# Photochromism of Dihydroindolizines Part XI: Synthesis of Novel Carbon-Rich Photochromic Dihydroindolizines-Based Potential Electronic Devices

Authors: Saleh Abdel-Mgeed Ahmed
Journal: Research Letters in Organic Chemistry
 (2008)

---

## Abstract

Novel carbon-rich photochromic dihydroindolizine (DHI) derivatives substituted in the fluorene part (region A) in addition to the new spirocyclopropene 6 have been synthesized. The synthesis of dimethyl2′,7′-diethynylspiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicarboxylate precursor 6 was accomplished in five steps, starting with the literature known conversion of fluorene to 2,7-dibromo-9H-fluoren-9-one in 56% yield over three steps. The chemical structures of the new synthesized materials have been elucidated by both analytical and spectroscopic tools. Three alterative synthetic pathways for the synthesis of DHI
9 have been established.


---

## Body

## 1. Introduction

Molecules that
respond to the application of external stimuli by undergoing reversible
transformations between two distinct structures have the potential to
significantly influence the development of numerous important materials science
and structural biology technologies [1, 2]. This potential is based on the fact
that, because the molecules typically undergo dramatic changes in their
electronic and topological characteristics, they can act as switching elements
and other dynamic components in various optoelectronic devices and functional
materials. Photons are particularly appealing stimuli because modern lasers can
be used to achieve fast response times, to focus a fine-tuned stimulus on small
localized domains without significant diffusion and to trigger photochemical
events under conditions mild enough to pose minimal danger to sensitive
biomaterials. Compounds that interconvert between different isomers having
unique absorption spectra when stimulated with light are referred to as photochromic,
and the process is called photochromism. In these systems, the changes in the
electronic patterns responsible for the changes in color also result in
variations in other practical physical properties such as luminescence [3], electronic
conductance [4, 5], refractive index [6], optical rotation [7], and viscosity [8, 9]. These materials, based on the
1,5-electrocyclization between two distinct isomeric states: ring-opening form
(betaine-form) and ring-closed form (DHI-form), are promising candidates for optical
storage media and electronic devices [10–29].As a
continuation of our research on photochromic dihydroindolizines (DHIs), this manuscript
is devoted to the synthesis of carbon-rich
fluorenyl-dihydroindolizines derivatives and represents the first step
toward the application of photochromic dihydroindolizines in electronic devices. Different synthetic approaches will be described.


