Synthesis of a photochromic fused 2H-chromene capable of generating a single coloured species

Article abstract of DOI:10.1002/ejoc.201101702

A new photochromic fused 2H-chromene that has a dehydropyran bridge between the pyran double bond and the benzene ring was prepared. Unlike standard 2H-chromenes that give rise to two coloured species (one short- and one long-lived) under UV irradiation, flash photolysis studies on this particular 2H-chromene show that the opening of the pyran ring led to the formation of a single, coloured, open species that bleaches to the uncoloured initial form in <1 ms. The design of this fused 2H-chromene avoids the formation of the undesirable long-lived, transoid-trans, coloured, open form; therefore, the colour fades very quickly, according to monoexponential kinetics, without the persistence of any residual colour commonly observed in 2H-chromenes. Acid treatment of 4-[(ethoxycarbonyl)methyl]-2H-chromenes led to the formation of lactones.

Full text of DOI:10.1002/ejoc.201101702

FULL PAPER
DOI: 10.1002/ejoc.201101702
Synthesis of a Photochromic Fused 2H-Chromene Capable of Generating a
Single Coloured Species
Céu M. Sousa,[a] João Pina,[b] João Seixas de Melo,[b] Jerome Berthet,[c]
Stephanie Delbaere,[c] and Paulo J. Coelho*[a]
Keywords: Photochromism / Chromene / Benzopyran / Photolysis / Kinetics
A new photochromic fused 2H-chromene that has a dehy-
dropyran bridge between the pyran double bond and the
benzene ring was prepared. Unlike standard 2H-chromenes
that give rise to two coloured species (one short- and one
long-lived) under UV irradiation, flash photolysis studies on
this particular 2H-chromene show that the opening of the
pyran ring led to the formation of a single, coloured, open
species that bleaches to the uncoloured initial form in Ͻ1 ms.
The design of this fused 2H-chromene avoids the formation
of the undesirable long-lived, transoid–trans, coloured, open
form; therefore, the colour fades very quickly, according to
monoexponential kinetics, without the persistence of any re-
sidual colour commonly observed in 2H-chromenes. Acid
treatment of 4-[(ethoxycarbonyl)methyl]-2H-chromenes led
to the formation of lactones.
Introduction
Diaryl-substituted benzopyrans (2H-chromenes) and naph-
thopyrans are photochromic, colourless molecules that ac-
quire colour under exposure to UV light. This phenomenon
is due to a UV-promoted electrocyclic pyran ring-opening
reaction, which leads to a mixture of two highly conjugated,
coloured species that, in the absence of light, returns ther-
mally to the uncoloured initial form (Scheme 1).[1] The in-
corporation of these substances, particularly the related
naphthopyrans, in glass and polymer-based lenses led to the
production of commercial plastic photochromic lenses,
which present rapid colour changes in sunlight over a wide
temperature range (0–40 °C).[2]
Scheme 1. Photochromic equilibrium for 2,2-diphenyl-2H-
chromene.
The two coloured, open forms, the transoid–cis (TC,
major product) and transoid–trans isomers (TT, minor
product; Scheme 1), have similar visible absorption spectra
but very different thermal stability. Therefore, when the
light source is removed, the system returns to the original
colourless state (CF) according to a biexponential kinetic
decay law. Initially, there is a fast colour decay due to the
TC Ǟ CF conversion, followed by a slow colour decay due
to the TT Ǟ TC double-bond isomerisation and TC Ǟ CF
thermal ring-closure reactions.[3] As a result, significant re-
sidual colour remains for several minutes/hours depending
on the structure of the photochromic molecule (Fig-
ure 1).[4–7]
To improve the photochromic properties of 2H-
chromenes and the parent naphthopyrans, many structural
modifications have been tried, in particular, annelation at
the f,g,h faces of the benzopyran and the introduction of
substituents at the 5- and 6-positions or at the aryl groups
located at the sp3 pyran carbon atom.[8–17] However, after
UV excitation, two photoisomers, in variable relative
amounts, are always formed, and after an initial fast colour
decay, they all show the slow bleaching of the more stable
TT isomer (Figure 1).[18–24] One way to prevent the forma-
tion of this long-lived TT photoisomer, and therefore to
avoid the persistence of residual colour, is to connect the
pyran double bond to the benzene core. We have recently
[a] Centro de Química – Vila Real, Universidade de Trás-os-
Montes e Alto Douro,
5001-801 Vila Real, Portugal
Fax: +351-259350480
E-mail: pcoelho@utad.pt
[b] Departmento de Química, Universidade de Coimbra,
3004-535 Coimbra, Portugal
[c] CNRS UMR 8516, UDSL, Faculté des Sciences
Pharmaceutiques et Biologiques,Université Lille Nord de
France,
59006 Lille, France
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101702.
