Photoreactive fused aziridinylpiperazines on the background of 4-substituted chalcones and their benzimidazolic analogs

Article abstract of DOI:10.1016/j.molstruc.2018.12.015

The reaction of bromo-substituted chalcones with various diamino-compounds leads to the fused heterocyclic products, aziridinylpiperazines, exhibiting photoreactivity in the crystalline state. Crystals of 4-nitrosubstituted compounds of this family change their color from yellowish to deep violet-blue, 4-cyanosubstituted ones – from yellowish to pink at UV irradiation. Discussion on the mechanism of this phototransformation is still in progress, however, several facts points to the free radial nature of the photogenerated colored semi-products stabilized only by crystalline state of the irradiated samples. Formation of a mixture of positional isomers at interaction of bromo-chalcones with asymmetric diamines of aliphatic/alicyclic or aromatic series at synthesis of the title compounds is of significant interest as well.

Full text of DOI:10.1016/j.molstruc.2018.12.015

Accepted Manuscript
Photoreactive fused aziridinylpiperazines on the background of 4-substituted
chalcones and their benzimidazolic analogs
Volodymyr M. Kotlyar, Oleksii O. Kolomoitsev, Dmytro V. Nikolaievskyi, Polina I.
Pedan, Andrii Yu. Chumak, Valery D. Orlov, Svitlana V. Shishkina, Andrey O. Doroshenko
PII:
S0022-2860(18)31436-4
10.1016/j.molstruc.2018.12.015
MOLSTR 25952
DOI:
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Accepted Date:
06 September 2018
04 December 2018
Please cite this article as: Volodymyr M. Kotlyar, Oleksii O. Kolomoitsev, Dmytro V. Nikolaievskyi,
Polina I. Pedan, Andrii Yu. Chumak, Valery D. Orlov, Svitlana V. Shishkina, Andrey O. Doroshenko,
Photoreactive fused aziridinylpiperazines on the background of 4-substituted chalcones and their
benzimidazolic analogs, Journal of Molecular Structure (2018), doi: 10.1016/j.molstruc.2018.12.015
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ACCEPTED MANUSCRIPT
Photoreactive fused aziridinylpiperazines on the background of 4-
substituted chalcones and their benzimidazolic analogs
Volodymyr M. Kotlyar1, Oleksii O. Kolomoitsev1, Dmytro V. Nikolaievskyi, Polina I. Pedan1,
Andrii Yu. Chumak1, Valery D. Orlov1, Svitlana V. Shishkina2, Andrey O. Doroshenko1
1 V.N. Karazin Kharkiv National University, 4 Svobody sq., Kharkiv 61022, Ukraine;
2 State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of
Ukraine, 60 Nauky ave., Kharkiv 61001, Ukraine;
e-mail: vnkotlyar@ukr.net, andreydoroshenko@ukr.net
R2
NH2
.2HCl
O
Br
R1
Et3N
H2N
N
N
CH3OH
Ar
Br
Ar'
+
R1
R2
Ar'
Br
Ar
R
N
R
NH2
.2HCl
O
Et3N
H2N
N
N
N
Ar
Ar'
+
+
CH3OH
R
Br
Ar'
Ar'
Ar
Ar
The reaction of bromo-substituted chalcones with various diamino-compounds leads to the fused
heterocyclic products, aziridinylpiperazines, exhibiting photoreactivity in the crystalline state. Crystals
of 4-nitrosubstituted compounds of this family change their color from yellowish to deep violet-blue,
4-cyanosubstituted ones – from yellowish to pink at UV irradiation. Discussion on the mechanism of
this phototransformation is still in progress, however, several facts points on the free radial nature of
the photogenerated colored semi-products stabilized only by crystalline state of the irradiated samples.
Formation of a mixture of positional isomers at interaction of bromo-chalcones with asymmetric
diamines of alyphatic/alycyclic or aromatic series at synthesis of the title compounds is of significant
interest as well.
Keywords: Solid state photoreactivity, photochromism, fused aziridinylpiperazines, chalcones,
benzimidazoles, positional isomers.
1

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Solid state organic photoreactive (photochromic) compounds, such as N-salycilideneanylines,
dinitrobenzylpyridines, diphenylmaleonitriles, ditiophenylethenes, triarylimidazole dimers, etc. attract
significant attention [1,2] due to their potential application in various optoelectronic devices such as
optical memory and information storage systems, optical switchers, sunscreens, displays and so on.
Fused aziridinylpiperazines containing the 1,4-diazabicyclo[4.1.0]hept-4-ene moiety can be
considered as a distinct subclass among organic photochromic compounds owing to their high
photosensitivity and high contrast of the color changes. No color appearance was typical to them in
fluid solutions, in polymer films decoloration of UV-irradiated samples is too fast [3-5]. The
photoreactivity of these compounds is determined by the presence of strained fused aziridine cycle in
their molecules, which is capable to opening at UV irradiation [3,4]. Recently, the sensitivity of
compounds of the title series to X-ray irradiation was reported as well [5]. In addition, biological
activity of azirydinylquinoxalines containing sidnone moiety was reported [6].
