Synthesis of novel (p-substituted styryl) spirobenzopyrans

Article abstract of DOI:10.1080/00397910701227366

A series of (p-substituted styryl) spirobenzopyrans were synthesized by the Wittig reaction of Fisher's bases with 5-(p-substituted styryl) salicylaldehyde derivatives. The final spirobenzopyrans were characterized by the 1H NMR, IR, UV, and GC-MS analyses. Copyright Taylor & Francis Group, LLC.

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Synthesis of Novel (p‐Substituted Styryl)
Spirobenzopyrans
Rui‐ren Tang a , Ke‐long Huang a , Zi‐long Tang b & Qing Yang a
a School of Chemistry and Chemical Engineering, Central South University,
Changsha, China
b School of Chemistry and Chemical Engineering, Hunan University of
Science and Technology, Xiangtan, China
Version of record first published: 12 Apr 2007.
To cite this article: Rui‐ren Tang, Ke‐long Huang, Zi‐long Tang & Qing Yang (2007): Synthesis of Novel
(p‐Substituted Styryl) Spirobenzopyrans, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:8, 1347-1354
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Synthetic Communicationsw, 37: 1347–1354, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701227366
Synthesis of Novel (p-Substituted Styryl)
Spirobenzopyrans
Rui-ren Tang and Ke-long Huang
School of Chemistry and Chemical Engineering, Central South
University, Changsha, China
Zi-long Tang
School of Chemistry and Chemical Engineering, Hunan University
of Science and Technology, Xiangtan, China
Qing Yang
School of Chemistry and Chemical Engineering, Central South
University, Changsha, China
Abstract: A series of (p-substituted styryl) spirobenzopyrans were synthesized by the
Wittig reaction of Fisher’s bases with 5-(p-substituted styryl) salicylaldehyde deriva-
1
tives. The final spirobenzopyrans were characterized by the H NMR, IR, UV, and
GC-MS analyses.
Keywords: photochromism, spirobenzopyrans, substituted styryl, synthesis
During the past 40 years, the chemistry of spirocyclic organic compounds has
been extensively investigated, with special regard to their remarkable photo-
chromic properties.[1] Particular attention has been focused on the spiropyrans
because of their potential applications in industrial fields such as nonlinear
optics, data recording, and optical memory storage for computers.[1]
The photochromic transformation mechanism of spiropyran compounds
involves spiro-bond photodissociation and cis-trans double-bond isomeriza-
tion to give the planar, highly colored merocyanines (Scheme 1). However,
Received in Japan June 15, 2006
Address correspondence to Rui-ren Tang, School of Chemistry and Chemical
Engineering, Central South University, Changsha, China. E-mail: trr@mail.csu.edu.cn
1347

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R.-r. Tang et al.
there are several important unresolved issues associated with this reversible
coloration–decoloration process. Primary among these is the photostability
of the merocyanines, which can undergo a photodegradation process known
as fatigue phenomenon during the reversible color change.[1a,b]
The structure formulae of the spirobenzopyrans (SP) (colorless closed, or
spiro, form) and their photoisomers, the merocyanines (MC) (colored open
form), and the ring numbering of the spirobenzopyrans are shown in
Scheme 1.
Several groups have investigated the effect of structural modifications on
the physical properties of spiropyrans, and it has been found that changes to
substituents on the parent spiropyran ring can influence the stability of the
spiropyran form of the molecule, in addition to the absorption associated
with the ring-opened merocyanine chromophore.[2–4] These properties are
particularly relevant for applications in ferroelectric liquid crystal switch tech-
nology, which is based on the principle of photo-resolution.[5] Herein we
report the design and synthesis of a new series of benzospiropyrans 6a–i,
which contain a styryl group bearing various substituents in the para
position. The key steps in the synthesis involve Wittig chemistry to
generate the 5-(p-substituted styryl) salicylaldehydes 5a–5i, followed by
coupling with Fisher’s base to introduce the spiro functionality. The
presence of a styryl moiety allows extended conjugation within the
molecule, which can help stabilize the colored merocyanines and thereby
improve the fatigue resistance of the system.[1c]
The synthetic route toward the benzospiropyrans 6a–6i is shown in
Scheme 2.
The 5-p-substituted styryl salicylaldehyde derivatives 5a–5i are key
intermediates in the synthesis of the spirobenzopyrans 6a–6i, and in this
article, Wittig chemistry is employed to introduce the p-substituted styryl
moiety of 5a–5i. To date, two methods for converting 5-chloromethylsalicy-
laldehyde (1) to the phosphonium salt 3 have been reported.[6] The first of
these involves reaction of 1 with PPh3, followed by introduction of the
3-nitro group using HNO3 in anhydrous acetic acid. However, the product
from the second step of this route is difficult to precipitate from solvent and
requires further purification by flash chromatography. In the second known
pathway, direct nitration of 5-chloromethylsalicylaldehyde (1) affords the
Scheme 1.