1768
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1768–1773

Synthesis of a Photochromic Fused 2H-Chromene
tuted benzopyrans in good yield. To prepare this fused
benzopyran, we chose the condensation of 2Ј-hydroxyace-
tophenones with benzophenones, which is known to pro-
duce benzopyranones, a good precursor of benzopyrans,
and an intermediate with a carbonyl group, which would
allow the building of the second dihydropyran ring.[26]
However, the reaction of the 2Ј,6Ј-dihydroxyacetophenone
(1) with benzophenone in a basic medium did not afforded
the expected hydroxybenzopyran, and a new aurone dye
was isolated instead.[27] As the presence of the second hy-
droxy group seemed to inhibit the formation of the benzo-
pyranone, we methylated one hydroxy group[28] and then
performed the condensation of methoxyacetophenone 2
with benzophenone in the presence of tBuONa to give an
intermediate, yellow, conjugated dye, which was treated
with H2SO4 at 0 °C to afford 5-methoxybenzopyranone (3,
Scheme 3). The 1H NMR spectrum of 3 displayed two sing-
lets at δ = 3.82 (3 H) and 3.47 (2 H) ppm, assigned to the
methoxy and methylene protons, and a characteristic signal
in the 13C NMR spectrum at δ = 85.08 ppm for C-2.
Figure 1. Absorbance evolution during UV/Vis irradiation and
darkness for 2,2-diphenyl-2H-chromene.
reported the photochromic properties of a new type of
fused dehydropyrano[2,3,4-de]benzopyran where the rota-
tion of the double bond, which produces the long-lived TT
isomer, is impossible due to the presence of a pyran bridge
that links the double bond to the benzene ring. UV irradia-
tion of this compound generated one coloured species that
faded completely to the closed form in a few milliseconds
according to a monoexponential decay law.[25] However, it
was observed that, in CDCl3, this unsymmetrical molecule
established an equilibrium between two different pyran
compounds due to the migration of the double bond, and
therefore one might consider that, in solution and under
UV irradiation, the opening of both pyran rings may occur
with the formation of two different, coloured, short-lived,
open forms.
To overcome this problem, we designed a new symmetri-
cal fused 2H-chromene with two pyran rings substituted by
the same phenyl groups (Scheme 2). Due to this symmetri-
cal pattern, even if the double bond migrates, the ring open-
ing will lead to the same molecule. In this paper, we describe
the synthesis of this new, symmetrical, fused 2H-chromene
and its photochromic behaviour under laser flash photolysis
conditions.
Scheme 3. Synthesis of 3.
To build the second dihydropyran ring, we performed a
Reformatsky reaction of 3 with ethyl bromoacetate in the
presence of zinc and iodine followed by reflux in acetic acid,
which gave a mixture of three compounds that were sepa-
rated by column chromatography: the dehydrobenzopyran
4 and the expected benzopyran 5 (major compound), both
formed by nucleophilic addition followed by acid-catalysed
dehydration, and the unexpected coumarin 6 (Scheme 4).
Scheme 2. New, symmetrical, fused 2H-chromene 10.
Scheme 4. Reformatsky reaction of 3.
Results and Discussion
Synthesis
1
The H NMR spectra of 4 and 5 are very similar, the
The synthesis of the target benzopyran 10 was more main differences being the chemical shifts of the signals of
complicated than expected. 2H-Chromenes are usually protons 3 and 9. For 4, the methylene 3-H signal is at δ =
prepared by the condensation of phenols with 1,1-di- 4.27 ppm, and the ethylene 9-H signal is at δ = 7.03 ppm,
1
arylprop-2-yn-1-ol, which affords double-bond-unsubsti- whereas the H NMR spectrum of 5 displayed a singlet for
Eur. J. Org. Chem. 2012, 1768–1773
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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C. M. Sousa, J. Pina, J. Seixas de Melo, J. Berthet, S. Delbaere, P. J. Coelho
FULL PAPER
allylic 9-H at δ = 3.57 ppm and a characteristic singlet at δ
= 5.89 ppm for pyran 3-H. The (E) configuration of the
double bond of 4 was established by 2D NOESY, which
showed a dipolar correlation between 9-H and the protons
1
of the methoxy group. The H NMR spectrum of 6 shows
the absence of the methylene protons and the terminal ester
ethoxy group and displayed two doublets at δ = 5.84 and
7.26 ppm, coupled through 4J = 1.4 Hz, assigned to the eth-
ylene protons 3-H and 9-H. 13C NMR spectroscopy sup-
ported the assignment of the structure by the presence of a
low-field signal at δ = 160.7 ppm for the lactone C=O
group. The structure of this compound was unambiguously
1
established by 2D NMR experiments: The H-13C HMBC
Scheme 6. Rearrangement of 4 and 5 to 6 and 7.
experiment displayed a long-range correlation between the
lactone quaternary carbon atom and ethylene 3-H at δ =
5.84 ppm. In addition, NOESY underlined the dipolar cor-
relation between the methoxy group (δ = 3.87 ppm) and
proton 9-H (δ = 7.26 ppm), which confirmed the structure
of 6.
