected poly-
heterocyclic compounds (Scheme 2).
1
The H NMR spectrum of the reaction mixture
containing 3,5-distyryl-1,2,4-oxadiazole (IIe) at the
equimplar ratio of all reagents demonstarated the
formation of two regioisomeric monoadducts IIIe, IIIe',
and diadduct IV in the ratio 80 : 15 : 5 (Scheme 3).
Because of the slow inversion in the NMR time scale
of the aziridine nitrogen atom [4] in the middle part of the
1H NMR spectra (δ 4.2–5.4 ppm) of compounds IIIa–
IIId two pairs of doublets are present corresponding to
the protons of the aziridine ring belonging to two
invertomers with the syn- and anti-position of the
phthalimide group and the heterocycle. The vicinal
coupling constants (5.0–5.9 Hz) observed there indicate
The double recrystallization of the residue after the
evaporation of the reaction mixture made it possible to
get rid of the diadduct and to obtain in 35% yield of the
compound containing the monoadducts IIIe and IIIe' in
the ratio 95 : 5. However at further recrystallization the
composition of the mixture did not change, and the attempt
at the separation of the regioisomers by column
chromatography on silica gel failed for these aziridine
Scheme 3.
Ph
N
Ph
N
Ph
N
NPi
NPi
PiNNH2
O
N
O
N
O
N
+
IIe
N
+
N
Pb(OAc)4
N
NPi
N
Ph
IIIe
Ph
Ph
NPi
IIIe'
IV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

BELETSKII et al.
680
like the adducts IIIa–IIId quickly decomposed on silica
gel.
the distyryloxadiazole IIe is approximately similar to the
relative reactivity of compounds IIa, IId. Therefore the
main monoadduct should be regioisomer IIIe in agree-
ment with the above assignment.
1
In the middle part of the H NMR spectra (δ 4.1–
5.4 ppm) of the monoadducts mixture the doublets of
aziridine protons of both invertomers of compound IIIe
are clearly seen (in the ratio 87 : 17) and of the main
invertomer of the minor regioisomer IIIe'. In the
downfield region for each invertomer of compound IIIe
the doublets appear belonging to one of the olefin protons
Diadduct IV was obtained and isolated in a pure state
by using the three-fold excess of the aziridinating
reagents. Its identification and confirmation of the
structure is complicated by its formation in the form of
two diastereomers, 3-[rel-(2R,3S)-3-phenyl-1-phthal-
imidoaziridin-2-yl]-5-[(2R,3S)-3-phenyl-1-phthal-imido-
aziridin-2-yl]-1,2,4-oxadiazole and 3-[rel-(2R,3S)-]-5-
[(2S,3R)-]-isomer; each of them can fundamentally exist
as four invertomers (anti-anti-, anti-syn-, syn-anti-, and
syn-syn-). As a result in the middle part of the 1H NMR
spectrum of the reaction mixture over a score of aziridine
protons signals are observed corresponding to two
diastereomeric diadducts present in the ratio ~3 : 2. This
is quite in contrast to the formation of a single
diastereomer of analogous diadduct from 2,5-distyryl-
1,3,4-oxadiazole [2].
3
(δ 6.9–7.1 ppm, J 16–17 Hz), but the signals of the
second proton are overlapped by the complex aromatic
multiplets. In the 13C NMR spectrum only the signals of
the aziridine carbon atoms of the main invertomer of
compound IIIe were reliably identified.
The assignment of the regioisomers structures
provided a certain problem. It is seen that the ranges of
the chemical shifts of the aziridine protons in the
compounds IIIe and IIIe' like those in the spectra of
regioisomeric aziridinyl-oxadiazoles IIIa, IIId are
overlapped and cannot be used for assignment. However
the comparison of δ values for the carbon atoms of the
oxadiazole fragment in initial compound IIe and in the
main regioisomer of the mono-adduct shows that the
formation of the aziridine ring causes an upfield shift of
the signal of atom C5 (by 2.7 ppm), and the position of
the signal of atom C3 nearly remains the same. This fact
makes it possible to ascribe with a high probability to the
main regioisomer IIIe the structure of the adduct to the
C=C bond of the styryl group linked to the atom C5.
The obtained diastereomers mixture was separated
1
by recrystallization. In the middle part of the H NMR
spectrum (δ 3.5–5.2 ppm) of the solution of the major
diastereomer of diaziridinyl-oxadiazole IV in CDCl3 three
set of signals (at the four theoretically probable inverto-
mers) of aziridine protons are observed in the ratio 85 :
11 : 4 (in DMSO d6 the ratio is 88 : 9 : 3). In the spectrum
of the minor diastereomer of compound IV the aziridine
signals of all four invertomers are present in the region
δ 3.9–5.4 ppm with the ratio 62 : 18 : 13 : 7 (in CDCl3).
