The photochemical addition of 2,2,2-trifluoroethanol to methoxy-substituted stilbenes

Article abstract of DOI:10.1021/jo040110e

The excited-state lifetime of the trans-stilbene chromophore in acetonitrile is prolonged by methoxy substituents in the meta positions. The long-lived singlet excited state of trans-3,5-dimethoxystilbene (trans-2d) is quenched upon the addition of 2,2,2-trifluoroethanol (TFE), and the Markovnikov ether is observed as the major product from steady-state irradiations. The results indicate that the reaction pathway proceeds through a carbocation intermediate.

Full text of DOI:10.1021/jo040110e

TABLE 1. P h otop h ysica l Ch a r a cter iza tion of
tr a n s-2a -e
Th e P h otoch em ica l Ad d ition of
2,2,2-Tr iflu or oeth a n ol to
Meth oxy-Su bstitu ted Stilben es
J effrey C. Roberts and J ames A. Pincock*
Department of Chemistry, Dalhousie University,
Halifax, Nova Scotia, Canada B3H 4J 3
a
a
a,b
λabs
ꢀmax
(M-1 cm-1
λfl
λ0,0
τS
(ns)
james.pincock@dal.ca
a,c
(nm)
)
(nm) (nm)
Φfl
0.07d 0.016c
Received J anuary 15, 2004
2a
2b 302, 317 28700, 27700
2c 295 25800
2d 299, 306 30100, 29800
2e 301, 321 20600, 24700
295, 307 28500, 27600
350
381
357
389
389
328
344
336
341
353
<0.5e
0.93
16.9
<0.5e
0.007
0.096
0.200
0.018
Abstr a ct: The excited-state lifetime of the trans-stilbene
chromophore in acetonitrile is prolonged by methoxy sub-
stituents in the meta positions. The long-lived singlet excited
state of trans-3,5-dimethoxystilbene (trans-2d ) is quenched
upon the addition of 2,2,2-trifluoroethanol (TFE), and the
Markovnikov ether is observed as the major product from
steady-state irradiations. The results indicate that the reac-
tion pathway proceeds through a carbocation intermediate.
a
Measured by using degassed acetonitrile solutions (3 freeze-
pump-thaw cycles) with absorbance of 0.25 at 295 nm (excitation
wavelength). Measured by single photon counting. c Measured
b
by comparing the integrated area under the fluorescence curve to
d
a standard (trans-stilbene 2a in acetonitrile, ref 12). In methanol,
ref 11. e Shorter than the time resolution of the instrument.
Recently, during an investigation of benzylic ester pho-
tochemistry, we observed the photochemical addition of
methanol and 2,2,2-trifluoroethanol (TFE) to trans-3,4′,5-
trimethoxystilbene 1, eq 1.1 This reaction occurred more
cleavage is more rapid than for other substitution pat-
terns and (2) cation- (not radical-) derived products are
observed in high yield. Recent work by Lewis and
co-workers6 has clearly shown that amino-substituted
stilbene derivatives display a meta-effect that leads to
significantly longer singlet lifetimes (τS for trans-4-
aminostilbene ) 0.1 ns; τS for trans-3-aminostilbene )
15 ns). Moreover, the photochemical addition of methanol
to 2-(3-aminostyryl)naphthalene was observed, in con-
trast to the para isomer, which was unreactive.6a Finally,
very recent publications by Lewis7 and Arai8 have
investigated the photochemistry of hydroxystilbenes in
water, and in the latter paper the addition of water to
trans-3-hydroxystilbene was reported. We were intrigued
by the possibility of (1) observing a similar effect for
methoxy-substituted stilbenes and (2) observing photo-
chemical reactivities that correlate with their photo-
physical properties. This note describes our success in
both of these areas.