The classical scheme of a synthesis of a fused aziridinylpiperazines includes two main stages:
bromination of chalcones and consequent cyclization of the formed dibromides with vicinal diamines
(scheme 1):
Scheme 1
X
O
Br
O
N
N
X
Br2
+
N
N
+
Ar
Ar'
Ar'
Ar
Ar'
Ar
Br
Traditionally compounds of the title series were synthesized on the background of ortho-
phenylenediamine. In the present paper we focus our attention of vicinal diamines of
methylcyclohexane series. 4-cyano-, 4-nitro-chalcones and their benzimidazolic analogs were selected
as starting compounds as well.
4-nitrochalcone was widely applied for the synthesis of a fused aziridinylpiperazine heterocyclic
system earlier [7]. The presence of a strong electron withdrawing nitro group provides the most
contrast color effects and high sensitivity to UV or visible light irradiation of solid samples of title
compounds (figure 1).
Figure 1. Irradiation of a crystalline sample of aziridinylpiperazine by near UV light results in
changing color from yellowish to deep violet-blue (λmax ~ 590 nm). Further slow decoloration of
irradiated crystals took place during several (tens) hours in the darkness.
The choice of heterocyclic moiety for insertion in the initial chalcone molecules was determined by
unique acid-base properties of benzimidazolic bicycle [8]. Replacing of nitro group by weaker electron
withdrawing cyano group results in obtaining of photoreactive compounds as well, however, their
color changes at UV irradiation were less pronounced – to pink or reddish only. This allows us to
assume, that photoreactivity of title aziridinylpiperazine is influenced by the electronic properties of
substituents in their molecules. Photoreactivity of cyano-substituted representatives of
aziridinylpiperazine series might demand definite corrections in the proposed earlier mechanism of
phototransformations [7]. One could consider also the ionic mechanism of photoinduced aziridine
cycle opening. Recently free radical coloration centers formation was proposed for description of the
2

ACCEPTED MANUSCRIPT
experimentally observed solid state photoreactivity of closely related to the title compounds
aziridinequinoxalines [9]: ESR signal intensity decrease and color loosing underwent practically
synchronously.
4-nitrochalcone synthesis was reported in [10]. Its special feature related to high probability of
formation of intermediate aldol and necessity of inclusion of an additional synthetic step - aldol
dehydratation under acidic catalysis, was discussed in [8]. 4-cyanochalcone was synthesized by
traditional scheme applicable to the majority of chalcone derivatives [11].
The bromination of initial nitro- and cyano-substituted chalcones was carried out in mild conditions
with nearly quantitative yields [10].
Scheme 2
N
N
O
N
O
O
N
N
X
Br2, CHCl3
Br2, CCl4
N
H
Br
CH
3Br
Br
1b
1a
+
+
N
N
– O
+
O
O
– O
N
O
– O
Contrary to the above mentioned cases, bromination of benzimidazolic chalcones was hampered by
the precipitation of their poorly soluble hydrobromic salts (their typical feature is significant
broadening and shifting to 4.0-4.2 ppm of a signal of residual water in DMSO-d6 in 1H NMR spectra)
and thus demanded special reactive conditions. At optimization of their synthesis by variation of the
stoichiometry of components, solvent and temperature regime, we have found, that boiling in CHCl3 or
CCl4 at ketone:bromine molar ratio 1:4 during 10-20 hours allowed to achieve the maximal yields of
80-90%.
However, even in this case we observed the formation of hydrobromic salts and partial
dehydrobromination. The latter results in formation of α-bromo-substituted chalcones in a mixture with
the expected α,β-dibromides (dibromide was the main product of N-H benzimidazolic chalcone
bromination, while α-bromo-derivative was obtained predominantly in the case of N-CH3-
benzimidazolic chalcone). We made several unsuccessful attempts of further bromination of 1b
hydrobromic salt, though increasing reaction time at significant Br2 excess leads to resinification of
reaction mixture.
Neutralization of hydrobromic salts with aqueous NaHCO3 was unsuccessful as well. At the same
time, we considered, that salt form does not interfere the next synthetic stage, thus they were used in
reaction with diamines “as is”.
Neutral benzimidazolic chalcones (di)bromides were obtained in glacial acetic acid at 4-fold Br2
excess.
1
Individual di- and mono-bromochalcones were identified by their H NMR spectra. Dibromides are
characterized by the presence of two doublet signals at 6.11 and 6.66 ppm with vicinal J-constants of
11.8 Hz, while as α-bromides demonstrate singlet signal at 8.9 ppm. As it was mentioned earlier,
formation of hydrobromic salts in case of benzimidazolic chalcones lead to appearance of a broad
signal at 4.0-4.2 ppm, the rest of the signals positions and multiplicity are similar to those for neutral
compounds (synthesized in acetic acid media instead of chloroform/carbon tetrachloride).
It seems, that the initial stage of interaction of chalcones (di)bromides with diamines requires
debromination, thus dibromides 1a and mono-bromides 1b lead to formation of the same final
products – fused aziridinylpiperazines.