(p-Substituted Styryl) Spirobenzopyrans
1349
Scheme 2.
5-nitro derivative 2, which can be treated with PPh3 to give the desired salt 3.
Using this method, the phosphonium salt 3 can be precipitated from the
reaction mixture and filtered off to give the pure product without chromato-
graphy. In our hands, the latter pathway provided the 3-nitrosalicylaldehyde
2 in an improved yield of 78% by heating the reaction at 408C for 5 h,
while the phosphonium salt 3 was obtained in 91% yield after recrystallization.
The ylide 4 could be generated in situ by treating 3 with NaOEt. However,
in the presence of strongly electron-withdrawing groups such as -NO2 and
-CHO, the negative charge of the carbanion will be delocalized, and the
nucleophilicity and reactivity of the carbon center will greatly decrease as a
consequence. In an attempt to overcome this, Brude and coworkers[6] chose
toluene as the reaction solvent and employed a larger excess of NaOEt.
However, this method only provided the desired product in 10% yield,
possibly because toluene was an unsuitable solvent for the phase-transfer
catalytic Wittig reaction.[7] Furthermore, the reaction workup proved to be
very difficult because of the insolubility of the by-product, Ph3P55O, in
toluene. We were able to improve the Wittig reaction by using ethanol as

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R.-r. Tang et al.
the solvent and increasing the reaction time. Moreover, during workup, water
was added to form a 1:1 ethanol–water mixture in which Ph3P55O was
soluble, and the desired alkene could be crystallized from solution. Using
this protocol, reaction of the ylide 4 with various aromatic aldehydes under
phase-transfer catalytic conditions afforded the alkenes 5a–5i in up to 71%
yield, with greater than 6:1 trans–cis selectivity and purity up to 98% as deter-
mined by high pressure liquid chromatography (HPLC) analysis.
Using literature chemistry,[8] the highly functionalized salicylaldehydes
5a–5i were reacted with Fisher’s base to give the spirobenzopyrans 6a–6i,
1
which were fully characterized by H NMR, IR, and UV spectroscopy and
GC-MS analysis.
The UV, IR, and 1H NMR spectra (see Experimental) showed that 6a–6i
all exist in the spiro ring configuration without exposure to light. In this form,
the indole ring lies almost perpendicular to the pyran ring, whereas in the ring-
opened merocyanine form, the molecule adopts a planar configuration where
conjugation is possible between the indole ring and the remainder of the
molecule through the extended p-electron system. In the UV/vis spectra,
the lmax values for 6a–6i in ethanol are within the 315- to 385-nm range,
which indicate that they exist predominantly in the colorless closed form.
The characteristic infrared absorptions of the C30-C40 double bond of the
pyran ring appear at 1630–1660 cm21, while weak bands for the C-O-C
stretching absorptions of the spiro functionality were observed at 1013–
1072 cm21 and 1255–1292 cm21
.
The spirobenzopyrans 6a–6i bear two types of ethylenic protons: H-30
and H-40 of the pyran ring and H-a and H-b of the styryl group, as indicated
in Scheme 1. The olefinic protons of the pyran ring display chemical shifts
in the range of d 5.76–6.14 for H-30 and d 5.41–6.86 for H-40, with
coupling constants of J ¼ 10.1–10.5 Hz, indicating their cis relationship.
Further, H-40 appears at lower field relative to H-30 because of the effect of
diamagnetic anisotropy of the neighboring benzene ring.[9] Each ethylenic
proton of the styryl group is strongly deshielded by a benzene ring, and as a
result, their chemical shifts are sufficiently downfield to overlap with the
aromatic protons. In the spiro form, the geminal dimethyl groups at C-3 are
expected to display different chemical shifts because the indole ring is
almost perpendicular to the pyran ring, placing the methyl groups in
different chemical environments. In contrast, in the ring-opened merocyanine
form, only one methyl signal is expected because the indole functionality is
almost planar to the pyran ring, placing the two methyl groups in the same
chemical environment. Experimentally, the 1H NMR spectra of 6a–6i
showed two geminal methyl singlets, which indicated that 6a–6i exist in
the spiropyran form under normal conditions.
The lifetime of the colored merocyanine form reverting back to the spiro
form (the decrease of absorbance during the decoloration process), namely the
decoloration rate of the colored form, was investigated in prelimimary studies
to evaluate the photostability in preliminary studies.[1a]