Stilbenes 2a -e were selected for this study. While cis-
and trans-2a are commercially available, the remaining
eight compounds were synthesized by traditional Wittig
chemistry. The photophysical characterization of 2a -e
is given in Table 1 for the trans isomers only. The values
for the absorption maxima and extinction coefficients are
similar to those of other substituted trans-stilbenes. For
the cis isomers, the absorption maxima are approxi-
mately 20 nm shorter than their trans counterparts, and
the extinction coefficients are on the order of 10000-
16000 M-1 cm-1. Furthermore, while all of the trans
isomers demonstrate measurable fluorescence, none of
the five cis-stilbenes fluoresce appreciably.9
rapidly in TFE, suggesting that the greater ionizing
ability and effective acidity of this solvent play an impor-
tant role in the addition process. Furthermore, the prefer-
ence for the Markovnikov product hinted at a pathway
involving carbocation intermediates. A review of the liter-
ature revealed that the photochemical addition of metha-
nol to unconstrained stilbene derivatives was originally
reported by Laarhoven and co-workers,2 although they
concluded that carbocation intermediates were not in-
volved in the reaction. This apparent disagreement
prompted us to investigate the addition of TFE to me-
thoxy-substituted stilbene derivatives in greater detail.
One significant structural motif that is present in 1
but not in the substrates investigated by Laarhoven is
the 3,5-dimethoxyphenyl substitution pattern. Previous
work in our laboratory3 and others4,5 has indicated that
such a pattern gives rise to the well-studied “meta-effect”
in benzylic ester photochemistry, where (1) C-O bond
(1) Roberts, J . C.; Pincock, J . A. Can. J . Chem. 2003, 81, 709.
(2) Woning, J .; Oudenampsen, A.; Laarhoven, W. H. J . Chem. Soc.,
Perkin Trans. 2 1989, 2147.
The data in Table 1 show substantial variations
depending on the position of the methoxy substituent.10
(3) (a) Pincock, J . A. Acc. Chem. Res. 1997, 30, 43. (b) Cozens, J . L.;
Pincock, A. L.; Pincock, J . A.; Smith, R. J . Org. Chem. 1998, 63, 434.
(c) Decosta, D. P.; Howell, N.; Pincock, A. L.; Pincock, J . A.; Rifai, S.
J . Org. Chem. 2000, 65, 4698.
(4) (a) Zimmerman, H. E.; Sandel, V. R. J . Am. Chem. Soc. 1963,
85, 915. (b) Zimmerman, H. E. J . Am. Chem. Soc. 1995, 117, 8988. (c)
Zimmerman, H. E. J . Phys. Chem. A 1998, 102, 5616.
(6) (a) Lewis, F. D.; Yang, J . S. J . Am. Chem. Soc. 1997, 119, 3834.
(b) Lewis, F. D.; Kalgutkar, R. S.; Yang, J . S. J . Am. Chem. Soc. 1999,
121, 12045. (c) Lewis, F. D.; Weigel, W. J . Phys. Chem. A 2000, 104,
8146. (d) Lewis, F. D.; Kalgutkar, R. S. J . Phys. Chem. A 2001, 105,
285. (e) Lewis, F. D.; Weigel, W.; Zuo, X. J . Phys. Chem. A 2001, 105,
4691.
(5) (a) Turro, N. J .; Wan, P. J . Photochem. 1985, 28, 93. (b) Wan,
P.; Chak, B. J . Chem. Soc., Perkin Trans. 2 1986, 1751. (c) Wan, P.;
Chak, B.; Krogh, E. J . Photochem. Photobiol. A: Chem. 1989, 46, 49.
(7) Lewis, F. D.; Crompton, E. M. J . Am. Chem. Soc. 2003, 125, 4044.
(8) Murohoshi, T.; Kaneda, K.; Ikegami, M.; Arai, T. Photochem.
Photobiol. Sci. 2003, 2, 1247.