The lactone 6 was probably formed from 5 by thermal
pyran ring opening followed by enolisation, rotation and
acid-catalysed lactone formation as observed previously in
naphthopyrans (Scheme 5).[29]
ethyl bromoacetate/Zn/I2 followed by reflux in HOAc gave
the fused dihydrobenzopyran 9 characterised by the disap-
pearance of the hydroxy signal and the emergence of a sing-
let at δ = 6.20 ppm assigned to the ethylene lactone proton
1
3-H in the H NMR spectrum. The change in the chemical
shift of the carbonyl low-field signal from δ = 197.1 ppm to
δ = 160.9 ppm confirmed the formation of the lactone ring.
Finally, the reaction of 9 with the Grignard reagent
1
PhMgBr gave, after acid hydrolysis, the target 10. The H
NMR spectrum of 10 displayed an upfield shift of the 3-H
proton signal from δ = 6.20 ppm to δ = 5.66 ppm indicative
of the formation of the 2,2-diphenylpyran ring. This trans-
formation was confirmed in the 13C NMR spectrum by two
signals at δ = 83.4 and 83.1 ppm, which are characteristic
of the two pyran sp3 C–O carbon atoms. The full NMR
spectroscopic characterisation of this compound can be
found in the Supporting Information. Thus, 10 was pre-
pared in five steps from 1.
Scheme 5. Mechanism for the formation of 6.
In order to form the pyranone ring, 5 was heated to re-
flux in a mixture of HBr/HOAc (1:1), a reagent known to
promote the cleavage of the methoxy group, but the reac-
tion led only to 6, which confirms that this compound, ob-
served in the Reformatsky reaction of 3 with ethyl bromo-
acetate/Zn/I2, is formed after acidic treatment. An attempt
to cleave the methoxy group of 4 by using BBr3/CH2Cl2 led
to a similar result: the reaction afforded the lactone 7
formed by a similar rearrangement to 6 followed by the
deprotection of the methoxy group (Scheme 6).
Scheme 7. Synthesis of 10.
As the acidic conditions needed to cleave the methoxy
group promoted the rearrangement of 4 and 5 to 7 and 6,
we decided to deprotect the methoxy group of 3 before we
performed the Reformatsky reaction, which was a better
Photochromic Behaviour
In acetonitrile solution, 10 is colourless with a maximum
solution (Scheme 7). Thus, treatment of 3 with BBr3/ absorption at 283 nm (Figure 2). Laser irradiation at
CH2Cl2 afforded after hydrolysis the 5-hydroxybenzopyr- 266 nm of 10–4 m solutions of 10 in acetonitrile or methylcy-
1
anone 8 in quantitative yield. The H NMR spectrum of 8 clohexane (MCH) led to the fast development of a broad
displayed a sharp singlet for the hydroxy proton at δ = absorption band with two maxima at around 400 and
11.5 ppm, and a signal at δ = 197.1 ppm in the 13C NMR 540 nm, which can be attributed to a highly conjugated
spectrum due to the carbonyl group. Treatment of 8 with benzopyran open form.
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Eur. J. Org. Chem. 2012, 1768–1773

Synthesis of a Photochromic Fused 2H-Chromene
oured state (Scheme 8). The lifetimes of this coloured pho-
toisomer seem to be independent of the solvent polarity
as very similar lifetimes (100–125 μs) were found in polar
(MeCN) and nonpolar (MCH) solvents (Table 1).
Scheme 8. Photochromic equilibrium for 10.
This behaviour contrasts with the biexponential decay
observed with the common double-bond-unsubstituted 2H-
chromenes that lead to some remaining colouration. There-
fore, one can establish that the presence of the dihydropyran
bridge in 10 prevents the formation of the undesirable, long-
lived TT isomer, and thus the coloured species fades more
quickly and without the persistence of residual colouration.
Figure 2. Normalised absorption spectra of 10 in 10–4 m degassed
acetonitrile, collected before and after laser irradiation at 266 nm.
The time evolution of the absorbance at 400 and 540 nm
indicates that the formation of the open form occurs within
the laser pulse (ca. 20 ns), and no additional signals (in de-
gassed solutions) were observed in the microsecond or milli-
second time range, which could be attributed to the triplet
state of the closed form (Table 1).
Conclusions
A new 2H-chromene that presents a dehydropyran ring
between the pyran double bond and the benzene ring was
prepared in five steps from 2Ј,6Ј-dihydroxyacetophenone
(1). Laser irradiation at 266 nm of this symmetrical fused
benzopyran led to the formation of a single short-lived col-
oured species that faded in less than 0.3 ms to the initial
closed form according to a monoexponential process. As
this structural modification of the benzopyran core pre-
vents the formation of the long-lived TT isomer, the unde-
sirable residual colouration, usually present in these photo-
chromic molecules, was successfully avoided.
