Directed synthesis of new spiro-fused photochromes of diarylethene series

Article abstract of DOI:10.1007/s10593-015-1731-4

[MediaObject not available: see fulltext.] The reaction of tetracyanoethylated 1,2-diarylethanones with morpholine was used for directed synthesis of spiro-fused diarylethenes, 8-amino-1-imino(oxo)-6-morpholino-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles. The intermediates in this process were tetracyanoalkanone salts. The formation of spiranes was sensitive to the nature of aromatic substituents at the carbonyl group of 3,4-diaryl-4-oxobutane-1,1,2,2-tetracarbonitriles. The obtained spiro-fused diarylethenes exhibited photochromic properties.

Full text of DOI:10.1007/s10593-015-1731-4

DOI 10.1007/s10593-015-1731-4
Chemistry of Heterocyclic Compounds 2015, 51(6), 518–525
Directed synthesis of new spiro-fused photochromes
of diarylethene series
Mikhail Yu. Belikov1*, Mikhail Yu. Ievlev1, Irina V. Belikova1,
Oleg V. Ershov1, Viktor A. Tafeenko2, Marina D. Surazhskaya3
1 Chuvash State University named after I. N. Ulyanov,
Moskovskiy Ave. 15, Cheboksary 428015, Russia; е-mail: belikovmil@mail.ru
2 M. V. Lomonosov Moscow State University,
Leninskie Gory 1, Bldg. 3, Moscow 119991, Russia; е-mail: tafeenko-victor@yandex.ru
3 N. S. Kurnakov Institute of General and Inorganic Chemistry,
Leninskiy Ave. 31, Moscow 119991, Russia; е-mail: mars1741@yandex.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2015, 51(6), 518–525
Submitted May 13, 2015
Accepted June 4, 2015
The reaction of tetracyanoethylated 1,2-diarylethanones with morpholine was used for directed synthesis of spiro-fused diarylethenes,
8-amino-1-imino(oxo)-6-morpholino-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles. The intermediates in this process were
tetracyanoalkanone salts. The formation of spiranes was sensitive to the nature of aromatic substituents at the carbonyl group of
3,4-diaryl-4-oxobutane-1,1,2,2-tetracarbonitriles. The obtained spiro-fused diarylethenes exhibited photochromic properties.
Keywords: 1,2-diarylethanones, diarylethenes, tetracyanoethylene, ethene linker, non-bonded strain, photochromes, spiro compounds,
spirofusion, tetracyanoethylation.
Diarylethenes (DAE, dihetarylethenes) are subject to
intense study due to the possibility of using these
compounds as photosensitive components in various
applications, in particular, information processing,1–4
optical switches for organic electronics,5–7 and biosensors.8
The potential for practical applications of DAE in the
indicated areas motivate synthetic studies of photochromes
with precisely designed photophysical parameters, such as
thermal stability of the photoinduced form,9–15 quantum
yield of the forward and reverse photoreaction,16–20 and the
phototransformation cyclicity.21–24 An important direction
of study, with the goal of improving the practical
characteristics of DAE, is the development of synthetic
methods for obtaining DAE with intramolecular non-
covalent interactions and steric hindrance.25–31 One of the
methods for creating a non-covalent interaction in DAE is
the introduction of spiro-fused structures at the ethene
linker. We should note that only isolated examples of spiro-
fused DAE are known.31–33 However, based on the current
data, it is expected that the presence of spiro-fused moiety
at the ethene linker could be used to confer certain useful
properties to DAE. For example, some of the best forward
quantum reaction yields have been demonstrated for spiro-
fused DAE specifically due to the non-covalent interaction,
caused by the presence of spirofusion.31 By introducing or
removing spirofusion it may be possible to tune the ability
of DAE to undergo photochromic transformations.32 The
introduction of spirofusion may also be used for the
preparation of DAE with several photoswitchable
fragments.33 The presented data show the importance of
developing new approaches to the synthesis of
diarylethenes featuring a rare combination of structural
moieties, in particular spiro-fused systems. With this in
mind, we set out to expand the range of available methods
for the synthesis of DAE with spirofusion at the ethene
linker.
Recently we demonstrated a new approach to the
synthesis of photochromic DAE, based on the transforma-
tions of intermediates obtained by reactions of tetracyano-
ethylene (TCNE) with 1,2-diarylethanones, namely, 3,4-di-
aryl-4-oxobutane-1,1,2,2-tetracarbonitriles.34 At the same
time, it is known that 4-oxoalkane-1,1,2,2-tetracarbonitriles
based on some aliphatic and alkylaromatic ketones react
with amines forming spiro compounds, containing an
0009-3122/15/5106-0518©2015 Springer Science+Business Media New York
518

Chemistry of Heterocyclic Compounds 2015, 51(6), 518–525
Scheme 1
alkylarylethene or dialkylethene fragment.35,36 The
introduction of tetracyanoethylated 1,2-diaryl ketones into
these reactions allows to obtain DAE with spirofusion at
the ethene linker.
Our initial objective was the preparation of tetra-
cyanoethylated 1,2-diarylethanones 2a,b. In order to
achieve this, tetracyanoethylene was reacted with the
simplest 1,2-diaryl ketone, deoxybenzoin (1a), as well as
its analog, 2-(2,5-dimethylthiophen-3-yl)-1-phenylethanone
(1b) (Scheme 1).
This reaction resulted in the formation of 3-aryl-4-oxo-
4-phenylbutane-1,1,2,2-tetracarbonitriles 2a,b in 83–87%
yields. The selection of ketones 1а,b as the starting materials
for tetracyanoethylation was based on the presence of a
phenyl substituent at the carbonyl group. It is known that
adducts of TCNE with other 1-phenyl ketones can be
converted to spiro compounds by the action of amines.35 The
next step in the synthesis of DAE with spirofusion in the
ethene bridge structure was the interaction of compounds
2а,b with morpholine. The final products of this reaction
were identified as 8-amino-4-aryl-1-imino-6-(morpholin-4-yl)
-3-phenyl-2-oxa-7-azaspiro[4.4]-nona-3,6,8-triene-9-
carbonitriles 4а,b (Scheme 1). The reaction was accompanied
by the formation of tetracyanoalkanone salts, morpholinium
3-aryl-4-oxo-4-phenyl-1,1,2,2-tetracyanobutan-1-ides 3а,b,
which were produced by the initial interaction of СН acids
2а,b with morpholine. These salts can be isolated as
individual compounds and transformed either to the starting
ketones 2а,b by the action of HCl or converted to spiranes
4а,b in the presence of morpholine.
