Contribution of the intramolecular hydrogen bond to the shift of the pKa value and the oxidation potential of phenols and phenolate anions

Article abstract of DOI:10.1039/b419361j

Intramolecularly OH...O=C hydrogen bonded phenols, 2-HO-C ₆H₂-3,5-(t-Bu)₂-CONH-t-Bu (1-OH), 2-HO-C ₆H₂-5-t-Bu-1,3-(CONH-t-Bu)₂ (2-OH) and 2-HO-C₆H₂-3,5-(t-Bu)₂

Full text of DOI:10.1039/b419361j

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A R T I C L E
Contribution of the intramolecular hydrogen bond to the shift of the
pKa value and the oxidation potential of phenols and phenolate
anions†
Daisuke Kanamori, Atsushi Furukawa, Taka-aki Okamura, Hitoshi Yamamoto and
Norikazu Ueyama*
Department of Macromolecular Science, Graduate School of Science, Osaka University,
Toyonaka, Osaka, 560-0043, Japan. E-mail: ueyama@chem.sci.osaka-u.ac.jp
Received 4th January 2005, Accepted 23rd February 2005
First published as an Advance Article on the web 10th March 2005
=
Intramolecularly OH · · · O C hydrogen bonded phenols, 2-HO–C6H2-3,5-(t-Bu)2–CONH–t–Bu (1–OH),
2-HO–C6H2-5-t-Bu-1,3-(CONH-t-Bu)2 (2–OH) and 2-HO–C6H2-3,5-(t-Bu)2–NHCO–t–Bu (4–OH), were synthesized
and their phenolate anions were prepared as tetraethylammonium salts (1–O−(NEt4 ), 2–O−(NEt4 ) and
+
+
4–O−(NEt4 )) with intramolecular NH · · · O(oxyanion) hydrogen bonds. 4-HO–C6H2-3,5-t-Bu2–CONH–t–Bu
+
+
(3–OH) and its phenolate anion, 3–O−(NEt4 ), were synthesized as non-hydrogen bonded references. The presence of
intramolecular hydrogen bonds was established through the crystallographic analysis and/or 1H NMR spectroscopic
results. Intramolecular NH · · · O(phenol) hydrogen bonds shift the pKa of the phenol to a more acidic value. The
=
results of cyclic voltammetry show that the intramolecular OH · · · O C hydrogen bond negatively shifts the
oxidation potential of the phenol. In contrast, the intramolecular NH · · · O(oxyanion) hydrogen bond positively
shifts the oxidation potential of the phenolate anion, preventing oxidation. These contributions of the hydrogen bond
to the pKa value and the oxidation potentials probably play an important role in the formation of a tyrosyl radical in
photosystem II.
Introduction
The oxidation process of tyrosine is of much interest because of
its importance in various enzymes.1,2 In many of the enzymes
containing a tyrosine residue, the formation of a hydrogen
bond to the tyrosyl radical has been implied.3–7 Among these
enzymes, much attention has been focused on photosystem II
(PSII), in which proton-coupled electron transfer (PCET) occurs
(Scheme 1). Studies conducted on model compounds of PSII
show that the hydrogen bond promotes the oxidation of phenol
and contributes to PCET.8–11 The model compounds used in
these studies realize the OH · · · N hydrogen bond between the
Scheme 1 Proton-coupled electron transfer in photosystem II.
tyrosine and histidine residues. The hydrogen bond acceptors in
the models are basic substituents such as primary and tertiary
amines. Because of the high basicity of the substituents, the
model systems are in acid–base equilibrium and probably show
an averaged character (2, below). It seems difficult to discuss
precisely the contribution of the hydrogen bond under such an
equilibrium. In this paper, we present new models that realize
two extreme situations (1) and (3), involving phenols with a
weakly basic hydrogen bond acceptor and phenolate anions
with a weakly acidic hydrogen bond donor. In these models, the
contribution of a hydrogen bond to the oxidation of phenols and
phenolate anions can be discussed individually. The contribution
of the hydrogen bonds to pKa values is also discussed. The acidity
of the tyrosine in PSII is one of the most important factors for
PCET because it relates to the degree of dissociation of the
phenolic proton.