Table 1. Lifetimes τ [μs] for the coloured open form of 10 collected
at 400 and 540 nm in MeCN and at 400 and 520 nm in MCH.
Solvent
τ at 400 nm
τ at 540 nm
MeCN
MeCN (degassed)
120
125
100
125
τ at 400 nm
τ at 520 nm
MCH
MCH (degassed)
105
107
110
105
After the pulse, the absorbance measured at the maxi-
mum wavelength decays monoexponentially over all the
spectra (Figure 3), and similar lifetimes of the coloured
open form (125 μs) were obtained when the decays were Experimental Section
collected at both maxima (400 and 540 nm). This is indica-
tive of the formation of a single, short-lived, coloured, TC
isomer that fades in less than 0.3 ms to the initial uncol-
General Methods: The reactions were monitored by TLC with alu-
minium plates precoated with Merck silica gel 60 F254 (0.25 mm).
Column chromatography (CC) was performed on silica gel 60 (70–
230 mesh). The new compounds were determined to be Ͼ 95%
pure by 1H NMR spectroscopy. 1H and 13C NMR spectra were
recorded at 298 K in CDCl3 by using a Bruker ARX400 spectrome-
ter (at 400.13 and 100.62 MHz) or in [D8]toluene by using a Bruker
500 spectrometer (at 500 and 125 MHz). UV/Vis spectra were re-
corded with a CARY 50 Varian spectrophotometer. IR spectra
were obtained with a Perkin–Elmer FTIR 1600 spectrometer by
using KBr disks (w: weak; m: medium; s: strong).
Flash Photolysis: The absorption spectra (and decays) of the col-
oured open form of 10 were obtained by irradiating acetonitrile or
MCH solutions of the sample with the fourth harmonic (266 nm)
of an Nd:YAG laser (Spectra Physics) and collected at 280–650 nm
with a laser flash photolysis apparatus (Applied Photophysics). The
detection system is at right angles to the excitation beam, and a
pulsed 150 W Xe lamp was used to analyse the absorption of the
open form. The signal was fed into a Tektronix TDS 3052B digital
analyser and transferred to an IBM RISC computer where the de-
cays were analysed with the appropriate software (Applied Pho-
tophysics). For further details, see ref.[30]
Figure 3. Decay traces for the open form of 10 in MeCN collected
at 400 and 540 nm. Also shown are the monoexponential fittings
to the decays and the corresponding residuals distribution.
Eur. J. Org. Chem. 2012, 1768–1773
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C. M. Sousa, J. Pina, J. Seixas de Melo, J. Berthet, S. Delbaere, P. J. Coelho
Synthesis of 2,3-Dihydro-5-methoxy-2,2-diphenylchromen-4-one (3): H), 3.57 (d, J = 0.9 Hz, 2 H), 1.31 (t, J = 7.0 Hz, 3 H) ppm. 13C
FULL PAPER
A suspension of 2Ј-hydroxy-6Ј-methoxyacetophenone (2) (893 mg,
5.38 mmol), benzophenone (3.00 g, 16.5 mmol) and sodium tert-
butoxide (2.60 g, 27.1 mmol) in toluene (30 mL) was heated under
reflux for 1 h. During heating, the suspension became progressively
orange. After cooling to room temperature, the solution was
quenched with water (100 mL), extracted with ethyl acetate
(3ϫ50 mL), and the combined organic layers were dried (Na2SO4)
and concentrated under reduced pressure to leave a brown oil.
H2SO4 (10 mL) was added, and the solution was stirred at 0 °C
for 30 min. The black solution was quenched with ice (100 g) and
extracted with ethyl acetate (3ϫ50 mL). The organic phases were
dried (Na2SO4) and concentrated under reduced pressure to leave
a brown oil, which was purified by CC (0–30% EtOAc/petroleum
ether) to give 3 as white crystals (1.137 g, 64%). M.p. 138–140 °C
NMR (100 MHz, CDCl3): δ = 171.8, 156.3, 154.0, 144.6, 129.8,
129.5, 128.0, 127.4, 127.2, 127.1, 112.0, 110.6, 104.4, 82.0, 60.5,
55.0, 41.6, 14.4 ppm. EI-MS (TOF): m/z (%) = 400 (9.5) [M]+, 371
(4) [M – Et]+, 354 (8.2), 327 [M – COOEt]+, 323 (42) [M –
C6H5]+, 313 (100) [M – CH2COOEt]+, 235 (12), 165 (10). HRMS:
calcd. for C26H24O4 [M]+ 400.1675; found 400.1671.
