Synthesis of polyarene derivatives of fused aziridines by Suzuki-Miyaura cross-coupling

Article abstract of DOI:10.1016/j.tet.2007.03.060

A convenient and effective synthetic approach to potentially radiochromic polyarene derivatives of bi- and tricyclic aziridines utilizing modified Suzuki-Miyaura cross-coupling with catalysis in micellar media has been developed. A series of polyarene substituents were introduced into 1,5-diaryl-3,5a-dihydro-1H-azireno[1,2-c]imidazoles, 1,6-diaryl-1,3,4,6a-tetrahydroazireno[1,2-a]pyrazines, and 1,2-diaryl-1,1a-dihydroazireno[1,2-a]quinoxalines without degradation of the highly reactive aziridine ring system.

Full text of DOI:10.1016/j.tet.2007.03.060

Tetrahedron 63 (2007) 4297–4303
Synthesis of polyarene derivatives of fused aziridines
by Suzuki–Miyaura cross-coupling
Alexander I. Zbruyev, Valery V. Vashchenko, Anastasiya A. Andryushchenko,
Sergey M. Desenko, Vladimir I. Musatov, Irina V. Knyazeva and Valentin A. Chebanov
*
State Scientific Institution ‘Institute for Single Crystals’ of National Academy of Sciences of Ukraine,
Lenin Ave., 60, Kharkiv 61001, Ukraine
Received 25 October 2006; revised 16 February 2007; accepted 8 March 2007
Available online 12 March 2007
Abstract—A convenient and effective synthetic approach to potentially radiochromic polyarene derivatives of bi- and tricyclic aziridines
utilizing modified Suzuki–Miyaura cross-coupling with catalysis in micellar media has been developed. A series of polyarene substituents
were introduced into 1,5-diaryl-3,5a-dihydro-1H-azireno[1,2-c]imidazoles, 1,6-diaryl-1,3,4,6a-tetrahydroazireno[1,2-a]pyrazines, and 1,2-
diaryl-1,1a-dihydroazireno[1,2-a]quinoxalines without degradation of the highly reactive aziridine ring system.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
(polyarene) fragment in one molecule can give rise to an
effective radiochromic compound.6
Derivatives of fused bi- and tricyclic aziridines are of interest
due to their chemical and photochromic properties promoted
by the presence of sterically strained three-membered het-
erocycle. Their thermo- and photoinduced cycloaddition re-
actions with various compounds containing multiple bonds
accompanied by cleavage of C–C bond of aziridine ring
have been studied.1,2 The photochromic properties of aziri-
dines are also linked with ring opening of the three-mem-
bered cycle.3
An established method for synthesizing aziridines I–III is
the reaction of 2,3-dibromo-1,3-diarylpropan-1-ones with
ammonia and carbonyl compounds or with the correspond-
ing 1,2-diamines (Scheme 1).1a,b,2,7 In most cases these
methods provide good yields of reaction products with
high purity. An alternative means to synthesize stereospe-
cific aziridines I is based on the microwave-assisted multi-
component reaction of phenacyl chloride with aldehydes in
the presence of ammonium acetate, which was reported re-
cently.8 A serious limitation of the described procedure is
the difficulties associated with the preparation of bicyclic
aziridines with different substituents in positions 2 and 8.
Among effective photochromes, 1,5-diaryl-3,5a-dihydro-
1H-azireno[1,2-c]imidazoles I, 1,6-diaryl-1,3,4,6a-tetrahy-
droazireno[1,2-a]pyrazines II, and 1,2-diaryl-1,1a-dihydro-
azireno[1,2-a]quinoxalines III containing a 4-nitrophenyl
substituent at the aziridine ring should be mentioned. These
substances in the crystalline state, initially white or yellow,
develop an intense blue color upon irradiation in the UV–vis
range (200–700 nm).
H
Ar1
H
H
H
Ar
Ar
Ar1
RCOR1
NH3
Ar
I
N
H
N
R1
N
O
R
Our preliminary experiments showed that aziridines I–III
possessed very low sensitivity toward X-ray and b-radia-
tion.4 At the same time, various polyarene aromatic com-
pounds are used to transform the energy of absorbed
ionizing radiation into an ultraviolet form.5 Therefore, com-
bining a photochromic (bicyclic aziridine) and a radiophoric
H
Ar1
H
NH3
Br
H2NCH2CH2NH2
II
N
N
O
Ar
Ar1
H2N
H2N
R
Ar
H
Br
N
N
H
R
III
Keywords: Heterocycles; Azireno[1,2-c]imidazoles; Azireno[1,2-a]pyr-
azines; Azireno[1,2-a]quinoxalines; Cross-coupling; Micellar media.
* Corresponding author. Tel.: +38 057 341 01 91; fax: +38 057 340 93 43;
e-mail: chebanov@isc.kharkov.com
Ar1
Scheme 1.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.060

4298
A. I. Zbruyev et al. / Tetrahedron 63 (2007) 4297–4303
Our attempts to prepare aziridines containing polyarene
fragments according to conventionally described procedures
in the most were unsuccessful, mainly due to the low solubil-
ity of starting materials, intermediates, and final products. In
some cases it was not possible to isolate target compounds at
all, others required complicated purification, which resulted
in a dramatic lowering of the yield. It is worth mentioning
that polyarene derivatives of 2,3-dibromopropan-1-ones
are also difficult to synthesize by known methods.9
of the investigation was elaboration of protocols for cross-
coupling reaction, which would be applicable both in case
of fused aziridines and for other unstable organic com-
pounds.