The considerable difference in the ratio of invertomers
is apparently due to the steric interactions of phthalimide
groups in one aziridine moiety with that in another
seemingly remote aziridine substituent. If these inter-
actions were insignificant the ratio of invertomers would
be the same for both diastereomers IV, and in event of
weak influence of the substituents at the heterocycle on
the invertomer stability taking into account the invertomers
ratio in CDCl3 solutions for aziridines IIIa (88 : 12) and
IIId (85 : 15) it would be 75 : 13 : 10 : 2.
The additional confirmation to this assumption was
obtained from the comparison of the relative reactivity
of regioisomeric 5- and 3-styryl-1,2,4-oxadiazoles (IIa,
IId). Although the yields of adducts IIIa, IIId in the
preparative runs were practically similar (69 and 66%),
in the reaction of the equimolar mixture of compounds
IIa, IId with the aziridinating reagents at the large deficit
of the latter the obtained ratio of aziridines IIIa, IIId
was ~3.5 : 1, which means that in the studied reaction 5-
styryl-oxadiazole IIa is 3.5 times more active than its
regioisomer IId. 3,5-Distyryl-oxadiazole IIe may be
regarded as resulting from the replacement of the para-
tolyl substituent by the similar in its electronic effect styryl
substituent (close values of constants σm and σp; although
The purity of obtained samples of diadduct IV dia-
1
stereomers was proved by the absence in the H NMR
spectrum of one diastereomer the signals of the main
form of the other diastereomer. Besides for both diadduct
IV diastereomers spectra EXSY-NOESYwere registered
that proved the presence in each spectrum of several
forms of a single compound.
+
σp are strongly different [5]) on the one hand, at the
atom C3 of oxadiazole IIa, and on the other hand, at the
atom C5 of oxadiazole IId. Inasmuch as this substitution
at the atom C3 should relatively weakly affect the C=C
bond at the atom C5 (and vise versa), we are able to
consider that the relative activity of the C=C bonds in
It can be stated in conclusion that the oxidative
phthalimidoazirination of styryl-substituted 1,2,4-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

OXIDATIVE ADDITION OF N-AMINOPHTHALIMIDE
681
oxadiazoles at –10°C cleanly affords the corresponding
aziridinyloxadiazoles, and the reactivity of the C=C bond
at the atom C5 is significantly higher, than at the atom
C3. Under the same conditions the phthalimido-
aziridination of 1,3,4-oxadiazoles proceeded to a lower
conversion of the initial compounds, and the yield of
adducts not exceeded 15–20% [2] demonstrating the
different effect of the isomeric heterocycles on the
activity of the multiple bond linked to the oxadiazole ring,
although both 1,2,4-oxadiazole and 1,3,4-oxadiazole are
π acceptor heterocycles.
with 1 ml of ethyl ether, was dissolved in 50 ml of
dichloromethane, and washed with 0.1 N HCl (2 ×
30 ml). The solvent was distilled off in a vacuum.
3-(4-Methylphenyl)-5-[(E)-2-phenylethenyl]-
1,2,4-oxadiazole (IIa). Yield 75%. Colorless powder,
1
mp 108–109°C. H NMR spectrum (CDCl3), δ, ppm:
2.43 s (3H, CH3), 7.06 d (1H, =CH, J 16.8 Hz), 7.27 da
(2H, p-Tol, Hm, J 8.4 Hz), 7.40–7.45 m (3H, Ph, Hm,p),
7.58–7.63 m (2H, Ph, H°), 7.87 d (1H, =CH, Hm,p), 7.58–
7.63 m (2H, Ph, H°), 7.87 d (1H, =CH, J 16.8 Hz), 8.02 d
(2H, p-Tol, H°, J 8.4 Hz). 13C NMR spectrum (CDCl3),
δ, ppm: 21.69 (CH3), 110.44 (=CH–Ht), 124.25 (p-Tol,
Cp), 127.50, 128.03, 129.17, 129.68, 130.59, 134.60 (Ph,
Ci), 141.57 (p-Tol, Ci), 142.65 (=CH–Ph), 168.83 (C3),
175.17 (C5). Mass spectrum, electron impact, m/z (Irel,
%): 262 (87) [M]+, 261 (100), 145 (11), 133 (51)
[C7H7CNO]+, 128 (46), 103 (26), 77 (31), 71 (10), 57
(12), 51 (13), 41 (10). Found, %: C 77.59; H 5.33;
N 10.66. C17H14N2O. Calculated, %: C 77.86; H 5.34;
N 10.69. M 262.31.
EXPERIMENTAL
1H (300 MHz) and 13C (75.4 MHz) were registered
on a spectrometer DPX-300 Bruker C using as internal
reference the signals of residual protons (δ 7.26 and
2.50 ppm) or of carbon atoms (δ 77.0 and 39.5 ppm
respectively) of the deuterated solvent. The assignment
of the signals in the 13C NMR spectra was performed
with the help of DEPT spectra. Mass spectra were
measured on instruments MKh-1321 (electron impact
ionization, energy of ionizing electrons 70 eV) and Finnigan
MAT 95 (electrospray ionization for methanol solutions).