4-(2,2-Diphenylvinyl)-2H-chromen-2-one (6): M.p. 122–128 °C. IR:
ν = 3023 (w, C–H), 2933, 2837, 1728 (s, C=O), 1602 (s, C=C),
˜
1
1468 (m), 1438, 1363, 1312, 1252 (m, C–O), 1185 cm–1. H NMR
(400 MHz, CDCl3): δ = 7.47 (t, J = 8.4 Hz, 1 H), 7.42–7.35 (m, 5
H), 7.30–7.24 (m, 4 H), 7.14 (m, 2 H), 6.97 (dd, J = 1.0, 8.4 Hz, 1
H), 6.79 (dd, J = 1.0, 8.4 Hz, 1 H), 5.84 (d, J = 1.4 Hz, 1 H), 3.87
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 160.7, 157.9,
155.3, 151.8, 144.0, 142.2, 138.9, 131.9, 130.3, 128.5, 128.3, 128.1,
127.9, 126.8, 115.4, 110.4, 110.1, 106.3, 56.4 ppm. EI-MS (TOF):
m/z (%) = 354 (100) [M]+, 337 (94), 323 (42) [M – OMe]+, 277 (48),
265 (30), 165 (62).
IR: ν = 3030 (w, C–H), 2985, 2941, 2830, 1691 (s, C=O), 1602,
˜
1572, 1468 (s), 1334, 1244 (s, C–O), 1208, 1088 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.42–7.40 (m, 4 H), 7.37 (t, J = 8.5 Hz, 1
H), 7.33–7.20 (m, 6 H), 6.74 (d, J = 8.3 Hz, 1 H), 6.42 (d, J =
8.3 Hz, 1 H), 3.82 (s, OCH3), 3.47 (s, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 189.8, 161.4, 160.4, 142.7, 136.0, 128.4,
127.7, 126.1, 111.6, 110.7, 103.9, 85.1, 56.0, 49.7 ppm. EI-MS
(TOF): m/z (%) = 330 (6.2) [M]+, 253 (100) [M – C6H5]+, 178 (41),
165 (29), 150 (83), 122 (39), 107 (62). HRMS: calcd. for C22H18O3
[M]+ 330.1256; found 330.1257.
Synthesis of 5-Hydroxy-4-(2,2-diphenylvinyl)-2H-chromen-2-one (7):
To a solution of 4 (53 mg, 0.13 mmol) in dry CH2Cl2 (5 mL) at 0 °C
was added dropwise BBr3 (200 μL, 1 m in CH2Cl2) under constant
stirring. After the addition was complete, the solution was main-
tained at room temperature for 22 h. Cold water (75 mL) was
added and the solution extracted with ethyl acetate (2ϫ75 mL).
The combined organic phases were dried (Na2SO4), and the solvent
was removed under reduced pressure. The residue was dissolved in
CH2Cl2 and crystallised after addition of petroleum ether to give
orange crystals, which were collected by filtration and washed with
Reformatsky Reaction of 3 with Ethyl Bromoacetate: A solution of
3 (300 mg, 0.91 mmol) and ethyl bromoacetate (600 μL, 5.4 mmol)
in diethyl ether/benzene (1:4, 10 mL) was slowly added to a mixture
of zinc (2.0 g, 31 mmol) and iodine (three small crystals) over 1 h
and heated with stirring under reflux. After the addition was com-
plete, the solution was maintained under reflux for 30 min and then
quenched with water (100 mL). The aqueous phase was extracted
with EtOAc (3ϫ50 mL), and the combined organic layers were
dried (Na2SO4) and concentrated under reduced pressure.
CH3COOH (5 mL) was added to the residue, and the solution
heated under reflux for 30 min. After cooling to room temperature,
water (75 mL) was added, and the solution was extracted with ethyl
acetate (3ϫ50 mL). The combined organic layers were washed
with water, dried (Na2SO4), and the solvent was evaporated under
reduced pressure to leave a brown oil, which was purified by silica
gel CC (0–12% EtOAc/petroleum ether) to give 4 (53 mg, 17%), 5
(100 mg, 33%) and 6 (15 mg, 5%).
petroleum ether (10 mg, 23%). M.p. 143 °C (dec.). IR: ν = 3432
˜
(m, O–H), 2904, 1674 (s, C=O), 1604 (s, C=C), 1498, 1453 (m),
1379, 1252, 1200, 1074 cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.43–7.33 (m, 6 H), 7.32–7.26 (m, 3 H), 7.23 (d, J = 1.4 Hz, 1 H),
7.15 (m, 2 H), 6.92 (dd, J = 1.0, 8.4 Hz, 1 H), 6.73 (dd, J = 1.0,
8.2 Hz, 1 H), 6.27 (s, 1 H), 5.85 (d, J = 1.4 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 160.6, 155.0, 154.3, 151.0, 148.2,
141.3, 138.0, 132.1, 130.1, 128.9, 128.6, 128.5, 128.4, 128.3, 123.9,
115.1, 111.7, 109.7, 108.9 ppm. EI-MS (TOF): m/z (%) = 340 (100)
[M]+, 323 (92) [M – OH]+, 312 (57), 263 (44) [M – C6H5]+, 235
(33),
178
(32).
