Synthesis and study of new photochromic unsymmetrical bis-spiropyrans with nonequivalent heteroarene fragments conjugated through the common 2H,8H-pyrano[2,3-f]chromene moiety

Article abstract of DOI:10.1016/j.molstruc.2020.128808

Four novel bis-spiropyrans possessing two different photochromic units based on indoline and 1,3-benzoxazine heterocycles which are connected through the common 2H,8H-pyrano[2,3-f]chromene moiety and modified with electron donating substituents were obtai

Full text of DOI:10.1016/j.molstruc.2020.128808

Journal Pre-proof
Synthesis and study of new photochromic unsymmetrical bis-spiropyrans with
nonequivalent heteroarene fragments conjugated through the common 2H, 8H-
pyrano[2,3-f]chromene moiety
Ilya V. Ozhogin, Eugene L. Mukhanov, Anatoly V. Chernyshev, Artem D. Pugachev,
Boris S. Lukyanov, Anatoly V. Metelitsa
PII:
S0022-2860(20)31133-9
DOI:
https://doi.org/10.1016/j.molstruc.2020.128808
MOLSTR 128808
Reference:
To appear in: Journal of Molecular Structure
Received Date: 27 February 2020
Revised Date: 8 June 2020
Accepted Date: 1 July 2020
Please cite this article as: I.V. Ozhogin, E.L. Mukhanov, A.V. Chernyshev, A.D. Pugachev, B.S.
Lukyanov, A.V. Metelitsa, Synthesis and study of new photochromic unsymmetrical bis-spiropyrans with
nonequivalent heteroarene fragments conjugated through the common 2H, 8H-pyrano[2,3-f]chromene
moiety, Journal of Molecular Structure (2020), doi: https://doi.org/10.1016/j.molstruc.2020.128808.
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Credit Author Statement.
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UV

BSP
IO
BO

Synthesis and study of new photochromic unsymmetrical bis-spiropyrans with
nonequivalent heteroarene fragments conjugated through the common
2H,8H-pyrano[2,3-f]chromene moiety
Ilya V. Ozhogin a, , Eugene L. Mukhanov a, Anatoly V. Chernyshev a, Artem D.
Pugachev a, Boris S. Lukyanova, Anatoly V. Metelitsaa
a Institute of Physical and Organic Chemistry, Southern Federal University, 194/2
Stachka ave., 344090, Rostov-on-Don, Russian Federation
Keywords: spiro compounds; bis-spiropyran; photochromism; 1,3-
benzoxazine; merocyanine; molecular switch; indoline
Abstract: Four novel bis-spiropyrans possessing two different photochromic
units based on indoline and 1,3-benzoxazine heterocycles which are connected
through the common 2H,8H-pyrano[2,3-f]chromene moiety and modified with
electron donating substituents were obtained by multistep synthesis starting with
2,4-dihydroxy-iso-phthalic aldehyde. The structure of the compounds was
1
confirmed by H and 13C NMR, FTIR and HRMS. All bis-spirocompounds
exhibited photochromic activity at room temperature. Investigation of
photochromic properties of bis-spiropyrans revealed that their once-opened
merocyanine isomers were more stable than the double-opened ones under
experimental conditions. It was also found that modification of the benzoxazine
moiety of the molecule with electron donating substituents along with introduction
of bulky benzyl group close to the oxazine spiro-center leads to an increase of the
merocyanine lifetime up to 148 s.
Corresponding author. E-mail: iozhogin@sfedu.ru
1

Spiropyrans (SP) represent one of the most interesting and well-studied
classes of the organic photochromic compounds [1-3], which can undergo
reversible isomerization between spirocyclic and merocyanine forms under the
activating irradiation. One of the main advantages of SPs over the other organic
photochromes is that their photoisomerization is accompanied by the significant
changes in the molecular structure, which lead not only to a redshift of the
absorption maxima, but also to the changes in other physical and chemical
characteristics, such as the dipole moment, fluorescent properties, the basicity, the
affinity to metal ions and other chemical species, etc. Applications of spiropyrans
include but are not limited by such areas as molecular electronics and photonics [4-
6], chemosensing [7-9], fluorescent microscopy and bio-imaging [10-13], targeted
drug delivery [14-17] and photopharmacology [18-19]. There are a lot of
recognized reviews devoted to spiropyrans in which one may get acquainted with
the main trends of their potential use [20-26].
In recent years, much attention has been paid to various multiphotochromes
[27-30], including bis-spiropyrans (BSP) – the compounds possessing two
potentially photochromic spiropyran fragments. The theoretically possible
consecutive or simultaneous opening of their pyran rings can lead to the formation
of different merocyanine isomers. Each of them should be characterized by
specific long-wavelength absorption maximum that allows us to consider these
compounds as potential components of multistable molecular switches. However,
the chemistry of BSP is a much less explored area compared to their mono-
spirocyclic analogues.
All the known bis- and poly-spirocompounds may be divided into several
structural groups differing by the manner in which photochromic centres are
connected in the molecule. The first group, more or less fully described in the
literature, consists of the molecules, in which there is no electronic conjugation
between two photoactive units. So, the spiropyran fragments are linked by the
simple σ-bond or other σ-linker [31-41]. In most of these cases, the absorption
2