We have recently demonstrated the conformational switch-
ing in salicylamide derivatives between the phenol and the
phenolate anion (Scheme 2).12,13 In the phenol, salicylamide
=
derivatives form an intramolecular OH · · · O C hydrogen bond.
In contrast, they form an intramolecular NH · · · O(oxyanion)
hydrogen bond in the phenolate anion. We synthesized the
phenols shown in Chart 1 as well as their phenolate anions,
which are adequate models for systematically discussing the
contribution of the hydrogen bond (details of these syntheses are
in the supplementary information). ortho-Substituted phenols,
1–OH, 2–OH and 4–OH, and their phenolate anions as
tetraethylammonium salts, 1–O−(NEt4 ), 2–O−(NEt4 ) and 4–
+
+
O−(NEt4 ), were used as hydrogen-bonding models. In 2–OH
+
and 2–O−(NEt4 ), the formation of an additional intramolecular
+
hydrogen bond is expected. Using these models enables us to
discuss the contribution of hydrogen bonded water to tyrosine
in PSII to the oxidation of the tyrosine. para-Substituted isomers,
Ar–O–H · · · B
Ar–Od− · · · H · · · Bd+
Ar–O− · · · H–B+
(1)
(2)
(3)
+
3–OH and 3–O−(NEt4 ), were employed as non-hydrogen
bonded references.
† Electronic supplementary information (ESI) available: synthetic meth-
ods and details of physical measurements. See http://www.rsc.org/
suppdata/ob/b4/b419361j/
Scheme 2 Conformational switching in salicylamide derivatives in
solution.
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 4 5 3 – 1 4 5 9
1 4 5 3
©

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Fig. 1 ORTEP drawings of crystal structures of (a) 1–OH, (b) 2ꢀ–OH, (c) anion part of 1ꢀ–O−(NEt4+)·(H2O), (d) anion part of 2ꢀ–O−(NMe4+) and
(e) 1–OH.
Results and discussion
Crystal structures
The crystal structures of hydrogen bonded phenols and phe-
nolate anions are shown in Fig. 1. The selected short contacts,
bond lengths and torsion angles are listed in Table 1. The short
distance between phenolic (O11) and carbonyl oxygen (O1) in
=
1–OH indicates the presence of an intramolecular OH · · · O C
hydrogen bond. In 2ꢀ–OH, which has two N-tert-butylcarbamoyl
groups at ortho-positions from the phenolic hydroxyl group, one
=
of these groups forms an intramolecular OH · · · O C hydrogen
bond similar to 1–OH, and the other forms an intramolecular
NH · · · O hydrogen bond. In the phenolate anions, short con-
tacts between phenoxy oxygen (O11) and carbamoyl nitrogen
ꢀ
−
+
ꢀ
˚
(N1) (2.690(4) in 1 –O (NEt4 )·(H2O) and 2.603(1) A in 2 –
O−(NMe4 )) suggest that all N-tert-butylcarbamoyl groups form
+
an intramolecular NH · · · O(oxyanion) hydrogen bond. In the
phenolate anions, no significant intermolecular interactions
were observed, except for the short contact between the pheno-
late oxygen atom and the water oxygen in 1ꢀ–O−(NEt4 )·(H2O).