2.1. Arylation of azireno[1,2-c]imidazole and
azireno[1,2-a]pyrazine derivatives
For arylation of a sensitive photochrome with a highly reac-
tive three-membered ring as in 1 we initially chose a standard
Suzuki–Miyaura reaction protocol providing mild enough
reaction conditions: reflux in toluene/water solution with
NaHCO3 and Pd(dppf)Cl2 (dppf¼1,10-bis(diphenylphos-
phino)ferrocene) (Scheme 2).
An alternative route to bi- and tricyclic aziridines containing
polyarene substituents would be use of aryl–aryl cross-cou-
pling reactions after formation of the aziridine fragment.
Amongst the wide variety of approaches to Ar–Ar bond for-
mation10 the Suzuki–Miyaura reaction11 seems to be most
suitable and promising in the case of aziridines taking into
account their rather high reactivity and instability at elevated
temperature and in the presence of acids or bases.1b,12 How-
ever, there are only a few examples of using Suzuki–Miyaura
coupling for compounds containing this heterocycle in non-
fused structures.13
The course of aziridine 1 treatment with phenylboronic
acid 6 was monitored by HPLC. It was established that
the concentration of the product 8 was increased for
the first 30 min of the reaction; afterward its amount re-
mained almost unchanged (w70% conversion), and only
by-products were accumulated after this point, which com-
plicated the work-up procedure and purification of the
required product.
2. Results and discussion
To improve the reaction efficiency we used the method
described in the preliminary report14 regarding catalysis in
micellar media.15 Since the reaction is heterogeneous, the
presence of a surfactant should promote emulsion formation,
bringing together a water-insoluble organic reactant and
The present work is devoted to the development of a con-
venient synthetic approach for potentially radiochromic
bi- and tricyclic aziridines containing polyarene fragments
utilizing Suzuki–Miyaura reaction. One of the main goals
R1
Br
B(OH)2
R
R
Pd(dppf)Cl2, SDS
toluene / H2O
+
N
N
N
N
R1
8-10
6: R1=H
1: R=NO2
2: R=H
1
-C H C12H25
4
7: R =
6
4
Br
Pd(dppf)Cl2, SDS
toluene / H2O
+
+
6
N
N
N
N
11
3
O2N
O2N
O2N
Pd(dppf)Cl2, SDS
toluene / H2O
6
N
N
N
H
N
N
N
+
H
H
12a
12b
4 (a+b)
Br
Br
O2N
O2N
Pd(dppf)Cl2, SDS
toluene / H2O
+
6
N
N
N
N
5
13
SDS = sodium dodecylsulfate
Scheme 2.

A. I. Zbruyev et al. / Tetrahedron 63 (2007) 4297–4303
Table 1. Polyarene derivatives of fused aziridines 8–13 and 19–23
4299
The same method was used for introducing various poly-
arene fragments into different parts of other dihydroazireno-
imidazoles. Compounds 9–12 were synthesized according to
the procedure developed by the reaction of compounds 1–4
with organoboronic acids 6 and 7 in high yields (see Table
1). It can be noted that compound 4 was used as a mixture
of endo- and exo-isomers and after the cross-coupling reac-
tion the mixture of the corresponding products 12a (endo)
and 12b (exo) was isolated and separated.
Entry
R
R1
Reaction
time, min
Yields of crude
products, %
8
9
10
NO2
H
H
5
5
5
5
5
99
83
99
88
98
91
85
87
83
79
87
H
4-C12H25C6H4
NO2
—
—
—
—
H
Et
Et
Ph
11
—
—
—
—
H
H
Ph
H
12 (a+b)
13
19
20 (c+d)
21 (c+d)
22 (c+d)
23 (c+d)
5
20
20
20
20
25
The protocol is also suitable for introducing polyarene frag-
ments into another class of fused aziridines, 1,6-diaryl-
1,3,4,6a-tetrahydroazireno[1,2-a]pyrazines. It was found
that reaction of 5 with 6 led to the corresponding aziridine
13 in a good yield and high purity.
a water-soluble inorganic reagent, therefore accelerating the
reaction. As the standard Suzuki–Miyaura cross-coupling
proceeds in a basic media we have chosen an anionic surfac-
tant—sodium dodecylsulfate (SDS), which is one of the
cheapest and most widespread microemulsion forming
agents.
2.2. Arylation of azireno[1,2-a]quinoxaline derivatives
The same reaction conditions were applied to the reac-
tion of 2-(4-bromophenyl) substituted dihydroazirenoqui-
noxaline 14 with 6. However, formation of the target
biphenyl-substituted aziridine 19 was complicated with
rapid appearance of large amounts of by-products within
5 min. Control experiments without 6 and a palladium
catalyst in reaction mixture showed that compound 14
was unstable under the selected reaction conditions. As a
solution to this problem, reduction of the reaction tempera-
ture was used. A replacement of toluene/water mixture with
Based on HPLC data the reaction of aziridine 1 with phenyl-
boronic acid 6 in the presence of SDS, about 98% conversion
was achieved even in 5 min. At that time, only traces of
by-products were detected. After the conventional work-up
procedure the product 8 was obtained in more than 95%
purity (according to HPLC).