10.1021/jo040110e CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/19/2004
J . Org. Chem. 2004, 69, 4279-4282
4279

SCHEME 1. P r od u cts fr om Ir r a d ia tion of tr a n s-
or cis-2
a
b
c
R ) CH3. R ) CH2CF3. For 6c and 6e, the yield given is the
sum of the two possible isomers.
quenching region (80-100% TFE) where Φ ≈ 0.02. The
fluorescence of trans-2d shows only a slight decrease in
methanol (Φfl ) 0.19), but preliminary experiments do
show quenching by solutions of anhydrous HCl in metha-
nol or acetonitrile. Such behavior is reminiscent of the
fluorescence quenching observed by Yates and co-work-
ers13 for substituted styrene derivatives in acidic solution.
Assuming a concentration of 13.7 M for pure TFE, the
quenching ratio of kTFE/kTFE-OD ) 3.3:1 also indicates rate-
determining proton transfer. Figure 1B shows the same
data plotted as a Stern-Volmer plot of Φfl/Φfl° versus %
TFE in acetonitrile.14 Even at very low concentrations of
TFE (i.e., 0-30%), the upward curvature is still obvious.
The curvature of this plot emphasizes that the quenching
of fluorescence by TFE is unlikely to be the result of a
simple bimolecular interaction. A likely explanation for
this effect is that higher concentrations of TFE not only
increase the number of available quenching molecules,
but also create a highly ionizing environment that
enhances the quenching mechanism (vide infra).
Irradiation of the five substrates (either cis or trans
isomer) in methanol or TFE resulted in the formation of
several products, Scheme 1. The isomeric ethers 3 and 4
are easily differentiated by the masses (GC-MS) of the
two benzylic carbocations that are produced following
fragmentation of each compound.15 The product yields
obtained following irradiation of trans-2a -e in methanol
(1 h) and TFE (10 min) are also shown in Scheme 1.
Particularly noteworthy points are (1) the higher percent
conversions in TFE, (2) the high yields of Markovnikov
ethers in TFE, and (3) the very high reactivity of trans-
2d .
F IGURE 1. Quenching of the fluorescence of trans-2d by
either TFE (crosses) or TFE-OD (diamonds). (A, top) Plot of
the quantum yield of fluorescence versus the percentage of
TFE in acetonitrile; (B, bottom) the same data presented as a
Stern-Volmer plot.
Most notably, the singlet lifetimes and fluorescence
quantum yields of the substrates are increased signifi-
cantly by m-methoxy substitutents. Indeed, both the
singlet lifetime and fluorescence quantum yield of the 3,5-
dimethoxy compound trans-2d in acetonitrile (τS ) 16.8
ns, Φfl ) 0.200) are much greater than those observed
for trans-stilbene itself (τS ) 0.07 ns,11 Φfl ) 0.01612), and
even greater than the diamino analogue studied by Lewis
and co-workers (τS ) 16.1 ns, Φfl ) 0.1006e).
To investigate the interaction of the long-lived excited
state of trans-2d with alcohols, the fluorescence quantum
yield of this substrate was determined in various mix-
tures of acetonitrile and TFE or TFE-OD. Figure 1A
shows the plot of Φfl versus percent alcohol. There appear
to be two plateau regions in Figure 1A: a low quenching
region (0-20% TFE), where Φ ≈ 0.20, and a high
(9) Lewis has investigated the fluorescence behavior of the three
monosubstituted cis-aminostilbenes (Lewis, F. D.; Kalgutkar, R. S. J .
Phys. Chem. A 2001, 105, 285), although fluorescence was only
observed for the meta isomer (τS ) 17.4 ns at 77 K). We observe weak
fluorescence from cis-2d in room temperature acetonitrile (Φfl ) 0.006
at 284 nm), but this signal could also be attributed to as little as 2.4%
impurity of trans-2d in the sample.