It should be noted that salts similar to compound 3 can
rarely be isolated and characterized. For example, such
salts are known for cations of copper and silver, as well as
ammonium.37 This is the first case when salts of this type
with organic cations have been isolated and characterized,
although their presence has been implied at the initial stage
of many transformations of 4-oxoalkane-1,1,2,2-tetra-
carbonitriles in basic media.35,38–41
Compounds 3a–c were found to be unstable in solutions,
therefore suitable NMR spectra could not be acquired. The
actual spectra contained a multitude of signals, which could
not be assigned. The structure of salts could be confirmed
by IR spectroscopy, mass spectrometry, and X-ray
structural analysis. The IR spectra contained carbonyl
group absorption bands at 1689–1694 cm–1, strong cyano
group bands of the C–(CN)2 fragment in the region of 2149–
2155 cm–1, and unconjugated CN group bands at 2243–
2247 cm–1. Mass spectral fragment ions corresponding to
the loss of cyanide and hydride from the structure of anion
([M–O(CH2)2NH–HCN]+) were detected with 19–41%
intensity.
The structure of salts 3a–c was unequivocally proved by
monocrystal X-ray structural analysis, using the salt 3c as
example (Fig. 1). The crystal structure featured an association
between morpholinium cation and two neutral morpholine
molecules, as shown in Figure 2. The molecular triad was
linked with strong hydrogen bonds: N(5)–H(51)···N(6i)
(1+x, y, z) and N(5)–H(5) ···N(7ii) (1–x, 1–y, –z). Taking
into account the possibility of proton transfer in the
crystalline state from one morpholine molecule to another,
the cation in this compound can be assigned with the
structure [O(CH2)2NH]3H+ (Fig. 2).
A possible reason why spirane 4c was not formed might
be the deactivation of carbonyl group by electron-donating
2,5-dimethylthienyl fragment, adjacent to the carbonyl
group of ketone 2c. In the case of analogous structure 2b,
containing a phenyl substituent instead of 2,5-dimethyl-
thienyl fragment at position 4, the formation of spirane 4b
was observed. This fact demonstrated the sensitivity of
The DAE with 1,2-dithienyl fragments is known to have
particularly promising practical properties.3 For this reason,
our next objective was to convert 3,4-bis(2,5-dimethyl-
thiophen-3-yl)-4-oxobutane-1,1,2,2-tetracarbonitrile 2c,
the synthesis of which we have described previously,34 to
the spiro compound 4с. We found that in this case the
process stopped at the stage of morpholinium 3,4-bis(2,5-di-
methylthiophen-3-yl)-1,1,2,2-tetracyano-4-oxobutan-1-ide
3c (Scheme 2).
Scheme 2
519

Chemistry of Heterocyclic Compounds 2015, 51(6), 518–525
+
Figure 2. The structure of cation [O(CH2)2NH]3H in crystal of
compound 3c with atoms represented by thermal vibration
ellipsoids of 50% probability.
-ethanone (6). The next stage was synthesis of 1-(5-chloro-
2-methylthiophen-3-yl)-2,2-dihydroxyethanone (7) by the
action of selenium oxide in 1,4-dioxane on acetylthiophene
6. The subsequent reaction of glyoxal 7 with 2,5-di-
methylthiophene in anhydrous benzene in the presence of
SnCl4 led to 1-(5-chloro-2-methylthiophen-3-yl)-2-hydroxy-2-
(2,5-dimethylthiophen-3-yl)ethanone (8). The acyloin 8
was then converted to 1-(5-chloro-2-methylthiophen-3-yl)-
2-(2,5-dimethylthiophen-3-yl)ethanone (1d) by the action
of methyl thioglycolate in trifluoroacetic acid with
subsequent treatment of reaction mixture with aqueous
methanol solution of NaOH. The interaction of ketone 1d
with tetracyanoethylene leading to the formation of adduct
2d was accomplished in 1,4-dioxane analogously to the
preparation of compounds 2a–c.
Figure 1. Molecular structure of compound 3c with atoms
represented by thermal vibration ellipsoids of 50% probability.
reactions leading to spiranes 4 to the nature of aromatic
substituent at the carbonyl group of compounds 2.
It has been proposed that the presence of electron-
withdrawing substituents in the thiophene ring adjacent to
the CO group of compounds 2 should facilitate the
formation of spiranes with the structure 4. For this reason,
reaction with morpholine was performed with the custom
synthesized 4-(5-chloro-2-methylthiophen-3-yl)-3-(2,5-dimethyl-
thiophen-3-yl)-4-oxobutane-1,1,2,2-tetracarbonitrile 2d,
containing a chlorine atom at position 5 of the thiophene
ring at the СО group (Scheme 3). As expected, the ketone 2d
could be converted to an analog of spiranes 4a,b, 8-amino-
3-(5-chloro-2-methylthiophen-3-yl)-4-(2,5-dimethylthiophen-
3-yl)-1-imino-6-(morpholin-4-yl)-2-oxa-7-azaspiro[4.4]nona-
3,6,8-triene-9-carbonitrile 4d, albeit at lower yield (44%).
We obtained the ketone 1d for the first time according to
Scheme 3 from 2-chloro-5-methylthiophene (5). Com-
pound 5 was acylated in anhydrous benzene in the presence of
SnCl4, leading to the known42 1-(5-chloro-2-methylthiophen-3-yl)
The structure of spiranes 4а,b,d was confirmed by IR
1
spectroscopy, Н and 13C NMR spectroscopy, as well as
mass spectrometry. The mass spectra contained characte-
ristic molecular ion peaks with 2–100% intensity.
