Photochromism of dihydroindolizines. Part XXIV: Exploiting “Click” chemistry strategy in the synthesis of fluorenyldihydroindolizines with multiaddressable photochromic properties

Article abstract of DOI:10.1016/j.jphotochem.2018.04.040

A new category of photochromic dihydroindolizines (DHIs) incorporating substituted 2,7- and 4-substituted tetrazole and oxadiazole moieties in the fluorene skeleton (region A) were efficiently prepared utilizing “Click” chemistry approaches. The structure elucidation for all synthesized precursors as well as the target photochromic DHIs was carried out using some analytical and spectroscopic techniques. A highly tunable photochromic behaviors of the parent dihydroindolizine are possible by the introduction of substituents in different positions of the DHI framework. For example, the substituents in 2,7 and 4-positions of fluorene part showed the ability for extending photochromism. The photochromic behaviors of photochromic DHIs substituted in fluorene part (region A) such as the reaction kinetics and fluorescence properties and their photo-fatigue resistance were studied. It has been disclosed that the replacement of the tetrazole moieties in 2,7-position in (region A) by oxadiazole moieties has strong effect on both the spectral, kinetic characteristics, fluorescence emission and photostability. The observations of this work imply that the substituent groups in the fluorene part influenced the thermal back-reaction rates and played an imperative role in controlling all photochromic properties of the open form. The new synthesized substituted (DHIs) in the fluorene by both tetrazole moieties in 2,7-position and by oxadiazole moieties in 2,7 and 4 positions in fluorene part made these materials act as fluorophores and postulate new opportunities for the design of the next generation of photochromic materials which will make it talented materials in many applications such as electronic smart materials, photochromic glasses, photonic devices and fluorescent fabrics. Because of their noticeable fluorescence emission high photostability, these materials can be used as fluorophores, recording or storage information for numerous periods without color fading.

Full text of DOI:10.1016/j.jphotochem.2018.04.040

Accepted Manuscript
Title: Photochromism of dihydroindolizines. Part XXIV:
Exploiting “Click” chemistry strategy in the synthesis of
fluorenyldihydroindolizines with multiaddressable
photochromic properties
Authors: Saleh A. Ahmed, Nizar El Guesmi, Ismail I.
Althagafi, Khalid S. Khairou, Hatem M. Altass, Aboel-Magd
A. Abdel-Wahab, Basim H. Asghar, Hanadi A. Katouah,
Mohamed A.S. Abourehab
PII:
S1010-6030(18)30175-8
DOI:
Reference:
https://doi.org/10.1016/j.jphotochem.2018.04.040
JPC 11255
To appear in:
Journal of Photochemistry and Photobiology A: Chemistry
Received date:
Revised date:
Accepted date:
8-2-2018
19-4-2018
19-4-2018
Please cite this article as: Saleh A.Ahmed, Nizar El Guesmi, Ismail
I.Althagafi, Khalid S.Khairou, Hatem M.Altass, Aboel-Magd A.Abdel-
Wahab, Basim H.Asghar, Hanadi A.Katouah, Mohamed A.S.Abourehab,
Photochromism of dihydroindolizines.Part XXIV: Exploiting “Click” chemistry
strategy in the synthesis of fluorenyldihydroindolizines with multiaddressable
photochromic properties, Journal of Photochemistry and Photobiology A:
Chemistry https://doi.org/10.1016/j.jphotochem.2018.04.040
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Photochromism of dihydroindolizines. Part XXIV: Exploiting “Click”
chemistry strategy in the synthesis of fluorenyldihydroindolizines with
multiaddressable photochromic properties
Saleh A. Ahmed*a,b, Nizar El Guesmia,c, Ismail I. Althagafia, Khalid S. Khairou a, Hatem M.
Altassa, Aboel-Magd A. Abdel-Wahabb, Basim H. Asghara, Hanadi A. Katouaha, Mohamed A. S.
Abourehabd,e
a Chemistry Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University,
21955 Makkah, Saudi Arabia
b Department of Chemistry, Faculty of Science, Assiut university, 71516 Assiut, Egypt
c Département de chimie, Faculté des Sciences de Monastir, Avenue de l’Environnement,
5019 Monastir, Tunisia
dDepartment of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi
Arabia
eDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University,
Minia, Egypt
*Correspondence may be addressed to:
Saleh A. Ahmed: E-mail address: saleh_63@hotmail.com

Tel./Fax: + 966 530435760
Graphical Abstract
Highlights


“Click” chemistry strategy has been effectively exploited for the synthesis of photochromic DHIs.
Photochromic dihydroindolizine (DHIs) bearing substituted tetrazoles and oxadiazole moieties
can act as fluorophores.