+
Crystal structure of 1ꢀOH was also analyzed. However, it gives
Chart 1
1 4 5 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 4 5 3 – 1 4 5 9

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+
Table 1 Selected short contacts, bond distance and torsion angles of 1–OH, 2ꢀ–OH, 1ꢀ–O−(NEt4+)·H2O and 2ꢀ–O−(NMe4
)
+
1–OH
2ꢀ–OH
1ꢀ–O−(NEt4+)·H2O
2ꢀ–O−(NMe4
)
1ꢀ–OH
O11 · · · O1
2.501(2)
2.514(3)
2.461(4)
2.471(4)
—
—
—
—
2.549(2)
2.606(2)
2.614(2)
—
(O11 · · · O1* for 1ꢀ–OH)
O11 · · · N2
O11 · · · N1
—
—
2.673(4)
2.654(4)
—
—
—
2.690(4)
2.603(1)
2.598(2)
2.652(2)
2.661(2)
1.361(3)
1.361(3)
1.363(3)
2.1(3)
−7.5(4)
−11.9(4)
—
C11–O11
1.353(3)
1.357(3)
1.341(4)
1.352(4)
1.294(5)
14.9(6)
—
1.307(2)
8.59(18)
—
C11–C12–C1–N1
C11–C16–C2–N2
−172.5(2)
−170.0(3)
169.2(2)
161.3(4)
—
13.5(6)
−7.2(6)
Table 2 Chemical shifts of phenolic OH and amide NH protons, 5 mM
less information about intramolecular hydrogen bond than 1–
in CD3CN
=
OH because it forms an intermolecular OH · · · O C hydrogen
bond (Fig. 1e).
OH
NH
All structures showed small torsion angles (high coplanarity)
between the aromatic and amide planes. The C11–O11 bond
lengths in the phenolate anions were shorter than those in the
corresponding phenols. This finding indicates that an increase
in the double bond character of the phenolate anion occurred
because of the delocalization of the negative charge on the
anionic oxygen atom to the aromatic ring. These structural
features are similar to the findings of our recent works.12,13
d/ppm (OH)
d/ppm (OH)
d/ppm (O−(NEt4+))
1–
2–
3–
13.18
6.80
7.81
6.41
13.21
11.92
5.74
Not observeda
5.75
a Even at −30 ◦C.
Solution structures
Intramolecular hydrogen-bond formation was confirmed by 1H
NMR measurement in acetonitrile-d3 solution (5 mM, suffi-
ciently dilute to neglect intermolecular interactions; experimen-
tal details are available in the supplementary information). The
phenol and the phenolate anion with the para-N-tert-butyl car-
bamoyl group, 3–OH and 3–O−(NEt4 ), were used as references
+
without any intramolecular hydrogen bond. Chemical shifts of
phenolic OH and amide NH protons are summarized in Table 2,
and schematic drawings of the solution structures indicating the
intramolecular hydrogen bonds are shown in Scheme 3. These
chemical shifts are effective in determining the conformation
of salicylamide derivatives. Hydrogen bonded phenolic OH
signals in phenol and amide NH signals in phenolate anion were
observed in an extremely low field (>11 ppm).12,13 The phenolic
OH signal of 1–OH was observed at 13.18 ppm, indicating the
=
formation of an intramolecular OH · · · O C hydrogen bond. A
similar hydrogen bond should be formed in 2–OH although the
OH signal of 2–OH was not observed even at −30 ◦C, which
is probably because of the proton exchange between the two
ortho-substituents (Scheme 4). In the case of 2ꢀ–OH, which is
an analogous compound to 2–OH, a broad singlet OH signal
was observed in a very low field, 14.00 ppm. The amide NH
Scheme 3 Solution structures of 1–OH, 2–OH, anion of 1–O−(NEt4
and anion of 2–O−(NEt4+).
)
+
signals of the phenolate anions, 1–O−(NEt4 ), 2–O−(NEt4 ) and
+
+
+
3–O−(NEt4 ), were observed at 13.21, 11.92 and 5.74 ppm,
respectively. The lower-field shifts of the NH signal strongly
indicate the presence of the intramolecular NH · · · O(oxyanion)
hydrogen bond. In acetonitrile solution, these phenols and
phenolate anions favor a hydrogen-bonding mode similar to
what is found in the crystal structures.
Scheme 4 Proton exchange on 2–OH in solution.