According to IR spectra, the structures contained amino and
imino groups (bands at 3130–3343 cm–1) and conjugated
cyano groups (strong bands at 2165–2171 cm–1). According
1
to the obtained data, there was duplication of Н and 13C
NMR signals. It was found that 1Н NMR spectra contained
amino group singlets at 7.05–7.21 ppm and imine proton
Scheme 3
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Chemistry of Heterocyclic Compounds 2015, 51(6), 518–525
1
peaks at 9.09–9.41 ppm. A notable feature in the Н NMR
forms in solution phase (Scheme 5). This assumption was
supported by the fact that we have previously described
compounds of type 4'' for structures that are analogous to
spiranes 4.39,40 This equilibrium may be the reason for the
less pronounced photochromic properties of spiranes 4.
In order to exclude the processes presented in Scheme 5,
we hydrolyzed the imino group in compounds 4а,b,d with
dilute HCl (Scheme 6). As a result, we obtained 8-amino-
3,4-diaryl-(6-morpholin-4-yl)-1-oxo-2-oxa-7-azaspiro[4.4]-
nona-3,6,8-triene-9-carbonitriles 10a,b,d.
spectra was the broadening of morpholine ring proton signals
in the region of 3.30–3.90 ppm. The 13C NMR signals of the CN
group carbon were observed in the spectrum of compound 4b at
119.0 and 119.2 ppm, while the signals of the C=NH group
and C atoms at positions 2 and 5 of the 3Н-pyrrole ring were
in the region of 163.8–172.2 ppm. The duplication of NMR
signals was explained by E- and Z-configuration of the
C=NН bond, in which the proton at the nitrogen atom can
assume various positions. A similar situation was earlier
described by us for analogs of compounds 4.35,36
The structure of spiranes 10a,b,d was confirmed by IR
1
The synthesized spiranes 4b,d, containing a potentially
photosensitive 1,2-diarylethene fragment, were found to be
photochromic (Scheme 4). The irradiation of colorless
solutions in MeCN with UV light at 312 nm caused the
formation of colored photoinduced form 9b,d. The
opposite transition, fading of the color, occurred under
irradiation of the solution with visible light.
spectroscopy, Н and 13С NMR spectroscopy, and mass
spectrometry. The mass spectra contained molecular ion
peaks with 8–76% intensity. The most informative IR
absorption bands were at 1785–1791 cm–1, corresponding
to the stretching vibrations of С=O bonds in the γ-lactone
moiety, as well as amino group absorption bands at 3154–
3345 cm–1, and strong bands due to conjugated cyano
groups at 2165–2173 cm–1. In contrast to 1Н and 13С
Compounds 4b,d, compared to known photochromes,1
were characterized by a low number of cycles: by-product
absorption bands appeared in the spectra after 2–3 cycles of
reversible phototransformations. A possible reason for the
poor photochromic properties may be molecular contact
between the morpholine fragment and aromatic substituent
at position 4 of the spiro system 4.
1
spectra of imines 4a,b,d, H and 13C NMR signals of
spiranes 10a,b,d were not duplicated due to the absence of
E/Z-isomerism after the C=NH→C=O conversion. There were
1Н NMR signals due to amino groups and aromatic protons at
7.23–7.46 ppm. Importantly, morpholine ring proton signals,
similarly to the case of spiranes 4a,b,d, appeared as
broadened peaks at 3.20–3.80 ppm. This observation
indicated the presence of a steric contact between the
morpholine fragment and aromatic substituent also in the
case of hydrolyzed derivatives 10a,b,d. In the case of
spiranes 10a,b,d, 13С NMR signals had similar chemical
shifts to the respective 13С NMR signals of compounds 4b,
indicating the preservation of carbon atom skeleton during
the treatment of imines 4 with hydrochloric acid.
This assumption was confirmed by the broadening of
morpholine ring proton H NMR signals, which appeared
1
as one significantly broadened signal at 3.30–3.90 ppm.
Morpholine proton signals would typically exist as two
triplets or two broadened singlets.43 The possibility of steric
contact between the NCH2 proton of the morpholine ring and
the neighboring substituents was also confirmed by X-ray
structural analysis data for an analog of compounds 4.39
The structure of spiranes 4 also allowed to propose the
existence of equilibrium between the enol 4' and ketone 4''
The structure of spiranes 10a,b,d was unequivocally
proved by X-ray structural analysis in the case of
compound 10а (Fig. 3). The X-ray structural data for
compound 10а showed the presence of non-bonded strain in
the molecule, caused by the position of the proton at the
morpholine С(9) carbon relative to the o-H atom at the phenyl
ring С(20) carbon, located within 2.23 Å of each other. This
distance was less than the sum of van der Waals radii for these
atoms. We should also note that the morpholine fragment in the
crystal of spirane 10а was disordered.
Scheme 4
The tautomeric processes described in Scheme 5 are
impossible for compounds 10. The structures 10, similarly
Scheme 5
Scheme 6
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Chemistry of Heterocyclic Compounds 2015, 51(6), 518–525
to their analogs 4, had unremarkable photochromic
left in a sealed vessel for 2–5 days at room temperature,
while checking for the presence of TCNE (formation of a
blue hydroquinone complex). After the disappearance of
TCNE, the solution was cooled to 0–5°С, treated with ice
water (100 ml), and stirred until the formation of
homogeneous suspension. The obtained precipitate was
filtered off, washed with water and cold 5:1 water–
isopropanol mixture.
3-(2,5-Dimethylthiophen-3-yl)-4-oxo-4-phenylbutane-
1,1,2,2-tetracarbonitrile (2b). Yield 1.49 g (83%), light-
beige powder, mp 68–69°С (decomp.). IR spectrum, ν, cm–1:
2252 (CN), 1692 (С=O). 1H NMR spectrum, δ, ppm: 2.32
(3H, s, СH3); 2.76 (3H, s, СH3); 5.79 (1H, s, СH); 5.94 (1H,
s, СH); 6.63 (1H, s, СH); 7.62–7.71 (3Н, m, Н Ph); 7.50–7.57
(2Н, m, Н Ph). Found, %: C 67.09; H 3.90; N 15.67.
C20H14N4OS. Calculated, %: C 67.02; H 3.94; N 15.63.
4-(5-Chloro-2-methylthiophen-3-yl)-3-(2,5-dimethyl-
thiophen-3-yl)-4-oxobutane-1,1,2,2-tetracarbonitrile (2d).
Yield 1.79 g (87%), light-beige powder, mp 86–87°С
(decomp.). IR spectrum, ν, cm–1: 2250 (CN), 1696 (С=O).