Br
O2N
O2N
Pd(dppf)Cl2, SDS
benzene / H2O
N
N
N
N
+
6
19
R
14
R
R
O2N
O2N
N
N
B(OH)2
N
N
+
O2N
Pd(dppf)Cl2, SDS
benzene / H2O
N
N
+
R1
c
d
Br
R1
R1
20-22
6: R1=H
15(c+d): R=H
16(c+d): R=Et
18: R1=Ph
Br
O2N
O2N
O2N
N
N
Pd(dppf)Cl2, SDS
benzene / H2O
N
N
N
N
+
6
+
Br
17 (c+d)
d
c
23
Scheme 3.

4300
A. I. Zbruyev et al. / Tetrahedron 63 (2007) 4297–4303
benzene/water allowed compound 19 to be formed in 95%
conversion after 15 min (Scheme 3).
was made on a EuroVector EA-3000. HPLC experiments
were performed on Bischoff module chromatograph. Moni-
toring of the reaction course for compound 8 and purity anal-
ysis for all compounds were carried out on RP C-18 column
using 50% acetonitrile–water mixture as eluant. Isomeric
composition of compounds 15–17 and 20–23 was deter-
mined using silica column and CH2Cl2 as eluant. Separation
of the isomeric mixture of 12a and 12b was carried out on
a Prontosil C18 (250ꢀ20 mm) column using acetonitrile
(w87%)–water azeotropic mixture as eluant.
To diversify polyarene derivatives of aziridine we also ex-
plored the possibility to carry out the cross-coupling reaction
on the quinoxaline fragment of dihydroazirenoquinoxalines.
Starting bromosubstituted derivatives 15–17 were obtained
in the reactions of the appropriate 2,3-dibromo-1,3-diaryl-
propan-1-ones with 4-bromo-1,2-phenylenediamine (see
Scheme 1) according to literature procedure.2,7a Products
15–17 represented mixtures of regioisomeric 5- and 6-bro-
modihydroazirenoquinoxalines with predominance for the
5-bromoderivative c, as previously recorded in an earlier in-
vestigation of 4-methyl-1,2-phenylenediamine derivatives.2
The isomer ratio for 15–17 was determined by HPLC and
1H NMR spectroscopic data according to the procedure
described2 (see Section 4). Mixtures of isomers c and d of
the compounds 15–17 could not be separated and were intro-
duced into Suzuki–Miyaura coupling giving rise to mixtures
of isomeric arylsubstituted compounds 20–23.
Phenylboronic acid (6) and Pd(dppf)Cl2$CH2Cl2 are
commercially available (Aldrich).
4.1.1. General procedure for the synthesis of arylboronic
acids 7 and 18. Grignard reagent was obtained from magne-
sium and the corresponding aryl bromide in absolute THF,
refluxed for 4 h, and cooled to 0 ꢁC. Trimethylborate was
added dropwise to the obtained solution. Reaction mixture
was mixed for 1 h, allowed to warm up to 20 ꢁC, and to stand
overnight. Then it was decomposed with 16% HCl solution
and mixed for 2 h. The precipitate obtained was filtered,
washed with water and heptane, and dried in vacuum.
It was also determined that both bromine atoms in dihydro-
azirenoquinoxaline 17 underwent arylation to give a mixture
of isomers 23c and 23d. No monobromo or dibromosubsti-
tuted aziridines were left remaining (as determined by
4.1.1.1. 4-(4-Dodecylphenyl)phenylboronic acid (7).
Quantities used: magnesium (0.56 g, 22.9 mmol), 4-bromo-
40-dodecylbiphenyl (8.5 g, 21.2 mmol), absolute THF
(55 mL), trimethylborate (7.1 mL, 63.6 mmol), and HCl so-
lution (400 mL). Yield: 6.55 g (84.4%) of white crystals. 1H
NMR (DMSO-d6): d 0.82 (t, J¼7.0 Hz, 3H, CH3), 1.13–1.33
(m, 18H, (CH2)9), 1.48–1.65 (m, 2H, CH2), 2.58 (t, J¼
7.4 Hz, 2H, CH2), 7.25 (d, J¼8.2 Hz, 2Harom), 7.57 (d,
J¼8.2 Hz, 2Harom), 7.58 (d, J¼8.2 Hz, 2Harom), 7.84 (d,
J¼8.2 Hz, 2Harom), 8.05 (s, 1.9H (exchangeable), (OH)3).
1
analysis of the crude material by H NMR and mass spec-
troscopy).
All compounds synthesized possess photochromic proper-
ties toward UV–vis radiation similar to those of the known
aziridines without polyarene fragments3 and will be studied
as possible radiochromic compounds toward X-ray and
b-radiation.
