Very efficient generation of quinone methides through excited state intramolecular proton transfer to a carbon atom

Article abstract of DOI:10.1002/chem.201201144

Irradiation of 2-phenyl-1-naphthol (6) in CH₃CN/D₂O (3:1) leads to very efficient incorporation of deuterium at the ortho-positions of the adjacent phenyl ring (overall φ=0.73±0.07), along with minor incorporation at the naphthalene positions 5 and 8. These finding are explained by excited state intramolecular proton transfer (ESIPT) from the phenolic OH group to the corresponding carbon atoms, the main pathway giving rise to quinone methide (QM) 7, which has been characterized by LFP (τ≈20 ns; 460 nm). The ESIPT reaction paths have been explored with the second order approximate coupled cluster (CC2) method. In nonprotic solvents the ESIPT from the naphthol O-H to the ortho-position of the phenyl ring proceeds in a barrierless manner along the ¹L_a energy surface via a conical intersection with the S₀ state, delivering 7. In aqueous solvent, clusters with H₂O are formed wherein proton transfer (PT) to solvent and a H ₂O-mediated relay mechanism gives rise to naphtholates and QMs. The results are compared with 2-phenylphenol (3) that also undergoes barrierless ESIPT giving a QM via a conical intersection. However, due to an unfavorable conformation in the ground state, the quantum efficiency for ESIPT of 3 is significantly lower (φ for D-exchange=0.041). These results show that ESIPT from phenol to carbon need not be an intrinsically inefficient process. Irradiation of 2-phenyl-1-naphthol in CH₃CN/D₂O (3:1) leads to very efficient incorporation of deuterium at the ortho-positions of the adjacent phenyl ring along with minor incorporation at the naphthalene positions 5 and 8. These findings are explained by excited state intramolecular proton transfer (ESIPT) from the phenol OH to the corresponding carbon atoms (see figure). Copyright

Full text of DOI:10.1002/chem.201201144

FULL PAPER
DOI: 10.1002/chem.201201144
Very Efficient Generation of Quinone Methides through Excited State
Intramolecular Proton Transfer to a Carbon Atom
Nikola Basaric´,*[a] Nada Dosˇlic´,*[b] Jakov Ivkovic´,[a] Yu-Hsuan Wang,[c]
¯
Momir Malisˇ,[b] and Peter Wan*[c]
Abstract: Irradiation of 2-phenyl-1-
naphthol (6) in CH3CN/D2O (3:1)
leads to very efficient incorporation of
deuterium at the ortho-positions of the
adjacent phenyl ring (overall F=
0.73Æ0.07), along with minor incorpo-
ration at the naphthalene positions 5
and 8. These finding are explained by
excited state intramolecular proton
transfer (ESIPT) from the phenolic
OH group to the corresponding carbon
atoms, the main pathway giving rise to
quinone methide (QM) 7, which has
been characterized by LFP (tꢀ20 ns;
460 nm). The ESIPT reaction paths
have been explored with the second
order approximate coupled cluster
(CC2) method. In nonprotic solvents
the ESIPT from the naphthol O-H to
the ortho-position of the phenyl ring
proceeds in a barrierless manner along
fer (PT) to solvent and a H2O-mediat-
ed relay mechanism gives rise to naph-
tholates and QMs. The results are com-
pared with 2-phenylphenol (3) that
also undergoes barrierless ESIPT
giving a QM via a conical intersection.
However, due to an unfavorable con-
formation in the ground state, the
quantum efficiency for ESIPT of 3 is
significantly lower (F for D-ex-
change=0.041). These results show
that ESIPT from phenol to carbon
need not be an intrinsically inefficient
process.
1
the La energy surface via a conical in-
tersection with the S0 state, delivering
7. In aqueous solvent, clusters with
H2O are formed wherein proton trans-
Keywords: ab initio calculations ·
deuterium exchange · naphthols ·
photochemistry · quinone methides
Introduction
ular proton transfer (the true ESIPT), concerted biprotonic
transfer, proton-relay tautomerization, and catalysis of
proton transfer.[11] The most common acidic group in the
ESIPT reactions is the phenolic OH or amine NH, whereas
the basic site is usually a heteroatom such as pyridine nitro-
gen or carbonyl oxygen.[1] Although some examples are
known wherein protonation of a carbon can compete with
the protonation of heteroatoms,[12] ESIPT to carbon usually
takes place with much lower quantum efficiency.[13–19] Conse-
quently, it is often overlooked as a possible nonradiative re-
laxation pathway in biological molecules,[20] or as a viable
synthetic route to quinone methides (QM).[21] The later are
important reactive intermediates in organic synthesis[22] ca-
pable of cross-linking DNA,[23] and involved in the antineo-
plastic action of some antibiotics.[24]
Excited state intramolecular proton transfer (ESIPT) has
been the focus of intensive research in the last four decades
because of its fundamental interest,[1] as well as many appli-
cations,[2] including sensing,[3] photolabeling,[4] laser dyes,[5]
photostabilizers,[6] scintillators,[7] photoswithing in fluores-
cent proteins,[8] long-lived pH jumps,[9] or switching of poly-
morphs.[10] According to Kasha, ESIPT can be divided into
several mechanistic scenarios including intrinsic intramolec-
´
´
[a] Dr. N. Basaric, J. Ivkovic
Department of Organic Chemistry and Biochemistry
Ruder Boskovic Institute
Bijenicka cesta 54, 10000 Zagreb, (Croatia)
ˇ
´
¯
ˇ
To date, several examples of ESIPT to carbon atoms of
the aromatic ring have been described.[12–20] One prominent
example is that of 1-naphthol (1). In S1, 1 becomes signifi-
cantly more acidic (pK*a =0.4),[13] and in addition to proton
transfer (PT) to solvent, a solvent-assisted transfer of the
OH proton to the carbon atom at position 5 of the ring
takes place giving quinone methide (QM) 2 with a quantum
efficiency of 0.11 (Reaction (1)).[13,14] In addition, as a gener-
al reaction, ESIPT from the phenol OH to the carbon atoms
of the adjacent phenyl,[15] naphthyl,[14,16] anthryl,[17] terphen-
yl,[18] or pyrenyl ring[19] have been reported. ESIPT in 2-phe-
nylphenol (3) gives QM 4, whereas solvent-assisted ESPT
gives rise to QM 5 (Reaction (2)). Formation of QMs 4 and
5 was inferred due to regiospecific incorporation of deuteri-
Fax : (+)385 (1) 4680-195
E-mail: nbasaric@irb.hr
ˇ
´
ˇ
[b] Dr. N. Doslic, M. Malis
Department of Physical Chemistry
ˇ
´
Ruder Boskovic Institute
¯
ˇ
Bijenicka cesta 54, 10000 Zagreb, (Croatia)
Fax : (+)385 (1) 4680-245
E-mail: nadja.doslic@irb.hr
[c] Dr. Y.-H. Wang, Dr. P. Wan
Department of Chemistry
University of Victoria
Box 3065, Victoria BC, V8W 3V6, (Canada)
Fax : (+)1 (250) 721-7147
E-mail: pwan@uvic.ca
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201201144.
