Photochemical formation and chemistry of long-lived adamantylidene-quinone methides and 2-adamantyl cations

Article abstract of DOI:10.1021/jo902004n

(Chemical Equation Presented) Hydroxymethylphenols strategically substituted with the 2-hydroxy-2-adamantyl moiety, AdPh 8-10, were synthesized, and their photochemical reactivity was investigated. On excitation to the singlet excited state, AdPh 8 undergoes intramolecular proton transfer coupled with a loss of H₂O giving quinone methide 8QM. The presence of 8QM has been detected by laser flash photolysis (CH₃CN-H₂O 1:1, τ = 0.55 s) and UV-vis spectroscopy. Singlet excited states of AdPh 9 and 10 in the presence of H₂O dehydrate giving 9QM and 10QM. Photochemically formed QMs are trapped by nucleophiles giving the addition products (e.g., Φ for methanolysis of 8 is 0.55). In addition, the zwitterionic 9QM undergoes an unexpected rearrangement involving transformation of the 2-phenyl-2-adamantyl cation into the 4-phenyl-2-adamantyl cation (Φ ～ 0.03). An analogous rearrangement was observed with methoxy derivatives 9a and 10a. Zwitterionic 9QM was characterized by LFP in 2,2,2-trifluoroethanol (τ = 1 μs). In TFE, in the ground state, AdPh 10 is in equilibrium with 10QM, which allowed for recording the ¹H and ¹³C NMR spectra of the QM. Introduction of the adamantyl substituent into the o-hydroxymethylphenol moiety increased the quantum yield of the associated QM formation by up to 3-fold and significantly prolonged their lifetimes. Furthermore, adamantyl substituent made the study of the alkyl-substituted quinone methides easier by LFP by prolonging their lifetimes and increasing the quantum yields of formation. 2009 American Chemical Society.

Full text of DOI:10.1021/jo902004n

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Photochemical Formation and Chemistry of Long-Lived Adamantylidene-
Quinone Methides and 2-Adamantyl Cations
,†
Nikola Basaric,* Ivana Zabcic, Kata Mlinaric-Majerski, and Peter Wan*
†
,‡
ꢁ ꢀ †
ꢀ
ꢁ
ꢀ
†
ꢁ
ꢀ
ꢁ
Department of Organic Chemistry and Biochemistry, Ru{er Boskovic Institute, Bijenicka cesta 54,
10000 Zagreb, Croatia and ‡Department of Chemistry, Box 3065, University of Victoria, British Columbia,
Canada V8W 3 V6
nbasaric@irb.hr; pwan@uvic.ca
Received September 16, 2009
Hydroxymethylphenols strategically substituted with the 2-hydroxy-2-adamantyl moiety, AdPh 8-
10, were synthesized, and their photochemical reactivity was investigated. On excitation to the singlet
excited state, AdPh 8 undergoes intramolecular proton transfer coupled with a loss of H2O giving
quinone methide 8QM. The presence of 8QM has been detected by laser flash photolysis
(CH3CN-H2O 1:1, τ = 0.55 s) and UV-vis spectroscopy. Singlet excited states of AdPh 9 and 10
in the presence of H2O dehydrate giving 9QM and 10QM. Photochemically formed QMs are trapped
by nucleophiles giving the addition products (e.g., Φ for methanolysis of 8 is 0.55). In addition, the
zwitterionic 9QM undergoes an unexpected rearrangement involving transformation of the 2-
phenyl-2-adamantyl cation into the 4-phenyl-2-adamantyl cation (Φ ∼ 0.03). An analogous
rearrangement was observed with methoxy derivatives 9a and 10a. Zwitterionic 9QM was
characterized by LFP in 2,2,2-trifluoroethanol (τ = 1 μs). In TFE, in the ground state, AdPh 10 is
in equilibrium with 10QM, which allowed for recording the 1H and 13C NMR spectra of the QM.
Introduction of the adamantyl substituent into the o-hydroxymethylphenol moiety increased the
quantum yield of the associated QM formation by up to 3-fold and significantly prolonged their
lifetimes. Furthermore, adamantyl substituent made the study of the alkyl-substituted quinone
methides easier by LFP by prolonging their lifetimes and increasing the quantum yields of formation.
Introduction
Michael systems (e.g., eq 1). Nucleophiles add to the methy-
lene position of QMs, and the driving force of the reaction is
the resulting rearomatization of the molecule. Recently, a
thorough DFT computational study has been performed to
explain the reactivity of QMs as Michael electrophiles with
sulfur, nitrogen, and oxygen nucleophiles2 and pyrimidine
bases.3 In addition, QMs react as dienophiles in [4 þ 2]
Quinone methides (QM) are ubiquitous intermediates in
chemistry and biology.1 The polar nature of these com-
pounds makes them both nucleophilic and electrophilic.
Consequently, they are very reactive and therefore usually
short-lived. The most common reaction of QMs is with
nucleophilic solvent (e.g., water) wherein they behave as
*To whom correspondence should be addressed. (N.B.) Tel: þ 385 1 4561
141. Fax: þ 385 1 4680 195. (P.W.) Tel: þ 1 (250) 721-8976. Fax: þ 1 (250)
721-7147.
ꢂ
(2) Di Valentin, C.; Freccero, M.; Zanaletti, R.; Sarzi-Amade, M. J. Am.
Chem. Soc. 2001, 123, 8366–8377.
(3) Freccero, M.; Di Valentin, C.; Sarzi-Amade, M. J. Am. Chem. Soc.
2003, 125, 3544–3553.
ꢂ
(1) Rokita, S. E., Ed. Quinone Methides; Wiley: Hoboken, 2009.
102 J. Org. Chem. 2010, 75, 102–116
Published on Web 12/03/2009
DOI: 10.1021/jo902004n
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2009 American Chemical Society

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Basaric et al.
JOCArticle
cycloadditions, so they have been used as valuable precur-
sors in synthesis.4
QMs can be generated in thermal reactions by oxidation
of phenols,5 extrusion of water,6 or other small molecules
from hydroxybenzyl alcohols7 and fluoride-induced desi-
lylation.8 The other approach for the generation of QMs
under mild conditions is the use of photochemical reac-
tions.9 Wan et al. developed a general photochemical
method for the generation of QMs by dehydration of
hydroxymethylphenols (e.g., eqs 1-3).10,11 The other
photochemical methods use Mannich bases,12 tertiary
ammonium derivatives of phenols,13 or hydroxybenzyl
acetate derivatives.14 Although quantum yields are higher
in the later reactions, dehydration of hydroxymethylphe-
nols is still a powerful method, primarily because of the
ready availability of the starting materials. On excitation
of phenols 1 and 10, excited-state intramolecular proton
transfer (ESIPT) from the phenol OH to the hydroxyl
group, coupled with a loss of H2O, takes place. That
delivers QM 2 and 20 which react with nucleophilic sol-
vents giving solvolysis products 3 and 30, respectively
(eq 1).10,11,15 Due to the presence of the intramolecular
H-bond in 1 and 10, ESIPT is probably very much facili-
tated. The quantum yield for the methanolysis reaction is
Φ = 0.23 and 0.46, respectively.11 In case of the meta (4, 40)
and the para derivatives (6, 60), the distance between the
phenol and the hydroxyl group is larger, so ESIPT cannot
take place. A protic solvent is required to mediate the
excited-state deprotonation of the phenol moiety and the
protonation of the alcohol. Overall, formal excited-state
proton transfer (ESPT) from the phenol to the alcohol and
dehydration gives QMs (5, 50, 7, 70) which are, however,
formed with lower quantum yields (eqs 2 and 3).10,11,15
The main reason for the widespread interest in the chem-
istry of QMs which blossomed two decades ago is their
reactivity in biological systems.1 It has been suggested that
QMs play a critical role in the biological action of several
classes of antibiotics such as mitomycin and anthracy-
clines.16 Furthermore, QMs react with nucleic acids17 and
amino acids.13 It is now well-established that QMs can act as
DNA cross-linking agents.18 From the discovery of biologi-
cal activity of QMs, derivatization of the parent structure
was performed in order (i) to examine QM reactivity and (ii)
to examine their biological applicability.19 It was shown that
introduction of electron-withdrawing groups make QMs
more electrophilic and hence shorter-lived, whereas elec-
tron-donating groups stabilized the structure.19 Another
way to stabilize such reactive intermediates is the use of a
transition-metal approach. Amouri et al. constructed several
organometallic π-complexes that contain the ring diene of
various o-quinone methides with rhodium and iridium metal
atoms.20 Furthermore, introduction of a steric hindrance at
the ortho position to the carbonyl group in QM results in
lower reactivity of the QM molecules, which has been
attributed to the shielding of the carbonyl oxygen from
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(8) Pande, P.; Shearer, J.; Yang, J.; Greenberg, W. A.; Rokita, S. E. J. Am.
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(9) Wan, P.; Barker, B.; Diao, L.; Fisher, M.; Shi, Y.; Yang, C. Can. J.
Chem. 1996, 74, 465–475.
(10) Wan, P.; Chak, B. J. Chem. Soc., Perkin Trans. 2 1986, 1751–1756.
(11) Diao, L.; Yang, C.; Wan, P. J. Am. Chem. Soc. 1995, 117, 5369–5370.
(12) Nakatani, K.; Higashida, N.; Saito, I. Tetrahedron Lett. 1997, 38,
5005–5008.
(17) (a) Zeng, Q.; Rokita, S. E. J. Org. Chem. 1996, 61, 9080–9081. (b)
Rokita, S. E.; Yang, J.; Pande, P.; Greenberg, W. A. J. Org. Chem. 1997, 62,
3010–3012.
(18) (a) Velhuyzen, W. F.; Pande, P.; Rokita, S. E. J. Am. Chem. Soc.
2003, 125, 14005–14013. (b) Zhou, Q.; Rokita, S. E. Proc. Natl. Acad. Sci. U.
S.A. 2003, 100, 15452–15457. (c) Wang, P.; Liu, R.; Wu, X.; Ma, H.; Cao, X.;
Zhou, P.; Zhang, J.; Weng, X.; Zhang, X. L.; Zhou, X.; Weng, L. J. Am.
Chem. Soc. 2003, 125, 1116–1117. (d) Richter, S. N.; Maggi, S.; Colloredo
Mels, S.; Palumbo, M.; Freccero, M. J. Am. Chem. Soc. 2004, 126, 13973–
13979.
(13) Modica, E.; Zanaletti, R.; Freccero, M.; Mella, M. J. Org. Chem.
2001, 66, 41–52.
(19) Weinert, E. E.; Dondi, R.; Colloredo-Melz, S.; Frankenfield, K. N.;
Mitchell, C. H.; Freccero, M.; Rokita, S. E. J. Am. Chem. Soc. 2006, 128,
11940–11947.
(20) (a) Amouri, H.; Besace, Y.; Le Bras, J. J. Am. Chem. Soc. 1998, 120,
6171–6172. (b) Amouri, H.; Vaissermann, J.; Rager, M. N.; Grotjahn, D. B.
Organometallics 2000, 19, 1740–1748. (c) Amouri, H.; Vaissermann, J.;
Rager, M. N.; Grotjahn, D. B. Organometallics 2000, 19, 5143–5148. (d)
Amouri, H.; Le Bras, J. Acc. Chem. Res. 2002, 35, 501–510.
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9854–9855. (b) Chiang, Y.; Kresge, A. J.; Zhu, Y. J. Am. Chem. Soc. 2001,
123, 8089–8094. (c) Chiang, Y.; Kresge, A. J.; Zhu, Y. J. Am. Chem. Soc.
2002, 124, 717–722. (d) Chiang, Y.; Kresge, A. J.; Zhu, Y. J. Am. Chem. Soc.