(p-Substituted Styryl) Spirobenzopyrans
1351
Solution of reference compounds[8] 6a, 6e, 6f and 6h and of the
compounds 6b, 6d, 6g, 6i (1.0 ꢀ 1023 mol L21) in cyclohexane were
prepared. The absorbance (A) of each solution and its lmax was recorded
immediately after 30 s of irradiation with a 400-W high-pressure mercury
lamp at room temperature.
When 6a–6i in the SP state was irradiated with a high-pressure mercury
lamp light, a strong absorption with high extinction coefficient appeared at
500–600 nm in the UV/vis spectra. Preliminary results showed the decolora-
tion rates of 6a–6i vary according to the nature of the aromatic substituent.
The presence of electron-withdrawing groups in the benzospiropyrans could
accelerate the discoloration of the SP isomer in the order shown: NO2 .
CN . F . Cl . Br . H . Me . NMe2 . OCH3. The substituent effect on
the stability of the MC isomer shows the same trend. Further detailed
studies on the photochromic behavior of the spirobenzopyrans 6a–6i will
be reported at a later stage.
EXPERIMENTAL
General Information
Uncorrected melting points were determined using a XRC-1 apparatus. IR
spectra were recorded using a Perkin-Elmer 1600 FT-IR spectrometer with
KBr disk samples. UV spectra were obtained using a Perkin-Elmer Lambda
17 spectrometer. MS were carried out using a HP5988A GC-MS spectrometer.
1HNMR spectra were recorded using a Varian 400 NMR spectrometer with
TMS as an internal standard. Elemental analyses with CHN were performed
using a Perkin-Elmer 2400 elemental analyzer. Reactions were monitored
by analytical thin-layer chromatography (TLC), which was performed on
Merck silica-gel 60 F254–covered aluminum sheets.
Compounds 5a, 5c, 5e, 5f, 5h, 6a, 6c, 6e, 6f, and 6h were synthesized
according to Refs. 6 and 9.
Synthesis of 3-Nitro-5-(chloromethyl)salicylaldehyde (2)
To a vigorously strirred solution of 5-(chloromethyl)salicylaldehyde (1)
(9.0 g, 52 mmol) in glacial acetic acid (12 mL) under a nitrogen atmosphere,
fuming nitric acid (2.5 mL) was slowly added through a condenser. The
speed of addition was regulated to maintain a reaction temperature of
408C. After the addition was complete, the reaction was stirred at 308C
for a further 3 h. The reaction mixture was cooled to 158C and the
precipitate filtered off to give 3-nitro-5-(chloromethyl)salicylaldehyde (2)
(8.8 g, 78%).

