Intramolecular thermal transformations of N-phthalimidoaziridines: 1,3-dipolar cycloaddition and rearrangements

Article abstract of DOI:10.1007/s10593-012-0921-6

The intramolecular thermal cycloaddition of N-phthalimidoaziridines at multiple bonds of substituents with the intermediate formation of azomethine ylides leads to condensed pyrrole derivatives, in which the five-membered ring is adjacent to a five-, six-, or seven-membered ring. Rearrangements, which sometimes become the predominant reactions, compete with cycloaddition. Thus, aziridines with aryl substituents readily isomerize to give imines with a 1,2-shift of the phthalimide group to one of the carbon atoms. Aziridines with one electron-withdrawing substituent probably do not open to give 1,3-dipoles but rather undergo a Cope-type rearrangement involving the three-membered ring and C=O bond of the second substituent. Even in intramolecular reactions, very low activity is found for the cyano group triple bond and aromatic ring bonds as dipolarophiles.

Full text of DOI:10.1007/s10593-012-0921-6

Chemistry of Heterocyclic Compounds, Vol. 47, No. 11, February, 2012 (Russian Original Vol. 47, No. 11, November, 2011)
INTRAMOLECULAR THERMAL TRANSFORMATIONS
OF N-PHTHALIMIDOAZIRIDINES: 1,3-DIPOLAR CYCLO-
ADDITION AND REARRANGEMENTS*
M. A. Kuznetsov1**, A. S. Pan'kova1, V. V. Voronin1, and N. A. Vlasenko1
The intramolecular thermal cycloaddition of N-phthalimidoaziridines at multiple bonds of substituents
with the intermediate formation of azomethine ylides leads to condensed pyrrole derivatives, in which
the five-membered ring is adjacent to a five-, six-, or seven-membered ring. Rearrangements, which
sometimes become the predominant reactions, compete with cycloaddition. Thus, aziridines with aryl
substituents readily isomerize to give imines with a 1,2-shift of the phthalimide group to one of the
carbon atoms. Aziridines with one electron-withdrawing substituent probably do not open to give
1,3-dipoles but rather undergo a Cope-type rearrangement involving the three-membered ring and
C=O bond of the second substituent. Even in intramolecular reactions, very low activity is found for the
cyano group triple bond and aromatic ring bonds as dipolarophiles.
Keywords: aziridines, azomethine ylides, benzoxepinopyrrole, chromenoimidazole, hexahydro-
indenopyrroles, 1,3-dipolar cycloaddition, rearrangements.
Intramolecular 1,3-dipolar cycloaddition of azomethine ylides at carbon–carbon multiple bonds is
commonly used in the synthesis of various heterocyclic compounds with condensed rings [1]. In previous work
[2], we showed that N-aminoaziridine derivatives may serve as azomethine ylides precursors in such reactions.
We found that heating a series of 2-allyl- and 2-propargyloxyphenyl-N-phthalimidoaziridines gave products
containing partially hydrogenated chromeno[4,3-b]pyrrole fragment with condensed five- and six-membered
rings.
_______
*Dedicated to Academician M. G. Voronkov on his 90th birthday.
**To whom correspondence should be addressed, e-mail: mak@mail.wplus.net.
1St. Petersburg State University, 26 Universitetskii Ave., St. Petersburg 198504, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1632-1648, November, 2011.
Original article submitted July 21, 2011.
0009-3122/12/4711-1353©2012 Springer Science+Business Media, Inc.
1353

Aim of the present work was to study the feasibility of using intramolecular thermal reactions of
substituted N-phthalimidoaziridines for constructing condensed structures, in which the five-membered ring is
fused not only with six-membered rings but also with five- and seven-membered rings. Furthermore, since even
unactivated multiple bonds often participate in intramolecular cycloaddition reactions [2-4], we hoped to effect
reactions of such inactive dipolarophiles as aromatic rings and C≡N multiple bonds.
We have studied trans-2,3-disubstituted N-phthalimidoaziridines 6-10, which were selected for the
following reasons. Firstly, all these compounds contain two (compounds 6-9) or, at least, one substituent
(compound 10) at carbon atoms of three-membered ring capable of stabilizing an intermediate azomethine ylide
and, thereby, activate opening of the aziridine ring at the C–C bond. Secondly, the side chains of these
compounds have various types of multiple bonds (including aromatic system bonds), which are sterically
accessible for reaction with the expected 1,3-dipoles obtained upon opening of the aziridine ring, leading us to
expect the formation of polycyclic condensed cycloadducts in these thermal reactions.
R
R
Pb(OAc)4
+ PhthNNH2
PhthN
6–10
1, 6 a R = CO2Me, R1 = 2-AllC6H4, b R = CN, R1 = 2-AllC6H4;
N
R1
K2CO3, CH2Cl2
R1
1–5
2, 7 a R = CN, R1 = 2-PropOCH2C6H4, b R = CN, R1 = 2-AllOCH2C6H4;
3, 8 a R = CO2Me, R1 = 2-BnOC6H4, b R = CN, R1 = 2-BnOC6H4,
c R = CN, R1 = 2-NCCH2OC6H4;
4, 9 a R = Ph, R1 = CO2All, b R = Ph, R1 = CO2Prop;
5, 10 a R = Ph, R1 = Ph–CC–CO2CH2, b R = Ph, R1 = 2-FurCO2CH2,
c R = Ph, R1 = PhCO2CH2, d R = Ph, R1 = 4-O2NC6H4CO2CH2
CH2 H-a
H-b
All =
–CH2CCH
Prop =
Aziridines 6-10 were synthesized by the oxidative addition of N-aminophthalimide to alkenes 1-5
according to the standard procedure [5]. This reaction is usually carried out at reduced temperature but in many
cases better yields of aziridines 6-10 are obtained at 13°C. As a consequence of the low activity of triple and
unconjugated terminal double bonds in oxidative aminoaziridination reactions [6], the addition of
N-aminophthalimide to compounds 1a,b, 2a,b, 4a,b, and 5a proceeded only at the double bonds of the styrene
fragment.
N-Phthalimidoaziridines 6-10 are colorless or yellow crystalline compounds stable under usual
conditions. Aziridines 9a,b and 10a form glassy masses, which foam with solidification only at high vacuum.
1
The structures and compositions of products 6-10 were supported by H and 13C NMR spectroscopy, mass
spectrometry, and/or elemental analysis.
The trans configuration of the double bond in the starting alkenes is retained in the products of their
oxidative aminoaziridination 6-10, which is indicated by the small vicinal coupling constants of the aziridine
protons (4.6-5.5 Hz). As the result of slow inversion of the endocyclic nitrogen atom (relative to the NMR time
1
scale) [7, 8], the H NMR spectra indicate the existence of aziridines 6a, b at room temperature as a mixture of
two invertomers. One of these invertomers is clearly predominant (the invertomer ratio was 1:≤0.12). The
content of the minor invertomer for aminoaziridines 7-9 is evidently so low that its signals could not be
observed in the NMR spectra. We can assume that the phthalimide group in the major or only spectrally detected
invertomer of compound 6-9 is in the anti position related to the aryl group, which is the bulkier of the two
substituents at the carbon atoms. The two invertomers for aziridines 10a-d exist in comparable amounts,
indicating similar effective bulk of the substituents.
1354

1
The proton signal of the major or only observed invertomer in the H NMR spectra of aziridines 6-9 at
4.40-4.76 ppm is lower and broader relative to the signal at 3.14-3.57 ppm. In our view, this broadening is a
manifestation of long-range spin-spin coupling of the proton geminal to the aryl group with the o-protons of this
aryl group and, thus, we assign the downfield signal to H-3 proton. The upfield signal is assigned to proton H-2.
The thermal transformations of N-phthalimidoaziridines 6-10 were carried out in a sealed, heat-stable
glass reactor in absolute benzene or toluene solutions. The optimal temperature for the reaction was determined
by thin-layer chromatographic monitoring of the change in the composition of the reaction mixture at
approximately 30 min intervals upon heating at constant temperature. The temperature was raised from 80°C in
1
steps of about 10°C until onset of the reaction. The H NMR spectrum of the reaction mixture was taken upon
the cessation of heating.
Heating of aziridines 6a,b led to good yields of the expected cycloadducts with two condensed
five-membered rings, namely, hexahydroindenopyrroles derivatives 11a,b. The three-dimensional structure of
these products was proved by two-dimensional 1H-1H NOESY spectroscopy and corresponds to
thermally-allowed conrotatory opening of the aziridine ring with subsequent concerted [3+2] cycloaddition. In
this case, as usually observed (see our previous work [2]), the yield of adduct 11b with a cyano group, which
strongly stabilizes the intermediate ylide, is slightly higher than for its analog 11a with an ester group and the
required temperature and reaction time for 11b are lower.
We expected to obtain benzoxepinopyrrole derivatives with a seven-membered ring from aziridines
7a,b. However, chromatographic separation of the reaction mixture obtained upon heating aziridine 7a gave
only dihydrobenzoxepinopyrrole 12 with 22% yield, which was probably formed as the result of the loss of
phthalimide from the initial intramolecular cycloaddition product. 1H and 13C NMR spectroscopy indicated the major
1355