1H NMR spectrum, , ppm: 2.37 (3H, s, СH3); 2.72 (3H, s,
СH3); 2.73 (3H, s, СH3); 5.61 (1H, s, СH); 5.73 (1H, s,
СH); 6.67 (1H, s, СH); 7.11 (1H, s, СH). Found, %:
C 55.30; H 3.13; N 13.59. C19H13N4ClOS2. Calculated, %:
C 55.27; H 3.17; N 13.57.
properties: substantial photodegradation was observed
already after 2–3 cycles of phototransformations. This fact
pointed to the key importance of steric contact between
morpholine and the aryl substituent, likely hindering the
phototransformations according to Scheme 4. The
assumption that spirofusion at the ethene linker may create
obstacles to photochromism in 1,2-dithienyl-substituted
DAE was confirmed by literature data.32 Other examples of
molecules with steric contacts between substituents in the
aryl group and substituents at the ethene linker also show
the absence of photochromism.44
Thus, we have developed a new method for the
synthesis of diarylethenes with spirofusion at ethene linker.
Non-bonded strain has been found in the molecules of
these compounds, caused by steric contact between atoms of
the spiro-fused systems. The presence of such
intramolecular contact may be one of the reasons for poor
photochromic properties of the obtained diarylethenes.
Experimental
UV spectra were recorded on an SF-2000
spectrophotometer for MeCN solutions. IR spectra were
obtained on an FSM-1202 FT-IR spectrometer for thin film
1
samples (suspensions in Nujol). Н and 13C NMR spectra
Preparation of salts 3а–d (General method).
Morpholine (0.13 g, 1.5 mmol) was added to a vigorously
stirred and cooled (–10°С) solution of the respective
3,4-diaryl-4-oxobutane-1,1,2,2-tetracarbonitrile 1 (0.5 mmol)
in EtOAc (2 ml). The stirring was continued for 30–60 min. The
precipitate started to form during stirring, and the precipitation of
salts was complete after 2–3 h. The solid product was filtered off,
washed with cooled Et2O, and dried in a vacuum desiccator until
constant mass.
Morpholinium 4-oxo-3,4-diphenyl-1,1,2,2-tetracyano-
butan-1-ide (3a). Yield 0.174 g (86%), light-brown
powder, mp 89–90°С (decomp.). IR spectrum, ν, cm–1: 2246
(CN), 2151 (CN), 1694 (C=O). Mass spectrum, m/z (Irel,%):
297 [M–O(CH2)2NH–HCN]+ (23), 105 (100). Found, %:
C 70.13; H 5.17; N 16.90. C24H21N5O2. Calculated, %:
C 70.06; H 5.14; N 17.02.
Morpholinium 3-(2,5-dimethylthiophen-3-yl)-4-oxo-
4-phenyl-1,1,2,2-tetracyanobutan-1-ide (3b). Yield 0.160 g
(72%), light-brown powder, mp 86–87°С (decomp.). IR
spectrum, ν, cm–1: 2243 (CN), 2149 (CN), 1691 (C=O). Mass
spectrum, m/z (Irel, %): 331 [M–O(CH2)2NH–HCN]+ (19), 105
(100). Found, %: C 64.76; H 5.23; N 15.63. C24H23N5O2S.
Calculated, %: C 64.70; H 5.20; N 15.72.
were acquired on a Bruker DRX-500 instrument (500 and
125 MHz, respectively) in acetone-d6 (compounds 2b,d)
and DMSO-d6 (the rest of the compounds), with TMS as
internal standard. Mass spectra were recorded on a Finnigan
МАТ INCOS-50 instrument (electron impact energy 70 eV).
Elemental analysis was performed on a vario MICRO cube
CHN-analyzer. Melting points were determined on an M-560
apparatus. The reaction progress and purity of the obtained
compounds were controlled by TLC on Sorbfil PTSH-AF-A-UF
plates (eluent 9:1 EtOAc–hexane), visualization under UV
light, with iodine vapor, or thermal decomposition. Tetracarbo-
nitriles 2а,c were synthesized according to a published
procedure.34
Preparation of 4-aryl-3-(2,5-dimethylthiophen-3-yl)-4-oxo-
butane-1,1,2,2-tetracarbonitriles 2b,d (General method).
TCNE (0.64 g, 5 mmol) and two drops of conc. HCl were
added to a solution of the corresponding 1,2-diarylethanone
1b,d (5 mmol) in 1,4-dioxane (20 ml). The obtained
colored solution was stirred for 2–3 min at 35–40°С, until
complete dissolution of TCNE. The reaction mixture was
Morpholinium 3,4-bis(2,5-dimethylthiophen-3-yl)-4-oxo-
1,1,2,2-tetracyanobutan-1-ide (3c). Yield 0.160 g (67%),
light-brown powder, mp 92–93°С (decomp.). IR spectrum, ν,
cm–1: 2247 (CN), 2155 (CN), 1689 (C=O). Mass spectrum,
m/z (Irel, %): 365 [M–O(CH2)2NH–HCN]+ (41), 139 (100).
Found, %: C 60.17; H 5.28; N 14.49. C24H25N5O2S2.
Calculated, %: C 60.10; H 5.25; N 14.60.
Morpholinium 4-(5-chloro-2-methylthiophen-3-yl)-
3-(2,5-dimethylthiophen-3-yl)-4-oxo-1,1,2,2-tetracyano-
butan-1-ide (3d). Yield 0.167 g (63%), light-brown
powder, mp 81–82°С (decomp.). IR spectrum, ν, cm–1:
Figure 3. Molecular structure of compound 10а with atoms
represented by thermal vibration ellipsoids of 50% probability.
522

Chemistry of Heterocyclic Compounds 2015, 51(6), 518–525
2249 (CN), 2153 (CN), 1686 (C=O). Mass spectrum,
1-(5-Chloro-2-methylthiophen-3-yl)ethanone
(6).
m/z (Irel, %): 387 [M(37Cl)–O(CH2)2NH–HCN]+ (9), 385
[M(35Cl)–O(CH2)2NH–HCN]+ (28), 161 (35), 159 (100).
Found, %: C 55.33; H 4.48; N 13.92. C24H25N5O2S2.
Calculated, %: C 55.25; H 4.43; N 14.01.
