Synthesis of 1′,3,3′,4-tetrahydrospiro[chromene-2,2′- indoles] as a new class of ultrafast light-driven molecular switch

Article abstract of DOI:10.1016/j.tet.2013.08.020

A new class of ultrafast light-driven molecular switch has been designed and synthesized. The reaction of 1-substituted 2-methylidene-3,3-dimethyl-2,3- dihydro-1H-indoles with 2-chloromethyl-4-nitrophenol afforded 1′,3,3′,4-tetrahydrospiro[chromene-2,2′-indoles], following a basic workup. The spectroscopic properties and nanosecond-resolved photoinduced dynamics of five compounds in the 1′,3,3′,4- tetrahydrospiro[chromene-2,2′-indole] family were investigated.

Full text of DOI:10.1016/j.tet.2013.08.020

Accepted Manuscript
Synthesis of 1’,3,3’,4-tetrahydrospiro[chromene-2,2’-indoles] as a new class of
ultrafast light-driven molecular switch
Miglė Dagilienė, Vytas Martynaitis, Mikas Vengris, Kipras Redeckas, Vladislava
Voiciuk, Wolfgang Holzer, Algirdas Šačkus
PII:
S0040-4020(13)01294-5
10.1016/j.tet.2013.08.020
TET 24709
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 8 May 2013
Revised Date: 28 July 2013
Accepted Date: 12 August 2013
Please cite this article as: Dagilienė M, Martynaitis V, Vengris M, Redeckas K, Voiciuk V, Holzer W,
Šačkus A, Synthesis of 1’,3,3’,4-tetrahydrospiro[chromene-2,2’-indoles] as a new class of ultrafast light-
driven molecular switch, Tetrahedron (2013), doi: 10.1016/j.tet.2013.08.020.
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2
Graphical Abstract
Synthesis of 1’,3,3’,4-tetrahydrospiro-
[chromene-2,2’-indoles] as a new class of
ultrafast light-driven molecular switch
Leave this area blank for abstract info.
Miglė Dagilienėa,b, Vytas Martynaitisb, Mikas Vengrisc, Kipras Redeckasc,
Me Me
Vladislava Voiciukc, Wolfgang Holzerd and Algirdas Šačkusa,b,*
aInstitute of Synthetic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19,
LT-50254 Kaunas, Lithuania
N
O
NO2
NO2
Me
bDepartment of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19,
LT-50254 Kaunas, Lithuania
∆
hν
Me Me
cDepartment of Quantum Electronics, Vilnius University, Saulėtekio 9,
LT-10222 Vilnius, Lithuania
+
N
-
dDepartment of Drug and Natural Product Synthesis, University of Vienna,
Althanstrasse 14, A-1090 Vienna, Austria
O
Me

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
Synthesis of 1’,3,3’,4-tetrahydrospiro[chromene-2,2’-indoles] as a new class of
ultrafast light-driven molecular switch
Miglė Dagilienėa,b, Vytas Martynaitisb, Mikas Vengrisc, Kipras Redeckasc, Vladislava Voiciukc, Wolfgang
Holzerd, and Algirdas Šačkusa,b
aInstitute of Synthetic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, LT-50254 Kaunas, Lithuania
bDepartment of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, LT-50254 Kaunas, Lithuania
cDepartment of Quantum Electronics, Vilnius University, Saulėtekio 9, LT-10222 Vilnius, Lithuania
dDepartment of Drug and Natural Product Synthesis, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria
ARTICLE INFO
ABSTRACT
Article history:
Received
A new class of ultrafast light-driven molecular switch has been designed and synthesized. The
reaction of 1-substituted 2-methylidene-3,3-dimethyl-2,3-dihydro-1H-indoles with 2-
Received in revised form
Accepted
Available online
chloromethyl-4-nitrophenol
afforded
1’,3,3’,4-tetrahydrospiro[chromene-2,2’-indoles],
following a basic workup. The spectroscopic properties and nanosecond-resolved photoinduced
dynamics of five compounds in the 1’,3,3’,4-tetrahydrospiro[chromene-2,2’-indole] family were
investigated.
Keywords:
Indoles
2013 Elsevier Ltd. All rights reserved.
Fisher’s base
Spiro[chromene-2,2’-indoles]
Molecular Switches
Photochromism
carbon atom.7 When this chiral species is dissolved in organic
solvent it undergoes a thermally driven interconversion between
1. Introduction
Molecular switches have the potential for use in a number of
advanced technologies. The defining characteristic of these
compounds is their ability to shift between different states when
influenced by various external stimuli, such as light, temperature,
electric current, other chemical reactions or changes in pH.1
Light-driven molecular switches are components of
photochromic systems that undergo reversible changes in their
ground state when irradiated with UV light and revert to the
original state when exposed to light of a different wavelength or
via thermal routes.2 Molecular machines,3 chemical sensors,4
optical data storage units5 and many other technically important
devices can be designed to utilize light-driven switches. One of
the most studied classes of photoactive molecular switches is
1’,3’-dihydrospiro[chromene-2,2’-indoles], also known in the
literature as spiro[2H-1-benzopyran-2,2’-indolines].2,6 A typical
representative of this class of photochromic compounds is 6-
nitro-1’,3’-dihydrospiro[chromene-2,2’-indole] 1, composed of
indole and benzopyran moieties linked at an asymmetric spiro
the (R)-1 and (S)-1 enantiomers via a planar ring-opened form,
which generally has a very low concentration in solution.8
Fig.
1.
Photochromism
of
1’,3’,3’-trimethyl-6-nitro-1’,3’-
dihydrospiro[chromene-2,2’-indole].