fraction is a mixture of isomeric imines 13a and 14a*. This mixture could not be separated by either
chromatography or recrystallization but we observed that one of its components completely converted to
amidine 15 over the course of a few days at room temperature with access to the air. Separation of the new
mixture resulted in isolation of pure crystalline compounds 13a and 15. Doublets for the protons of the NCHN
1
and CH=N fragments in the downfield region of the H NMR spectrum as well as corresponding signals in the
13C NMR spectrum are characteristic for imine 13a. Cross peaks corresponding to NOE of the CH=N proton
with the o-proton of the adjacent phenyl ring and with the NCHN proton, which is spatially-proximate in the
1
(E)-isomer, are seen in the H-1H NOESY spectrum of compound 13a. We note that the formation of such
imines has been observed previously upon heating several tri- and tetrasubstituted N-phthalimidoaziridines [9].
The thermolysis of aziridine 7b with a double bond less active as a dipolarophile did not lead to the
expected cycloadduct. Only a mixture of imines 13b and 14b could be isolated in this case, which was
1
confirmed by elemental analysis and mass spectrometry. The H NMR spectra of this mixture showed two sets
of signals for the allyloxymethylene group, two doublets in the downfield region corresponding to the
CH=N-CH< fragment of imine 13b (by analogy with imine 13a), and a doublet of one of these protons in 14b
(the second doublet is apparently superposed by the aromatic proton signals) in addition to the aromatic proton
multiplets. Thus, the intramolecular 1,3-cycloaddition of azomethine ylides at unactivated double bond with
concurrent formation of a seven-membered ring proves so unfavorable that rearrangements of such compounds
with migration of the phthalimide fragment leading to imines 13 and 14 become the major reactions for these
compounds.
The thermolysis of aziridine 8a did not lead to products of the 1,3-dipolar cycloaddition of the
azomethine ylide at a formal multiple bond of the phenyl ring. 5-Methoxyoxazole 16, which may be seen as the
product of the 1,5-electrocyclization of the intermediate azomethine ylide with subsequent loss of a phthalimide
molecule and formation of the aromatic oxazole system (see our previous works [10, 11]) was isolated from the
reaction mixture in addition to phthalimide and 2-benzyloxybenzaldehyde.
This is the first report of the preparation of 5-methoxyoxazole 16 but due to the instability of this
1
compound at room temperature, we were able to record only its H NMR spectrum displaying a singlet at
_______
*The yields of imines 13a and 14a were calculated using the 1H NMR spectrum of the reaction mixture relative
1
to isolated product 12, while the yields of imines 13b and 14b were calculated from the H NMR spectrum of
their mixture.
1356

6.26 ppm assigned to proton H-4 of the heterocycle and signals for the aromatic protons and OCH3 group in
their usual regions.
Thermolysis of the analogous aziridine 8b with a cyano group, which facilitates generation of the
azomethine ylide but is incapable of participating in 1,5-electrocyclization, led only to decomposition products,
namely, phthalimide and 2-benzyloxybenzaldehyde. Heating aziridine 8c, which proceeds with considerable tar
formation, gave a low yield of the product of the intramolecular cycloaddition of the intermediate ylide, namely,
tetrahydrochromenoimidazole 17 as well as hydrazone 18. Thus, the usually inert C≡N bond proved nevertheless a
better dipolarophile than the aromatic system multiple bond.
Attempting to carry out the intramolecular 1,3-dipolar cycloaddition in aziridines 9a,b with a more
flexible unsaturated side chain than in previously studied 6a,b, we have observed only isomerization to
imines 19a,b. These imines could not be isolated as pure compounds and thus we estimated their yield from the
1H NMR spectra of the reaction mixtures using an internal standard.
O
O
O
O
O
O
O

10a–d
X
N
N
N
NPhth
Ph
NPhth
NPhth
180oC
5 h
Ph
Ph
Ph
20b
20a
20c,d
PhthNN=CHMe
21 (6–45%)
20 c X = H, d X = NO2
The 1H NMR spectra of imines 19a,b display characteristic signals for the alcoholic residues of the ester
groups, while the NCHN and CH=N protons signals appear in vicinity of 6.12 and 8.40 ppm, respectively. The
structure of imine 19a was confirmed by its 1H-1H NOESY spectrum, in which, as in the spectrum of compound
13a, cross peaks are seen corresponding to NOE of the CH=N proton with the o-protons of the adjacent phenyl
ring and with the NCHN proton.
We expected that heating aziridines 10a-d would yield products of the intramolecular cycloaddition at
the triple bond (compound 20a), at the C=C bond of the slightly aromatic furan ring (compound 20b), and even
at the formally multiple bonds of aryl substituents (compounds 20c,d) since Henke et al. [4] had already
reported the synthesis of similar compounds from N-alkylaziridines through flash vacuum pyrolysis.
Ph
NPhth
Ph
O
Ph
N
NPhth
NPhth
180°C
O
N
HN
H2O
NPhth
HO
N
– RCO2H
– PhCHO
R
O
R
III
21
II
I
10a–d
1357

However, although starting aziridines 10a-d were no longer detected in the reaction mixtures upon
1
heating for 5 h at 180°C, the H NMR spectra of these mixtures lacked signals of the expected cycloadducts in
the region of 2-6 ppm. Furthermore, in all cases, we observed characteristic multiplets of the aliphatic protons of
acetaldehyde phthaloylhydrazone (21) (quartet at 8.66 ppm and doublet with triple intensity at 2.21 ppm), which
we have isolated from the reaction mixture with aziridine 10a and identified by comparison with an authentic
sample.
Our proposed reaction scheme for formation of this rather unexpected product features a key step of the
starting aziridine conversion into the compound I through a hetero-Cope rearrangement (the three-membered
ring here is a double bond analog) followed by hydrolysis to give aminal II. Then, compounds II decomposes to
give enhydrazine III, which isomerizes to hydrazone 21.
Aziridines 10a-d differ significantly from compounds 6-9 in that the aziridine ring carbon atom in
compounds 10a-d has only a single phenyl substituent capable of stabilizing the intermediate azomethine ylides.
Thus, formation of 1,3-ylides in the case of compounds 10a-d is energetically unfavored and thermolysis of
these aziridines probably proceeds without the participation of such ylides.
With the exception of the latter reaction, the rearrangement of N-phthalimidoaziridines to give imines
almost always proceeds along with intramolecular 1,3-dipolar cycloaddition or instead of this process. In order
to clarify how common this rearrangement is, we carried out the thermolysis of previously known
N-phthalimidoaziridines 22a-c [12-14], which possess substituents incapable of participating in other
intramolecular transformations.
R
N
R
PhthN
N
PhthN
PhthN
N
+
R1
Ph
NC
R1
22a
b
c
120°C, 6 h
180°C, 5 h
120°C, 5 h
23a (~100%)
23c (23%)
24 (6%)
22, 23 a R = R1 =Ph; 22b R = R1 = CN; 22, 23 c R = CN, R1 = Ph
The thermolysis results indicated that 2,3-diphenylaziridine 22a converts upon heating quantitatively to
corresponding imine 23a: the 1H and 13C NMR spectra of the reaction mixture show signals only for compound
23a. In absolute benzene, imine 23a remains unchanged for a rather long period, but only phthalimide in almost
quantitative yield could be isolated in attempts to separate out this compound by chromatography or
crystallization. However, heating aziridine 22b, which has two cyano groups, led only to complete
decomposition of the starting compound and tar formation; formation of rearrangement products could not be
detected in this case.
In the case of unsymmetrical aziridine 22c, the reaction is also accompanied by heavy tar formation but
1
products 23c and 24 could be isolated as pure compounds after chromatography. The H NMR spectrum of the
reaction mixture showed that these compounds were formed in ~4:1 ratio, which corresponds to the amounts
1
isolated. The H and 13C NMR spectra of imine 23c are similar to the spectra of compounds 13, 19, and 23a.
Structures of compounds 23a,c were additionally confirmed by 2D 1H-1H NOESY spectroscopy.
1
The H NMR spectrum of hydrazone 24 displays a singlet for the CH2 group protons at  4.48 ppm in
addition to the signals for the phthalimide and phenyl group protons. Chemical shift of the CH2 group carbon
atom at 39.8 ppm corresponds to a position adjacent to a phenyl substituent since this atom would appear at
much higher field if it were adjacent to a cyano group (~20 ppm). The 1H NMR spectrum of hydrazone 24 could
also correspond to the structure of the imine obtained as a result of migration of the double bond in compound
23c to a carbon atom at the phthalimide and cyano group. However, the signal of the CH2 group carbon atom in
the 13C NMR spectrum would be found at much lower field (~50 ppm). Since it is more favorable for the bulky
1358