Contribution of hydrogen bonds to pKa shift
solution consisting of two heterogeneous layers, hydrophobic
and hydrophilic, the phenols are buried in the hydrophobic layer,
where the intramolecular hydrogen bonds discussed above are
supported. Under these conditions, pKa values are verified as
accurate in hydrophobic environments like the inside of a protein
(not in a mixture of aqueous and organic media) because of
The pKa values in an aqueous micellar solution of 1ꢀ–
OH, 2ꢀ–OH, 3ꢀ–OH and 5ꢀ–OH, which forms intramolecular
12
=
OH · · · O C and NH · · · O hydrogen bonds, were determined
by potentiometric titration to be 9.2, 7.5, 9.4 and 8.1, respec-
tively, and are summarized in Fig. 2. In an aqueous micellar
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 4 5 3 – 1 4 5 9
1 4 5 5

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Table 3 Oxidation potentials of phenol and phenolate anion deriva-
tives and sum of Hammett constants
Epa/V (OH) Epa/V (O−(NEt4+)) Rr+
1–
1.45
1.53
1.61
1.25
1.57
1.50b
1.54
1.44b
0.24
0.58
0.04
−0.11
0.37
0.14
2–
3–
4–
−0.05
−0.83
5–
0.31a
0.34
2,4,6-(t-Bu)3C6H2–
2,6-(t-Bu)2C6H2–
2,6-(t-Bu)2-4-MeC6H2–
−0.23b
−0.19c,d
−0.35b
−0.40b
−0.03c
−0.60
−0.34
−0.65
−1.12
−0.19
Fig. 2 Summary of pKa values.
2,6-(t-Bu)2-4-MeOC6H2– 1.16b
rapid proton transfer between two layers.14,15 The OH · · · O C
and NH · · · O hydrogen bonds in the model compounds are
regarded as simulating the OH · · · N and OH(water) · · · O hy-
drogen bonds in PSII (Scheme 1), respectively. It has been
reported that salicylamide derivatives show a low pKa value
due to the NH · · · O(oxyanion) hydrogen bond in both aqueous
and dimethylacetamide solutions,16 where the intramolecular
=
4-Br-2,6-(t-Bu)2C6H2–
1.49
a Ref. 12. b Ref. 21. c Ref. 22 (tetramethylammonium salt). d Oxidation
potential is slightly more positive (ca. +0.05 V) than this value because
the value is given as a redox potential.
=
OH · · · O C hydrogen bond is not supported and the existence
of NH · · · O–hydrogen bonded conformer has been proposed
as a result of intermolecular hydrogen bonding with solvent
molecules (similar conformation to the crystal structure of 1ꢀ–
OH (Fig. 1e). On the other hand, in an aqueous micellar solution
1ꢀ–OH showed a negligible pKa shift from that of 3ꢀ–OH,
which has similar electronic effects of the N-tert-butylcarbamoyl
group to 1ꢀ–OH. In an aqueous micellar solution, NH · · · O–
hydrogen bonded conformer does not exist because the in-
=
tramolecular OH · · · O C hydrogen bond is supported under
these conditions. These results indicate that lowering the pKa
value of salicylamide derivatives is due to not the formation of
NH · · · O(oxyanion) hydrogen bond in the phenolate anion but
the formation of NH · · · O hydrogen bond from pre-locating
NH to the phenolic hydroxyl group in the deprotonation
ꢀ
=
process. The OH · · · O C hydrogen bond in 1 –OH does not
raise the pKa value, in contrast to a process proposed for
the OH · · · O(carboxylate) hydrogen bond in salicylate mono-
anions.17 This is probably due to the difference of hydrogen-
accepting abilities between carbonyl and carboxylate groups.
The energy barrier of a local proton transfer between phenolic
and carbonyl oxygen atoms should be low, as observed in the
two-centered short hydrogen bonds.18 The phenols, 2ꢀ–OH and
5ꢀ–OH, which form the NH · · · O hydrogen bond adding to the
=
OH · · · O C hydrogen bond, showed lower pKa values. These
Fig. 3 Correlation of oxidation potential with sum of Hammett
constants, (a) phenols and (b) phenolate anions. Solid circles and squares
are our results, including ref. 12, and open circles are from ref. 21 and ref.
