Magnesium acetate – an effective electrophilic activator of the carbonyl group in transesterification of dialkylaziridine dicarboxylates

Article abstract of DOI:10.1007/s10593-020-02744-y

[Figure not available: see fulltext.] A method for transesterification of the ester groups in dialkylaziridine dicarboxylates by electrophilic activation of the carbonyl group in the presence of magnesium acetate with the preservation of the aziridine ring was developed and the use of modified aziridine dicarboxylates in the synthesis of sterically hindered derivatives of fullerenes C60, 2',5'-disubstituted fulleropyrrolidines, was demonstrated.

Full text of DOI:10.1007/s10593-020-02744-y

DOI 10.1007/s10593-020-02744-y
Chemistry of Heterocyclic Compounds 2020, 56(7), 875–880
Magnesium acetate – an effective electrophilic activator
of the carbonyl group in transesterification of
dialkylaziridine dicarboxylates
Angelina V. Kazakova1, Dmitriy V. Androsov1,
Alexander S. Konev1*, Alexander F. Khlebnikov1
1 Institute of Chemistry, Saint Petersburg State University,
7/9 University Embankment, Saint Petersburg 199034, Russia; е-mail: a.konev@spbu.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2020, 56(7), 875–880
Submitted April 27, 2020
Accepted May 25, 2020
R3O2C
CO2R3
R1O2C
CO2R1
CO2R1
CO2R1
R3OH
H+
R3OH
R2
N
N
N
H
Mg(OAc)2
R2
R2
R1 = Me, Et; R2 = Bn, PMP; R3 = Me, Bu, (CH2)2OH
A method for transesterification of the ester groups in dialkylaziridine dicarboxylates by electrophilic activation of the carbonyl group in
the presence of magnesium acetate with the preservation of the aziridine ring was developed and the use of modified aziridine di-
carboxylates in the synthesis of sterically hindered derivatives of fullerenes C60, 2',5'-disubstituted fulleropyrrolidines, was demonstrated.
Keywords: aziridines, fullerenes, 1,3-dipolar cycloaddition, electrophilic activation, stereodirected synthesis, transesterification.
Aziridines are convenient synthetic blocks for producing
five-membered nitrogen heterocycles such as pyrroli-
dines,1,2 oxazolidines,3,4 imidazolidines,5,6 thiazolidines,7,8
important structural blocks of many drugs, via the
1,3-dipolar cycloaddition reaction. Oxazolidine-based
drugs are used to treat diseases of the central nervous
system,9-12 severe infectious diseases of the skin and soft
tissues,13 as well as cancer.10,14 Thiazolidines are used to
treat type 2 diabetes mellitus,15,16 inflammatory15,17,18 and
tumor processes.15,17,19 Imidazolidines exhibit anticonvul-
sant,12,20,21 antiviral,22 antimicrobial,21 antitumor,21,23 and
antioxidant24 activity. The pyrrolidine moiety is the fifth
most frequent structural element in drugs approved in the
USA.25,26 Pyrrolidines exhibit activity against a wide range
of pathologies,26 including mental disorders27 and
tuberculosis.28 The advantage of using aziridines in the
synthesis of five-membered nitrogen heterocycles is the
possibility of realizing a stereoselective reaction sequence,
involving electrocyclic opening of the aziridine ring to
azomethine ylides and their subsequent 1,3-dipolar
cycloaddition to the multiple bond of dipolarophiles. The
formation of the pyrrolidine ring using the 1,3-dipolar
cycloaddition reaction was used to obtain derivatives
of pyrrolofullerene-2',5'-dicarboxylates 129 and 230 with
antiHIV activity (Fig. 1). Compounds were obtained as
mixtures of stereoisomers using precursors other than
aziridines to generate azomethine ylides.