The elemental analyses were carried out on an automatic
CHN-analyzer HP-185B. The composition of the reaction
mixtures and the purity of compounds obtained was
checked by TLC on Alugram SIL G/UV254 plates.
N-Aminophthalimide was obtained by procedure [6].
3-(4-Methylphenyl)-5-[(E)-2-(4-methoxyphenyl)-
ethenyl]-1,2,4-oxadiazole (IIb). Yield 53%. Colorless
powder, mp 120–121°C. 1H NMR spectrum (CDCl3), δ,
ppm: 2.42 s (3H, CH3), 3.85 s (3H, OCH3), 6.88−6.98 m
(3H, =CH and p-MeOC6H4, Hm), 7.29 d (2H, p-Tol, Hm,
J 8.4 Hz), 7.55 d (2H, p-MeOC6H4, H°, J 8.4 Hz),
7.82 d (1H, =CH, J 16.8 Hz), 8.01 d (2H, p-Tol, H°,
J 8.4 Hz). 13C NMR spectrum (CDCl3), δ, ppm: 21.60
(CH3), 55.66 (OCH3); 108.00, 114.66 (=CH–Ht and p-
MeOC6H4, Cm); 124.39 (p-Tol, Cp), 127.39, 127.50 (p-
MeOC6H4, Ci), 129.68, 129.72, 141.50 (p-Tol, Ci), 142.32
(=CH–Ar), 161.71 (C–O), 168.76 (C3), 175.58 (C5).
Mass spectrum, electron impact, m/z (Irel, %): 292 (66)
[M]+, 291 (37), 205 (24), 161 (100) [M –C7H7CN2]+,
133 (37) [C7H7CNO]+, 89 (13), 77 (27). Found, %:
C 73.89; H 5.52; N 9.39. C18H16N2O2. Calculated, %:
C 73.97; H 5.48; N 9.59. M 292.34.
4-Toluoylamidoxime (Ia) and cinnamoyl-
amidoxime (Id). A solution of 7.22 g (44 mmol) of
hydroxylamine sulfate in 10 ml of water was added to
a dispersion of 12 g (90 mmol) potassium carbonate in
the solution of 44 mmol of carboxylic acid nitrile in 50 ml
of methanol. The mixture was heated at reflux for 2 h,
cooled, and diluted with water. The precipitated colorless
crystals were filtered off. Yield of amidoxime Ia 75%,
mp 140°C (mp 141°C [7]). Yield of amidoxime Id 58%,
3-(4-Methylphenyl)-5-[(E)-2-(4-nitrophenyl)-
ethenyl]-1,2,4-oxadiazole (IIc). Yield 40%. Yellow
1
mp 91°C (mp 93°C [8]). H NMR spectrum (CDCl3), δ,
1
powder, mp 189–190°C. H NMR spectrum (DMSO-
ppm: 4.77 br.s (2H, NH2), 6.52 d (1H, =CH, J 16.0 Hz),
6.86 d (1H, =CH, J 16.0 Hz), 7.30–7.48 m (5H, Ph).
d6), δ, ppm: 2.39 s (3H, CH3), 7.38 d (2H, p-Tol, Hm,
J 8.9 Hz), 7.58 d (1H, =CH, J 16.8 Hz), 7.93 d (2H, p-
NO2C6H4, H°, J 7.9 Hz), 8.00 d (1H, =CH, J 16.8 Hz),
8.07 d (2H, p-Tol, H°, J 8.9 Hz), 8.26 d (2H, p-NO2C6H4,
5-Styryl-3-p-tolyl-1,2,4-oxadiazoles IIa–IIc.
A dispersion of 1.50 g (10 mmol) of p-toluoylamidoxime
(Ia), 1.45 g (11 mmol) of K2CO3, and 10 mmol of the
corresponding cinnamoyl chloride in 30 ml of benzene
was heated at reflux with stirring for 3 h. The reaction
mixture was filtered, the solvent was distilled off in
a vacuum. The obtained light-yellow powder was washed
a
Here and hereinafter in describing the signals of aromatic protons
whose spectra belong to the second order we report the apparent
multiplicity of complex signals and the distance between the main
peaks of the complex multiplets and not the calculated values of
coupling constants.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

BELETSKII et al.