Multiaddressable properties of the synthesized DHIs have been monitored.
High photo-fatigue resistance of the corresponding betaines has been detected.
Going more deeply in the chemical structures of these DHIs maybe open new era in the field of
photochromism.
Abstract:
A new category of photochromic dihydroindolizines (DHIs) incorporating substituted 2,7- and 4-
substituted tetrazole and oxadiazole moieties in the fluorene skeleton (region A) were efficiently
prepared utilizing “Click” chemistry approaches. The structure elucidation for all synthesized
precursors as well as the target photochromic DHIs was carried out using some analytical and

spectroscopic techniques. A highly tunable photochromic behaviors of the parent
dihydroindolizine are possible by the introduction of substituents in different positions of the DHI
framework. For example, the substituents in 2,7 and 4-positions of fluorene part showed the ability
for extending photochromism. The photochromic behaviors of photochromic DHIs substituted in
fluorene part (region A) such as the reaction kinetics and fluorescence properties and their photo-
fatigue resistance were studied. It has been disclosed that the replacement of the tetrazole moieties
in 2,7-position in (region A) by oxadiazole moieties has strong effect on both the spectral, kinetic
characteristics, fluorescence emission and photostability. The observations of this work imply that
the substituent groups in the fluorene part influenced the thermal back-reaction rates and played
an imperative role in controlling all photochromic properties of the open form. The new
synthesized substituted (DHIs) in the fluorene by both tetrazole moieties in 2,7-position and by
oxadiazole moieties in 2,7 and 4 positions in fluorene part made these materials act as fluorophores
and postulate new opportunities for the design of the next generation of photochromic materials
which will make it talented materials in many applications such as electronic smart materials,
photochromic glasses, photonic devices and fluorescent fabrics. Because of their noticeable
fluorescence emission high photostability, these materials can be used as fluorophores, recording
or storage information for numerous periods without color fading.
Keywords: photochromic materials, “Click” chemistry, betaines, half-Lives (t1/2), fluorophores,
photo-fatigue
1. Introduction
Photochromism is one of the most important branch of photochemistry which pertains to the
reversible photoinduced conversion of the molecules among two different chemical structures of

conspicuously dissimilar absorption spectra.1-8 In addition to the color change, photochromic
materials, which tolerate to reversible modulate an abundant additional miscellaneous set of
properties are remain demonstrating their advantages in contemporary materials science.9-11 In the
last decades, numerous modulation of microscopic and macroscopic physical and chemical
properties by light have been achieved.12 These moderated properties range from absorption of
light, light emission, reactivity including noncovalent interactions as well as covalent bonding and
π-conjugation.13-14 The functionalized materials with optical properties and photoswitches have
deliberated as greatest stimulating themes in field of materials chemistry. This is due to their
applications in the manufacture of optoelectronic devices and switchable materials. 5-15 It is well-
known that the organic photochromic materials can modify their geometry and electronical
structures under the effect of ultraviolet irradiation. They have the high possibility to change-back
to the initial state when light-irradiation has been terminated. The thermal back reaction to initial
structure could be stimulated through thermal process or during irradiation by visible light.16-19
Due to the back reaction, structural changes arise, photochromism develop dormant attracting in
diminishing optic mechanism for applications in opto-electronics photo-switching technology by
involvement opportunity to superintendent the properties of these materials such as emission
spectra, absorptivity and photochromic reactivity.20-24 Up till now, captivating photochromic
compounds, most particularly diarylethenes, azobenzenes, spirooxazines, fulgides and spiropyrans
have been extensively used as significant components to control functional molecules, assemblies,
and materials used in optoelectronic devices for data storage and logic operations as well as
biotechnological and pharmacological applications. These accomplishments have only become
conceivable due to a cumulative number of active scientists in the field, offering tremendous
efforts to design novel photoswitchable molecules and utilize their inimitable functions in

developing applications. Since the discovery of photochromic di- & tetrahydroindolizines, by H.
Dürr 25-29, they became one of the prominent families of photochromic materials that fascinated
countless consideration from the perspectives of essential illumination of electrocyclic process and
probable applications (Scheme 1). These applications included mutable optical density, optical
devices, sun glasses, dental filling materials, organogelators, IR-sensitive materials and security
inks.30-39 These sounding applications were established by tuning the chemical structure of DHI
by changing the substituents in the moiety (region A), ester part (region b) and heterocyclic base
(region c).25-49 These promising photochromic materials exhibit two dissimilar isomeric states
established by a 1,5-electrocyclization process . These states are ring open form (betaine-form)
and ring closed form (DHI-form). These photochromic materials showed probable applications for
optical storage media, fluorescent materials, and recently as anticancer drug delivery in cervical
carcinoma.40-49
Scheme 1. 1,5-electrocyclization of the ring opening betaine (colored form) and closed form
DHI (colorless form)

It noted that the only disadvantage of using these bulky groups for photochromic systems is the
steric factor and increase the molecular weight which decreases pronouncedly the half-lives and
colors of the opened betaines and become undetectable at room temperature.43-47 In addition,
sometimes the bulky group fixes the betaine in one form (cis-form) and prevents reversing back to
DHI again.29,32 The tetrazole and oxadiazole units are known as very prevalent chromophores in
50
organic compounds and considerable much attention passed two decades. This is due to their
sounding applications in the photonic cells, exceptionally those based on organic polymeric light-
emitting diodes 51, photovoltaics devices 52, electroluminescent colloidal inks 53 nonlinear optical
properties 54 stable membrane in fuel cells. 55 Tetrazole and oxadiazole derivatives show not only
high electron affinity but also some brilliant electron-transporting possessions in multilayer
56-58
electroluminescent diodes.
Because of their high stability and emission quantum yields,
fluorene derivatives are used in many optoelectronic applications.
Furthermore, a successful synthesis of photochromic dihydroindolizines incorporating carbon-rich
acetylenic bridges and substituted triazoles via “Click” chemistry condition and by using different
coupling reaction conditions have been reported by us. 40-42 The aim behind the performed work
is to get footing of new properties and applications appropriate for electronic devices applications.
The promising results obtained encouraged us to further explore the synthesis of newly substituted
DHIs bearing both tetrazole and oxadiazole moieties. In continuation of the previous research on
the synthesis of photochromic di- & tertrhydroindolizes and exploiting “Click” chemistry
strategies, the current work reports the synthesis of some dihydroindolizine fluorophores and their
photochromic performances in solution.
2 Results and discussion