Recently, we proposed a method for the stereoselective
synthesis of fullerene derivatives containing the fullero-
pyrrolidine pharmacophore fragment based on reactions of
fullerenes with dialkylaziridine dicarboxylates.31–35 The
search for suitable candidates for the development of drugs
based on pyrrolofullerene-2',5'-dicarboxylates supposes
structural modification of the environment of the
pharmacophore. However, in the case of sterically hindered
substrates, such as pyrrolofullerene-2',5'-dicarboxylates, the
transformation of substituents is difficult or impossible. In
Figure 1. Derivatives of fullerene C60 with antiviral activity.
0009-3122/20/56(7)-0875©2020 Springer Science+Business Media, LLC
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Chemistry of Heterocyclic Compounds 2020, 56(7), 875–880
particular, in our studies on the diversification of the
protic acid (cationite KU-2-8, 50 wt %) or very weak Lewis
acids (Si(EtO)4), aziridine 3a practically did not change.
The use of H2SO4 as a catalyst expectedly led to the
quantitative isomerization of aziridine 3a to enamine 4.36
The formation of a mixture of enamine 4, methoxyethoxy-
substituted aziridine 5, and dimethoxy-substituted aziridine
3b in different ratios was observed during catalysis by
SiO2, LiBr, BF3·Et2O, PPTS, and Mg(OAc)2. The latter
gave the highest proportion of dimethoxy-substituted
aziridine 3b, and, after optimizing the reaction time,
allowed the conversion of aziridine 3a to aziridine 3b with
a 96% preparative yield.
The Mg(OAc)2 catalyst allows selective activation of the
carbonyl group also in the case of N-alkylaziridines, which
are stronger bases than N-arylaziridines. Heating of diethyl-
substituted N-benzylaziridine 3c in MeOH under reflux
with Mg(OAc)2 leads to the formation of dimethoxy-
carbonyl-substituted aziridine 3d in 64% yield.
pharmacophore environment in pyrrolofullerene-2',5'-di-
carboxylates, the ester groups at positions 2' and 5' of the
pyrrolidine ring of the fulleropyrrolidines were found to be
inert to amidation, transesterification, and hydrolysis. An
alternative approach to the preparation of pyrrolofullerene
structures with various substituents is to introduce
structurally modified aziridine dicarboxylates in the
reaction with fullerene. However, the reactivity of the
aziridine ring in the presence of acids significantly narrows
the range of reactions applicable for the functionalization
of substituents in the starting aziridine, which necessitates
the search for new approaches to their modification.
In this work, we developed a method for the transforma-
tion of ester groups in dialkylaziridine dicarboxylates by
electrophilic activation of the carbonyl group while
preserving the aziridine ring and demonstrated the
application of this approach to the synthesis of 2',5'-di-
substituted fulleropyrrolidines, sterically hindered deri-
vatives of fullerene C60.
Transesterification of the ester substituents in aziridine
3a required electrophilic activation of the carbonyl group
(Scheme 1, Table 1). In the presence of trace amounts of a
Although the cis arrangement of the two ester groups in
aziridine 3a potentially provides the possibility for the
formation of a chelate complex with the magnesium ion,
which may contribute to a shift in the equilibrium between
N-coordination and O-coordination in favor of
Scheme 1. Transesterification of ester groups in aziridines
Table 1. Optimization of transesterification of aziridine 3a to aziridine 3b in MeOH*
Yield of compound, %
Reaction
time, h
Reaction
Concentration of
Catalyst
Catalyst loading, wt %
temperature, °С aziridine 3a, mM
3a
5
3b
4
PPTS
Cationite KU-2-8
Cationite KU-2-8
H2SO4
33
33
98
64
38
50
98
98
87
87
87
50
57
87
57
57
57
57
50
24
24
24
24
3
18
18
18
18
65
18
18
18
40
65
65
65
65
65
65
65
65
65
18
3
3
3
3
3
3
3
3
3
3
3
3
3
34
34
3
3
34
97
97
73
0
98
98
93
78
83
22
17
93
4
1
1
0
0
0
17
0
0
6
0
0
0
6
19
15
46
43
0
28
14
16
2
0
0
0
0
0
0
0
2
1
28
31
5
66
82
80
94
92
96
17
3
3
32
100
2
2
1
1
1
4
9
2
2
3
3
4
4
4
32
KAl(SO4)2
Si(OEt)4
SiO2
SiO2
SiO2
SiO2
SiO2
LiBr
Mg(OAc)2
Mg(OAc)2
Mg(OAc)2
Mg(OAc)2
Mg(OAc)2
Mg(OAc)2
BF3·Et2O
12
24
72
24
12
24
22
22
24
25
40
51
96
24
4
0
34
3
* The conversion and yields of reaction products were determined by 1H NMR spectroscopy with CH2Br2 as internal standard.