HRMS:
calcd.
for
C23H16O3
[M]+ 340.1099; found 340.1086.
Synthesis of 2,3-Dihydro-5-hydroxy-2,2-diphenylchromen-4-one (8):
To a suspension of 3 (0.928 g, 2.81 mmol) in dry diethyl ether
(10 mL) at 0 °C was added dropwise BBr3 (11 mL, 1 m in CH2Cl2)
under constant stirring. After the addition was complete, the solu-
tion was maintained at 0 °C for 30 min, quenched with ice (75 g)
and extracted with ethyl acetate (2ϫ75 mL). The organic phases
were dried (Na2SO4), and the solvent was removed under reduced
pressure give to 8 as slightly yellow crystals, which were collected
by filtration, washed with ethyl ether and air-dried (0.870 g, 98%).
Ethyl
2-[(E)-2,3-Dihydro-5-methoxy-2,2-diphenylchromen-4-ylid-
ene]acetate (4): M.p. 164–166 °C. IR: ν = 3060 (w, C–H), 2979,
˜
2933, 1728 (s, C=O), 1646, 1565 (m), 1476, 1460 (m), 1371, 1327,
1282 (s), 1237 (s, C–O), 1200 (s) cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.50 (d, J = 8.2 Hz, 4 H), 7.25 (m, 7 H), 7.03 (t, J =
1.3 Hz, 1 H), 6.80 (dd, J = 1.1, 8.3 Hz, 1 H), 6.46 (dd, J = 1.0,
8.4 Hz, 1 H), 4.27 (q, J = 7.0 Hz, 2 H), 4.18 (d, J = 1.3 Hz, 2 H),
3.84 (s, 3 H), 1.36 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 168.3, 159.3, 156.7, 144.1, 143.8, 131.0, 128.3, 127.3,
126.1, 117.1, 111.1, 111.0, 103.3, 82.3, 59.9, 55.6, 35.8, 14.5 ppm.
EI-MS (TOF): m/z (%) = 400 (2.8) [M]+, 355 (7.5) [M – OEt]+, 327
(72) [M – COOEt]+, 326 (100), 276 (16), 167 (35). HRMS: calcd.
for C26H24O4 [M]+ 400.1675; found 400.1673.
M.p. 176–177 °C. IR: ν = 3224 (w, O–H), 3023 (w, C–H), 2979,
˜
1639 (s, C=O), 1565, 1498, 1460 (s), 1363, 1230 (s, C–O), 1208,
1155 cm–1. 1H NMR (400 MHz, CDCl3): δ = 11.48 (OH), 7.42–
7.37 (m, 4 H), 7.35–7.28 (m, 5 H), 7.28–7.23 (m, 2 H), 6.58 (d, J
= 8.2 Hz, 1 H), 6.41 (d, J = 8.3 Hz, 1 H), 3.51 (s, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 197.1, 161.7, 159.6, 142.4, 138.3,
128.6, 128.0, 126.2, 109.4, 108.6, 108.2, 85.5, 47.8 ppm. EI-MS
(TOF): m/z (%) = 316 (10) [M]+, 239 (100) [M – C6H5]+, 178 (19),
165 (19), 136 (17), 108 (16). HRMS: calcd. for C21H16O3 [M]+
316.1099; found 316.1093.
Ethyl 2-(5-Methoxy-2,2-diphenyl-2H-chromen-4-yl)acetate (5): M.p.
163–164 °C. IR: ν = 3041 (w, C–H), 2997, 2971, 2833, 1730 (s,
˜
C=O), 1651, 1599 (m), 1566, 1481 (m), 1462, 1409, 1364, 1272 (s),
1233 (s, C–O), 1201 (s) cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.51 (d, J = 8.5 Hz, 4 H), 7.36–7.21 (m, 6 H), 7.06 (t, J = 8.3 Hz,
1 H), 6.62 (dd, J = 1.0, 8.1 Hz, 1 H), 6.39 (dd, J = 1.0, 8.3 Hz, 1
Synthesis of 5,6-Dihydro-6,6-diphenylpyrano[2,3,4-de]chromen-2-one
(9): A mixture of zinc (2.0 g, 31 mmol) and iodine (three small crys-
H), 5.89 (t, J = 1.0 Hz, 1 H), 4.22 (q, J = 7.0 Hz, 2 H), 3.72 (s, 3 tals) in diethyl ether/benzene (1:4, 4 mL) was stirred and heated
1772 Eur. J. Org. Chem. 2012, 1768–1773
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Synthesis of a Photochromic Fused 2H-Chromene
[2]
[3]
[4]
[5]
[6]
[7]
[8]
S. N. Corns, S. M. Partington, A. D. Towns, Color. Technol.
2009, 125, 249.