2002, 124, 6349–6356.
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J. Org. Chem. Vol. 75, No. 1, 2010 103

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solvent interactions.21 However, it was also shown that these
QMs exhibit high toxicity in the lung tissue of mice.22 On the
other hand, introduction of the steric hindrance at the
give rise to methanolysis products via QM intermediates.
Therefore, we performed photolyses (Rayonet reactor,
254 nm, argon purged) of AdPh 8-10 and 11 in
CH3OH-H2O (3:1) and neat CH3OH. The photochemical
reaction in CH3OH-H2O (3:1) could be run to completion
for 8 (7 lamps, 20 min) and to 70% conversion for 10 (30% of
the starting material can be recovered), giving only ethers 8b
and 10b (eq 4), which were isolated quantitatively, or in 70%
yield, respectively. Similarly, photolysis (16 lamps, 1 h) of
phenol 11 gave cleanly ether 11b (66% according to NMR,
40% isolable yield). On the other hand, under the same
photolysis conditions 9 gave two products, ether 9b (10%)
and the unexpected rearranged alcohol 9c (8%) (eq 5). In the
low conversion photolysis experiments, the unreacted 9
(70%) could be recovered. Photolysis of 8 in neat CH3OH
was also clean, giving quantitatively ether 8b. On the other
hand, irradiation of 9 in CH3OH gave ether 9b (4%) and
rearranged alcohol 9c (20%), whereas 10 gave ether 10b
(20%) and the reduction product 12 (10%). The unreacted 9
or 10 can be recovered by chromatography.
methylene position of QMs lowered cytotoxic effects.23
A
logical continuation in the research on QMs reactivity and
biological activity is further elaboration of the structure-
reactivity and the structure-activity pattern by making new
derivatives with more significant sterical congestion at the
methylene position.
Herein, we report synthesis of three adamantylphenols
8-10 that are expected to give rise to sterically congested
QMs on photochemical excitation. These QMs should have
altered reactivity due to the presence of the bulky adamantyl
substituents at the methylene position. We aim to study their
reactivity with nucleophiles and compare it to the reactivity
of the model compounds (without adamantyl substituents)
such as 1 and 11. Additionally, more insight into the me-
chanism of the photochemical reactions of 8-10 that lead to
the formation of QMs will be obtained by performing
product studies, fluorescence measurements, and time-re-
solved absorption spectroscopy. Indeed, by investigating
photochemistry of AdPh 9 and methoxy derivatives 9a and
10a, we discovered a photoinduced rearrangement of a 2-
adamantyl cation.
Results and Discussion
Materials. Adamantylphenols (AdPh 8-10) were pre-
pared by cleavage of the corresponding methyl ether deriva-
tives 8a-10a by use of Lewis acid (BBr3). The methoxy
derivatives 8a-10a were obtained by Grignard reactions of
the corresponding bromoanisoles and 2-adamantanone.
Compound 11 was prepared from 11a (obtained by the
Grignard reaction of o-bromoanisole and acetone) by the
methyl ether cleavage in the reaction with sodium ethylthio-
late, according to the modification of a known procedure.24
Photochemical Reactions. In view of previously reported
photochemical reactions of hydroxymethylphenols,11,15 it
is anticipated that photolysis of AdPh in CH3OH should
The structure of the rearranged alcohol 9c was determined
by spectroscopic methods. In the aliphatic region of the 1H
NMR spectrum, two characteristic signals are present at δ
3.86 and 3.10 ppm corresponding to the H atoms at positions
2 and 4 of the adamantane ring. Furthermore, in the 13C
NMR spectrum in the aliphatic region six doublets and four
triplets are seen (as compared to one quarternery carbon,
three doublets, and three triplets for 9). 2D homonuclear and
heteronuclear spectra are fully in accordance with the as-
signed structure. The stereochemistry of the product was
determined from the NOESY spectrum and NOE difference
spectra. Namely, there is no NOE interaction between the
H-atoms at positions 2 and 4 of the adamantane ring. On the
other hand, there is an NOE interaction between the H atom
adjacent to the adamantyl OH group and the phenyl H
atoms.
(21) (a) McCracken, P. G.; Bolton, J. L.; Thatcher, G. R. J. J. Org. Chem.
1997, 62, 1820–1825. (b) Lewis, M. A.; Graff Yoerg, D.; Bolton, J. L.;
Thompson, J. A. Chem. Res. Toxicol. 1996, 9, 1368–1374.
(22) (a) Bolton, J. L.; Sevestre, H.; Ibe, B. O.; Thompson, J. A. Chem. Res.
Toxicol. 1990, 3, 65–70. (b) Bolton, J. L.; Thompson, J. A. Drug. Metab.
Dispos. 1991, 19, 467–472.
1
In the H NMR spectrum of 12 a characteristic broad
(23) (a) Filar, L. J.; Winstein, S. Tetrahedron Lett. 1960, 1 (25), 9–16. (b)
Mizutani, T.; Ishida, I.; Yamamoto, K.; Tajima, K. Toxicol. Appl. Pharma-
col. 1982, 62, 273–281.
singlet appears at δ 2.9 ppm that is assigned to the signal of
the adamantyl-benzylic H atom. In addition, in the aliphatic
region of the 13C NMR spectrum four doublets and three
(24) Mirrington, R. N.; Feutrill, G. I. Org. Synth. 1973, 53, 90–94.
104 J. Org. Chem. Vol. 75, No. 1, 2010

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triplets are seen. However, there is no signal in the aliphatic
region of the spectrum corresponding to the quarter-
nary carbon atom, all in accordance with the assigned struc-
ture 12.
Irradiation of 8 and 10 was also performed in CH3CN with
ethanolamine as nucleophile. In both reactions the corre-
sponding ethanolamine adducts were formed. On photolysis
of 8, the adduct 13 was formed quantitatively so it was
isolated and fully characterized. Additionally, irradiation
of AdPh 8 in CH3CN in the presence of excess of ethyl vinyl
ether gave Diels-Alder adduct 8DA, 50% (eq 6). The
isolation of the Diels-Alder adduct undoubtedly indicate
the intermediacy of the quinone methide 8QM in the photo-
lysis of 8.
FIGURE 1. Methanolysis product yields as a function of the acidity
of the irradiated solution. Irradiation was performed in
CH3OH-H2O (3:1), by using 7 lamps, 254 nm for 20 min (three
lamps, 3 min for 8). pH of the aqueous part was measured by pH-
meter and adjusted by addition of NaOH or H2SO4. The composi-
tion of the solution was analyzed by HPLC. The points in parenth-
eses correspond to thermally formed methanolysis products.
Formation of the rearranged alcohols 9c, 9ac, and 10ac
suggests the intermediacy of the carbocations that could
arise via an acid-catalyzed protonation of the alcohol moiety
and dehydration (vide infra). Since that represents a compet-
ing, not thoroughly investigated pathway in the photosolvo-
lysis of hydroxymethylphenols, we performed additional
experiments to probe for the influence of acidity to the
photosolvolysis. Therefore, photochemical reactions of
AdPh 8-10 were carried out in CH3OH-H2O (3:1) at
different acidities. The pH of the aqueous part was measured
by a pH-meter and adjusted by the addition of NaOH or
H2SO4. The composition of the irradiated solutions was
analyzed by HPLC. Control experiments were performed
in which the solution was kept in the dark to check for the
possible competing thermal methanolysis pathway. The
results are summarized in Figure 1. It should be noted that
at low pH (<2.5) methanolysis products 8b and 10b are
formed in a thermal reaction. On the other hand, thermal
methanolysis at pH 2.2 for the meta isomer 9 was possible,
but it was much slower compared to the photochemical.
Photolysis of 9 (CH3OH-H2O 3:1, pH 2.2, 7 lamps, 20 min)
gave 9b in 48% yield, whereas at the same time the thermal
reaction gave only 1.6% of 9b. Prolonged stirring of the
solution of 9 gave 40% of 9b in 2 days, and to achieve the
total conversion, 10 days were required. The photolysis
results at different pH indicate that the efficiency of the
photochemical formation of 8b is not influenced by acidity in
the range studied, whereas 9b and 10b can also be formed by
an acid catalyzed pathway.
Since we observed formation of the rearranged alcohol 9c
on photolysis of 9, irradiations of 8 and 10 were also carried
out in CH3CN-H2O 3:1 to check for the possibility of
rearranged alcohols due to an analogous rearrangement.
However, 1 h irradiation (CH3CN and CH3CN-H2O 3:1)
gave no observable products from 8 and 10, whereas alcohol
9c was formed from 9 in 30% yield (70% of the starting
material was recovered). Furthermore, assuming that the
phenolic OH in AdPh is essential in the excited-state proton
transfer giving rise to QMs that subsequently give methano-
lysis products 8b-10b, the corresponding methoxy deriva-
tives 8a-10a should under the irradiation in CH3OH remain
unreactive. Indeed, they were significantly less reactive than
the corresponding phenols. Only photolysis (CH3OH-H2O
3:1, 16 lamps 254 nm, 2 h) of 8a gave rise to dimethoxy
compound 8ab (10%), whereas 9a and 10a gave rearranged
alcohols 9ac (20%) and 10ac (30%), respectively (eq 7). The
unreacted starting materials can be recovered from these
experiments by chromatography.
Since photolyses at different acidities indicated the possi-
bility of an acid-catalyzed pathway for the formation of the
methanolysis products, we carried out irradiations of 9, 10,
J. Org. Chem. Vol. 75, No. 1, 2010 105

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TABLE 1. Quantum Yields of Photochemical Reactions, ΦR
a
TABLE 2. Fluorescence Properties of AdPh 8-10 and 11
compd
ΦR
compd
Φf (CH3CN)a
Φf (CH3CN-H2O 1:4)
0.13 ( 0.02
τf (CH3CN)b/ns
1
8
9
10
11
8a
9a
10a
0.23b
0.51
8
0.085 ( 0.005
4.0 ( 0.1
0.2 ( 0.1
4.1 ( 0.1
0.3 ( 0.1
4.70 ( 0.01
3.60 ( 0.05
(0.06)c,d
0.19
0.16
9
0.24 ( 0.05
0.18 ( 0.08
10
11
0.22 ( 0.03
0.30 ( 0.02
0.13 ( 0.03
0.15 ( 0.02
(<0.002)
(0.02)c,e
(0.06)c,e
aMeasured using anisole in cyclohexane as a reference (Φf = 0.29).28
bMeasured using single-photon timing technique.
aQuantum yields were determined using methanolysis of 1 as a
secondary actinometer. Photolyses were performed in CH3OH-H2O
3:1. Composition of the irradiated solution was analyzed by NMR and
HPLC; estimated errors on the reported values are 10%. bTaken from
ref 11. cEstimated value obtained in the experiment wherein compound
is photolyzed longer than the actinometer. dQuantum yield for the
formation of 9b and 9c. eQuantum yield for the formation of rearranged
alcohol products.
It is known that in the neutral aqueous media singlet
excited-state phenols deprotonate, whereas in CH3CN it
does not occur since CH3CN cannot solvate protons.25
Therefore, addition of H2O to the CH3CN solution of o-
hydroxymethylphenols can in principle change the mechan-
ism of the proton transfer from intrinsic ESIPT to H2O-
mediated ESPT giving rise to phenolates. In addition, for the
meta and the para derivatives, H2O-mediated ESPT giving
rise to dehydration and QMs can become operative.15,26 The
influence of added H2O and the change of the photochemical
reaction mechanism is evidenced from fluorescence which is
being quenched.27
To investigate the influence of added H2O on the photo-
chemistry of AdPh, the fluorescence titrations of the CH3CN
solutions of 8-10 and 11 with H2O were performed. On
addition of H2O no changes to the maxima in the absorption
spectra could be detected. The emission maxima shifted 2 nm
batochromically due to a weak stabilization of the excited
state by H-bonding. Interestingly, on addition of H2O in the
concentration range 0-20 M the fluorescence of 11 was
quenched, whereas no quenching for 8-10 could be detected.