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Chemistry of Heterocyclic Compounds 2020, 56(7), 875–880
O-coordination, the reaction of trans-aziridine 3e under the
same conditions also led to the formation of
dimethoxycarbonyl-substituted trans-aziridine 3f with a
high preparative yield of 95%. This indicates a higher
energy of the O–Mg coordination bond, in comparison with
the N–Mg bond, as the main reason for the selectivity
attained using Mg(OAc)2.
Among the factors affecting the course of the reaction, it
is necessary to highlight the steric hindrance of the reaction
center and the polarity of the medium. Transesterification
proceeds more smoothly when replacing methoxy groups
in aziridine 3b than when replacing ethoxy groups in
aziridine 3a. Alcohols with longer alkyl chains which have
a low dielectric constant, for example, butan-1-ol, lead to a
lower yield of the bisubstituted product (37% for aziridine
3g) than alcohols with a high dielectric constant, for
example, ethylene glycol (46% for aziridine 3h).
The stereoconfiguration of the new compounds was
1
established on the basis of NMR spectra. The H NMR
spectra of symmetric N-aryl-substituted cis-aziridines
contain a characteristic31,32 singlet at 2.56–3.13 ppm with a
satellite doublet of doublets with the direct SSCC
1JCH = 168.1–172.0 Hz and vicinal SSCC 3JHH = 6.6–7.2 Hz,
which agrees with literature data.37–39 An independent
confirmation of the cis configuration of aziridines with
1
such a signal pattern in the H NMR spectrum is provided
by X-ray structural analysis of aziridine 3k (Fig. 2), which
1
possesses the cis configuration and H NMR spectrum of
the same type. For symmetrical trans-aziridines, the signal
of aziridine protons is observed as a singlet at 3.46 ppm
with a satellite doublet of doublets with direct SSCC
3
1JCH = 181.9 Hz and vicinal SSCC JHH = 2.4 Hz, which is
also consistent with published data.37–39 For cis-aziridines,
the presence of asymmetrically substituted aziridines in the
spectra of reaction mixtures was determined by the
characteristic signal of the aziridine protons in the form of
an AB system centered at ~3.1 ppm with a coupling
constant of 6.6–6.9 Hz. The reaction proceeded faster with
trans-aziridines than with cis-aziridines, and the formation
of only the final symmetrical product was determined in
the reaction mixtures. In the case of N-alkyl-substituted
cis-aziridines 3c,d, the signal of the aziridine protons is
Due to the lower steric hindrance, aziridine 3b was also
convenient for the transformation of the ester groups into
amides: primary, secondary, and tertiary amides can be
obtained smoothly by this method. The reaction proceeds
with both cis-aziridines and trans-aziridines. Hydrazine
and hydroxylamine are unreactive (Scheme 2).