phthalimide group to be located near the small cyano group, we propose (Z)-configuration for the C=N bond in
hydrazone 24. We attribute the formation of phthaloylhydrazones 18 and 24 to opening of the aziridine ring at a
C–N bond under the rigorous reaction conditions.
Thus, isomerization to imines is indeed a common feature of the thermal transformations of disubstituted
N-phthalimidoaziridines. Aryl substituents at the aziridine ring facilitate this process. Opening of the
three-membered ring to give the corresponding azomethine ylide evidently precedes this isomerization, while at
least three mechanisms for shifting the phthalimide fragment to the adjacent carbon atom are theoretically
possible: a concerted 1,2-shift and cleavage of the phthalimide group with subsequent recombination of the two
species through an ion or radical pair. Person et al. [9] presented experimental data serving as evidence against
mechanisms involving participation of an ion or radical pair in their work on a similar isomerization of tri- and
tetrasubstituted N-phthalimidoaziridines. These authors found no cross reactions, a high reaction rate in nonpolar
solvents, and the lack of EPR signals. Thus, we consider that this reaction in our case as well proceeds as a
1,2-shift of the phthalimide group from the nitrogen atom to a carbon atom in the azomethine ylide, most likely
through a concerted mechanism.
Summarizing, we conclude that heating N-phthalimidoaziridines with unsaturated substituents leads to
intramolecular cycloaddition at the multiple bonds of these substituents competing with rearrangements. The
ratio of these processes depends both on the steric accessibility and activity of the multiple bond serving as the
dipolarophile and the nature of the aziridine ring substituents. Five-membered rings form smoothly from
(2-allylphenyl)aziridines, while heating esters of aziridinecarboxylic acid with a side chain of the same length
leads only to rearrangement products. Seven-membered rings, as might have been expected, close with greater
difficulty than five- and six-membered rings [see, 2] and rearrangements become predominant in this case. Very
low activity is found for the cyano group triple bond and phenyl ring formal multiple bonds as dipolarophiles,
even in intramolecular reactions. Adducts in these cases either are not formed at all or are obtained with
extremely low yields. Aziridines possessing an aryl substituent readily isomerize to give imines via a 1,2-shift of
the phthalimide group to one of the carbon atoms in the intermediate azomethine ylide. Phthalimidoaziridines
with only one substituent capable of stabilizing the azomethine ylide do not give 1,3-dipoles upon heating but
rather undergo a Cope type rearrangement.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on a Bruker DPX-300 spectrometer at 300 and 75 MHz,
respectively, in CDCl3 solution with the signal of the residual protons ( 7.26 ppm) as internal standard for the
1H NMR spectra and solvent carbon atom signal at  77.2 ppm as internal standard for the 13C NMR spectra. The
high-resolution ESI mass spectra were performed on a Bruker micrOTOF spectrometer. The elemental analyses
were taken on a Hewlett-Packard HP-185B automatic CHN analyzer. The composition of reaction mixtures and
the fractions obtained upon separation as well as the purity of the isolated compounds were monitored by
thin-layer chromatography on Macherey-Nagel Polygram SIL G/UV254 and Alugram SIL G/UV254 plates.
N-Aminophthalimide was obtained according to Drew and Hatt [15].
N-Phthalimidoaziridines 6-10 (General Method). N-Aminophthalimide (0.729 g, 4.5 mmol) and
Pb(OAc)4 (1.995 g, 4.5 mmol) were added consecutively in 7-15-mg portions to a stirred suspension of
anhydrous K2CO3 (1.863 g, 13.5 mmol) in a solution of alkene 1-5 (3.0 mmol) in anhydrous CH2Cl2 (30 ml) at
the indicated temperature over 20 min. The mixture was then stirred for an additional 20-30 min at the same
temperature and filtered through a 1.5-cm-thick silica gel layer. The residue was washed with 40-150 ml
CH2Cl2. The combined filtrates were treated as described below.
Methyl (2R',3S')-3-(2-Allylphenyl)-1-phthalimidoaziridine-2-carboxylate (6a). The reaction was
carried out at -20°C. The combined filtrates were evaporated in vacuum. The residue was separated by
chromatography on a column packed with 30 g silica gel using CH2Cl2 as the eluent to give compound 6a. Yield
1359