Solution of SnCl4 (31.8 g, 0.122 mol) in anhydrous
benzene (30 ml) was added dropwise to a solution of
2-chloro-5-methylthiophene (5) (13.2 g, 0.1 mol) and Ac2O
(10.2 g, 0.1 mol) in anhydrous benzene (100 ml), while
keeping the temperature not higher than 15–20°С. The
reaction mixture was stirred for 4 h at room temperature,
then poured into a mixture of ice water (220 ml) and conc.
HCl (55 ml). The organic layer was separated, washed with
water (100 ml), saturated NaHCO3 solution (100 ml), and
again with water (100 ml). The solvent was removed by
evaporation and the residue was distilled at reduced pres-
sure, collecting the fraction with bp 140–150°C (25 mmHg).
Care should be taken to prevent crystallization of the
product in the condenser. Yield 13.6 g (78%), transparent
crystals, mp 30–31°С. IR spectrum, ν, cm–1: 1695 (C=O).
1H NMR spectrum, , ppm: 2.45 (3H, s, СH3); 2.60 (3H, s,
COСH3); 7.51 (1H, s, Н thiophene). Mass spectrum, m/z
(Irel, %): 176 [М(Cl37)]+ (18), 174 [М(Cl35)]+ (51), 161
[М(Cl37)–CH3]+ (42), 159 [М(Cl35)–CH3]+ (98), 133 [М(Cl37)–
Ac]+ (6), 131 [М(Cl35)–Ac]+ (18), 43 [CH3СО]+ (100), 15
[CH3]+ (59). Found, %: C 48.09; H 4.11. C7H7ClOS.
Calculated, %: C 48.14; H 4.04.
Preparation of spiranes 4а,b,d (General method).
Morpholine (0.13 g, 1.5 mmol) was added to a stirred and
cooled (–10°С) solution of the respective 3,4-diaryl-4-oxo-
butane-1,1,2,2-tetracarbonitrile 1 (0.5 mmol) in EtOAc
(4 ml). The process was accompanied by the formation of
yellow-orange solution. The reaction mixture was left in a
sealed vessel at –10°С. The solids that formed after 3–5 days
were filtered off and washed with cold EtOAc.
8-Amino-1-imino-6-(morpholin-4-yl)-3,4-diphenyl-2-oxa-
7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitrile (4а). Yield
0.156 g (76%), light-beige powder, mp 155–156°С (decomp.).
IR spectrum, ν, cm-1: 3146–3343 (NH, NH2), 2169 (CN).
UV spectrum, λmax, nm (log ε): 339 (3.80). 1H NMR spectrum,
, ppm: 3.35–3.80 (8H, m, Н morpholine); 7.10 (1.1H, s) and
7.17 (0.9H, s, NH2); 7.18–7.22 (10Н, m, H Ph); 9.18 (0.55H,
s) and 9.41 (0.45H, s, NH); isomer ratio 55:45. Mass
spectrum, m/z (Irel, %): 411 [М]+ (4), 105 (45), 77 (100).
Found, %: C 70.11; H 5.11; N 17.09. C24H21N5O2. Calculated,
%: C 70.06; H 5.14; N 17.02.
1-(5-Chloro-2-methylthiophen-3-yl)-2,2-dihydroxy-
ethanone (7). A solution of SeO2 (7.7 g, 0.070 mol) in a
mixture of 1,4-dioxane (50 ml) and water (3 ml) was
stirred, heated to 50–55°С, and treated by the addition of
acetylthiophene 6 (10.2 g, 0.059 mol). The obtained mixture
was stirred and refluxed for 5 h, then cooled to room
temperature, and the precipitated selenium was removed by
filtration. The filtrate was evaporated under reduced
pressure (25 mmHg), the residue was recrystallized from
distilled water. Yield 7.65 g (63%), transparent crystals, mp
117–118°С. IR spectrum, ν, cm–1: 3453 (ОН), 1695 (CO).
1H NMR spectrum, , ppm (J, Hz): 2.63 (3H, s, СH3); 5.36
(1H, t, J = 6.5, СH); 5.71 (2H, d, J = 6.5, 2OH); 7.58 (1H, s,
Н thiophene). Mass spectrum, m/z (Irel, %): 208 [М(Cl37)]+
(1), 206 [М(Cl35)]+ (3), 161 [М(Cl37)–CH(OH)2]+ (41), 159
[М(Cl35)–CH(OH)2]+ (100). Found, %: C 40.58; H 3.44.
C7H7ClO3S. Calculated, %: C 40.69; H 3.41.
8-Amino-1-imino-4-(2,5-dimethylthiophen-3-yl)-
6-(morpholin-4-yl)-3-phenyl-2-oxa-7-azaspiro[4.4]nona-
3,6,8-triene-9-carbonitrile (4b). Yield 0.154 g (69%),
light-beige powder, mp 131–132°С (decomp.). IR
spectrum, ν, cm-1: 3130–3339 (NH, NH2), 2165 (CN). UV
1
spectrum, λmax, nm (log ε): 316 (3.96). H NMR spectrum,
, ppm: 1.92 (1.62H, s) and 1.94 (1.38H, s, СH3); 2.37
(1.38H, s) and 2.39 (1.62H, s, СH3); 3.30–3.90 (8H, m,
Н morpholine); 6.44 (0.46H, s) and 6.48 (0.54H, s,
Н thiophene); 7.05 (1.08H, s) and 7.15 (0.92H, s, NH2);
7.30–7.40 (5Н, m, Н Ph); 9.16 (0.54H, s) and 9.38 (0.46H,
s, NH); isomer ratio 54:46. 13C NMR spectrum, , ppm:
13.8; 13.9; 15.1; 45.4; 46.5; 60.5; 65.5; 65.6; 66.5; 68.5;
110.1; 110.4; 119.0; 119.2; 124.9; 125.1; 126.2; 126.7;
126.8; 128.7; 128.8, 129.8; 135.3; 136.2; 136.3; 148.6;
149.0; 163.8; 168.4; 169.9; 170.3; 171.3; 172.2. Mass
spectrum, m/z (Irel, %): 445 [М]+ (100), 340 (20), 105 (15),
77 (19). Found, %: C 64.74; H 5.17; N 15.74. C24H23N5O2S.