682
Hm, J 7.9 Hz). 13C NMR spectrum (DMSO-d6), δ, ppm:
21.08 (CH3), 114.40 (CH=), 123.30 (Ci), 123.99, 126.96,
129.40, 129.81, 140.11 (CH=), 140.62 (Ci), 141.61 (p-
Tol, Ci), 148.04 (Ci), 168.12 (C3), 174.64 (C5). Mass
spectrum, electron impact, m/z (Irel, %): 307 (100) [M]+,
306 (43), 176 (38) [M–C7H7CN2]+, 133 (95)
[C7H7CNO]+, 102 (24), 91 (14), 77 (33), 51 (10). Found,
%: C 66.20; H 4.37; N 13.50. C17H13N3O3. Calculated,
%: C 66.45; H 4.23; N 13.68. M 307.31.
(80), 103 (38), 89 (16), 77 (31), 63 (11), 51 (15). Found,
%: C 78.58; H 5.17; N 10.25. C18H14N2O. Calculated,
%: C 78.83; H 5.11; N 10.22. M 274.32.
General procedure of addition of N-amino-
phthalimide to styryl-1,2,4-oxadiazoles IIa–IIe. Into
a solution of 1 mmol of oxadiazole IIa–IIe in 30 ml of
dichloromethane cooled to –10°C where was dispersed
0.7 g (5 mmol) of potassium carbonate was added in
turns by small portions within 15 min 162 mg (1 mmol) of
N-aminophthalimide and 443 mg (1 mmol) of lead
tetraacetate. Then the stirring was continued for 10 min,
the mixture was filtered, the precipitate of the inorganic
salt was washed with 20 ml of dichloromethane. The
solvent was distilled off in a vacuum. The reaction product
was recrystallized from a mixture of ethanol with DMF,
5 : 1.
3-Styryl-1,2,4-oxadiazoles IId and IIe. To a solu-
tion of 810 mg (5 mmol) of cinnamoylamidoxime (Id)
and 5 mmol of p-toluoyl or cinnamoyl chloride in 10 ml of
dichloromethane was added dropwise at stirring 0.62 ml
(560 mg, 5.5 mmol) of N-methylmorpholine. The solution
was stirred for 10 min, heated to boiling, washed with
1N HCl (3 × 10 ml). The organic layer was dried with
anhydrous magnesium sulfate, the solvent was distilled
off in a vacuum. To the residue 30 ml of toluene was
added and the solution was heated at reflux for 10 h.
The solvent was distilled off in a vacuum, the residue
was recrystallized from ethanol.
3-(4-Methylphenyl)-5-[rel-(2R,3S)-3-phenyl-1-
phthalimidoaziridin-2-yl]-1,2,4-oxadiazole (IIIa),
invertomers mixture, 88 : 12.Yield 69%. Colorless powder,
1
mp 178–180°C. H NMR spectrum (CDCl3), δ, ppm:
2.35 s, 4.24 d (J 5.1 Hz), 4.86 d (J 5.1 Hz) CH3 group
and aziridine protons of the main invertomer; 2.42 s, 4.43 d
(J 5.8 Hz), 5.37 d (J 5.8 Hz) the same of minor invertomer,
overall 5H; 7.14 d (J 8.0 Hz), 7.28–7.32 m, 7.39–7.47 m,
7.55 d (J 8.0 Hz), 7.54–7.65 m, 8.04 d (J 8.0 Hz) overall
13H, 2Ar + PiN. 13C NMR spectrum of the main
invertomer (CDCl3), δ, ppm: 21.63 (CH3), 42.62 (CHN),
51.62 (CHN), 123.41 (PiN, Cb), 123.46 (p-Tol, Cp),
127.31, 127.68, 128.96, 129.11, 129.56, 130.14 (PiN, Ca),
134.18 (Ph, Ci), 134.33 (PiN, Cc), 141.78 (p-Tol, Ci),
164.83 (NCO), 168.45 (C3), 172.70 (C5). Mass spectrum,
electrospray, m/z (Irel, %): 422.3 (31) [M]+, 276.2 (23)
[M – PiN]+, 221.2 (27), 202.2 (92), 173.1 (56), 159.1
(31), 147.1 (31) [PiNH]+, 132.1 (62), 104.1 (100)
[C6H4CO]+, 76.1 (51). Found, %: C 71.09; H 4.21;
N 13.30. C25H18N4O3. Calculated, %: C 71.08; H 4.29;
N 13.26. M 422.44.
5-(4-Methylphenyl)-3-[(E)-2-phenylethenyl]-
1,2,4-oxadiazole (IId). Yield 55%. Colorless powder,
1
mp 100–101°C. H NMR spectrum (CDCl3), δ, ppm:
2.46 s (3H, CH3), 7.09 d (1H, =CH, J 16.7 Hz), 7.33 m
(5Hapom), 7.61 d (2H, Ph, H°, J 8.7 Hz), 7.81 d (1H, =CH,
J 16.7 Hz), 8.08 d (2H, p-Tol, H°, J 8.7 Hz). 13C NMR
spectrum (CDCl3), δ, ppm: 21.87 (CH3), 113.20 (=CH–
Ht), 121.63 (p-Tol, Cp), 127.58, 128.25, 128.99, 129.50
(Ph, Cp), 129.93, 135.60 (Ph, Ci), 139.16 (=CH–Ph),
143.62 (p-Tol, Ci), 168.49 (C3), 175.28 (C5). Mass
spectrum, electron impact, m/z (Irel, %): 262 (52) [M]+,
261 (100), 128 (28), 119 (58) [C7H7CO]+, 116 (14), 91
(28), 65 (22), 63 (12), 52 (11), 39 (13). Found, %: C 77.93;
H 5.32; N 10.66. C17H14N2O. Calculated, %: C 77.86;
H 5.34; N 10.69. M 262.31.