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um on irradiation in D2O (D-exchange F=0.041).[15] How-
ever, QMs 4 and 5 from these ESIPT reactions have never
been detected spectroscopically. In addition, the efficiency
of the QM formation by ESIPT or ESPT to carbon in all ex-
amples known to date is low.
indicating presence of mostly dideuterated species. On pho-
tolysis in CH3CN/D2O (3:1, c(D2O)=14m) under the same
AHCTUNGTRENNUNG
conditions, in addition to the formation of 6-D and 6-2D,
1H NMR spectrum showed incorporation of deuterium at
the naphthalene position 5 (51%), 8 (37%), and 4, 6, or 7
(30%), whereas MS indicated the presence of 30% dideu-
terated, 36% trideuterated, and 18% of tetradeuterated
species. Parallel irradiations of the samples with different
D2O concentration taken to lower conversions indicated
that D-exchange is up to 10–20% more efficient at lower
D2O content and primarily takes place at the adjacent
phenyl ring. Irradiation of the corresponding methoxy deriv-
ative, 6OMe under the identical conditions gave no D-ex-
change, indicating that the phenolic OH is essential for the
D-exchange. These findings are in agreement with operation
of ESIPT and solvent-assisted PT, delivering QMs (see
below) that on subsequent tautomerization give rise to deu-
terated compounds. The alternative mechanism which in-
volves protonation of the naphthol by H2O (D2O) and for-
mation of carbocations, as demonstrated by Shizuka and
Tobita for methoxynaphthalenes,[28] at pH 7 probably does
not take place or takes place with significantly lower quan-
tum efficiency.
Our combined experimental and theoretical study de-
scribes very efficient ESIPT in 2-phenyl-1-naphthol (6)
where the ortho-carbon atom of the adjacent phenyl ring is
the basic site. The process has been investigated by irradia-
tions in the presence of D2O, wherein regiospecific incorpo-
ration of deuterium denotes the ESIPT pathway. We show
that ESIPT operates via a conical intersection with the
ground state which is the dominant de-excitation pathway
from the singlet excited state surface in nonprotic solvent.
In aqueous media, PT to solvent delivers naphtholate and
a relay mechanism gives rise to QMs. By demonstrating that
protonation of an adjacent carbon atom takes place more
efficiently than PT to H2O bulk, our results additionally sup-
port the finding that the intrinsic rate constant for the proto-
nation of carbon is not necessarily lower than for the proto-
nation of heteroatoms.[25] Furthermore, this work demon-
strate that QMs can be delivered in high yields through an
efficient photochemical reaction - ESIPT to carbon atom.
Quantum yield of D-incorporation was determined by use
of a secondary actinometer, D-exchange in 2-phenylphenol
(2, F=0.041),[15] and a primary one (photolysis of valero-
phenone to give acetophenone F=0.65).[29] Both standards
gave similar values for the D-exchange F, with the mean
value 0.73Æ0.07. Taking into account the expected isotope
effect (assuming the similar values as in the thermal reversal
noncatalyzed enolization giving phenols and naphthols kH2O
k
/
D2O =1.5),[30] such a high F for the exchange suggests that
Results and Discussion
approximately 90% of the molecules deactivate from the S1
giving the corresponding QMs 7, and some smaller amounts
of QM 8 and zwitterion 9, as shown in Scheme 1.[31] To the
best of our knowledge this is the most efficient ESIPT to
carbon ever reported.
Naphthol 6 was prepared from 1-naphthol (1) and penta-
phenyl bismuth according to an already described proce-
dure.[26] 1-Methoxy-2-phenylnaphthalene (6OMe)[27] was ob-
tained from 6 by methylation using CH3I under basic condi-
tions (K2CO3) in a nonprotic solvent.