1.065 g (98%). Colorless crystals, mp 107-108°C. The 1H NMR spectrum indicates that this compound exists as
1
a 25:1 mixture of two invertomers. H NMR spectrum, , ppm (J, Hz): 3.26 (0.96H, d, J = 5.1, H-2); 3.49 (1H,
dd, J = 16.0, J = 6.2) and 3.56 (1H, dd, J = 16.0, J = 6.2, CH2); 3.74 (2.88H, s) and 3.90 (0.12H, s,CH3); 4.38
(0.04H, d, J = 5.5) and 4.80 (0.04H, d, J = 5.5, H-2,3); 4.45 (0.96H, d, J = 5.1, H-3); 4.95 (1H, dd, J = 17.4,
J = 1.5, H-a); 5.06 (1H, dd, J = 10.2, J = 1.5, H-b); 5.94 (1H, ddt, J = 17.4, J = 10.2, J = 6.2, CH); 7.20-7.30
(3H, m) and 7.48 (1H, dd, J = 7.2, J = 2.0, H Ar); 7.66-7.79 (4H, m, H PhthN). 13C NMR spectrum of major
invertomer, , ppm: 37.5 (CH2); 46.7, 47.8 (C-2,3); 53.0 (CH3); 116.3 (=CH2); 123.3 (C-b); 126.5, 127.0, 128.5,
129.7 (C-3',4',5',6'); 130.4 (C-a); 133.3, 138.3 (C-1',2'); 134.2 (C-c); 136.4 (CH=CH2); 164.8 (NCO); 166.9
(CO2). Found, m/z: 363.1310 [M+H]+. C21H19N2O4. Calculated, m/z: 363.1340. Found, %: C 69.42; H 4.80;
N 7.92. C21H18N2O4. Calculated, %: C 69.60; H 5.00; N 7.73.
(2R',3S')-3-(2-Allylphenyl)-1-phthalimidoaziridine-2-carbonitrile (6b). The reaction was carried out
at 13°C. The combined filtrates were evaporated in vacuum. The residue was separated by chromatography on a
column packed with 30 g silica gel using CH2Cl2 as the eluent to give compound 6b. Yield 0.495 g (50%).
Colorless crystals, mp 122-123°C. The 1H NMR spectrum indicates that compound 6b exists as an 8.3:1 mixture
1
of two invertomers. H NMR spectrum, , ppm (J, Hz): 3.14 (0.89H, d, J = 5.0, H-2); 3.54 (1H, dd, J = 16.0,
J = 6.2) and 3.63 (1H, dd, J = 16.0, J = 6.2, CH2); 4.52 (0.11H, d, J = 5.1) and 4.56 (0.11H, d, J = 5.1, H-2,3);
4.61 (0.89H, d, J = 5.0, H-3); 5.06 (1H, dd, J = 17.2, J = 1.5, H-a); 5.18 (1H, dd, J = 10.2, J = 1.5, H-b); 6.02
(1H, ddt, J = 17.2, J = 10.2, J = 6.2, CH); 7.23-7.42 (4H, m, H Ar); 7.75-7.89 (4H, m, H PhthN). 13C NMR
spectrum of major invertomer, , ppm: 35.4 (C-2); 37.5 (CH2); 47.6 (C-3); 114.9 (CN); 116.9 (=CH2); 123.9
(C-b); 126.3, 127.2, 129.3, 130.1 (C-3',4',5',6'); 130.2 (C-a); 131.5, 138.5 (C-1',2'); 136.1 (CH=CH2); 164.9
(NCO). Found, m/z: 352.1010 [M+Na]+. C20H15N3NaO2. Calculated, m/z: 352.1057. Found, %: C 73.01; H 4.53;
N 12.68. C20H15N3O2. Calculated, %: C 72.94; H 4.59; N 12.76.
(2R',3S')-3-[2-(Propargyloxymethyl)phenyl]-1-phthalimidoaziridine-2-carbonitrile
(7a).
The
reaction was carried out at 13°C. The combined filtrates were evaporated in vacuum. The residue was separated
by chromatography on a column packed with 30 g silica gel using CH2Cl2 as the eluent to give compound 7a.
Yield 0.579 g (54%). Yellow crystals, mp 165°C. 1H NMR spectrum, , ppm (J, Hz): 2.51 (1H, t, J = 2.3, ≡CH);
3.24 (1H, d, J = 5.0, H-2); 4.27 (2H, d, J = 2.3, CH2C≡); 4.71 (1H, d, J = 11.4) and 4.91 (1H, d, J = 11.4,
OCH2Ar); 4.76 (1H, d, J = 5.0, H-3); 7.34-7.45 (4H, m, H Ar); 7.75-7.89 (4H, m, H PhthN). 13C NMR spectrum,
, ppm: 35.6 (C-2); 47.4 (C-3); 57.7 (CH2C≡); 69.9 (CH2Ar); 75.7 (C≡CH); 79.2 (C≡CH); 114.9 (CN); 123.9
(C-b); 126.5, 129.1, 129.1, 130.0 (C-3',4',5',6'); 130.2 (C-a); 132.7, 135.9 (C-1',2'); 134.8 (C-c); 164.9 (NCO).
Found, m/z: 358.1119 [M+H]+. C21H16N3O3. Calculated, m/z: 358.1186. Found, %: C 70.63; H 4.26; N 11.50.
C21H15N3O3. Calculated, %: C 70.58; H 4.23; N 11.76.
(2R',3R')-3-(2-Allyloxymethyl)phenyl)-1-phthalimidoaziridine-2-carbonitrile (7b). The reaction was
carried out at 13°C. The combined filtrates were evaporated in vacuum. The residue was separated by
chromatography on a column packed with 30 g silica gel using CH2Cl2 as the eluent to give compound 7b. Yield
0.496 g (46%). Colorless crystals, mp 121-122°C. 1H NMR spectrum, , ppm (J, Hz): 3.23 (1H, d, J = 5.0, H-2);
4.07 and 4.13 (total 2H, two dddd, J = 12.5, J = 5.8, J = 1.3, J = 1.3, CH2CH=); 4.57 (1H, d, J = 11.5) and 4.81
(1H, d, J = 11.5, H-b); 4.73 (1H, d, J = 5.0, H-3); 5.24 (1H, ddt, J = 10.3, J = 1.3, J = 1.3, H-b); 5.33 (1H, ddt,
J = 17.2, J = 1.3, H-a); 5.99 (1H, ddt, J = 17.2, J = 10.3, J = 5.8, CH=CH2); 7.32-7.36 (3H, m) and 7.42-7.46
(1H, m, H Ar); 7.57-7.89 (4H, m, PhthN). 13C NMR spectrum, , ppm: 35.5 (C-2); 47.5 (C-3); 70.7 (OCH2);
71.8 (OCH2); 115.0 (CN); 118.1 (CH=CH2); 123.8 (C-b); 126.5, 128.8, 129.0, 129.7 (C-3',4',5',6'); 130.2 (C-a);
132.5, 136.8 (C-1',2'); 134.3 (CH=CH2); 134.8 (C-c); 164.9 (NCO). Found, m/z: 398.0900 [M+K]+.
C21H17KN3O3. Calculated, m/z: 398.0902. Found, %: C 70.05; H 4.80; N 11.65. C21H17N3O3. Calculated, %:
C 70.58; H 4.77; N 11.69.
Methyl (2R',3S')-3-(2-Benzyloxyphenyl)-1-phthalimidoaziridine-2-carboxylate (8a). The reaction
was carried out at 13°C. The combined filtrates were evaporated in vacuum. The residue was dissolved in a
minimal amount of dichloromethane and hexane was added dropwise until the onset of crystallization. The
precipitate formed was filtered off and dried in the air to give compound 8a. Yield 0.964 g (75%). Yellow
1360

crystals, mp 172-174°C. 1H NMR spectrum, , ppm (J, Hz): 3.32 (1H, d, J = 5.1, H-2); 3.66 (3H, s, OCH3); 4.57
(1H, d, J = 5.1, H-3); 5.14 (2H, s, OCH2); 6.99-7.10 (2H, m, H-3',5'); 7.26-7.41 (6H, m, H Ph, H-4'); 7.53 (1H,
dd, J = 7.3, J = 1.5, H-6'); 7.66-7.80 (4H, m, H PhthN). 13C NMR spectrum, , ppm: 46.0, 46.5 (C-2,3); 52.8
(CH3); 70.2 (OCH2); 111.8 (C-3'); 121.2 (C-5'); 123.2 (C-b); 123.9 (C-1'); 127.1, 127.9, 128.0,
128.6,129.5(C-4',6', m,o,p-C); 130.5 (C-a); 134.1 (C-c); 137.0 (i-C); 157.0 (C-2'); 164.8 (NCO); 167.2 (CO2).
Found, m/z: 429.1455 [M+H]+. C25H21N2O5. Calculated, m/z: 429.1455. Found, %: C 70.08; H 4.61; N 4.61.
C25H20N2O5. Calculated, %: C 70.08; H 4.71; N 6.54.
(2R',3S')-3-(2-Benzyloxyphenyl)-1-phthalimidoaziridine-2-carbonitrile (8b). The reaction was
carried out at 13°C. The combined filtrates were evaporated in vacuum. The residue was dissolved in a minimal
amount of dichloromethane and hexane was added until the solution became turbid. The mixture was then left
overnight in a refrigerator. The precipitate was filtered off and dried in the air to give compound 8b. Yield 0.403
g (34%). Colorless crystals. 1H NMR spectrum, , ppm (J, Hz): 3.22 (1H, d, J = 5.1, H-2); 4.73 (1H, d, J = 5.1,
H-3); 5.19 (2H, s, OCH2); 6.93-7.03 (2H, m, H-3',5'); 7.28-7.50 (7H, m, H Ph, H-4',6'); 7.70-7.90 (4H, m,
H PhthN). 13C NMR spectrum, , ppm: 34.9 (C-2); 46.1 (C-3); 70.4 (OCH2); 112.1 (C-3'); 115.1 (CN); 121.3
(C-5'); 121.9 (C-1'); 123.8 (C-b); 127.2 (o-C); 127.7, 128.2 (C-4',6', p-C); 128.8 (m-C); 130.3 (C-a); 134.7 (C-c);
136.6 (i-C); 157.2 (C-2'); 164.9 (CO). Found, m/z: 396.1313 [M+H]+. C24H18N3O3. Calculated, m/z: 396.1343.
(2R',3S')-3-[2-(Cyanomethoxy)phenyl]-1-phthalimidoaziridine-2-carbonitrile (8c). The reaction was
carried out at 13°C. The combined filtrates were evaporated in vacuum. The residue was dissolved in a minimal
amount of dichloromethane and hexane was added dropwise until the onset of crystallization. After several
hours, the precipitate formed was filtered off and dried in vacuum to give compound 8c. Yield 0.837 g (81%).
1
Colorless crystals, mp 127-129°C. H NMR spectrum, , ppm (J, Hz): 3.25 (1H, d, J = 5.1, H-2); 4.69 (1H, d,
J = 5.1, H-3); 4.92 (1H, d, J = 16.4) and 4.93 (1H, d, J = 16.4, OCH2); 7.07 (1H, d, J = 8.7, H-3'); 7.14 (1H, dd,
J = 7.3, J = 7.3, H-5'); 7.38-7.47 (2H, m, H-4',6'); 7.75-7.88 (4H, m, H PhthN). 13C NMR spectrum, , ppm: 35.1
(C-2); 45.1 (C-3); 54.2 (CH2O); 112.3 (C-3'); 114.8 (CN); 114.9 (CN); 121.5 (C-5'); 123.6, 123.9 (C-b, C-1');
128.0 (C-6'); 130.2, 130.6 (C-4', C-a); 134.8 (C-c); 155.2 (C-2'); 164.8 (CO). Found, m/z: 345.0968 [M+H]+.
C19H13N4O3. Calculated, m/z: 345.0983. Found, %: C 66.38; H 3.52; N 16.22. C19H12N4O3. Calculated, %:
C 66.28; H 3.51; N 16.27.
Allyl (2R',3S')-3-Phenyl-1-phthalimidoaziridine-2-carboxylate (9a). The reaction was carried out at
13°C. The combined filtrates were evaporated in vacuum. The residue was separated by chromatography on a
column packed with 30 g silica gel using dichloromethane as the eluent to give compound 9a. Yield 0.627 g
1
(60%). A yellow oil. H NMR spectrum, , ppm (J, Hz): 3.55 (1H, d, J = 4.6, H-2); 4.40 (1H, d, J = 4.6, H-3);
4.56-4.68 (2H, m, OCH2); 5.25 (1H, ddt, J = 10.4, J = 1.2, J = 1.2, H-b); 5.34 (1H, ddt, J = 17.2, J = 1.4, J = 1.4,
H-a); 5.90 (1H, ddt, J = 17.2, J = 10.4, J = 5.9, CH=CH2); 7.28-7.48 (5H, m, H Ph); 7.65-7.81 (4H, m,
H PhthN). 13C NMR, , ppm: 46.3, 49.8 (C-2,3); 66.8 (OCH2); 119.3 (CH=CH2); 123.3 (C-b); 127.3, 128.8
(m,o-C, CH=CH2, signals overlap); 130.4 (C-a); 131.3 (p-C); 134.2 (C-c); 134.6 (i-C); 164.8 (NCO); 166.1
(CO2). Found, m/z: 349.1136 [M+H]+. C20H17N2O4. Calculated, m/z: 349.1183.
Propargyl (2R',3S')-3-Phenyl-1-phthalimidoaziridine-2-carboxylate (9b). The reaction was carried
out at 13°C. The combined filtrates were evaporated in vacuum. The residue was separated by chromatography
on a column packed with 30 g silica gel using from 3:1 to 5:1 dichloromethane−hexane as the eluent to give
1
compound 9b. Yield 0.770 g (74%). A pale-yellow glassy substance. H NMR spectrum, , ppm (J, Hz): 2.48
(1H, t, J = 2.4, C≡CH); 3.57 (1H, d, J = 4.9, H-2); 4.41 (1H, d, J = 4.9, H-3); 4.63 (1H, dd, J = 15.5, J = 2.4) and
4.81 (1H, dd, J = 15.5, J = 2.4, OCH2); 7.34-7.48 (5H, m, H Ph); 7.66-7.81 (4H, m, H PhthN). 13C NMR
spectrum, , ppm (J, Hz): 45.9, 50.0 (C-2,3); 53.6 (OCH2); 75.8 (C≡CH); 123.3 (C-b); 127.4, 128.8 (m,o-C);
128.9 (p-C); 130.3 (C-a); 134.2 (C-c); 134.3 (i-C); 164.7 (NCO); 165.7 (CO2). The C≡CH signal is apparently
overlapped by the solvent signal. Found, m/z: 385.0513 [M+K]+. C20H14KN2O4. Calculated, m/z: 385.0586.
(2R',3S')-(3-Phenyl-1-phthalimidoaziridin-2-yl)methyl 3-Phenylprop-2-ynoate (10a). The reaction
was carried out at 0°C. The combined filtrates were evaporated in vacuum. The residue was separated by
chromatography on a silica gel column with 350:1 dichloromethane−methanol as the eluent to give compound
1361