3-(4-Methylphenyl)-5-[rel-(2R,3S)-3-(4-
methoxyphenyl)-1-phthalimidoaziridin-2-yl]-1,2,4-
oxadiazole (IIIb), invertomers mixture, 82 : 18. Yield
64%. Colorless powder, mp 162–163°C (decomp).
1H NMR spectrum (CDCl3), δ, ppm: 2.34 s, 3.83 s,
4.22 d (J 5.0 Hz), 4.79 d (J 5.0 Hz) CH3, CH3O groups
and aziridine protons of the main invertomer; 2.42 s, 3.74 s,
4.38 d (J 5.9 Hz), 5.30 d (J 5.9 Hz) the same of minor
invertomer, overall 8H; 6.81 d (J 8.4 Hz), 6.96 d
(J 8.4 Hz), 7.13 d (J 8.4 Hz), 7.26–7.32 m, 7.47 d
(J 8.4 Hz), 7.63–7.74 m, 8.02 d (J 8.4 Hz) overall 12H,
2Ar + PiN. 13C NMR spectrum of the main invertomer
(CDCl3), δ, ppm: 21.63 (CH3), 42.49 (CHN), 51.50
3,5-Bis[(E)-2-phenylethenyl]-1,2,4-oxadiazole
(IIe). Yield 56%. Colorless powder, mp 114–115°C.
1H NMR spectrum (CDCl3), δ, ppm: 7.03 d (1H, =CH,
J 16.0 Hz), 7.09 d (1H, =CH, J 16.7 Hz), 7.36–7.44 m
(6H, Hm and Hp), 7.58–7.62 m (4H, H°), 7.75 d (1H,
=CH, J 16.7 Hz), 7.86 d (1H, =CH, J 16.0 Hz). 13C NMR
spectrum (CDCl3), δ, ppm: 110.29 (=CH–Ht), 113.09
(=CH–Ht), 127.59, 128.06 (Ph, Cp), 129.02, 129.21 (Ph,
Cp), 129.57, 130.68, 134.54 (Ph, Ci), 135.54 (Ph, Ci),
139.15 (=CH–Ph), 142.92 (=CH–Ph), 168.33 (C3), 174.66
(C5). Mass spectrum, electron impact, m/z (Irel, %): 274
(58) [M]+, 273 (100), 245 (18), 131 (38), 128 (42), 115
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OXIDATIVE ADDITION OF N-AMINOPHTHALIMIDE
683
(CHN), 55.50 (OCH3), 114.40 (p-Anys, Cm), 123.39
(PiN, Cb), 123.45 (p-Tol, Cp), 126.10 (p-Anys, Ci), 127.28,
128.62, 129.55, 130.12 (PiN, Ca), 134.31 (PiN, Cc), 141.77
(p-Tol, Ci), 160.29 (C–O), 164.87 (NCO), 168.43 (C3),
172.81 (C5). Mass spectrum, electrospray, m/z (Irel, %):
452.3 (6) [M]+, 319.2 (100) [M–C7H7CNO]+, 305.2 (13)
[M–PiNH]+, 187.1 (13), 147.1 (15) [PiNH]+, 132.1 (56),
104.1 (35) [C6H4CO]+, 76.0 (11). Found, %: C 69.01;
H 4.46; N 12.40. C26H20N4O4. Calculated, %: C 69.02;
H 4.46; N 12.38. M 452.47.
[C7H7CO]+, 104 (56) [C6H4CO]+, 91 (20), 77 (32). Found,
%: C 70.97; H 4.17; N 13.11. C25H18N4O3. Calculated,
%: C 71.08; H 4.29; N 13.26. M 422.44.
3-[(E)-2-phenylethenyl]-5-[rel-(2R,3S)-3-phenyl-
1-phthalimidoaziridin-2-yl]-1,2,4-oxadiazole (IIIe),
invertomers mixture, 87 : 13, and 5% of regioisomer IIIe'.
The reaction product was twice recrystallized from
ethanol. Yield 35%. Colorless powder, mp 155–156°C.