2.1. Synthesis of (R)-dimethyl 2',7'-di(2H-tetrazol-5-yl)spiro[cycloprop[2]ene-1,9'-fluorene]-
2,3-dicarboxylate 7 precursor via “Click” chemistry approach.
2,7-dibromo-9H-fluoren-9-one 1 was prepared via bromination of flourene-9-one with N-
N-bromosuccinimide 41-50 and 9-oxo-9H-fluorene-2,7-dicarbonitrile 2 was prepared by cyanation
59-73
of 2,7-dibromo-9H-fluoren-9-one 1 with copper cyanide in refluxing DMF
with some
modifications. The spirocyclopropenes 7 was synthesized using both chemical and photochemical
reactions (scheme 2). “Click” reaction of 9-oxo-9H-fluorene-2,7-dicarbonitrile 2 with sodium
azide in DMF and ammonium chloride at 100 ºC for 5 h afforded the desired 2,7-di(2H-tetrazol-
5-yl)-9H-fluoren-9-one 3 in moderate yield (57%). Condensation of the di-tetrazolo derivative 3
with anhydrous hydrazine in refluxing ethanol for 6 h afforded the 5,5'-(9-hydrazono-9H-fluorene-
2,7-diyl)bis(2H-tetrazole) 4 in excellent yield (94%) after crystallization from ethanol. On the
other hand, heterogenous oxidation of the hydrazone derivative 4 with freshly activated manganese
dioxide under dry nitrogen atmosphere in freshly dried ether at room temperature in complete light
prevention yielded the 5,5'-(9-diazo-9H-fluorene-2,7-diyl)bis(2H-tetrazole) 5 in 47% yield. 1,3-
Cycloaddition of 9-diazofluorene derivative 5with methyl acetylene-dicarboxylate (MADC) in
freshly dry diethyl ether under dark condition and nitrogen atmosphere for 48 h affords dimethyl
2,7-di(2H-tetrazol-5-yl)spiro[fluorene-9,3'-pyrazole]-4',5'-dicarboxylate 6 in low yield (36%). The
target precursor (R)-dimethyl 2',7'-di(2H-tetrazol-5-yl)spiro[cycloprop[2]ene-1,9'-fluorene]-2,3-
dicarboxylate 7 is successfully obtained in 28% yield via photolysis of the bis-tetrazole derivative
6 using ultraviolet mercury lamp (125 W) in freshly distilled ether and dry nitrogen for 5 h. The
spectroscopic and analytical tools were used to characterize the chemical structures of the
synthesized compounds (3-7). For instance, the 1H NMR spectrum of the (R)-dimethyl 2',7'-di(2H-
tetrazol-5-yl)spiro[cycloprop[2]ene-1,9'-fluorene]-2,3-dicarboxylate 7 demonstrate these signals:
 11.32 (s, 2H, 2NH), 8.20 (s, 2H, 1,8 CH-fluorene), 7.97 (d, J=7.8 Hz, 2H, 4,5 CH-fluorene),

7.86 (d, J=7.8 Hz, 2H, 3,6 CH-fluorene), 3.84 (s, 6H, 2´, 3´-CH3) ppm. In addition, the following
13
signals are monitored form the C NMR spectrum of the spirocyclopropene 7: 162.10 (C=O of
both 2´,3´-COOCH3), 155.20 (C=N of tetrazole rings), 151.28, 147.39 (C1,C8 of fluorene), 145.31
(two quaternary carbons between the two phenyl rings of fluorene), 141.99 (C=C of
spirocyclopropene ring), 131.69 (2,7-quaternary C of fluorene), 128.10 (4,5-C of fluorene), 125.28
( 3,6-C of fluorene), 62.78 (C-spiro) and at 52.02 (2 CH3 of 2´,3´-COOCH3). Furthermore, the
HRMS show the exact mass of 442.1109 which exactly fit with the theoretical calculated value.

Scheme 2. Synthetic outline of (R)-dimethyl 2',7'-di(2H-tetrazol-5-yl)spiro[cycloprop[2]ene-1,9'-
fluorene]-2,3-dicarboxylate 7 precursor via “Click” chemistry strategy.
2.2. Solid state synthesis of photochromic dimethyl 2,7-di(2H-tetrazol-5-yl)-4a'H-spiro[fluorene-
9,5'-pyrrolo[1,2-b]pyridazine]-6',7'-dicarboxylate 10.
Grinding using mortar and pestle of equimolar amount of spirocyclopropene 7 obtained via the
43-46
pyrazole route
with pyridazine 8 and quantity of silica gel (2 gm) as drying agent for 30
minutes, was left standing for 1h, then grinding started gain for further 30 minutes at ambient
temperature while keeping the mixture in complete protection from light for 5 hours (TLC-
controlled) afforded the desired photochromic dimethyl 2,7-di(2H-tetrazol-5-yl)-4a'H-
spiro[fluorene-9,5'-pyrrolo[1,2-b]pyridazine]-6',7'-dicarboxylate 10 in 82% yield (Fig. 1, table 1).
Formation of photochromic DHI 10 occurs through nucleophilic attack of the nitrogen atom of N-
heterocycle pyridazine 8 to electron-deficient spirocyclopropene 7 and accordingly opened via a
cyclopropyl-allyl intermediate 6` to afford colored betaine intermediate 6 that closes to the DHI
10 in a slightly slow 1,5-electrocyclization process (scheme 3).