3. Conclusions
4.1.1.2. 4-Phenylphenylboronic acid (18).16 Quantities
used: magnesium (0.169 g, 7.0 mmol), 4-bromobiphenyl
(1.5 g, 6.4 mmol), absolute THF (25 mL), trimethylborate
(2.2 mL, 19.2 mmol), and HCl solution (130 mL). Yield:
0.847 g (67%) of white crystals.
In summary, this report describes a novel and effective
approach to bi- and tricyclic derivatives of fused aziridines
containing polyarene fragments based on modified
Suzuki–Miyaura cross-coupling. A protocol was developed
utilizing catalysis in micellar media for the introduction of
polyarene fragments into various positions of the aziridines,
which accelerated significantly the reaction rate, increased
the yields, and purity of the products. It was shown that
micellar-catalyzed procedures were less sensitive to the
leakage of air in the course of the reaction in comparison
with a more prolonged standard protocol, and allowed avoid-
ing side reactions.
4.1.2. Synthesis of the starting aziridines. Starting aziri-
dines 1–5 and 14–17 were obtained by known methods.1b,2,7a
4.1.2.1. 5(6)-Bromo-1-(4-nitrophenyl)-2-phenyl-1,1a-
dihydroazireno[1,2-a]quinoxaline (15cDd). Yield: 68%
(73% (c) and 27% (d)) of yellowish crystals. 1H NMR
(CDCl3): d 2.95 (d, J¼2.7 Hz, 1H, 1-CH (c)), 2.98 (d, J¼
2.7 Hz, 1H, 1-CH (d)), 3.41 (d, J¼2.7 Hz, 1H, 1a-CH (d)),
3.43 (d, J¼2.7 Hz, 1H, 1a-CH (c)), 7.15 (d, J¼8.2 Hz, 1H,
7-CH (c)), 7.25 (dd, J¼1.8, 8.2 Hz, 1H, 6-CH (c)), 7.28 (dd,
J¼1.7, 8.4 Hz, 1H, 5-CH (d)), 7.31 (d, J¼8.4 Hz, 1H, 4-CH
(d)), 7.38–7.42 (m, 2Harom (c+d)), 7.45 (br s, 1H, 7-CH (d)),
7.46–7.48 (m, 3Harom (c+d)), 7.60 (d, J¼1.8 Hz, 1H, 4-CH
(c)), 7.84 (d, J¼7.7 Hz, 2Harom (c+d)), 8.20 (d, J¼8.5 Hz,
2Harom (c+d)). MS (EI, 70 eV): m/z (%)¼419 (2%) [M+],
421 (2%) [M+], 284 (10%), 286 (10%), 257 (19%), 259 (22%);
156 (22%), 154 (17%). Anal. Calcd for C21H14BrN3O2: C,
60.02; H, 3.36; N, 10.00. Found: C, 60.15; H, 3.45; N, 9.97.
4. Experimental
4.1. General
Melting points were determined with a Boetius apparatus
1
and are uncorrected. The H and 13C NMR spectra were
recorded in DMSO-d6 or in CDCl3 at 200 MHz (50 MHz
for 13C) on a Varian Mercury VX-200 spectrometer or at
500 MHz on a Bruker Avance-500 spectrometer and ana-
lyzed with ADVASPÔ Analyzer program (Umatek Interna-
tional Inc.). Mass spectra were measured on a GC–MS
Varian 1200L instrument (EI, 70 eV). Elemental analysis
4.1.2.2.
5(6)-Bromo-2-(4-ethylphenyl)-1-(4-nitro-
phenyl)-1,1a-dihydroazireno[1,2-a]quinoxaline (16cDd).
Yield: 63% (72% (c) and 28% (d)) of yellowish crystals.

A. I. Zbruyev et al. / Tetrahedron 63 (2007) 4297–4303
4301
1H NMR (CDCl3): d 1.18 (t, J¼7.6 Hz, 3H, CH3 (c+d)), 2.64
(quart, J¼7.6 Hz, 2H, CH2 (c+d)), 2.93 (d, J¼2.9 Hz, 1H,
1-CH (c)), 2.96 (d, J¼2.9 Hz, 1H, 1-CH (d)), 3.41 (d,
J¼2.9 Hz, 1H, 1a-CH (d)), 3.42 (d, J¼2.9 Hz, 1H, 1a-CH
(c)), 7.14 (d, J¼8.2 Hz, 1H, 7-CH (c)), 7.22 (d, J¼8.2 Hz,
2Harom (c+d)), 7.23 (dd, J¼2.3, 8.2 Hz, 1H, 6-CH (c)),
7.27 (dd, J¼2.0, 8.3 Hz, 1H, 5-CH (d)), 7.30 (d, J¼8.3 Hz,
1H, 4-CH (d)), 7.44 (d, J¼2.0 Hz, 1H, 7-CH (d)), 7.46 (d,
J¼8.7 Hz, 2Harom (c+d)), 7.59 (d, J¼2.2 Hz, 1H, 4-CH
(c)), 7.77 (d, J¼8.2 Hz, 2Harom (c+d)), 8.20 (d, J¼8.8 Hz,
2Harom (c+d)). MS (EI, 70 eV): m/z (%)¼449 (29%) [M+],
447 (31%) [M+], 314 (100%), 312 (95%), 300 (9%), 298
(12%), 287 (5%), 285 (8%), 156 (23%), 154 (18%), 105
(24%). Anal. Calcd for C23H18BrN3O2: C, 61.62; H, 4.05;
N, 9.37. Found: C, 61.50; H, 4.20; N, 9.34.
silica gel (20 cc), evaporated to dryness, and stored in vac-
uum desiccator to afford products 8–13.