In contrast, fluorescence of 8 and 10 increased (Figure 2).
The increase of the fluorescence for the ortho derivative 8
may be ascribed to the disruption of the intramolecular H-
bond between the phenol OH and the alcohol, which de-
creases quantum yield of the intrinsic ESIPT. However, that
cannot explain the fluorescence behavior of 9 and 10. It
should be recalled that adamantane is a very big and lipo-
philic substituent. Therefore, AdPh derivatives are probably
more solvated by CH3CN than by H2O molecules. Hence,
the dependence of fluorescence on H2O content in 8-10
cannot be compared to typical phenol behavior.
9a, and 10a in 2,2,2-trifluoroethanol (TFE), which is a more
acidic but less nucleophilic solvent than H2O. Irradiations
were preformed in analytical quantities by irradiating 2-3
mL of solution in UV-vis cuvettes. In all cases after the
removal of the solvent, the characteristic multiplets at δ 3.2
ppm were observed that are associated to the methylene
group adjacent to the CF3 of the corresponding ethers. In
addition, we performed control experiments by keeping the
solutions in the dark to check for the possibility of thermal
reaction. For derivatives 10 and 10a, no exposure to irradia-
tion was necessary to induce formation of the trifluoroethyl
ether. Indeed, formation of the ether from 10a was so
efficient and clean that evaporation of the solvent afforded
pure ether 14.
Quantum yields of the photochemical reactions were
determined using a secondary actinometer, the methanolysis
of compound 1.11 To avoid absorption of the light by
products, photolyses were performed to low conver-
sions (<30%). The composition of the irradiated solution
was analyzed by NMR and HPLC. For the reactions with
low quantum yields (photolysis of 9 and 8a-10a), longer
photolysis was required than for compound 1, so only
approximated results are reported. The results are compiled
in Table 1.
Fluorescence. It is generally accepted that ESIPT and ESPT
reactions of phenols are singlet excited-state processes.11
Therefore, we studied fluorescence properties of 8-11 to gain
more insight into their reactivity. Generally, fluorescent prop-
erties of 8-11 in CH3CN (Table 2) are comparable to other
alkylphenols.15 They are moderately fluorescent and show
maxima in the emission spectra at λ ∼300 nm. The excitation
spectra resemble the absorption spectra with maxima at 275.
Singlet state lifetimes in CH3CN were measured by the single-
photon timing technique. Whereas decay of the fluorescence of
10 and 11 can be well-fitted to a single-exponential function
giving lifetimes of 4.7 and 3.6 ns, respectively, two-exponential
functions were required to fit the decays of 8 and 9. Two decay
times might be ascribed to the presence of conformers which
have different singlet state lifetimes, due to the bulky adaman-
tane. However, no unambiguous assignment can be made at
this point.
Fluorescence was also recorded for the solutions of 8-11
containing 80% of H2O. In these solutions, quantum yields
of fluorescence were lower (except for 8) than in neat CH3CN
(Table 2), in accordance with previous reports. Wan re-
ported15 that addition of H2O to the CH3CN solution of 10
results in initial increase of the fluorescence which is
quenched on addition of sufficient amount of H2O, which
can mediate formation of phenolates and the formal long-
range proton transfer from the phenol to the hydroxyl
group.15 However, no emission from the phenolates from
8-11 could be detected, indicating that phenolates are not
emissive in the aqueous solution. Indeed, no emission from
the solutions (CH3CN-H2O 1:3) of 8-10 could be detected
when the pH of the aqueous part was adjusted to 12 (higher
than pKa of alkylphenols ∼10-10.5).
(26) (a) Fisher, M.; Wan, P. J. Am. Chem. Soc. 1998, 120, 2680–2681. (b)
Lukeman, M.; Wan, P. J. Am. Chem. Soc. 2002, 124, 9458–9464. (c)
Brousmiche, D. W.; Xu, M.; Lukeman, M.; Wan, P. J. Am. Chem. Soc.
2003, 125, 12961–12970.
(25) (a) Solntsev, K. M.; Huppert, D.; Agmon, N.; Tolbert, L. M. J. Phys.
Chem. A 2000, 104, 4658–4669. (b) Tolbert, L. M.; Solntsev, K. M. Acc.
Chem. Res. 2002, 35, 19–27. (c) Agmon, N. J. Phys. Chem. A 2005, 109,
13–35.
(27) Fischer, M.; Wan, P. J. Am. Chem. Soc. 1999, 121, 4555–4562.
106 J. Org. Chem. Vol. 75, No. 1, 2010

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FIGURE 2. Stern-Volmer plots: fluorescence of 8 (a) and 10 (b) in
CH3CN as a function of H2O concentration.
FIGURE 3. Stern-Volmer plots: fluorescence of 9 (a) and 10 (b) in
CH3CN-H2O (1:4) as a function of HClO4 concentration.
Since we found that acid can catalyze photosolvolysis of 9
and 10 (vide supra), we investigated influence of the added
acid to the fluorescence properties of these AdPh. Therefore,
solutions (CH3CN-H2O 1:4) of 9 and 10 were titrated with
0.03 M HClO4. Initial addition induced quenching of the
fluorescence for both AdPh, which for 10 leveled off reaching
a plateau (at ∼0.01 M), whereas for 9 started showing an
increase (Figure 3). This fluorescence behavior clearly in-
dicates two different mechanisms. At lower acidity, fluores-
cence of 9 and 10 is probably quenched due to the
protonation of the excited state. The linear part of the
Stern-Volmer plots can be used to estimate bimolecular
quenching constant (taking the mean value of the decay time
for 9 τ = 1.5 ns), kq = 4.7 ꢀ 109 M-1 s-1 and kq =3.2 ꢀ 109
M-1 s-1 for 9 and 10, respectively. The adamantyl is an
electron donating group (e.g., tert butyl σm = -0.10 and
σp = -0.10).29 According to the well-known meta-effect in
photochemistry,30 the adamantylphenyl in the singlet excited
state is probably more electron donating in the meta position
than in the para. Hence, 9 is probably less acidic in the singlet
excited state than 10. Thus, as the acidity of the solution of 9
is approaching the equilibrium pKa*, the phenol moiety
should deprotonate less in the excited state, resulting in the
increase of the fluorescence. No reverse behavior of the
fluorescence was observed for 10, in accordance with the
probable higher acidity in the excited state. We did not study
influence of the further acidity increase (above 0.01 M
HClO4) where the thermal acid catalyzed pathways would
also be possible (vide supra).
UV-vis and NMR Study. AdPh derivatives 8-10, their
corresponding methoxy derivatives 8a-10a, and phenols 1
and 11 were studied by UV-vis spectrometry and NMR in
CH3CN and CH3CN-H2O (and the corresponding deuter-
ated solvents for NMR) to test if photolysis could give rise to
long-lived transient species (presumably QMs) that could be
detected without the use of nanosecond laser flash photo-
lysis. CH3CN solutions (c = 3-5 ꢀ 10-4 M) were placed in
UV-vis quartz cuvettes or NMR tubes and irradiated in a
merry-go-round in the Rayonet reactor using 254 nm lamps.
After each exposure to irradiation, UV-vis or NMR spectra
were recorded. Irradiations of methoxy derivatives 8a-10a,
or aqueous solutions did not result in any observable
changes. In addition, no changes were observed on irradia-
tion of 9 in CH3CN. These findings are in accordance with
the inability of the methoxy compounds to form QMs, or the
short lifetimes of the zwitterionic QMs that are derived from
the meta isomers.
Contrary to the experiments with methoxy or meta deri-
vatives and aqueous solutions, already a short exposure of
the CH3CN solution of 8 to 254 nm irradiation produced a
strong new absorption band with a maximum at 400 nm
(Figure 4) and changed the color to yellow. This transient
absorption decayed with kinetics that could be described by
first order (τ ∼ 130 min) and was quenched by H2O, CH3OH,
(28) Berlman, I. B. Handbook of Fluorescent Spectra of Organic Mole-
cules; Academic Press: New York, 1971.
(28) Berlman, I. B. Handbook of Fluorescent Spectra of Organic Mole-
cules; Academic Press: New York, 1971.
(29) Montalti, M.; Credi, A.; Prodi, L.; Gandolfi, M. T. Handbook of
photochemistry; CRC Taylor and Francis: Boca Raton, 2006; p 627.
(30) (a) Zimmermann, H. E.; Sandel, V. R. J. Am. Chem. Soc. 1963, 85,
915–922. (b) Zimmermann, H. E. J. Am. Chem. Soc. 1995, 117, 8988–8991.
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TABLE 3. Lifetimes of Transient Species Observed by UV-vis Spec-
troscopy after Photolysis of Phenols in CH3CN Solutionsa
irradiated phenol
τ/min
1
8
10
11
0.80 ( 0.05
130 ( 20
100-300
6.3 ( 0.3
aThe reported values correspond to the mean of 3-5 decays.
FIGURE 4. Difference absorption spectrum obtained by UV-vis
spectrometer after photolysis (3 min, 16 lamps, 254 nm) of 8 in
CH3CN; inset: decay kinetics at 400 nm.
and ethyl vinyl ether (EVE). Hence, we assign the transient to
8QM. The quenching with EVE was performed in the
concentration range 0-2 M and revealed the relatively low
value of the second-order quenching constant kq = 3.5 ꢀ
10-4 M-1 s-1. The low value of the quenching constant is in
accordance with the steric congestion of the QM moiety and
the difficulty to attain planar 6π transition state in the
Diels-Alder reaction. Since 2 and 8QM have similar chro-
mophores, the difference absorption spectrum obtained by
UV-vis spectrometer on photolysis of 8 (Figure 4) resembles
the one assigned to 2 obtained on LFP of 1.13 Analogous
ortho derivatives without the adamantane (1 and 11) did not
produce as distinct transient absorptions detectable by
UV-vis spectrometer with a maximum at 400 nm. However,
much weaker transients were detected with maxima at ∼300
nm and shoulders stretching to longer wavelengths. This,
however, allowed for the estimation of the lifetimes of the
associated transient species (compiled in Table 3).
FIGURE 5. Absorption spectra of the solutions of 10 (full line) and
10a (dash line) in 2,2,2-trifluoroethanol (c = 8 ꢀ 10-4 M).
SCHEME 1
UV-vis study of the para derivative 10 in CH3CN also
gave rise to a transient species. A new band was apparent in
the absorption spectrum with a maximum at 350 nm.
Although we were not able to record a representative spec-
trum that could be associated only with the presence of
10QM, this transient absorption decayed with kinetics that
could be described as first order (τ ∼ 200 min) and was
quenchable by CH3OH and H2O.
This finding suggests that in TFE in the ground state there is
an equilibrium between phenol 10, ether 10TFE, and 10QM
(Scheme 1), with the QM being the dominant species. Since
TFE is an acidic and ionizing solvent, in principle it can
protonate the alcohol and form a cation via a loss of H2O.
No light is needed to initiate formation of 10QM. The other
two AdPh derivatives 8 and 9 did not show this behavior in
TFE. The inability of 8QM to exist as a stable molecule in
TFE might be ascribed to a higher basicity of the carbonyl
oxygen in 8QM (as compared to 10QM). However, no
unambiguous conclusion can be made at this point. In
addition, 9QM, which is a zwitterion, also probably does
not exist as a stable species in TFE.