Under UV-irradiation, compound
1
undergoes fast
(picosecond scale) Cspiro-O bond cleavage, converting to the
planar colored trans-merocyanine form 2, possessing the p-
nitrophenolate moiety.9 However, the subsequent thermal
reversion of the merocyanine 2 to 1 is relatively slow at room
temperature due to the required structural changes, such as trans-
cis isomerization.7b,10
Recently, a new class of ultrafast organic optical switch based
on the indolo[2,1-b][1,3]benzoxazine ring system11 has been
developed (Fig. 2). These photochromes (3), obtained by the
reaction of 3H-indoles with 2-chloromethyl-4-nitrophenol,
———
Corresponding author. Tel.: +37037451401; fax: +37037451432; e-mail: algirdas.sackus@ktu.lt
NO2
H3C CH3
H3C CH3
hν
+
N
∆
-
N
O
NO2
O
CH3
CH3
(R,S)-1
2

ACCEPTED MANUSCRIPT
2
Tetrahedron
undergo C-O bond cleavage of the [1,3]benzoxazine ring upon
It is known that the methylation of 2-methylidene-1,3,3-
dimethyl-2,3-dihydro-1H-indole 6a (Fisher’s base) takes place at
the β-carbon atom of the enamine moiety to afford 2-ethylidene
side-chain products.19 The products of similar β-C-alkylations of
the aforementioned compound with 2-bromoethanol or oxirane
underwent intramolecular spirocyclization to afford 1’,3’,4,5-
tetrahydro-3H-spiro[furan-2,2’-indole] derivatives.20
UV excitation, resulting in the formation of colored 4-
nitrophenolate anions (4) within picoseconds and thermal
reversion to starting material within 102 nanoseconds after
excitation.12 The high speed of photochrome’s ‘on-off’ switching
was explained by the lack of significant structural transformation
during the photoinduced reversible ring-opening process in
contrast to 1’,3’-dihydrospiro[chromene-2,2’-indoles]. These
compounds have also found application in the preparation of pH-
sensitive luminescent quantum dots13 and chemosensors.14
We carried out the reaction of 2-methylidene-1,3,3-dimethyl-
2,3-dihydro-1H-indole 6a with 2-chloromethyl-4-nitrophenol 7 in
acetonitrile at room temperature. After 3 h the crystalline
precipitate was filtered to afford the chloride 8a. The structure of
8a was confirmed by the presence of the following characteristic
H3C CH3
R
H3C CH3
1
signals in the H NMR spectrum (DMSO-d6): the singlet at 1.61
R'
R'
hν
(chemically equivalent protons of the 3’,3’-CH3 groups) and
multiplets in the area of 2.96-3.42 ppm (the protons of the
CH2CH2 moiety). The appearance of a signal at 195.7 ppm in the
13C NMR spectrum was indicative of an N+=C carbon and
characteristic of 3H-indolium salts.21 When treated with aqueous
ammonia, the chloride 8a underwent an intramolecular
nucleophilic addition of the phenolic oxygen to the α-carbon of
the indole moiety to yield 1’,3,3’,4-tetrahydrospiro[chromene-
2,2’-indole] 9a, which possesses the asymmetric spiro C-2’
carbon.
R
O
+
O-
∆
N
N
R = Me, aryl;
NO2
R' = H, NO2, aryl
3
NO2
4
Fig. 2. Photochromism of 2-nitro-5a,6-dihydro-12H-indolo[2,1-
b][1,3]benzoxazines.
This study is focused on the design, syntheses and
investigations of a new class of molecular switch based on the
1’,3,3’,4-tetrahydrospiro[chromene-2,2’-indole] ring system,
which is notable for the single C3-C4 bond of its pyran ring. This
single bond eliminates the drawbacks associated with the
relatively slow cis–trans- and trans–cis-isomerizations about the
C3=C4 double bond in the ring opening-closing process of 1’,3’-
dihydrospiro[chromene-2,2’-indoles], thereby speeding up the
reversible transformations of these light-driven molecular
switches.
H3C CH3
N
O
NO2
NO2
CH3
(R)-9a
H3C CH3
2. Results and discussion
N
The synthesis strategy for the target 1’,3,3’,4-
tetrahydrospiro[chromene-2,2’-indoles] 9a-e is outlined in
Scheme 1. The starting 1,2,3,3-tetramethyl-, 1-ethyl-2,3,3-
trimethyl-, 1,2,3,3,5-pentamethyl-3H-indolium iodides15-17 5a-c
and 1-allyl-2,3,3-trimethyl-3H-indolium perchlorate18 5d were
synthesized by known methods. 1-Ethyl-2,3,3-trimethyl-5-nitro-
3H-indolium iodide 5e was prepared by the reaction of 2,3,3-
trimethyl-5-nitro-3H-indole with ethyl iodide. The corresponding
2-methylidene-2,3-dihydro-1H-indoles 6a-e were obtained from
the salts 5a-e by their treatment with sodium carbonate and used
in the reactions without further purification.
O
CH3
10a
H3C CH3
N
O
NO2
CH3
(S)-9a
(a)
(b)
Fig. 3. (a) Partial 1H NMR spectra (400 MHz, chloroform-d) of 9a at
variable temperatures; (b) interconversion of the (R)-9a and (S)-9a
enantiomers via the ring-open form 10a.
OH
H3C CH3
CH2
H3 C CH3
CH3
R1
R1
ClH2C
(i)
(ii)
+
+
The structure of 9a was determined by spectroscopic methods.