1H NMR spectrum (CDCl3), δ, ppm: 4.23 d (J 5.1 Hz),
4.85 d (J 5.1 Hz), 6.90 d (J 16.0 Hz) aziridine protons
and =CH of the main invertomer; 4.42 d (J 5.8 Hz), 5.34 d
(J 5.8 Hz), 7.11 d (J 16.7 Hz) the same of minor
invertomer, overall 3H; 7.24–7.50 m, 7.55–7.60 m, 7.64–
7.82 m, overall 15H, 2Ph + =CH + PiN; 4.19 (J 5.1 Hz),
4.81 (J 5.1 Hz) aziridine protons of compound IIIe'.
13C NMR spectrum of the main invertomer (CDCl3), δ,
ppm: 42.43 (CHN), 51.48 (CHN), 113.03 (=CH–Ht),
123.39 (PiN, Cb), 127.14, 127.34, 128.79, 128.83, 128.99,
129.53 (PiN, Ca), 129.99, 133.94 (Ph, Ci), 134.23 (PiN,
Cc), 134.96 (Ph, Ci), 139.39 (=CH–Ph), 164.67 (NCO),
167.79 (C3), 172.02 (C5). Mass spectrum, electron
impact, m/z (Irel, %): 434 (1.5) [M]+, 331 (4), 302 (1), 262
(5), 247 (5), 186 (3), 147 (100) [PiNH]+, 129 (42), 104
(79) [C6H4CO]+, 76 (71). Found, %: C 71.79; H 4.08;
N 12.75. C26H18N4O3. Calculated, %: C 71.88; H 4.18;
N 12.90. M 434.45.
3-(4-Methylphenyl)-5-[rel-(2R,3S)-3-(4-nitro-
phenyl)-1-phthalimidoaziridin-2-yl]-1,2,4-oxadiazole
(IIIc), invertomers mixture, 91:9.Yield 34%. Light yellow
powder, tdecomp 173–175°C. 1H NMR spectrum (CDCl3),
δ, ppm: 2.35 s, 4.25 d (J 5.1 Hz), 4.91 d (J 5.1 Hz) CH3
group and aziridine protons of the main invertomer,
2.42 s, 4.52 d (J 5.9 Hz), 5.37 d (J 5.9 Hz) the same of
minor invertomer, overall 5H; 7.14 d (J 7.6 Hz), 7.28–
7.35 m, 7.64–7.75 m, 8.00 d (J 7.6 Hz), 8.17 d (J 7.6 Hz),
8.30 d (J 8.4 Hz) overall 12H, 2Ar + PiN. 13C NMR
spectrum of the main invertomer (CDCl3), δ, ppm: 21.66
(CH3), 42.92 (CHN), 50.42 (CHN), 123.20 (p-Tol, Cp),
123.61 (PiN, Cb), 124.19, 127.31, 128.34, 129.64, 129.94
(PiN, Ca), 134.58 (PiN, Cc); 141.33, 142.03 (p-Tol, Ci
and p-C6H4NO2, Ci); 148.45 (CNO2), 164.68 (NCO),
168.46 (C3), 171.89 (C5). Mass spectrum, electrospray,
m/z (Irel, %): 467.3 (10) [M]+, 319.2 (16), 202.2 (11), 173.1
(20), 147.1 (92) [PiNH]+, 132.1 (25), 117.1 (37), 104.1
(100) [C6H4CO]+, 76.1 (71). Found, %: C 64.19; H 3.80;
N 14.96. C25H17N5O5. Calculated, %: C 64.24; H 3.67;
N 14.98. M 467.44.
Estimation of the relative reactivity of oxadi-
azoles IIa and IId in the oxidative addition of N-
aminophthalimide. To a solution of equimolar amounts
of oxadiazoles IIa and IId (each 131 mg, 0.5 mmol) in
30 ml of dichloromethane and containing dispersed
potassium carbonate (0.5 g) cooled to –10°C was added
at stirring in turns by small portions 16 mg (0.1 mmol) of
N-aminophthalimide and 44 mg (0.1 mmol) of lead
tetraacetate. The mixture was stirred for 10 min more,
then filtered through a thin layer of Na2SO4. The
precipitate of inorganic salts was washed with 20 ml of
dichloromethane. The solvent was distilled off in
a vacuum. The ratio of aziridines IIIa and IIId in the
5-(4-Methylphenyl)-3-[rel-(2R,3S)-3-phenyl-1-
phthalimidoaziridin-2-yl]-1,2,4-oxadiazole (IIId),
invertomers mixture, 85 : 15.Yield 66%. Colorless powder,
1
mp 208–210°C. H NMR spectrum (CDCl3), δ, ppm:
2.38 s, 4.20 d (J 5.2 Hz) and 4.82 d (J 5.2 Hz) aziridine
protons and CH3 group of the main invertomer; 2.45 s,
4.41 d (J 5.8 Hz) and 5.28 d (J 5.8 Hz) the same of
minor invertomer, overall 5H; 7.20 d (J 7.8 Hz), 7.25–
7.46 m, 7.55–7.76 m, 8.08 d (J 8.0 Hz) overall 13H,
2Ar + PiN. 13C NMR spectrum of the main invertomer
(CDCl3), δ, ppm: 21.83 (CH3), 43.62 (CHN), 49.84
(CHN), 121.02 (p-Tol, Cp), 123.21 (PiN, Cb), 127.36,
128.06, 128.74, 128.84, 129.85, 130.31 (PiN, Ca), 134.09
(PiN, Cc), 135.07 (Ph, Ci), 143.91 (p-Tol, Ci), 164.96
(NCO), 165.74 (C3), 175.82 (C5). Mass spectrum,
electron impact, m/z (Irel, %): 422 (5) [M]+, 395 (4), 319
(19), 318 (12), 276 (19) [M–PiN]+, 262 (11), 236 (13),
200 (19), 147 (20) [PiNH]+, 132 (15), 119 (100)
1
dry residue was evaluated at 3.5 : 1 by H NMR from
the intensity ratio of the aziridine protons belonging to
the main invertomers (for aziridine IIIa δ 4.24 ppm,
invertomer content 88%; for compound IIId δ 4.20 ppm,
invertomer content 85%).