To verify the existence of the equilibrium and to show that
absorption at 350 nm is due to 10QM, we recorded 1H and
13C NMR spectra of 10 and 10a in 1,1,1,3,3,3-hexafluoro-2-
propanol-d2 (HFIP) which is a readily available deuterated,
acidic, and non-nucleophilic solvent. In the 1H NMR spec-
trum of the solution of 10a, two species were detected that
were associated to 10a and the solvolysis product 10aHFIP.
Therefore, the aromatic part of the spectrum shows two
The surprising finding was the absorption spectrum ob-
served for AdPh 10 in TFE. Whereas the corresponding
methoxy derivative 10a shows the maximum of absorption in
TFE at 270 nm, the absorption for 10 was shifted to 350 and
only a weak band at 270 nm could be observed (Figure 5).
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FIGURE 7. Transient absorption spectrum of 8 in CH3CN re-
corded 17 μs after the laser pulse. Inset: decay kinetics in
CH3CN-H2O 1:1 at 380 nm without CH3OH and with addition
of 10% of CH3OH.
FIGURE 6. 1H NMR spectra obtained on recording the solutions
of 10 (bottom) and 10a (top) in 1,1,1,3,3,3-hexafluoro-2-propanol-
d2 (the multiplet at δ 4.40 ppm corresponds to the solvent
(CF3)2CDOD). The dominant species in the bottom spectrum
corresponds to 10QM, whereas the top spectrum indicates the
presence of a mixture of 10a and 10aHFIP.
TABLE 4. Lifetimes and Relative Quantum Yield of Formation (Φrel) of
QMs 2, 8QM, and 11QM in CH3CN-H2O 1:1a
b
QM
τ/sa
Φrel
multiplets at δ ∼7.59 and 7.07 ppm (Figure 6). On the other
1
hand, in the H NMR spectrum of the solution of 10 in
2
8QM
11QM
0.2
0.50 ( 0.05
0.35
0.27
1
0.36
HFIP, signals at δ ∼7.59 and 7.07 ppm correspond to minor
species 10 and 10HFIP (10%). The dominant species that
corresponds to 10QM shows proton resonances appearing
as two doublets at δ ∼8.08 and 6.65 ppm (J = 9.9 Hz), in
accordance with published NMR data for other related
QMs.31 In addition, the aliphatic part of the spectrum
appears as two broad singlets and two doublets, indicating
increased symmetry of the adamantyl part of the molecule.
The 13C NMR DEPT spectrum of the HFIP solutions of 10
shows in the aromatic region two doublets at δ 138.2 and
124.6 ppm, whereas in the aliphatic region two triplets at δ
40.9 and 35.4 and two doublets at 38.1 and 27.6 ppm can be
seen, all consistent with the structure of 10QM.
aN2 purged. bAssuming that 2, 8QM, and 11QM have the same molar
absorption coefficients, Φrel are obtained from the intensities of the ΔA
of optically matched solutions of 1, 8, and 11, respectively; the absolute
value of Φ for methanolysis of 8 was estimated at 0.51.
TABLE 5. Bimolecular Quenching Constants of 8QM and 9QM by
Ethanolamine and Methanol
kq/QM
kq (CH3OH)/M-1 s-1
8QMa
9QMb
1.4
3.7 ꢀ 102
6.1 ꢀ 106
kq (H2NCH2CH2OH) M-1 s-1
4.1 ꢀ 106
aIn CH3CN-H2O 1:1. bIn TFE.
Laser Flash Photolysis (LFP). Studying reactions by
UV-vis spectroscopy can indicate the intermediacy of
long-lived transient species (e.g., QMs) but cannot give
insight in the early events after excitation of the sample or
the presence of short-lived species such as zwitterionic QMs
or carbonium ions. Therefore, we performed a study of 8-11
by LFP. LFP of 8 was carried out in CH3CN and
CH3CN-H2O 1:1. After the laser pulse, in both solvent
systems transients were observed with the maximum of
absorption at 400 nm. The transient decaying with the
rate constant k = 3.3 ꢀ 105 s-1 (τ 3 μs) in N2-purged
CH3CN-H2O 1:1 that was quenched by O2 (O2 purged
CH3CN-H2O 1:1, k = 2.5 ꢀ 107 s-1, τ = 40 ns) was
assigned to the triplet state of 8. The persistent transient that
remained after decay of the triplet was not quenched by O2.
Its absorption spectrum (Figure 7) resembled the one col-
lected after the photolysis in CH3CN (Figure 4). Since this
transient was quenched by CH3OH and ethanolamine (the
quenching constants are compiled in Table 5) it was assigned
to 8QM. In O2-purged CH3CN-H2O 1:1, 8QM decays with
the rate constant k = 2 s-1, whereas in CH3CN it is too long-
lived to measure its decay kinetics by LFP. However, its
decay kinetics in CH3CN was measured by a UV-vis
spectrometer (Table 3).
The transients observed by LFP of 1 and 11 are similar to
those from 8. The presence of triplets was detected at
380-400 nm, that in N2-purged CH3CN-H2O 1:1 decayed
with rate constants k = 1.7 ꢀ 105 s-1 (τ 5.7 μs) and k = 2.2 ꢀ
105 s-1 (τ 4.6 μs) for 1 and 11, respectively. The triplets were
quenched by O2, but longer lived transients that remained
after the triplet had decayed were not quenched. Their
maxima of absorption was at 400 nm, and decay kinetics
was much slower (Table 4), all consistent with being due to 2
and 11QM. Assuming that 2, 8QM, and 11QM have the
same molar absorption coefficients, the relative intensities of
the transient absorptions obtained from optically matched
solutions of 1, 8, and 11, respectively, are directly propor-
tional to the relative quantum yields of the QM formation
(Φrel, Table 4). It can be seen that 8QM is formed with
the quantum yield 2.5 times higher than QMs without
the adamantane, in accordance with the quantum yields
of methanolysis (vide supra, Table 1). In addition, 8QM is
2-3 times longer lived than QMs without adamantyl sub-
stituents at the methylene position.
The LFP results of 9 and 10 turned out to be more
complex. The observed transient spectra in CH3CN and
CH3CN-H2O 1:1 in early times after the laser pulse were
(31) (a) Dyall, L. K.; Winstein, S. J. Am. Chem. Soc. 1972, 94, 2196–2199.
(b) Kurata, H.; Shimoyama, T.; Matsumoto, K.; Kawase, T.; Oda, M. Bull.
Chem. Soc. Jpn. 2001, 74, 1327–1332.
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on the substitution on the phenyl ring the maxima of benzyl
cation absorptions are generally in the range 350-400 nm,
and their decay kinetics ranges from 100 ns to 100 μs.32
Furthermore, 2-adamantyl cation (without stabilizing phenyl
substituent) has also been studied by LFP, and it has lifetime
in TFE of 0.33 ns.33
Therefore, we performed LFP of 9a in TFE whereupon we
can expect formation of cation 9aþ, but not the QM. The
transient absorption spectrum from 9a in TFE (Figure 8b)
resembles the one from 9, with a maximum at 370 nm.
However the transient from 9a decays faster than the one
from 9; in N2- and O2-purged TFE the rate constant is k =
4.8 ꢀ 106 s-1 (210 ns). Furthermore, we should take into
account that the phenyl ring with the methoxy or hydroxy
group in the meta position is an electron-withdrawing group
(σm = þ0.12), whereas the phenoxide (O-) in the meta
position is an electron-donating group (σm = -0.47).29
Consequently, decay kinetics obtained on LFP of 9 and 9a
are consistent with the assignation of the transients as being
due to 9QM and cation 9aþ, respectively. We also attempted
to detect cation 10aþ that is expected to be formed on LFP of
10a in TFE. Cation 10aþ should be longer lived than 9aþ due
to the stabilizing effect of the p-methoxy group (σp
=
-0.27).29 However, in O2-purged solution, besides the triplet
which decayed with rate constant k = 3.3 ꢀ 107 s-1 (30 ns) no
other transient was observed.
FIGURE 8. Transient absorption spectrum of (a) 9 in TFE and (b)
9a in TFE recorded at 200 ns after the laser pulse. Insets: decays at
370 nm.
obscured due to the overlapping with the signals of triplets
with maxima at 400 nm. The triplets of 9 and 10 decayed in
N2 purged CH3CN-H2O 1:1 with the rate constants k = 3.3 ꢀ
105 s-1 (τ 3 μs) and k = 3.1 ꢀ 105 s-1 (τ 3.2 μs), respectively.
In addition to triplets, transients were observed with maxima
at 400 nm and shoulders stretching to longer wavelengths
(600 nm) that were more persistent and may be associated to
phenoxy radicals and/or species from the secondary photo-
chemical processes. However, the intensity of the residual
transient absorption of 10 in CH3CN-H2O 1:1 at longer
times (after decay of triplets and secondary photochemical
species) that may be associated to 10QM was too weak for
recording reliable spectra and decay kinetics. The low in-
tensity of the transient absorption is consistent with its low
quantum yield of formation.
The lifetime of zwitterionic 9QM that is anticipated inter-
mediate from 9 is probably too short-lived in aqueous
solvent to be detected by nanosecond LFP. Therefore, we
carried out LFP of 9 in TFE. Since it is significantly less
nucleophilic solvent than aqueous CH3CN, zwitterionic
9QM could be detectable. Thus, after the laser pulse in N2-
purged solution we observed transient absorption with a
maximum at 370 nm that decayed with the rate constant k =
6.2 ꢀ 105 s-1 (τ 1.6 μs) that was partly overlapped with the
triplet of 9. However, in O2-purged solution at 370 nm, the
same transient was observed (Figure 8a) that decayed with
the rate constant k = 1.0 ꢀ 106 s-1. This transient was
quenched by CH3OH and ethanolamine (quenching con-
stants are compiled in Table 5). Such a transient is consistent
with being due to zwitterion 9QM or cation 9þ. Depending
Mechanism of Reaction. The phenolic OH group in AdPh 8
is intramolecularly hydrogen bonded to the oxygen atom of
the alcohol OH group, as clearly indicated from the NMR
spectrum of AdPh 8 recorded in CDCl3. Namely, the signal
corresponding to the phenolic OH in 8 shows the resonance
at δ 7.8 ppm whereas for 9 and 10 it is at 4.6-4.8 ppm. The
presence of the intramolecular H-bond suggests that on
excitation of 8, an efficient ESIPT takes place. Indeed,
dehydration of 8 giving rise to 8QM is an efficient process.
The lower limit for the quantum yield of the photochemical
formation of 8QM is 0.51, as determined for the methano-
lysis reaction giving 8b. The corresponding methoxy deriva-
tive 8a is significantly less reactive (Table 1) showing that the
free phenolic OH is required for the efficient formation of the
photosolvolysis products. In addition, H2O is probably not
(32) (a) McClelland, R. A.; Chan, C.; Cozens, F. L.; Modro, A.;
Steenken, S. Angew. Chem., Int. Ed. 1991, 30, 1337–1339. (b) Cozens,
F. L.; Kanagasabapathy, V. M.; McClelland, R. A.; Steenken, S. Can. J.
Chem. 1999, 77, 2069–2082.
(33) Pezacki, J. P.; Shukla, D.; Lusztyk, J.; Warkentin, J. J. Am. Chem.
Soc. 1999, 121, 6589–6598.