spectra of the BSPs’ open forms differ a little from their mono-spiroanalogues,
indicating the opening of only one spirocycle.
Much more interest is aroused by the BSP, whose photoactive centers are
connected through the common π-electronic systems of their heteroarene [42-47]
or 2H-chromene moieties [48-52]. In this case, the opening of one of the pyran
rings leading to serious structural and electronic transformations of the molecule
must have a critical impact on the photodynamic characteristics of the second
photochromic fragment. In modern literature there are several references related to
the observation of the photochemically induced double opening of conjugated BSP
[46, 51], but these observations are not fully confirmed by experimental and
theoretical data. At the same time a critical factor determining the prospects of
using multiphotochromic compounds as multistate molecular switches is to have
the possibility of selective switching between the spectrally distinguishable
photoisomers.
In our previous studies we have reported and theoretically substantiated the
photoinduced opening of both pyran rings in a series of unsymmetrical indoline-
benzoxazine BSPs [53-56]. In these compounds the nonequivalent hetarene
moieties of the molecule are connected through a common conjugated 2H,8H-
pyrano[2,3-f]chromene fragment. The presence of unsymmetrical conjugated
system combined with seriously differing properties of the hetarene fragments
makes possible the existence of the several merocyanine isomers with different
conjugation chain length and different positions of the absorption bands in the
electronic spectra accordingly (Scheme 1).
3

IO
UV
, ∆
Vis
, ∆
Vis
UV
, ∆
Vis
UV
UV
, ∆
Vis
BO
DO
Scheme 1. Possible photoisomerization transformations of asymmetric BSPs
In the present study, we decided to synthesize BSPs with improved
photochromic properties resulted in the increased stability of their merocyanine
forms and therefore increased lifetimes. One of the well-known methods to
increase stability of merocyanine isomers of SP is an introduction of donor
substituents into the hetarene fragment. This fact may be explained due to the
delocalization of the positive charge, appearing in the corresponding fragment of
the molecule after the reaction of the pyran ring opening. The other way to
stabilize merocyanine which was realized by us is an introduction of bulky
substituent at the closest position to the benzoxazine spiro-centre. This
modification should create steric hindrance for the thermal recyclization reaction.
Thus, this work was aimed at synthesis and investigation of new BSPs (1),
containing methyl or methoxy groups at different positions of the benzoxazine
moiety and methyl or benzyl group linked to the nitrogen atom of the oxazine
cycle (Table 1).
4

Table 1. Structure and numbering of target bis-spiropyrans (1)
R1
R2
R3
Me
H
H
Me
a
b
c
4'
3'
5'
6'
5
Me
Me
Me
6
8
10'
7
R2
9'
7''
6'
H
OMe
OMe
R1
(1)
4''
5''
H
CH2Ph
d
2. Experimental
2.1. Materials and spectroscopic methods
All reagents were purchased from Alfa Aesar or Merck and used as received.
Organic solvents used were purified and dried according to standard methods.
1
13
NMR H and C spectra were recorded on a Bruker DPX-250 (250 MHz)
spectrometer at the Scientific and Educational Laboratory of Resonance
Spectroscopy, Department of Natural and High Molecular Compounds Chemistry
of Southern Federal University. The signals were assigned relatively to the signals
of residual protons of the deuterated solvent (CDCl3, δ = 7.26 ppm). IR spectra of
compounds were recorded on a Varian Excalibur 3100 FT-IR by the partial
internal reflection method. High-resolution mass spectra were obtained from a
TOF mass spectrometer Bruker micrOTOF with an ESI source. Melting points
were determined on a Fisher-Jones apparatus (Fisher Scientific Co). Elemental
analysis was carried out by a conventional method [57].
2.1.1 Spectral and photokinetic studies
The electronic absorption spectra and kinetic curves of thermal reactions of
the studied compounds were recorded on an "Agilent 8453" spectrophotometer
equipped with a temperature-controlled cell holder. Irradiation light was brought
5