4.1.4.1. 3,3-Dimethyl-1-(4-nitrophenyl)-5-(4-phenyl-
phenyl)-3,5a-dihydro-1H-azireno[1,2-c]imidazole
(8).
Yield: 99% of colorless crystals, mp 198 ꢁC (from acetone).
1H NMR (CDCl3): d 1.60 and 1.62 (2s, 6H, CH3), 2.63 (d,
J¼1.6 Hz, 1H, 1-CH), 3.64 (d, J¼1.6 Hz, 1H, 5a-CH),
7.38–7.53 (m, 5Harom), 7.60–7.70 (m, 4Harom), 7.93 (d,
J¼8.4 Hz, 2Harom), 8.20 (d, J¼8.8 Hz, 2Harom). Anal. Calcd
for C24H21N3O2: C, 75.18; H, 5.52; N, 10.96. Found: C,
75.10; H, 5.41; N, 10.93. 13C NMR (CDCl3): d 23.7, 31.3,
43.8, 56.2, 95.9, 123.7, 127.2, 127.4, 127.4, 128.0, 128.7,
129.0, 130.7, 140.1, 144.3, 146.0, 147.4, 167.3.
4.1.4.2. 3,3-Dimethyl-1-phenyl-5-(4-phenylphenyl)-
3,5a-dihydro-1H-azireno[1,2-c]imidazole (9). Yield: 83%
4.1.2.3.
5(6)-Bromo-2-(4-bromophenyl)-1-(4-nitro-
1
phenyl)-1,1a-dihydroazireno[1,2-a]quinoxaline (17cDd).
Yield: 57% (73% (c) and 27% (d)) of yellowish crystals.
1H NMR (CDCl3): d 2.94 (d, J¼2.9 Hz, 1H, 1-CH (c)),
2.97 (d, J¼2.9 Hz, 1H, 1-CH (d)), 3.36 (d, J¼2.9 Hz, 1H,
1a-CH (d)), 3.37 (d, J¼2.9 Hz, 1H, 1a-CH (c)), 7.15 (d,
J¼8.2 Hz, 1H, 7-CH (c)), 7.26 (dd, J¼2.3, 8.2 Hz, 1H,
6-CH (c)), 7.28 (m, 2H, 5-CH (d)+4-CH (d)), 7.45 (d, 1H,
7-CH (d)), 7.46 (d, J¼8.8 Hz, 2Harom (c+d)), 7.52 (d, J¼
8.8 Hz, 2Harom (c+d)), 7.58 (d, J¼2.2 Hz, 1H, 4-CH
(c)), 7.71 (d, J¼8.8 Hz, 2Harom (c+d)), 8.20 (d, J¼8.8 Hz,
2Harom (c+d)). MS (EI, 70 eV): m/z (%)¼501 (2%) [N+],
499 (3%) [N+], 497 (2%) [N+], 366 (37%), 364 (77%),
362 (33%), 339 (3%), 337 (6%), 335 (3%), 183 (12%), 181
(14%), 156 (14%), 154 (14%). Anal. Calcd for
C21H13Br2N3O2: C, 50.53; H, 2.63; N, 8.42. Found: C,
50.59; H, 2.51; N, 8.39.
of colorless crystals, mp 108 ꢁC (from hexane). H NMR
(CDCl3): d 1.64 (s, 6H, CH3), 2.60 (d, J¼1.7 Hz, 1H, 1-
CH), 3.66 (d, J¼1.7 Hz, 1H, 5a-CH), 7.27–7.53 (m, 8Harom),
7.62–7.71 (m, 4Harom), 7.98 (d, J¼8.2 Hz, 2Harom). Anal.
Calcd for C24H22N2: C, 50.53; H, 2.63; N, 8.42. Found: C,
50.44; H, 2.78; N, 8.39. 13C NMR (CDCl3): d 23.7, 31.5,
44.9, 55.6, 95.5, 126.6, 127.2, 127.4, 127.6, 128.0, 128.5,
128.8, 129.0, 131.0, 138.4, 140.2, 144.0, 168.1. MS (EI,
70 eV): m/z (%)¼338 (81%) [M+], 323 (100%), 296 (7%),
261 (30%), 234 (41%), 180 (30%).