1
10a. Yield 0.620 g (49%). A pale-yellow glassy substance, mp 76-77°C. The H NMR spectrum indicated a
1
1:0.58 mixture of two invertomers. H NMR spectrum, , ppm (J, Hz): 3.21-3.26 (0.37H, m) and 4.38-4.43
(0.63H, m, H-2); 3.80 (0.63H, d, J = 5.5) and 4.14 (0.37H, d, J = 5.5, H-3); 4.48 (0.37H, dd, J = 12.5, J = 5.2);
4.77 (0.37H, dd, J = 12.5, J = 5.8); 4.57 (0.63H, dd, J = 11.9, J = 6.0) and 4.69 (0.63H, dd, J = 11.9, J = 4.9,
OCH2); 7.22-7.65 (12.52H, m, H Ph, H PhthN maj.); 7.68-7.83 (1.48H, m, H Ph, H PhthN min.). 13C NMR
spectrum, , ppm: 42.3; 46.2; 47.0 and 49.6 (C-2,3); 62.1 (OCH2 min.); 65.5 (OCH2 maj.); 80.0 (C≡CCO2 min.);
80.4 (C≡CCO2 maj.); 87.4 (C≡CCO2 maj.); 87.8 (C≡CCO2 min.); 119.4 and 119.6 (i-C Ph at C≡C); 123.0 and
123.4 (C-b); 127.3; 128.3; 128.4; 128.7; 129.0; 129.6, 130.9; 131.0 and 133.2 (m,o,p-C); 130.1, 130.4, 130.6,
and 135.8 (C-a, i-C 3-Ph); 134.0 and 134.4 (C-c); 153.9 (CO2); 165.5 and 165.9 (NCO). Found, m/z: 445.1198
[M+Na]+. C26H18N2NaO4. Calculated, m/z: 445.1159. Found, %: C 74.22; H 4.37; N 6.61. C26H18N2O4.
Calculated, %: C 73.92; H 4.29; N 6.63.
(2R',3S')-(3-Phenylphthalimidoaziridin-2-yl)methyl Furan-2-carboxylate (10b). The reaction was
carried out at 13°C. The combined filtrates were evaporated in vacuum but not to dryness. Hexane was added
dropwise to the residue until the onset of crystallization with concurrent rubbing the walls of the flask using a glass
rod. The precipitate was filtered off to give compound 10b. Yield 0.594 g (51%). Yellow crystals, mp 150-151°C.
1
1
The H NMR spectrum indicated the existence of a 1.3:1 mixture of two invertomers. H NMR spectrum, , ppm
(J, Hz): 3.24-3.28 (0.43H, m) and 4.38-4.44 (0.57H, m, H-2); 3.79 (0.57H, d, J = 5.7, H-3) and 4.24 (0.43H, d,
J = 5.5, H-3); 4.53-4.59 (0.86H, m) and 4.64-4.81 (1.14H, m, OCH2); 6.48 (0.43H, dd, J = 3.5, J = 1.7) and 6.53
(0.57H, dd, J = 3.5, J = 1.7, H-4'); 7.15-7.52 (7H, m, H-3',5' and H Ph); 7.57-7.64 (2.28H, m) and 7.68-7.81 (1.72H,
m, H PhthN). 13C NMR spectrum, , ppm: 42.8; 45.5; 47.4 and 49.5 (C-2,3); 60.8 and 64.6 (OCH2); 112.1 (C-4');
118.8 (C-3'); 123.0 and 123.3 (C-b); 127.3, 128.3. 128.4, 128.7, 129.0 and 129.6 (m,o,p-C); 130.1, 130.5, 130.6,
and 135.9 (C-a and i-C); 134.0 and 134.3 (C-c); 144.0 and 144.4 (C-2'); 146.8 and 146.9 (C-5'); 158.0 and 158.6
(CO2); 165.5 and 165.9 (NCO). Found, m/z: 411.1027 [M+Na]+. C22H16N2NaO5. Calculated, m/z: 411.0952. Found,
%: C 68.11; H 4.08; N 7.09. C22H16N2O5. Calculated, %: C 68.04; H 4.15; N 7.21.
(2R',3S')-(3-Phenyl-1-phthalimidoaziridin-2-yl)methyl Benzoate (10c). The reaction was carried out
at 0°C. The combined filtrates were evaporated in vacuum but not to dryness. Hexane was added to the residue
until the onset of crystallization. The precipitate formed was filtered off and discarded. Diethyl ether was added
to the remaining solution and cooled to 0°C. The precipitate formed was filtered off and washed with diethyl
ether to give compound 10c. Yield 0.560 g (47%). Colorless flakes with a greenish tinge, mp 123-124°C. The
1
1H NMR spectrum indicated the existence of a 1.4:1 mixture of two invertomers. H NMR spectrum, , ppm
(J, Hz): 3.27-3.32 (0.42H, m) and 4.44-4.50 (0.58H, m, H-2); 3.80 (0.58H, dd, J = 5.5) and 4.25 (0.42H, d,
J = 5.5, H-3); 4.56 (0.58H, dd, J = 11.7, J = 6.6); 4.82 (0.58H, dd, J = 11.7, J = 4.1) and 4.68-4.76 (0.84H, m,
OCH2); 7.21-7.64 (10.32H, m, H Ar, H PhthN maj.); 7.67-7.80 (1.68H, m, H PhthN min.); 7.97 (0.84H, d,
J = 7.4) and 8.16 (1.16H, d, J = 7.3, o-H PhCO2). 13C NMR spectrum, , ppm: 42.9, 45.5, 47.6, 49.5 (C-2,3);
60.9, 64.9 (OCH2); 123.0, 123.3, 127.3, 128.3, 128.5, 128.7, 128.9, 129.7, 129.8, 130.0, 133.2 and 133.4 (C-b,
m,o,p-C); 130.1, 130.5, 130.6 and 135.9 (C-a, i-C); 134.0 and 134.3 (C-c); 165.5, 165.9, 166.1 and 166.6 (NCO,
CO2). Found, m/z: 421.1139 [M+Na]+. C24H18N2NaO4. Calculated, m/z: 421.1158.
(2R',3S')-(3-Phenyl-1-phthalimidoaziridin-2-yl)methyl 4-Nitrobenzoate (10d). The reaction was
carried out at 0°C. The combined filtrates were evaporated in vacuum but not to dryness. Hexane was added
dropwise to the residue until the onset of crystallization with concurrent rubbing the walls of the flask using a
glass rod. The precipitate was filtered off to give compound 10d. Yield 0.652 g (49%). Yellowish flake crystals,
1
1
mp 159°C. The H NMR spectrum indicated a 1.9:1 mixture of two invertomers. H NMR spectrum, , ppm
(J, Hz): 3.32 (0.35H, ddd, J = 7.3, J = 5.5, J = 3.9) and 4.96 (0.65H, ddd, J = 9.1, J = 7.3, J = 4.8, H-2); 3.79
(0.65H, d, J = 4.8) and 4.24 (0.35H, dd, J = 5.5, H-3); 4.43-4.48 (1.30H, m); 4.64 (0.35H, dd, J = 12.9, J = 7.3)
and 4.84 (0.35H, dd, J = 12.9, J = 3.9, OCH2); 7.20-7.48 and 8.19-8.38 (9H, m, H Ar); 7.61 (2.60H, br. s) and
7.70-7.81 (1.40H, m, H PhthN). 13C NMR spectrum, , ppm: 42.8, 45.3, 47.2 and 49.3 (C-2,3); 61.7
(OCH2 min.); 65.9 (OCH2 maj.); 123.7 (C-b maj.); 123.1, 123.3, 127.3, 128.4, 128.5, 128.7, 129.1 and 129.6
(C-b min., o-C Ar, m,o,p-C Ph both invertomers); 131.0 (m-C Ar min.); 131.2 (m-C Ar maj.); 134.1 (C-c maj.);
1362