Scheme 2. Amidation of ester groups in aziridines
3
shifted upfield to 2.58 ppm, but the vicinal SSCC JHH of
6.5 Hz is typical of cis-aziridines.
The singlet of pyrrolidine protons at 6.56–6.57 ppm is a
characteristic31,32 signal of fulleropyrrolidines 6 and 7. Its
position is typical of trans-fulleropyrrolidines. The
presence of 30 signals of the fullerene ring in the 13C NMR
spectrum of compound 7 is an independent confirmation of
the determined configuration: one signal of the sp3-hybri-
dized carbon atom at 71.3 ppm and 29 signals of the
sp2-hybridized carbon atoms in the 114.3–154.7 ppm range,
in complete accordance with the symmetry of a C2
molecule.40
To conclude, magnesium acetate can be used for
selective electrophilic activation of the carbonyl group in
the presence of acid-susceptible compounds such as
aziridines. The use of this reaction for the preliminary
modification of substituents in aziridine synthetic blocks
To show the promise of the approach of aziridine re-
functionalization for the synthesis of sterically hindered
five-membered nitrogen heterocycles, aziridines 3h,j were
reacted with fullerene C60 (Scheme 3). When heated, cis-
aziridines open with the formation of S-ylides, the 1,3-di-
polar cycloaddition of which across the C=C bond, common
to two six-membered rings of the fullerene core, leads to
the formation of trans-2',5'-disubstituted fulleropyrrolidines
6 and 7 in 41 and 64% yields, respectively.
Scheme 3. Synthesis of fulleropyrrolidines 6, 7
Figure 2. Molecular structure of aziridine 3k with atoms
represented as thermal vibration ellipsoids of 50% probability.
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Chemistry of Heterocyclic Compounds 2020, 56(7), 875–880
makes it possible to functionalize sterically hindered
residue was recrystallized from pentane–Et2O mixture.
Yield 30.6 mg (64%), colorless crystals, mp 48–50°С.
IR spectrum, ν, cm–1: 1750, 1738 (C=O). 1H NMR spectrum
(CDCl3), δ, ppm: 2.60 (2H, s, 2NCH); 3.75 (8H, s, CH2,
2OCH3); 7.29–7.40 (5H, m, H Ph). 13C NMR spectrum
(CDCl3), δ, ppm: 43.0; 52.5; 62.4; 121.6; 128.2; 128.5;
136.0; 167.8. Found, m/z: 250.1069 [M+H]+. C13H16NO4.
Calculated, m/z: 250.1074. Found, m/z: 272.0892 [M+Na]+.
C13H15NNaO4. Calculated, m/z: 272.0893. Found, m/z:
288.0627 [M+K]+. C13H15KNO4. Calculated, m/z: 288.0633.
Dimethyl trans-1-(4-methoxyphenyl)aziridine-2,3-di-
carboxylate (3f).41 A mixture of aziridine 3e (62.9 mg,
0.21 mmol) and Mg(OAc)2 (85 mg, 0.60 mmol) in MeOH
(6.5 ml) was stirred at 65°C for 21 h. The reaction mixture
was diluted with H2O, extracted with CH2Cl2, and the
organic phase was dried over Na2SO4. The desiccant was
filtered, the solvent was removed on a rotary evaporator.
Yield 54.1 mg (95%), yellow oil. IR spectrum, ν, cm–1:
cycloadducts that are inaccessible by postmodification.
Experimental
IR spectra were recorded on a Shimadzu FTIR-8400S
FTIR spectrometer in KBr pellets. 1H and 13C NMR spectra
were acquired on a Bruker Avance III 400 spectrometer
(400 and 100 MHz, respectively) with TMS as internal
standard. Assignment of signals in 13C NMR spectrum of
1
1
compound 3l was based on H–13C HSQC and H–13C
HMBC 2D NMR experiment data. Mass spectra were
recorded on a Bruker MaXis mass spectrometer (electro-
spray ionization). Silica gel 60 M (Macherey-Nagel), 40–
63 μm, was used to separate the reaction mixtures by
column chromatography.
The solvents were dried by standard routines. Aziridines
3a,e31 were obtained following published methods.