Calculated, %: C 64.70; H 5.20; N 15.72.
1-(5-Chloro-2-methylthiophen-3-yl)-2-hydroxy-2-(2,5-di-
methylthiophen-3-yl)ethanone (8). 2,5-Dimethylthiophene
(1.85 g, 0.016 mol) was added to a solution of glyoxal
hydrate 7 (3.10 g, 0.015 mol) in anhydrous benzene (75 ml),
followed by slow dropwise addition of SnCl4 (3.92 g, 0.015 mol).
The obtained solution was stirred for 4 h at room tempera-
ture. The mixture was then poured into ice water (150 ml),
phases were separated, the aqueous layer was extracted
with Et2O (3×30 ml). The combined organic phases were
washed with water (100 ml), saturated NaHCO3 solution
(100 ml), water (100 ml) and dried over anhydrous MgSO4.
The solvents were removed under vacuum, the residue was
crystallized from п-C6H14. IR spectrum, ν, cm–1: 1691
8-Amino-3-(5-chloro-2-methylthiophen-3-yl)-1-imino-
4-(2,5-dimethylthiophen-3-yl)-6-(morpholin-4-yl)-2-oxa-
7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitrile (4d).
Yield 0.101 g (44%), light-beige powder, mp 125–127°С
(decomp.). IR spectrum, ν, cm–1: 3151–3322 (NH, NH2),
2171 (CN). UV spectrum, λmax, nm (log ε): 303 (3.85).
1H NMR spectrum, , ppm: 1.81 (1.71H, s) and 1.82
(1.29H, s, СH3); 2.02 (1.71H, s) and 2.03 (1.29H, s, СH3);
2.33 (1.29H, s) and 2.35 (1.71H, s, СH3); 3.30–3.85 (8H,
m, Н morpholine); 6.39 (0.43H, s) and 6.43 (0.57H, s,
Н thiophene); 6.87 (0.57H, s) and 6.89 (0.43H, s,
Н thiophene); 7.11 (1.14H, s) and 7.21 (0.86H, s, NH2);
9.09 (0.57H) and 9.36 (0.43H, s, NH); isomer ratio 57:43.
Mass spectrum, m/z (Irel, %): 499 [М(Cl35)]+ (2), 161 (33),
159 (100). Found, %: C 55.29; H 4.41; N 14.09.
C23H22N5ClO2S2. Calculated, %: C 55.25; H 4.43; N 14.01.
1
(C=O). Yield 3.36 g (75%), beige powder, mp 83–84°С. H
NMR spectrum, , ppm: 2.28 (3H, s, СH3); 2.35 (3H, s,
СH3); 2.57 (3H, s, СH3); 5.65 (1H, s, СH); 6.48 (1H, s,
Н thiophene); 7.40 (1H, s, Н thiophene); OH was
exchanged. Mass spectrum, m/z (Irel, %): 302 [М(Cl37)]+ (1),
300 [М(Cl35)]+ (3), 161 (6), 159 (18), 141 (100), 113 (53).
523

Chemistry of Heterocyclic Compounds 2015, 51(6), 518–525
Found, %: C 51.84; H 4.39. C13H13ClO2S2. Calculated, %:
(C=O). UV spectrum (MeCN), λmax, nm (log ε): 307 (3.83).
1H NMR spectrum, , ppm: 1.83 (3H, s, CH3); 2.00 (3H, s,
CH3); 2.36 (3H, s, CH3); 3.20–3.80 (8H, m, Н morpholine);
6.44 (1H, s, Н thiophene); 7.02 (1H, s, Н thiophene); 7.46
(2H, s, NH2). 13C NMR spectrum, , ppm: 13.7; 14.9; 15.2;
46.5; 57.5; 65.7; 66.8; 111.4; 118.2; 125.3; 125.4; 129.1;
131.2; 134.3; 135.5; 135.8; 139.8; 149.7; 170.2; 171.0;
173.5. Mass spectrum, m/z (Irel, %): 502 [М(Cl37)]+ (3), 500
[М(Cl35)]+ (8), 161 (35), 159 (100). Found, %: C 55.23;
H 4.16; N 11.28. C23H21ClN4O3S2. Calculated, %: C 55.14;
H 4.22; N 11.18.
X-ray structural investigation of salt 3c. Crystals
suitable for X-ray structural analysis were obtained by slow
evaporation of reaction mixture without stirring. Monocrystal
X-ray structural analysis of salt 3c was performed on a
STOE StadiVari Pilatus 100K diffractometer, using MoKα
radiation. The data collection and processing, determina-
tion and refinement of unit cell parameters were performed
with the STOE X-Area software suite. The structure was
solved by direct method, using the SHELXS-97 software
suite.45 The visual rendering of molecule in crystalline state
was performed with the DIAMOND program.46 The
complete X-ray structural data set for compound 3c was
deposited at the Cambridge Crystallographic Data Center
(deposit CCDC 1059042).
C 51.91; H 4.36.
1-(5-Chloro-2-methylthiophen-3-yl)-2-(2,5-dimethyl-
thiophen-3-yl)ethanone (1d). Acyloin 8 (1.38 g, 0.0046 mol)
was added to a stirred mixture of trifluoroacetic acid (6 ml)
and methyl thioglycolate (2.4 g, 0.023 mol). The obtained
dark-green solution was stirred for 30 min at room
temperature, then carefully diluted while stirring with cold
(5°С) solution of NaOH (9.0 g) in a mixture of MeOH
(25 ml) and water (25 ml). The obtained mixture was refluxed
for 2 h, then cooled to room temperature and diluted with ice
water (200 ml). The obtained precipitate was filtered off
under vacuum, washed with ice water until the washes
became neutral. Yield 1.08 g (83%), beige powder, mp 38–
39°С. IR spectrum, ν, cm–1: 2247 (CN), 1697 (С=O). 1H NMR
spectrum, , ppm: 2.22 (3H, s, СH3); 2.32 (3H, s, СH3); 2.59
(3H, s, СH3); 4.02 (2H, s, СH2); 6.48 (1H, s, Н thiophene);
7.62 (1H, s, Н thiophene). Mass spectrum, m/z (Irel, %): 286
[М(Cl37)]+ (19), 284 [М(Cl35)]+ (45), 161 (35), 159 (100).