Traditional diamino compounds for the synthesis of aziridinylpiperazines were 1,2-
phenylenediamine and 1,2-ethylenediamine [3,5] (scheme 3).
3

ACCEPTED MANUSCRIPT
Scheme 3
H2N
NH2
N
N
Ar'
Ar'
Ar
O
Br
NH2
NH2
Ar
Ar'
Br
N
N
Ar
In the present work several asymmetric diamines were tested in the form of dihydrobromides. Their
synthesis and identification was described in [12] and briefly shown in Scheme 4. The most interesting
case is the application of cyclic ketones (such as cyclohexanone) in the synthesis of diamines, because
final aziridinylpiperazines include additional carbocycle spiro-annealed to the existed biheterocyclic
system.
Scheme 4
BOCNH
NaBH4, Boc2O
NiCl2
NH2
N
N
O
H
KCN, NH4Cl
R'
H
NH2 Boc2O
R'
BOC
HCl
N
NBOC
NH2
R'
*2HCl
R
R'
R
R
R'
R
R
The interaction of the bromo-derivatives of chalcones with diamines hydrobromic salts were carried
out in methanol solutions at presence of triethylamine, which acts as cyclization catalyst and HBr-
neutralizing/binding agent as well.
The title compounds 2a-d, 3a-e and 4a-e were obtained in high yields. All of them demonstrate
pronounced photoreactivity in the solid state, which is the first and qualitative evidence for the
formation of target compounds of the title series. Finally, all the products were characterized by NMR
spectroscopy and mass spectrometry data.
The ortho-phenylenediamine- and ethylenediamine-based derivatives were identical with those of
reported earlier [13] (Schemes 5,6). In the case of asymmetric diamines, a pair of positional isomers
can be formed owing to steric non-equivalence of their vicinal amino groups (Scheme 6).
Scheme 5
N
N
NH2
NH2
N
N
X
, Et3N
2(a+c)
O
N
Br
N
N+
N
X
Br
N
O
O
NH2
*2HCl, Et3N
N
N
N+ O
X
NH2
O
2(b+d)
N+
X = H (2a-b), CH3 (2c-d)
O
O
4

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Scheme 6
R2
R1
N
N
O
Br
NH2
R
3a-e, 4a-e
R2
Et3N
NH2
R2
*2HCl
+
R1
R1
Br
R2
R1
R
N
N
N
N
+
R = NO2 (3a-g), CN (4a-g)
R1 = R2 = CH3 (3a, 4a)
R
R
3f-g, 4f-g
R1, R2: (-CH2-)n : n =3 (3b, 4b), n = 4 (3c, 4c),
3f-g, 4f-g
n = 5 (2b, 2d, 3d, 4d), n = 6 (3e, 4e);
R1 = H, R2 = cyclopropyl (3f, 4f)
R1 = H, R2 = Ph (3g, 4g)
As compounds 2b, 2d, 3a-e and 4a-e were synthesized from diamines with non-equivalent amino
groups, the question of their involvement in formation of a fused aziridine cycle or condensation with
chalcone carbonyl group demands additional arguments, which is especially important for compounds
with spiro-annealing of cyclohexane moiety. The existed NMR spectra were not sufficient to formulate
the grounded answer.
The necessary arguments were obtained with the help of X-ray structural analysis (figure 2). We
favored to obtain appropriate single crystals only for compound 3d. It should be considered as a model
compound for the whole series, because its 1H NMR spectrum contains all the characteristic signals of
aziridinylpiperazine system, which are typical to other representatives of this class of compounds.
Figure 2. Compound 3d molecular structure and scheme of atom numbering according to X-ray
structural analysis data.
The obtained results evidence, that six-membered cyclohexane moiety is spiro-annealed with 1,4-
diazabicyclo[4.1.0]hept-4-enic backbone in its position 3 (atom C4 in figure 2). This means, that the
less sterically hindered amino group of the asymmetric diamine is involved in formation of a fused
5

ACCEPTED MANUSCRIPT
aziridine cycle, while as more sterically hindered one takes part in the cyclocondensation with carbonyl
group of bromo-chalcone and finally - in formation of a fused piperazine cycle. This corresponds well
to the earlier proposed mechanism of the reaction of chalcone dibromides with diamines [10],
according to which the dehydrobromination should occur on the first step with formation of α-
bromochalcone. Then, Michael addition of one of amino groups to double bond and consequent
formation of aziridine cycle takes place. Finally, spatial approaching of a second amino and carbonyl
groups favors their condensation with formation of partially hydrogenated fused pyrazine cycle.
Spiro-joined cycles are arranged in such a way that the dihedral angle between the mean square
planes drawn through all the atoms of each of the cycles is 82°. The cyclohexane ring adopts a chair
conformation (the puckering parameters [14] are: S = 1.1, Θ = 3.1°, Ψ = 35.6°). The deviations of the
C4 and C8 atoms from the mean plane of the remaining atoms of the cycle are -0.61 Å and 0.67 Å
respectively. The diazine cycle is in the conformation, intermediate between the “distorted sofa” and
the “twist-boat”, as evidenced by the puckering parameters (S = 0.74, Θ = 55.9°, Ψ = 23.2°) and the
deviations of the N1 and C5 atoms from the mean plane of the remaining atoms of the cycle (0.41 Å
and 0.92 Å, respectively).