To probe for the ESIPT pathway involving carbon atoms
as the basic site, irradiations of 1 were performed in
CH3CN/D2O (3:1). After aqueous work-up the samples
were analyzed by MS and NMR to determine the extent
and position of deuteration. After 1 h photolysis of 6 in
The absorption spectrum of 6 is characterized by a broad
low-energy band between 275 and 350 nm, typical for a-
naphthols due to overlapped La and Lb transitions. However,
fluorescence spectra of 6 in aprotic solvents are narrower
than those of a-naphthols (half band with 3773 cmÀ1), more
similar to b-naphthols. In cyclohexane or CH3CN, fluores-
cence of 6 is weak, with fluorescence quantum yields of Ff =
0.0108Æ0.0002, and Ff =0.031Æ0.001, respectively. Fluores-
cence decays in CH3CN and cyclohexane can be best fitted
to a three-exponential function, suggesting presence of three
fluorescent excited states. In CH3CN the measured decay
times are: 0.3Æ0.1 (30%), 1.7Æ0.1 (20%), and 10.3Æ0.3 ns
CH3CN/D2O (cACHTUNGTRENNUNG(D2O)=0.3m) we observed almost complete
exchange of the H-atoms by deuterium at the ortho-position
1
of the adjacent phenyl ring (see H NMR in the Supporting
Information) indicating formation of 6-D and 6-2D (reac-
tion (3)). Mass spectra were in accordance with the NMR,
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Generation of Quinone Methides through Excited State Intramolecular Proton Transfer
FULL PAPER
transient. Consequently, we
assign the observed transient to
QM 7. The assignation is addi-
tionally corroborated by the
calculated excitation energies
of the QM 7-H2O clusters esti-
mated in the range between
3.0–3.2 eV (see Figure 3). To
the best of our knowledge, this
is the first reported optical de-
tection of a transient spectrum
of a QM formed by ESIPT to
an aromatic carbon atom. The
Scheme 1.
(50%). The low Ff and short average tf is in accordance
with the efficient ESIPT deactivation pathway from S1
giving QM 7. On addition of H2O to the CH3CN solution,
fluorescence increases, that is, H2O lowers F of ESIPT.
However, at high concentrations of H2O, an additional
shoulder appears at longer wavelength (475 nm) in the fluo-
rescence spectrum corresponding to the naphtholate formed
from 6 by an adiabatic PT to the solvent. The PT to the sol-
vent with concomitant protonation of the distal carbon sites
ultimately leads to the formation of QMs 8 and 9, however
with quantum yields that are lower by an order of magni-
tude.
transient spectra taken at longer times after the laser pulse
(see Figure S16 in the Supporting Information) reveal ab-
sorptions with a maximum at 350 nm, and at 400–600 nm
(k=1ꢁ105 À8ꢁ104 sÀ1, t=5–12 ms). According to the com-
parison with the published spectra of naphthoxyl and phe-
noxyl radicals, the observed more persistent transient at
400–600 nm probably corresponds to minor formation of
phenoxyl radicals by two-photon ionization giving radical
cations and solvent electron, and subsequent deprotonation
of radical cations.[32]
Ab initio calculations were employed to gain a deeper un-
derstanding of the efficient ESIPT in 6. With respect to the
À
Laser flash photolysis (LFP) was performed to probe for
QMs that are formed by ESIPT or solvent-assisted PT
(Figure 1 and Figures S14–S20 in the Supporting Informa-
rotation about the C O bond (and orientation of the OH-
and the adjacent phenyl), we distinguish between the syn-
(S) and the anti-(A) conformations. Under experimental
conditions for D-exchange, (cACHTNUGTRENUNG(D2O)=0.3m), the number of
D2O molecules exceeded the number of reactant molecules
by two orders of magnitude. Therefore, it is plausible to
assume that clusters with H2O are ubiquitously formed in
solution. The minimum energy structures of 6 and the corre-
sponding H2O-cluster are syn-(S6 and S6·W). The anti-con-
formations A6 and A6·W are found 3.79 (2.63) and 3.94
(3.06) kcalmolÀ1 higher in energy in the gas phase (polariza-
ble continuum, see Table S1 in the Supporting Information).
The RI-CC2 calculations of S6 yield two energetically
close p–p* transitions at 290 nm (S1) and 273 nm (S2) with
comparable oscillator strengths (Table 1). In the first state,
1
characterized as La according to E. Pines,[33] the transition
dipole is approximately directed along the long naphthalene
axis. In the second state, 1Lb, the dipole points along the
short axis. Due to the phenyl interaction with the naphthol
ring both transitions have charge transfer character. The
Figure 1. Transient absorption spectrum of 1 in O2-purged CH3CN solu-
tion 60 ns after the laser flash (inset: decay at 480 nm).
1
leading excitations contributing to La are shown in Figure 2
(insets, left). At its optimized geometry the 1La state lies
almost DEꢀ0.74 eV below the vertical excitation. This is
a consequence of substantial geometrical changes that the
system experiences which include a 20 degree rotation of
the phenyl ring. Specifically, the tilt of 57.18 between the
two rings at S0 minimum energy geometry is reduced to 36.0
tion). In CH3CN, LFP of 6 showed the presence of a short-
lived transient absorbing at 350–570 nm (3.54–2.18 eV) with
a lifetime of ꢀ20 ns. The transient was not affected by O2 in
accordance with its formation from the singlet excited state.
In CH3CN/D2O (3:1) the decay kinetics of the transient was
slower (tꢀ60–70 ns) than in CH3CN-H2O (tꢀ35–50 ns).