S. Delbaere, J. C. Micheau, G. Vermeersch, J. Org. Chem. 2003,
68, 8968–8973.
under reflux. A solution of 8 (1.00 g, 3.16 mmol) and ethyl bromo-
acetate (1.60 mL, 14.5 mmol) in diethyl ether/benzene (1:4, 4 mL)
was slowly added over 1 h. After the addition was complete, the
suspension was maintained under reflux for 2 h and then poured
into water (100 mL). The aqueous phase was extracted with ethyl
acetate (3ϫ50 mL), and the combined organic layers were dried
(Na2SO4) and concentrated under reduced pressure. CH3COOH
(5 mL) was added to the residue, and the solution was heated under
reflux for 30 min. After cooling to room temperature, water
(75 mL) was added, and the solution extracted with ethyl acetate
(3ϫ50 mL). The combined organic phases were washed with water,
dried (Na2SO4), and the solvent was evaporated under reduced
pressure to leave a brown oil, which was purified by silica gel CC
(0–10% EtOAc/petroleum ether) to give 9 as slightly yellow crystals
X. Sallenave, S. Delbaere, G. Vermeersch, A. Saleh, J. L. Pozzo,
Tetrahedron Lett. 2005, 46, 3257.
S. V. Paramonov, V. Lokshin, H. Ihmels, O. A. Fedorova, Pho-
tochem. Photobiol. Sci. 2011, 10, 1279.
F. Ortica, L. Bougdid, C. Moustrou, U. Mazzucato, G. Favaro,
J. Photochem. Photobiol. A: Chem. 2008, 200, 287.
J. N. Moorthy, P. Venkatakrishnan, S. Samanta, D. K. Kumar,
Org. Lett. 2007, 9, 919.
S. Paramonov, S. Delbaere, O. Fedorova, Y. Fedorov, V. Lok-
shin, A. Samat, G. Vermeersch, J. Photochem. Photobiol. A:
Chem. 2010, 209, 111.
M. M. Oliveira, M. A. Salvador, S. Delbaere, J. Berthet, G. Ver-
meersch, J. C. Micheau, P. J. Coelho, L. M. Carvalho, J. Pho-
tochem. Photobiol. A: Chem. 2008, 198, 242.
J. N. Moorthy, P. Venkatakrishnan, S. Samanta, Org. Biomol.
Chem. 2007, 5, 1354.
M. J. R. P. Queiroz, R. Dubest, J. Aubard, R. Faure, R. Gugli-
elmetti, Dyes Pigm. 2000, 47, 219.
[9]
(0.296 g, 28%). M.p. 169–172 °C. IR: ν = 3062 (w, C–H), 3023,
˜
2971, 1730 (s, C=O), 1632, 1606 (m), 1462 (m), 1442, 1285, 1253,
1207, 1168, 1102 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.45–7.20
(m, 11 H), 6.91 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.3 Hz, 1 H), 6.20
(s, 1 H), 3.62 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
160.9, 153.4, 153.2, 147.7, 142.5, 132.9, 128.5, 128.0, 126.4, 112.2,
109.9, 108.8, 107.4, 83.4, 39.0 ppm. EI-MS (TOF): m/z (%) = 340
(100) [M]+, 323 (95), 312 (52), 263 (41), 235 (27), 178 (35), 165 (31).
HRMS: calcd. for C23H16O3 [M]+ 340.1099; found 340.1087.
[10]
[11]
[12]
[13]
J. L. Pozzo, A. Samat, R. Guglielmetti, V. Lokshin, V. Minkin,
Can. J. Chem. 1996, 74, 1649.
P. J. Coelho, L. M. Carvalho, S. Rodrigues, A. M. F. Oliveira-
Campos, R. Dubest, J. Aubard, A. Samat, R. Guglielmetti, Tet-
rahedron 2002, 58, 925.
G. Favaro, F. Ortica, A. Romani, P. Smimmo, J. Photochem.
Photobiol. A: Chem. 2008, 196, 190.
Synthesis
of
5,6-Dihydro-2,2,5,5-tetraphenylpyrano[2,3,4-de]-
chromen-2-one 10: A solution of 9 (100 mg, 0.29 mmol) in dry di-
ethyl ether (4 mL) was treated with PhMgBr (8 mL, 1 m in Et2O)
and heated at reflux for 20 min. After removal of the solvent under
reduced pressure, the residue was hydrolysed with HCl (5%, 20 mL)
and stirred for 3 d. The solution was extracted with ethyl acetate
(3ϫ50 mL) and dried with anhydrous Na2SO4. Removal of the
solvent under reduced pressure left a brown oil, which was purified
by silica gel CC (0–4% EtOAc/petroleum ether) to give 10 as white
[14]
[15]
[16]
S. Higgins, Chem. Br. 2003, 39, 26.
B. Van Gemert, Mol. Cryst. Liq. Cryst. 2000, 344, 57.
[17] D. A. Clarke, B. M. Heron, C. D. Gabbutt, J. D. Hepworth,
S. M. Partington, S. N. Corns (James Robinson Ltd),
US6248264, 2001.