4.1.4.3. 5-{4-[4-(4-Dodecylphenyl)phenyl]phenyl}-3,3-
dimethyl-1-(4-nitrophenyl)-3,5a-dihydro-1H-azireno-
[1,2-c]imidazole (10). Yield: 99% of white solid, mp 168 ꢁC
(from acetone). 1H NMR (CDCl3): d 0.87 (m, 3H, Alk-CH3),
1.13–1.42 (m, 20H, (CH2)10), 1.51–1.73 (m, 8H, 2CH3+
CH2), 2.57–2.70 (m, 3H, 1-CH+ArCH2), 3.64 (d, J¼1.6 Hz,
1H, 5a-CH), 7.20–7.30 (m, 2Harom), 7.45–7.60 (m, 4Harom),
7.62–7.75 (m, 6Harom), 7.92 (d, J¼8.4 Hz, 2Harom), 8.20 (d,
J¼8.8 Hz, 2Harom). Anal. Calcd for C42H49N3O2: C, 80.34;
H, 7.87; N, 6.69. Found: C, 80.44; H, 7.79; N, 6.67. 13C
NMR (CDCl3): d 14.1, 22.7, 23.7, 29.3, 29.4, 29.5, 29.6,
29.7, 29.7, 31.3, 31.4, 31.9, 35.7, 43.8, 56.2, 95.9, 123.7,
126.9, 127.2, 127.4, 127.5, 127.5, 128.8, 128.9, 130.7, 137.7,
138.5, 141.0, 142.5, 143.8, 146.0, 147.4, 167.3. MS (EI,
70 eV): m/z (%)¼627 (32%) [M+], 492 (49%), 478 (92%),
465 (34%), 424 (22%), 335 (46%), 323 (63%), 268 (100%).
4.1.3. Non-micellar procedure for synthesis of 3,3-
dimethyl-1-(4-nitrophenyl)-5-(4-phenylphenyl)-3,5a-
dihydro-1H-azireno[1,2-c]imidazole 8. A mixture of
aziridine 1 (1.00 g, 2.59 mmol), phenylboronic acid 6
(0.379 g, 3.1 mmol), toluene (30 mL), water (15 mL), and
1-butanol (3 mL) in a three-necked flask was degassed in
vacuum and flashed with argon under vigorous stirring,
then Pd(dppf)Cl2$CH2Cl2 (56 mg, 0.069 mmol) was added.
The degassing was repeated again, and the mixture was
heated to rfflux under argon atmosphere and solution of
NaHCO3 (870 mg, 10.36 mmol) in water (15 mL) was
added in one portion. The reflux was continued whereas
samples of reaction mixture for HPLC analysis were taken
after 3, 5, 10, 30, 70, and 140 min after addition of the base.
4.1.4.4. 3,3-Dimethyl-1-(4-phenylphenyl)-5-phenyl-
3,5a-dihydro-1H-azireno[1,2-c]imidazole (11). Yield:
1
88% of colorless crystals, mp 116 ꢁC (from hexane). H
NMR (DMSO-d6): d 1.60 and 1.62 (2s, 6H, CH3), 2.72 (d,
J¼1.6 Hz, 1H, 1-CH), 3.89 (d, J¼1.6 Hz, 1H, 5a-CH),
7.34–7.50 (m, 8Harom), 7.57–7.65 (m, 4Harom), 7.88 (d,
J¼7.1 Hz, 2Harom). Anal. Calcd for C24H22N2: C, 50.53;
H, 2.63; N, 8.42. Found: C, 50.40; H, 2.71; N, 8.39. 13C
NMR (CDCl3): d 23.7, 31.5, 44.6, 55.7, 95.6, 127.0, 127.1,
127.3, 127.4, 128.3, 128.7, 128.8, 131.3, 132.2, 137.5,
140.6, 140.9, 168.4. MS (EI, 70 eV): m/z (%)¼338 (78%)
[M+], 323 (100%), 220 (13%), 185 (35%), 158 (28%).
4.1.4. General procedure for micellar-catalyzed synthesis
of aziridines 8–13. Procedure with micellar catalysis is sim-
ilar to the one described above, except addition of surfactant
to mixture of reactants. Quantities used: an appropriate bro-
mosubstituted aziridines 1–5 (2.59 mmol), phenylboronic
acid 6 (0.379 g, 3.1 mmol), SDS (0.300 g), toluene
(30 mL), water (15 mL), 1-butanol (3 mL), Pd(dppf)Cl2$
CH2Cl2 (56 mg, 0.069 mmol), and a solution of NaHCO3
(870 mg, 10.36 mmol) in water (15 mL). After addition of
the base, the reaction mixture was refluxed for 5 min and
cooled to room temperature. The organic layer was sepa-
rated, water layer was extracted with CH2Cl2 (2ꢀ15 mL),
the combined organic extract was washed with water
(50 mL), dried over Na2SO4, filtered through short plug of
4.1.4.5. endo-1-(4-Nitrophenyl)-5-phenyl-3-(4-phenyl-
phenyl)-3,5a-dihydro-1H-azireno[1,2-c]imidazole (12a).
Colorless crystals, mp 174 ꢁC. 1H NMR (DMSO-d6):
d 2.68 (d, J¼1.9 Hz, 1H, 1-CH), 4.22 (d, J¼1.9 Hz, 1H,
5a-CH), 6.76 (s, 1H, 3-CH), 7.30–7.68 (m, 14Harom), 8.02

4302
A. I. Zbruyev et al. / Tetrahedron 63 (2007) 4297–4303
(d, J¼6.7 Hz, 2Harom), 8.15 (d, J¼8.4 Hz, 2Harom). 13C
NMR (DMSO-d6): d 41.6, 57.7, 95.6, 124.1, 127.3, 127.4,
128.2, 128.5, 129.2, 129.6, 129.7, 132.0, 132.4, 138.6, 140.1,
140.3, 146.8, 147.4, 171.5. Anal. Calcd for C28H21N3O2: C,
77.94; H, 4.91; N, 9.74. Found: C, 77.88; H, 5.01; N, 9.71.