22. Squares are plots for hydrogen bonded compounds and circles are
the other. All the phenols and phenolate anions have tert-butyl groups
at the ortho- and para-positions if not specified in the plots.
pKa shifts also indicate the contribution of the pre-locating NH,
and similar shifts were found in our previous results on phenols,14
thiophenols19 and benzoic acids.15 Lowering pKa values by pre-
locating hydrogen-bonding donor is important in terms of the
shift of the acid–base equilibrium between the tyrosine and
histidine residues to a more polarized state. In PSII, the hydrogen
bonded water presumably plays an important role not only in
the reduction of the tyrosyl radical as a hydrogen source,20 but
also in lowering the pKa value.
The oxidation potentials and the sum of the electronic
effects of the substituents, Rr+, are summarized in Table 3.
The plot of the oxidation potentials of the phenol against
Rr+ is shown in Fig. 3a. Non-hydrogen bonded phenols, with
the exception of 2,6-di-tert-butyl-4-methoxyphenol, show good
linearity. The deviation of the oxidation potential of 2,6-di-tert-
butyl-4-methoxyphenol is attributed to the stabilization of the
corresponding radical with the favorable resonance structure
by the 4-methoxy group.25 The overall trend (with one minor
exception) is that the hydrogen bonded phenols show a relatively
negative oxidation potential compared with the non-hydrogen
Contribution of hydrogen bonding to the shift of oxidation
potential
The oxidation potential of phenols 1–OH to 5–OH and phe-
+
+
nolate anions 1–O−(NEt4 ) to 5–O−(NEt4 ) were measured in
acetonitrile. In all of the phenols and phenolate anions, including
related compounds,21,22 two substituents with a similar bulkiness
were introduced to the ortho-positions because the bulkiness at
these positions has been reported to affect the redox potentials
of the phenolate anion.22 Hammett constants, r+, for CONH-
t-Bu and NHCO-t-Bu have not been reported, thus alternative
values for COOEt and NHCOMe were used, respectively.23 The
electronic effect of an ortho-substituent is related to that of a
para-substituent in (4).24
=
bonded ones. The formation of an intramolecular OH · · · O C
hydrogen bond in 4–OH was indicated by the crystal structure
of the 4–OH analogue, bis-(3,5-di-tert-butyl-2-phenol)-oxamide
(Scheme 5).26 In the case of 2–OH and 5–OH, the formation
of another intramolecular hydrogen bond, NH · · · O(phenol),
was suggested by the crystal structures. However, an additional
shift of the oxidation potential caused by the NH · · · O(phenol)
hydrogen bond was not observed. This type of hydrogen bond,
where phenolic oxygen acts as a hydrogen bond acceptor, has
+
+
ro = 0.66 rp
(4)
1 4 5 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 4 5 3 – 1 4 5 9

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Scheme 5 Predominant solution structure of 4–OH.
been reported to contribute to the high antioxidant activity of
phenol by lowering the bond dissociation enthalpy of the O–
H bond.27,28 The inconsistency is probably due to the fact that
electrochemical oxidation in this study did not include the O–
H bond dissociation. The contribution of the intramolecular
=
OH · · · O C hydrogen bond to the oxidation potential of phenol
is similar to the reported results that the OH · · · N(amine)
hydrogen bond, where the phenolic hydroxyl group acts as a
hydrogen-bonding donor, negatively shifts the redox potential of
the phenol (ca. 0.7–1.1 V).9–11,29 However, the effect is relatively
small and vague because the basicity of carbonyl oxygen is lower
than that of amino nitrogen in the other studies.
A similar plot for phenolate anions is shown in Fig. 3b. Non-
hydrogen bonded phenolate anions show a good linearity in the
correlation as reported previously.22 On the other hand, all of the
hydrogen bonded phenolate anions show more positive oxida-
tion potentials than expected from the sum of electronic effects.
The results indicate that the intramolecular NH · · · O(oxyanion)
hydrogen bonds positively shift the oxidation potential of
the phenolate anion. A positive shift caused by the double
Fig. 4 UV-vis spectral changes in the reaction of (a) 1–O−(NEt4+) and
(b) 3–O−(NEt4+) with dioxygen in acetonitrile at 298 K (60 min interval
spectra, after 7 weeks for 1–O−(NEt4+) and 1 week for 3–O−(NEt4+)).