The IR spectrum of 9a contained characteristic absorption bands
at 3068 (C-H arom.) and 1509 (NO2 asymm.) cm-1, whereas no
absorption was able to be assigned to the OH group in the area of
N
N
R
-
X
R
6a-e
NO2
7
5a-e
X = I, ClO4
NO2
3400–3100 cm-1. The H NMR spectrum (chloroform-d) of 9a
1
H3C CH3
H3C CH3
R1
R1
revealed a broadened six-proton singlet, indicative of the geminal
3,3’-CH3 groups, at 1.26 ppm, while the resonances of the
CH2CH2 moiety appeared as broadened multiplets in the range of
2.25–3.20 ppm. In the 13C NMR spectrum of 9a, the geminal
methyl groups at C-3’ gave separate signals at 21.8 and 25.5 ppm,
which were both significantly broadened. All of the other carbon
signals of 9a remained sharp, including the characteristic signal
of the sp3-hybridized C-2’ carbon at 104.2 ppm, which was
indicative of a covalent C-O bond.11c,12 It is known that the
broadening of NMR spectral lines very often reflects dynamic
structural or conformational transformations of molecules in
(iii)
+
N
R
N
O
NO2
HO
Cl-
R
a R = CH3, R1 = H;
1
8a-e
b
R = CH2CH3, R = H;
9a-e
c R = R1 = CH3;
d R = CH2CH=CH2, R1 = H;
e R = CH2CH3, R1 = NO2
Scheme 1. Reagents and conditions: (i) H2O, Na2CO3; (ii) acetonitrile, rt, 3 h;
(iii) H2O, NH4OH.

ACCEPTED MANUSCRIPT
3
solution.22 In our case, the observed broadness and coalescence
relatively stable nature of the ring-closed spiro system in the
solution.
of the proton resonance signals of the diastereotopic geminal
methyl groups can be explained by the inversion of the chiral
center at C-2’ in the interconversion of the (R)- and (S)-
enantiomers of 9a, when the aforementioned methyl groups get
into two magnetically nonequivalent environments. A similar
phenomenon has been observed in indoline spiropyrans8,23 and
indole benzoxazines.1a,b,12a,b At ambient temperature, the
interconversion involving thermally induced C(2)-O bond
cleavage to form the ring-opened intermediate 10a and
subsequent closure via attack on either face of the planar
intermediate is relatively fast on the NMR timescale. We
investigated this process by variable temperature NMR
experiments. When the 1H NMR spectrum of 9a was recorded at
-50 °C, the geminal methyl groups revealed two well-defined
singlets (frequency difference of 9.6 Hz) as a result of slowing
down the interconversion between enantiomers (Fig. 3a, a). The
coalescence of the geminal methyl group signals was observed at
0 °C (Fig. 3a, f). The rate constant k for the inversion of
configuration at C-2,8a calculated by the Gutowsky–Holm
equation,24 was thus 21 sec-1 at 0 °C. It is necessary to note that
the signals corresponding to intermediate 10a were not observed
by 1H NMR spectroscopy as its concentration in solution was too
low to be detected.
The compounds 9b-e were obtained in a similar manner to 9a,
via the reaction of enamines 6b-e with 2-choromethyl-4-
nitrophenol 7. The 1H NMR spectra (chloroform-d, ambient
temperature) of compounds 9b-d displayed the broadened singlet
corresponding to the geminal 3,3’-CH3 observed with 9a.
However, in the 1H NMR spectrum of 5’,6-dinitro-1’,3,3’,4-
tetrahydrospiro[chromene-2,2’-indole] 9e, the geminal 3,3’-CH3
groups resonated as separate singlets at 1.28 and 1.29 ppm, while
the protons of the all three CH2 groups revealed well-defined
multiplets in the range of 2.24-3.52 ppm. Therefore, it could be
concluded that the presence of the electron withdrawing nitro
substituent in the indoline part of molecule shifts the ring-chain
tautomeric equilibria toward the ring-closed form 9e due to
1.26 (br s)
(a)
NOE
enhanced electrophilicity of the indoline α-carbon atom.26
2.25-2.45 (br m)
3.12 (br m)
NOE
H3C CH3
The structure of 9e was investigated by single crystal X-ray
analysis (Fig. 5).27 The compound consists of indole and
benzopyran moieties connected through the spiro atom C(2).
These moieties reside in nearly perpendicular planes, where the
indole-plane intersects the plane of the benzopyran moiety at
C(2) and cuts across the C(4’)-C(10’) bond. The C(3’) atom sits
outside the plane containing the remainder of the benzopyran
moiety. Substituents at C(2) and C(3’) are in staggered
conformation with a N(1)-C(2)-C(3’)-C(4) dihedral angle of
171.28º. The sum of the valent angles at the indoline nitrogen is
357.5º, indicating sp2 hybridization. The C(8)-N(1) bond length
(1.378 Å) is similar to those of N,N-disubstituted aniline
derivatives,28 whereas the C(2)-O(1) bond length (1.483 Å)
resembles those of 1’,3’-dihydrospiro[chromene-2,2’-indoles]
(1.48–1.50 Å).29
7.06 (dd,
7.3, 1.1 Hz)
H
3.04 (br m)
H H H
8.4 (d, 2.8 Hz)
H
H
H
3
4
4'
3'
5'
1N' 2'
2
6.85 (dt,
5
O1
NO2
7.98 (dd, 9.0, 2.8 Hz)
7.5,1.0 Hz)
H
8
7.21 (dt,
CH3
H
7.7, 1.3 Hz)
H
H
6.60 (d, 7.7 Hz)
NOE
2.86 (s)
6.78 (d, 9.0 Hz)
NOE
(b)
25.5 (br.)
21.8 (br.)
H3C CH3
121.2
23.3
121.4
136.8
104.2
125.0
140.4
119.2
127.8
24.0
49.4
N
O
NO2
Fig. 5. ORTEP drawing of the (R)-enantiomer of compound 9e.
148.4
107.2
CH3
-11.9
124.1
116.7
-298.6
161.8
The single crystal of 9e consisted of enantiomeric molecules
in racemic columns. These columns are held by extensive
intermolecular hydrogen bonding utilizing both nitro groups of
the molecules (Fig. 6). The benzopyran-based nitro groups in
both the R- and S-enantiomers form two pairs of hydrogen bonds
apiece: H(10a)…O(12’) (the bond length 2.567 Å) and
H(3’a)…O(13’) (2.498 Å). Similarly, three hydrogen bonds are
formed with the nitro groups of indole moieties: H(13a)…O(16)
(2.552 Å), H(11c)…O(15) (2.641 Å), H(11c)…N(14) (2.873 Å).