The diazine and aziridine rings are joined in cis-type (the H2-C2-N1-Lp(N1) torsion angle is 3°).
The hydrogen atoms of the aziridine ring have trans-orientation with the H2-C2-C1-H1 torsion angle
of 149°. It is worth to focus reader’s attention to high degree of pyramidality of the N1 atom (the sum
of the valence angles centered on it is 287°) and to non-equivalence of the N1-C1 and N1-C2 bonds
(1.477(2) Å and 1.456(2) Å respectively). The asymmetry of N-C bonds lengths and high nitrogen
pyramidality of the aziridine ring could be among the structural factors favoring cleavage of its C1-C2
bond [9] at UV irradiation.
Calculated spin-spin interaction constants by classical Karplus equation utilizing the X-ray structural
data demonstrated good correspondence to 1H NMR experimental spectra.
The seeming exceptions from the general rules are the compounds 3f-g and 4f-g, which were
synthesized with the use of cyclopropylethylenediamine and phenylethylenediamine correspondently.
According to NMR data, they are the equimolar mixtures of positional isomers. However, they exhibit
expressed photosensitivity in the solid state, like any other examined compounds of the title series.
In conclusion, it is necessary to emphasize, that bromination of benzimidazolic chalcones undergo
specifically with formation of α-monobromo-derivatives or α,β-dibromides. Condensation of the latter
with vicinal diamines leads to fused aziridinepiperazines possessing expressed photoreactivity in the
solid state. Photochromic behavior demonstrate both nitro- and cyano-substituted derivatives, however,
coloration is significantly deeper in the case of stronger electron withdrawing substituent (violet-blue
in case of nitro- versus pink in case of cyano-compounds). Introduction of asymmetric diamines in the
main synthetic scheme leads to formation of equimolar mixture of positional isomers. Cyclic diamines
form individual tricyclic spiro-annealed products, in which less sterically hindered amino group
participates in formation of a fused aziridine cycle.
Experimental part
All the starting materials and solvents were purchased via Aldrich local representatives in Ukraine
and used without additional purification. Reaction progress was controlled by TLC on Silufol UV-254
plates and acetone-hexane (1:1), ethyl acetate-toluene (1:1), chloroform-hexane (1:1) or pure
chloroform as eluents. Melting points (uncorrected) were detected on a Koffler device.
13
1H and C NMR spectra were registered in DMSO-d6 or CDCl3 on Varian MR-400 spectrometer
(working frequencies were 400 and 100 MHz correspondently). Mass-spectra were measured on GS-
MS Varian 1200L device (EI, 70 eV).
Synthesis of initial chalcones was realized according to recommendations of [10], their
benzimidazloic compounds – according to [8]. Diamines for cyclocondensation with chalcones
(di)bromides were prepared according to prescription reported in [12].
1-(1Н-benzimidazole-2-yl)-2,3-dibromo-3-(4-nitrophenyl)propan-1-one (1а).
Solution of 12 mmol of Br2 in 15 ml of chloroform was added dropwise to 3 mmol of correspondent
6

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chalcone in 200 ml of chloroform. The reaction mixture was boiled during 20 hours, the forming
precipitate was filtered off and dried on air.
Compound 1a. Yield 80%, mp 120°C (crystallized from acetic acid). 1H NMR, δ, ppm (J, Hz): 6.11
(1Н, d, J = 12.0, –CO–(CHBr)–(CHBr)–C–); 6.66 (1Н, d, J = 11.9, –CO–(CHBr)–(CHBr)–C–); 7.43
(2H, m, Ar); 7.78 (2H, m, Ar); 8.09 (2H, d, J = 8.7, 4-NO2Ph); 8.29 (2H, d, J = 8.8, 4-NO2Ph).
2-bromo-1-(1-methylbenzimidazol-2-yl)-3-(4-nitrophenyl)propan-2-en-1-one (1b).
Solution of 12 mmol of Br2 in 15 ml of carbon tetrachloride was added dropwise to 3 mmol of
correspondent chalcone in 200 ml of carbon tetrachloride. The reaction mixture was boiled during 20
hours, the forming precipitate was filtered off and dried on air.
Compound 1b. Yield 88%, mp 140°C (crystallized from methanol). 1H NMR, δ, ppm (J, Hz): 4.04
(3Н, s, CH3); 7.44 (2H, m, Ar); 7.81 (2H, m, Ar); 8.10 (2H, d, J = 8.7, 4-NO2Ph); 8.35 (2H, d, J = 8.8,
4-NO2Ph); 8.91 (1H, s, –CBr=CH–).
2-[1-(4-nitrophenyl)-1,1a-dihydroazirino[1,2-a]-quinoxalin-2-yl]benzimidazoles (2a and 2с).