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SCHEME 2
SCHEME 3
required to mediate this process. Furthermore, comparing
photochemical reactivity of 1, 8, and 11 (judged by the values
of the quantum yield for the QM formation), clearly shows
that 8 is the most reactive. That may be ascribed to the
electron-donating effect of the adamantyl substituent which
stabilizes the QM structure.
the lipophilic adamantyl substituent. Wan and co-workers11,15
suggestedthatinthem-benzhydrol systems deprotonation of the
phenol moiety by H2O molecules takes place almost simulta-
neously with the loss of hydroxyl group, giving rise to zwitter-
ionic QMs. However, it was also suggested that deprotonation of
the phenol is essential to trigger the expulsion of the hydroxyl
moiety.15 Neither of these processes can be disregarded in the
case of 9. However, the high rate constant of the fluorescence
quenching by acid (although inefficient) and higher efficiencies
of the methanolysis at low pH indicate that an acid-catalyzed
pathway (as shown in Scheme 3) should be possible. That is, in
the excited state AdPh 9 can be protonated and on loss of H2O
give cation 9þ that is subsequently stabilized by deprotonation
(in the excited state or the ground state) giving 9QM. Formation
of rearrangement product 9c on irradiation of 9 in CH3CN also
suggests that heterolysis pathway via cation 9þ can operate at
pH 7, although probably less efficiently than the simultaneous
loss of OH- and Hþ. In addition, it is very suggestive that
formation of the rearranged product 9ac on photolysis of 9a has
to stem from the pathway that involves acid-catalyzed formation
of cation 9aþ.
On addition of H2O to the system containing 8, the
intramolecular H-bonding is partly disrupted which prob-
ably leads to the decreased quantum yield of ESIPT. That is
indicated from (a) the decrease of the intensity of the
transient absorption (in CH3CN-H2O 1:1 the intensity of
the ΔA decreases 50%) and (b) the fluorescence quantum
yield which increases. Contrary to previous reports for the
ortho-hydrogen bonded systems, in this case we have not
observed quenching of the fluorescence by H2O even with
80% of H2O. That may be ascribed to the different solvation
of the AdPh, which is very lipophilic and preferably solvated
by CH3CN. However, the mechanism shown in Scheme 2,
wherein H2O molecules participate in the formation of 8QM,
cannot be completely ruled out, although it probably does
not contribute much to the overall formation of 8QM. The
independence of the solvolysis quantum yield on acidity
additionally corroborates the intrinsic ESIPT pathway.
Comparing reactivity of QMs 2, 8QM, and 11QM, as judged
from the lifetimes in CH3CN and CH3CN-H2O, clearly shows
that 8QM is the least reactive. Lower reactivity is in accordance
with its selectivity in reaction with nucleophiles, being 2 orders of
magnitude more reactive with amino-nucleophile (ethanol-
amine) than with oxygen nucleophiles (CH3OH and H2O). That
finding may be of importance in biological systems regarding
cytotoxicity of QMs.23 Furthermore, it is interesting to note that
neither 8 nor 8a undergoes rearrangement of the adamantyl
skeleton that was seen with meta and para derivatives.
What is the mechanism for the unusual rearrangement
leading to 2,4-disubstituted adamantanes? The thermal sol-
volysis reactions of 2-substituted adamantanes that involve
2-adamantyl cations have been intensively studied.34 Many
(34) (a) Schleyer, P. v. R.; Lam, L. K. M.; Raber, D. J.; Fry, J. L.;
McKervey, M. A.; Alford, J. R.; Cuddy, B. D.; Keizer, V. G.; Geluk, H. W.;
Schlatmann, J. L. M. A. J. Am. Chem. Soc. 1970, 92, 5246–5247. (b) Raber,
D. J.; Harris, J. M.; Hall, R. E.; Schleyer, P. v. R. J. Am. Chem. Soc. 1971, 93,
ꢁ
ꢀ
ꢁ ꢀ
4821–4828. (c) Kovacevic, D.; Majerski, Z.; Borcic, S.; Sunko, D. E.
Tetrahedron 1972, 28, 2469–2477. (d) Harris, J. M.; Becker, A.; Fagan,
J. F.; Walden, F. A. J. Am. Chem. Soc. 1974, 96, 4484–4489. (e) Schadt, F. L.;
Bentley, T. W.; Schleyer, P. v. R. J. Am. Chem. Soc. 1976, 98, 7667–7675. (f )
Bentley, T. W.; Bowen, C. T.; Morten, D. H.; Schleyer, P. v. R. J. Am. Chem.
Soc. 1981, 103, 5466–5475. (g) McManus, S. P.; Kamkar Safavy, K.;
Roberts, F. E. J. Org. Chem. 1982, 47, 4388–4389. (h) Ta-Shma, R.;
Rappoport, Z. J. Am. Chem. Soc. 1983, 105, 6082–6095. (i) Laureillard, J.;
Casadevall, A.; Casadevall, E. Tetrahedron 1984, 40, 4921–4928. ( j) Paradisi,
C.; Bunnett, J. F. J. Am. Chem. Soc. 1985, 107, 8223–8233. (k) Maskill, H.;
Thompson, J. T.; Wilson, A. A. J. Chem. Soc., Perkin Trans. 2 1984, 1693–
1703.
The mechanism of photochemical reaction of 9 and 10 clearly
has to be different from 8, since the phenolic OH is further away
from the alcohol moiety. Intramolecular hydrogen bonding
cannot exist; hence, the presence of a protic solvent is required
to ferry the proton from the acidic to the basic site. We have not
observed quenching of the fluorescence of 9 on addition of H2O.
However, that could be ascribed to the unusual solvation due to
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SCHEME 4
SCHEME 5
authors suggest that the 2-adamantyl cation exist as
σ-bridged or as an equilibrium between 2-adamantyl and
protoadamantyl structures (Scheme 4).35 Such a description
of the 2-adamantyl cation can best account for some experi-
mental findings, especially those involving rearrangement to
the protoadamantyl system. However, it has been shown by
theoretical calculations36 and X-ray structural analysis37
that the actual structure of the 2-adamantyl cation does
not involve bridging, but rather hyperconjugation,38 and
the distortion of the bridge bearing the positive charge. Thus,
photochemical reaction of 9 or 9a is expected to give rise to
cations 9þ (or 9QM), or 9aþ, respectiþvely, that are the most
accurately represented by drawings 90 and 9a0þ (Scheme 5).
If a tunneling of the proton taþkes place in such a cation
it would give rise to structures 900 and 9a0þ0þ that are actually
less stable than the starting 9’þ and 9a0 . However, when
these rearranged cations are trapped by nucleophiles,
products of the reactions can not revert to the starting
material. That is, the rearranged alcohols are photochemi-
cally stable. Therefore, although rearrangement takes place
with low quantum yield, it is possible since it is irreversible.
The presence of the zwitterion 9QM, and cation 9aþ has
been detected by LFP in TFE. Although we were not able to
study their rearrangement by spectroscopic methods, LFP
data gave insight into the reactivity of the zwitterion 9QM
with nucleophiles. Generally, one can see low selectivity of
this QM in reactions with N and O nucleophiles, which is not
surprising taking into account the zwitterionic nature.
In view of the above findings and previous reports it is
clear that photochemistry of 10 has to be similar to that of 9;
that is, H2O is required to mediate the ESPT. In addition,
the observed fluorescence quenching by acid and equilibrium
(phenol and QM) seen in the ground state in TFE
strongly suggests that acid catalyzed pathway (via cation
10þ, Scheme 6) can compete with H2O-mediated simulta-
neous loss of both, Hþ and OH-. However, if 10þ was
formed in the excited state, it is reasonably to assume that
it would very rapidly deprotonate giving 10QM. Therefore,
it is not surprising that we have not observed the rearranged
products on photolysis of 10, whereas it was the case on
photolysis of methoxy derivative 10a.
(35) (a) Faulkner, D.; McKervey, M. A.; Lenoir, D.; Senkler, C. A.;
Schleyer, P. v. R. Tetrahedron Lett. 1973, 14, 705–708. (b) Lenoir, D. Chem.
Ber. 1973, 106, 2366–2378. (c) Lenoir, D.; Hall, R. E.; Schleyer, P. v. R.
J. Am. Chem. Soc. 1974, 96, 2138–2148. (d) Lenoir, D.; Raber, D. J.;
Schleyer, P. v. R. J. Am. Chem. Soc. 1974, 96, 2149–2156. (e) Lenoir, D.;
Mison, P.; Hyson, E.; Schleyer, P. v. R.; Saunders, M.; Vogel, P.; Telkowski,
L. A. J. Am. Chem. Soc. 1974, 96, 2157–2164. (f ) Storesund, H. J.; Whiting,
M. C. J. Chem. Soc., Perkin Trans. 2 1975, 1452–1458. (g) Bone, J. A.; Pritt,
J. R.; Whiting, M. C. J. Chem. Soc., Perkin Trans. 2 1975, 1447–1452. (h)
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Kovacevic, D.; Goricnik, B.; Majerski, Z. J. Org. Chem. 1978, 43, 4008–4013.
(i) Nordlander, J. E.; Haky, J. E.; Landino, J. P. J. Am. Chem. Soc. 1980, 102,
7487–7493. ( j) Gassman, P. G.; Saito, K.; Talley, J. J. J. Am. Chem. Soc.
1980, 102, 7613–7615. (k) Schleyer, P. v. R.; Lenoir, D.; Mison, P.; Liang, G.;
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Conclusion
The results presented for AdPh derivatives suggest that the
intrinsic ESIPT coupled with a dehydration gives rise to
8QM, and H2O-mediated formal ESPT and dehydration
gives rise to 9QM and 10QM. The incorporation of the
adamantyl substituent into the hydroxymethylphenol moi-
ety increased the quantum yield of the photochemical re-
activity by up to 3 times and significantly prolonged lifetimes
of the associated QMs. The fluorescence of 8-10 is not
quenched by H2O, suggesting different solvation than for
the usual phenol derivatives. On the contrary, fluorescence
quenching by acid for 9 and 10, as well as results of photo-
lyses at low pH suggest that an acid catalyzed pathway giving
rise to solvolysis products can compete with H2O-mediated
ꢀ
Quintanilla, E.; Davalos, J. Z. J. Phys. Org. Chem. 2003, 16, 546–554.
(36) Dutler, R.; Rauk, A.; Sorensen, T. S.; Whitworth, S. M. J. Am.
Chem. Soc. 1989, 111, 9024–9029.
(37) Laube, T.; Hollenstein, S. Helv. Chim. Acta 1994, 77, 1773–1780.
(38) Finne, E. S.; Gunn, J. R.; Sorensen, T. S. J. Am. Chem. Soc. 1987,
109, 7816–7823.
112 J. Org. Chem. Vol. 75, No. 1, 2010

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SCHEME 6
(100, Mþ), 240 (11), 137 (23), 136 (18), 135 (89), 121 (7), 107 (9);
HRMS calcd for C17H22O2 258.16198, obsd 258.16184.
2-Hydroxy-2-(4-methoxyphenyl)adamantane (10a):39 2.29 g
(67%); colorless crystals.
2-(2-Metoxyphenyl)-2-propanol (11a).40 Grignard reagent
was prepared from 2-bromoanisole (3.56 mL, 28.5 mmol)
and magnesium (0.72 g, 29.6 mmol) and reacted with acetone
(10 mL, 136 mmol). The reaction furnished 5.4 g of the crude
product that was additionally purified on a column with silica
gel using dichloromethane as eluent: 3.52 g (74%) of 11a.