28.3
Fig. 4. (a) 1H NMR (500 MHz, chloroform-d) chemical shifts (ppm; ref.
TMS) and relevant NOE correlations for 9a; (b) 13C and 15N NMR (bold)
chemical shifts [ppm; ref. TMS (13C) and CH3NO2 (15N)] for 9a.
1
The full assignment of chemical shifts obtained from the H,
13C and 15N NMR spectra of compound 9a (Fig. 4) were based on
a combination of standard NMR techniques, such as NOE-
difference, NOESY, APT, DEPT, HSQC, HMBC and long-range
INEPT spectra with selective excitation.25 It is worth noting that
the NOESY spectrum (Fig. 4, a) of 9a revealed a cross-peak
between the aromatic 8-H proton and the 1’-CH3 group protons,
while the protons of the geminal 3’,3’-CH3 groups showed
NOE’s both with the aromatic 4’-H proton and the methylene
protons at C-3 and C-4. These observations testify to the
Spectroscopic measurements of 9a-e were carried out in
acetonitrile. Steady state absorbance spectra of all compounds
revealed only absorption in the UV-region of electronic spectra
(Table 1). Interestingly, a significant red shift was observed in
the UV spectrum of 9e when compared to those of the rest
compounds.

ACCEPTED MANUSCRIPT
4
Tetrahedron
Fig. 6. Hydrogen bonds in the racemic columns of the single crystal of 9e.
Table 1. UV-VIS spectral and flash photolysis experiment data for the benzo[e]indoline derivatives 9a-e.
UV-VIS spectral data
Flash photolysis experiment data
ε × 103 (dm3 mol-1
λmax of the photoinduced
form 10 (nm)
λmax of 9 (nm)
Relaxation time, τ (ns)
Quantum yield, Φ (%)
cm-1)
51.4
16.3
14.6
42.3
14.4
12.5
46.3
15.7
13.6
46.1
16.7
12.4
14.1
14.6
22.1
205
1
2
4
3
5
9a
9b
9c
9d
9e
243
450
450
450
450
420
27
36
5.5
326
205
246
5.8
5.6
5.7
9.2
326
206
245
22
313
205
244
37
313
230 (shoulder)
330 (shoulder)
380
484
Flash-photolysis experiments were performed and transient
As shown in Fig. 7, the electronic spectrum of compound 9a
measured 5 ns after excitation has an absorption with a sharp
maximum at 450 nm, possibly originating from the p-
nitrophenolate chromophore 10a formed upon excitation. This
feature is accompanied by a broad plateau with an amplitude
approximately five times less than the maximum. The
photoinduced absorption spectra of 9b-d were similar to that of
9a and may be interpreted as evidencing the formation of the
corresponding chromophores 10b-d (Table 1).
absorption data in the nanosecond to microsecond time window
were collected using a flash-photolysis spectrometer (based on a
Nd:YAG laser), as previously described.12c Irradiation of 9a-e
(0.2 mM solutions in acetonitrile) with nanosecond laser pulses
yielded cleavage of C-O bonds in the 3,4-dihydro-2H-pyran
rings, forming short-lived colored species identified as p-
nitrophenolate chromophores 10a-e.30
These compounds
subsequently revert back to the ground state thermally (Scheme
2).
In contrast, the induced absorption spectrum of 9e is
dominated by a broad band covering the entire blue-green-yellow
part of the visible spectrum with a red tail extending to 800 nm.
Superimposed on the blue part of this band, a sharp feature
peaking at 420 nm related to the p-nitrophenolate chromophore
10e can be discerned, but the amplitude of this peak is only 20%
larger than of that of the underlying band. The different character
of the induced absorption spectrum of 9e can be explained by the
presence of the photoactive N,N-disubstituted p-nitroaniline unit,
as a second chromophore.31
NO2
H3C CH3
H3C CH3
R'
R'
hν
+
N
R
∆
-
N
R
O
NO2
O
9a-e
10a-e
Scheme 2. Photochromism of 6-nitro-1’,3’-dihydrospiro[chromene-2,2’-
indoles].
It must be noted that the photoinduced spectra of 9a and 9e
bear significant differences from the absorbance spectra of these

ACCEPTED MANUSCRIPT
5
compounds
measured
after
treatment
with
tetra-n-
Fig. 8. Diff. absorption traces of 10a and 10e for selected time delays.
butylammonium hydroxide (Bu4N+OH-), suggesting that the ring
opening by strong base results in a different molecular and
conformational form, e.g., 2-hydroxyindoline derivatives 11a, e32
(Scheme 3).
During the collection of the flash-photolysis data, the
photostability of the investigated compounds was also evaluated.
Compound 9a exhibited the highest photostability, withstanding
4000 pulses of approximately 3.5 mJ with negligible change in
its steady-state and transient absorption spectra.
O2N
H3 C CH3
3. Conclusion
R1
Bu4N+OH-
O-
Bu4N+
9a, e
In summary, a new class of ultrafast light-driven organic
molecular switch was designed and synthesized. The reaction of
OH
N
R
1
a
R = CH3, R = H;
e R = CH2CH3, R1 = NO2
2-methylidene-1,3,3-dimethyl-2,3-dihydro-1H-indole
and
11a, e
analogous compounds with 2-chloromethyl-4-nitrophenol
resulted in the formation of 1-alkyl-[2-(2-hydroxy-5-
nitrophenyl)ethyl-1]-3,3-dimethyl-3H-indolium chlorides, which
underwent spirocyclization by treatment with a base to afford
1’,3,3’,4-tetrahydrospiro[chromene-2,2’-indoles]. Irradiation of
the 1’,3,3’,4-tetrahydrospiro[chromene-2,2’-indole] solutions in
acetonitrile with nanosecond laser pulses generated short-lived
colored chromophores able to thermally revert back to the ground
state over 20-500 ns. The significant differences in both the
decay time constants and the induced absorption spectra of 9a-d
and 9e indicated the strong influence of the additional nitro group
on the indole portion of the compound.