Fig. 1. Representation and conversions of the one-pot solid state synthesis of photochromic DHIs
10, 18, 27 (A: reactants before grinding; B: after grinding for 1 h; C: after keeping in absence of
light).

Scheme 3: Solid state synthesis of photochromic substituted dimethyl 2,7-di(2H-tetrazol-5-yl)-
4a'H-spiro[fluorene-9,5'-pyrrolo[1,2-b]pyridazine]-6',7'-dicarboxylate 10.
A noticeable advantage of the one-pot solid state synthesis of the photochromic DHI 10
involves obtaining the spectroscopically pure product after a single column chromatography trial.
Further benefits of this mechanochemical are the short reaction time, pronounced high product
yield without any undesired products. This leads to effortless purification and separation processes.

Moreover, the current developed method will help in getting over many synthetic and purification
challenges for new compounds subsequently discovered in this class of photochromic materials.
Furthermore, the chemical structure and the purity of photochromic DHI 10 is examined by both
1
analytical and spectroscopic measurements. For example, the H NMR spectrum of the
photochromic DHI 10 represents the following signals:  = 7.92 (d, J=7.20 Hz, 2H, 4,5-CH-
flourene), 7.82 (dd, J=1.54 Hz, 2H, 1,8-CH-fluorene), 7.64 (dd, J=7.56, J=1.54 Hz, 2H, 3,6-CH-
fluorene), 6.95 (dd, J=1.54 Hz, 1H, J=1.54 Hz, 6´-CH-pyradizine), 5.60-6.63 (m, 1H, 7´-CH-
pyradzaine), 5.45 (t, J=2.20 Hz, 1H, 8a´-CH-pyradazine), 5.04 (dt, J=9.70 Hz J=1.75 Hz, 8´-CH-
pyradazine), 4.05 (s, 3H, 3´-CH3 of the ester group), 3.31 (s, 3H, 2´-CH3 of the ester group) ppm.
13
3
In addition, the C NMR (CDCl ) reveled the following signals:  = 166.82 (3´-CO), 164.99 (2´-
CO), 155.09 (C=N of tetrazole rings), 148.89, 146.43, 141.79, 139.00, 138.81, 137.00, 133.87,
132.34, 128.34, 127.81, 124.99, 124.49, 123.32, 120.79, 120.67, 118.13, 102.82, 66.36 (8´a-C),
63.32 (Spiro-C), 53.38 (3´-CH3), 51.33 (2´-CH3) ppm. Furthermore, The IR (KBr) spectrum of the
photochromic DHI 10 represents the following signals: 1/= 3226 (NH-of tetrazole rings), 3032-
3165 (C-H, arom.), 2912-2988 (C-H, aliph.), 1742 (3´-C=O), 1685 (2´-C=O), 1610 (C=N), 1564
-1
(C=C), 1446, 1323, 1247, 1232, 1149, 1136, 1028, 979, 840, 810, 759 cm .
2.3. Synthesis
of
(R)-dimethyl
2',7'-bis(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-
yl)spiro[cycloprop[2]ene-1,9'-fluorene]-2,3-dicarboxylate 16.
Spirocyclopropene precursor 16 which bearing oxadiazole moieties in 2,7-position the fluorene
part (region A) is achieved (Scheme 4) starting from the reaction of previously prepared 2,7-di(2H-
tetrazol-5-yl)-9H-fluoren-9-one 3 with 4-tert-butylbenzoyl chloride 11 in freshly dried pyridine to
afford the oxadiazoles derivative 12 in 73% yield after crystallization from isopropanol.

Condensation of 2,7-bis(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)-9H-fluoren-9-one 12 with
hydrazine hydrate in refluxing ethanol for about 6 h afforded the condensation product 5,5'-(9-
hydrazono-9H-fluorene-2,7-diyl)bis(2-(4-tert-butylphenyl)-1,3,4-oxadiazole) 13 in moderate
yield (56%), The obtained product is pure enough (TLC-controlled) and used in the next oxidation
step without additional purification. The IR-spectrum of compound 13 shows two peaks at 3320
and 3210 cm-1 which is corresponding the NH2 group and disappearance of the signal at 1710
which corresponding to the carbonyl group at 9-postion of the fluorene moiety.

Scheme 4. Synthetic outline of spirocyclopropene 16 bearing oxadiazole moieties as precursor
for the synthesis of photochromic DHI 18.