NH · · · O(oxyanion) hydrogen bond in 2–O−(NEt4 ) and 5–
+
O−(NEt4 ) is comparable to that caused by a single hydrogen
+
bond in 1–O−(NEt4 ) and 4–O−(NEt4 ).
+
+
Protection by NH · · · O(oxyanion) hydrogen bond from
oxidation by dioxygen
The shift in oxidation potential of the phenolate anion caused
by the presence of NH · · · O(oxyanion) hydrogen bonds may be
of biological importance in another aspect. In nature, there are
phenolate anions, such as phenolic chromophores in photoactive
yellow protein (PYP)30 and green fluorescent protein (GFP)31
that are rarely oxidized. If these phenolate anions have typical
oxidation potentials for phenolate anions, they should be easily
oxidized by dioxygen. It is possible that they are protected from
oxidation by hydrogen bonds to the phenolate anions proposed
in proteins. From this viewpoint, the oxidation of phenolate
Fig. 5 UV-vis spectrum of 2–O−(NEt4+) in acetonitrile at 298 K.
the pKa value of the phenolic OH group. The intramolecular
=
OH · · · O C hydrogen bond negatively shifts the oxidation
potential of the phenol. In contrast, another NH · · · O(phenol)
hydrogen bond in 2–OH and 5–OH shows a negligible ad-
ditional shift of the oxidation potential. The intramolecular
NH · · · O(oxyanion) hydrogen bonds positively shift the oxida-
tion potential of the phenolate anion.
anions by dioxygen was examined using 1–O−(NEt4 ), 2–
+
O−(NEt4 ) and 3–O−(NEt4 ). Introduction of quantified excess
+
+
Based on these results, the role of hydrogen bonds in PSII
can be considered. The hydrogen bond between the tyrosine and
histidine residues finely adjusts the oxidation potential of the
tyrosine to an adequate value for electron transfer (Fig. 6). It also
decreases the energy barrier of a local proton transfer between
the tyrosine and histidine residues. The hydrogen bond between
the tyrosine residue and water lowers the pKa of the phenolic OH
group. Lowering the pKa value is important in terms of shifting
the acid–base equilibrium between the tyrosine and histidine
residues to a more polarized state, resulting in an increased
+
dioxygen into the acetonitrile solution containing 1–O−(NEt4 )
and 3–O−(NEt4 ) resulted in a decrease in the absorption band
+
at 350 and 332 nm, respectively, which indicates oxidation of
the phenolate anions (Fig. 4).32,33 In a dioxygen atmosphere, 3–
O−(NEt4 ) was almost completely oxidized after 2 d. However,
+
+
only ca. 10% of 1–O−(NEt4 ) was oxidized under the same
+
conditions. In the case of 2–O−(NEt4 ), the absorption spectrum
did not show a meaningful change for at least 2 d (Fig. 5 shows
+
the UV-vis spectrum of 2–O−(NEt4 )). The positive oxidation
potential shift caused by the NH · · · O(oxyanion) hydrogen
bonds results in an increased stability of the phenolate anions
against oxidation by dioxygen. The hydrogen bonds to phenolate
anion in PYP, GFP and other proteins also prevent the oxidation
of the phenolate anions by dioxygen.
Conclusions
=
The intramolecular OH · · · O C, NH · · · O(phenol), and
NH · · · O(oxyanion) hydrogen bonds in phenols and phenolate
anions were established through crystallographic analyses and
1H NMR spectroscopic results. In phenol, the intramolecular
NH · · · O(phenol) hydrogen bond from pre-located NH lowers
Fig. 6 Schematic diagram of shift of oxidation potentials by hydrogen
bonds (OH · · · A and DH · · · O(oxyanion)). A and DH represent a
hydrogen-bond acceptor and donor, respectively.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 4 5 3 – 1 4 5 9
1 4 5 7

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anionic character of the tyrosine. In PSII, the hydrogen bonded
water is important not only in the reduction of the tyrosyl radical
as a hydrogen source but also in terms of lowering the pKa of
the tyrosine.