General Procedure for Removal of the Methyl Ether Group
from Phenols with BBr3. The reaction was carried out under N2
inert atmosphere in a three-neck round-bottom flask (250 mL)
equipped with a septum and a syringe. In the flask was placed the
methoxy derivative 8-10 (10 mmol), dissolved in dry CH2Cl2
(100 mL), and the solution cooled to 0 °C by ice bath. To the
cooled solution, by use of a syringe, was added dropwise a
solution of BBr3 in CH2Cl2 (1 M, 50 mL) during 1 h. After
addition was completed, the stirring was continued 1 h at 0 °C
and at rt overnight. The next day, to the reaction mixture was
added 100 mL of cold water, the layers were separated, and the
aqueous layer was extracted with CH2Cl2 (3 ꢀ 50 mL). The
combined organic extracts were dried over anhydrous MgSO4,
solid was removed by filtration, and solvent was removed on a
rotary evaporator. The obtained crude product was purified on
a column filled with silica gel by use of CH2Cl2 and CH2Cl2-
EtOAc 4:1 as eluent.
proton transfer. Hence, from the methoxy derivatives 9a
and 10a, photoinitiated acid catalyzed heterolysis gives
2-adamantyl cations that undergo rearrangements giving
2,4-disubstituted adamantyl derivatives. The same type
of rearrangement was observed for AdPh 9 giving 9c,
probably taking place on the zwitterion 9QM, Further-
more, in the TFE acidic media, in the ground state, phenol
10 is in the equilibrium with 10QM which allowed for
the recording of the associated UV-vis, 1H NMR, and
13C NMR spectra. The results reported herein show that
photolsyes of AdPh 9 and the methoxy derivatives 9a
and 10a represent a new method to generate adamantyl
cations and probe for their intramolecular (viz. rearrange-
ments) and intermolecular reactivity with nucleophiles.
Finally, a new class of QMs bearing sterical hindrance
at the methylene position is described, that may find
importance in the biological systems due to higher selectivity
in nucleophilic additions, and potentially, lower cytotoxi-
city.
2-Hydroxy-2-(2-hydroxyphenyl)adamantane (8).41 Reaction
with 2-hydroxy-2-(2-methoxyphenyl)adamantane (1.26 g, 4.88
mmol) and a solution of BBr3 (24.42 mL) gave 1.34 g of the crude
product that was purified by chromatography to furnish 0.60 g
(45%) of the pure product in the form of colorless crystals.
2-Hydroxy-2-(3-hydroxyphenyl)adamantane (9). Reaction
with 2-hydroxy-2-(3-methoxyphenyl)adamantane (1.43 g,
4.54 mmol) and a solution of BBr3 (27.73 mL) gave 1.42 g of
the crude product that was purified by chromatography to
furnish 1.14 g (85%) of the pure product in the form of
colorless crystals: mp 160-161 °C; IR (KBr) νmax/cm-1
3567, 3378, 3075, 2901, 2885; 1H NMR (DMSO-d6, 600 MHz)
δ/ppm 9.17 (s, 1H, OH), 7.11 (t, 1H, J = 7.7 Hz), 6.87-6.90
(m, 2H), 6.60 (ddd, 1H, J = 0.9 Hz, J = 2.3 Hz, J = 7.7 Hz),
4.48 (s, 1H, OH), 2.37 (br s, 3H), 2.35 (br s, 1H), 1.79 (br s, 1H),
1.52-1.68 (m, 9H); 13 C NMR (DMSO-d6, 150 MHz, APT) δ/
ppm 157.2 (s), 147.7 (s), 128.9 (d), 116.2 (d), 113.2 (d), 112.7
(d), 73.4 (s), 37.4 (t), 34.9 (d, 2C), 34.3 (t, 2C), 32.6 (t, 2C), 26.9
(d), 26.6 (d); MS (EI) m/z 244 (100, Mþ), 243 (20, Mþ), 151
(10), 121 (95); HRMS calcd for C16H20O2 244.14633, obsd
244.14653.
Experimental Section
Grignard Reaction: General Procedure. The reaction was
carried out in dry THF. The Grignard reagent was prepared
from bromoanisole (2.75 g, 14.63 mmol) and magnesium (0.36 g,
14.63 mmol) and reacted with 2-adamantanone (2 g, 13.31
mmol). The crude products were purified by crystallization
from hexane.
2-Hydroxy-2-(2-methoxyphenyl)adamantane (8a): 1.86 g (54%);
colorless crystals; mp 87 - 88 °C; IR (KBr) νmax/cm-1 3543,
1
2965, 2899, 2854, 2842; H NMR (CDCl3, 300 MHz) δ/ppm
2-Hydroxy-2-(4-hydroxyphenyl)adamantane (10). Reaction
with 2-hydroxy-2-(3-methoxyphenyl)adamantane (1.50 g,
5.81 mmol) and a solution of BBr3 (29 mL) gave 1.42 g of
the crude product that was purified by chromatography to
furnish 1.26 g (94%) of the pure product in the form of
colorless crystals: mp 301-302 °C; IR (KBr) νmax/cm-1
3408, 3254, 3025, 2913, 2901, 2856; 1H NMR (DMSO-d6,
300 MHz) δ/ppm 9.20 (s, 1H, OH), 7.24 (d, 2H, J = 8.6 Hz),
6.71 (d, 2H, J = 8.6 Hz), 4.30 (s, 1H, OH), 2.37 (br s, 3H), 2.31
7.44 (dd, 1H, J = 1.5 Hz, J = 7.7 Hz), 7.21 (dt, 1H, J = 1.5 Hz,
J = 8.1 Hz), 6.93 (dt, 1H, J = 1.5 Hz, J = 7.7 Hz), 6.90 (d, 1H,
J = 8.1 Hz), 3.85 (s, 3H), 3.42 (s, 1H, OH), 2.66 (br s, 2H), 2.54
(br s, 1H), 2.50 (br s, 1H), 1.65-1.90 (m, 8H), 1.61 (d, J = 12.5
Hz, 2H); 13C NMR (CDCl3, 75 MHz, APT) δ/ppm 157.6 (s),
133.5 (s), 128.0 (d), 127.8 (d), 120.3 (d), 111.4 (d), 76.5 (s), 54.8
(q), 37.9 (t), 35.4 (d, 2C), 35.3 (t, 2C), 33.1 (t, 2C), 27.3 (d), 26.9
(d); MS (EI) m/z 259 (9, Mþ), 258 (46, Mþ), 240 (13), 137 (42),
135 (100), 121 (7); HRMS calcd for C17H22O2 258.16198,
obsd 258.16217.
13
(br s, 1H), 1.78 (br s, 1H), 1.50-1.68 (m, 9H); C NMR
2-Hydroxy-2-(3-methoxyphenyl)adamantane (9a): 2.77
g
(66%); colorless crystals; mp 122 - 123 °C; IR (KBr) νmax
/
cm-1 3519, 2931, 2911, 2878, 2852; 1H NMR (CDCl3, 300 MHz)
δ/ppm 7.30 (dd, 1H, J = 8.0 Hz, J = 8.8 Hz), 7,13 (d, 1H, J =
8.0 Hz), 7.09 (dd, 1H, J = 2.2 Hz, J = 1.7 Hz), 6.81 (dd, 1H, J =
8.1 Hz, J = 2.2 Hz), 3.81 (s, 3H), 2.53 (br s, 2H), 2.42 (br s, 1H),
2.38 (br s, 1H), 1.50-1.95 (m, 11H); 13C NMR (CDCl3, 75 MHz,
APT) δ/ppm 159.8 (s), 147.0 (s), 129.5 (d), 117.6 (d), 112.0 (d),
111.8 (d), 75.5 (s), 55.1 (q), 37.5 (t), 35.6 (d, 2C), 34.8 (t, 2C),
32.9 (t, 2C), 27.2 (d), 26.8 (d); MS (EI) m/z 259 (19, Mþ), 258
(39) (a) Kelly, D. P.; Jenkins, M. J.; Mantello, R. A. J. Org. Chem. 1981,
46, 1650–1653. (b) Lin, M. H.; Silver, J. E.; Le Noble, W. J. J. Org. Chem.
1988, 53, 5155–5158. (c) Kovalev, V. V.; Rozov, A. K.; Shokova, E. A.
Synlett 1990, 739–740.
(40) (a) Sengupta, S. K.; Biswas, R. N.; Bhattacharyya, B. K. J. Ind.
Chem. Soc. 1959, 36, 659–668. (b) Tsuruta, H.; Mukai, T. Bull. Chem. Soc.
Jpn. 1968, 41, 2489–2494. (c) Yamashita, A.; Hara, K.; Aizawa, S.; Hirota,
M. Bull. Chem. Soc. Jpn. 1974, 47, 2508–2510. (d) Boger, D. L.; Coleman,
R. S. J. Org. Chem. 1986, 51, 5436–5439.
(41) Talley, J. J.; Evans, I. A. J. Org. Chem. 1984, 49, 5267–5269.
J. Org. Chem. Vol. 75, No. 1, 2010 113

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Basaric et al.
JOCArticle
(DMSO-d6, 75 MHz, APT) δ/ppm 155.6 (s), 136.6 (s), 126.7
(d, 2C), 114.7 (d, 2C), 73.1 (s), 37.6 (t), 35.0 (d, 2C), 34.4 (t, 2C),
32.6 (t, 2C), 27.1 (d), 26.6 (d); MS (EI) m/z 245 (5, Mþ), 244 (28,
Mþ), 227 (23), 226 (100), 158 (7), 123 (19), 121 (55), 120 (14),
106 (14), 91 (10), 79 (13); HRMS, calculated for C16H20O2
244.14633; obsd 244.14641.
c = 4.1 ꢀ 10-3 M) of AdPh 9 (100 mg, 0.41 mmol) and irradiated
in a Rayonet reactor using 16 lamps at 254 nm over 1 h. After
irradiation, extraction with CH2Cl2 was carried out (3 ꢀ 75 mL),
and the extracts were dried over anhydrous MgSO4. After filtra-
tion, the solvent was removed on a rotary evaporator and the
residue chromatographed on a thin layer of silica gel using
CH2Cl2-EtOAc (30%) as eluent to afford 30 mg of 9c and recover
70 mg of the starting material.
2-(2-Hydroxyphenyl)-2-propanol (11).42 Obtained by the
modification of the published procudere.24
Photolysis Experiments: General. In a quartz vessel was
placed a CH3OH, CH3OH-H2O (3:1), or CH3CN-H2O solu-
tion (100 mL, c = 4.1 ꢀ 10-3 M) of adamantane phenol (100 mg,
0.41 mmol) which was irradiated in a Rayonet reactor using 16
lamps (unless stated otherwise) at 254 nm. Prior to and during
the irradiation the solution was continuously purged with a
stream of Ar and cooled by a coldfinger condenser. After
irradiation, the solvent was removed on a rotary evaporator
and the residue chromatographed on a thin layer of silica gel
using CH2Cl2 or CH2Cl2-EtOAc (30%) as eluent.