The slower decay kinetics in the presence of D2O is in
agreement with slower H(D)-transfer due to the expected
deuterium isotope effect.[30] LFP of 6OMe that cannot un-
dergo ESIPT did not give rise to the observed short-lived
1
at the La optimized geometry leading to an effective short-
ening of the proton transfer distance from 2.38 on the S0 to
1
1.99 ꢂ on La. Figure S4 and the graphical abstract display
1
the difference in the electron densities between La and the
ground state. The transfer of negative charge from the naph-
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Table 1. Vertical and adiabatic excitation energies of the lowest two excited singlet states of S6, S6·W, and A6·W computed using the RI-CC2/cc-pVDZ
method and the components of the transition strength, fx and fy, directed approximately along the naphthalene long and short axes, respectively.[a]
State
S6
S6·W
A6·W
DE [nm]
fx
fy
DE [nm]
fx
fy
DE [nm]
fx
fy
1p p* (1La)
1p p* (1Lb)
290 (325)[a]
273
0.44
0.10
0.01
0.50
292 (356)[a]
275
0.53
0.001
0.13
0.58
293 (342)[a]
281
0.30
0.18
0.003
0.68
[a] The value in parenthesis corresponds to adiabatic excitation energy.
The electronic character of the first two states of S6·W is
À
analogous to S6. Upon stretching of the O H bond, the
energy of the La state gradually rises as the proton is trans-
1
ferred from the OH group to the H2O molecule (Figure 3).
The barrier for the PT to H2O amounts to DEad =0.61 eV
and DEad =0.68 eV at the RI-CC2/cc-pVDZ and RI-CC2/
aug-cc-pVDZ levels, respectively. In both cases this is com-
parable to the nuclear kinetic energy gain of the system at
Figure 2. Linearly interpolated path (LIP) and relaxed scan of the S6 1La
state along the OH stretching coordinate. Insets: occupied (bottom) and
1
unoccupied (top) molecular orbitals of the La state at the vertical geom-
etry (left) and at ROH =1.59 ꢂ (right).
thol oxygen (blue) to the phenyl ortho-carbon atom (red)
and to the bond connecting the two subunits is apparent.
Clearly, the charge redistribution sets the stage for the sub-
Figure 3. Minimum energy profiles of the 1La state along the proton
transfer coordinate in S6·W. The energies of the Spp
*
and 1La have been
0
sequent ESIPT.
Stretching of the O H bond in the La state of 6 promotes
1
calculated at the partially optimized La geometries. In the region around
the reaction barrier single point calculations along the linearly interpolat-
ed path (LIP) are performed to preserve the orientation of the system.[43]
1
À
ESIPT to the phenyl ring, delivering QM 7. The potential
energy profiles for the ESIPT reaction path along the
À
O H···p bond is shown in Figure 2. A negligible barrier of
<0.05 eV was found along this path. The elongation of the
1
the La minimum, that is, the difference in energy between
À
O H bond and the increase of the torsional angle from 36.0
the vertical and the adiabatic excitations of 0.77 eV (RI-
CC2/cc-pVDZ) and 0.58 eV (RI-CC2/aug-cc-pVDZ). The
subsequent PT to the ortho-position of the phenyl ring is
barrierless and leads to a CI with the S0. However, at
around at ROH =1.2 ꢂ the potential energy surface is very
flat, with an almost negligible gradient between the oxygen
and transferring H-atom suggesting the presence of a long-
living species. This is in accordance with the measured life-
time of QM 7 in CH3CN/H2O, as well as with the observed
increase of the QM 7 lifetime in CH3CN/D2O (3:1; see
above). Moreover, since the H2O-mediated ESPT pathway
requires a localization of vibrational energy in the high fre-
to 45.8 degrees, disrupt the conjugation of the naphthol p-
electron system and leads to the strong destabilization of
the ground state. The conical intersection (CI) of the 1La
and the ground electronic state is encountered ꢀ2.5 eV
1
above the S0 equilibrium structure. The analysis of the La
state along the PT coordinate reveals a gradual increase in
the charge transfer character. No CI with other electronic
states have been found along the reaction path.[34] Once on
the S0 surface, the excess vibrational energy from QM 6 is
efficiently removed by back PT in accordance with the mea-
sured lifetime of QM 7 in CH3CN of only 20 ns (see above).
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Generation of Quinone Methides through Excited State Intramolecular Proton Transfer
FULL PAPER
À
quency O H stretching mode, it is expected to occur on
Conclusion
a longer time scale, and take place with lower quantum
yield than direct ESIPT. The finding is consistent with the
experimental observation of more efficient D-exchange at
lower D2O concentration.
In nonprotic solvents, 6 undergoes efficient ultrafast barrier-
1
less ESIPT along the surface of the La state, delivering QM
7 via a CI with the S0. Increase of H2O concentration leads
to an overall decrease in the quantum yield of ESIPT to the
ortho-position of the adjacent phenyl. At the same time
H2O-cluster formation promotes PT to the distal naphtha-
lene positions. The present photochemical and theoretical
investigation has delineated the requirements for ESIPT to
carbon to be an efficient process and thus opens the way to
develop new examples and potential new applications of
photochemical QM generation in biological and chemical
systems.
De-excitation from S1 provides the vibrational energy the
system requires to overcome the S6 syn to anti isomerization
barrier of 4.54 kcalmolÀ1 (0.2 eV), leading to the higher pop-
ulation of A6·W. The electronic excitation of A6·W opens
up new pathways; formation of naphtholate and solvent-
mediated PT to the distal naphthalene positions 5, 7, and 8.