1352
R.-r. Tang et al.
Synthesis of the (3-Formyl-4-hydroxy-5-nitrobenzyl)phosphonium
Salt 3
To a solution of 3-nitro-5-(chloromethyl)salicylaldehyde (2.6 g, 12 mmol) in
benzene (20 mL), triphenyl phosphine (3.4 g, 12 mmol), was added and the
reaction heated at reflux for 3 h. The mixture was cooled, and the yellow pre-
cipitate filtered off to give the crude product, which was recrystallized from
ethanol to give the phosphonium salt 3 (5.23 g, 91.0%).
General Procedure for Synthesis of 4-Nitro-5-(p-substituted Styryl)
Salicylaldehyde Derivatives 5a–5i
A mixture of the phosphonium salt 3 (3.5 g, 7.3 mmol), benzaldehyde (0.98 g,
7.3 mmol), and sodium ethoxide (1.0 g, 16 mmol) in absolute ethanol (50 mL)
was heated at reflux under a nitrogen atmosphere for 4 h. The reaction mixture
was cooled to room temperature and acidified to pH3 using 5% hydrochloric
acid. Water (50 mL) was added to the acidified mixture, and the resulting pre-
cipitate was collected by filtration, washed with water, and recrystallized from
absolute EtOH to give the alkenes 5b (1.24 g).
Data
5b. Yield: 57%, mp 146–1478C. IR (KBr): 3200, 2910, 1665, 963, 760 cm21. 1H
NMR (CDCl3): d 10.5 (s, 1H, OH), 10.3 (s, 1H, CHO), 7.19–8.32 (m, 2H, Ar-H),
7.13–7.28 (d, J ¼ 8.2 Hz, 2H, Ar-H), 6.50–6.85 (d, J ¼ 16.0 Hz, 2H, CH55CH),
2.59 (q, J ¼ 7.3 Hz, 2H, CH2), 2.59 (t, J ¼ 7.4 Hz, 3H, CH3). Anal. calcd. for
C17H15NO4: C, 68.68; H, 5.09; N, 4.71; found: C, 68.81; H, 5.11; N, 4.68.
5d. Yield: 62%, mp 174–1768C. IR (KBr): 3250, 3030, 2920, 2820, 2720,
1
1663, 957, 780 cm21. H NMR (CDCl3): d 10.5 (s, 1H, OH), 10.3 (s, 1H,
CHO), 7.70–7.83 (m, 2H, Ar-H), 6.97–7.31 (m, J ¼ 8.6 Hz, 4H, Ar-H),
7.14–7.41 (d, J ¼ 14 Hz, 2H, CH55CH). Anal. calcd. for C15H10FNO4: C,
62.72; H, 3.51; N, 4.88; found: C, 62.81; H, 3.51; N, 4.87.
5g. Yield: 65%, mp 149–1508C. IR (KBr): 3325, 3015, 2820, 2220, 1660,
1
960, 785 cm21. H NMR (CDCl3): d 10.5 (s, 1H, OH), 10.4 (s, 1H, CHO),
7.78–7.89 (m, 2H, Ar-H), 7.43–7.67 (dꢁ2, J ¼ 7.8 Hz, 4H, Ar-H), 7.18–
7.45 (m, 2H, CH55CH). Anal. calcd. for C16H10N2O4: C, 65.31; H, 3.42; N,
9.52; found: C, 65.41; H, 3.41; N, 9.53.
5i. Yield: 71%, mp 179–1818C. IR (KBr): 3330, 3010, 2980, 2821, 2718,
1
1665, 1340, 770 cm21. H NMR (CDCl3): d 10.7 (s, 1H, OH), 10.4 (s, 1H,
CHO), 7.73–7.81 (m, 2H, Ar-H), 6.43–7.14 (m, 4H, Ar-H), 7.15–7.45