into the thermostatic cell compartment at 90° from a 200W high-pressure mercury
lamp "Newport" equipped with glass filters for the allocation of mercury lines.
The values of the rate constants of the reverse thermal reactions were
determined from the dependence of the optical densities at the maxima of the long-
wavelength absorption bands of merocyanine isomers on the time of bleaching of
the solution according to the equation corresponding to the monoexponential
nature of the attenuation:
τ1
D = D∞ + D1e−t /
,
where D is current optical density value; D∞ is the equilibrium optical density
in the absence of irradiation; D0 is the maximum optical density; t is time, s; τ1 is
the lifetime of the merocyanine form.
2.2. Synthetic methods
2,3,7-Trimethyl-1,3-benzoxazin-4-onium perchlorate (5a),
2,3,8-
Trimethyl-1,3-benzoxazin-4-onium perchlorate (5b), 2,3-Dimethyl-8-methoxy-
1,3-benzoxazine-4-onium perchlorate (5с) and 3-Benzyl-8-methoxy-2-methyl-
1,3-benzoxazine-4-onium perchlorate (5d) were obtained from 4-methyl-, 3-
methyl- or 3-methoxysalicylic acid as white crystalline solids according to the
previously described procedure [58] and used further without characterization.
Yields: 5.50 g (95%) for (5a); 5.21 g (90%) for (5b); 5.38 g (88%) for (5c); 6.87 g
(90%) for (5d).
3,7-Dimethyl-8'-formyl-7'-hydroxy-4-oxo-spiro[1,3-benzoxazine-2,2'-
chromene] (7a). 2.90 g (0.01 mol) of perchlorate (5a) was added to a hot solution
of 1.83 g (0.011 mol) of aldehyde (2) in 10 mL of glacial acetic acid. The reaction
mixture was heated at reflux for 7–10 min, then sealed and left overnight. The
precipitated bright yellow styryl salt (6a) was filtered and washed with dry diethyl
ether (3 x 15 mL). Dry salt was placed in absolute diethyl ether (50 mL) and an
equimolar amount of triethylamine was added dropwise. After a day of staying in
the dark, the ether was decanted, the solvent was distilled off and the residue was
6

chromatographed on SiO2 with chloroform as the eluent. Yield 1.010 g (30%). mp
о
176–178 С. IR spectrum, ν, cm-1: 1683 (С=О); 1636, 1608 (С=С); 949, 929
(Сspiro–О ). NMR 1H (CDCl3) δ, ppm (J, Hz): 2.32 (3Н, s, 7- СН3), 3.15 (3Н, s, N-
СН3), 5.95 (1Н, d, J = 9.8, 3′-Н), 6.60 (1Н, d, J = 8.6, 6′-Н), 6.67 (1Н, s, 8-Н), 6.9
(1Н, d, J = 9.8, 4′-Н ), 6.98 (1Н, d, J = 7.9, 6-Н), 7.36 (1Н, d, J = 8.6, 5′-Н), 7.91
(1Н, d, J = 7.9, 5-Н), 9.84 (1Н, s, 8′-СНО), 11.69 (1Н, s, 7′-ОН). Anal. calc. for
C19H15NO5: C 67.65; H 4.48; N 4.15. Found: C 67.56; H 4.50; N 4.12.
3,8-Dimethyl-8'-formyl-7'-hydroxy-4-oxo-spiro[1,3-benzoxazine-2,2'-
chromene] (7b) was obtained by the method used for the synthesis of (7a) starting
о
with 2.90 g (0.01 mol) of compound (5b). Yield 977 mg (29%). mp 168–170 С.
IR spectrum, ν, cm-1: 1677 (С=О); 1647, 1600 (С=С); 949, 921 (Сspiro–О ). NMR
1H (CDCl3) δ, ppm (J, Hz): 2.01 (3Н, s, 8- СН3), 3.17 (3Н, s, N-СН3), 5.98 (1Н, d,
J = 9.8, 3′-Н), 6.60 (1Н, d, J = 8.6, 6′-Н), 6.92 (1Н, d, J = 9.8, 4′-Н), 7.07 (1Н, t, 6-
Н), 7.30 (1Н, d, 7-Н), 7.37 (1Н, d, J = 8.6, 5′-Н), 7.88 (1Н, d, 5-Н), 9.78 (1Н, s, 8′-
СНО), 11.68 (1Н, bs, 7′-ОН). Anal. calc. for C19H15NO5: C 67.65; H 4.48; N 4.15.
Found: C 67.54; H 4.49; N 4.11.
8'-Formyl-7'-hydroxy-8-methoxy-3-methyl-4-oxo-spiro[1,3-benzoxazine-
2,2'-chromene] (7c) was obtained by the method used for the synthesis of (7a)
starting with 3.06 g (0.01 mol) of compound (5c). Yield 777 mg (22%). mp 157–
159 оС. IR spectrum, ν, cm-1: 1679 (С=О); 1641, 1594 (С=С); 946, 921 (Сspiro–О ).
NMR 1H (CDCl3) δ, ppm (J, Hz): 3.14 (3Н, s, N-СН3), 3.74 (3Н, s, 8-OСН3), 5.97
(1Н, d, J = 9.8, 3′-Н), 6.59 (1Н, d, J = 8.6, 6′-Н), 6.94 (1Н, d, J = 9.8, 4′-Н), 7.03-
7.13 (2Н, m, 6-Н, 7-H), 7.36 (1Н, d, J = 8.6, 5′-Н), 7.63 (1Н, d, 5-Н), 9.85 (1Н, s,
8′-СНО), 11.69 (1Н, s, 7′-ОН). Anal. calc. for C19H15NO6: C 64.58; H 4.28; N
3.96. Found: C 64.48; H 4.30; N 3.92.
3-Benzyl-8'-formyl-7'-hydroxy-8-methoxy-4-oxo-spiro[1,3-benzoxazine-
2,2'- chromene] (7d) was obtained by the method used for the synthesis of (7a)
starting with 3.82 g (0.01 mol) of compound (5d). Yield 858 mg (20%). mp 148–
о
150 С. IR spectrum, ν, cm-1: 1678 (С=О); 1635, 1597 (С=С); 930 (Сspiro–О).
7