134.5 (C-c min.); 130.0, 130.2, 130.5, 135.0, 135.4 and 135.6 (C-a, i-C); 150.7 (p-C Ar); 164.4, 164.8, 165.4
and 165.9 (NCO, CO2). Found, m/z: 444.1222 [M+H]+. C24H18N3O6. Calculated, m/z: 444.1196. Found, %:
C 64.97; H 3.96; N 9.26. C24H17N3O6. Calculated, %: C 65.01; H 3.86; N 9.48.
Thermolysis of Aziridines 6 and 7 (General Method). A solution of aziridine 6 or 7 (1 mmol) in
anhydrous toluene (10 ml) was heated in a thick-walled glass reactor. The solvent was then distilled off in
vacuum. The residue was separated by chromatography on a silica gel column using from 6:1 to 3:1 hexane–
ethyl acetate mixture as eluent.
Methyl (2R',3aR',8bS')-1-phthalimido-1,2,3,3a,4,8b-hexahydroindeno[1,2-b]pyrrole-2-carboxylate
(11a) was obtained after 3 h heating of aziridine 6a at 150°C. Yield 213 mg (59%). Colorless crystals,
mp 133°C. 1H NMR spectrum, , ppm (J, Hz): 1.96 (1H, ddd, J = 11.0, J = 11.0, J = 11.0, endo-H-3); 2.51-2.60
(1H, m, exo-H-3); 2.85 (1H, d, J = 16.4, endo-H-4); 3.15 (1H, dd, J =16.4, J = 8.0, exo-H-4); 3.42-3.47 (1H, m,
H-3a); 3.56 (3H, s, CH3); 4.72 (1H, dd, J = 11.0, J = 6.4, H-2); 5.03 (1H, d, J = 8.6, H-8b); 7.18-7.20 (3H, m)
and 7.29-7.31 (1H, m, H Ar); 7.75-7.91 (4H, m, H PhthN). 13C NMR spectrum, , ppm: 34.3, 36.6 (C-3,4); 40.2
(C-3a); 52.1 (CH3); 64.9 (C-2); 75.0 (C-8b); 123.6 (C-b); 125.4, 125.7, 127.4, 128.2 (C-5',6',7',8'); 130.3 (C-a);
134.5 (C-c); 141.2, 142.7 (C-4a,8a); 167.0 (NCO); 171.3 (CO2). Found, m/z: 385.1157 [M+Na]+.
C21H18N2NaO4. Calculated, m/z: 385.1164. Found, %: C 69.45; H 5.21; N 7.71. C21H18N2O4. Calculated, %:
C 69.60; H 5.01; N 7.73.
(2R',3aR', 8bS')-1-Phthalimido-1,2,3,3a,4,8b-hexahydroindeno[1,2-b]pyrrole-2-carbonitrile (11b) was
obtained after 2.5 h heating aziridine 6b at 120°C. Yield 230 mg (70%). Colorless crystals, mp 188-189°C.
1H NMR spectrum, , ppm (J, Hz): 2.09 (1H, ddd, J = 11.2, J = 11.2, J = 11.2, endo-H-3); 2.65-2.74 (1H, m,
exo-H-3); 2.89 (1H, d, J = 16.4, endo-H-4); 3.19 (1H, dd, J = 16.4, J = 8.0, exo-H-4); 3.41-3.53 (1H, m, H-3a);
4.86 (1H, dd, J = 11.2, J = 6.1, H-2); 5.02 (1H, d, J = 8.4, H-8b); 7.21-7.32 (4H, m, H Ar); 7.81-7.95 (4H, m,
H PhthN). 13C NMR spectrum, , ppm: 36.0, 36.3 (C-3,4); 40.8 (C-3a); 53.8 (C-2); 74.4 (C-8b); 118.3 (CN);
123.9 (C-b); 125.5, 125.7, 127.6, 128.6 (C-5',6',7',8'); 129.9 (C-a); 134.9 (C-c); 140.6, 141.7 (C-4a,8a). The
phthalimide group NCO signals are not visible due to strong broadening attributed to slow rotation about the
N–N bond. Found, m/z: 368.0774 [M+K]+. C20H15KN3O2. Calculated, m/z: 368.0801. Found, %: 72.95;
H 4.52; N 12.52. C20H15N3O2. Calculated, %: C 72.94; H 4.59; N 12.76.
4,6-Dihydro-1H-[2]benzoxepino[5,4-b]pyrrole-2-carbonitrile (12) was obtained after 2 h heating
1
aziridine 7a at 130°C. Yield 46 mg (22%). Colorless crystals, mp 196-198°C. H NMR spectrum, , ppm
(J, Hz): 4.69 (2H, s, OCH2); 4.98 (2H, s, OCH2); 6.72 (1H, d, J = 2.6, H-3); 7.23-7.30 (2H, m, H-7,9); 7.37 (1H,
ddd, J = 7.0, J = 7.0, J = 2.4, H-8); 7.49 (1H, d, J = 7.6, H-10); 9.41 (1H, br. s, NH). 13C NMR spectrum, ,
ppm: 69.5, 72.9 (C-4,6); 102.1 (C-2); 114.6 (CN); 118.5 (C-3); 123.9 (C-3a); 124.1, 128.0, 128.8, 129.1
(C-7',8',9',10'); 129.9, 132.0, 138.2 (C-6a,10a,10b). Found, m/z: 233.0648 [M+Na]+. C13H10N2NaO. Calculated,
m/z: 233.0691. Found, %: C 74.39; H 4.76; N 13.12. C13H10N2O. Calculated, %: C 74.27; H 4.79; N 13.33.
The fractions containing imines 13a and 14a were combined, concentrated in vacuum, and left for
10 days at room temperature. The product was separated by chromatography on a silica gel column using
4:1 hexane–ethyl acetate as eluent. Products 13a and 15 were dissolved in a minimal amount of methylene
chloride. Diethyl ether and hexane were added in volumes equal to the volume of the methylene chloride
solution. After 1.5-2.0 h, the precipitates were filtered off and dried in the air.
(E)-2-[2-(Propargyloxymethyl)benzylidenamino]-2-phthalimidoacetonitrile (13a). Yield 55 mg
(15%). Colorless crystals, mp 103-105°C. 1H NMR spectrum, , ppm (J, Hz): 2.47 (1H, t, J = 2.4, C≡CH); 4.24
(2H, d, J = 2.4, OCH2C≡); 4.80 (1H, d, J = 12.4) and 4.90 (1H, d, J = 12.4, ArCH2); 6.78 (1H, d, J = 1.4,
NCHN); 7.35-7.46 (4H, m, H Ar); 7.78-7.95 (4H, m, H PhthN); 9.10 (1H, J = 1.4, CH=N). 13C NMR spectrum,
, ppm: 57.8 (OCH2C≡); 59.6 (NCHN); 69.3 (OCH2Ar); 75.4 (C≡CH); 79.3 (C≡CH); 112.9 (CN); 124.3 (C-b);
128.6, 129.3, 129.7, 132.2 (C-3',4',5',6'); 131.5 (C-a); 132.5, 138.4 (C-1',2'); 135.0 (C-c); 164.8 (CH=N); 165.5
(NCO). Found, m/z: 358.1182 [M+H]+. C21H16N3O3. Calculated, m/z: 358.1192. Found, %: C 70.48; H 4.32;
N 11.49. C21H15N3O3. Calculated, %: C 70.58; H 4.23; N 11.76.
1363