Dimethyl cis-1-(4-methoxyphenyl)aziridine-2,3-di-
carboxylate (3b).41 A mixture of aziridine 3a (367 mg,
1.25 mmol) and Mg(OAc)2 (487 mg, 3.43 mmol) in MeOH
(37 ml) was stirred at 65°C for 96 h. The reaction mixture
was diluted with H2O, extracted with CH2Cl2, and the
organic phase was dried over Na2SO4. The desiccant was
filtered, the solvent was removed on a rotary evaporator.
Yield 299 mg (96%), yellow oil. 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 3.06 (2H, s, 2NCH); 3.77 (3H, s,
OCH3 Ar); 3.83 (6H, s, 2COOCH3); 6.81 (2H, AA'BB'
system, J = 8.9, H-2,6(3,5)); 6.96 (2H, AA'BB' system,
J = 8.9, H-3,5(2,6)).
1
1742 (C=O). H NMR spectrum (CDCl3), δ, ppm (J, Hz):
3.46 (2H, s, 2NCH); 3.73 (6H, s, 2COOCH3); 3.76 (3H, s,
OCH3 Ar); 6.81 (2H, AA'BB' system, J = 9.2, H-2,6(3,5));
6.84 (2H, AA'BB' system, J = 9.2, H-3,5(2,6)). 13C NMR
spectrum (CDCl3), δ, ppm: 42.2; 52.6; 55.3; 114.3; 120.6;
140.1; 155.9; 167.4. Found, m/z: 288.0855 [M+Na]+.
C13H15NNaO5. Calculated, m/z: 288.0842.
Dibutyl cis-1-(4-methoxyphenyl)aziridine-2,3-dicarb-
oxylate (3g).42 A mixture of aziridine 3b (43.9 mg,
0.17 mmol) and Mg(OAc)2 (68 mg, 0.48 mmol) in n-BuOH
(4.5 ml) was stirred at 65°C for 214 h. The reaction mixture
was diluted with H2O, extracted with CH2Cl2, and the
organic phase was dried over Na2SO4. The desiccant was
filtered, the solvent was removed on a rotary evaporator.
The residue was separated by column chromatography on
SiO2, eluent petroleum ether – EtOAc, 10:1. Yield 22 mg
Diethyl cis-1-benzylaziridine-2,3-dicarboxylate (3c).
A mixture of benzylamine (107 mg, 1 mmol) and ethyl
glyoxylate (112 mg, 1.1 mmol) in PhMe (8 ml) was stirred
at room temperature for 20 h, then the solvent was removed
under reduced pressure. The residue was dissolved in
anhydrous Et2O (18 ml), and BF3·Et2O (4 drops) and a
solution of ethyl diazoacetate (171 mg, 1.5 mmol) in
anhydrous Et2O (2 ml) were added. The reaction mixture
was stirred at room temperature for 2 h, then Et3N (4 drops)
followed by H2O (2 ml) was added. The two-phase system
was transferred into a separatory funnel. The organic layer
was separated, the aqueous layer was extracted with
CH2Cl2 (2×5 ml). The combined organic phase was washed
with saturated aqueous NaCl and dried over Na2SO4. The
desiccant was filtered, the solvent was removed on a rotary
evaporator, and the residue was separated by column
chromatography on SiO2, eluent petroleum ether – EtOAc,
9:1. Yield 119 mg (43%), yellow oil. IR spectrum, ν, cm–1:
1
(37%), yellow oil. H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 0.96 (6H, t, J = 7.3, 2CH3CH2C); 1.36–1.48 (4H, m,
2CH3CH2C); 1.64–1.74 (4H, m, 2CH2CH2O); 3.03 (2H, s,
2NCH); 3.77 (3H, s, CH3O); 4.22 (4H, t, J = 6.9,
2CH2CH2O); 6.81 (2H, AA'BB' system, J = 8.9, H-2,6(3,5));
6.96 (2H, AA'BB' system, J = 8.9, H-3,5(2,6)).
Bis(2-hydroxyethyl) cis-1-(4-methoxyphenyl)aziridine-
2,3-dicarboxylate (3h). A mixture of aziridine 3b (50.1 mg,
0.19 mmol), ethylene glycol (5 ml), and Mg(OAc)2 (76 mg,
0.54 mmol) in CH2Cl2 (3 ml) was stirred at 65°C for 70 h.