Found, %: C 54.89; H 4.54. C13H13ClOS2. Calculated, %:
C 54.82; H 4.60.
Preparation of spiranes 10а,b,d (General method).
Suspension of the respective spirane 4а,b,d (0.2 mmol) in 5:1
water–isopropanol mixture (2 ml) was treated with 2–3 drops
of concentrated hydrochloric acid. The obtained suspension
was stirred for 3–4 h at room temperature until the reaction
was complete (TLC control), the precipitate that formed
was filtered off, washed with water and isopropanol.
8-Amino-6-(morpholin-4-yl)-1-oxo-3,4-diphenyl-2-oxa-
7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitrile (10a). Yield
75 mg (91%), white powder, mp 294–295°С (decomp.). IR
spectrum, ν, cm–1: 3154–3320 (NH2), 2165 (CN), 1788
(C=O). UV spectrum (MeCN), λmax, nm (log ε): 332 (3.62).
1H NMR spectrum, , ppm: 3.40–3.75 (8H, m,
Н morpholine); 7.23–7.45 (12H, m, Н Ph, NH2). 13C NMR
spectrum, , ppm: 46.3; 57.2; 65.7; 66.8; 110.8; 118.2;
126.1; 126.6; 127.0; 127.5; 128.8; 129.4; 129.6; 130.4; 148.7;
170.5; 171.1; 173.8. Mass spectrum, m/z (Irel,%): 412 [М]+ (17),
105 (92), 77 (100). Found, %: C 69.81; H 4.83; N 13.68.
C24H20N4O3. Calculated, %: C 69.89; H 4.89; N 13.58.
8-Amino-4-(2,5-dimethylthiophen-3-yl)-6-(morpholin-
4-yl)-1-oxo-3-phenyl-2-oxa-7-azaspiro[4.4]nona-3,6,8-
triene-9-carbonitrile (10b). Yield 77 mg (86%), white
powder, mp 275–276°С (decomp.). IR spectrum, ν, cm–1:
3161–3339 (NH2), 2170 (CN), 1791 (C=O). UV spectrum
X-ray structural investigation of spirane 10а. Crystals
suitable for X-ray structural analysis were obtained by slow
evaporation of compound 10а solution in a 5:1 mixture of
isopropanol–conc. HCl. Monocrystal X-ray structural
analysis of spirane 10a was performed on an Enraf-Nonius
CAD4 diffractometer. The complete X-ray structural data
set for compound 10а was deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 1058585).
This work received financial support from the Grants
Council of the President of Russian Federation (grant MK-
97.2014.3).
X-ray structural investigation of salt 3c was performed
by using equipment obtained with financial support from
the Development Program of the Moscow University and
within the framework of Cooperation Agreement between
the Department of Chemistry of M. V. Lomonosov Moscow
State University and the Chemistry and Pharmacy
Department of Chuvashia State University named after
I. N. Ulyanov.
1
(MeCN), λmax, nm (log ε): 318 (3.82). H NMR spectrum,
References
, ppm: 1.94 (3H, s, CH3); 2.39 (3H, s, CH3); 3.40–3.80
(8H, m, Н morpholine); 6.50 (1H, s, Н thiophene); 7.34–
7.44 (7H, m, Н Ph, NH2). 13C NMR spectrum, , ppm: 14.0;
15.7; 46.6; 57.4; 65.7; 66.9; 111.0; 118.7; 124.9; 125.2; 126.8;
128.9; 129.8; 135.1; 135.7; 136.4; 149.3; 170.3; 170.9;
173.7. Mass spectrum, m/z (Irel, %): 446 [М]+ (79), 105
(100), 77 (98). Found, %: C 64.65; H 4.90; N 12.64.
C24H22N4O3S. Calculated, %: C 64.56; H 4.97; N 12.55.
8-Amino-3-(5-chloro-2-methylthiophen-3-yl)-4-(2,5-di-
methylthiophen-3-yl)-6-(morpholin-4-yl)-1-oxo-2-oxa-7-aza-
spiro[4.4]nona-3,6,8-triene-9-carbonitrile (10d). Yield
89 mg (89%), white powder, mp 266–267°С (decomp.). IR
spectrum, ν, cm–1: 3151–3345 (NH2), 2173 (CN), 1785
1. Irie, M.; Fukaminato, T.; Matsuda, K.; Kobatake, S. Chem.
Rev. 2014, 114, 12174.
2. Shirinian, V. Z.; Lonshakov, D. V.; Lvov, A. G.; Krayushkin, M. M.
Russ. Chem. Rev. 2013, 82, 511. [Usp. Khim. 2013, 82, 511.]
3. Irie, M. Chem. Rev. 2000, 100, 1685.
4. Myles, A. J.; Branda, N. R. Adv. Funct. Mater. 2002, 12, 167.
5. Natali, M.; Giordani, S. Chem. Soc. Rev. 2012, 41, 4010.
6. Orgiu, E.; Samorì, P. Adv. Mater. 2014, 26, 1827.
7. Minkin, V. I. Russ. Chem. Bull. 2008, 57, 687. [Izv. Akad.
Nauk, Ser. Khim. 2008, 673.]
8. Szymañski, W.; Beierle, J. M.; Kistemaker, H. A. V.; Velema, W. A.;
Feringa, B. L. Chem. Rev. 2013, 113, 6114.
9. Lonshakov, D. V.; Shirinian, V. Z.; Lvov, A. G.; Krayushkin, M. M.
Russ. Chem. Bull. 2012, 61, 1769. [Izv. Akad. Nauk, Ser.
524

Chemistry of Heterocyclic Compounds 2015, 51(6), 518–525
Mater. 2007, 19, 3479.
Khim. 2012, 1753.]
10. Yang, Y.; Xie, Y.; Zhang, Q.; Nakatani, K.; Tian, H.; Zhu, W.
Chem.–Eur. J. 2012, 18, 11685.
29. Shirinian, V. Z.; Lvov, A. G.; Yanina, A. M.; Kachala, V. V.;
Krayushkin, M. I. Chem. Heterocycl. Compd. 2015, 51, 234.
[Khim. Geterotsikl. Soedin. 2015, 51, 234.]