The following signals of (E)-{[2-(propargyloxymethyl)phenyl](phthalimido)methyl}iminoaceto-
1
nitrile (14a) were identified in the H NMR spectrum of the mixture of imines 13a and 14a, , ppm (J, Hz):
2.37 (1H, t, J = 2.4, C≡CH); 3.99 (2H, d, J = 2.4, OCH2C≡); 4.53 (1H, d, J = 11.1) and 4.69 (1H, d, J = 11.1,
ArCH2); 7.22 (1H, d, J = 2.3, HCHN or CH=N).
({(Z)-[2-(Propargyloxymethyl)phenyl](phthalimido)methylidene}aminoacetonitrile (15). Yield 20
mg (6%). Colorless crystals, which turn pink over time, mp 126°C. 1H NMR spectrum, , ppm (J, Hz): 2.37 (1H,
t, J = 2.2, C≡CH); 3.94 (2H, d, J = 2.2, OCH2C≡CH); 4.54 (2H, s) and 4.72 (2H, s, ArCH2, NCH2); 7.35-7.55
(4H, m, H Ar); 7.81-7.95 (4H, m, H PhthN). 13C NMR spectrum in DMSO-d6, , ppm: 40.3 (NCH2); 57.2
(OCH2C≡); 68.6 (OCH2Ar); 77.4 (C≡CH); 79.7 (C≡CH); 117.9 (CN); 124.1 (C-b); 127.9, 129.0, 129.5, 130.9
(C-3',4',5',6'); 131.5 (C-a); 133.4, 136.9 (C-1',2'); 135.3 (C-c); 149.6 (NC=N); 165.3 (NCO). Found, m/z:
358.1162 [M+H]+. C21H16N3O3. Calculated, m/z: 358.1192. Found, %: C 70.37; H 4.28; N 11.23. C21H15N3O3.
Calculated, %: C 70.58; H 4.23; N 11.76.
A mixture of (E)-2-[2-(allyloxymethyl)benzylideneamino]-2-phthalimidoacetonitrile (13b) and
(E)-{[2-(allyloxymethyl)phenyl](phthalimido)methyl}iminoacetonitrile (14b) was obtained after 2 h heating
of aziridine 7b at 130°C. Yield 140 mg (39%) of a 3:2 mixture of 13b and 14b. Yellow crystals, mp 79-82°C.
1H NMR spectrum, , ppm (J, Hz): 3.87-3.90 (0.8H, m, CH2CH=CH2 14b); 4.09-4.11 (1.2H, m,
CH2CH=CH2 13b); 4.46 (0.4H, d, J = 11.2) and 4.59 (0.4H, d, J = 11.2, ArCH2 14b); 4.70 (0.6H, d, J = 12.3)
and 4.80 (0.6H, d, J = 12.3, ArCH2 13b); 5.03 (0.4H, ddt, J = 10.4, J = 1.5, J = 1.5, H-b 14b); 5.14 (0.4H, ddt,
J = 17.2, J = 1.5, J = 1.5, H-a 14b); 5.20 (0.6H, ddt, J = 10.4, J = 1.6, J = 1.6, H-b isomer 13b); 5.31 (0.6H, ddt,
J = 17.2, J = 1.6, J = 1.6, H-a 13b); 5.67 (0.4H, ddt, J = 17.2, J = 10.4, J = 5.7, CH=CH2 14b); 5.98 (0.6H, ddt,
J = 17.2, J = 10.4, J = 5.7, CH=CH2 13b); 6.78 (0.6H, d, J = 1.9, NCHN 13b); 7.24 (0.4H, d, J = 2.4); 7.28-7.45
(m) and 7.72-7.96 (total 8.4H, m, NCHN and CH=N 14b, H Ar and H PhthN of both isomers); 9.12 (0.6H, d,
J = 1.9, CH=N isomer 13b). 13C NMR spectrum, , ppm: 59.6, 70.7 (NCHN); 70.0, 70.6, 71.6, 71.8 (OCH2);
112.9, 114.2 (CN); 117.5, 117.8 (CH=CH2); 123.8, 124.3 (C-b); 128.3, 128.8, 129.1, 130.5, 130.8, 132.1, 134.0,
134.4, 134.6, 135.0 (C-3',4',5',6', C-b, CH=CH2); 131.4, 131.6 (C-a); 132.4, 134.6, 135.6, 139.3 (C-1',2'); 137.6
(CH=N 14b); 164.9 (CH=N 13b); 165.5, 167.1 (NCO). Several signals in the 13C NMR spectrum overlap.
Found, m/z: 398.0885 [M+K]+. C21H17KN3O3. Calculated, m/z: 398.0907. Found, %: C 70.33; H 4.75; N 11.56.
C21H17N3O3. Calculated, %: C 70.18; H 4.77; N 11.69.
Thermolysis of Aziridine 8a. A solution of aziridine 8a (0.860 g, 2 mmol) in anhydrous benzene
(12 ml) was heated for 5 h at 150°C. The solvent was distilled off in vacuum. The residue was separated
chromatographically on silica gel using 1:1 hexane–ethyl acetate as the eluent to give 100 mg (18%)
1
2-(2-benzyloxyphenyl)-5-methoxyoxazole (16) as a green oil. H NMR spectrum, , ppm (J, Hz): 3.91 (3H, s,
OCH3); 5.24 (2H, s, OCH2); 6.26 (1H, s, H-4); 7.00-7.05 (2H, m, H-3',5'); 7.29-7.40 (5H, m, H Ph); 7.52-7.59
(2H, m, H-4',6').
Thermolysis of Aziridine 8b. A solution of aziridine 8b (534 mg, 1.4 mmol) in anhydrous benzene
1
(15 ml) was heated for 4 h at 150°C. The H NMR spectrum of the reaction mixture showed only signals of
phthalimide and 2-benzyloxybenzaldehyde (identified by comparison with the spectra of authentic samples).
Thermolysis of Aziridine 8c. The reaction was carried out twice, isolating one of the products in each
case. A solution of aziridine 8c (650 mg, 1.9 mmol) in anhydrous benzene (15 ml) was heated for 4 h at 150C.
The solvent was distilled off in vacuum. The residue was dissolved in 50 ml methylene chloride and washed
with 0.025 M NaOH (830 ml). The organic layer was separated and dried over sodium sulfate. The solvent was
distilled off in vacuum. The residue was subjected to chromatography on silica gel using from 2:1 to
1:2 hexane–ethyl acetate as the eluent.
(2R',9bS')-1-Phthalimido-1,2,4,9b-tetrahydrochromeno[3,4-d]imidazole-2-carbonitrile
(17) was
additionally purified by recrystallization from ethanol. Yield 20 mg (3%).Colorless crystals, mp 200-202°C.
1H NMR spectrum, , ppm (J, Hz): 4.84 (1H, dd, J = 16.7, J = 1.8, endo-H-4); 5.17 (1H, dd, J = 3.2, J = 3.1,
exo-H-4); 5.67 (1H, d, J = 2.8, H-2); 6.33 (1H, ddd, J = 3.2, J = 2.8, J = 1.8, H-9b); 7.01 (1H, d, J = 7.9, H-6);
7.11 (1H, dd, J = 7.5, J = 7.1, H-8); 7.20-7.30 (1H, m, H-7); 7.58 (1H, d, J = 7.7, H-9); 7.80-8.00 (4H, m,
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H PhthN). 13C NMR spectrum, , ppm: 66.9 (C-4); 69.7 (C-9b); 83.6 (C-2); 115.6 (C-6); 117.9 (CN); 124.1
(C-9a); 124.3, 124.6 (C-8, C-b); 126.2, 129.6 (C-7,9); 129.7 (C-a); 135.4 (C-c); 153.2 (C-5a); 165.9 (NCO);
177.7 (C-3a). Found, m/z: 345.0971 [M+H]+. C19H13N4O3. Calculated, m/z: 345.0982. Found, %: C 66.34;
H 3.56; N 16.38. C19H12N2O3. Calculated, %: C 66.28; H 3.51; N 16.27.
3-[2-(Cyanomethoxy)phenyl]-3-(2-phthalimidoimino)propanenitrile (18). A solution of aziridine 8c
(343 mg, 1 mmol) in anhydrous benzene (15 ml) was heated for 4 h at 150°C. The solvent was distilled off in
vacuum. The residue was separated chromatographically on silica gel using pure methylene chloride as the