NMR 1H (CDCl3) δ, ppm (J, Hz): 3.80 (3H, s, 8-OСН3), 4.81 (1H, d, J = 15.8, N–
СН2), 5.06 (1H, d, J = 15.8, N–СН2), 5.89 (1H, d, J = 9.9, 3′-Н), 6.58 (1H, d, J =
8.6, 6′-Н), 6.89 (1H, d, J = 9.9, 4′-Н), 7.12 – 7.25 (7H, m, arom. H), 7.33 (1H, d, J
= 8.6, 5′-Н), 7.73 (1H, dd, J = 7.5, 1.7, 5-Н), 9.73 (1H, s, 8′-СНО), 11.67 (1H, s,
7′-ОН). Anal. calc. for C25H19NO6: C 69.92; H 4.46; N 3.26. Found: C 69.80; H
4.51; N 3.22.
1′′,3,3′′,3′′,7-Pentamethyl-4-oxo-dispiro(1,3-benzoxazine-2,2′-pyrano[2,3-
f]chromene-8′,2′′-indoline) (1a). 355 mg (1 mmol) of spiropyran (7a) and 274 mg
(1 mmol) of 3H-indolium perchlorate were dissolved in 10 mL of i-propanol. 0.1
mL (1.1 mmol) of piperidine was added dropwise to the resulting mixture under
heating. After 10 minutes of refluxing the mixture was left in a dark place for the
night. The formed precipitate was filtered off, washed with hexane and
chromatographed on silica gel with chloroform as an eluent. Yield 393 mg (80%).
mp 229–232 оС. IR spectrum, ν, cm-1: 1681 (С=О); 1644, 1606 (С=С); 933 (Сspiro
–
О ). NMR 1H (CDCl3) δ, ppm (J, Hz): 1.08 (3Н, s, 3′′-СН3), 1.24 (3Н, s, 3′′-СН3),
2.34 (3Н, s, 7-СН3), 2.65 (3Н, s, 1′′-СН3), 3.14 (3Н, s, 3-СН3), 5.51 (1H, dd, J =
10.4, 8.4 Hz, 9′-Н), 5.84 (1Н, d, J = 9.8, 3′-Н), 6.39 (1Н, d, J = 8.3, 6′-Н), 6.46
(1Н, dd, J = 2.4, 7.7, 7′′-Н), 6.71 (1H, s, 8-H), 6.73 (1H, dd, J = 10.3, 18.2, 10′-Н),
6.77 – 6.91 (2H, m, 5′′-Н (t, J = 7.8), 4′-Н (d, J = 9.8)), 6.91 – 7.07 (3H, m, 5′-Н,
13
6-H, 4′′-Н), 7.12 (1Н, t, J = 7.6, 6′′-Н), 7.95 (1Н, d, J = 7.9, 5-Н). NMR C
(CDCl3) δ, ppm: 20.0 (3′′-CH3), 21.9 (7-CH3), 25.8 (3′′-CH3), 28.8 (N(3)-CH3),
30.0 (N(1′′)-CH3), 51.8 (C-3′′), 104.7, 106.8 (C-7′′), 107.0, 107.6, 109.2 (C-6′),
110.9, 113.8, 115.5 (C-3′), 116.9 (C-7), 118.5 (C-9′), 119.2 (C-5′′), 121.5 (C-4′′),
122.5 (C-10′), 124.0 (C-6), 127.5 (C-5), 127.6 (C-6′′), 127.9 (C-5′), 129.6 (C-4′),
136.6, 145.7, 146.8, 148.0, 152.7, 156.2, 161.8 (C=O). HRMS (ESI-TOF) m/z
[M+H]+ calcd for C31H28N2O4 493.2122, found 493.2102.
1′′,3,3′′,3′′,8-Pentamethyl-4-oxo-dispiro(1,3-benzoxazine-2,2′-pyrano[2,3-
f]chromene-8′,2′′-indoline) (1b) was obtained by the method used for the
о
synthesis of (1a) from spiropyran (7b). Yield 363 mg (74%). mp 156–158 С. IR
8