Suspension of 2 mmol of correspondent chalcone dibromide in 50 ml of methanol was mixed with 2
mmol of triethylamine in a 100 ml round-bottom flask. The flask was heated to complete dissolution of
solid phase, than 2 mmol of ortho-phenylenediamine was added. After this reaction mixture was boiled
during 10 minutes, then left to stay 24 hours at room temperature. The precipitate was filtered off,
washed with a small amount of methanol.
Compound 2a. Yield 65%, mp 135°C (crystallized from methanol). 1Н NMR, δ, ppm (J, Hz): 3.53
(1H, d, J = 2.9, –C–(CH)–(CH)–C–); 4.11 (1H, dd, J = 3.0, –C–(CH)–(CH)–C–); 7.40 (1Н, dd, J = 5.8,
3.2, Ar); 7.51 (1H, dd, J = 5.8, 3.2, Ar); 7.19-7.40 (4Н, m, Ar); 7.63 (4H, dd, J = 9.1, 4.3, 4-NO2Ph);
8.25 (2H, d J = 8.8, Ar).
1
Compound 2с. Yield 75%, mp 125°C (crystallized from methanol). Н NMR, δ, ppm (J, Hz): 3.53
(1H, d, J = 2.9, –C–(CH)–(CH)–C–); 4.11 (1H, d, J = 3.0, –C–(CH)–(CH)–C–); 4.30 (3Н, s, CH3);
7.18-7.46 (4H, m, Ar); 7.48-7.57 (1Н, m, Ar); 7.65 (2H, d, J = 8.7, 4-NO2Ph); 7.67 (3H, d, J = 12.5,
8.7, Ar); 8.26 (2H, d, J = 8.7, 4-NO2Ph).
2-[7-(4-nitrophenyl)spyro[1,4-diazabicyclo-hept-4-en-3,1'-cyclohexane]-5-yl]benzimidazoles 2b
and 2d. Suspension of 2 mmol of correspondent chalcone dibromide in 50 ml of methanol was mixed
with 2 mmol of corresponding diamine in a 100 ml round-bottom flask. The flask was heated to
complete dissolution of solid phase, than 1.5 ml of triethylamine was added. After this reaction mixture
was boiled during 30 minutes, then left to stay 24 hours at room temperature. The precipitate was
filtered off, washed with a small amount of methanol.
Compound 2b. Yield 63%, mp 150°C (crystallized from methanol). 1Н NMR, δ, ppm (J, Hz): 1.65
(10H, m, (CH2)5; 2.09 (1H, d, J = 3.0 –C–(CH)–(CH)–C–); 2.60 (1H, d, J = 3.0, –C–(CH)–(CH)–C–);
2.63 (1H, d, J = 12.3, =N–C–(CH2)–N–); 3.62 (1H, d, J = 12.3, =N–C–(CH2)–N–); 7.19 (2Н, s, Ar);
7.35 (2H, s, Ar); 7.43 (2Н, d, J = 8.4, 4-NO2Ph); 7.75 (1H, d, J = 6.0, Ar); 8.17 (2H, d, J = 8.7, 4-
NO2Ph).
Compound 2d. Yield 72%, mp 135°C (crystallized from methanol). 1Н NMR, δ, ppm (J, Hz): 1.67
(10H, m, (CH2)5; 2.15 (1H, d, J = 3.0 –C–(CH)–(CH)–C–); 2.63 (1H, d, J = 3.0, –C–(CH)–(CH)–C–);
2.65 (1H, d, J = 12.3, =N–C–(CH2)–N–); 3.57 (1H, d, J = 12.3, =N–C–(CH2)–N–); 4.30 (3Н, s, CH3);
7.41 (2Н, broad, Ar); 7.55 (2H, d, J = 8.4, 4-NO2Ph); 7.81 (2Н, d, J = 6.0, Ar); 8.09 (2H, d, J = 8.7, 4-
NO2Ph).
Analogous procedure was applied for the synthesis of compounds 3a-g, 4a-g.
1
Compound 3а. Yield 65%, mp 171-172°C (crystallized from methanol). Н NMR, δ, ppm (J, Hz):
1.37 (3Н, s, CH3); 1.38 (3Н, s, CH3); 2.25 (1H, d, J = 12.1, =N–C–(CH2)–N–); 2.66 (1H, d, J = 2.3, –
C–(CH)–(CH)–C–); 2.73 (1H, d, J = 2.3, –C–(CH)–(CH)–C–); 3.56 (1H, d, J = 12.1, =N–C–(CH2)–N–
); 7.40 (3Н, m, Ph); 7.50 (2H, d, J = 8.4, 4-NO2Ph); 7.79 (2Н, m, Ph); 8.23 (2H, d, J = 8.4, 4-NO2Ph).
13C NMR, δ, ppm: 3.3, 26.6, 29.7, 38.8, 51.8, 54.6, 60.1, 124.0, 126.2, 127.7, 128.8, 130.7, 137.7,
147.5, 147.8, 162.0.