(CDCl3): d 3.01 (d, J¼2.8 Hz, 1H, 1-CH (c)), 3.02 (d,
J¼2.8 Hz, 1H, 1-CH (d)), 3.46 (d, J¼2.7 Hz, 1H, 1a-CH
(c+d)), 7.27–7.57 (m, 12Harom), 7.72 (d, J¼2.1 Hz, 1H,
4-CH (c)), 7.88 (d, J¼7.6 Hz, 2Harom (c+d)), 8.21 (d, J¼
8.6 Hz, 2Harom (c+d)). MS (EI, 70 eV): m/z (%)¼417 (3%)
[M+], 282 (73%), 255 (5%), 152 (25%), 103 (24%), 102
(100%). Anal. Calcd for C27H19N3O2: C, 77.68; H, 4.59;
N, 10.07. Found: C, 77.57; H, 4.68; N, 10.04.
4.1.4.6. exo-1-(4-Nitrophenyl)-5-phenyl-3-(4-phenyl-
phenyl)-3,5a-dihydro-1H-azireno[1,2-c]imidazole (12b).
Colorless crystals, mp 196 ꢁC. 1H NMR (DMSO-d6):
d 2.68 (d, J¼1.8 Hz, 1H, 1-CH), 3.09 (d, J¼1.8 Hz, 1H,
5a-CH), 6.33 (s, 1H, 3-CH), 7.30–7.69 (m, 14Harom), 7.99
(d, J¼7.1 Hz, 2Harom), 8.20 (d, J¼8.1 Hz, 2Harom). 13C
NMR (DMSO-d6): d 47.2, 56.7, 96.8, 124.1, 127.4, 128.1,
128.2, 128.5, 129.2, 129.5, 129.6, 132.0, 132.3, 140.5, 140.6,
141.2, 147.1, 147.4, 170.1. Anal. Calcd for C28H21N3O2: C,
77.94; H, 4.91; N, 9.74. Found: C, 77.87; H, 4.99; N, 9.70.
4.1.5.3.
2-(4-Ethylphenyl)-1-(4-nitrophenyl)-5(6)-
phenyl-1,1a-dihydroazireno[1,2-a]quinoxaline (21cDd).
Yield: 83% (77% (c) and 23% (d)) of yellowish crystals.
1H NMR (CDCl3): d 1.19 (t, J¼7.7 Hz, 3H, CH3 (c+d)),
2.65 (quart, J¼7.7 Hz, 2H, CH2 (c+d)), 2.99 (d, J¼2.9 Hz,
1H, 1-CH (c)), 3.00 (d, J¼2.9 Hz, 1H, 1-CH (d)), 3.46 (d,
J¼2.9 Hz, 1H, 1a-CH (c+d)), 7.23 (d, J¼7.9 Hz, 2Harom
(c+d)), 7.27–7.42 (m, 4Harom (c+d)), 7.49–7.57 (m, 5Harom
(c+d)), 7.71 (d, J¼2.1 Hz, 1H, 4-CH (c)), 7.80 (d, J¼8.2 Hz,
2Harom (c+d)), 8.21 (d, J¼8.7 Hz, 2Harom (c+d)). MS
(EI, 70 eV): m/z (%)¼445 (2%) [M+], 310 (99%), 283
(3%), 152 (25%), 102 (100%). Anal. Calcd for
C29H23N3O2: C, 78.18; H, 5.20; N, 9.43. Found: C, 78.27;
H, 5.29; N, 9.40.
4.1.4.7. 1-(4-Nitrophenyl)-6-(4-phenylphenyl)-1,3,4,
6a-tetrahydroazireno[1,2-a]pyrazine (13). Yield: 91% of
1
yellowish crystals, mp 145 ꢁC (from acetone). H NMR
(DMSO-d6): d 2.69–2.84 (m, 1H, CH2), 3.16–3.27 (m, 2H,
1-CH+CH2), 3.25 (d, J¼2.2 Hz, 1H, 6a-CH), 3.67–3.84
(m, 2H, CH2), 3.95, 7.31–7.50 (m, 3Harom), 7.59–7.72 (m,
6Harom), 7.85 (d, J¼8.5 Hz, 2Harom), 8.21 (d, J¼8.8 Hz,
2Harom). 13C NMR (DMSO-d6): d 39.6, 39.8, 43.7, 124.2,
127.2, 127.3, 127.4, 128.3, 128.6, 129.7, 138.0, 140.0,
142.3, 147.4, 147.7, 162.6. Anal. Calcd for C23H19N3O2:
C, 74.78; H, 5.18; N, 11.37. Found: C, 74.70; H, 5.29; N,
11.36.
4.1.5.4.