Heterogenous oxidation of the hydrazine derivative 3 with yellow mercuric oxide in freshly
dried THF in presence of catalytic of amount of KOH/Na2SO4 at ambient temperature in absence
of light affords the 5,5'-(9-diazo-9H-fluorene-2,7-diyl)bis(2-(4-tert-butylphenyl)-1,3,4-
oxadiazole) 14 in low yield (29%). Cycloaddition of MADC to 9-diazofluorene compound 14
under dark condition for 32 h afforded dimethyl 2,7-bis(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-
yl)spiro[fluorene-9,3'-pyrazole]-4',5'-dicarboxylate 15 in 42
%
yield. The precursor
spirocyclopropene derivative 16 is obtained in 26 % yield by UV-light irradiation of the pyrazole
derivative 15 with high pressure mercury lamp (125W) in freshly dried ether for three hours under
dry nitrogen atmosphere. The product is used for building-up the target photochromic DHI 18
without further purification. Confirmation of the chemical structures of the synthesized
compounds 12-16 (scheme 4) were established by both spectroscopic and analytical tools. The 1H
NMR (500 MHz, CDCl3) of the spirocyclopropene precursor 16 represented signals at:  8.12-8
(d, 4H, J=7.69, 4-CH-phenyl rings); 7.84 (d, J=7.69, 2H, 4,5-CH-fluorene), 7.75 (s, 2H, 1,8-CH-
fluorene), 7.69 (d, J=7.68, 2H, 3,6-CH-fluorene), 7.52 (dt, J=7.60, J=1.75, 4H, 4-CH-phenyl
rings), 7.40 (dd, H, J=7.69, J=1.74, 2H, CH-phenyl ring), 3.88 (s, 6H, 2´,3´-COOCH3), 1.32 (s,
18H, C(CH3)3 ppm. In addition, the following signals are monitored form the 13C NMR (125 MHz,
CDCl3) spectrum of the spirocyclopropene 16: 167.69 (C=O of both 2´,3´-COOCH3), 164.51 (C=N
of oxadiazole rings), 144.20 (C1,C8 of fluorene), 142.36(two quaternary carbons between the two
phenyl rings of fluorene), 136.80 (C=C of spirocyclopropene ring), 133.56 (quaternary C of the
phenyl ring), 131.23 (CH-phenyl ring), 130.78 (CH-phenyl; ring), (131.67 (2,7-quaternary C of
fluorene), 129.02 (CH-phenyl ring), 128.78 (4,5-C of fluorene), 126.02 ( 3,6-C of fluorene), 63.79
(C-spiro) and at 52.08 (2 CH3 of 2´,3´-COOCH3) 31.49 (C(CH3)3), 28.99 (3CH3) ppm.

2.4. Synthesis of photochromic dimethyl 2,7-bis(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)-
4a'H-spiro[fluorene-9,5'-pyrrolo[1,2-b]pyridazine]-6',7'-dicarboxylate 18 via solid state
synthesis methodology.

Scheme 5. Synthesis of photochromic dimethyl 2,7-bis(5-(4-tert-butylphenyl)-1,3,4-
oxadiazol-2-yl)-4a'H-spiro[fluorene-9,5'-pyrrolo[1,2-b]pyridazine]-6',7'-dicarboxylate 18.
Similar method described in the synthesis of photochromic DHI 10 is applied for the synthesis of
the DHI 18. Thus, nucleophilic attack of the nitrogen atom of the of pyridazine heterocycle 8 to
spirocyclopropene 16 using the cyclopropene route (schemes 5) through grinding both compounds
in presence of some amount of silica gel for 30 min. and keeping the mixture for 30 min. then
grinding started again for addition 30 min. and the reaction mixture kept at room temperature under
dark condition (TLC-controlled using CH2Cl2 as eluent) for 6 h for completing reaction. The pure
photochromic DHI 18 is obtained as yellow powder in 84 % yield via elution of the mixture
through column chromatography using dichloromethane as eluent. As mentioned previously, the
reaction happened via the addition electrophilically of the electron-deficient spirocyclopropene 16
to the nitrogen of the N-heterocyclic pyridazine 8 which afforded ring opening through a
cyclopropyl-allyl conversion 17` to betaines 8A successive ring-closure to DHI 16 takes place in
a moderately slow thermal 1,5-electrocyclization back reaction (scheme 5) which can be upturned
to the colored betaine upon exposure to light. The chemical structure of the photochromic DHI 18
elucidated by both spectroscopic and analytical tools. For example, 1H NMR (500 MHz, CDCl3)
of DHI 18 reveled the following signals:  8.26-8.29 (d, 2H, 2-CH-phenyl rings); 7.95-7.98 (d,
2H, 4,5-CH-fluorene), 7.85 (s, 2H, 1,8-CH-fluorene), 7.73-7.75 (d, 2H, 3,6-CH-fluorene), 7.49-
7.52 (dt, 2H, 2-CH-phenyl rings), 7.43-7.45 (dd, H, 1H, CH-phenyl ring), 6.94-6.96 (dd, 1H,
J=1.54 Hz, 6´-CH-pyradazine), 5.79-6.84 (m, 1H, 7´-CH-pyradzaine), 5.49-5.52 (t, 1H, 8a´-CH-
pyradazine), 5.13-5.16 (dt, 8´-CH-pyradazine), 3.99 (s, 3H, 3´-CH3 of the ester group), 3.49 (s,
3H, 2´-CH3 of the ester group) 1.37 (s, 18H, C(CH3)3 ppm.

2.5. Synthesis dimethyl 4'-(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)spiro[cycloprop [2]ene-
1,9'-fluorene]-2,3-dicarboxylate precursor 25.
As presented in scheme 6, the synthesis of spirocyclopropene precursor 25 is achieved through
five steps chemical and photochemical reactions. Reaction of equimolar from 9-oxo-9H-fluorene-
4-carbonyl chloride 19 and 5-(4-tert-butylphenyl)-1H-tetrazole 20 [61-66] in pyridine at 100 ºC
for 5 h led to the formation of 4-(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)-9H-fluoren-9-one
21 as yellow needles in 61% after crystallization from ethanol. Condensation of fluorenone
derivative 21 with hydrazine in refluxing ethanol for 7 h yielded the corresponding hydrazone
derivative 22 as orange solid powder in 49% yield. The IR spectrum of the hydrazone derivative
22 shows two peaks as 3280 and 3175 due to the presence of NH2 group. In addition, the
appearance of broad single at around 5.79 ppm for NH2 protons which disappeared by deuteration
with deuterium oxide.