The reaction mixture was diluted with H2O, extracted with
CH2Cl2, and the organic phase was dried over Na2SO4.
The desiccant was filtered, the solvent was removed on a
rotary evaporator. The residue was separated by column
chromatography on SiO2, eluent petroleum ether – EtOAc,
1
1751, 1734 (C=O). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 1.28 (6H, t, J = 7.2, 2CH3CH2); 2.56 (2H, s,
2NCH); 3.76 (2H, s, PhCH2); 4.21 (4H, q, J = 7.2,
2CH3CH2); 7.28–7.42 (5H, m, H Ph). 13C NMR spectrum
(CDCl3), δ, ppm: 14.0; 43.1; 61.4; 62.5; 127.5; 128.1;
128.4; 136.2; 167.3. Found, m/z: 300.1219 [M+Na]+.
C15H19NNaO4. Calculated, m/z: 300.1206.
1
1:2. Yield 28.4 mg (46%), yellow oil. H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 3.13 (2H, s, 2NCH); 3.26 (2H, br. s,
2OH); 3.77 (3H, s, OCH3); 3.79–3.89 (4H, m, 2CH2); 4.27–
4.38 (4H, m, 2CH2); 6.82 (2H, AA'BB' system,
J = 8.9, H-2,6(3,5)); 6.98 (2H, AA'BB' system, J = 8.9,
H-3,5(2,6)). 13C NMR spectrum (CDCl3), δ, ppm: 43.5;
55.5; 60.4; 67.6; 114.6; 120.9; 143.4; 156.6; 167.3. Found, m/z:
348.1069 [M+Na]+. C15H19NNaO7. Calculated, m/z: 348.1054.
cis-1-(4-Methoxyphenyl)aziridine-2,3-dicarboxamide (3i).
A solution of aziridine 3a (53 mg, 0.18 mmol) in a mixture
of MeCN–aqueous NH3, 1:1 (2 ml) was stirred at room
temperature for 1 day. The product that precipitated from
Dimethyl cis-1-benzylaziridine-2,3-dicarboxylate (3d).
A mixture of aziridine 3c (52.9 mg, 0.19 mmol) and
Mg(OAc)2 (70 mg, 0.49 mmol) in MeOH (5.5 ml) was
stirred at 65°C for 152 h. The reaction mixture was diluted
with H2O, extracted with CH2Cl2, and the organic phase
was dried over Na2SO4. The desiccant was filtered, the
solvent was removed on a rotary evaporator, and the
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Chemistry of Heterocyclic Compounds 2020, 56(7), 875–880
the reaction mixture was centrifuged, washed with H2O,
121.5 (C-3,5(2,6)); 140.0 (C-1); 156.0 (C-4); 164.4 (C=O).
Found, m/z: 398.1692 [M+Na]+. C19H25N3NaO5.
Calculated, m/z: 398.1686.
and dried under reduced pressure. Yield 22 mg (50%),
colorless crystals, mp >220°С (decomp.). IR spectrum,
ν, cm–1: 3393, 3376 (NH2), 1655 (C=O), 1614 (NH2).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.85 (2H,
s, 2NCH); 3.70 (3H, s, OCH3); 6.84 (2H, AA'BB' system,
J = 9.0, H-2,6(3,5)); 6.94 (2H, AA'BB' system, J = 9.0,
H-3,5(2,6)); 7.34 (4H, d, J = 9.3, 2NH2). 13C NMR
spectrum (DMSO-d6), δ, ppm: 44.9; 55.3; 114.3; 120.9;
144.2; 155.5; 168.4. Found, m/z: 258.0859 [M+Na]+.
C11H13N3NaO3. Calculated, m/z: 258.0849.