2-Methoxy-2-(2-hydroxyphenyl)adamantane (8b). A methanol
solution (25 mL) of AdPh 8 (10 mg, 0.041 mmol) was irradiated in a
Rayonet reactor at 254 nm using seven lamps for 20 min. After
evaporation of the solvent, pure product 8b was obtained: colorless
crystals; mp 59-60 °C; IR (NaCl) νmax/cm-1 3350, 2904, 2855; 1H
NMR (CDCl3, 300 MHz) δ/ppm 8.11 (s, 1H, OH), 7.34 (dd, 1H,
J = 1.1 Hz, J = 7.9 Hz), 7.18 (dt, 1H, J = 1.4 Hz, J = 7.4 Hz), 6.86
(dt, 1H, J = 1.1 Hz, J = 7.9 Hz), 6.83 (dd, 1H, J = 1.1 Hz, J = 7.4
Hz), 3.01(s, 3H, OCH3), 2.63 (br s, 1H), 2.57 (br s, 1H), 2.50 (d, 1H,
J = 12.6 Hz), 2.39 (dd, 1H, J = 2.9 Hz, J = 12.9 Hz), 2.20 (dd, 1H,
J = 2.4 Hz, J = 12.4 Hz), 1.96 (dq, 1H, J = 2.9 Hz, J = 12.9 Hz),
1.89 (br s, 1H), 1.83 (br s, 1H), 1.73 (br s, 2H), 1.60-1.70 (m, 2H),
1.57 (dq, 1H, J = 2.4 Hz, J = 12.4 Hz), 1.38 (dd, 1H, J = 1.9 Hz,
J = 12.9 Hz); 13C NMR (CDCl3, 75 MHz, APT) δ/ppm 156.1 (s),
129.3 (d), 128.7 (d), 126.6 (q), 118.8 (d), 117.5 (d), 83.7 (s), 48.5 (q),
37.6 (t), 36.0 (t), 35.2 (d), 34.4 (t), 33.0 (t), 32.6 (t), 30.5 (d), 27.0 (d),
26.7 (d); MS (EI) m/z 259 (1, Mþ), 258 (3, Mþ), 227 (18), 226 (100),
184 (13), 183 (31), 158 (13), 131 (7); HRMS calcd for C17H22O2
258.16198 obsd 258.16182.
2-(3-Hydroxyphenyl)-4-hydroxyadamantane (9c): 30 mg (30%);
colorless crystals; mp 68-70 °C; IR (NaCl) νmax/cm-1 3368, 2913,
2854; 1H NMR (CDCl3, 500 MHz) δ/ppm 7.16 (t, 1H, J = 7.8 Hz),
6.88 (ddd, 1H, J = 0.7 Hz, J = 1.0 Hz, J = 7.8 Hz), 6.81 (dd, 1H,
J = 0.7 Hz, J = 1.5 Hz), 6.63 (ddd, 1H, J = 0.7 Hz, J = 1.0 Hz,
J=7.8Hz), 5.06(brs, 1H, OH), 3.86(t, 1H, J=3.1Hz), 3.10(brs,
1H), 2.47 (br s, 1H), 2.38 (br s, 1H), 2.31 (dq, 1H, J = 2.8 Hz, J =
12.8 Hz), 2.06 (dq, 1H, J = 2.8 Hz, J = 12.8 Hz), 1.94 (dq, 1H, J =
2.8 Hz, J = 12.2 Hz), 1.78-1.90 (m, 4H), 1.69 (dq, 1H, J = 2.8 Hz,
J=12.8Hz),1.63(dq,1H,J=2.4Hz,J= 12.8 Hz), 1.60 (br s, 1H,
OH), 1.52 (dq, 1H, J = 2.6 Hz, J = 12.8 Hz); 13C NMR (CDCl3,
125 MHz, COM, DEPT) δ/ppm 155.7 (s), 145.2 (s), 129.3 (d), 118.8
(d), 113.5 (d), 112.3 (d), 69.8 (d), 47.5 (d), 38.7 (t), 37.4 (d), 34.5 (d),
32.1 (t), 31.6 (t), 30.9 (t), 29.7 (d), 26.9 (d); MS (EI) m/z 244 (100,
Mþ), 243 (20, Mþ), 226 (30), 150 (100), 107 (30), 95 (30); HRMS
calcd for C16H20O2 244.14633, obsd 244.14645.
2-Methoxy-2-(3-hydroxyphenyl)adamantane (9b). To the solu-
tion of AdPh 9 (100 mg, 0.041 mmol) in CH3OH-H2O (3:1) a drop
of concentrated sulfuric acid was added and the solution was stirred
at rt over 7 days. The progress of the ether formation was monitored
by HPLC. When all the starting material disappeared, to the solution
was added sodium bicarbonate, methanol was removed on the rotary
evaporator and the aqueous residue extracted with CH2Cl2 (3 ꢀ 50
mL). The extracts were dried over anhydrous MgSO4, and the
solvent was removed on a rotary evaporator to afford pure product
9b: colorless crystals; mp 140-142 °C; IR (NaCl) νmax/cm-1 3306,
1
2910, 2855; H NMR (DMSO-d6, 300 MHz) δ/ppm 9.27 (s, 1H,
OH), 7.15 (t, 1H, J = 7.7 Hz), 6.82-6.90 (m, 2H), 6.67 (dd, 1H, J =
1.4 Hz, J = 7.7 Hz), 2.69 (s, 3H), 2.50 (br s, 2H), 2.22 (br s, 1H), 2.18
(br s, 1H), 1.50-1.80 (m, 10 H); 13C NMR (DMSO-d6, 75 MHz,
APT) δ/ppm 157.2 (s), 142.1 (s), 129.8 (d), 117.9 (d), 114.1 (d), 114.0
(d), 79.0 (s), 47.6 (q), 37.2 (t), 34.1 (t, 2C), 32.4 (t, 2C), 32.2 (d, 2C),
27.0 (d), 26.3 (d); MS (EI) m/z 258 (10, Mþ), 259 (3, Mþ), 244 (10),
229 (30), 227 (100), 165 (10), 137 (15), 121 (10), 107 (13); HRMS
calcd for C17H22O2 258.16198, observed 258.16197.
2-Methoxy-2-(4-hydroxyphenyl)adamantane (10b). AdPh 10
(100 mg, 0.41 mmol) was dissolved in CH3OH-H2O (3:1, 100
mL) and irradiated in Rayonet reactor at 254 nm using 7 lamps
for 20 min. After evaporation of the solvent the residue was
Spiro[2-ethoxychroman-4,20-adamantane] (8DA). In a quartz
vessel was placed a CH3CN solution (20 mL, c = 3.3 ꢀ 10-3 M) of
8 (20 mg, 0.082 mmol) and ethyl vinyl ether (5 mL, 55 mmol). The
solution was purged with argon for 15 min, sealed, and irradiated in a
Rayonet reactor using four lamps at 254 nm. The solution was
irradiated 6 times for 15 min, and after each irradiation the solution
was kept in the dark for 3 h. After the irradiations, the solvent was
evaporated and the residue chromatographed on a column of silica gel
using CH2Cl2 as eluent. The chromatography furnished 12 mg (49%)
of product 8DA and 8 mg (40%) of AdPh 8: 12 mg (49%); colorless
oil; 1H NMR (CDCl3, 300 MHz) δ/ppm 7.53 (dd, 1H, J = 1.2 Hz,
J = 7.8 Hz), 7.13 (dt, 1H, J = 1.5 Hz, J = 7.7 Hz), 6.94 (dt, 1H, J =
1.5 Hz, J = 7.7 Hz), 6.87 (dd, 1H, J = 1.2 Hz, J = 7.8 Hz), 5.41 (dd,
1H, J=6.1Hz, J=8.3Hz),4.00(dd, 1H, J=7.0Hz, J= 14.1 Hz),
3.60 (dd, 1H, J=7.0Hz,J=14.1Hz),2.98(dd,1H,J=6.1Hz,J=
13.8 Hz), 2.76 (d, 1H, J = 12.0 Hz), 2.35 (br s, 1H), 2.31 (d, 1H, J =
13.4 Hz), 2.21 (d, 1H, J = 13.4 Hz), 2.04 (br s, 1H), 1.95 (br s, 1H),
1.65-1.90(m,6H),1.54-1.58 (m, 2H), 1.36 (dd, 1H, J=8.3Hz,J=
13.8 Hz), 1.22 (t, 3H, J=7.0Hz);13CNMR(CDCl3,75MHz,APT)
δ/ppm 153.1 (s), 136.8 (s), 126.8 (d), 126.1 (d), 121.2 (d), 118.6 (d),
99.5 (d), 63.5 (t), 39.9 (t), 38.9 (t), 35.2 (t), 34.2 (s), 33.97 (t), 33.94 (d),
33.89 (t), 33.5 (t), 31.2 (d), 27.7 (d), 27.5 (d), 15.2 (q); MS (FAB) m/z
299 (Mþ, 20), 298 (Mþ, 70), 265 (100), 190 (75); HRMS calcd for
C20H26O2 þ K 337.1564, obsd 337.1558.
chromatographed on
a thin layer of silica gel using
CH2Cl2-EtOAc (30%) to furnish 70 mg of the ether 10b and
20 mg of the starting material: colorless crystals; mp 124-
126 °C; IR (NaCl) νmax/cm-1 3360, 2905, 2854; 1H NMR
(DMSO-d6, 300 MHz) δ/ppm 9.35 (s, 1H, OH), 7.23 (d, 2H,
J = 8.7 Hz), 6.75 (d, 2H, J = 8.7 Hz), 2.66 (s, 3H), 2.53 (br s,
2H), 2.22 (br s, 1H), 2.18 (br s, 1H), 1.50-1.80 (m, 10H); 13C
NMR (DMSO-d6, 75 MHz, APT) δ/ppm 156.1 (s), 130.6 (s),
128.2 (d, 2C), 114.6 (d, 2C), 78.8 (s), 47.3 (q), 37.3 (t), 34.1 (t, 2C),
32.4 (t, 2C), 32.1 (d, 2C), 27.2 (d), 26.3 (d); MS (EI) m/z 259 (1,
Mþ), 258 (7, Mþ), 228 (22), 227 (100), 226 (47), 106 (20); HRMS
calcd for C17H22O2 258.16198, obsd 258.16183.
2-(4-Hydoxyphenyl)adamantane (12).43 AdPh 10 (100 mg,
0.41 mmol) was dissolved in CH3OH (100 mL) and irradiated
in Rayonet reactor at 254 nm using 16 lamps for 20 min. After
evaporation of the solvent, the residue was chromatographed on
Photolysis of 2-Hydroxy-2-(3-hydroxyphenyl)adamantane (9). In
a quartz vessel was placed a CH3CN-H2O (3:1) solution (100 mL,
~
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~
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a thin layer of silica gel using CH2Cl2-EtOAc (30%) to furnish
20 mg of ether 10b, 10 mg of product 12 (10%), and 50 mg of
recovered starting material.
1H, J = 2.8 Hz, J = 12.2 Hz), 1.78-1.90 (m, 4H), 1.56-1.75 (m,
3H), 1.52 (dq, 1H, J = 2.1 Hz, J = 12.6 Hz); 13C NMR (CDCl3,
75 MHz, COM, DEPT) δ/ppm 159.7 (s), 144.9 (s), 129.1 (d),
118.8 (d), 112.9 (d), 110.1 (d), 69.7 (d), 55.0 (q), 47.7 (d), 38.7 (t),
37.6 (d), 34.5 (d), 32.1 (t), 31.6 (t), 31.0 (t), 29.6 (d), 27.0 (d); MS
(EI) m/z 259 (19, Mþ), 258 (100, Mþ), 150 (71), 135 (9), 122 (26),
121 (18), 108 (55), 107 (10), 106 (10), 91 (10); HRMS calcd for
C17H22O2 258.16198, obsd 258.16184.