Scheme 6. Preparation outline of spirocyclopropene precursor 25.

The diazofluorene derivatives 23 is obtained after hydrazone 22 oxidation by yellow mercuric
oxide in dry THF and in presence of catalytic amount of KOH/Na2SO4 at room temperature with
exclusion from light as orange crystals in 52 % yield. On the other hand, when MADC added to
the 9-diazofluorene derivative 23 in freshly dried ether and dark condition for 29 h, (R)-dimethyl
4-(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)spiro[fluorene-9,3'-pyrazole]-4',5'-dicarboxylate
24 is obtained in poor yield (43%).
The target precursor spirocyclopropene derivative, namely, dimethyl 4'-(5-(4-tert-
butylphenyl)-1,3,4-oxadiazol-2-yl)spiro[cycloprop[2]ene-1,9'-fluorene]-2,3-dicarboxylate 25 is
obtained as yellow powder in 33% yield via photolysis of the pyrazole derivative 24. Photolysis
done using high pressure mercury lamp (125Wt) in freshly distilled acetonitrile for five hours
under dry condition. The chemical structure of the newly synthesized spirocyclopropene 25
(scheme 6) is elucidated by means of and analytical tools. the 1H NMR (500 MHz, CDCl3) of the
precursor 25 showed signals at:  8.24 (d, 2H, 2-CH-phenyl ring); 7.92 (d, J=7.69, 2H, 4,5-CH-
fluorene), 7.80 (t, J=6.79, 1H 2-CH-flouorene); 7.75 (s, 1H, 1,8-CH-fluorene), 7.69 (d, J=7.68,
2H, 3,6-CH-fluorene), 7.37 (dt, J=7.69, J=1.74, 2H, 2-CH-phenyl rings), 7.22 (dd, H, J=7.80,
J=1.76, 1H, 1-CH-phenyl ring), 3.42 (s, 6H, 2´,3´-COOCH3), 0.96 (s, 9H, 3CH3-tert-butyl group).
In addition, the following characteristic signals are monitored form the 13C NMR (125 MHz,
CDCl3) spectrum of the spirocyclopropene 25: 166.41 (C=O of both 2´,3´-COOCH3), 163.99 (C=N
of oxadiazole rings), 146.49 (C1,C8 of fluorene), 143.01 (two quaternary carbons between the two
phenyl rings of fluorene), 135.99 (C=C of spirocyclopropene ring), 134.29 (quaternary C of the
phenyl ring), 130.99 (CH-phenyl ring), 129.20 (CH-phenyl; ring), 131.67 (2-quaternary C of
fluorene), 130.19 (CH-phenyl ring), 127.70 (4,5-C of fluorene), 125.46 ( 3,6-C of fluorene), 124.36

(7-CH-fluorene); 64.34 (C-spiro), 69.16 (quaternary carbon of tert-butyl group) and at 55.19 (2
CH3 of 2´,3´-COOCH3), 19.23 (3CH3-tert-butyl group).
2.6. Synthesis (5'R)-dimethyl 4-(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)-4a'H-spiro[fluorene-
9,5'-pyrrolo[1,2-b]pyridazine]-6',7'-dicarboxylate 27.
Scheme 7. Synthetic presentation of photochromic (5'R)-dimethyl 4-(5-(4-tert-butylphenyl)-
1,3,4-oxadiazol-2-yl)-4a'H-spiro[fluorene-9,5'-pyrrolo[1,2-b]pyridazine]-6',7'-dicarboxylate 27.
The photochromic dihydroindolizine 27 is achieved by nucleophilic addition pyridazine 8 to
spirocyclopropene 25 using cyclopropene-DHI pathway (scheme7). The reaction occurs by
continuous pestle hand-grinding of the spirocyclopropene 25 with pyridazine 8 for 30 minutes,

then, resting for 1h then, grading started again for 30 minutes, then, keeping the mixture in dark
condition at ambient temperature for 9 h. The pure photochromic DHI 27 is obtained using column
chromatography by elution the mixture with dichloromethane on silica gel as stationary phase.
The pure product is obtained as yellow needles in 76% yield. The chemical structure of the
photochromic DHI 27 is well-confirmed by both NMR spectroscopy and HRMS analysis (the
HRMS analysis for the DHI 27 detected the exact molecular weight of 586.2201 and C%=
1
71.67001; H% = 5.1493; N%= 9.5459). The following H NMR (500 MHz, CDCl3) signals is
monitored in spectrum of the DHI 27:  8.48 (d, J=6.72, 2H, 2-CH-phenyl ring); 7.83 (d, J=7.69,
2H, 4,5-CH-fluorene), 7.72 (t, J=6.79, 1H 2-CH-flouorene); 7.69 (s, 1H, 1,8-CH-fluorene), 7.61
(d, J=7.68, 2H, 3,6-CH-fluorene), 7.51 (dt, J=7.69, J=1.74, 2H, 2-CH-phenyl rings), 6.83 (dd,
J=1.54 Hz, 1H, J=1.54 Hz, 6´-CH-pyradazine), 5.69-6.72 (m, 1H, 7´-CH-pyradzaine), 5.23 (t,
J=2.20 Hz, 1H, 8´-CH-pyradazine), 5.11 (dt, J=9.70 Hz J=1.75 Hz, 8´a-CH-pyradazine), 3.86 (s,
3H, 3´-CH3 of the ester group), 3.43 (s, 3H, 2´-CH3 of the ester group), 1.29 (s, 9H, 3CH3-tert-
butyl group) ppm. In addition, the following signals are monitored form the 13C NMR (125 MHz,
CDCl3) spectrum of the DHI 27: 167.41 (2`-C=O of ester), 165.03 (3`-C=O of the ester group),
164.32 (C=N of oxadiazole ring), 152.03 (C-phenyl ring), 143.03 (C-fluorene), 142.63 (C-phenyl
ring), 141.8 (C-fluorene ), 140.36 (C-fluorene ), 137.10 (8`-C-pyradazine), 136.46 (6`-C-
pyradazine), 135.87 (4C-fluorene), 135.01 (C-fluorene), 135.64 (C-fluorene),128.12 (2C-
fluorene), 128.41 (1,8-C-fluorene), 127.99 (7C-fluorene), 127.46 (C-phenyl ring), 126.89 (7C-
fluorene), 126.20 (6C-fluorene), 125.63 (C-phenyl ring), 122.65 (7`-C-pyradazine), 69.31 (8`a-C-
pyradazine), 66.97 (C-spiro), 64.34 (C-spiro), 52.30 (3`-CH3 of the ester group), 50.99 (2`-CH3 of
the ester group), 38.03 (C-tert-butyl group). Additional assignments of 8`-CH, 8`a-CH and some
other fluorene protons are recorded with the help of NOESY spectrum of DHI 27. Its worthy to