In contrast to S6·W, the H2O-mediated PT to the H2O-bulk
and to the naphthalene position 8 in A6·W is a barrierless
reaction (Figure 4). In the first step, the naphthol OH
proton is transferred to the H2O molecule. The subsequent
PT to the naphthalene position 8 delivers zwitterion 9. The
PT to the naphthalene position 8 corresponds to the lowest
Experimental Section
General: 1H and 13C NMR spectra were recorded on the machines oper-
ating at 300, 500, or 600 MHz. The NMR spectra were taken in CDCl3 or
[D6]acetone at RT using TMS as a reference and chemical shifts were re-
ported in ppm. For the assignation of the signals 2D homonuclear COSY
and NOESY, and heteronuclear HSQC and HMBC correlation tech-
niques were applied. UV/Vis spectra were recorded at rt. For the sample
analysis the HPLC equipped with a Diode-Array detector and a C18
column was used. Mobile phase was CH3OH/H2O (15%). For the chro-
matographic separations silica gel (0.05–0.2 mm) was used. Analytical
thin layer chromatography was performed on silica gel plates. MS were
recorded on a HPLC-MS system using negative mode electrospray ioni-
zation technique. The deprotonation was achieved by use of triethyla-
mine. Irradiation experiments were performed in reactors equipped with
2, 8 or, 16 lamps with the output at 254 nm or 300 nm. Chemicals (1-
naphthol, triphenylbismuth and butyl lithium) were purchased from the
usual commercial sources and were used as received. Solvents were puri-
fied by distillation.
Irradiation in CH3CN/D2O: To a solution of 2-phenyl-1-naphthol (6,
5 mg, 0.023 mmol) in CH3CN (38 mL) was added D2O (12 mL). The solu-
tion was purged with Ar for 30 min and irradiated in a Rayonet reactor
at 254 or 300 nm (16 lamps) for 1 or 10 min. During irradiation, solution
was continuously purged with Ar and cooled by a cold-finger condenser.
After irradiation, 50 mL of H2O was added and extractions with CH2Cl2
(3ꢁ50 mL) were carried out. The extracts were dried over anhydrous
MgSO4. After filtration and evaporation of the solvent, crude mixture
was analyzed by NMR and MS.
Figure 4. Minimum energy profiles of the 1La state along the proton
transfer coordinate in A6·W. The energies of the Spp
*
and 1La, states
0
1
have been calculated at the partially optimized geometries of La. Occu-
1
pied (bottom) and unoccupied (top) molecular orbitals of the La state at
the minimum energy geometry (left) and at ROH =1.35 ꢂ (right).
Alternatively, 2-phenyl-1-naphthol (6, 10 mg, 0.046 mmol) was dissolved
in CH3CN (10 mL). The solution was divided into two parts and poured
into two quartz cuvettes. To the first cuvette CH3CN (10 mL) and D2O
(100 mL) were added, and to the second CH3CN (5 mL) and D2O (5 mL).
Both solutions were purged with Ar (30 min), sealed and irradiated at
the same time in a Luzchem reactor equipped with a merry-go-round
using 8 lamps with the output at 300 nm for 1 h. To the irradiated solu-
tions H2O (20 mL) was added and extractions with CH2Cl2 (3ꢁ30 mL)
were carried out. The extracts were dried over anhydrous MgSO4. After
filtration and evaporation of the solvent, crude mixture was analyzed by
NMR and MS.
energy pathway, while PT to the positions 5 and 7 is favored
by the largest negative charge on these atoms (See Table
S11 in the Supporting Information).
Why is the quantum efficiency for ESIPT in 6 much
higher than in any other investigated system?[13–19] For ex-
ample in 3, the optimization of the S1 state of S3, leads di-
rectly to CI with S0 as there is no minimum on the S1 sur-
face. However, the minimum energy structure of 3·W is anti
(see the Supporting Information). The energy difference of
1.46 kcalmolÀ1 between A3·W and S3·W corresponds to
a Boltzmann population of the syn conformer of approxi-
mately 7% which is close to the observed F of D-incorpora-
tion in 3 (F=0.041). This is an example of the operation of
the NEER principle (nonequilibration of the excited-state
rotamers) in control of the photochemical reactivity.[35]
Control experiments were performed by preparing the same solution as
described above that were kept in dark and worked-up with H2O. After
extractions with CH2Cl2 drying over anhydrous MgSO4, filtration and
evaporation of the solvent, the mixture was analyzed by NMR and MS.
Quantum yields for the D-incorporation: Solutions of 6 in CH3CN/D2O
(3:1), as well as a solution of valerophenone in CH3CN/H2O (1:1) were
freshly prepared and their concentrations adjusted to have absorbances
0.4–0.8 at 254 nm. After adjustment of the concentration and measure-
ment of the corresponding UV/Vis spectra the solutions were filled in
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N. Basaric, N. Doslic, P. Wan et al.