## 2. Results and Discussion

### 2.1. Synthesis of Fluorenylacetylene Spirocyclopropene Precursor 6

The synthesis of
spirocyclopropene6 was accomplished in five steps, starting with the previously
known conversion of fluorene to 2,7-dibromo-9H-fluoren-9-one in 56% yield in over
three steps [10–13] (see Scheme 1). The Sonogashira-coupling of 2,7-dibromo-9H-fluoren-9-one
with trimethylsilylacetylene (TMSA) in the presence of Pd(PPh)3Cl2 (5 wt%)/CuI/Et2NH in THF at room temperature for 24 hours afforded
the coupling product 2,7-bis((trimethylsilyl)ethynyl)-9H-fluoren-9-one
2 in
good yield (79%). Interestingly, condensation of compound 2 with hydrazine
hydrate in boiling ethanol for 6 hours leads not only to the formation of the condensation product (2,7-bis((trimethylsilyl)ethynyl)-9H-fluoren-9-hydrazone  but also to the occurrence of dimethyl silylation, and to the obtainment
of (2,7-di(prop-1-ynyl)-9H-fluoren-9-ylidene)hydrazone 3 in 47% yield. The
evidence for the formation of compound 3 was established by
1HNMR which
showed the complete disappearance of the trimethylsilyl protons which appear as singlet at 0.4 ppm in compound 2 and the appearance of a singlet at 4.05 ppm in
compound 3 which is related to the acetylenic proton in
addition to the presence of a broad singlet at 5.32 ppm corresponding to the NH2 protons which disappeared upon treatment with deuterium oxide. Oxidation of the
hydrazone 3 with manganese dioxide in dry ether at room temperature in the absence
of light afforded the 9-diazo-2,7-di(prop-1-ynyl)-9H-fluorene 4 in moderate
yield (56%). Addition of methyl acetylenedicarboxylate (MADC) to the
9-diazofluorene derivative 4 in dry ether in dark condition for 24 hours led to
the formation of dimethyl
2,7-diethynylspiro[fluorene-9,3′-pyrazole]-4′,5′-dicarboxylate 5 pyrazole
derivative 6 in 37% yield.Scheme 1
The synthesis of dimethyl
2′,7′-diethynylspiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicarboxylate precursor 6.Photolysis
of the pyrazole derivative5 with high pressure mercury lamp (125 W) in dry
ether solution for two hours under nitrogen atmosphere gave the target dimethyl
2′,7′-diethynylspiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicarboxylate 6 in low
yield (22%).  The reaction was accompanied with the formation of some
unidentified product which is expected to be related to some addition polymerization on the two
acetylenic groups in the fluorene part (region A) which leads to the decreasing
of the yield of the desired spirocyclopropene derivative 6. The chemical
structure of the newly synthesized compounds 2–6 (see Scheme 1) was
confirmed and established by both spectroscopic (NMR, IR, and mass
spectrometry) and analytical tools (give satisfactory elemental analysis data).
For example, the 1HNMR (400 MHz, CDCl3) of the
spirocyclopropene precursor 6 showed the following signals: δ 7.82–7.86 (d, J  =  1.76 Hz, 1H, CH-arom.), 7.63–7.67 (d, J  =  1.32 Hz, 1H, CH-arom.), 7.52–7.57 (m, 4H,
CH-arom.), 4.11 (s, 2H, acetylenic protons in 2,7 position), 3.82 (s, 6H, 2′,3′-CH3) ppm.


### 2.2. Different Attempts for Synthesis of the Photochromic Dihydroindolizine 9

Nucleophilic
addition of pyridazine7 to spirocyclopropene 6 using the cyclopropene route [10–29] (see Scheme 2)
in dry ethereal solution at room temperature under dry nitrogen in the absence
of light (TLC-controlled using CH2Cl2 as eluent) led to
the formation of the photochromic dihydroindolizine (DHI) 9 in low yield (26%).
The reaction occurs through the electrophilic addition of the
electron-deficient spirocyclopropenes 6 tothe nitrogen of the N-heterocyclic  pyridazine 7 which led to ring opening via
a cyclopropyl-allyl conversion 8′ to the colored betaines 8. A subsequent ring closure to DHI 9 results in a slow thermal 1,5-electrocyclization
back reaction (see Scheme 2) which can be reversed upon exposure to light. Pure
photochromic DHI 9 was obtained in all cases by two successive column
chromatography operations on silica gel using dichloromethane as the eluent.Scheme 2
Preparation outline of photochromic DHI9 from spirocyclopropene 6.Another
successful alternative method for the synthesis of the target photochromic DHI9
was achieved through the following multistep synthesis (see Scheme 3). The
Sonogashira coupling  of dimethyl
2,7-dibromo-4a′H-spiro[fluorene-9,5′-pyrrolo[1,2-b]pyridazine]-6′,7′-dicarboxylate
which was previously prepared by us [10–13] with
trimethylsilylacetylene in presence of palladium-catalyzed reaction (5%) and
CuI/Et2N in T  =  dry THI for 12 hours [29, 30] yielded the  desired
product dimethyl
2,7-bis((trimethylsilyl)ethynyl)-4a′H-spiro[fluorene-9,5′-pyrrolo[1,2-b]pyridazine]-6′,7′-dicarboxylate 11 in 34% yield after purification by flash chromatography on silica gel and CH2Cl2 as eluent. Treatment of DHI 11 with tetrabutyl ammonium fluoride (TBAF) in dry
THF for 17 hours afforded the trimethylsilylated product 9 in 68% yield. A good
proof for the trimethylsilylation that occurs during the condensation of
compound 2 with hydrazine hydrate is that detrimethylsilylation occurs when DHI
11 was treated with hydrazine hydrate in ethanol under mild conditions and at
low temperature (0°C) for 2 hours in 43% yield. Thus, acetylenic DHI 9 could
successfully prepared through three reactions’ pathways as shown in Schemes 2
and 3. The three products obtained from the different pathways showed the same
analytical and spectroscopic data as well as m.p and m.m.p.Scheme 3
Another reaction pathway for the synthesis
of the target photochromic DHI9.