Bis(2-hydroxyethyl) trans-1'-(4-methoxyphenyl)-2',5'-di-
hydropyrrolo[3',4':1,9](C60-Ih)[5,6]fullerene-2',5'-dicarb-
oxylate (6). A solution of aziridine 3h (15.5 mg,
0.05 mmol) and fullerene C60 (84.9 mg, 0.12 mmol) in
1,2-dichlorobenzene (5 ml) was stirred at 100°C for 21 h.
The reaction mixture was separated by column chromato-
graphy on SiO2, eluent PhMe, gradient to PhMe–1,4-di-
oxane, 3:1. Yield 20.5 mg (41%), brown powder. 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 1.46–1.54 (2H, m,
2OH); 3.64–3.78 (4H, m, 2CH2); 3.88 (3H, s, OCH3); 4.26–
4.38 (4H, m, 2CH2); 6.56 (2H, s, 2NCH); 7.06 (2H,
AA'BB' system, J = 8.9, H-2,6(3,5)); 7.40 (2H, AA'BB'
system, J = 8.9, H-3,5(2,6)).
N,N'-Dibenzyl-cis-1-(4-methoxyphenyl)aziridine-2,3-di-
carboxamide (3j). A solution of aziridine 3b (48.9 mg,
0.18 mmol) in benzylamine (2 ml) was stirred at 65°C for
48 h. The reaction mixture was diluted with H2O, extracted
with CH2Cl2, and the organic phase was dried over Na2SO4.
The desiccant was filtered, the solvent was removed on a
rotary evaporator, and the residue was recrystallized from
CH2Cl2–Et2O mixture. Yield 65.0 mg (87%), colorless
crystals, mp 175–176°С. IR spectrum, ν, cm–1: 1665
N2,N3-Dibenzyl-trans-1'-(4-methoxyphenyl)-2',5'-di-
hydropyrrolo[3',4':1,9](C60-Ih)[5,6]fullerene-2',5'-dicarb-
oxamide (7). A solution of aziridine 3j (31.8 mg,
0.08 mmol) and fullerene C60 (135.6 mg, 0.19 mmol) in a
mixture of 1,2-dichlorobenzene (9 ml) and PhCN (2 ml)
was stirred at 100°C for 103 h. The reaction mixture was
separated by column chromatography on SiO2, eluent
PhMe, gradient to PhMe–1,4-dioxane, 100:2. Yield 58.0 mg
(64%), brown powder. IR spectrum, ν, cm–1: 1650 (C=O),
1510 (NHR). 1H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 3.85 (3H, s, OCH3); 4.20–4.33 (4H, m, 2CH2);
6.57 (2H, s, 2NCH); 6.95–7.01 (4H, m, 2H-2,6 Ph); 7.04
(2H, AA'BB' system, J = 8.9, H-2,6(3,5) Ar); 7.09–7.15
(6H, m, 2H-3–5 Ph); 7.34 (2H, AA'BB' system,
J = 8.9, H-3,5(2,6) Ar). 13C NMR spectrum (DMSO-d6),
δ, ppm: 42.1; 55.3; 71.3; 74.7; 114.3; 121.1; 126.6; 127.2;
128.0; 136.1; 136.6; 138.7; 138.8; 138.9; 139.1; 141.1;
141.2; 141.4; 141.5; 141.6 (2C); 142.0; 142.1; 142.5;
144.0; 144.1; 144.6; 144.7; 144.8; 145.0; 145.3; 145.4;
145.5; 145.7; 145.8; 146.0; 146.4; 146.8; 152.7; 154.5;
154.7; 169.1. Found, m/z: 1136.1959 [M+H]+. C85H26N3O3.
Calculated, m/z: 1136.1969.
X-ray structural analysis of compound 3k was per-
formed on an Agilent Technologies (Oxford Diffraction)
Supernova single crystal diffractometer. Crystals of
compound 3k (C19H25N3O5, M 375) are monoclinic, space
symmetry group P21/c; a 11.44929(12), b 9.67666(11),
c 16.82329(19) Å; α 90, β 98.7711(10), γ 90°; d 1.354 g/cm3.