2-Hydroxy-4-(2-methoxyphenyl)adamantane (10ac). Methoxy-
phenol 10a (114 mg, 0.44 mmol) was dissolved in CH3-
OH-H2O (3:1, 100 mL) and the mixture irradiated in Rayonet
reactor at 254 nm using 16 lamps for 2 h. After evaporation of
the solvent, the residue was chromatographed on a thin layer
of silica gel using CH2Cl2 to furnish 70 mg of the start-
ing material and 30 mg (30%) of the product: colorless
crystals; mp 66 - 68 °C; IR (NaCl) νmax/cm-1 3368, 29051,
2851; 1H NMR (CDCl3, 300 MHz) δ/ppm 7.22 (d, 2H, J = 8.7
Hz), 6.84 (d, 2H, J = 8.7 Hz), 3.85 (t, 1H, J = 2.7 Hz), 3.78 (s,
3H), 3.10 (br s, 1H), 2.47 (br s, 1H), 2.38 (br s, 1H), 2.31
(dq, 1H, J = 2.7 Hz, J = 12.8 Hz), 2.06 (dq, 1H, J = 2.8 Hz,
J = 12.8 Hz), 1.72-1.98 (m, 5H), 1.48-1.75 (m, 4H);
13C NMR (CDCl3, 75 MHz, COM, DEPT) δ/ppm 157.2 (s),
135.0 (s), 127.2 (d), 113.5 (d), 69.6 (d), 55.1 (q), 47.0 (d),
38.7 (t), 37.5 (d), 34.6 (d), 32.1 (t), 31.4 (t), 31.0 (t), 29.6 (d),
26.9 (d); MS (EI) m/z 258 (100, Mþ), 259 (20, Mþ), 150 (20),
135 (10), 121 (30); HRMS calcd for C17H22O2 258.16198, obsd
258.16180.
2-(2-Hydroxyphenyl)-2-methoxypropane (11b).44 Phenol 11
(116 mg, mmol) was dissolved in CH3OH-H2O (25%, 100
mL) and irradiated in a Rayonet reactor at 254 nm using 16
lamps for 1 h. After irradiation, extraction with CH2Cl2 (3 ꢀ 75
mL) was carried out, and the extracts were dried over anhydrous
MgSO4. After filtration, the solvent was removed on a rotary
evaporator and the residue was chromatographed on a thin
layer of silica gel using CH2Cl2 to furnish 50 mg (40%) of the
product 11b and 20 mg (17%) of the starting material.
N-(2-Hydroxyethyl)-2-(2-hydroxyphenyl)-2-aminoadamantane
(13). AdPh 8 (8.2 mg, 0.033 mmol) was dissolved in CH3CN
(2100 mL) and to the solution was added ethanolamine (100 μL,
1.63 mmol). The solution was irradiated in a Rayonet reactor at
254 nm using 16 lamps for 5 min. After irradiation, the solvent
was removed on a rotary evaporator and to the residue H2O (50
mL) was added. Extraction with CH2Cl2 was carried out (3 ꢀ 50
mL), and extracts were dried over anhydrous MgSO4. After
filtration and removal of the solvent pure product was obtained
quantitatively: colorless crystals; mp 130-132 °C; IR (NaCl)
ν
max/cm-1 3368, 2910, 2855; 1H NMR (CDCl3, 300 MHz) δ/ppm
7.31 (dd, 1H, J = 1.3 Hz, J = 7.7 Hz), 7.12 (dt, 1H, J = 1.6 Hz,
J = 7.3 Hz), 6.73-6.82 (m, 2H), 3.55-3.70 (m, 2H), 2.65-2.75
(m, 2H), 2.65 (br s), 2.52 (br s, 2H), 2.02-2.14(m, 3H), 1.86-1.96
(m, 2H), 1.68-1.84 (m, 6H), 1.61 (dq, 1H, J = 3.0 Hz, J = 12.8
Hz), 1.43 (dd, 1H, J = 2.3 Hz, J = 12.7 Hz); 13C NMR (CDCl3,
75 MHz, COM, DEPT) δ/ppm 157.4 (s), 129.4 (d), 128.10 (d),
128.06 (s), 118.1 (d), 117.6 (d), 62.6 (s), 62.3 (t), 42.1 (t), 38.2 (t),
35.3 (t), 34.5 (t), 34.0 (d), 32.8 (t), 32.3 (t), 30.3 (d), 27.3 (d), 26.4
(d); MS (EI) m/z 287 (30, Mþ), 288 (10, Mþ), 267 (30), 258 (25),
252 (25), 226 (100), 183 (20); HRMS calcd for C18H25NO2
287.18853, obsd 287.18858.
2-Methoxy-2-(2-methoxyphenyl)adamantane (8ab). Methoxy-
phenol 8a (102 mg, 0.39 mmol) was dissolved in CH3OH-H2O
(3:1, 100 mL) and irradiated in Rayonet reactor at 254 nm using 16
lamps for 2 h. After evaporation of the solvent the residue was
chromatographed on a thin layer of silica gel using CH2Cl2 to
furnish 70 mg of the starting material and 20 mg (20%) of the
product: colorless crystals; mp 64 - 66 °C; 1H NMR (CDCl3, 300
MHz) δ/ppm 7.36 (dd, 1H, J = 1.3 Hz, J = 8.0 Hz), 7.24 (dt, 1H,
J = 1.7 Hz, J = 8.1 Hz), 6.88-6.95 (m, 2H), 3.79 (s, 3H, OCH3),
3.36 (br s, 1H), 2.85 (s, 3H), 2.64 (br s, 1H), 2.38 (d, 1H,
J = 12.4 Hz), 2.23 (dd, 1H, J = 2.7 Hz, J = 12.3 Hz), 1.94 (dd,
1H, J = 2.5 Hz, J = 12.3 Hz), 1.60-1.85 (m, 7H), 1.54 (dq, 1H,
J = 2.7 Hz, J = 12.4 Hz), 1.44 (d, 1H, J = 12.8 Hz); 13C NMR
(CDCl3, 75 MHz, COM, DEPT) δ/ppm 159.6 (s), 130.5 (d), 128.4
(d), 128.2 (s), 119.6 (d), 112.5 (d), 81.7 (s), 55.5 (q), 48.4 (q), 37.7 (t),
35.2 (t), 34.7 (t), 34.4 (d), 33.0 (t), 32.9 (t), 31.2 (d), 27.5 (d), 26.7 (d);
MS (EI) m/z 273 (2, Mþ), 272 (12, Mþ), 242 (20), 241 (100), 151
(24), 121 (20); HRMS calcd for C18H24O2 272.17763, obsd
272.17753.
2-(4-Methoxyphenyl)-2-(2,2,2-trifluoroethoxy)adamantane
(14). Methoxyphenol 10a (10 mg, mmol) was dissolved in 5
mL of trifluoroethanol and stirred at rt overnight. The next
day, solvent was removed on a rotary evaporator to furnish
the pure product: colorless crystals; mp 56-58 °C; IR (NaCl)
1
ν
max/cm-1 2906, 2856; H NMR (CDCl3, 300 MHz) δ/ppm
7.36 (d, 2H, J = 8.8 Hz), 6.88 (d, 2H, J = 8.8 Hz), 3.81 (s, 3H),
3.20 (q, JH-F3 = 8.8 Hz), 2.55 (br s, 2H), 2.34 (br s, 1H), 2.30
(br s, 1H), 1.88 (br s, 1H), 1.60-1.80 (m, 9H); 13C NMR
(CDCl3, 75 MHz, COM, DEPT) δ/ppm 158.8 (s), 137.7 (s),
128.4 (d, 2C), 124.4 (q, JCF = 278 Hz), 113.5 (d, 2C), 81.0
(s), 59.2 (qd, JCF3 = 34 Hz), 55.1 (q), 37.5 (t), 34.2 (t, 2C), 33.2
(d, 2C), 32.5 (t, 2C), 27.5 (d), 26.6 (d); MS (EI) m/z 340 (10,
Mþ), 341 (3, Mþ), 242 (20), 241 (100), 219 (100), 135 (5),
121 (10); HRMS calcd for C19H23F3O2 340.16501, obsd
340.16486.
4-(Adamantan-2-ylidene)cyclohexa-2,5-dienone (10QM).
AdPh 10 (10 mg, 0.041 mmol) was dissolved in 1 mL of
1,1,1,3,3,3-hexafluoro-2-propanol-d2 (HFIP), and NMR spec-
tra were taken: 1H NMR (HFIP-d2, 500 MHz) δ/ppm: 8.08 (d,
2H, J = 9.9 Hz), 6.65 (d, 2H, J = 9.9 Hz), 3.70 (br s, 2H), 2.33 (d,
4H, J = 12.4 Hz), 2.08 (br s, 4H), 2.03 (d, 4H, J = 12.4 Hz); 13
C
NMR (HFIP-d2, 125 MHz) δ/ppm 197.8 (s), 191.3 (s), 138.2 (d,
2C), 124.6 (d, 2C), 124.2 (s), 40.9 (t, 4C), 38.1 (d, 2C), 35.4 (t),
27.6 (d, 2C).
Laser Flash Photolysis (LFP). All LFP studies were con-
ducted at the University 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. The absorbance of the solutions at 266 nm
was ∼0.4-0.6.
2-Hydroxy-4-(3-methoxyphenyl)adamantane (9ac). Methoxy-
phenol 9a (107 mg, 0.41 mmol) was dissolved in CH3OH-H2O
(3:1, 100 mL) and irradiated in Rayonet reactor at 254 nm using
16 lamps for 2 h. After evaporation of the solvent the residue was
chromatographed on a thin layer of silica gel using CH2Cl2 to
furnish 60 mg of the starting material and 20 mg (20%) of the
product: colorless oil: IR (NaCl) νmax/cm-1 3400, 2911, 2852;
1H NMR (CDCl3, 300 MHz) δ/ppm 7.22 (t, 1H, J = 7.8 Hz),
6.92 (d, 1H, J = 8.1 Hz), 6.87 (br s, 1H), 6.70 (dd, 1H, J = 2.4
Hz, J = 8.1 Hz), 3.85 (t, 1H, J = 2.8 Hz), 3.78 (s, 3H), 3.13 (br s,
1H), 2.48 (br s, 1H), 2.40 (br s, 1H), 2.31 (dq, 1H, J = 2.8 Hz,
J = 12.6 Hz), 2.07 (dq, 1H, J = 2.8 Hz, J = 12.6 Hz), 1.95 (dq,
Steady-State and Time-Resolved Fluorescence Measurements.
The samples were dissolved in CH3CN, and the concentrations
were adjusted to have optical densities of <0.1 at the excitation
wavelength (270 nm). Solutions were purged with nitrogen
for 15 min prior to analysis. The measurements were performed
at 20 °C and were not corrected. Fluorescence quantum
yields were determined by comparison of the integral of emis-
sion bands with the one of anisole (Φ = 0.29).28 Typically,
three absorption traces and three fluorescence emission traces
(44) Oude-Alink, B. A. M.; Chan, A. W. K.; Gutsche, C. D. J. Org. Chem.
1973, 38, 1993–2001.
J. Org. Chem. Vol. 75, No. 1, 2010 115

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were recorded, exciting at three different wavelengths (260, 265,
and 270 nm). Three quantum yields were calculated and the
mean value reported.
quality of the fit that included plots of surfaces (“carpets”) of the
weighted residuals vs channel number.
Fluorescence decay histograms were obtained on an instru-
ment equipped with hydrogen flash lamp, using time-correlated
single-photon timing technique in 1023 channels. Histograms of
the instrument response functions (using LUDOX scatterer)
and sample decays were recorded until they typically reached
3 ꢀ 103 counts in the peak channel. The half width of the
instrument response function was typically ∼1.3 ns. The time
increment per channel was 0.04883 ns. Obtained 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-expo-
nential factors) were determined by minimizing the reduced chi-
square χ2g. Additional graphical method was used to judge the
Acknowledgment. We thank the Ministry of Science Edu-
cation and Sports of the Republic of Croatia (Grant No. 098-
0982933-2911), the Croatian Academy of Sciences and Arts
(HAZU), the Natural Sciences and Engineering Research
Council (NSERC) of Canada, and the University of Victoria
for financing. N.B. thanks N. Cindro for help with the
synthesis of phenols 11 and 11a.
Supporting Information Available: General and detailed
1
experimental procedures, characterization of compounds, H
and 13C NMR spectra, and fluorescence and LFP data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
116 J. Org. Chem. Vol. 75, No. 1, 2010