## 2.1. Synthesis of Fluorenylacetylene Spirocyclopropene Precursor 6

The synthesis of
spirocyclopropene6 was accomplished in five steps, starting with the previously
known conversion of fluorene to 2,7-dibromo-9H-fluoren-9-one in 56% yield in over
three steps [10–13] (see Scheme 1). The Sonogashira-coupling of 2,7-dibromo-9H-fluoren-9-one
with trimethylsilylacetylene (TMSA) in the presence of Pd(PPh)3Cl2 (5 wt%)/CuI/Et2NH in THF at room temperature for 24 hours afforded
the coupling product 2,7-bis((trimethylsilyl)ethynyl)-9H-fluoren-9-one
2 in
good yield (79%). Interestingly, condensation of compound 2 with hydrazine
hydrate in boiling ethanol for 6 hours leads not only to the formation of the condensation product (2,7-bis((trimethylsilyl)ethynyl)-9H-fluoren-9-hydrazone  but also to the occurrence of dimethyl silylation, and to the obtainment
of (2,7-di(prop-1-ynyl)-9H-fluoren-9-ylidene)hydrazone 3 in 47% yield. The
evidence for the formation of compound 3 was established by
1HNMR which
showed the complete disappearance of the trimethylsilyl protons which appear as singlet at 0.4 ppm in compound 2 and the appearance of a singlet at 4.05 ppm in
compound 3 which is related to the acetylenic proton in
addition to the presence of a broad singlet at 5.32 ppm corresponding to the NH2 protons which disappeared upon treatment with deuterium oxide. Oxidation of the
hydrazone 3 with manganese dioxide in dry ether at room temperature in the absence
of light afforded the 9-diazo-2,7-di(prop-1-ynyl)-9H-fluorene 4 in moderate
yield (56%). Addition of methyl acetylenedicarboxylate (MADC) to the
9-diazofluorene derivative 4 in dry ether in dark condition for 24 hours led to
the formation of dimethyl
2,7-diethynylspiro[fluorene-9,3′-pyrazole]-4′,5′-dicarboxylate 5 pyrazole
derivative 6 in 37% yield.Scheme 1
The synthesis of dimethyl
2′,7′-diethynylspiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicarboxylate precursor 6.Photolysis
of the pyrazole derivative5 with high pressure mercury lamp (125 W) in dry
ether solution for two hours under nitrogen atmosphere gave the target dimethyl
2′,7′-diethynylspiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicarboxylate 6 in low
yield (22%).  The reaction was accompanied with the formation of some
unidentified product which is expected to be related to some addition polymerization on the two
acetylenic groups in the fluorene part (region A) which leads to the decreasing
of the yield of the desired spirocyclopropene derivative 6. The chemical
structure of the newly synthesized compounds 2–6 (see Scheme 1) was
confirmed and established by both spectroscopic (NMR, IR, and mass
spectrometry) and analytical tools (give satisfactory elemental analysis data).
For example, the 1HNMR (400 MHz, CDCl3) of the
spirocyclopropene precursor 6 showed the following signals: δ 7.82–7.86 (d, J  =  1.76 Hz, 1H, CH-arom.), 7.63–7.67 (d, J  =  1.32 Hz, 1H, CH-arom.), 7.52–7.57 (m, 4H,
CH-arom.), 4.11 (s, 2H, acetylenic protons in 2,7 position), 3.82 (s, 6H, 2′,3′-CH3) ppm.