1
Compound 3b. Yield 63%, mp 159-161°C (crystallized from methanol). Н NMR, δ, ppm (J, Hz):
1.90-2.44 (6Н, m, (CH2)3); 2.92 (1H, d, J = 2.3, –C–(CH)–(CH)–C–); 2.99 (1H, d, J = 13.4, =N–C–
(CH2)–N–); 3.07 (1H, d, J = 2.3, –C–(CH)–(CH)–C–); 3.36 (1H, d, J = 13.4, =N–C–(CH2)–N–); 7.36-
7

ACCEPTED MANUSCRIPT
7.44 (3Н, m, Ph); 7.48 (2H, d, J = 8.9, 4-NO2Ph); 7.71-7.81 (2Н, m, Ph); 8.21 (2H, d, J = 8.9, 4-
13
NO2Ph). C NMR, δ, ppm: 15.3, 34.5, 37.9, 39.1, 44.8, 51.4, 58.1, 123.9, 126.5, 127.9, 128.8, 130.6,
138.2, 147.2, 147.3, 161.0.
1
Compound 3с. Yield 60%, mp 156-157°C (crystallized from methanol). Н NMR, δ, ppm (J, Hz):
1.55-2.09 (8Н, m, (CH2)4); 2.60 (1H, d, J = 12.5, =N–C–(CH2)–N–); 2.73 (1H, d, J = 2.2, –C–(CH)–
(CH)–C–); 2.91 (1H, d, J = 2.2, –C–(CH)–(CH)–C–); 3.41 (1H, d, J = 12.5, =N–C–(CH2)–N–); 7.31-
7.45 (3Н, m, Ph); 7.50 (2H, d, J = 8.4, 4-NO2Ph); 7.77 (2Н, m, Ph); 8.23 (2H, d, J = 8.5, 4-NO2Ph).
13С NMR, δ, ppm: 24.5, 24.8, 39.1, 49.8, 56.7, 65.1, 124.1, 124.4, 126.2, 126.6, 127.7, 128.9, 129.1,
129.3, 130.3, 130.7, 138.2, 147.2, 161.0.
Compound 3d. Yield 69%, mp 140°C (crystallized from methanol). 1Н NMR, δ, ppm (J, Hz): 1.37-
1.90 (10Н, m, (CH2)5); 2.15 (1H, d, J = 12.2, =N–C–(CH2)–N–); 2.66 (1H, d, J = 3.0, –C–(CH)–(CH)–
C–); 2.72 (1H, d, J = 3.0, –C–(CH)–(CH)–C–); 3.69 (1H, d, J = 12.2, =N–C–(CH2)–N–); 7.35-7.43
(3Н, m, Ph); 7.50 (2H, d, J = 8.8, 4-NO2Ph); 7.76-7.86 (2Н, m, Ph); 8.24 (2H, d, J = 8.8, 4-NO2Ph).
13С NMR, δ, ppm: 3.3, 21.5, 22.4, 26.2, 36.4, 38.0, 52.2, 56.6, 59.3, 124.0, 126.2, 127.6, 128.8, 130.8,
137.7, 147.5, 147.8, 161.9.
Compound е 3е. Yield 58%, mp 131-133°C (crystallized from methanol). 1Н NMR, δ, ppm (J, Hz):
1.30-1.94 (12Н, m, (CH2)6); 2.09 (1H, d, J = 12.1, =N–C–(CH2)–N–); 2.61 (1H, br. s, –C–(CH)–(CH)–
C–); 2.71 (1H, br. s, –C–(CH)–(CH)–C–); 3.65 (1H, d, J = 12.2, =N–C–(CH2)–N–); 7.40 (3Н, m, Ph);
7.50 (2H, d, J = 8.3, 4-NO2Ph); 7.81 (2Н, m, Ph); 8.23 (2H, d, J = 8.3, 4-NO2Ph). 13С NMR, δ, ppm:
3.3, 22.2, 23.3, 29.8, 30.0, 37.1, 49.0, 52.5, 58.9, 60.0, 123.9, 126.2, 127.7, 128.8, 130.7, 137.8, 147.5,
147.8, 161.0.
Compounds 3f and 3g were obtained as a mixture of positional isomers according to their NMR
spectra. GC-MS indicated their presence in molar ratio 1:1. Attempts to separate them one from
another were unsuccessful. The spectral characteristics of the mixture were given below.
Compound 3f. Yield 63%, mp 180-181°C (crystallized from methanol). 1Н NMR, δ, ppm: 0.39-0.48
(m), 0.51-0.65 (m), 0.87-0.96 (m), 2.21-2.30 (m), 2.60-2.63 (m), 2.64-2.70 (m), 2.72-2.78 (m),3.01-
3.09 (m), 3.18-3.25 (m), 3.47-3.52 (m), 3.52-3.56 (m), 3.79-3.86 (m), 7.34-7.52 (m),7.71-7.77 (m),
7.78-7.83 (m), 8.18-8.27 (m). 13С NMR, δ, ppm: 1.6, 2.0, 3.3, 14.7, 15.1, 39.5, 46.3, 52.5, 123.8,
124.0, 126.2, 126.5, 127.7, 128.1, 128.7, 128.8, 130.3, 130.8, 139.2, 147.4, 162.3.