Scheme 3. The ring-opening reaction of 9a, e induced by a strong base.
A study of the time dependence of interconversion (Table 1)
revealed that 10a-d reverted to their original ground states 9a-d
via thermal pathways over tens of nanoseconds (for 9a: τ = 27 ns,
Fig. 8). However,
a return to the ground state 9e was
substantially slower (τ = 484 ns), which indicates that structural
transformations of the molecule is also significantly influenced
by the presence of the aforementioned photoactive p-nitroaniline
unit.
Quantum yields (Φ) of the photocoloration of 9a-e were
determined applying the method described by Raymo et al.12a,b
Benzophenone in acetonitrile was used as a reference. For 9a-e,
observed Φ values ranged between 5.5% (9a) and 9.2% (9e)
(Table 1).
4. Experimental
4.1. General
Reagents and solvents were purchased from Sigma-Aldrich
and used without further purification. Reactions were monitored
by TLC analysis on precoated silica gel plates (Kieselgel 60F254
,
70
60
50
40
30
20
10
0
1.5
1.0
0.5
0.0
Merck). Compounds were visualized with UV light and charring
after treatment with a 1% KMnO4 solution spray. Column
chromatography was performed on silica gel SI 60 (43-60 ꢀm, E.
Merck). Melting points were determined in open capillary tubes
with a Büchi B-540 melting point apparatus and are uncorrected.
Infrared spectra were recorded on a Perkin Elmer Spectrum One
9a + h
ν
9e + h
ν
9a + Bu4N+OH-
9e + Bu4N+OH-
1
spectrometer using potassium bromide pellets. H NMR spectra
were recorded at 300 MHz on a Varian Unity Inova spectrometer
at 400 MHz on a Bruker Avance III and at 500 MHz on a Bruker
Avance 500 spectrometer. 13C NMR spectra were collected using
the same instruments at 75, 100 and 125 MHz. Chemical shifts
are expressed in ppm downfield relative to TMS and coupling
constants (J), referring to apparent peak multiplicity, are reported
in Hz. 15N NMR spectra (50.69 MHz) were obtained on a Bruker
Avance 500 spectrometer using a ‘directly’ detecting broadband
observe probe and were referenced against neat, external
nitromethane (coaxial capillary). Mass spectra were recorded on
an Agilent 110 (series MS with VL) apparatus. High-resolution
ESI-TOF mass spectra were measured on a Bruker maXis
spectrometer. Diffraction data were collected on a Bruker-Nonius
KappaCCD diffractometer at room temperature and also at -100
°C. The crystal structures were solved using known programs.33
Elemental analyses were conducted using an Elemental Analyzer
CE-440 (Exeter Analytical, Inc.) by the Microanalytical
Laboratory, Department of Organic Chemistry, Kaunas
University of Technology. An in-house flash-photolysis
spectrometer, described previously,12c was used to collect
transient absorption data in nanosecond to microsecond time
domain. Flash photolysis experiments were performed using a
Nd:YAG laser (EKSPLA NL30) and pulses of the third harmonic
(wavelength - 355 nm, duration - 6.5 ns, energy – 3.5 mJ) were
applied for excitation. Difference absorption was registered by
measuring the intensity of a Xe flash lamp’s emission passing
through a cuvette containing the sample. The collected time-
400
500
600
700
800
Wavelength (nm)
Fig. 7. Photo-induced absorption spectra of 9a and 9e measured at 5 ns
after the excitation and normalized absorption spectra of 9a and 9e after
treatment with Bu4N+OH-.
50
40
10e, 420 nm
= 484 ns
τ
30
20
10
0
10a, 450 nm
= 27 ns
τ
0
200
400
600
800
1000
Time (ns)

ACCEPTED MANUSCRIPT
6
Tetrahedron
resolved spectra and traces were analyzed using global analysis
126.6, 129, 129.7, 139.3, 140.6, 142.6, 162.2, 195.8. IR (cm-1):
techniques described elsewhere.34
3462 (O-H), 3050, 2971, 1520 (NO2-asymm.), 1338 (NO2-
symm.). MS m/z (%): 339.4 (M+, 100). Anal. Calcd for
C20H23ClN2O3 (374.86): C 64.08; H 6.18; N 7.47. Found: C
63.98; H 6.25; N 7.31.
4.2. Procedure for the synthesis of 1-ethyl-2,3,3-trimethyl-5-
nitro-3H-indolium iodide (5e).
To a solution of 2,3,3-trimethyl-5-nitro-3H-indole35 (1.02 g, 5
mmol) in acetonitrile (10 mL), iodoethane (1.42 g, 10 mmol) was
added and the reaction mixture was heated at reflux. After 24 h
the resultant crystalline material was filtered and recrystallized
from ethanol to afford the title iodide 5e (0.96 g, 53%) as brown
4.3.3.