The full set of X-ray structural data was deposited at the
Cambridge Crystallographic Data Center (deposit CCDC
1999256).
1
(C=O), 1506 (NHBn). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 3.06 (2H, s, 2NCH); 3.77 (3H, s, OCH3); 4.23–4.30
(2H, m, CH2); 4.35–4.42 (2H, m, CH2); 6.66 (2H, t, J = 5.5,
2NH); 6.80 (2H, AA'BB' system, J = 9.0, H-2,6(3,5) Ar);
6.91 (2H, AA'BB' system, J = 9.0, H-3,5(2,6) Ar); 7.22
(4H, AA'BB' system, J = 7.0, 2H-2,6 Ph); 7.28–7.36 (6H,
m, 2H-3–5 Ph). 13C NMR spectrum (DMSO-d6), δ, ppm:
42.0; 45.0; 55.3; 114.3; 121.1; 126.8; 127.3; 128.2; 139.0;
144.0; 155.6; 166.0. Found, m/z: 438.1771 [M+Na]+.
C25H25N3NaO3. Calculated, m/z: 438.1788.
[cis-1-(4-Methoxyphenyl)aziridine-2,3-diyl]bis(mor-
pholinomethanone) (3k). A solution of aziridine 3b
(50.9 mg, 0.19 mmol) in morpholine (5 ml) was stirred at
65°C for 112 h. The reaction mixture was diluted with
H2O, extracted with CH2Cl2, and the organic phase was
dried over Na2SO4. The desiccant was filtered, the solvent
was removed on a rotary evaporator, and the residue was
recrystallized from CH2Cl2–Et2O mixture. Yield 24.7 mg
(35%), colorless crystals, mp 156–157°С. 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 3.13 (2H, s, 2NCH);
3.57–3.80 (17H, m, 7CH2, OCH3); 3.88–3.97 (2H, m,
CH2); 6.83 (2H, AA'BB' system, J = 8.9, H-2,6(3,5)); 6.94
(2H, AA'BB' system, J = 8.9, 2H-3(2)). 13C NMR spectrum
(CDCl3), δ, ppm: 42.7; 44.0; 45.8; 55.5; 66.7; 66.8; 114.7;
120.8; 144.0; 156.3; 164.6. Found, m/z: 398.1697 [M+Na]+.
C19H25N3NaO5. Calculated, m/z: 398.1686.
[trans-1-(4-Methoxyphenyl)aziridine-2,3-diyl]bis(mor-
pholinomethanone) (3l). A solution of aziridine 3f
(49.3 mg, 0.19 mmol) in morpholine (5 ml) was stirred at
65°C for 99 h. The reaction mixture was diluted with H2O,
extracted with CH2Cl2, and the organic phase was dried
over Na2SO4. The desiccant was filtered, the solvent was
removed on a rotary evaporator, and the residue was
recrystallized from CH2Cl2–Et2O mixture. Yield 22.7 mg
(32%), colorless crystals, mp 160–163°С. IR spectrum,
This work was supported by the Russian Science
Foundation (project 19-13-00039).
Analytical and spectral studies were performed at the
Resource Centers of the Science Park of Saint Petersburg
State University: Magnetic Resonance Research Center,
Center for X-ray Diffraction Studies, and Chemical
Analysis and Materials Research Center.
1
ν, cm–1: 1642 (C=O). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 3.46–3.88 (21H, m, 2NCH, OCH3, 4OCH2,
4NCH2); 6.79 (2H, AA'BB' system, J = 9.1, H-2,6(3,5));
6.83 (2H, AA'BB'-system, J = 9.1, H-3,5(2,6)). 13C NMR
spectrum (CDCl3), δ, ppm: 41.6 (NCH); 42.6 (NCH2); 46.0
(NCH2); 55.3 (OCH3); 66.7 (2OCH2); 114.2 (C-2,6(3,5));
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