1
Compound 3g. Yield 65%, mp 170-173°C (crystallized from methanol). Н NMR, δ, ppm: 2.27-
2.37 (m), 2.53-2.63 (m), 2.76-2.87 (m), 3.16-3.21 (m), 3.64-3.73 (m), 3.75-3.81 (m), 3.88-3.95 (m),
4.58-4.66 (m), 4.84-4.91 (m), 7.28-7.53 (m), 7.54-7.64 (m), 7.84-7.90 (m), 7.90-7.96 (m), 8.20-8.29
(m). 13С NMR, δ, ppm: 39.2, 48.2, 50.8, 53.8, 58.1, 59.8, 124.0, 124.1, 126.3, 126.7, 127.0, 127.3,
127.5, 127.6, 127.7, 128.2, 128.8, 128.9, 129.1, 130.7, 131.3, 137.0, 138.9, 142.9, 143.0, 147.2, 147.5,
162.9, 164.9.
1
Compound 4а. Yield 48%, mp 135°C (crystallized from methanol). Н NMR, δ, ppm (J, Hz): 1.36
(3Н, s, CH3); 1.37 (3Н, s, CH3); 2.23 (1H, d, J = 12.1, =N–C–(CH2)–N–); 2.63 (1H, d, J = 3.0, –C–
(CH)–(CH)–C–); 2.68 (1H, d, J = 3.0, –C–(CH)–(CH)–C–); 3.54 (1H, d, J = 12.1, =N–C–(CH2)–N–);
7.34-7.43 (3Н, m, Ph); 7.45 (2H, d, J = 8.1, 4-CNPh); 7.66 (2Н, m, Ph); 7.79 (2H, d, J = 8.1, 4-CNPh).
13С NMR, δ, ppm: 26.5, 29.6, 38.8, 39.5, 52.0, 54.6, 60.2, 110.3, 119.3, 126.2, 127.4, 128.9, 130.9,
132.8, 137.2, 145.6, 162.0.
Compound 4b. Yield 44%, mp 130°C (crystallized from methanol). 1Н NMR, δ, ppm (J, Hz): 1.96-
2.44 (6Н, m, (CH2)3); 2.89 (1H, d, J = 2.1, –C–(CH)–(CH)–C–); 2.99 (1H, d, J = 13.3, =N–C–(CH2)–
N–); 2.99 (1H, br. s, –C–(CH)–(CH)–C–); 3.31 (1H, d, J = 13.3, =N–C–(CH2)–N–); 7.35-7.40 (3Н, m,
Ph); 7.42 (2H, d, J = 7.9, 4-CNPh); 7.63 (2Н, m, Ph); 7.77 (2H, d, J = 7.9, 4-CNPh). 13С NMR, δ, ppm:
15.4, 34.5, 37.9, 39.0, 44.9, 51.3, 58.1, 110.5, 119.3, 126.5, 127.7, 128.9, 130.6, 132.7, 138.3, 145.1,
161.1.
Compound 4с. Yield 52%, mp 128°C (crystallized from methanol). 1Н NMR, δ, ppm (J, Hz): 1.55-
2.08 (8Н, m, (CH2)4); 2.59 (1H, d, J = 12.5, =N–C–(CH2)–N–); 2.70 (1H, d, J = 2.5, –C–(CH)–(CH)–
C–); 2.86 (1H, d, J = 2.4, –C–(CH)–(CH)–C–); 3.39 (1H, d, J = 12.5, =N–C–(CH2)–N–); 7.34-7.42
13
(3Н, m, Ph); 7.44 (2H, d, J = 8.2, 4-CNPh); 7.65 (2Н, m, Ph); 7.78 (2H, d, J = 7.9, 4-CNPh). С
NMR, δ, ppm: 24.5, 24.9, 39.1, 49.9, 56.7, 65.1, 110.3, 119.3, 126.2, 127.5, 128.9, 130.7, 132.8, 137.7,
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145.5, 161.2.
Compound 4d. Yield 56%, mp 122°C (crystallized from methanol). 1Н NMR, δ, ppm (J, Hz): 1.40-
2.09 (10Н, m, (CH2)5); 2.13 (1H, d, J = 12.1, =N–C–(CH2)–N–); 2.63 (1H, d, J = 2.9, –C–(CH)–(CH)–
C–); 2.66 (1H, d, J = 2.8, –C–(CH)–(CH)–C–); 3.67 (1H, d, J = 12.1, =N–C–(CH2)–N–); 7.34-7.43
(3Н, m, Ph); 7.44 (2H, d, J = 8.2, 4-CNPh); 7.65 (2H, d, J = 8.2, 4-CNPh); 7.81 (2Н, d, J = 6.8, Ph);
8.24. 13С NMR, δ, ppm: 21.3, 22.4, 26.2, 36.1, 37.7, 49.0, 52.3, 56.5, 59.4, 110.3, 119.4, 126.1, 127.4,
128.2, 130.8, 132.7, 137.3, 145.7, 162.0.