[2-(2-Hydroxy-5-nitrophenyl)ethyl-1]-1,3,3,5-
tetramethyl-3H-indolium chloride (8c): off-white crystals, yield
0.843 mg (45%), mp 192–194 ºC. H NMR (300 MHz, DMSO-
1
1
d6): δ 1.58 (s, 6H, 2×3‘-CH3), 2.45 (s, 3H, 5’-CH3), 2.99–3.05
(m, 2H, CH2), 3.32–3.38 (m, 2H, CH2), 4.10 (s, 3H, NCH3), 7.27
(d, J = 9 Hz, 1H, Ar-H), 7.45 (d, J = 8.25 Hz, 1H, Ar-H), 7.66 (s,
1H, Ar-H), 7.83 (d, J = 8.25 Hz, 1H, Ar-H), 8.07 (dd, J = 9.0, 3.0
Hz, 1H, Ar-H), 8.34 (d, J = 3.0 Hz, 1H, Ar-H), 11.98 (s, 1H,
OH). 13C NMR (75 MHz, DMSO-d6): δ 21.1, 21.4 (2×CH3), 26.2,
26.4, 35.1, 54.2, 115.1, 115.4, 123.7, 124.7, 126.5, 126.6, 129.3,
139.4, 139.9, 140.1, 141.9, 162.3, 194.5. IR (cm-1): 3394 (O-H),
3029, 2975, 1523 (NO2-asymm.), 1337 (NO2-symm.). MS m/z
(%): 339.4 (M+, 90). Anal. Calcd for C20H23ClN2O3 (374.86): C
64.08; H 6.18; N 7.47. Found: C 63.71; H 6.33; N 7.39.
crystals, mp 202–204 ºC (with decomp.). H NMR (400 MHz,
TFA-d): δ 1.80 (t, J = 7.6 Hz, 3H, CH2CH3), 1.87 (s, 6H, 2×3-
CH3), 3.12 (s, 3H, 2-CH3), 4.82 (q, J = 7.6 Hz, 2H, CH2CH3),
8.14 (d, J = 8.8 Hz, 1H, 7-H), 8.72 (s, 1H, 4-H), 7.73 (dd, J = 8.8,
2.0 Hz, 1H, 6-H). 13C NMR (100 MHz, TFA-d): δ 14.1, 16.4,
23.8 (2×CH3), 47.5, 58.3, 118.8, 121.7, 128.5, 146.0, 147.4,
151.3, 204.0. IR (cm-1): 3027, 2978, 1627 (C=N+), 1532 (NO2-
asymm.), 1348 (NO2-symm.). MS m/z (%): 233.0 ([M-I]+, 100).
Anal. Calcd for C13H17IN2O2 (233.29): C 43.35; H 4.76; N 7.78.
Found C 43.05; H 4.66; N 7.85.
4.3. General procedure for the preparation of 1-alkyl-[2-(2-
hydroxy-5-nitrophenyl)ethyl-1]-3,3-dimethyl-3H-indolium
chlorides (8)
4.4. General procedures for the preparation of 1’-substituted
6-nitro-1’,3,3’,4-tetrahydrospiro[chromene-2,2’-indoles] (9)
To a stirred solution of the corresponding iodide (5a-c, 5
mmol) in distilled water (15 mL), sodium carbonate (1.06 g, 10
mmol) was added at rt. The mixture became turbid and was
extracted with diethyl ether (3 × 20 mL). The combined organic
phase was dried over anhydrous sodium sulfate and the solvent
was evaporated under reduced pressure to afford the
corresponding 2-methylidene-2,3-dihydro-1H-indole (6a, 6b and
6c, respectively) as an oil. The obtained by such way crude
intermediate enamine was dissolved in acetonitrile (10 mL), 2-
chloromethyl-4-nitrophenol 7 (938 mg, 5 mmol) was added and
the mixture was stirred at rt. After 6 h the resultant crystalline
material was filtered, washed with cold acetonitrile (1 mL) and
dried in vacuo to afford the title compound (8a-c).
4.4.1. Method A: A solution of the corresponding [2-(2-
hydroxy-5-nitrophenyl)ethyl-1]-3H-indolium chloride (8a-c, 3
mmol) in ethanol (5 mL) was diluted with water (15 mL) and to
the mixture an aqueous ammonia solution (10%) was added by
drops under stirring till the mixture became turbid. The separated
product was extracted with diethyl ether (3 × 20 mL), the
combined extract was dried over anhydrous sodium sulfate and
the solvent was evaporated under reduced pressure. The solid
residue was recrystallized from acetonitrile to give the title
spiro[chromene-2,2’-indole] (9a-c).
4.4.1.1.
1',3',3'-Trimethyl-6-nitro-1',3,3',4-
4.3.1. [2-(2-Hydroxy-5-nitrophenyl)ethyl-1]-1,3,3-trimethyl-
tetrahydrospiro[chromene-2,2'-indole] (9a): yellowish crystals,
yield 720 mg (74%), mp 187–189 ºC (acetonitrile). 1H NMR (500
MHz, CDCl3): δ IR (cm-1): 1.26 (br s, 6H, 2×3‘-CH3), 2.25–2.45
(m, 2H, CH2), 2.86 (s, 3H, NCH3), 3.02–3.06 (m, 1H, 4-H), 3.10-
3.14 (m, 1H, 4-H), 6.60 (d, J = 7.7 Hz, 1H, 7’-H), 6.78 (d, J = 9.0
Hz, 1H, 8-H), 6.85 (dt, J = 7.5, 1.0 Hz, 1H, 5’-H), 7.06 (dd, J =
7.3, 1.1 Hz, 1H, 4’-H), 7.21 (dt, J = 7.7, 1.3 Hz, 1H, 6’-H), 7.98
(dd, J = 9.0, 2.8 Hz, 1H, 7-H), 8.40 (d, J = 2.8 Hz, 1H, 5-H). 13C
NMR (125 MHz, CDCl3): δ 21.8, 23.3, 24.0, 25.5, 28.3, 49.4,
104.2, 107.2, 116.7, 119.2, 121.2, 121.4, 124.1, 125.0, 127.8,
136.8, 140.4, 148.4, 161.8. 15N NMR (50.69 MHz, CDCl3): δ -
11.9, -298.6. IR (cm-1): 3068, 2965, 1509 (NO2-asymm.), 1329
(NO2-sym m.). Anal. Calcd for C19H20N2O3 (324.37): C 70.35; H
6.21; N 8.64. Found: C 70.03; H 6.30; N 9.03. ESI-HRMS:
[M+H+], found 325.1548. [C19H20N2O3+H+ ] requires 325.1547.