eluent. Isolated hydrazone 18 was further purified by recrystallization from ethanol. Yield 10 mg (3%).
Colorless crystals. 1H NMR spectrum, , ppm (J, Hz): 4.46 (2H, s, OCH2CN); 4.58 (2H, s, CCH2CN); 6.85 (1H,
d, J = 8.0, H-3); 7.24-7.29 (1H, m, H-5); 7.51 (1H, dd, J = 7.3, J = 7.3, H-4); 7.82-8.01 (5H, m, H PhthN, H-6).
13C NMR spectrum, , ppm: 40.1 (CCH2CN); 54.1 (OCH2); 112.3 (C-3'); 113.7 (CN); 116.6 (CN); 124.0 (C-5');
124.3 (C-1'); 124.8 (C-b); 131.7 (C-a); 132.9, 133.3 (C-4',6'); 135.5 (C-c); 154.5 (C-2'); 162.5 (C=N); 165.5
(NCO). Found, m/z: 345.0979 [M+H]+. C19H13N4O3. Calculated, m/z: 345.0982.
1
Determination of the Aziridines 9 and 10 Thermolysis Products Yield by H NMR Spectroscopy
with Internal Standard. After heating the starting aziridine, the solvent was distilled off in vacuum. The
1
residue was dissolved in CDCl3 and the H NMR spectrum was recorded. Then, 1 eq. N-benzylmaleimide was
added into ampule and the 1H NMR spectrum was recorded again.
Thermolysis of Aziridines 9a,b. A solution of aziridine 9a,b (0.3 mmol) in anhydrous benzene (5 ml)
was heated at 150°C. After 6 h heating of aziridine 9a, the spectral yield of the allyl
1
(E)-2-benzylideneamino-2-phthalimidoacetate (19a) was 40%. H NMR spectrum, , ppm (J, Hz): 4.73 (2H,
dd, J = 5.8, J = 1.3, OCH2); 5.21 (1H, ddt, J = 10.3, J = 1.2, J = 1.2, H-b); 5.30 (1H, ddt, J = 17.2, J = 1.4,
J = 1.4, H-a); 5.86 (1H, ddt, J = 17.2, J = 10.3, J = 5.8, CH=CH2); 6.11 (1H, d, J = 0.9, NCHN); 7.35-7.90 (9H,
m, H Ph, H PhthN). 8.40 (1H, s, CH=N).
After 10 h heating of aziridine 9b, the spectral yield of the propargyl (E)-2-benzyl-
1
ideneamino-2-phthalimidoacetate (19b) was 41%. H NMR spectrum, , ppm (J, Hz): 2.49 (1H, t, J = 2.5,
C≡CH); 4.80 (1H, dd, J = 15.5, J = 2.5) and 4.89 (1H, dd, J = 15.5, J = 2.5, OCH2); 6.13 (1H, s, NCHN);
7.35-7.90 (9H, m, H Ph, H PhthN); 8.40 (1H, s, CH=N).
Thermolysis of aziridine 10a. A solution of aziridine 10a (210 mg, 0.5 mmol) in anhydrous benzene
(10 ml) was heated for 5 h at 180°C. The solvent was then distilled off in vacuum. The residue was separated
chromatographically on silica gel using from 1:0 to 100:1 dichloromethane–methanol as the eluent. The yield of
N-ethylideneaminophthalimide was 35 mg (37%, spectral yield 43%). Colorless crystals, subl.p 168-172°C.
1H NMR spectrum, , ppm (J, Hz): 2.21 (3H, d, J = 5.3, CH3); 7.72-7.77 (2H, m) and 7.83-7.88 (2H, m,
H PhthN); 8.66 (1H, q, J = 5.3, CH=N). The structure of product 21 was confirmed by counter synthesis from
acetaldehyde and N-aminophthalimide.
Thermolysis of Aziridines 10b-d. A solution of aziridine 10b-d (15-17 mg) in anhydrous benzene
(2 ml) was heated for 5 h at 180°C. The spectral yield of N-ethylideneaminophthalimide (21) for
aziridines 10b, 10c, and 10d was 13, 6, and 45%, respectively.
Thermolysis of aziridines 22a-c. A solution aziridine 22a-c [12-14] (0.7 mmol) in anhydrous benzene
(10 ml) was heated in a thick-walled reactor and the solvent was then distilled off in vacuum. After 6 h heating
aziridine 22a at 120°C, the 1H NMR spectrum of the reaction mixture showed only signals for
N-[(E)-1-(benzylideneamino)benzyl]phthalimide (23a) but this product could not be isolated as a pure
compound due to its instability. 1H NMR spectrum, , ppm (J, Hz): 6.87 (1H, d, J = 1.4, NCHN); 7.30-7.46 (6H,
m, m,p-H); 7.58 (2H, d, J = 7.3, o-H benzyl); 7.70-7.74 (2H, m) and 7.84-7.90 (4H, m, H PhthN,
o-H benzylidene); 8.40 (1H, d, J = 1.4, CH=N). 13C NMR spectrum, , ppm: 73.9 (NCHN); 123.6 (C-b); 127.6,
128.4, 128.7, 129.0 (m,o-C); 128.3 and 131.6 (p-C); 131.9 (C-a); 134.3 (C-c); 135.4 and 138.8 (i-C); 162.7
(CH=N); 167.5 (NCO).
Heating aziridine 22b for 2 h at 180°C leads to its complete decomposition and tar formation. Only
signals for phthalimide could be identified in the 1H NMR spectrum of the reaction mixture.
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The residue obtained after heating aziridine 22c at 120°C was separated on silica gel using
1.7:1 dichloromethane–hexane as the eluent. The fractions containing major products were combined and
evaporated in vacuum. The residues were dissolved in dichloromethane and the products were precipitated from
solution by adding hexane to give 45 mg (23%) (E)-2-benzylideneamino-2-phthalimidoacetonitrile 23c and
12 mg (6%) (Z)-2-(phthalimido)imino-3-phenylpropanenitrile (24).
(E)-2-Benzylideneamino-2-phthalimidoacetonitrile (23c). Colorless crystals, mp 145-146°C.
1H NMR spectrum, , ppm (J, Hz): 6.78 (1H, d, J = 1.4, NCHN); 7.41-7.53 (3H, m, m,p-H); 7.78-7.84 (4H, m)
and 7.91-7.96 (2H, m, H PhthN, o-H Ph); 8.77 (1H, d, J = 1.4, CH=N). 13C NMR spectrum, , ppm: 59.3
(NCHN); 112.8 (CN); 124.3 (C-b); 128.9 and 129.6 (m,o-C); 131.5 (C-a); 132.7 (p-C); 134.0 (i-C); 135.0 (C-c);
165.6 (NCO); 165.9 (CH=N). Found, m/z: 328.0481 [M+K]+. C17H11KN3O2. Calculated, m/z: 328.0482.
1
(Z)-2-(Phthalimido)imino-3-phenylpropanenitrile (24). Colorless needles, mp 185-186°C. H NMR
spectrum, , ppm: 44.8 (2H, s, CH2); 7.39-7.45 (2H, m, m-H Ph); 7.50-7.55 (1H, m, p-H Ph); 7.72 (2H, m,
o-H Ph); 7.86-7.91 (2H, m) and 7.96-8.02 (2H, m, H PhthN). 13C NMR spectrum, , ppm: 39.8 (CH2); 116.4
(CN); 124.8 (C-b); 128.2 and 129.0 (m,o-C); 131.4 (C-a); 132.5 (p-C); 133.3 (i-C, C=N); 135.5 (C-c); 165.4
(NCO). Found, m/z: 290.0914 [M+H]+. C17H12N3O2. Calculated, m/z: 290.0925.
This work was carried out with the financial support of St. Petersburg State University
(Grant No. 12.38.16.2011).
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