(p-Substituted Styryl) Spirobenzopyrans
1353
(m, J ¼ 16.8 Hz, 2H, CH55CH), 3.04 (s, 6H, NMe2). Anal. calcd. for
C17H16N2O4: C, 65.38; H, 5.16; N, 8.97; found: C, 65.42; H, 5.20; N, 8.95.
General Procedure for the Synthesis of the Spirobenzopyrans 6a–i
To a solution of 5b (2.69 g, 10.0 mmol) in anhydrous ethanol (20 mL) and
THF (10 mL), Fisher’s base (3.74 g, 20.0 mmol) was added, and the
reaction was heated at reflux for 8 h. The solvent was evaporated under
reduced pressure, and the crude residue was purified by column chromato-
graphy, eluting with 1:1 EtOAc–petroleum ether (bp 60–808C) to give the
spirobenzopyran 6b (3.21 g, 72%).
Data
6b. Yield: 72%, mp 113–1158C. IR (KBr): 3010, 2960, 2930, 1660, 1610,
1
1490, 1272, 1014, 1320, 1530, 1355, 972, 913, 860, 813, 735 cm21. H
NMR (d6-acetone): d 7.75 (s, 1H, 70-H), 6.48–7.56 (m, 11H, 50-H, 4-7-H,
a-d-H), 5.80–6.47 (d, J ¼ 10.5 Hz, 2H, 30-H and 40-H), 3.13 (s, 3H,
N-CH3), 2.35 (s, 3H, Ar-CH3), 1.23 (s, 3H, 3-CH3), 1.07 (s, 3-CH3). m/z
(FAB): 453 (M þ H). Anal. calcd. for C29H28N2O3: C, 76.97; H, 6.24; N,
6.19; found: C, 76.79; H, 6.26; N, 6.14.
6d. Yield: 54%, mp 134–1368C. IR (KBr): 3011, 2931, 2815, 1638, 1614, 1483,
1382, 1285, 1073, 978 cm21. 1H NMR (d6-acetone): d 7.89 (d, J ¼ 1.9 Hz, 1H,
70-H), 6.52–7.72 (m, 11H, 50-H, 4-7-H, a-d-H), 5.83–6.46 (dd, J ¼ 10.8 Hz,
2H, 30-H and 40-H), 3.25 (s, 3H, N-CH3), 1.13 (s, 3H, 3-CH3), 0.96 (s, 3H,
3-CH3). m/z (FAB): 443 (M þ H). Anal. calcd. for C27H23FN2O3: C, 73.29;
H, 5.24; N, 6.33; found: C, 73.42; H, 5.27; N, 6.25.
6g. Yield: 71%, mp 178–1808C. IR (KBr): 3011, 2942, 2820, 2221, 1638,
1
1600, 1478, 1293, 1015, 981, 931, 734 cm21. H NMR (d6-acetone): d 7.84
(s, 1H, 70-H), 6.53–7.48(m, 11H, 50-H, 4-7-H, a-d-H), 5.84–6.50 (dd,
J ¼ 10.4 Hz, 2H, 30-H, 40-H), 3.12 (s, 3H, N-CH3), 1.24 (s, 3H, 3-CH3),
1.09 (s, 3H, 3-CH3). m/z (FAB): 460(M þ H). Anal. calcd. for
C28H23N3O3: C, 74.82; H, 5.16; N, 9.35; found: C, 74.87; H, 5.21; N, 9.37.
6i. Yield: 64%, mp 163–1658C. IR (KBr): 3021, 2935, 2821, 1644, 1598,
1478, 1382, 1285, 1019, 977, 914, 735, 879, 811 cm21 1H NMR (d6-
.
acetone): d 7.63 (s, 1H, 70-H), 6.38–7.34 (m, 11H, 50-H, 4-7-H, a-d-H),
5.94–6.82 (dd, J ¼ 10.1 Hz, 2H, 30-H, 40-H), 3.36 (s, 6H, NMe2), 3.16
(s, 3H, N-CH3), 1.25 (s, 3H, 3-CH3), 0.98 (s, 3H, 3-CH3). m/z (FAB): 468
(M þ H). Anal. calcd. for C29H29N3O3: C, 74.50; H, 6.25; N, 8.99; found:
C, 74.21; H, 6.24; N, 8.93.

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R.-r. Tang et al.
ACKNOWLEDGMENTS
Financial support from National Natural Science Foundation of China (No.
50573019) is gratefully acknowledged.
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