3H-indolium chloride (8a): off-white crystals, yield 704 mg,
(39%), mp 208–211 ºC. H NMR (300 MHz, DMSO-d6): δ 1.61
1
(s, 6H, 2×3‘-CH3), 2.96–3.07 (m, 2H, CH2), 3.32–3.42 (m, 2H,
CH2), 4.13 (s, 3H, NCH3), 7.26 (d, J = 9.0 Hz, 1H, Ar-H), 7.63–
7.66 (m, 2H, Ar-H), 7.83–7.86 (m, 1H, Ar-H), 7.95–7.98 (m, 1H,
Ar-H), 8.09 (dd, J = 9.0, 2.8 Hz, 1H, Ar-H), 8.35 (d, J = 2.8 Hz,
1H, Ar-H), 11.98 (s, 1H, OH). 13C NMR (75 MHz, DMSO-d6): δ
21.3 (2×CH3), 26.3, 26.5, 35.1, 54.5, 115.4, 115.5, 123.3, 124.8,
126.5, 126.7, 128.9, 129.7, 139.4, 141.8, 142.2, 162.3, 195.7. IR
(cm-1): 3416 (O-H), 3041, 2976, 1517 (NO2-asymm.), 1347
(NO2-symm.). MS m/z (%): 325.4 (M+, 100). Anal. Calcd for
C19H21ClN2O3 (360.83): C 63.24; H 5.87; N 7.76. Found: C
63.33; H 5.99; N 7.75.
4.3.2.
1-Ethyl-[2-(2-hydroxy-5-nitrophenyl)ethyl-1]-3,3-
dimethyl-3H-indolium chloride (8b): off-white crystals, yield 693
mg (37%), mp 195-199 ºC. 1H NMR (300 MHz, DMSO-d6): 1.55
(t, J = 6.9 Hz, 3H, CH2CH3), 1.64 (s, 6H, 2×3‘-CH3), 3.00–3.07
(m, 2H, CH2), 3.33–3.44 (m, 2H, CH2), 4.63–4.73 (m, 2H,
CH2CH3), 7.27 (d, J = 9 Hz, 1H, Ar-H), 7.64–7.67 (m, 2H, Ar-
H), 7.86–7.89 (m, 1H, Ar-H), 8.02–8.05 (m, 1H, Ar-H), 8.08 (dd,
J = 9.0, 2.7 Hz, 1H, Ar-H), 8.38 (d, J = 2.7 Hz, 1H, Ar-H), 12.01
(s, 1H, OH). 13C NMR (75 MHz, DMSO-d6): δ 21.5 (2×CH3),
26.4, 26.9, 30.1, 43.5, 54.9, 115.4, 115.9, 123.5, 124.7, 126.4,
4.4.1.2.
1‘-Ethyl-3',3'-dimethyl-6-nitro-1',3,3',4-
tetrahydrospiro[chromene-2,2'-indole] (9b): yellowish crystals,
yield 305 mg (30%), mp 154–156 ºC (acetonitrile). 1H NMR (300
MHz, CDCl3): δ 1.23 (t, J = 7.2 Hz, 3H, CH2CH3), 1.25 (br s, 6H,
2×3‘-CH3), 2.21–2.48 (m, 2H, CH2CH3), 2.95–3.44 (m, 4H,
2×CH2), 6.58–6.61 (m, 1H, 7‘-H), 6.76 (d, J = 9.3 Hz, 1H, 8-H),
6.82 (dt, J = 7.5, 0.9 Hz, 1H, 5‘-H), 7.06 (dd, J = 7.5, 0.9 Hz, 1H,
4‘-H), 7.19 (dt, J = 7.5, 0.9 Hz, 1H, 6‘-H), 7.98 (dd, J = 9.0, 2.7
Hz, 1H, 7-H), 8.04 (d, J = 2.7 Hz, 1H, 5-H). 13C NMR (75 MHz,

ACCEPTED MANUSCRIPT
7
CDCl3): δ 15.1, 22.0, 23.6, 24.8, 25.9, 37.5, 49.7, 104.7, 106.5,
116.9, 118.8, 121.3, 121.4, 124.2, 125.2, 128.0, 136.7, 140.5,
147.6, 161.9. IR (KBr, cm-1): 3068, 2970, 1510 (NO2-asymm.),
1331 (NO2-symm.). Anal. Calcd for C20H22N2O3 (338.40): C
70.99; H 6.55; N 8.28. Found: C 70.89; H 6.61; N 8.24. ESI-
HRMS: [M+H+], found 339.1705. [C20H22N2O3+H+] requires
339.1703.
4.4.2.2.
1'-Ethyl-3',3'-dimethyl-5’,6-dinitro-1',3,3',4-
tetrahydrospiro[chromene-2,2'-indole] (9e): Rf
=
0.11
(hexane/ethyl acetate 9:1, v/v), yellow crystals, yield 997 mg
(52%), mp 179–180 ºC (acetonitrile). 1H NMR (300 MHz,
CDCl3): δ 1.26 (t, J = 7.2 Hz, 3H, CH2CH3), 1.28 (s, 3H, 3‘-
CH3), 1.29 (s, 3H, 3‘-CH3), 2.24–2.35 (m, 1H, ½ 3-CH2), 2.42–
2.52 (m, 1H, ½ 3-CH2), 3.0–3.20 (m, 2H, 4-CH2), 3.33–3.52 (m,
2H, N-CH2), 6.55 (d, J = 8.7 Hz, 1H, 7‘-H); 6.78 (d, J = 9.0 Hz,
1H, 8-H), 7.91 (d, J = 2.3 Hz, 1H, 4‘-H), 7.99 (dd, J = 9.0, 2.7
Hz, 1H, 7-H), 8.05 (d, J = 2.7 Hz, 1H, 5-H), 8.17 (dd, J = 8.7, 2.3
Hz, 1H, 6‘-H). 13C NMR (75 MHz, CDCl3): δ 14.6, 21.7, 23.3,
24.5, 25.7, 37.5, 49.3, 104.1, 105.1, 116.9, 118.1, 121.0, 124.4,
125.2, 126.5, 137.6, 140.3, 141.1, 152.9, 160.7. IR (cm-1): 3068,
2990, 1501 (NO2-asymm.), 1321 (NO2-symm.). Anal. Calcd for
C20H21N3O5 (383.40): C 62.65; H 5.52; N 10.96. Found: C 62.33;
4.4.1.3.