Addition of a triple excess of N-aminophthalimide
to oxadiazole IIe. To a solution of 274 mg (1 mmol) of
oxadiazole IIe in 30 ml of dichloromethane where was
dispersed 0.7 g of potassium carbonate cooled to –10°C
was added at stirring in turns by small portions within
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

BELETSKII et al.
684
163.88 (NCO), 165.04 (C3), 173.28 (C5). Found, %: C
68.60; H 3.91; N 14.00. C34H22N6O5. Calculated, %: C
68.68; H 3.73; N 14.13.
15 min 486 mg (3 mmol) of N-aminophthalimide and
1.33 g (3 mmol) of lead tetraacetate. The mixture was
stirred for 10 min more, then filtered , and the precipitate
of inorganic salts was washed with 20 ml of dichloro-
methane. The solvent was distilled off in a vacuum. The
recrystallization from the mixture of ethanol with DMF,
5 : 1, furnished a mixture of diastereomers of 3,5-bis-
[rel-(2R,3S)-3-phenyl-1-phthalimido-aziridin-2-yl]-1,2,4-
oxadiazole (IV) in a ratio 5 : 1 (1H NMR spectrum). Yield
69%. Colorless powder, mp 210°C (decomp.). Mass
spectrum, m/z (Irel, %): 594 (4) [M]+, 447 (10) [M–
PiNH]+, 289 (13), 248 (25), 220 (37), 147 (67) [PiNH]+,
117 (33), 104 (100) [C6H4CO]+, 103 (83), 77 (88). Found,
%: C 68.64; H 3.70; N 14.07. C34H22N6O5. Calculated,
%: C 68.68; H 3.73; N 14.13. M 594.59.
Minor diastereomer of diadduct IV. The filtrate
after recrystallization of the diastereomers mixture was
poured into 50 ml of water, the precipitate was filtered
off and recrystallized ftom ethyl acetate. Yield 8%.
Colorless powder, mp 195–196°C.According to 1H NMR
spectrum it exists as a mixture of four invertomers, 62 :
18 : 13 : 7 in CDCl3, 54 : 25 : 17 : 4 in DMSO-d6. 1H NMR
spectrum (CDCl3), δ, ppm: 3.90 d (J 5.7), 4.07 d
(J 5.7 Hz), 4.66 d (J 5.7 Hz), 4.69 d (J 5.7 Hz) aziridine
protons of the main invertomer; 3.83 d (5.7 Hz), 4.13 d
(J 5.7 Hz), 4.21 d (J 5.7 Hz), 4.27 d (J 5.7 Hz), 4.41 d
(J 5.7 Hz), 4.78–4.83 br.t, 5.05 d (J 5.7 Hz), 5.16 d
(J 5.7 Hz) aziridine protons of minor invertomers, overall
4H; 7.22–7.35 m, 7.38–7.48 m, 7.52–7.60 m, 7.62–
Major diatereomer of diadduct IV. To a solution
of 274 mg (1 mmol) of oxadiazole IIe in 30 ml of
dichloromethane where was dispersed 0.7 g of potassium
carbonate cooled to –10°C was added at stirring in turns
by small portions within 15 min 486 mg (3 mmol) of
N-aminophthalimide and 1.33 g (3 mmol) of lead
tetraacetate. The mixture was stirred for 10 min more,
then filtered , and the precipitate of inorganic salts was
washed with 20 ml of dichloromethane. The solvent was
distilled off in a vacuum. The residue was recrystallized
from the mixture of ethanol with DMF, 5:1, filtered at
40°C, minor diastereomer was isolated from the filtrate.