report that, 8`a-CH at  = 5.10 ppm is proximal to 8`-CH at  = 5.23 ppm, and 1-CH of the fluorene
moiety at  = 7.69 ppm. This suggests that 8`a-CH is in 8`a-position and not at 8`-position. Indeed,
the connectivity between 8`-CH and 8-CH of the fluorene part at  = 7.69 ppm was observed. This
vicinity of 8`-CH with 8-CH indicates that the pyridazine moiety is perpendicular to the fluorene
skeleton. This surveillance supported also by molecular mechanics calculation (MM2) of DHI 27
(Fig. 2). The MM2 calculation represented the distance between both 8`a-CH and 8`-CH connected
to the 6`-CH and 1-CH of the fluorene moiety is < 3 Å and this in good matching with the NMR
data (Fig. 2).
Fig. 2. Optimized (MM2) structure of DHI 27.
3. Photophysical properties of the newly synthesized photochromic DHIs 10, 18, 27 and their
corresponding betaines 9, 17, 26 in dichloromethane solution at ambient temperature.

3.1. Absorption spectra
The absorption spectra of the newly synthesized photochromic DHIs 10,18, 27 were
recorded using a UV/VIS/NIR spectrophotometer in concentration of 1x10-5 mol/L at room
temperature. The photochromic DHIs under examination displays yellow color in both solution
and solid state (table 1). The absorption maxim for the DHIs 10, 18 and 27 was monitored in far
UV-region exhibiting absorption maxima in the range of 387 and 397 nm (Figs. 3-5, table 1). These
monitored absorptions are reliant on number of triazole and oxazole moieties substituted the
fluorene region. A noticeable bathochromic shift by about 10 nm by changing the substituents
from tetrazoles as in DHI 8 to oxadiazoles as in DHI 18 in the 2,7 was recorded. This may be
ascribed to the different in the aromaticity of both heterocyclic tetrazole and oxadiazole moieties
of the DHI after “click” reaction. In general, the “click” chemistry on the 4-position of the fluorene
moiety as in DHI 27 (396 nm) did not display a pronounced effect on the absorption maxima of
the DHI system compared with the oxadiazole DHI derivative 18 (397 nm).
1.3
521 nm
1.2
387 nm
1.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
DHI 10
Betaine 9
300
350
400
450
500
550
600
650
700
750
Wavelength (nm)

Fig. 3. UV/VIS/NIR of photochromic DHI 10 and the corresponding betaine form 9 after UV
irradiation in CH2Cl2 (c= 1x10-5mol/L) at room temperature.
0.5
625 nm
397 nm
DHI 18
0.4
Betaine 17
490 nm
0.3
0.2
0.1
0.0
300 350 400 450 500 550 600 650 700 750 800 850
Wavelength (nm)
Fig. 4. UV/VIS/NIR of photochromic DHI 18 and the corresponding betaine form 17 after UV
irradiation in CH2Cl2 (c= 1x10-5mol/L) at ambient temperature.
1.0
612 nm
0.9
DHI 18
0.8
396 nm
Betaine 17
0.7
472 nm
0.6
0.5
0.4
0.3
0.2
0.1
0.0
300 350 400 450 500 550 600 650 700 750 800 850
Wavelength (nm)