2-(4-Ethylphenyl)-1-(4-nitrophenyl)-5(6)-
(4-phenylphenyl)-1,1a-dihydroazireno[1,2-a]quinoxaline
(22). Yield: 79% (80% (c) and 20% (d)) of yellowish crys-
tals. 1H NMR (CDCl3): d 1.19 (t, J¼7.7 Hz, 3H, CH3
(c+d)), 2.65 (quart, J¼7.7 Hz, 2H, CH2 (c+d)), 2.99 (d,
J¼2.8 Hz, 1H, 1-CH (c)), 3.00 (d, J¼2.8 Hz, 1H, 1-CH
(c)), 3.46 (d, J¼2.9 Hz, 1H, 1a-CH (c+d)), 7.21–7.68 (m,
15Harom (c+d)), 7.75 (d, J¼1.9 Hz, 1H, 4-CH (c)), 7.81 (d,
J¼8.2 Hz, 2Harom (c+d)), 8.22 (d, J¼8.7 Hz, 2Harom
(c+d)). MS (EI, 70 eV): m/z (%)¼493 (100%) [M+], 494
(46%) [M+], 358 (65%), 359 (18%), 228 (12%), 178
(21%). Anal. Calcd for C33H23N3O2: C, 80.31; H, 4.70; N,
8.51. Found: C, 80.22; H, 4.79; N, 8.47.
4.1.5. General procedure for micellar-catalyzed synthesis
of dihydroazirenoquinoxalines 19–22. A mixture of the
corresponding bromosubstituted dihydroazirenoquinoxaline
(2.59 mmol), phenylboronic acid (3.1 mmol), SDS
(0.300 g), benzene (30 mL), water (15 mL), and 1-butanol
(3 mL) in a three-necked flask was degassed in vacuum
and flashed with argon under vigorous stirring, then
Pd(dppf)Cl2$CH2Cl2 (56 mg, 0.069 mmol) was added. The
degassing was repeated again, and the mixture was heated
to reflux under argon atmosphere and the solution of
Na2CO3 (10.36 mmol) in water (15 mL) was added in one
portion. After addition of the base, the reaction mixture
was refluxed for 20 min and cooled to room temperature.
The organic layer was separated, water layer was extracted
with CH2Cl2 (2ꢀ15 mL), the combined organic extract
was washed with water (50 mL), dried over Na2SO4, filtered
through short plug of silica gel (20 cc), evaporated to dry-
ness, and dried in vacuum desiccator. The residue was
recrystallized from acetone to afford products 19–22.
4.1.6. Micellar-catalyzed synthesis of 1-(4-nitrophenyl)-
5(6)-phenyl-2-(4-phenylphenyl)-1,1a-dihydroazireno[1,2-
a]quinoxaline 23. The procedure is similar to the one
described above (Section 4.1.5), except the quantity of the
starting dibromosubstituted aziridine 17 (mixture of c and
d) was 1.28 mmol and reaction time was 25 min.
4.1.6.1. 1-(4-Nitrophenyl)-5(6)-phenyl-2-(4-phenyl-
phenyl)-1,1a-dihydroazireno[1,2-a]quinoxaline
(23).
Yield: 87% (80% (c) and 20% (d)) of yellowish crystals.
1H NMR (CDCl3): d 2.97 (d, J¼2.7 Hz, 1H, 1-CH (c)),
2.99 (d, J¼2.7 Hz, 1H, 1-CH (d)), 3.47 (d, J¼2.7 Hz, 1H,
1a-CH (c+d)), 7.28–7.65 (m, 17Harom (c+d)), 7.92 (d,
J¼8.3 Hz, 2Harom (c+d)), 8.22 (d, J¼8.6 Hz, 2Harom (c+d)).
MS (EI, 70 eV): m/z (%)¼493 (1%) [M+], 358 (100%),
179 (26%), 152 (29%), 102 (70%). Anal. Calcd for
C33H23N3O2: C, 80.31; H, 4.70; N, 8.51. Found: C, 80.24;
H, 4.65; N, 8.48.
4.1.5.1. 1-(4-Nitrophenyl)-2-(4-phenylphenyl)-1,1a-
dihydroazireno[1,2-a]quinoxaline (19). Yield: 85% of yel-
1
lowish crystals, mp 147–148 ꢁC (from acetone). H NMR
(DMSO-d6): d 3.47 (d, J¼2.6 Hz, 1H, 1-CH), 3.94 (d,
J¼2.6 Hz, 1H, 1a-CH), 7.21–7.51 (m, 7Harom), 7.67–7.73
(m, 4Harom), 7.81 (d, J¼8.4 Hz, 2Harom), 8.03 (d, J¼
8.4 Hz, 2Harom), 8.27 (d, J¼8.7 Hz, 2Harom). Anal. Calcd
for C27H19N3O2: C, 77.68; H, 4.59; N, 10.07. Found: C,
77.59; H, 4.66; N, 10.05.
Acknowledgements
4.1.5.2. 2,5(2,6)-Diphenyl-1-(4-nitrophenyl)-1,1a-di-
hydroazireno[1,2-a]quinoxaline (20cDd). Yield: 87%
(85% (c) and 15% (d)) of yellowish crystals. 1H NMR
The present work was supported by grant of National Acad-
emy of Sciences of Ukraine. We thank Dr. Thomas Gurley
for the editorial contribution.

A. I. Zbruyev et al. / Tetrahedron 63 (2007) 4297–4303
4303
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