1',3',3',5’-Tetramethyl-6-nitro-1',3,3',4-
tetrahydrospiro[chromene-2,2'-indole] (9c): yellowish crystals,
yield 812 mg, (80%), mp 178–179 ºC (acetonitrile). 1H NMR
(300 MHz, CDCl3): δ 1.25 (br s, 6H, 2×3‘-CH3), 2.32 (s, 3H, 5‘-
CH3), 2.34–2.38 (m, 2H, CH2), 2.83 (s, 3H, NCH3), 3.01–3.12
(m, 2H, CH2), 6.5 (d, J = 8.1 Hz, 1H, 7‘-H); 6.78 (d, J = 9 Hz,
1H, 8H), 6.86–6.88 (m, 1H, 4‘-H), 6.98–7.02 (m, 1H, 6‘-H), 7.97
(dd, J = 9.0, 2.7 Hz, 1H, 7-H), 8.03 (d, J = 2.7 Hz, 1H, 5-H). 13C
NMR (75 MHz, CDCl3): δ 21.1, 22.1, 23.6, 24.2, 25.8, 28.7,
49.7, 104.8, 107.2, 116.9, 121.6, 122.3, 124.3, 125.2, 128.3,
128.7, 137.2, 140.6, 146.5, 162.1. IR (cm-1): 3065, 2940, 1499
(NO2-asymm.), 1332 (NO2-symm.). Anal. Calcd for C20H22N2O3
(338.40): C 70.99; H 6.55; N 8.28. Found: C 70.64; H 6.60; N
8.45. ESI-HRMS: [M+H+], found 339.1708. [C20H22N2O3+H+]
requires 339.1704.
H
5.48; N
11.13. ESI-HRMS: [M+H+], found 384.1552.
[C20H21N3O5+H+] requires 384.1554.
Acknowledgements
This research was funded by a grant (No. 022/2013) from the
Research Council of Lithuania.
4.4.2. Method B: To a stirred suspension of the corresponding
3H-indolium salt (5d, e, 5 mmol) in distilled water, sodium
carbonate (1.06 g, 10 mmol) was added at rt. The separated
organic material was extracted with diethyl ether (3 × 20 mL),
the combined organic phase was dried over anhydrous sodium
sulfate and the solvent was evaporated under reduced pressure to
afford the corresponding 2-methylene-2,3-dihydro-1H-indole
(6d,36 6e). The obtained intermediate enamine was dissolved in
acetonitrile (10 mL), 2-chloromethyl-4-nitrophenol 5 (938 mg, 5
mmol) was added and the mixture was stirred at rt. After 6 h the
reaction mixture was poured into water (50 mL) and an aqueous
ammonia solution (10%) was added by drops under stirring till
the mixture became turbid. The separated product was extracted
with diethyl ether (3 × 20 mL), the combined extract was dried
over anhydrous sodium sulfate and the solvent was evaporated
under reduced pressure. The residue was subjected to flash
chromatography on silica gel (hexane/acetone 7:1, v/v for 9d and
hexane/ethyl acetate 9:1, v/v for 9e) to yield the title compound
(9d, e).
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1‘-Allyl-3',3'-dimethyl-6-nitro-1',3,3',4-
0.16
tetrahydrospiro[chromene-2,2'-indole] (9d): Rf
(hexane/acetone 7:1, v/v) yellowish crystals, yield 0.49 g (28%),
mp 160–161 ºC (acetonitrile). H NMR (300 MHz, CDCl3): δ
=
1
1.29 (br s, 6H, 2×3‘-CH3), 2.35 (br s, 2H, 3-CH2), 3.06 (br s, 2H,
NCH2), 3.88 (br s, 2H, 4-CH2), 5.14 (dq, J = 10.2, 1.8 Hz, 1H,
C=CH2) 5.27(dq, J = 17.1, 1.8 Hz, 1H, C=CH2), 5.94 (ddt, J =
17.1 Hz, J = 10.2 Hz, J = 4.5 Hz, 1H, -CH=), 6.56 (d, J = 7.5 Hz,
1H, 7‘-H), 6.78 (d, J = 9 Hz, 1H, 8-H), 6.85 (t, J = 7.5 Hz, 1H,
5‘-H), 7.07 (d, J = 7.5 Hz, 1H, 4‘-H), 7.17 (dt, J = 7.5 Hz, J = 1.2
Hz, 1H, 6‘-H), 7.98 (dd, J = 9 Hz, J = 3 Hz, 1H, 7-H), 8.04 (d, J
= 3 Hz, 1H, 5-H). 13C NMR (75 MHz, CDCl3): δ 22.0, 23.5, 24.9,
26.0, 45.8, 49.8, 104.6, 107.3, 115.3, 116.9, 119.3, 121.3, 121.4,
124.3, 125.2, 128.0, 135.2, 136.8, 140.6, 147.8, 161.8. IR (cm-1):
3031, 2935, 1511 (NO2-asymm.), 1339 (NO2-symm.). Anal.
Calcd for C21H22N2O (350.41): C 71.98; H 6.33; N 7.99. Found:
C 71.97; H 6.25; N 8.12. ESI-HRMS: [M+H+], found 351.1709.
[C21H22N2O3+H+] requires 351.1705.

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