Fig. 5. UV/VIS/NIR of photochromic DHI 27 and the corresponding betaine form 26 after UV
irradiation in CH2Cl2 (c= 1x10-5mol/L) at ambient temperature.
3.2. Kinetics of the 1,5 electrocyclization of betaines 9,17, 26 to their corresponding DHIs 10,18,
27.
The polychromatic light irradiation of DHIs 10, 18, 27 leads to produce of the opened betaines
9, 17, 26 (Figs. 2-4). The colored betaines 9, 17, 26 found to be red to blue color is observable in
CH2Cl2 solution with concentration of 1x10-5 mol/L at room temperature. The observable
coloration is attributed to their slower 1,5-electrocyclization which signifies the stabilization of the
zwitter-ionic betaine adopted by different heterocyclic rings substitution in the fluorene region.
All the absorption maxima of the colored betaines 9, 17, 26 were recorded in the visible region
between 521 nm (betaine 9) and 625 nm (betaine 17). The monitoring of different isosbestic points
exhibits that the 1,5- electrocyclization of the back reaction of the colored betaines obeys the first
order reaction kinetics. Furthermore, a drastic and highly pronounced bathochromic shift of about
114 nm was monitored upon changing the substituents from tetrazole as in betaine 9 (521 nm, red
color) to oxadiazole moieties (625 nm, blue color) in 2,7- fluorene position. This may be due to
increasing of aromaticity and conjugation in presence of the substituted oxadiazole derivatives. In
addition, a small bathochromic shift of about 13 nm by changing the substituents from 2,7-position
as in betaine 17 (625 nm, blue color) and 4- position substitution of the fluorene skeleton as in
betaine 26 (612 nm, blue color) is recoded. The most obvious influence is found on the colorability
which found to be strongly dependent on the substitution which led the pronounced effect on the
absorbance of the colored betaines 9, 17, 26 (Figs. 6-8). This may be ascribed to increasing of the
conjugation and aromaticity in the betaine forms of the DHI skeleton. 39-46
.

521 nm
zero s
1.2
1.0
0.8
0.6
0.4
0.2
387 nm
600 s
350
400
450
500
550
600
650
700
750
Wavelength (nm)
Fig. 6. Kinetic FT-UV/VIS spectrum of the thermal fading of betaine 9 to DHI 10 function of
time (cycle time = 30 s, run time = 600 s) in CH2Cl2 (c= 1x10-5 mol/L at 253 K.
0.5
625 nm
zero s
397 nm
0.4
300 s
0.3
490 nm
0.2
0.1
0.0
300 350 400 450 500 550 600 650 700 750 800 850
Wavelength (nm)
Fig. 7. Kinetic FT-UV/VIS spectrum of the thermal fading of betaine 18 to DHI 17 function of
time (cycle time = 30 s, run time = 300 s) in CH2Cl2 (c= 1x10-5 mol/L at 253 K.

1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
612 nm
zero s
2000 s
396 nm
472 nm
300 350 400 450 500 550 600 650 700 750 800 850
Wavelength (nm)
Fig. 8. Kinetic FT-UV/VIS spectrum of the thermal fading of betaine 26 to DHI 27 function of
time (cycle time = 30 s, run time = 2000 s) in CH2Cl2 (c= 1x10-5 mol/L at 253 K.
To study the photochromic performances of the DHIs 10, 18, 27 and their corresponding betaines
9, 17, 26 in solution, kinetic measurements done by the help of FT-UV-Vis spectrophotometry
(Figs. 6-8). The rate constants of the 1, 5 electrocyclization of the betaines 9, 17, 26 were regulated
at constant temperature by measuring the decrease in the maximum absorption intensity (max
)
with time. The half-lives (t1/2) and rate constants (k) of betaines were estimated by plotting time
(t) with lnA. The 1,5-electrocyclization reaction of the examined betaines found to be well- fit with
a first-order mechanism which is good agreement with reported literature results. 39-48 The t1/2 of
betaines 9, 17 and 26 could be determined by UV-VIS-NIR spectrophotometer due to their slow
rate constant (k). The half-lives ambient temperature of the coloured betaines 9, 17 and 26 are
found to be 469 s, 171s and 1369 s, respectively (Table 1). The pronounced increasing in the half-
life of the betaine 26 which bearing oxadiazole moiety in 4-position of the fluorene part compared
with the 2- and 2,7-tetrazolo substituted fluorene 9,17, respectively may be due to the stabilization

of the positive charge on the betaine forms by hyper conjugation effect. Furthermore, it is plausible
that the closeness of the 2- and 2,7- disubstituted fluorene by tetrazole moiety to the reacting centre
on the pyridazine moiety accelerate the 1,5- electrocyclization process. The pronounced tuning of
the photophysical properties by varying the fluorene substitution position as well as the type of
heterocyclic moieties maybe assist this class of photochromic materials to find some applications.
3.3. Fluorescence emission spectra of the newly synthesized photochromic DHIs 10, 18 and 27 in
dichloromethane solution (c= 1x 10-6 mol/L) at 273 K.
The fluorescence emission offers the possibility for an excited molecule to be deactivated. The
emission energy is responsible for the electromagnetic radiation which is the fluorescence light.
When a molecule absorbs light, its electronic configuration along with its total energy changes,
starting from the ground state (S0) to singlet state (Sn). The electronic transitions are faster (10-15
s) than vibration (10-3s), so that the stimulated state has the same geometry (normally according to
the Frank-Crudan-principle and the same bond length as given in the ground state. To the best of
our knowledge, few photochromic classes such as anthracenes, spiropyrans74 and fulgimides75
showed fluorescence emission. For example, no emission has been recorded for
spiroindolinooxazines although the quantum yield of the ring-opening of the spiro skeleton is ca.
0.5042). The spiro derivatives for which a fluorescence emission has been reported with a quantum
yield of about 0.001 belongs to the dihydroindolizine series.39-43. For the possible application in
the field of information recording, fast ring-opening of the spiro molecule to the betaine-type form
is highly anticipated.
In the current work, a successful synthesis of such systems having a quantum yield of ranged
between 0.98 and 5.01x10-3 depending on the substituents in the fluorene regions. In general, the