spectrum, ν, cm-1: 1675 (С=О); 1604 (С=С); 950, 925 (Сspiro–О). NMR 1H (CDCl3)
δ, ppm (J, Hz): 1.07 (3Н, s, 3′′-СН3), 1.23 (3Н, s, 3′′-СН3), 2.0 (3Н, s, 8-СН3), 2.63
(3Н, s, 1′′-СН3), 3.17 (3Н, s, 3-СН3), 5.5 (1Н, dd, J = 10.4, 9′-Н), 5.9 (1Н, d, J =
9.7, 3′-Н), 6.39 (1Н, d, J = 8.4, 6′-Н), 6.48 (1Н, d, J = 7.7, 7′′-Н), 6.6-6.7 (1Н, dd,
J = 10.4, 10′-Н), 6.8 (1Н, t, J = 7.6, 6-Н), 6.9 (1Н, d, J = 9.7, 4′-Н), 6.95 (1Н, d, J
= 8.4, 5′-Н), 7.02 – 7.17 (3Н, m, 4′′-Н, 5′′-Н, 6′′-Н), 7.31 (1Н, d, J = 7.3, 7-Н),
13
7.91 (1Н, d, J = 7.6, 5-Н). NMR C (CDCl3) δ, ppm (J, Hz): 14.8, 20.0, 25.8,
28.8, 30.1, 51.7, 104.7, 106.8, 107.7, 109.2, 111.3, 115.8, 116.3, 118.7, 119.0,
119.2, 121.5, 122.3, 122.4, 125.2, 126.2, 127.6, 127.8, 129.8, 135.4, 136.6, 146.7,
147.99), 150.7, 156.2, 162.0. HRMS (ESI-TOF) m/z [M+H]+ calcd for C31H28N2O4
493.2122, found 493.2116.
8-Methoxy-1′′,3,3′′,3′′-tetramethyl-4-oxo-dispiro(1,3-benzoxazine-2,2′-
pyrano[2,3-f]chromene-8′,2′′-indoline) (1c) was obtained by the method used
for the synthesis of (1a) from spiropyran (7c). Yield 183 mg (36%). mp 149–151
1
оС. IR spectrum, ν, cm-1: 1681 (С=О); 1605 (С=С); 941, 925 (Сspiro–О). NMR H
(CDCl3) δ, ppm (J, Hz): 1.07 (3Н, s, 3′′-СН3), 1.22 (3Н, s, 3′′-СН3), 2.64 (3Н, s,
1′′-СН3), 3.15 (3Н, s, 3-СН3), 3.74 (3Н, s, 8-ОСН3), 5.51 (1Н, dd, J = 10.45, 9′-Н),
5.88 (1Н, d, J = 9.8, 3′-Н), 6.38 (1Н, d, J = 8.4, 6′-Н), 6.48 (1Н, d, J = 7.7, 7′′-Н),
6.70 (1Н, dd, J = 10.45, 10′-Н), 6.81 (1Н, t, J = 7.4, 5′′-Н), 6.90 (1Н, d, J = 9.8, 4′-
Н), 6.95 (1Н, d, J = 8.4, 5′-Н), 7.02 (1Н, d, J = 7.4, 4′′-Н), 7.07 – 7.17 (3Н, m, 7-
13
Н, 6-Н, 6′′-Н), 7.91 (1Н, d, 5-Н). NMR C (CDCl3) δ, ppm: 20.4 (3′′-CH3), 26.2
(3′′-CH3), 29.2 (N(1′′)-CH3), 30.3(N(3)-CH3), 52.1 (C-3′′), 56.9(O-CH3), 105.1,
107.2 (C-7′′), 107.4, 107.9, 109.6 (C-6′), 111.2, 115.4 (C-3′), 117.4, 117.7, 119.0
(9′-C), 119.4, 119.5 (C-5′′), 119.6 (C-5), 121.9 (C-4′′), 122.9 (C-10′), 128.0 (C-6′′),
128.4 (C-5′), 130.5 (C-4′), 137.0, 142.8, 147.2, 148.4, 148.6, 156.6, 162.0 (C=O).
HRMS (ESI-TOF) m/z [M+H]+ calcd for C31H28N2O5 509.2071, found 509.2051.
3-Benzyl-8-methoxy-1′′,3′′,3′′-trimethyl-4-oxo-dispiro(1,3-benzoxazine-
2,2′-pyrano[2,3-f]chromene-8′,2′′-indoline) (1d) was obtained by the method
used for the synthesis of (1a) from spiropyran (7d). Yield 175 mg (30%). mp 188–
9