quartz cuvettes (15 mL), purged with a stream of N2 (20 min each), and
sealed with a septum. The cuvettes were irradiated at the same time in
a Luzchem reactor equipped with a merry-go-round and 2 lamps with the
output at 254 nm for 0.5, 1, and 2 min. After each irradiation, the samples
were taken from the cuvettes by use of a syringe and analyzed by ESI
MS (the D content was determined from the difference of the intensity
of signals of irradiated and nonirradiated sample), whereas the conver-
sion of valerophenone was analyzed by HPLC. Quantum yields for the
D-exchange was calculated using valerophenone actinometer (formation
of acetophenone in aqueous media, F=0.65Æ0.03).[29]
Alternatively, 2-phenyl-1-naphthol (1, 5 mg, 0.023 mmol) was dissolved in
CH3CN (32 mL). To the solution was added D2O (12 mL). The solution
was purged with Ar for 30 min and irradiated in a Rayonet reactor at 254
(16 lamps) for 1 min. During irradiation, solution was continuously
purged with Ar and cooled by a cold-finger condenser. After irradiation,
50 mL of H2O was added and extractions with CH2Cl2 (3ꢁ50 mL) were
carried out. The extracts were dried over anhydrous MgSO4. Under the
same conditions 2-phenylphenol (2, 6 mg, 0.03 mmol), dissolved in
CH3CN/D2O (3:1, 50 mL) was irradiated for 10 min. After aqueous
workup, extraction and removal of the solvent extent of the deuterium
incorporation was determined by 1H NMR. Quantum yield for the D-ex-
change was calculated using D-exchange in 2-phenylphenol as a secondary
actinometer (F=0.041Æ0.03).[15]
Steady state and time-resolved fluorescence measurements: The steady
state measurements were performed on a luminescence spectrometer.
The samples were dissolved in cyclohexane, CH3CN, or CH3CN/H2O
(1:4) and the concentrations were adjusted to have absorbance at the ex-
citation wavelength (300, 310, and 320 nm) <0.1. Solutions were purged
with nitrogen for 30 min prior to analysis. The measurements were per-
formed at 208C. Fluorescence quantum yields were determined by com-
parison of the integral of the emission bands with the one of quinine sul-
fate in 0.05m H2SO4 (Ff =0.54).[36] Typically, three absorption traces were
recorded (and averaged) and three fluorescence emission traces, exciting
at three different wavelengths (300, 310, and 320 nm). Three quantum
yields were calculated and the mean value reported.
region between the vertical and adiabatic geometries a set of single point
calculations for geometries along the linearly interpolated path (LIP)
have been performed. LIP geometries have been obtained by interpolat-
ing between terminal geometries in internal coordinates. All coupled
cluster calculations have been performed with the TURBOMOLE pack-
age.[42]
Acknowledgements
This work was financed by the Foundation for Science, Higher Education
and Technological Development of Croatia (HRZZ grant No. 02.05/25),
the Ministry of Science Education and Sports of Croatia (grant No. 098–
0352851–2921), the University of Victoria, and the Natural Sciences and
Engineering Research Council (NSERC) of Canada.
[1] a) J. F. Ireland, P. A. H. Wyatt, Adv. Phys. Org. Chem. 1976, 12,
131–221; b) S. J. Formosinho, L. G. Arnaut, J. Photochem. Photo-
biol. A: Chem. 1993, 75, 21–48; c) S. M. Ormson, R. G. Brown,
Prog. React. Kinet. 1994, 19, 45–91; d) D. Le Gourrierec, S. M.
Ormson, R. G. Brown, Prog. React. Kinet. 1994, 19, 211–275; e) A.
Sinicropi, R. Pogni, R. Basosi, M. A. Robb, G. Gramlich, W. M.
Nau, M. Olivucci, Angew. Chem. Int. Ed. 2001, 40, 4185–4189.
[2] J. I. Kwon, S. Y. Park, Advan. Mater. 2011, 23, 3615–3642.
[3] a) K. Choi, A. D. Hamilton, Angew. Chem. Int. Ed. 2001, 40, 3912–
3915; b) A. S. Klymchenko, A. P. Demchenko, J. Am. Chem. Soc.
2002, 124, 12372–12379; c) X. Peng, Y. Wu, J. Fan, M. Tian, K. Han,
J. Org. Chem. 2005, 70, 10524–10531; d) R. M. F. Batista, E. Oli-
veira, S. P. G. Costa, C. Lodeiro, M. M. M. Raposo, Org. Lett. 2007,
9, 3201–3204.
[4] S. Arumugam, V. V. Popik, J. Am. Chem. Soc. 2011, 133, 5573–5579.
[5] a) D. A. Parthenopoulos, D. P. McMorrow, M. Kasha, J. Phys. Chem.
ˇ
1991, 95, 2668–2674; b) A. Douhal, F. Amat-Guerri, A. U. Acuna,
Fluorescence decay histograms were obtained on an, equipped with
a light emitting diode (excitation wavelength 310 nm), using time-corre-
lated single photon counting technique in 1023 channels. Histograms of
the instrument response functions (using LUDOX scatterer), and sample
decays were recorded until they reached 3ꢁ103 counts in the peak chan-
nel. The half width of the instrument response function was typically
around 1.5 ns. The time increment per channel was 0.02 or 0.049 ns. Ob-
tained histograms were fitted as sums of exponential using Gaussian-
weighted nonlinear least-squares fitting based on Marquardt–Levenberg
minimization implemented in the software package of the instrument.
The fitting parameters (decay times and pre-exponential factors) were
determined by minimizing the reduced chi-square c2. Additional graphi-
cal method was used to judge the quality of the fit that included plots of
surfaces (“carpets”) of the weighted residuals vs. channel number.
K. Yoshihara, Chem. Phys. Lett. 1994, 217, 619–625; c) S. Park, O.-
H. Kwon, S. Kim, S. Park, M.-G. Choi, M. Cha, S. Y. Park, D.-J.
Jang, J. Am. Chem. Soc. 2005, 127, 10070–10074.
[6] a) G. J. Stueber, M. Kieninger, H. Schettler, W. Busch, B. Goeller, J.
Franke, H. E. A. Kramer, H. Hoier, S. Henkel, P. Fischer, H. Port, T.