[18] M. M. Oliveira, M. A. Salvador, P. J. Coelho, L. M. Carvalho,
Tetrahedron 2005, 61, 1681.
crystals (65 mg, 47%). M.p. 182–183 °C. IR: ν = 3060 (w, C–H),
˜
[19] N. Cerqueira, L. M. Rodrigues, A. M. F. Oliveira-Campos,
L. H. M. Carvalho, P. J. Coelho, R. Dubest, J. Aubard, A. Sa-
mat, R. Guglielmetti, Helv. Chim. Acta 2003, 86, 3244.
[20] C. I. Martins, P. J. Coelho, L. M. Carvalho, A. M. F. Oliveira-
Campos, A. Samat, R. Guglielmetti, Helv. Chim. Acta 2003,
86, 570.
[21] P. L. Gentili, E. Danilov, F. Ortica, M. A. J. Rodgers, G. Fav-
aro, Photochem. Photobiol. Sci. 2004, 3, 886.
[22] N. Cerqueira, A. M. F. Oliveira-Campos, P. J. Coelho, L. H. M.
Carvalho, A. Samat, R. Guglielmetti, Helv. Chim. Acta 2002,
85, 442.
3030 (w, C–H), 2963, 2904, 1662 (m, C=C), 1609 (m), 1572 (m),
1490 (m), 1460, 1438, 1363, 1267 (m, C–O), 1208, 1074 cm–1. 1H
NMR (500 MHz, [D8]toluene): δ = 7.48–7.44 (m, 4 H), 7.35–7.22
(m, 6 H), 7.20–7.10 (m, 10 H), 7.01 (t, J = 8.2 Hz, 1 H), 6.59 (d, J
= 8.2 Hz, 1 H), 6.37 (d, J = 8.0 Hz, 1 H), 5.66 (s, 1 H), 3.35 (s, 2
H) ppm. 13C NMR (125 MHz, [D8]toluene): δ = 152.3, 152.0,
144.6, 143.5, 130.3, 128.4, 128.0, 127.5, 127.2, 127.1, 126.6, 125.0,
121.5, 109.3, 108.4, 108.2, 83.4, 83.1, 38.2 ppm. EI-MS (TOF): m/z
(%) = 478 (31) [M]+, 401 (100), 323 (17), 311 (20), 298 (15), 165
(31). HRMS: calcd. for C35H26O2 [M]+ 478.1933; found 478,1934.
[23] P. J. Coelho, L. M. Carvalho, J. C. Silva, A. M. F. Oliveira-
Campos, A. Samat, R. Guglielmetti, Helv. Chim. Acta 2001,
84, 117.
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra for all new compounds.
[24] M. M. Oliveira, C. Moustrou, L. M. Carvalho, J. A. C. Silva,
A. Samat, R. Guglielmetti, R. Dubest, J. Aubard, A. M. F. Ol-
iveira-Campos, Tetrahedron 2002, 58, 1709.
Acknowledgments
[25] C. M. Sousa, J. Pina, J. Seixas de Melo, J. Berthet, S. Delbaere,
P. J. Coelho, Org. Lett. 2011, 13, 4040–4043.
[26] J. Cottam, R. Livingstone, M. Walshaw, K. D. Bartle, D. W.
Jones, J. Chem. Soc. 1965, 5261–5265.
[27] C. M. Sousa, J. Berthet, S. Delbaere, P. J. Coelho, Dyes Pigm.
2011, 92, 537–541.
[28] C. K. Lau, P. C. Belanger, C. Defresne, J. Scheigetz, J. Org.
Chem. 1987, 52, 1670.
[29] C. M. Sousa, P. J. Coelho, L. M. Carvalho, G. Vermeersch, J.
Berthet, S. Delbaere, Tetrahedron 2010, 66, 8317.
[30] J. Seixas de Melo, L. M. Silva, M. Kuroda, J. Chem. Phys.
2001, 115, 5625.
We acknowledge the FCT (Portugal’s Foundation for Science and
Technology) and FEDER for financial support through the re-
search unit Centro de Química-Vila Real (POCTI-SFA-3-616) and
project PTDC/QUI/66012/2006. The 300 and 500 MHz NMR spec-
troscopy facilities were funded by the Région Nord-Pas de Calais
(France), the Ministère de la Jeunesse de l’Education Nationale et
de la Recherche (MJENR) and the Fonds Européens de Dévelop-
pement Régional (FEDER). J. P. also acknowledges the FCT for a
postdoc grant (SFRH/BPD/65507/2009).
[1] J. D. Hepworth, B. M. Heron, Functional Dyes (Ed.: S-H.
Kim), Elsevier, Amsterdam, 2006, pp. 85–135.
Received: November 28, 2011
Published Online: February 6, 2012
Eur. J. Org. Chem. 2012, 1768–1773
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1773