(10) During the preparation of this paper, Majima and co-workers
published an investigation of the photophysical behavior of some of
these same methoxy-substituted stilbenes, Hara, M.; Tojo, S.; Majima,
T. J . Photochem. Photobiol. A: Chem. 2004, 162, 121. Surprisingly,
several of the quantum yields and fluorescence lifetimes reported are
much lower than our values. For example, in the case of trans-2d Φfl
) 0.023 and τS ) 4 ns. In light of this discrepancy, we have repeated
our measurements and calculations, but find essentially no change
from our original values in Table 1.
(13) (a) Wan, P.; Culshaw, S.; Yates, K. J . Am. Chem. Soc. 1982,
104, 2509. (b) McEwen, J .; Yates, K. J . Am. Chem. Soc. 1987, 109,
5800.
(14) A reviewer pointed out that a true Stern-Volmer plot should
o
show Φfl/Φfl versus the molarity of the quencher rather than the
percentage in TFE.
(15) For example, the base peak in the mass spectrum of 3d (TFE)
is m/z 249, while the isomer 4d (TFE) has a base peak of m/z 189.
Both ions are diagnostic for the regiochemistry of the TFE addition
reaction.
(11) Kim, S. K.; Courney, S. H.; Fleming, G. R. Chem. Phys. Lett.
1989, 159, 543.
(12) Mazzucato, U. Pure Appl. Chem. 1982, 54, 1705.
4280 J . Org. Chem., Vol. 69, No. 12, 2004

F IGURE 3. Combined yields of cis- and trans-2d (diamonds)
and combined yields of ethers 3d and 4d (crosses) as a function
of percent TFE in acetonitrile.
compared to methanol. This was expected based on the
rapid quenching of excited trans-2d by TFE (Φfl ) 0.018)
but not by methanol (Φfl ) 0.190). Second, substrates
with m-methoxy substituents are more reactive than
unsubstituted or para-substituted compounds. In metha-
nol, where quenching by the solvent is quite slow, the
more reactive substrates give high yields of phenanthrene
product 6;16 in TFE, addition products 3 and 4 are
favored. The correlation between the propensity toward
TFE-adduct formation and excited-state lifetime is strik-
ing, with trans-2d having both the longest singlet lifetime
(τS ) 16.9 ns) and the highest reactivity (100% conversion
after 10 min in TFE, 96% total ether product formed).
Obviously, a longer lived excited state allows more time
for an intermolecular reaction to intercept the excited
stilbene. To provide further evidence for the connection
between the fluorescence quenching behavior shown in
Figure 1 and the photochemical addition of TFE, the
irradiation of trans-2d was repeated in a series of TFE-
acetonitrile mixtures. Figure 3 shows a comparison of the
combined yield of stilbenes (cis- and trans-2d ) and the
combined yield of the ethers (3d and 4d ) after 10 min of
irradiation as a function of % TFE in acetonitrile. The
lack of substantial ether formation for % TFE < 40% and
the rapid increase in yield thereafter strongly suggests
that the mechanism responsible for the quenching of
trans-2d fluorescence leads to formation of the addition
products. In addition, these results point to the excited
state of the trans isomer being the species responsible
for ether formation.
F IGURE 2. (A, top) Yield versus time plot for the irradiation
of the unsubstituted stilbene trans-2a in TFE for 1 h. Products
are labeled as follows: trans-2a (diamonds), cis-2a (squares),
3a (triangles), 6a (circles). (B, bottom) Yield versus time plot
for the irradiation of the 3,5-dimethoxy compound trans-2d
in TFE for 10 min. Products are labeled as follows: trans-2d
(diamonds), cis-2d (squares), 3d (triangles), 4d (crosses), and
6d (circles). Product 5 (<2% yield in all cases) has been omitted
for clarity.
The most rapid reaction for any of the five substrates
is trans-cis isomerization, which leads to a photosta-
tionary state of the two isomers within 2 min of starting
the irradiation. For this reason, the table shows the
percent conversion of the mixture of stilbene isomers,
which provides a much better indication of the reactivity
of each substrate. This issue is best considered by
examining Figure 2, which shows the change in the
photolysis mixture as a function of time for trans-2a (A)
and trans-2d (B) upon irradiation in TFE. In both cases,
the starting trans isomer is >90% consumed within 5
min. However, for the unsubstituted trans-2a , isomer-
ization is the major reaction pathway, while trans-2d
demonstrates significant formation of the ether 4d .