Yield of the major diastereomer 22%. Colorless powder,
1
7.77 m, overall 18H, 2Ph + 2PiN. H NMR spectrum
(DMSO-d6), δ, ppm: 4.26 d (J 5.5 Hz), 4.46 d (J 5.5 Hz),
4.57 d (J 5.5 Hz), 4.72 d (J 5.5 Hz) aziridine protons of
the main invertomer; 3.95 d (J 5.5 Hz), 4.88 d (J 5.5 Hz),
4.94 d (J 5.5 Hz), 4.05 d (J 5.5 Hz), 5.19 d (J 5.5 Hz),
5.39 d (J 5.5 Hz) aziridine protons of minor invertomers,
overall 4H; 7.15–7.27 m, 7.30–7.55 m, 7.60–7.77 m,
overall 18H, 2Ph + 2PiN. 13C NMR spectrum (DMSO-
d6), δ, ppm: 40.96 (CHN), 41.98 (CHN), 49.70 (CHN),
51.16 (CHN), 122.83 (PiN, Cb), 122.91 (PiN, Cb), 122.99
(PiN, Cb), 123.07 (PiN, Cb), 127.34, 127.47, 127.55,
127.59, 127.86, 128.42, 128.47, 128.50, 128.72, 129.27
(PiN, Ca), 129.30 (PiN, Ca), 129.37, 129.40 (PiN, Ca),
129.45, 133.83 (Ph, Ci), 134.13 (PiN, Cc), 134.28 (PiN,
Cc), 134.50 (Ph, Ci), 134.56 (PiN, Cc), 134.68 (PiN, Cc),
164.22 (NCO), 164.28 (NCO), 164.34 (NCO), 164.84
(C3), 172.85 (C5). Found, %: C 68.52; H 3.89; N 14.08.
C34H22N6O5. Calculated, %: C 68.68; H 3.73; N 14.13.
1
mp 221–223°C (decomp.). According to the H NMR
spectrum exists as a mixture of three invertomers , 85 :
11 : 4 in CDCl3 and 88 : 9 : 3 in DMSO-d6. 1H NMR
spectrum (CDCl3), δ, ppm: 3.92 d (J 5.5 Hz), 3.94 d
(J 5.2 Hz), 4.03 m (two doublets overlapped into
a broadened triplet) aziridine protons of the main
invertomer; 3.53 d (J 5.5 Hz), 4.26 m, 4.79 d (J 5.5 Hz),
4.84 d (J 5.5 Hz), 5.07 d (J 5.5 Hz), 5.14 d (J 5.5 Hz)
aziridine protons of minor invertomers, overall 4H; 7.10–
7.18 m, 7.22–7.45 m, 7.50–7.65 m, 7.72–7.88 m, overall
REFERENCES
1
18H, 2Ph + 2PiN. H NMR spectrum (DMSO-d6), δ,
1. Ignatenko, O.A., Blandov, A.N., and Kuznetsov, M.A., Zh.
Org. Khim., 2005, vol. 41, p. 1830.
2. Ignatenko, O.A., Kuznetsov, M.A., and Selivanov, S.I., Zh.
Org. Khim., 2007, vol. 43, p. 1048.
3. Clapp, B.L. Adv. Heterocycl. Chem., 1976, vol. 20, p. 65.
4. Atkinson, R.S. and Malpass, J.R., J. Chem. Soc., Perkin
Trans. I, 1977, p. 2242.
5. Hansch, C., Leo, A., and Taft, R.W., Chem. Rev., 1991,
vol. 91, p. 165.
ppm: 3.47–3.52 br.s, 4.52 d (J 4.6 Hz), 4.80 d (J 5.5 Hz)
aziridine protons of the main invertomer; 4.63 d (J4.6 Hz),
4.71 d (J 5.5 Hz), 4.91 d (J 4.6 Hz), 5.01 d (J 5.5 Hz)
aziridine protons of the first minor invertomer, overall 4H;
7.05–7.12 m, 7.32–7.47 m, 7.55–7.75 m, 7.77–7.95 m,
overall 18H, 2Ph + 2PiN. 13C NMR spectrum of the main
invertomer (DMSO-d6), δ, ppm: 39.48 (CHN), 41.02
(CHN), 49.38 (CHN), 52.33 (CHN), 123.13 (PiN, Cb),
123.32 (PiN, Cb), 127.24, 128.40, 128.46, 128.50, 128.64,
128.91, 129.13 (PiN, Ca), 129.26 (PiN, Ca), 133.17 (Ph,
Ci), 133.83 (Ph, Ci), 134.67 (PiN, Cc), 134.87 (PiN, Cc),
6. Drew, N.D.K. and Hatt, N.H., J. Chem. Soc., 1937, p. 16.
7. Quan, C. and Kurth, M., J. Org. Chem., 2004, vol. 69, p. 1470.
8. Wolff, H., Ber., 1886, 19, p. 1507.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010