Hirsch, G. Rytz, J.-L. Birbaum, J. Phys. Chem. 1995, 99, 10097–
10109; b) J. Keck, H. E. A. Kramer, H. Port, T. Hirsch, P. Fischer, G.
Rytz, J. Phys.Chem. 1996, 100, 14468–14475.
[7] a) J. M. Kauffman, Radiation Phys. Chem. 1993, 41, 365–371; b) A.
Pla-Dalmau, J. Org. Chem. 1995, 60, 5468–5473.
[8] L. V. Schꢃfer, G. Groenhof, A. R. Klingen, G. L. Ullmann, M.
Boggio-Pasqua, M. A. Robb, H. Grubmꢄller, Angew. Chem. Int. Ed.
2007, 46, 530–536.
[9] R. M. D. Nunes, M. Pineiro, L. G. Arnaut, J. Am. Chem. Soc. 2009,
131, 9456–9462.
[10] T. Mutai, H. Tomoda, T. Ohkawa, Y. Yabe, K. Araki, Angew. Chem.
Int. Ed. 2008, 47, 9522–9524.
Laser flash photolysis (LFP): All LFP studies were conducted at the Uni-
versity of Victoria LFP facility employing a YAG laser, with a pulse
width of 10 ns and excitation wavelength 266 nm. Static cells (0.7 cm)
were used and solutions were purged with nitrogen or oxygen for 20 min
prior to measurements. Absorbances at 266 nm were approximately 0.4.
[11] M. Kasha, J. Chem. Soc. Faraday Trans. 2 1986, 82, 2379–2392.
´
[12] a) N. Basaric, P. Wan, Photochem. Photobiol. Sci. 2006, 5, 656–664;
Computational methods: The ground state equilibrium geometries of 2-
phenylphenol (3) and 2-phenyl-1-naphthol (6) and their 1:1 H2O-clusters,
3·W and 6·W, have been determined with the second order Møller–Ples-
set (MP2) method and the triple-zeta valence plus polarization (TZVP)
basis set.[37] Solvation effects were estimated with the polarizable continu-
um model (PCM)[38] using the dielectric constant of CH3CN as imple-
mented in the Gaussian09 program package.[39] The vertical excitation en-
ergies, optimized geometries, and ESIPT reaction paths have been deter-
mined with the second order approximate coupled cluster (CC2) method
with the cc-pVDZ and aug-cc-pVDZ basis sets.[40] The resolution of iden-
tity (RI) approximation has been used for the evaluation of the electron
repulsion integrals.[41] Two types of reaction path calculations have been
employed. In the relaxed scans, apart from the driving coordinate all
other internal degrees of freedom have been allowed to relax. In the
b) N. Behin Aein, P. Wan, J. Photochem. Photobiol. A: Chem. 2009,
ˇ
´
ˇ ´
´
208, 42–49; c) N. Basaric, N. Cindro, Y. Hou, I. Zabcic, K. Mlinaric-
Majerski, P. Wan, Can. J. Chem. 2011, 89, 221–234.
[13] S. P. Webb, L. A. Philips, S. W. Yeh, L. M. Tolbert, J. H. Clark, J.
Phys. Chem. 1986, 90, 5154–5164.
[14] M. Lukeman, D. Veale, P. Wan, R. N. Munasinghe, J. E. T. Corrie,
Can. J. Chem. 2004, 82, 240–253.
[15] a) M. Lukeman, P. Wan, Chem. Commun. 2001, 1004–1005; b) M.
Lukeman, P. Wan, J. Am. Chem. Soc. 2002, 124, 9458–9464.
[16] M. Lukeman, P. Wan, J. Am. Chem. Soc. 2003, 125, 1164–1165.
[17] a) M. Flegel, M. Lukeman, L. Huck, P. Wan, J. Am. Chem. Soc.
´
2004, 126, 7890–7897; b) N. Basaric, P. Wan, J. Org. Chem. 2006, 71,
2677–2686; c) L. Y.-H. Wang, P. Wan, Photochem. Photobiol. Sci.
2011, 10, 1934–1944.
&
6
&
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Generation of Quinone Methides through Excited State Intramolecular Proton Transfer
FULL PAPER
[18] M. K. Nayak, P. Wan, Photochem. Photobiol. Sci. 2008, 7, 1544–
1554.
d) T. A. Gadosy, D. Shukla, L. J. Johnston, J. Phys. Chem. A 1999,
103, 8834–8839.
[19] M. Lukeman, M.-D. Burns, P. Wan, Can. J. Chem. 2011, 89, 433–
440.
[33] E. Pines, in The Chemistry of Phenols, (Ed.: Z. Rappoport), Wiley,
New York, 2003.
[20] a) S. S. Lehrer, J. Am. Chem. Soc. 1970, 92, 3459–3462; b) H. Shizu-
ka, M. Serizawa, H. Kobayashi, K. Kameta, H. Sugiyama, T. Mat-
suura, I. Saito, J. Am. Chem. Soc. 1988, 110, 1726–1732.
[21] Ed. S. E. Rokita, Quinone Methides, Wiley, New York, 2009.
[22] T. P. Pathak, M. S. Sigman, J. Org. Chem. 2011, 76, 9210–9215.
[23] a) H. Kang, S. E. Rokita, Nucl. Acid Res. 1996, 24, 3896–3902; b) Q.
Zhou, Q. S. E. Rokita, Proc. Natl. Acad. Sci. U. S. A. 2003, 100,
15452–15457; c) H. Wang, M. S. Wahi, S. E. Rokita, Angew. Chem.