The hydrogen bond to a phenolate anion greatly shifts the
oxidation potential of the phenolate anion. Based on this
finding, the reaction rate of oxidation by dioxygen is remarkably
reduced. These results indicate that the phenolate anions in
PYP, GFP and other proteins (tyrosinate anions certainly exist
in various proteins even if they have been seldom noted) are
probably protected from oxidation by the presence of hydrogen
bonds formed to the phenolate anion.
5561 unique (Rint = 0.063), R1 = 0.061, wR2 = 0.227 (all data).
CCDC reference number 259700.
Crystal data for 1ꢀ–O−(NEt4 )·H2O‡. C19H34N2O2·H2O,
+
¯
M = 340.50, triclinic, space group P1, a = 10.0678(16), b =
◦
◦
˚
12.211(3), c = 9.0829(12) A, a = 97.147(15) , b = 92.285(15) ,
◦
3
˚
c = 109.753(14) , V = 1038.8(3) A , Z = 2, l(Mo–Ka) =
0.073 mm−1, 5729 reflections measured, 4752 unique (Rint
=
0.035), R1 = 0.069, wR2 = 0.277 (all data). CCDC reference
number 259699.
Crystal data for 2ꢀ–O–(NMe4 )‡. C20H35N3O3, M = 365.51,
+
orthorhombic, space group Cmc21, a = 13.2912(6), b =
3
˚
˚
13.0775(5), c = 12.1094(5) A, V = 2104.80(15) A , Z = 4, l(Mo–
Ka) = 0.078 mm−1, 2451 reflections measured, 2171 unique
(Rint = 0.036), R1 = 0.039, wR2 = 0.093 (all data). CCDC
reference number 259701.
Experimental
pH titration
The pH of 10 mM solution of each phenol was determined
using a Metrohm 716 DMS titrino combined with a Metrohm
728 stirrer and a saturated calomel LL micro pH glass electrode.
The saturated calomel micro glass electrode was calibrated with
the 0.05 M KHC6H4(COO)2 buffer (pH = 4.01) and the 0.025 M
KH2PO4–Na2HPO4 buffer (pH = 6.86) at 30 ◦C. The sample
was dissolved in a small amount of THF and to the solution
was added Triton X-100. After removal of THF under reduced
pressure, the obtained residue was diluted with degassed water
to give a micellar solution. The final concentration is 10% Triton
X-100 aqueous solution containing 10 mM of the sample. The
solution was titrated with 0.1 M NaOH aq. at 30 ◦C. The pKa
value was estimated by the following equation: pKa = pH −
log[Na+] + log{[phenol]0 − [Na+]}.
Crystal data for 1ꢀ–OH‡. C11H15NO2, M = 193.24, mon-
oclinic, space group P21/c, a = 14.266(6), b = 12.599(4),
◦
3
˚
˚
c = 19.587(4) A, b = 100.86(2) , V = 3457.3(18) A , Z =
12, l(Mo–Ka) = 0.077 mm−1, 7518 reflections measured, 7197
unique (Rint = 0.055), R1 = 0.048, wR2 = 0.159 (all data). CCDC
reference number 259698.
Acknowledgements
One of the authors (D.K.) expresses his special thanks for the
Center of Excellence (21COE) program “Creation of Integrated
EcoChemistry of Osaka University”.
References
Oxidation by dioxygen
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Each single crystal of 1ꢀ–OH, 1ꢀ–O−(NEt4 ) and 2ꢀ–OH was
+
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+
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¯
space group P1, a = 10.6747(6), b = 12.0073(3), c = 15.3190(11)
◦
◦
◦
˚
A, a = 101.634(3) , b = 99.209(4) , c = 90.717(4) , V =
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˚
1896.34(18) A , Z = 4, l(Mo–Ka) = 0.068 mm , 8344
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 4 5 3 – 1 4 5 9
1 4 5 9