о
1
191 С. IR spectrum, ν, cm-1: (С=О); (С=С); (Сspiro–О). NMR H (CDCl3) δ, ppm
(J, Hz): 1.10 (3H, d, J = 6.4, 3′′-СН3), 1.25 (3H, d, J = 8.8, 3′′-СН3), 2.66 (3H, d, J
= 5.3, N′′-СН3), 3.76 (3H, d, J = 1.8, 8-OCH3), 4.63 (1H, dd, J = 15.9, 3.5, N-
CH2), 5.19 (1H, dd, J = 16.0, 6.3, N-CH2), 5.50 (1H, dd, J = 10.4, 4.9, 9′-H), 5.77
(1H, d, J = 9.7, 3′-H), 6.37 (1H, d, J = 8.3, 6′-H), 6.50 (1H, d, J = 7.6, 7′′-H), 6.65
(1H, dd, J = 10.2, 10′-H), 6.82 (2H, m, 4′-H+5′′-H), 6.91 (1H, d, J = 8.4, 5′-H),
13
7.00 – 7.32 (m, 9H, arom. H), 7.76 (1H, dd, J = 7.2, 1.5, 5-H). NMR C (CDCl3)
δ, ppm: 20.0, 25.9, 28.8, 47.0, 51.8, 56.5, 104.7, 106.8, 107.3, 107.4, 109.2, 110.7,
114.6, 117.1, 117.5, 118.5, 119.0, 119.3, 121.5, 122.5, 122.6, 127.1, 127.4 (2C),
127.7, 128.0, 128.5 (2C), 130.2, 136.6, 137.8, 142.6, 146.5, 148.0, 148.3, 156.3,
161.7. HRMS (ESI-TOF) m/z [M+H]+ calcd for C37H32N2O5 585.2384, found
585.2353.
3. Results and discussion
3.1. Synthesis
Preparation of all target unsymmetrical BSP has been succeeded due to the
use of 2,4-dihydroxy-iso-phthalic aldehyde (2) synthesized from resorcinol by
Reimer – Thiemann excess formylation as it was described previously [59]. To
obtain the desired products (1a-d) a five-step synthesis has been carried out
(Scheme 2). N-substituted amides (4) were prepared from chloranhydrides of the
corresponding salicylic acids (3) by treatment of latter with the excess of
methylamine or benzylamine. Synthesis of cyclic 1,3-benzoxazin-4-onium
perchlorates (5) was carried out on the basis of methylamides (4) in acetic
anhydride by the action of perchloric acid [58], after which they were involved into
the condensation reaction with 2,4-dihydroxy-iso-phthalic aldehyde (2) to finally
isolate bright-colored styryl salts (6). Spiropyrans (7a-d) were obtained by the
action of triethylamine on the salts (6) in diethyl ether. With ortho-located formyl
and hydroxyl functions, compounds (7a-d) were found to be the derivatives of
salicylaldehyde and the precursors of bis-spirocompounds. Cyclocondensation of
10

these SPs with 1,2,3,3-tetramethyl-3H-indolium perchlorates in presence of
piperidine afforded the final BSPs (1a-d) with moderate to good yields.
O
O
O
3
3
R
NHR
O 1) SOCl
H
N
Ac O
2
2
-
4
ClO
+
O
1
1
2) R3NH2
1
HClO
R
R
OH
OH
(4)
4
R
2
2
2
R
R
R
(5)
(3)
O
CHO
3
R
OH
N
+
O
OH
1
CHO
R
(2)
CHO
OH
-
4
2
ClO
R
Et O
Et N
3
2
AcOH, HClO4
(6)
OH
3
R
4'
O
3'
5'
O
3
N
R
6'
N
O
O
5
+
-
O
1
N
ClO
R
O
O
4
6
8
10'
2
N
2
R
piperidine
7
9'
R
7''
1
R
OHC
6''
OH
4''
(7 a-d)
(1 a-d)
5''
R1= Me (a), H (b-d); R2 = Me (b), OMe (c-d), H (a); R3 = Me (a-c), CH2Ph (d)
Scheme 2. Synthesis of the target bis-spiropyrans (1)
3.2 FT-IR and NMR studies.
The structure of the obtained bis-spirocompounds was proved by IR, NMR 1H
13
and C spectroscopy. FT-IR spectra of the compounds demonstrate the presence
of strong absorption bands corresponding to the stretching vibrations of the
carbonyl group of the oxazinone fragment in the range of 1671-1686 cm-1, as well
as the stretching vibrations of the double bonds of -C=C- vinyl fragments of the
pyranochromene ring in the region of 1604-1647 cm-1. Absorption of the C(2')–
N(3) bond of the oxazine ring occurs in the 1351-1364 cm-1 range, while the
vibrations of the analogous C(8')–N(1'') bonds of the indoline part are located in
the range of 1275-1286 cm-1. Characteristic vibrational frequencies of Cspiro–O
11