## 2.2. Different Attempts for Synthesis of the Photochromic Dihydroindolizine 9

Nucleophilic
addition of pyridazine7 to spirocyclopropene 6 using the cyclopropene route [10–29] (see Scheme 2)
in dry ethereal solution at room temperature under dry nitrogen in the absence
of light (TLC-controlled using CH2Cl2 as eluent) led to
the formation of the photochromic dihydroindolizine (DHI) 9 in low yield (26%).
The reaction occurs through the electrophilic addition of the
electron-deficient spirocyclopropenes 6 tothe nitrogen of the N-heterocyclic  pyridazine 7 which led to ring opening via
a cyclopropyl-allyl conversion 8′ to the colored betaines 8. A subsequent ring closure to DHI 9 results in a slow thermal 1,5-electrocyclization
back reaction (see Scheme 2) which can be reversed upon exposure to light. Pure
photochromic DHI 9 was obtained in all cases by two successive column
chromatography operations on silica gel using dichloromethane as the eluent.Scheme 2
Preparation outline of photochromic DHI9 from spirocyclopropene 6.Another
successful alternative method for the synthesis of the target photochromic DHI9
was achieved through the following multistep synthesis (see Scheme 3). The
Sonogashira coupling  of dimethyl
2,7-dibromo-4a′H-spiro[fluorene-9,5′-pyrrolo[1,2-b]pyridazine]-6′,7′-dicarboxylate
which was previously prepared by us [10–13] with
trimethylsilylacetylene in presence of palladium-catalyzed reaction (5%) and
CuI/Et2N in T  =  dry THI for 12 hours [29, 30] yielded the  desired
product dimethyl
2,7-bis((trimethylsilyl)ethynyl)-4a′H-spiro[fluorene-9,5′-pyrrolo[1,2-b]pyridazine]-6′,7′-dicarboxylate 11 in 34% yield after purification by flash chromatography on silica gel and CH2Cl2 as eluent. Treatment of DHI 11 with tetrabutyl ammonium fluoride (TBAF) in dry
THF for 17 hours afforded the trimethylsilylated product 9 in 68% yield. A good
proof for the trimethylsilylation that occurs during the condensation of
compound 2 with hydrazine hydrate is that detrimethylsilylation occurs when DHI
11 was treated with hydrazine hydrate in ethanol under mild conditions and at
low temperature (0°C) for 2 hours in 43% yield. Thus, acetylenic DHI 9 could
successfully prepared through three reactions’ pathways as shown in Schemes 2
and 3. The three products obtained from the different pathways showed the same
analytical and spectroscopic data as well as m.p and m.m.p.Scheme 3
Another reaction pathway for the synthesis
of the target photochromic DHI9.


## 3. Conclusion

We
have successfully extended the photochromism of photochromic DHI through the
coupling reactions in the fluorene part. New spirocyclopropene and photochromic
dihydroindolizines (DHIs) substituted in the fluorene part (region A) with
acetylenic bridge for future using in electronic devices have been furnished. Further
modification of the chemical structure of DHI system and their photochromic
properties as well as supporting onto the surface of metals such as gold,
silicon, and titanium will be discussed in details in the forthcoming paper.


## 4. Experimental

Spirocyclopropene
derivatives were obtained via photolysis of the corresponding pyrazoles
prepared according to reported procedures [10–23]. Photolysis
was carried out in the photochemical reactor of Schenck [31] made from Pyrex (λ>290 nm). The source of irradiation was a high-pressure mercury lamp
Philips HPK 125 W. Solutions to be photolyzed were flushed with dry nitrogen for
30 minutes before switching on the UV lamp. The progress of the reaction and
the purity of the products isolated were monitored using TLC. Separation and
purification of all synthesized photochromic materials were carried out using
column chromatography (80 cm length×2 cm diameter) on silica gel and CH2Cl2 as eluent. Melting points were determined on (Electrothermal
Eng. Ltd., Essex, UK) melting point apparatus and are uncorrected. All
NMR spectra were collected on a Brüker DRX-400 spectrometer (400 MHz) in CDCl3 using TMS as the internal standard. Chemical shifts (δ) are reported in ppm. Experimental details,
procedures, and full characterizations of the new synthesized compounds will be
described elsewhere.



---

*Source: 959372-2008-12-18.xml*