Int. Ed. 2008, 47, 1291–1293; d) H. Wang, S. E. Rokita, Angew.
Chem. Int. Ed. 2010, 49, 5997–5960.
[34] a) A. L. Sobolewski, W. Domcke, J. Phys. Chem. A 2001, 105, 9275–
9283; b) Z. Lan, W. Domcke, V. Vallet, A. L. Sobolewski, S. Maha-
patra, J. Chem. Phys 2005, 122, 224315–224313; c) A. L. Sobolewski,
W. Domcke, J. Phys Chem. A 2007, 111, 11725–11735.
[35] a) H. J. Jacobs, E. Havinga, Adv. Photochem. 1979, 11, 305–373;
b) U. Mazzucato, F. Momicchioli, Chem. Rev. 1991, 91, 1679–1719.
[36] W. R. Dawson, M. W. Windsor, J. Phys. Chem. 1968, 72, 3251–3260.
[37] K. Eichkorn, O. Treutler, H. ꢅhm, M. Hꢃser, R. Ahlrichs, Chem.
Phys. Lett. 1995, 242, 652–660.
[38] J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 2005, 105, 2999–
3094.
[24] a) S. E. Wolkenberg, D. L. Boger, Chem. Rev. 2002, 102, 2477–2495;
b) P. Wang, Y. Song, L. Zhang, H. He, X. Zhou, Curr. Med. Chem.
2005, 12, 2893–2913.
[39] Gaussian 09, Revision A.02, M. J. Frisch, G. W. Trucks, H. B. Schle-
gel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V.
Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X.
Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Son-
nenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven,
J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J.
Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar,
J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox,
J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W.
Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A.
Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, ꢅ.
Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, and D. J. Fox,
Gaussian, Wallingford CT, 2009.
[25] a) J. Wirz, Pure Appl. Chem. 1998, 70, 2221–2232; b) A. P. Pelliccio-
ˇ
li, P. Sebej, J. Wirz, Photochem. Photobiol. Sci. 2012, 11, 967–971.
[26] a) D. H. R. Barton, J. C. Blazejewski, B. Charpiot, D. J. Lester, W. B.
Motherwell, M. T. B. Papoula, J. Chem.Soc. Chem. Commun. 1980,
827–829; b) D. H. R. Barton, N. Y. Bhatnagar, J. C. Blazejewski, B.
Charpiot, J. P. Finet, D. J. Lester, W. B. Motherwell, M. T. B. Papou-
la, S. P. J. Stanforth, Chem. Soc. Perkin Trans. 1 1985, 2657–2665.
[27] Y. Ahmad, D. H. Hey, J. Chem. Soc. 1959, 3819–3822.
[28] H. Shizuka, S. Tobita, J. Am. Chem. Soc. 1982, 104, 6919–6921.
[29] H. J. Kuhn, S. E. Braslavsky, R. Schmidt, Pure Appl. Chem. 2004, 76,
2105–2146.
[30] a) M. Capponi, I. G. But, B. Hellrung, G. Persy, J. Wirz, Can. J.
Chem. 1999, 77, 605–613; b) I. Glynne Gut, L. C. Scheibler, J. Wirz,
Photochem. Photobiol. Sci. 2010, 9, 901–907.
[31] According to NMR spectra of the deuterated sample obtained on
photolysis in CH3CN/D2O (3:1) relative ratio of 7/8/9 is estimated to
be 10:1.3:1. Formation of 10–12 may also be possible in an overall
quantum yield similar to that of 8. Due to the overlapping signals of
the naphthalene H-atoms at the positions 4, 6, and 7 their relative
ratio cannot be given.
[32] a) F. G. Bordwell, J.-P. Cheng, J. Am. Chem. Soc. 1991, 113, 1736–
1743; b) H. Mohan, R. Hermann, S. Naumov, J. P. Mittal, O. Brede,
J. Phys. Chem. A 1998, 102, 5754–5762; c) D. Shukla, N. P. Schepp,
N. Mathivanan, L. J. Johnston, Can. J. Chem. 1997, 75, 1820–1829;
[40] O. Christiansen, H. Koch, P. Jorgensen, Chem. Phys. Lett. 1995, 243,
409–418.
[41] F. Weigend, M. Hꢃser, Theor. Chem. Acc. 1997, 97, 331–340.
[42] R. Ahlrichs, M. Bꢃr, M. Hꢃser, H. Horn, C. Kçlmel, Chem. Phys.
Lett. 1989, 162, 165–169.
[43] B. Auer, L. E. Fernandez, S. Hammes-Schiffer, J. Am. Chem. Soc.
2011, 133, 8282–8292.
Received: April 4, 2012
Published online: && &&, 0000
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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´
ˇ ´
N. Basaric, N. Doslic, P. Wan et al.
Irradiation of 2-phenyl-1-naphthol in
CH3CN/D2O (3:1) leads to very effi-
cient incorporation of deuterium at the
ortho-positions of the adjacent phenyl
ring along with minor incorporation at
the naphthalene positions 5 and 8.
These findings are explained by
excited state intramolecular proton
transfer (ESIPT) from the phenol OH
to the corresponding carbon atoms
(see figure).
Photochemistry
´
ˇ ´
ˇ
´
N. Basaric,* N. Doslic,* J. Ivkovic,
Y.-H. Wang, M. Malis,
P. Wan* ........................ &&&& — &&&&
Very Efficient Generation of Quinone
Methides through Excited State Intra-
molecular Proton Transfer to a Carbon
Atom
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ÝÝ
These are not the final page numbers!