1
Compound 4е. Yield 58%, mp 131-133°C (crystallized from methanol). Н NMR, δ, ppm (J, Hz):
1.33-2.04 (12Н, m, (CH2)6); 2.07 (1H, d, J = 12.6, =N–C–(CH2)–N–); 2.59 (1H, d, J = 2.2, –C–(CH)–
(CH)–C–); 2.62 (1H, d, J = 2.2, –C–(CH)–(CH)–C–); 3.63 (1H, d, J = 12.2, =N–C–(CH2)–N–); 7.34-
7.42 (3Н, m, Ph); 7.44 (2H, d, J = 8.0, 4-CNPh); 7.65 (2Н, m, Ph); 7.80 (2H, d, J = 7.2, 4-CNPh). 13С
NMR, δ, ppm: 22.0, 23.2, 30.4, 30.6, 36.4, 46.1, 49.0, 52.5, 58.5, 59.8, 110.2, 119.4, 126.1, 127.4,
128.8, 130.9, 132.8, 137.4, 145.7, 160.8.
The analogous presence of two positional isomers in molar ratio 1:1 was observed for compounds 4f
and 4g using NMR and GC-MS.
Compound 4f. Yield 55%, mp 148-150°C (crystallized from methanol). 1H NMR, δ, ppm: 0.36-0.48
(m), 0.50-0.64 (m), 0.84-0.96 (m), 2.16-2.31 (m), 2.53-2.75 (m), 2.96-3.12 (m), 3.16-3.27 (m), 3.39-
3.56 (m), 3.73-3.86 (m), 4.52-4.68 (m), 7.31-7.47 (m), 7.57-7.68 (m), 7.69-7.75 (m), 7.76-7.84 (m).
13С NMR, δ, ppm: 1.8, 1.9, 2.2, 2.4, 14.6, 14.9, 40.0, 46.0, 51.7, 53.3, 56.4, 59.2, 111.3, 111.4, 118.8,
126.0, 126.3, 126.6, 127.0, 128.5, 128.6, 130.2, 130.8, 132.4, 132.5, 136.7, 138.9, 144.0, 144.4, 163.0,
163.8.
1
Compound е 4g. Yield 60%, mp 119-121°C (crystallized from methanol). Н NMR, δ, ppm: 1.35-
1.49 (m), 2.27-2.36 (m), 2.52-2.61 (m), 2.72-2.82 (m), 3.04-3.14 (m), 3.13-3.17 (m), 3.59-3.69 (m),
3.70-3.73 (m), 3.85-3.93 (m), 4.57-4.64 (m), 4.83-4.89 (m), 7.27-7.48 (m), 7.49-7.54 (m), 7.63-7.69
(m), 7.84-7.89 (m), 7.89-7.94 (m). 13С NMR, δ, ppm: 9.0, 39.0, 46.0, 48.2, 51.0, 53.8, 58.2, 59.8,
110.4, 110.5, 119.3, 126.4, 126.8, 127.0, 127.3, 127.5, 127.6, 128.0, 128.7, 128.9, 129.0, 130.6, 131.3,
132.8, 132.9, 137.1, 139.0, 143.0, 143.1, 145.1, 145.3, 163.0, 165.0.
X-ray structural investigation of compound 3d. Monoclinic crystals, C22H23N3O2, 20°С, a=
9.5038(8), b= 10.531(1), c= 18.790(2) Å, β= 98.041(9)°, V = 1862.1(3) Å3, Mr = 361.43, Z = 4, space
group P21/n, dcalc= 1.289 g/cm3, μ(MoKα) = 0.084 mm-1, F(000) = 768. Intensities of 18357 reflections
(5429 independent, Rint=0.044) were measured on the «Xcalibur-3» diffractometer (graphite
monochromated MoKα radiation, CCD detector, ω-scaning, 2Θmax = 60).
The structure was solved by direct method using SHELXTL software [15]. Positions of the
hydrogen atoms were located from electron density difference maps and refined by “riding” model
with Uiso = 1.2Ueq of the carrier atom. Full-matrix least-squares refinement against F2 in anisotropic
approximation for non-hydrogen atoms using 5333 reflections was converged to wR2 = 0.138 (R1 =
0.052 for 2833 reflections with F>4σ(F), S = 0.925). The final atomic coordinates, and crystallographic
data for molecule 3d have been deposited to Cambridge Crystallographic Data Centre and are available
on request quoting the deposition number CCDC 1857585.
Acknowledgement
This investigation was supported in part by the science projects of the Ministry of Education and
Science of Ukraine (0115U000484 and 116U000835).
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Cyclocondensation of chalcones (di)bromides with vicinal diamines results in formation of a
series of fused aziridinylpiperazines.
Asymmetric vicinal diamines on the base of methylcyclohexane core result in formation of only
one positional isomer with spiro-attached cyclohexane moiety.
The title compounds demonstrate expressed solid state photochromism with highly contrast
color change.