Furthermore, the observation that the concentration of
the cis isomer decreases over time does not necessarily
mean that the cis isomer gives rise to addition products.
Given that a photostationary state is attained very early
in these irradiation experiments, determining which
isomer leads to product formation is not possible from
these data. Indeed, irradiation of cis-2a -e in TFE leads
to essentially the same product yields as shown in
Scheme 1 (Supporting Information).
Importantly, Markovnikov ethers are preferred for all
five substrates, keeping in mind that m-methoxy sub-
stituents are electron withdrawing with respect to the
benzylic position. This preference provides further evi-
dence for the presence of carbocation intermediates in
the addition reaction, as indicated earlier by the quench-
ing studies. A reviewer pointed out that, on the basis of
a direct comparison with the meta-effect in benzylic ester
chemistry, the expected major product from irradiation
of trans-2d should be 3d rather than 4d . However, a
significant difference between these two reactions is that
the former involves an excited-state bond cleavage,
The results from the irradiation experiments compli-
ment the photophysical properties in many respects.
First, the substrates are much more reactive in TFE
(16) The efficient cyclization of m-methoxy stilbenoid systems has
been observed previously. Noller, K.; Dosteyn, F.; Meier, H. Chem. Ber.
1988, 121, 1609.
J . Org. Chem, Vol. 69, No. 12, 2004 4281

SCHEME 2. 1H NMR An a lysis of th e Ad d ition of
TF E a n d TF E-OD to tr a n s-2d
phile trapping (to yield the product ethers) or deproto-
nation (to re-form the stilbene substrates).
The results described in this report are summarized
as follows: (1) The “meta effect” described by Lewis and
co-workers for amino-substituted stilbene derivatives is
also important for methoxy-substituted derivatives; m-
methoxy substituents prolong the excited-state lifetime
of the stilbene chromophore, and lead to high fluorescence
quantum yields. (2) The meta effect also increases the
reactivity of the substrate, leading to high yields of phen-
anthrene products in methanol, and high yields of solvent
adduct in TFE. The higher reactivity of these substrates
is likely due to the long singlet lifetimes, which in turn
make subsequent reactions more probable. (3) The com-
bination of the highly ionizing environment of TFE and
the stabilization of a zwitterionic excited state appears
to lead to rapid photoprotonation of trans-2d , the sub-
strate for which the meta effect is the greatest. Further
studies are required to identify any cationic intermedi-
ates that are formed on the reaction pathway, and to fully
understand these results in relation to the investigations
of Laarhoven and co-workers. This work is currently in
progress, and we will report our findings in due course.
whereas the current work deals with an excited-state
bond formation. The excited-state electron-donating abil-
ity of the m-methoxy substituents appears to effectively
increase the basicity of the benzylic position, thereby
leading to more rapid protonation by TFE. With this in
mind, we believe that 4d should be the expected product
based on both excited-state transmission of electron
density and relative stability of the two possible carbocat-
ion intermediates.
Exp er im en ta l Section
Syn th esis of Su bstr a tes 2b-e. Benzyltriphenylphospho-
nium bromide was produced by addition of triphenylphosphine
(15.3 g, 0.058 mol) to a solution of benzyl bromide (10.0 g, 0.058
mol) in benzene (50 mL). The resulting mixture was stirred
overnight at room temperature, and the precipitate (20.0 g, 80%
yield) was isolated by suction filtration and washed with diethyl
ether. The isolated bromide salt (10.0 g, 0.023 mol) was reacted
with 1 equiv of sodium ethoxide, followed by an equimolar
amount of the appropriate aldehyde. The reaction mixture was
heated to 80 °C while stirring overnight, and the cooled reaction
mixture was extracted with methylene chloride. The trans- and
cis-stilbenes were separated by column chromatography, giving
yields of 10-15% for each isomer.