11. Liu, G.; Pu, S.; Wang, R. Org. Lett. 2013, 15, 980.
12. Kitagawa, D.; Sasaki, K.; Kobatake, S. Bull. Chem. Soc. Jpn.
2011, 84, 141.
30. Fukumoto, S.; Nakagawa, T.; Kawai, S.; Nakashima, T.;
Kawai, T. Dyes Pigm. 2011, 89, 297.
13. Takami, S.; Kobatake, S.; Kawai, T.; Irie, M. Chem. Lett.
2003, 32, 892.
31. Morinaka, K.; Ubukata, T.; Yokoyama, Y. Org. Lett. 2009,
11, 3890.
32. Kühni, J.; Belser, P. Org. Lett. 2007, 9, 1915.
33. Kobatake, S.; Kuma, S.; Irie, M. J. Phys. Org. Chem. 2007,
20, 960.
34. Belikov, M. Yu.; Ievlev, M. Yu.; Ershov, O. V.; Lipin, K. V.;
Legotin, S. A; Nasakin, O. E. Russ. J. Org. Chem. 2014, 50,
1372. [Zh. Org. Khim. 2014, 50, 1387.]
35. Belikov, M. Yu.; Ershov, O. V.; Lipovskaya, I. V.; Fedoseev, S. V.;
Nasakin, O. E. Russ. J. Org. Chem. 2013, 49, 864. [Zh. Org.
Khim. 2013, 49, 880.]
36. Belikov, M. Yu.; Ershov, O. V.; Lipovskaya, I. V.; Fedoseev, S. V.;
Lipin, K. V.; Nasakin O. E. Russ. J. Org. Chem. 2013, 49,
1195. [Zh. Org. Khim. 2013, 49, 1211.].
37. Carlucci, L.; Ciani, G.; Proserpio, D. M.; Sironi, A. Angew.
Chem., Int. Ed. 1996, 35, 1088.
38. Belikov, M. Yu.; Ershov, O. V.; Eremkin, A. V.; Kayukov, Ya. S.;
Nasakin O. E. Russ. J. Org. Chem. 2010, 46, 597. [Zh. Org.
Khim. 2010, 46, 604.]
39. Belikov, M. Yu.; Ershov, O. V.; Eremkin, A. V.; Nasakin, O. E.;
Tafeenko, V. A.; Nurieva, E. V. Tetrahedron Lett. 2011, 52, 6407.
40. Belikov, M. Yu.; Ershov, O. V.; Lipovskaya, I. V.; Eremkin, A. V.;
Nasakin, O. E. Russ. J. Org. Chem. 2011, 47, 1426. [Zh. Org.
Khim. 2011, 47, 1401.]
14. Kobatake, S.; Shibata, K.; Uchida, K.; Irie, M. J. Am. Chem.
Soc. 2000, 122, 12135.
15. Nakamura, S.; Yokojima, S.; Uchida, K.; Tsujioka, T.;
Goldberg, A.; Murakami, A.; Shinoda, K.; Mikami, M.;
Kobayashi, T.; Kobatake, S.; Matsuda, K.; Irie, M.
J. Photochem. Photobiol., A 2008, 200, 10.
16. Yamaguchi, T.; Irie, M. J. Photochem. Photobiol., A 2006,
178, 162.
17. Kitai, J.; Kobayashi, T.; Uchida, W.; Hatakeyama, M.;
Yokojima, S.; Nakamura, S.; Uchida, K. J. Org. Chem. 2012,
77, 3270.
18. Shirinian, V. Z.; Lvov, A. G.; Krayushkin, M. M.; Lubuzh, E. D.;
Nabatov, B. V. J. Org. Chem. 2014, 79, 3440.
19. Göstl, R.; Kobin, B.; Grubert, L.; Pätzel, M.; Hecht, S. Chem.–
Eur. J. 2012, 18, 14282.
20. Takeshita, M.; Mizukami, E.; Murakami, K.; Wada, Y.;
Matsuda, Y. Eur. J. Org. Chem. 2014, 3784.
21. Jean-Ruel, H.; Gao, M.; Kochman, M. A.; Lu, C.; Liu, L. C.;
Cooney, R. R.; Morrison, C. A.; Miller, R. J. D. J. Phys.
Chem., B 2013, 117, 15894.
22. Hanazawa, M.; Sumiya, R.; Horikawa, Y.; Irie, M. J. Chem.
Soc., Chem. Commun. 1992, 206.
23. Celani, P.; Ottani, S.; Olivucci, M.; Bernardi, F.; Robb, M. A.
J. Am. Chem. Soc. 1994, 116, 10141.
41. Fedoseev, S. V.; Ershov, O. V.; Belikov, M. Yu.; Lipin, K. V.;
Bardasov, I. N.; Nasakin, O. E.; Tafeenko, V. A. Tetrahedron
Lett. 2013, 54, 2143.
42. Chen, Y.; Zeng, D. X.; Fan, M. G. Org. Lett. 2003, 5, 1435.
43. Correia, C.; Carvalho, M. A.; Proença, M. F. Tetrahedron
2009, 65, 6903.
44. Li, X.; Ma, Y.; Wang, B.; Li, G. Org. Lett. 2008, 10, 3639.
45. Sheldrick, G. M. Acta Crystallogr., Sect. A: Found.
Crystallogr. 2008, A64, 112.
24. Jeong, Y.-C.; Park, D. G.; Lee, I. S.; Yang, S. I.; Ahn, K.-H.
J. Mater. Chem. 2009, 19, 97.
25. Kobatake, S.; Uchida, K.; Tsuchida, E.; Irie, M. Chem. Lett.
2000, 1340.
26. Morimitsu, K.; Shibata, K.; Kobatake, S.; Irie, M. J. Org.
Chem. 2002, 67, 4574.
27. Kitagawa, D.; Sasaki, K.; Kobatake, S. Bull. Chem. Soc. Jpn.
2011, 84, 141.
46. Diamond – Crystal and Molecular Structure Visualization;
Release 2.1d; Crystal Impact – Dr. H. Putz & Dr. K. Brandenburg
GbR: Bonn, 2000. http://www.crystalimpact.com/diamond
28. Kawai, S.; Nakashima, T.; Atsumi, K.; Sakai, T.; Harigai, M.;
Imamoto, Y.; Kamikubo, H.; Kataoka, M.; Kawai, T. Chem.
525