bonds are observed at 923-958 cm-1. It should be noted that passing from oxazine
SPs (7) to BSPs (1), intensification of this band is observed, as well as its splitting
or appearance of the shoulder, which is associated with the appearance of the
second spirocycle in the molecule.
1
In the NMR H spectra of the obtained BSP, the characteristic signals of all
the proton-containing groups are present, which in accordance with the values of
the integrated absorption intensities, chemical shifts, and J-constants completely
correspond to the proposed structures. In the "strong" field of the spectra of BSP in
the range of 1.0 – 1.2 ppm, there are characteristic signals of hem-dimethyl groups
appearing in the form of two 3H singlet signals, which confirm the proximity to the
asymmetric carbon spiro-atom. The proton signals of the methyl groups bound to
the nitrogen atoms of the indoline and oxazine moieties are at about 2.6 and 3.1
ppm, respectively. The characteristic signals of the 3' and 9' protons of the
pyranochromene fragment appear as doublets near 5.8 – 6.0 and 5.5 ppm and form
AB-systems with protons 4' and 10' respectively. The values of the coupling
constants of these AB-systems lie in the ranges of 9.7 – 9.8 Hz for J3’,4’ and 10.4
Hz for J9’,10’ which are characteristic for cis-configuration of corresponding
protons.
In the spectrum of the compound (1d) the signals of the methylene protons of
benzyl fragment are manifested as nonequivalent split doublets in the 4.6 – 5.3
ppm region, which is due to the proximity of these fragments to asymmetric carbon
atoms and is also the evidence of the cyclic structure of the BSP molecules.
In order to correctly assign the signals of the aromatic protons, compounds
(1a) and (1c) were investigated using two-dimensional NMR techniques, namely
1
1
1
COSY H-1H (Fig. 1), NOESY H-1H (Fig. 2) and HMQC H-13C. The
combination of these methods made it possible to unambiguously identify the
signal of each aromatic proton in spectra.
12

Fig. 1. NMR spectrum COSY 1Н–1Н of the compound (1с), aromatic protons area.
Fig. 2. NMR spectrum NOESY 1Н–1Н of the compound (1с).
13

13
NMR C spectra of BSP (1a-d) showed the presence of signals from all the
carbon atoms of their molecules. In all of the spectra the signal of the C=O carbon
atom of benzoxazine moiety appears in the region of 161.7 – 162.0 ppm.
3.3 Photochemical investigation
Photochemical studies of BSPs (1) containing electron donating substituents
were carried out in acetonitrile solutions under irradiation with UV light (λ = 313
nm). The solutions of all the compounds at ambient temperature were colorless,
which indicates a complete shift of the thermal equilibrium towards the bis-
spirocyclic form under these conditions. This fact is consistent with our previous
studies [12]. Under the influence of activating irradiation, an appearance of the
long-wavelength maxima in the regions of 413–420 nm and 600–607 nm was
observed in the absorption spectra of BSP (Figs. 3 and S24). In previous works,
these absorption bands were assigned to the once opened merocyanine isomers (IO
and BO, Scheme 1) with help of DFT quantum chemical calculations.
Fig. 3. Absorption spectra changes of BSP (1a) under UV irradiation (λirr = 313 nm, dt =
10 s) in acetonitrile, T = 288 K.
14