In the earlier studies by Laarhoven and co-workers,2
the photochemical addition of methanol to unsubstituted
trans-stilbene (2a in this study) was concluded to occur
via two competing mechanisms: (1) direct addition across
the central alkene unit and (2) rearrangement via a 1,2-
hydride shift to give a carbene intermediate, followed by
insertion into the O-H bond of the solvent. The presence
of a carbene intermediate was suggested based on the
observation (1H NMR) that irradiation in CH3OD led to
deuterium incorporation on the same carbon as the
nucleophile. The authors determined the carbene inser-
tion:direct addition ratio to be 0.9 following irradiation
at 300 nm. Furthermore, the fluorescence of trans-
stilbene was not quenched in 6 M H2SO4, indicating that
excited-state protonation is not an important decay
pathway for the substrate.
P h otolysis P r oced u r e. A 1 × 10-3 M solution (50 mL) of
the substrate of interest was thermostated at 25 °C in a quartz
reaction vessel and purged with nitrogen for 30 min. Irradiations
were performed in a Rayonet reactor with 10 low-pressure
mercury lamps (300 nm emission). Aliquots taken during the
reaction were analyzed by GC-FID to determine product yields.
The mass balances were greater than 90% in all cases. The yields
listed in Scheme 1 (and the yield versus time plots) have been
normalized to the initial response of the starting materials 2a -
e. After the reaction was complete, the solvent was removed
under reduced pressure, and the residue was taken up in
methylene chloride for GC-MS analysis.
In contrast, trans-2d reacts with TFE-OD to give
products that exclusively have the deuterium and the
nucleophile on adjacent carbons, Scheme 2. These results
are supported by the GC-MS spectrum of deuterated 4d
(TFE), which shows no enhancement of the M + 1 signals
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada (NSERC)
for financial support and Sepracor Canada Ltd., Wind-
sor, Nova Scotia for the donation of chemicals. J .C.R.
also thanks NSERC for a postgraduate scholarship.
Su p p or tin g In for m a tion Ava ila ble: The 1H, 13C, and MS
characterization of the eight synthesized starting materials,
and the 500-MHz spectra used for the analysis of the addition
of TFE and TFE-OD to trans-2d ; also, the yield versus time
plots for trans-2b, trans-2c, and trans-2e in TFE, cis-2a -e in
TFE, and trans-2a -e in methanol. This material is available
free of charge via the Internet at http://pubs.acs.org.
1
for the m/z 189 ion. Moreover, the H NMR data indicate
that the addition gives two diasteriomers17 as expected
for a reaction proceeding through a carbocation interme-
diate. Assuming that only the trans isomer reacts (due
to the expected short excited-state lifetime of the cis
isomer), the ratio of syn:anti addition is 3:1. The prefer-
ence for syn addition suggests that the poorly stabilized
intermediate ion pair undergoes rapid collapse to give
the observed product.18 In addition, the lack of deuterium
incorporation on the nucleophile-bearing carbon indicates
that the carbocation intermediate does not undergo
rearrangement via a 1,2-hydride shift. This substantiates
our earlier work,1 which indicated that the rate of such
rearrangements is low compared to the rates of nucleo-
J O040110E
(18) Laser flash photolysis of styrene in TFE leads to a transient
cation intermediate (λmax ) 315 nm), which decays with a rate constant
greater than 5 × 107 s-1. Cozens, F. L.; Kanagasabapathy, V. M.;
McClelland, R. A.; Steenken, S. Can. J . Chem. 1999, 77, 2069.
(17) Kingsbury, C. A.; Thorton, W. B. J . Org. Chem. 1965, 31, 1000.
4282 J . Org. Chem., Vol. 69, No. 12, 2004