The absence of a pronounced maximum at 505 nm, which is characteristic for
double opened (DO) isomers [53-55], can be associated with an increase in the
relative stability of the once opened isomers in polar acetonitrile due to the
solvation effects, which leads to an increase in the absorption maximum at 600 nm
and possible superposition with a less pronounced peak at about 505 nm. In some
cases, a maximum near 500 nm can be detected as a shoulder in the electron
absorption spectrum of BSP under conditions of photo-stationary equilibrium.
After irradiation of BSP solutions had been stopped, a thermal discoloration
reaction proceeded with a complete return of the spectra to their initial form (Fig.
4). Table 2 shows the spectral and kinetic characteristics of new BSPs modified
with EDG (1a-d), and synthesized earlier but not investigated under these
conditions BSPs (1e) and (1f) that do not contain EDG in their hetarene parts (R1 =
R2 = H; R3 = Me (1e), CH2Ph (1f)).
Fig. 4. Logarithm of the relative change in optical density at the maximum of the colored form of
BSPs during thermal relaxation
15

Table 2. Spectral and kinetic characteristics of target BSPs (1) in acetonitrile at 293 K.
ε (
λSmPax ) ,
M-1cm-1
τ MC
SP
max
λMmaCx , nm
, s
λ
, nm
Structure
205
248
275 sh
281 sh
328 sh
340 sh
72200
44040
25800
21300
2800
600
413
510 sh
97
(1a)
2200
206
249
275 sh
339 sh
73400
44300
26500
2300
600
415
98
(1b)
(1c)
(1d)
206
249
277
292
339
78400
45300
26700
22600
2400
600
420
106
148
206
249
276
289
341
65300
35800
21000
18400
2100
~605
326 sh
341
3270
2310
600
415
99
(1e)
16

CH Ph
2
O
N
O
246
37500
25930
22600
3460
O
274 sh
290 sh
325 sh
340
601
412
136.4
O
N
2370
(1f)
Analysis of the obtained data (Table 2, Figs. 3-4) showed that the
introduction of donor substituents in the benzoxazine fragment of the molecule, as
well as the replacement of the methyl substituent at the nitrogen atom of this
fragment with a more bulky benzyl group, leads to a decrease in the rate constant
of the reaction of thermal discoloration, and, accordingly, to an increase in the
lifetime of photoinduced isomers. Comparing the obtained results with the
photodynamic characteristics of the previously obtained compounds (1e, f), we can
conclude that the introduction of such a donor substituent as a methoxy group leads
to an increase of the lifetime τ of the once-opened isomers (IO and BO) in about
1.1 times. The introduction of a methyl group into the benzene ring of the
benzoxazine fragment does not lead to any increase in the lifetime of merocyanines
due to the weak +I donor effect of this substituent. At the same time, the
replacement of the methyl group by the benzyl substituent at the nitrogen atom of
the oxazine ring allowed us to increase the lifetime of merocyanine isomers by
40%. This fact can be explained by steric hindrance that arises during the thermal
recyclization reaction due to the presence of a bulky substituent in the immediate
vicinity to the spiro-atom. The longest lifetime in the series of BSP under the
study, equal to 148 s, was shown by compound (1d) equipped with a methoxy
group at position 8 and a benzyl substituent at the oxazine nitrogen atom. BSP (1a,
b) and (1e) differing only by presence or absence of an additional methyl group
have the same values of τ within the experimental error.
4. Conclusions
17

In summary, four novel spiropyrans of 1,3-benzoxazine series and four novel
unsymmetrical bis-spiropyrans with nonequivalent heteroarene fragments modified
with methyl, methoxy and benzyl groups were synthesized via multi-step
technique. The structure of the bis-spirocompounds was thoroughly studied and
1
13
confirmed by NMR H and C, FT-IR and high-resolved mass-spectroscopy or
elemental analysis. Photochemical studies revealed photochromic properties of
target bis-spiropyrans at room temperature in their acetonitrile solutions. It was
found out that the once opened merocyanine isomers of the compounds are more
stable and can be better identified in such a polar solvent after irradiation with UV-
light. Also, it can be concluded that the introduction of electron donating
substituents in the benzoxazine moiety of the molecule, as well as the replacement
of the methyl substituent at the nitrogen atom of this fragment with a more bulky
benzyl group, leads to an increase in the lifetimes of the photoinduced isomers up
to 146 s.
We envisage that the unsymmetrical bis-spiropyrans and their derivatives can
be used in future as multistable chromogenic systems for different biomedical
applications, while the data obtained will be useful for the development of new
polyfunctional materials with predetermined properties. Our future research will be
aimed at the study of the selective switching possibilities of bis-spiropyrans of this
series.
Acknowledgements.
This work was financially supported by the Ministry of Education and
Science of the Russian Federation within the framework of the State Assignment
for Research (project No. 4.9645.2017/8.9).
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22

•
New unsymmetrical bis-spiropyrans with indoline and 1,3-benzoxazine photochromic units
were synthesized
•
•
Once-opened merocyanine isomers were found to be more stable than the double-opened ones
Introduction of bulky substituent close to benzoxazine spiro-atom increases merocyanine
lifetime

Declaration of interests
✓The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: