pubs.acs.

org/joc

Scales of Oxidation Potentials, pKa, and BDE of Various Hydroquinones

and Catechols in DMSO
Xiao-Qing Zhu,* Chun-Hua Wang, and Hao Liang
State Key Laboratory of Elemento-Organic Chemistry, Department of Chemistry,
Nankai University, Tianjin 300071, China

xqzhu@nankai.edu.cn
Received July 25, 2010

The one-electron oxidation potentials [EoxNHE(H2Q)], pKa (pKa1 and pKa2) values, and bond dissociation
energies (BDE1 and BDE2) of 118 important p- and o-dihydroquinones in DMSO were systematically
predicted for the first time by using DFT method and the PCM cluster continuum model. The calculated
results agree well with the available experimental determinations. The study shows that all the five ther-
modynamic parameters correlate well with the Hammett substituent parameters σp (for p-H2Q, EoxNHE-
(H2Q 3 þ/H2Q) = 1.66Σσp þ 0.54, pKa1 = -5.69Σσp þ 16.54, pKa2 = -5.19Σσp þ 23.91, BDE1 = 3.43Σσp þ
82.29, BDE2 =4.64Σσp þ 67.70 and for o-H2Q, EoxNHE(H2Q 3 þ/H2Q)=1.85Σσp þ 0.46, pKa1 =-5.53Σσp þ
13.28, pKa2 = -5.24Σσp þ 26.70, BDE1 = 3.54Σσp þ 82.08, BDE2 = 3.82Σσp þ 75.93), which hints that we
can get these thermodynamic parameters as long as the structure of the hydroquinones were known.
The comparisons of the calculated five thermodynamic parameters between p-hydroquinones and
o-hydroquinones and the number of the phenyl ring effects on these thermodynamic parameters were
also studied. At last, intramolecular hydrogen bond energies in hydroquinones at neutral, radical
cation, radical, anion different state were systematically calculated and analyzed. Combined with the
papers published in our group before, we will have a systematic thermodynamic picture of the transfer
details between different kinds of quinones and corresponding hydroquinones, which strongly promote
the fast development of the understanding and applications of quinones.

Introduction hydrogenation of polycyclic hydroacromatic compounds,2

cyclic ketones, and nitrogen heterocycles.3 Quinone/hydroqui-
Hydroquinones and catechols are well-known two-electron
none redox couples have been widely used in electrochemical
reductants, which play important roles in chemistry, biology,
studies because they are readily available and exhibit well
industries and our environmental science.1 For example, in
behaved electrochemistry.4 Hydroquinone derivatives are also
organic syntheses, hydroquinones are valuable reagents for the
active in cellular respiration,5 photosynthesis,6 and blood
(1) (a) Brodovitch, J. C.; McAuley, A.; Oswald, T. Inorg. Chem. 1982, 21,
3442. (b) Macartney, D. H.; McAuley, A. J. Chem. Soc., Dalton Trans. 1984, (4) Richard, D. A.; Shaobin, M. J. Am. Chem. Soc. 2004, 126, 5056.
103. (c) Giraudi, G.; Mentasti, E. Transition Met. Chem. 1981, 6, 230. (5) (a) Larsen, P. L.; Clarke, C. F. Science 2002, 295, 120123. (b) Do,
(d) Herbert, J. W.; Macartney, D. H. J. Chem. Soc., Dalton Trans. 1986, T. Q.; Hsu, A. Y.; Jonassen, T.; Lee, P. T.; Clarke, C. F. J. Biol. Chem. 2001,
1931. (e) Castro, C. E.; Hathaway, G. M.; Havlin, R. J. Am. Chem. Soc. 1977, 276, 18161. (c) Reynolds, C. A; King, P. M.; Richards, W. G. Nature 1988,
99, 8032. (f) Clemmer, J. D.; Hogaboom, G. K.; Holwerda, R. A. Inorg. Chem. 334, 80. (d) Lister, S. G.; Reynolds, C. A.; Richards, W. G. Int. J. Quantum
1979, 18, 2567. (g) Hoddenbagh, J. M. A.; Macartney, D. H. J. Chem. Soc., Chem. 1992, 41, 293. (e) Reyolds, C. A.; Richards, W. G.; Goodford, P. J.
Dalton Trans. 1990, 615. (h) Kustin, K.; Liu, S.-T.; Nicolini, C.; Toppen, D. L. Anti-Cancer Drug Des. 1987, 1, 291.
J. Am. Chem. Soc. 1974, 96, 7410. (i) Kamau, P.; Jordan, R. B. Inorg. Chem. (6) (a) Steinberg-Yfrach, G.; Liddell, P. A.; Hung, S.-C.; Moore, A. L.; Gust,
2002, 41, 3076. (j) Binstead, R. A.; McGuire, M. E.; Dovletoglou, A.; Seok, D.; Moore, T. A. Nature 1997, 385, 239. (b) Diner, B. A.; Babcock, G. T. In
W. K.; Roecker, L. E.; Meyer, T. J. J. Am. Chem. Soc. 1992, 114, 173. Oxygenic Photosynthesis: The Light Reactions; Ort, D. R., Yocum, C. F., Eds.;
(2) Fu, P. P.; Harvey, R. G. Chem. Rev. 1978, 78, 317. Kluwer: Dordrecht, The Netherlands, 1996; pp 213-247. Antennas and Reaction
(3) Becker,H.-D.;Turner, A. B. In The Chemistry of Quinonoid Com- Centers of Photosynthetic Bacteria; Michel-Beyerle, M. E., Ed.; Springer-Verlag:
pounds; Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1988; Vol. 2, Berlin, 1985. Functions of Quinones in Energy Conserving Systems; Trumpower,
Chapter 23, pp 1351. B. L., Ed.; Academic Press: New York, 1986.

7240 J. Org. Chem. 2010, 75, 7240–7257 Published on Web 09/28/2010 DOI: 10.1021/jo101455m
r 2010 American Chemical Society
Zhu et al.
JOC Article
SCHEME 1. Chemical Conversion Pathways from H2Q to Q groups near the OH group, hydrogen bonding characteristics
of the solvent may play a role in determining which mecha-
nisms of the hydroquinone oxidation process,13 it is clear,
however, that as long as molecular specific properties are
concerned, the oxidation potentials, proton dissociation
energies and bond dissociation energies are of particular
importance. For example, many authors stated that the three
mechanisms mentioned above are active and occur in
parallel, but this begs a question as to which one is dominant
or by how much. As a consequence, experimental chemists
paid substantial research activities to the determinations of
coagulation.7 Propyl gallate and nordihydroguaiaretic acid, the these three thermodynamic parameters in the past decades.
skeleton of which is catechols, are commericial antioxidants In 1983, L. E. Friedrich obtained the bond dissociation
which widely used as food additives to prevent oxidation of energies of hydroquinones by using half cell reactions in
fats.8 water,14 and in 1991, Bordwell reported the pKa values and
The oxidation of hydroquinones and catechols to corre- oxidation potentials of hydroquinones.15 Recently, Lucarini
sponding quinones has been a subject of great interest and is and co-workers determined the bond dissociation energies of
increasing drawing the attention of researchers. From the polyphenols by using EPR equilibration technique.16 How-
chemists’ viewpoint, there are three pathways mainly for the ever, experimental determinations of the thermodynamic
oxidation of hydroquinones and catechols. The first is initial parameters of the hydroquinones and catechols are relative
electron transfer followed by rapid proton transfer. The net small. The reason could be that the low stability of some
result is the hydrogen atom transfer and this mechanism hydroquinones, the difficulty of achieving high purity state,
usually occur between hydroquinones and transition metal difficulties of handling of harmful compounds and so usually
complexs.9 The second mechanism is initial proton transfer inconsistent with each other.17 Furthermore, experimental
followed by electron transfer. This mechanism is not un- techniques are not adequate to determine bond dissociation
common for ArOH/dpph (2,2-diphenyl-1-picrylhydrazil energies or proton dissociation energies in compounds con-
radical) in solvents that support ionization.10 The last one taining more than one O-H bond, and provide only either
is the hydrogen-atom transfer and can be widely seen in an average of the several O-H bonds or the lowest O-H
biological process since hydroquinones and catecholes are bonds in the molecule.18
also phenol derivatives.11 The final step of these three Considering the difficulty in obtaining these three impor-
mechanisms of the oxidation process of the hydroquinones tant thermodynamic parameters for the O-H bonds in these
is the conversion from semiquinones to quinones (eq 1).12 compounds, it is necessary to develop some theoretical
methods to predict these important quantities. These meth-
2HQ• f Q þ H2 Q ð1Þ
ods would be useful for researchers in a variety of traditional
Although other factors, such as biological context, solu- as well as emerging areas. Fox et al. used DFT in an attempt
bility, transport to specific tissues, the presence of bulky to determine whether a biochemical reaction mechanism
proceeds via hydrogen atom transfer or electron transfer,19
(7) (a) Cross, J. V.; Deak, J. C.; Rich, E. A.; Qian, Y.; Lewis, M.; Parrott, and Wright et al. used the DFT approach to determine
L. A.; Mochida, K.; Gustafson, D.; VandePol, S.; Templeton, D. J. J. Biol. accurate BDE and IE values of phenols (including hydro-
Chem. 1999, 274, 31150. (b) Reynolds, C. A. J. Am. Chem. Soc. 1990, 112,
7545. quinone and catechol) in the gas-phase.18 Recently, Leopoldini
(8) (a) De Heer, M. I.; Korth, H. G.; Mulder, P. J. Org. Chem. 1999, 64, et al. studied a series of phenols at the DFT level to specify
6969. (b) De Heer, M. I.; Mulder, P.; Korth, H. G.; Ingold, K. U.; Lusztyk, J.
J. Am. Chem. Soc. 2000, 122, 2355.
whether the antioxidant activity of these compounds proceeds
(9) Chambers, J. Q. In The Chemistry of Quinonoid Compounds; Patai, S., via hydrogen atom transfer or sequence electron transfer, in
Rappaport, Z., Eds.; John Wiley and Sons: New York, 1988; Vol. II, p 719. the gas-phase, and for the first time, in two solvents (water
(b) Lemberg, R. Barret, J. Cytochromes; Academic Press: London, 1973.
(c) Rich, P. R. Faraday Discuss. Chem. Soc. 1982, 74, 349. and benzene).20 More recently, E. G. Bakalbassis first reported
(10) (a) Erik, K.; Vladimir, L. J. Phys. Chem. A 2006, 110, 12312. the theoretical insights of the 2-monosubstituted phenols.21
(b) Musialik, M.; Litwinienko, G. Org. Lett. 2005, 7, 4952. (c) Litwinienko, All of the previous theoretical predictions have contributed
G.; Ingold, K. U. J. Org. Chem. 2003, 68, 3433. (d) Litwinienko, G.; Ingold,
K. U. J. Org. Chem. 2004, 69, 5888. (e) Foti, M. C.; Daquino, C.; Geraci, C.
J. Org. Chem. 2004, 69, 2309. (f) Litwinienko, G.; Ingold, K. U. J. Org. Chem. (13) (a) Pedulli, G. F.; Lucarini, M.; Pedrielli, P. Free Radicals in Biology
2005, 70, 8983. and Enviroment; Minisci, F., Ed.; Kluwer Academic Publishers: Dordrecht,
(11) (a) Bakalbassis, E. G.; Lithoxoidou, A. T.; Vafiadis, A. P. J. Phys. The Netherlands, 1997; p 169. (b) Burton, G. W.; Ingold, K. U. Acc. Chem.
Chem. A 2003, 107, 8594. (b) Vafiadis, A. P.; Bakalbassis, E. G. Chem. Phys. Res. 1986, 19, 194. (c) Valgimigli, L.; Ingold, K. U.; Lusztyk, J. J. Am. Chem.
2005, 316, 195. (c) Bordwell, F. G.; Zhang, X.-M.; Satish, A. V.; Cheng, J.-P. Soc. 1996, 118, 3545. (d) Barclay, L. R. C.; Edwards, C. E.; Vinqvist, M. R. J.
J. Am. Chem. Soc. 1994, 116, 6605. (d) Wayner, D. D. M.; Lusztyk, E.; Pag
e, J. Am. Chem. Soc. 1999, 121, 6226.
D.; Ingold, K. U.; Mulder, P.; Laarhoven, L. J. J.; Aldrich, H. S. J. Am. (14) Friedrich, L. E. J. Org. Chem. 1983, 48, 3852.
Chem. Soc. 1995, 117, 8737. (e) de Heer, M. I.; Korth, H.-G.; Mulder, P. (15) Bordwell, F. G.; Cheng, J. P. J. Am. Chem. Soc. 1991, 113, 1736.
J. Org. Chem. 1999, 64, 6969. (f) Pratt, D. A.; DiLabio, G. A.; Mulder, P.; (16) Lucarini, M.; Mugnaini, V.; Pedulli, G. F. J. Org. Chem. 2002, 67,
Ingold, K. U. Acc. Chem. Res. 2004, 37, 334. (g) Johnson, E. R.; Clarkin, 928.
O. J.; DiLabio, G. A. J. Phys. Chem. A 2003, 107, 9953. (h) DiLabio, G. A.; (17) Li, M. J.; Liu, L.; Fu, Y.; Guo, Q. X. J. Molec. Struct. (THEOCHEM)
Pratt, D. A.; LoFaro, A. D.; Wright, J. S. J. Phys. Chem. A 1999, 103, 1653. 2007, 815, 1.
(i) Brinck, T.; Haeberlein, M.; Jonsson, M. J. Am. Chem. Soc. 1997, 119, (18) Wright, J. S.; Carpenter, D. J.; McKay, D. J.; Ingold, K. U. J. Am.
4239. (j) Cabral, B. J. C.; Canuto, S. Chem. Phys. Lett. 2005, 406, 300. Chem. Soc. 1997, 119, 4252.
(k) Yao, X.-Q.; Hou, X.-J.; Jiao, H.; Xiang, H.-W.; Li, Y.-W. J. Phys. Chem. (19) Fox, T.; Kollman, P. A. J. Phys. Chem. 1996, 100, 2950.
A 2004, 108, 10834. (l) Est
acio, S. G.; do Couto, P. C.; Cabral, B. J. C.; (20) Leopoldini, M.; Marino, T.; Russo, N.; Toscano, M. J. Phys. Chem.
da Piedade, M. E. M.; Sim~ oes, J. A. M. J. Phys. Chem. A 2003, 107, 9991. A 2004, 108, 4916.
(12) William, W. Y. L.; Mendy, F. W. L.; Lau, T. C. Inorg. Chem. 2006, (21) Lithoxoidou, A. T.; Bakalbassis, E. G. J. Phys. Chem. A 2005, 109,
45, 315. 366.

J. Org. Chem. Vol. 75, No. 21, 2010 7241

JOC Article Zhu et al.

positively to the understanding of the chemistry of hydro- tion free energies.24 In this work, we choose Bondi’s atomic
quinones, nevertheless, it is worth mentioning that none of the radii, and the solvent here is DMSO.
previous studies have provided systematically ionization poten- From the calculated Gibbs free energies in the gas-phase and
tials in the gas-phase, oxidation potentials, bond dissociation, solution phase, we defined following quantities:
and proton dissociation energies of the O-H bond of hydro-
quinones and catechols in the solution phase. Although the
bond dissociation energies of some catechols have been esti-
mated, the predictions were made only with fairly low level
theoretical methods such as AM1 or only in the gas-phase.22
Furthermore, the comparisons of the first and second bond
dissociation energies or proton dissociation energies of hydro- IP ¼ GðH2 QÞg - GðH2 Q•þ Þg
quinones and catechols have not been released in the literatures
until now. The structure-activity relationships for the chemical ðionization potential in gas phaseÞ ð2Þ
activities also remain to be established.
We recently initiated a long-term project to study the Eox ¼ ½GðH2 QÞsol - GðH2 Q•þ Þsol =F
fundamental chemistry of quinones and hydroquinones ðoxidation potential of hydroquinones in DMSOÞ ð3Þ
and we successfully developed a theoretical method that
could calculate the hydride affinities, the first and second
reduction potentials of a variety of quinones. As a continua-
tion of our previous research, this paper will investigates
the oxidation potentials, the first and second proton disso-
ciation and bond dissociation energies of various hydroqui-
nones and catechols by accurate DFT-based calculations.
The structures of the hydroquinones and catechols of
interest in the present paper are shown in Scheme 2. Knowl- PA1g ¼ GðHQ - Þg þ GðHþ Þg - GðH2 QÞg
edge of these values was expected to be very valuable to
organic chemists and biochemists who want to know the ðthe first proton dissociation energy in gas phaseÞ ð4Þ
detailed oxidation mechanisms of the hydroquinones and
catechols. PA1sol ¼ GðHQ - Þsol þ GðHþ Þsol - GðH2 QÞsol
ðthe first proton dissociation energy in DMSOÞ ð5Þ
Computational Methods
All the calculations were conducted by using Gaussian 03
packages.23 The geometries of all species were fully optimized at
the B3LYP/6-31þG* level of theory without any constraints.
The optimized structures were confirmed to be real minima by
frequency calculation (no imaginary frequency). For the species
having more conformers, all conformers were investigated. The
conformer with the lowest electronic energy was used in this work.
Considering the large number of molecules and three parameters PA2g ¼ GðQ2 - Þg þ GðHþ Þg - GðHQ - Þg
that will be calculated, in this work, single-point energies were
estimated at B3LYP/6-311þþG (2df, p) level based on the B3LYP/ ðthe second proton dissociation energy in gas phaseÞ ð6Þ
6-31þG* geometry, corrected with the zero point energies and
thermal corrections. PA2sol ¼ GðQ2 - Þsol þ GðHþ Þsol - GðHQ - Þsol
To attain maximum accuracy of the solvation energy calcula- ðthe second proton dissociation energy in DMSOÞ ð7Þ
tions, herein we utilized the most recent version of the polarized
continuum model, that is IEF-PCM (integral equation formal-
ism PCM), at the B3LYP/6-31þG* level to calculate the solva-

(22) Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F; Stewart, J. J. P. J. Am.

Chem. Soc. 1985, 107, 3902.
(23) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci,
B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, BDE1g ¼ GðHQ• Þg þ GðH• Þg - GðH2 QÞg
T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.;
Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
ðthe first hydrogen dissociation energy in gas phaseÞ ð8Þ
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Ragha-
vachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; (24) (a) Fu, Y.; Shen, K.; Liu, L.; Guo, Q. X. J. Am. Chem. Soc. 2007, 129,
Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komar- 13510. (b) Qi, X. J.; Liu, L.; Fu, Y.; Guo, Q. X. Organometallics 2006, 25,
omi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; 5879. (c) Fu, Y.; Liu, L.; Yu, H. Z.; Wang, Y. M.; Guo, Q. X. J. Am. Chem.
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Soc. 2005, 127, 7227. (d) Fu, Y.; Liu, L.; Li, R. Q.; Liu, R.; Guo, Q. X. J. Am.
Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, revision C.01; Chem. Soc. 2004, 126, 814. (e) Fu, Y.; Wang, H. J.; Chong, S. S.; Guo, Q. X.;
Gaussian, Inc.: Wallingford, CT, 2004. Liu, L. J. Org. Chem. 2009, 74, 810.

7242 J. Org. Chem. Vol. 75, No. 21, 2010

Zhu et al.
JOC Article
SCHEME 2. Chemical Structures and Numbers of the Hydroquinones and Catechols

J. Org. Chem. Vol. 75, No. 21, 2010 7243

JOC Article Zhu et al.

BDE1sol ¼ GðHQ• Þsol þ GðH• Þsol - GðH2 QÞsol where ΔG12 in eqs 14, 16, and 18 denotes the Gibbs free energy
changes of the electron, proton and hydrogen atom interchange
ðthe first hydrogen dissociation energy in DMSOÞ ð9Þ in the gas-phase, respectively, while ΔG13 in eqs 15, 17, and 19
denotes the Gibbs free energy changes of the electron, proton
and hydrogen atom interchange in DMSO, respectively. F is the
Faraday constant equal to 23.06 kcal/(mol 3 V).

Results
The calculated solution phase oxidation potentials, the first
and second proton dissociation and hydrogen dissociation
BDE2g ¼ GðQÞg þ GðH• Þg - GðHQ• Þg energies (O-H) were summarized in Table 1. The corresponding
gas-phase energies were summarized in Supporting Information.
ðthe second hydrogen dissociation energy in gas phaseÞ ð10Þ
Discussion
BDE2sol ¼ GðQÞsol þ GðH• Þsol - GðHQ• Þsol 1. Reliability of the Calculated Results. It is well-known
ðthe second hydrogen dissociation energy in DMSOÞ ð11Þ that the electron, proton, and hydrogen atom transfer driving
forces of H2Q are very important thermodynamic parameters
Since it has been shown that DFT methods tend to system- for H2Q, which can be used as indicators of the mechanism
atically overestimate or underestimate chemical properties, and the analyses of the oxidation processes of H2Q. Examination of the
solvation energy of protons remains uncertain, we decided to past publications shows that much attention has been paid to
utilize three isodesmic reaction to improve the accuracy of the the determinations of these three thermodynamic parameters
calculation of the oxidation potentials, pKa values and bond of phenol series,15 very little research has hitherto been reported
dissociation energies of hydroquinones in DMSO, respectively, on the corresponding determinations of H2Q. Thus, it is
and phenol was chosen as a reference to construct, that is, electron, impossible to evaluate the reliability of the theoretical predic-
proton, and hydrogen atom interchange reaction (Scheme 3). tions by comparing some of the predicted values with the
According to the thermodynamic cycle shown in Scheme 3,
corresponding experimental data of H2Q. To solve this prob-
the ionization potentials, oxidation potentials, proton dissocia-
tion energies and bond dissociation energies can be obtained by lem, we hypothesized that a theoretical method must be able
eqs 14-19, respectively. to reliably handle H2Q series as long as the same method was
known to be successful for handling phenols. The scientific
IPðH2 QÞg ¼ IPðphenolÞg - ΔG12 ð14Þ basis of this hypothesis is that H2Q, actually, are special
substituted phenols.
E ox NHE ðH2 QÞ ¼ E ox NEH ðphenolÞ þ ΔG13 =F ð15Þ In Supporting Information (Table S1), we collected num-
bers of experimental and theoretical proton, electron and
hydrogen atom transfer driving forces of phenols. From
pKa ðH2 QÞg ¼ pKa ðphenolÞg þ ΔG12 =ð2:303RT Þ ð16Þ
Table S1, it is clear that the theoretical proton, electron
and hydrogen atom transfer thermodynamic driving forces
pKa ðH2 QÞsol ¼ pKa ðphenolÞsol þ ΔG13 =ð2:303RT Þ ð17Þ of phenols obtained in this work all are very close to the
corresponding previously reported experimental observa-
BDEg ¼ BDEðphenolÞg þ ΔG12 ð18Þ tions (MD = 0.29, 0.02, 0.58 and r = 0.98, 0.97, 0.98 for
proton, electron, and hydrogen atom transfer driving forces
BDEsol ¼ BDEðphenolÞsol þ ΔG13 ð19Þ of phenols, respectively), indicating that the theoretical

SCHEME 3. Thermodynamic Conversion from Gas Phase to the Solution Phase

7244 J. Org. Chem. Vol. 75, No. 21, 2010

Zhu et al.
JOC Article
TABLE 1. Solution Phase Oxidation Potentials (V), the First and Second Proton Dissociation (pKa), and Hydrogen Dissociation Energies (kcal/mol)
of the Hydroquinones and Catechols Calculated by IEFPCM//B3LYP/6-311þþG(2df,p)//B3LYP/6-31þG(d) Method
pKa1 pKa2 BDE1 BDE2
compound EoxNHE a b a b a b a b
1 1.607 19.1 25.2 83.4 69.4
2 1.138 18.1 18.3 24.5 24.3 75.5 81.6 69.0 62.8
3 1.188 16.8 19.7 25.4 22.5 72.4 79.0 69.7 63.1
4 1.400 20.0 18.0 24.2 26.3 84.0 81.7 65.0 67.2
5 1.472 15.5 18.5 24.9 21.9 78.1 82.9 70.3 65.5
6 1.579 16.3 17.5 15.5 14.3 79.8 84.1 70.8 66.5
7 1.543 18.3 18.0 25.4 25.7 81.5 82.3 68.1 67.3
8 1.638 15.4 17.9 25.6 23.1 81.8 83.9 70.7 68.5
9 1.724 15.7 17.2 24.1 22.6 82.9 84.4 70.9 69.4
10 1.730 14.5 18.2 21.4 25.0 84.7 83.1 68.8 70.4
11 1.730 16.5 16.9 22.7 22.3 83.3 84.6 71.2 70.0
12 1.823 15.8 19.2 23.2 19.8 88.6 89.9 73.7 72.3
13 1.780 17.3 17.3 24.4 24.4 87.6 85.7 72.4 74.3
14 1.914 13.7 16.5 23.8 21.0 83.2 86.5 72.5 69.3
15 1.966 11.5 16.0 23.3 18.8 83.7 87.3 74.3 70.8
16 1.850 18.3 24.7 81.8 69.3
17 1.473 18.1 27.2 80.3 65.9
18 1.859 15.8 20.5 83.7 70.0
19 1.820 15.1 21.4 84.0 69.5
20 2.537 9.3 15.4 87.9 74.7
21 1.699 17.3 26.3 78.4 65.5
22 1.431 18.5 26.1 80.8 65.9
23 1.818 15.8 21.0 83.4 69.8
24 1.837 14.6 21.4 84.3 69.8
25 2.504 9.8 17.5 87.0 73.9
26 1.619 21.5 19.1 24.8 27.2 85.2 84.3 59.0 59.9
27 1.445 19.0 18.4 25.6 26.2 80.0 82.4 66.7 64.3
28 1.551 9.5 11.4 21.9 19.9 74.9 78.5 72.0 68.3
29 1.851 13.0 15.9 20.0 22.8 86.0 82.5 68.0 71.5
30 2.507 6.8 13.7 21.2 14.3 85.3 90.5 77.2 72.0
31 1.663 19.3 19.1 22.7 23.0 82.2 83.6 62.1 60.7
32 1.339 17.8 20.4 28.1 25.5 81.0 79.6 62.7 64.1
33 1.963 12.8 14.3 20.0 18.5 82.7 84.4 70.6 68.9
34 1.923 13.3 12.6 20.0 19.3 85.1 83.1 68.5 70.5
35 2.798 4.4 7.1 14.0 11.4 88.5 90.4 77.1 75.1
36 1.823 16.8 25.7 79.8 64.9
37 1.294 20.0 27.8 78.9 61.9
38 2.086 12.1 17.5 83.6 69.9
39 1.995 11.5 18.1 84.1 69.1
40 2.897 2.0 9.35 91.2 77.9
41 2.040 16.1 20.8 92.1 84.9
42 1.181 11.7 19.0 21.8 14.5 72.5 77.8 72.5 67.1
43 0.970 12.8 15.3 70.8 61.1
44 1.114 11.7 19.5 22.1 14.3 72.1 77.2 70.2 65.1
45 1.076 10.4 18.9 22.4 13.8 70.0 76.9 71.8 64.9
46 1.148 18.9 24.6 76.7 64.2
47 1.824 14.6 27.6 83.3 76.5
48 1.963 15.8 15.9 27.5 27.4 83.1 86.0 73.3 70.5
49 1.995 15.1 14.6 28.5 29.0 81.8 82.7 76.2 75.2
50 1.982 13.3 16.6 24.9 21.5 82.8 86.7 77.7 73.8
51 2.204 12.1 13.1 26.3 25.3 82.9 84.5 77.4 75.8
52 2.124 8.3 10.9 24.8 22.2 82.9 84.4 78.6 77.2
53 1.472 14.3 14.7 26.0 25.6 79.8 77.7 71.7 73.8
54 1.663 14.8 15.0 27.5 27.2 82.1 80.8 74.7 75.9
55 1.816 13.8 15.1 26.8 25.5 82.9 82.0 75.6 76.4
56 1.855 13.0 13.6 26.4 25.9 83.9 83.0 76.2 77.1
57 2.163 11.9 10.3 23.5 25.1 86.8 86.7 79.9 79.9
58 1.454 15.6 16.3 26.9 26.1 83.4 81.8 71.5 73.0
59 1.701 15.9 15.5 27.7 28.1 82.0 81.5 74.5 75.0
60 1.977 11.8 13.8 25.2 23.2 82.8 83.3 76.8 76.3
61 1.952 10.9 12.3 25.5 24.1 83.1 83.9 76.9 76.1
62 2.471 5.1 6.2 19.9 18.8 86.5 87.7 82.4 81.3
63 1.341 17.7 15.7 25.5 27.5 78.8 84.8 70.0 64.0
64 1.605 15.6 14.9 28.5 29.2 81.0 81.9 74.4 73.5
65 1.980 13.2 12.7 24.1 24.6 81.7 84.8 77.8 74.7
66 1.971 11.0 11.4 24.3 23.9 82.3 84.9 78.1 75.5
67 2.444 4.2 8.1 21.9 18.1 86.2 87.6 81.7 80.3
68 1.399 16.9 27.9 85.0 70.4
69 1.712 14.4 30.2 80.6 75.2
70 2.151 11.9 23.3 84.0 77.4

J. Org. Chem. Vol. 75, No. 21, 2010 7245

JOC Article Zhu et al.

TABLE 1. Continued
pKa1 pKa2 BDE1 BDE2
ox
compound E NHE a b a b a b a b
71 2.127 10.6 23.7 84.0 76.9
72 2.423 5.5 18.7 85.5 79.4
73 1.247 15.6 24.0 82.1 60.1
74 1.515 15.0 27.0 80.0 74.4
75 1.844 13.9 25.4 82.1 75.2
76 1.898 12.1 24.7 83.7 77.4
77 2.483 7.8 21.0 89.7 82.5
78 1.300 14.4 14.9 27.8 27.3 83.1 79.5 70.6 74.1
79 1.499 15.0 15.3 30.6 30.4 80.1 78.7 73.3 74.8
80 2.131 10.7 11.9 22.9 21.7 84.6 82.9 76.1 77.7
81 2.086 9.5 9.9 23.0 22.7 84.3 83.3 76.2 77.1
82 2.748 2.4 1.2 14.1 15.3 88.8 88.6 82.7 82.9
83 1.254 15.6 15.6 26.5 26.5 80.9 82.6 65.4 63.7
84 1.455 15.4 14.0 28.5 29.9 78.8 79.3 74.1 73.6
85 2.004 11.8 12.6 25.1 24.4 81.7 83.6 76.8 74.9
86 2.003 10.2 11.1 24.9 24.0 83.1 84.9 78.1 76.3
87 2.769 1.5 3.7 17.5 15.3 89.3 90.4 84.8 83.8
88 1.400 13.2 28.3 78.6 69.3
89 1.458 15.0 31.9 78.6 73.6
90 2.168 10.5 24.4 83.2 76.5
91 2.106 9.0 24.4 83.9 77.1
92 3.050 -1.7 11.5 91.3 85.9
93 1.251 16.7 25.3 77.7 62.8
94 1.051 20.2 17.5 23.0 25.6 74.7 75.3 67.0 66.4
95 1.198 18.9 19.2 23.6 23.3 75.7 77.4 63.8 62.2
96 1.350 16.1 16.6 22.2 21.7 76.9 78.2 64.8 63.4
97 1.373 15.7 16.7 22.3 21.2 77.2 78.8 65.6 64.0
98 1.608 11.0 16.3 21.7 16.4 77.7 81.9 69.3 65.2
99 1.043 17.8 23.4 74.9 63.0
100 0.856 20.0 17.2 22.7 25.5 75.0 72.5 57.0 59.6
101 0.987 18.4 18.5 23.3 23.3 73.1 74.6 61.8 60.4
102 1.115 17.0 16.0 20.4 21.4 74.4 75.1 62.2 61.6
103 1.144 15.4 16.5 21.8 20.7 74.5 76.3 63.9 62.1
104 1.357 10.4 16.2 21.5 15.7 74.8 79.4 68.0 63.3
105 0.920 14.2 25.2 69.8 54.9
106 0.824 20.9 19.7 23.9 25.1 74.4 69.5 56.7 61.6
107 0.894 17.2 17.7 24.0 23.5 69.2 69.4 56.6 56.3
108 0.949 17.4 15.7 22.4 24.0 71.2 70.0 57.5 58.7
109 0.952 17.3 15.8 22.6 24.1 71.4 70.1 57.3 58.6
110 1.094 13.7 13.8 21.2 21.1 69.3 70.8 58.4 56.8
111 0.825 17.3 16.3 22.2 23.2 68.6 68.7 56.2 56.1
112 0.879 17.0 16.5 22.9 23.4 69.2 69.3 56.6 56.5
113 1.002 16.9 15.7 22.4 23.6 70.6 70.3 57.2 57.5
114 1.006 16.2 15.9 22.4 22.7 70.4 70.5 57.7 57.6
115 1.104 13.2 15.3 22.2 20.2 70.4 71.4 59.4 58.4
116 1.405 15.0 15.0 26.6 26.5 76.0 78.0 71.2 69.2
117 1.727 13.8 24.9 83.8 86.2
118 1.298 12.4 29.2 73.5 67.2

method used in this work can reach the experimental un- poor electron donors and most of 1,4-H2AQ and 9,10-H2AQ
certainties and the results from this method are very reliable. belong to strong electron donors. 1,4-H2NQ are due to
On the basis of these data we can discuss, for the first time, middle strong electron donors (Figure 1). Detailed examina-
some important yet unanswered questions concerning the tion of the calculated results indicate that the oxidation
structure-property relationships behind the proton, elec- potential scales of each series of H2Q are from 0.970 to 2.987 V
tron and hydrogen atom transfer driving forces of H2Q. for p-H2Q, from 1.247 to 3.050 V for o-H2Q, from 1.051 to
2. Oxidation Potentials Scale of Various Hydroquinones in 1.608 V for1,4-H2NQ, from 0.856 to 1.357 V for 1,4-H2AQ,
DMSO. From the second column in Table 1, it is clear that and from 0.824 to 1.104 V for 9,10-H2AQ, respectively. The
the oxidation potentials of the H2Q range from 0.824 V for one-electron oxidation potentials of o-H2Q are similar to those
106 to 3.050 V for 92. This large scale of oxidation potentials of corresponding phenols,15 and both of them are larger by
of H2Q indicates that these H2Q can construct a large and about 0.2 V than those of p-H2Q, which suggest that p-H2Q
useful library of organic reductants, which can provide have largest electron-donating abilities than those of corre-
several of electron donors one needs. Comparison of the sponding o-H2Q and phenols, which may be rationalized by
one-electron oxidation potentials of H2Q with those of some noting that the combination results from electron-donating
well-known organic one-electron donors, such as BNAH, effect of OH group and the intramolecular hydrogen bond (see
AcrH2 and XnH25 shows that most of p-H2Q and o-H2Q are Scheme 5).
Comparison of the one electron oxidation potentials of p-
(25) Cheng, J. P.; Lu, Y.; Zhu, X. Q.; Mu, L. J. Org. Chem. 1998, 63, 6108. H2Q, 1,4-H2NQ, and 1,4-H2AQ shows that the electron-donating
7246 J. Org. Chem. Vol. 75, No. 21, 2010
Zhu et al.
JOC Article

FIGURE 2. pKa scales of hydroquinones and catechols in DMSO.

FIGURE 1. Standard oxidation potentials scale of various hydro-

quinones in DMSO.

abilities of H2Q with the same substituents decrease in the

order p-H2Q>1,4-H2NQ>1,4-H2AQ, indicating that the
larger the aromatic system of the hydroquinone is, the smaller
the oxidation potential of the hydroquinone is. The main
factor causing this could be that the hydroquinone radical
cation with larger aromatic system could have larger stability
in thermodynamics, which makes the hydroquinone easier to
release the electron. The oxidation potentials of 9,10-H2AQ
are generally smaller than those of corresponding 1,4-H2AQ
by about 0.1 V, the reason for this small difference can be
explained by the fact that 9,10-H2AQ radical cation is more
stable than the corresponding 1,4-H2AQ. FIGURE 3. Bond dissociation energy scales of the O-H bonds in
hydroquinones and catechols in DMSO.
3. pKa Scale of Various Hydroquinones and Catechols in
DMSO. The propensity of a compound to donate or accept a the pKa values are between 5 and 15, such as 38, 45, 52, and
proton, measured by its acidity or basicity, is fundamental to so on. These hydroquinones are due to middle strong organic
understanding many chemical and biochemical processes.26 acid. The third category is that the pKa values are between 15
In the past decades, considerable efforts have been devoted and 18, such as 13, 36, 93, and so on, and they are due to
to the determination of the pKa values of phenols by using normal organic acid. The forth categories is the pKa values
experimental methods.27,28 However, since the similarity of are between 18 and 31, such as 31, 42 anion, 106, and so on.
the two hydrogen atoms in hydroquinones, the pKa values of In this category, the hydroquinones are due to weak organic
the hydroquinones have not been released in the literature acid. The last categories is that the pKa values are larger than
until now. By using theoretical methods developed in this paper, 31, such as 79 anion, 89 anion, and so on. These hydro-
the systematical calculations of these values were done for the quinones are due to very weak organic acid. In one world,
first time and the results were summarized in Table 1. most of the hydroquinones are strong or middle strong
From Table 1, it is clear that the pKa1 values of the organic acid. However, Figure 2 shows that the pKa2 values
hydroquinones in DMSO range from 2 to 21.5 for hydro- of HQ- in DMSO are relatively high, which indicates that the
quinones, from -1.7 to 17.7 for catechols, and the pKa2 acidities of these anions are very weak.
values range from 9.4 to 28.1 for hydroquinone anion and 4. BDE Scales of Various Hydroquinones and Catechols in
from 11.5 to 31.9 for catechols anions. Since CF3COOH, DMSO. To the best of our knowledge, the calculations of the
CH3COOH, PhOH, and H2O are well-known organic strong hydrogen releasing abilities of various hydroquinones
acid, middle strong acid, weak acid, and very weak acid in and catechols are very important since most of literatures
DMSO, respectively,29 the hydroquinones and catechols can support that the most likely oxidation process from
be divided into five categories according to the pKa values of hydroquinone to quinone is direct hydrogen atom transfer
these molecules. The first category is that the pKa values are and large numbers of hydroquinones are antioxidants and
less than 5, such as 35, 82, 92, and so on. These hydroqui- the bond dissociation energy of the O-H bond is an
nones are strong organic acid. The second category is that important parameter in determing the antioxidant activi-
ty. However, little attention has been paid to the bond
(26) Bell, R. P. The Proton in Chemistry; Chapman and Hall: London, 1973. dissociation energies of the two O-H bonds in hydroqui-
(27) Albert, A.; Serjeant, E. P. The Determination of Ionization Constants;
Chapman and Hall: New York, 1984.
nones and catechols. In the present study, we bridged this
(28) (a) Fu, Y.; Liu, L.; Li, R. Q.; Liu, R.; Guo, Q. X. J. Am. Chem. Soc. gap and the detailed calculation results were summarized
2004, 126, 814. (b) Fu, Y.; Shen, K.; Liu, L.; Guo, Q. X. J. Am. Chem. Soc. in Table 1.
2007, 129, 13510.
(29) Fu, Y.; Liu, L.; Li, R. Q.; Liu, R.; Guo, Q. X. J. Am. Chem. Soc. 2004, Our calculated energies changed from 70 to 92.1 kcal/mol
126, 814. for the BDE1 of hydroquinones, from 77.7 to 91.3 kcal/mol
J. Org. Chem. Vol. 75, No. 21, 2010 7247
JOC Article Zhu et al.

for the BDE1 of catechols, from 59 to 84.9 kcal/mol for the but also suggesting that the concerted effects of the multiple
BDE2 of hydroquinones, and from 60 to 86 kcal/mol for the substituents have good linear additivity on the oxidation
BDE2 of catechols, which suggest that the hydrogen donat- potentials and proton and hydrogen atom releasing Gibbs
ing abilities of the hydroquinones decrease in the following free energy changes. From the slopes and the intercepts of the
order: p-HQ• ≈ o-HQ• >p-H2Q ≈ o-H2Q. The small differ- ten straight lines, the corresponding ten mathematical for-
ence the hydrogen donor abilities between hydroquinone mulas can be easily derived, respectively. Evidently, for any
and catechol will be discussed in the following part. Calcula- one- or multisubstituted hydroquinones or catechols, it is not
tions have shown that in catechol, the two hydroxyl groups difficult to safely estimate the values of the corresponding
afford almost identical to the experiment BDE of 81.83 oxidation potentials, proton, and hydrogen dissociation
kcal/mol. We consider here that there is only one BDE value energies, as long as the corresponding Hammett substituent
for catechol, regardless of which O-H bond is broken in the parameters σp are available. Since the family of the hydro-
parent molecule. This is because the radical is allowed to quinones and catechols are very large and most of the
rearrange, at room temperature, affording the most stable Hammett substituent parameters are easily obtained from
toward conformer. literature, it is evidently that the ten formulas should have
Most of the BDEs of these hydroquinones and catecholes very extensive applications in the prediction of the related
are lower than that of phenol, suggesting that most of these thermodynamic driving forces of various hydroquinones to
compounds are good antioxidants. In order to get a detailed provide electron, proton and hydrogen atom.
knowledge of the antioxidant activity of the hydroquinones
and catecholes, we conducted a comparison of the bond dis- p-H2Q
sociation energies of various antioxidants, including coenzyme X
Q, flavonoids, olives, curcumins, indolinonic hydroxylamines, E ox NHE ðH2 Q•þ =H2 QÞ ¼ 1:66 σp þ 0:54 ð20Þ
phenothiazines, edaravones and antioxidants used as food X
additives which were listed in Table 2. pKa1 ¼ - 5:69 σp þ 16:54 ð21Þ
If the bond dissociation energies of hydroquinones were
X
compared with those of various antioxidants listed in Table 2, pKa2 ¼ - 5:19 σp þ 23:91 ð22Þ
the following suggestions can be offered: (1) The hydrogen
donating abilities of all the HQ• are not only smaller than X
those of phenothiazine (N-H) and edaravone (C-H) but BDE1 ¼ 3:43 σ p þ 82:29 ð23Þ
also smaller than those of flavonoids, olives, curcumins, X
indolinonic hydroxylamines, and so on (O-H). They are BDE2 ¼ 4:64 σ p þ 67:70 ð24Þ
always very good hydrogen donors. (2) More hydroxyl groups
on the ring will significantly decrease the O-H BDEs, which o-H2Q
holds consistence with experimental observations, the reason X
could be that the intramolecular hydrogen bond adds the E ox NHE ðH2 Q•þ =H2 QÞ ¼ 1:85 σp þ 0:46 ð25Þ
coplanatity of all the ring, which increase the antioxidant X
reactivity. (3) Different substituents have little effect on the pKa1 ¼ - 5:53 σp þ 13:28 ð26Þ
O-H BDEs in flavonide, olive, and edaravone but have large
X
effect on those of hydroquinones, indicating that various pKa2 ¼ - 5:24 σp þ 26:70 ð27Þ
organic reducing hydroquinones agents can be obtained by
only change the substituents on the hydroquinone rings. X
Substituted hydroquinones can construct a large and useful BDE1 ¼ 3:54 σ p þ 82:08 ð28Þ
library of dynthetic antioxidants. (4) Electron-donating X
groups decrease the BDE values, while electron-withdrawing BDE2 ¼ 3:82 σ p þ 75:93 ð29Þ
groups make hydrogen abstraction more energetically de-
manding, which is in accordance with experimental observa-
tion of phenols. Equations 23, 24, 28, and 29 show that all the correlation
5. Substituent Effects. From Table 1, it is clear that the slopes are positive, suggesting electron-donating groups de-
oxidation potentials, the Gibbs free energies of H2Q and HQ crease the hydrogen atom releasing energies and increase the
to release proton and hydrogen atoms are strongly depen- hydrogen atom donating abilities. However, electron-with-
dent on the nature of the substituents. To elucidate the drawing groups show the opposite effect. This is in accor-
relations of the nature of the substituents with the oxidation dance with the former experimental observation of the
potentials and the proton and hydrogen atom releasing substituent effects on the bond dissociation energies of the
Gibbs free energies, the effects of the remote substituents O-H bonds in phenols. These positive slopes also indicate
were examined on the EoxNHE(H2Q•þ/H2Q), pKa1, pK a2, that electron-donating groups decrease the bond disso-
BDE1, and BDE2, and the results show that the EoxNHE- ciation energies and electron-withdrawing groups decrease
(H2Q•þ/H2Q), pK a1, pKa2, BDE1, and BDE2 of the ten the proton dissociation energies, which suggest that more
chemical and electrochemical processes (five for hydro- electron-donating groups should be added if we need an
quinones and five for catechols) all are linearly depen- antioxidant and more electron-withdrawing groups should
dent on the sum of Hammett substituent parameters σp be added if we need a strong acid. Concerning the hydro-
with very good correlation coefficients, which not only quinone reduction mechanism, we can predict that the
indicating that the Hammett linear free energy relationship all hydroquinones with more electron-donating groups may
holds in the ten electrochemical and chemical processes proceed direct hydrogen atom transfer and those with more
7248 J. Org. Chem. Vol. 75, No. 21, 2010
Zhu et al.
JOC Article
TABLE 2. O-H Bond Dissociation Energies of Various Antioxidants (kcal/mol)

a
86.1 for weaker phenolic OH group (left side on drawing), 86.6 for the stronger.

J. Org. Chem. Vol. 75, No. 21, 2010 7249

JOC Article Zhu et al.

SCHEME 4. Possible Pathways of the Conversion of Hydroquinones to Hydroquinone Radicals

electron-withdrawing groups may proceed proton dissociation following thermodynamic cycle. Combined with some other
and then electron transfer mechanisms. thermodynamic cycles (see Supporting Information), eqs
Equations 23, 24, 28, and 29 also show that the correlation 30-32 were derived.
intercept between BDE and σp are similar for hydroquinoes
and catechols, indicating that with the same groups, hydro- E ox NHE ðHQ - =HQ• Þ ¼ ðBDE1 - 2:303RT p Ka1 Þ=
quinoes have similar hydrogen atom donating abilities to the F þ E ox NHE ðHþ =H• Þ ð30Þ
corresponding catechols. Because of the electronic repulsion
effect, hydroquinone radicals have larger hydrogen atom pKa ðH2 Q•þ Þ ¼ fBDE1 - F½E ox NHE ðH2 Q=H2 Q•þ Þ
donating abilities than those of corresponding catechol radicals.
- E ox NHE ðHþ =H• Þg=ð2:303RTÞ ð31Þ
Furthermore, hydroquinone radicals or catechol radicals
have smaller hydrogen atom releasing energies than those
ΔGðH2 Q=QÞ ¼ BDE1 þ BDE2 - 2ΔG0 f ðH• Þ ð32Þ
of corresponding hydroquinone or catechol, not only indicat-
ing radicals have samller hydrogen atom donating abilities According to these three equations, linear correlations
than those of corresponding hydroquinones, but also suggest- between oxidation potentials of hydroquinone anions, pKa
ing that the reactions of hydroquinone radicals would usually values of hydroquinone radical caitons, and the hydrogen
associate with the releasion of the hydrogen atoms. energies of quinines against the Hammett substituent σp were
As stated in the Introduction section, the hydrogen atom summarized in eqs 33-38.
transfer from the H2Q generally were initiated by single electron
transfer, an incipient radical cation intermediate H2Q•þ should p-H2Q
be formed, from which proton transfer is believed to follow X
in the second reaction step, or initiated by proton transfer E ox NHE ðHQ - =HQ• Þ ¼ 0:49 σp þ 0:11 ð33Þ
from which electron transfer is believed to follow in the X
second reaction step. The proton dissociation energies of pKa ðH2Q•þ Þ ¼ - 25:58 σ p þ 9:27 ð34Þ
hydroquinone radical cations or the oxidation potentials of
hydroquinone anions can be obtained according to the X
ΔGðH2 Q=QÞ ¼ 8:07 σp þ 44:79 ð35Þ
(30) (a) Espinosa-Garcia, J. J. Am. Chem. Soc. 2004, 126, 920. (b) o-H2Q
Espinosa-Garcia, J. J. Phys. Chem. A. 2004, 108, 2508. (c) Aberg, F.;
Appelkvist, E. L.; Dallner, G.; Ernter, L. Arch. Biochem. Biophys. 1992,
X
295, 230. E ox NHE ðHQ - =HQ• Þ ¼ 0:48 σp þ 0:29 ð36Þ
(31) Li, M. J.; Liu, L.; Fu, Y.; Guo, Q. X. J. Mol. Struct.(THEOCHEM)
2007, 815, 1. X
(32) Leopoldini, M.; Marino, T.; Russo, N.; Toscano, M. J. Phys. Chem. pKa ðH2 Q•þ Þ ¼ - 28:72 σp þ 10:48 ð37Þ
A 2004, 108, 92.
(33) Menadis, N.; Wang, L. F.; Tsimidou, M. Z.; Zhang, H. Y. J. Agric. X
Food. Chem. 2005, 53, 295.
(34) Sun, Y. M.; Zhang, H. Y.; Chen, D. Z.; Liu, C. B. Org. Lett. 2002, 4, ΔGðH2 Q=QÞ ¼ 7:36 σp þ 52:81 ð38Þ
2909.
(35) Wright, J. S. J. Mol. Struct.(THEOCHEM) 2002, 591, 207. According to these equations, EoxNHE(HQ-/HQ•), pKa(H2Q•þ),
(36) Zhang, H. Y.; Wang, L. F. Bioorg. Med. Chem. Lett. 2002, 12, 225.
(37) Wright, J. S.; Johnson, E. R.; Di Labio, G. A. J. Am. Chem. Soc. and ΔG(H2Q/Q) can be easily estimated by only knowing the
2001, 123, 1173. structures of the hydroquinones (hydroquinones, catechols,
(38) Lucarini, M.; Pedrielli, P.; Pedulli, G. F.; Valgimili, L.; Gigmes, D.; and the substituents attached on them).
Tordo, P. J. Am. Chem. Soc. 1999, 121, 11546.
(39) Pratt, D. A.; Dilabio, G. A.; Valgimigli, L.; Pedulli, G. F.; Pedulli, 6. Difference between Hydroquinones and Catechols. Ac-
G. F.; Ingold, K. U. J. Am. Chem. Soc. 2002, 124, 11085. cording to our earlier discussion, we know that hydroqui-
(40) Bordwell, F. G.; Zhang, X. M.; Cheng, J. P. J. Org. Chem. 1993, 58,
6410.
none is a stronger electron donor than catechol. The main
(41) Gomes, J. R. B.; Ribeiro da Silva, M. D. M. C.; Ribeiro da Silva, reason could be that the state free energies of hydroquinone
M. A. V. J. Phem. Chem. A 2004, 108, 2119. and catechol, as well as hydroquinone radical cation and
(42) MacFaul, P. A.; Wayner, D. D. M.; Ingold, K. U. J. Org. Chem.
1993, 58, 6410. catechol radical cation could be different from each other
(43) Wang, L. F.; Zhang, H. Y. Bioorg. Med. Chem. Lett. 2003, 13, 3789. (Figure 4). From Figure 4, it is clear that the state free energy
7250 J. Org. Chem. Vol. 75, No. 21, 2010
Zhu et al.
JOC Article

FIGURE 4. Difference of oxidation potentials between hydroqui-

none and catechol calculated by theoretical methods.

FIGURE 6. Difference of hydrogen dissociation energies between

hydroquinone and catechol calculated by theoretical methods.

none dianion in the gas phase. However, the case is reversed in

DMSO since the solvation effects on the catechol dianion is
much larger than that on the corresponds hydroquinone
dianion, which makes the catechol dianion more stable than
hydroquinone dianion in DMSO (Figure 5).
Equations 21, 22, 26, and 27 show that the four linear
correlations have similar slopes (-5.2 to -5.7), suggesting
that the substituents have similar effects on the proton
releasing energies of hydroquinoes, catecholes as well as
corresponding anions. Electron-donating groups increase
FIGURE 5. Difference of proton dissociation energies between the proton dissociation energies and decrease the proton
hydroquinone and catechol in DMSO. donating abilities, whereas electron-withdrawing groups
show the reverse effect. However, the correlation intercepts
of hydroquinone is very similar to that of catechol. However, are different from each other. The intercepts of the correla-
the state free energy of catechol radical cation is much larger tion between pKa1 values against σp of hydroquinones are
than that of hydroquinone radical cation, the reason could generally smaller than that of the correlation between pKa2
be that the intramolecular hydrogen bond is very weak in values against σp of correspond anions by about 7.4, suggesting
catechol radical cation, whereas the electronic repulsion hydroquinone anions are more difficult to release the pro-
effect is similar to that of catechol. Evidently, combination tons than corresponding hydroquinones, the reason could be
of the two factors mentioned above makes the oxidation that oxygen anion is, in fact, an strong electron-donating
potential of hydroquinone is much smaller than that of groups. The difference of the intercept of the correlations,
catechol. pKa1 vs σp and pKa2 vs σp, for catechols follows the similar
Equations 20 and 25 show catecholes have larger oxida- trends. Because of the intramolecular hydrogen bond, the
tion potentials (more positive) than hydroquinones when the pKa1 values of hydroquinones are generally larger than those
same substituents attached on them. The line slopes of of catechols and the cases are reversed in the order of the
EoxNHE against σp are 1.66 and 1.85 for hydroquinones pKa2 values of hydroquinone anions and catechol anions.
and catechols, respectively. The positive slopes of the two Concerning the bond dissociation energies, Table 1 indi-
regressions indicate that the oxidation of the hydroquinones cates that hydroquinone and catechol have very similar bond
would be mainly dependent on the stabilities of the corre- dissociation energies. The reason could be that the state free
sponding radical cations. By comparing the magnitude of the energies of hydroquinone and catechol as well as corre-
line slopes for hydroquinones and catechols, it is found that sponding neutral radicals are similar to each other, respec-
the effect of the substituents in the case of catechols is slightly tively. However, the hydrogen atom releasing ability of
larger than that in the case of hydroquinones, the reason hydroquinone radical is much larger than that of catechol
could be that the delocalization of the positive charge on radical, suggesting that hydroquinone radical is a better
hydroquinones is much delocalized than those of catechols. hydrogen atom donor than catechol radical. This can be
Table 1 also indicates that the proton dissociation energy of attributed to the fact that the state free energy of o-quinone is
catechol is smaller by about 6.2 kcal/mol than that of hydro- higher than that of p-quinone (Figure 6).
quinone, the reason could be the existence of the intramole- 7. Hydrogen Bond Effects. From the above discussion, it is
cular hydrogen bond in catechol anion. However, hydroqui- not difficult to conclude that the oxidation potentials be-
none anion has smaller proton releasing energy than that of tween hydroquinones and catechols with the same substitu-
catechol anion by about 3.3 kcal/mol, which indicates that ents are similar to each other, whereas the pKa values and
catechol dianion is more stable than that of hydroquinone hydrogen dissociation energies are different from each other.
dianion by about 3.1 kcal/mol. In fact, because of the electro- The main reason could be the existence of the intramolecular
static repulsion effect occurs between the two oxygen anions in hydrogen bonds in catechols. In fact, the cooperativity of
catechol, catechol dianion is more unstable than hydroqui- hydrogen bond plays an important role in controlling and
J. Org. Chem. Vol. 75, No. 21, 2010 7251
JOC Article Zhu et al.

SCHEME 5. Hydrogen Bonds of the Interesting Compounds

FIGURE 7. Relative hydrogen bond energies (Gibbs free energies),

with respect to the most stable neutral, radical cation, radical, and
anion conformers of 47 in DMSO.
TABLE 3. Intramolecular Hydrogen Bond Energies (Gibbs Free
Energies) of Neutral, Radical Cation, Radical, and Anion Species
hydrogen bond energies in DMSO (kcal/mol)
compounds neutral radical cation radical anion
47 -0.68 -0.29 -2.37 -4.94
116 -0.71 -1.46 a: -2.65 a: -3.45
b: -4.93 b: -3.70
117 -0.95 -0.53 -2.25 -4.44
118 -1.51 -1.57 -3.90
42 -6.17 -5.61 -7.91 -8.14
41 (first) -6.57 -5.97
41 (second) -3.52 -2.45 -8.01 -13.21
43 (first) -3.67 -3.08 -8.64 -12.72
43 (second) -4.03 -3.20 -2.94 -2.84

regulating the processes occurring in living organisms. Many

physical and chemical properties of materials are determined
by hydrogen bonding cooperativity.44 However, despite the
great importance of the intramolecular hydrogen bonds, FIGURE 8. Hydrogen bond energies (Gibbs free energies) of hydr-
only a few experimental and theoretical studies dealing with quinones and catechols with different charge and spin densities in
the estimation of their intramolecular hydrogen bond DMSO.
enthalpies.45 Furthermore, although the vast majority of
the computed intramolecular hydrogen bond energies deter- In this connection, we take some compounds, 47, 116, 117,
mined in the literature refer to gas-phase reactions, most of 118, 41, 42, and 43, which have classical intramolecular
the chemistry to which they are applied occurs in solution. In hydrogen bonds, as examples (Scheme 5). Intramolecular
the present study, we have a unique opportunity to bridge the hydrogen bond energies of these species in neutral, radical
gap to reliably investigate the intramolecular hydrogen bond cation, radical, and anion conformers, which were calculated
in neutral, radical cation, radical and anion species in by comparing the Gibbs free energies at 298 K for the
DMSO. Undoubtedly, these results would be very useful in intramolecular hydrogen conformer and the lowest energy,
material chemistry and physical chemistry. fully optimized conformer, in which the hydroxyl group is
pointing away from the other hydroxyl, were summarized in
(44) Steiner, T. Angrew. Chem. Int. Ed. 2002, 41, 48 and references Table 3.46 To illustrate the intramolecular hydrogen bond
therein.
(45) (a) Lampert, H.; Mikenda, W.; Karpfen, A. J. Phys. Chem. 1996, more clearly, the detailed conformations of neutral, radical
100, 7418. (b) Catal

an, J.; Palomar, J.; De Paz, J. L. G. J. Phys. Chem. A 1997, cation, radical and anion of compound 47 were listed in
101, 7914. (c) Chung, G.; Kwon, O.; Kwon, Y. J. Phys. Chem. A 1997, 101, Figure 7.
9415. (d) Levy, J. B.; Martin, N. H.; Hargittai, I.; Hargittai, M. J. Phys.
Chem. A 1998, 102, 274. (e) Kov
acs, A.; Hargittai, M. J. Phys. Chem. A 1998, Examination of the calculated results summarized in
102, 3415. (f) Simperler, A.; Lampert, H.; Mikenda, W. J. Mol. Struct. 1998, Table 3, the following conclusions can be made:
448, 191. (g) Kov
acs, A.; Macs
ari, I.; Hargittai, M. J. Phys. Chem. A 1999, (1) The strongest intramolecular hydrogen bond is in
103, 3110. (h) Cuma, M.; Scheiner, S.; Kar, T. J. Mol. Struct. (THEO-
CHEM) 1999, 467, 37. (i) Palomar, J.; De Paz, J. L. G.; Catal
an, J. J. Phys. anion state of compound 41 (32.7 kcal/mol in the
Chem. A 2000, 104, 6453. (j) Broquier, M.; Lahmani, F.; Zehnacker-Rentien,
A.; Brenner, V.; Milli
e, Ph.; Peremans, A. J. Phys. Chem. A 2001, 105, 6841.
(k) Rozas, I.; Alkorta, I.; Elguero, J. J. Phys. Chem. A 2001, 105, 10462. (46) Lithoxoidou, A. T.; Bakalbassis, E. G. J. Phys. Chem. A. 2005, 109,
(l) Korth, H.-G.; de Heer, M. I.; Mulder, P. J. J. Phys. Chem. A 2002, 106, 366.
8779. (m) de Heer, M. I.; Korth, H.-G.; Mulder, P. J. Org. Chem. 1999, 64, (47) Del Bene, J. E.; Frisch, M. J.; Pople, J. A. J. Phys. Chem. 1988, 89,
6969. 3669.

7252 J. Org. Chem. Vol. 75, No. 21, 2010

Zhu et al.
JOC Article
gas-phase and 13.2 kcal/mol in DMSO), similar to the SCHEME 6. Shift Energy and Hydrogen Bond Energy
intermolecular hydrogen bond [H2O-H-OH2]þ (33
kcal/mol in the gas-phase).47 The weakest intramolec-
ular hydrogen bond is in neutral state of compound
117 (4.0 kcal/mol in the gas-phase and 0.40 kcal/mol in
DMSO). Such a large scale of hydrogen bond energies
shows that the strength of the intramolecular hodro-
gen bonds are different so much between hydroqui-
nones and catechols. In this sense, we should also be
cautious with the gas-phase hydrogen bond energies
since hydrogen bonds are always influenced by their
environment.
(2) Concerning the same molecule, one may conclude that
the hydrogen bond energies in different charge and
spin states are in the order of anion > radical >
radical cation ≈ neutral, not only indicates that the
hydrogen bonds in anion and radical state are all membered rings. For example, the O-H 3 3 3 O bond
red-shifting hydrogen bonds48 but also suggests that lengths in 41, 42, 43 radicals are1.63, 1.68, 1.63 Å,
larger polarity of the molecule corresponding to larger respectively, smaller by about 0.3-0.4 Å than those in
intramolecular hydrogen bond. Because of the oppo- 116, 117, 118 radicals (they are 2.02, 2.06, 2.00 Å,
site orientation of the electronic properties of the respectively). The stronger intramolecular hydrogen
molecules and the solvation effects in determining bonds also result in the more stability of the com-
the solution phase molecular properties, we can expect pound. Based on this fact, it is reasonable to predict
that intramolecular hydrogen bond will be smaller in that the proton and hydrogen atom releasing process
more polar/protic solvent. This prediction agrees well from the proton acceptor oxygen atom will be more
with the experimental observations. The hydrogen easily from the six membered rings than those from the
bond energies in anions are larger than those in five member rings, in both of which there are intra-
corresponding radicals, and much larger than that in molecular hydrogen bonds. From Table 1, it is clear
neutral species, which can be traced by examining the that the bond dissociation energies of the O-H bonds
charge densities of the proton acceptor oxygen atom are 72.5 and 70.8 kcal/mol in 42 and 43, respectively,
(O-H 3 3 3 O) from natural population analysis. For whereas those in 116 and 117 are 76.0 and 83.3 kcal/mol,
instance, the charge densities of the proton acceptor respectively. These calculated results agree well with
oxygen atom is -0.8157, -0.5609, and -0.221 for our predictions.
anion, radical, and neutral catechol, respectively. The (4) The intramolecular hydrogen bond Gibbs free energies
more negative charge densities the proton acceptor of catechol and of corresponding radical are 0.7 and 1.4
oxygen atom has, the larger the hydrogen bond is. kcal/mol, respectively, whereas corresponding intramo-
Interestingly, the intramolecular hydrogen bonds in lecular hydrogen bond enthalpies are 2.5 and 3.5 kcal/
radical cation are similar to those of corresponding mol, respectively,49 suggesting the entropic contribution
neutral state species. For example, the intramolecular to the hydrogen bond Gibbs free energies are very
hydrogen bonds for radical cation and neutral state small. This is easily understandable by considering that
catechol are 1.42 and 0.68 kcal/mol, respectively. This there is only one hydrogen atom changed from one place
result should be attributed to the large solvation to another. However, intermolecular hydrogen bond
energies of the radical cation species. In fact, due to usually associated with large entropic changes.
the more negative charge densities of the proton (5) From the above discussion, it is clear that the catechol
acceptors (-0.221 vs -0.0846) and smaller bond is more stable than hydroquinone by about 0.25 kcal/
length of the O-H 3 3 3 O in neutral species than those mol, while the intramolecular hydrogen bond in cat-
in radical cation state(2.15 vs 2.17 Å), the intramolec- echol is 0.68 kcal/mol, it is conceived to estimate the
ular hydrogen bonds in neutral state are larger than shift energy of the hydroxyl bond from position 4
those in corresponding radical cation state in the gas- to the position 2 is 0.43 kcal/mol. The shift of
phase. the hydroxyl bond is an endothermic process since
(3) In view of the intramolecular hydrogen bond in 47, the repulsion of the σ-electron-donating group. If the
117, 118, 119 and 41, 42, 43, it is not difficult to find reaction is the isomeric conversion from hydroqui-
that the hydrogen bond energies in the former series none to catechol (Scheme 6), we can estimate that
are smaller than those in the latter series, indicating isomer II may be one of the intermediates. The
the intramolecular hydrogen bond in five membered hydroxyl group first departs from position 4 to form
rings are weaker than those in the six-membered rings, intermediates II (endothermic), which then produce
the reason could be that the O-H 3 3 3 O bond lengths the final product catechol because of the intramolec-
in six membered rings are smaller than those in five ular hydrogen bond (exothermic).By using similar
process, it is not difficult to predict the shift energies
(48) (a) Li, Q.; An, X.; Gong, B.; Cheng, J. J. Phys. Chem. A 2007, 111,
10166. (b) Klein, R. A. Chem. Phys. Lett. 2006, 433, 165. (c) Ziokowski, M.; (49) (a) Schaefer, T. J. Phys. Chem. 1975, 79, 1888. (b) Kollman, P.; Allen,
Grabowski, S. J.; Leszczynski, J. J. Phys. Chem. A 2006, 110, 6514. L. C. J. Am. Chem. Soc. 1971, 93, 4991.

J. Org. Chem. Vol. 75, No. 21, 2010 7253

JOC Article Zhu et al.

TABLE 4. NICS(1) Values of Compound 116, 117, and 118

SCHEME 7. Intramolecular Hydrogen Bonds in 116 Radical SCHEME 8. First and the Second Hydrogen Bond of Compound 41

intramolecular hydrogen bonds by experimental

methods at present.
(7) Examination of Table 3 also shows that there are two
intramolecular hydrogen bonds for compound 41 and
43 (Scheme 8). Contrary to the observation that the
first hydrogen bond becomes stronger with the in-
creasing of the polarity of the molecule, the second
of the hydroxyl bond in 93 is 0.1 kcal/mol. According hydrogen bond follows the opposite trend. For example,
to these results, we can rationalize that the shift the second hydrogen bond is 4.16 kcal/mol in neutral
energies of 99 and the hydrogen bond energies of the 43, larger than that in radical cation 43 by about
corresponding isomers of 99 will be smaller. In other 0.8 kcal/mol and much larger than that in radical 43
words, with the increasing of the aromaticity of the by about 0.95 kcal/mol. However, the differences of
system, the isomer energies between hydroquinones the hydrogen bond energies are very small between the
and corresponding catechols will become smaller and radical cation state and radical state, as well as in
smaller. On the basis of this conclusion, it is rationale anion state of compound 43, indicating that the charge
to predict that anthracene-1,4-diol and corresponding densities and spin densities of the molecule have little
anthracene-1,2-diol could not be separated by con- effect on the second hydrogen bond energies. Based on
ventional experimental methods. this conclusion, it is not difficult to estimate that
(6) For radical and anion species of compound 116, there solvation will have little effect on the second hydrogen
are two possible isomers a and b (Scheme 7). Accord- bond energies. If there are three or more hydrogen
ing to our calculated results (take the radical state as bonds in the same molecule, the third hydrogen bond
an example), the intramolecular hydrogen bond in energies in radical cation, radical, as well as anion,
isomer a is 2.7 kcal/mol, smaller by about 1.0 kcal/mol state of the molecule will be closer to each other and
than that in b, the reason could be that the state free smaller than 4 kcal/mol.
energies of radical isomers a and b, as well as isomers a0
and b0 , in which the hydroxyl group is pointing away 8. Phenyl Ring Effect. To the best of our knowledge,
from the oxygen atom are different from each other. hydroquinones and their phenyl ring substituted series occupy
Isomer a is more stable than isomer b by about 2.0 a central place in electron transfer chemistry and biological
kcal/mol because of the lower spin densities of the energy conversion. For example, menaquinone, or vitamin
proton acceptor oxygen radical (0.2667 and 0.2845 for K2, is made up of a 1,4-naphthoquinone headgroup with a
a and b, respectively). In addition, because of the large methyl substituent at the 2 position and an isoprenoid chain
repulsion effect between the hydrogen atoms (Hm and of varying length at the 3 position. Some forms of vitamin K
Hn) exist in b0 , which does not exist in a0 , isomer a0 is are known to be critical in the blood-clotting cascade and in
more stable than b0 by about 3.0 kcal/mol. Evidently, calcium momeostasis, and the Rieske FeS center in certain
combination of the two factors mentioned above baceria uses a menaquinone pool, rather than plastoquinone
makes the hydrogen bond energies in a is smaller by or ubiquinone. Various properties of these molecules, such as
1.0 kcal/mol than that in b. However, the difference of their fundamental vibrational frequencies and their hyper-
the intramolecular hydrogen bond between a and b is fine interactions, are used to infer information such as
only a theoretical estimation result, we may not binding sites and protein interaction in the photosynthetic
separate these two isomers and their corresponding reaction center. However, a knowledge of thermodynamic
7254 J. Org. Chem. Vol. 75, No. 21, 2010
Zhu et al.
JOC Article

FIGURE 9. Relationship of oxidation potentials of aromatic hy-

droquinones in DMSO with the number of benzene rings in the FIGURE 10. Relationship of proton dissociation energies of aro-
aromatic hydroquinones. matic hydroquinones in DMSO with the number of benzene rings in
the aromatic hydroquinones.
properties, such as oxidation potentials, proton and hydro-
gen atom releasing energies are still unreleased in the litera-
ture until now.
Detailed thermodynamic parameters of substituted hy-
droquinone-naphthoquinones and hydro-anthraquinones
were listed in Table 1, and their scales and substituent effects
have been discussed in detail in the former part. In this
connection, we mainly examine the phenyl ring effects on the
oxidation potential, proton and hydrogen atom releasing
energies of hydroquinone, hydro-naphthoquinone and hydro-
anthraquinone.
By examining the oxidation potentials of hydroquinones
with aromatic structures (hydroquinones 1, 93, and 105 and
catechols 47, 117, and 118) in Table 1, it is found that the
oxidation potentials of the hydroquinones decrease in the
order of 1>93>105, and the oxidation potentials of catechols
decreased in the order 47>117>118, which indicates that
the larger the aromatic system of the hydroquinone is, the FIGURE 11. Relationship of hydrogen atom releasing energies of
smaller the oxidation potential of the hydroquinone is. The aromatic hydroquinones in DMSO with the number of benzene
rings in the aromatic hydroquinones.
main reason causing this could be that the odd electron can
delocalized in the three phenyl rings in hydro-anthraquinone
radical cation whereas it only delocalized in one phenyl ring effects on the proton releasing process, the main reason
in hydroquinone. When the oxidation potentials of hydro- causing this could be that the hydroquinones with larger
quinones (1, 93, and 105) and catecholes (47, 117, and 118) aromatic system could have larger ability to delocalize the
were plotted against the number of benzene rings of the anion, which ultimately stabilize the corresponding proton
hydroquinones and catechols, respectively, it was unex- releasing product.
pected to found that the oxidation potentials of hydroqui- Concerning the hydrogen atom releasing process, Table 1
nones and catechols have good linear relationships to and Figure 11 indicate that bond dissociation energies of the
decrease with the increase of the number of benzene rings O-H bond in hydroquinones have a good linear correlation
in the hydroquinones and catechols (Figure 9). According to with the numbers of the phenyl ring. However, the O-H
this relationship, the oxidation potentials of aromatic hydro- bond dissociation energy in 117 is larger than that in 47,
quinones and catechols containing three or more benzene suggesting the linear relation between the BDE and the
rings can be predicted. Furthermore, it is clear that aromatic numbers of the phenyls do not exist in hydrocatechol series,
hydroquinones will be very effective electron donors and the reason could be that the releasing of the hydrogen atom
may thus be useful in the invention of new materials and new from 117 makes the large change of the molecular structure,
reactions. which can be shown from the structure parameters and the
From Table 1, we can also find that the proton releasing calculated NICS (1) values. From Table 4 it can be found the
energies of the hydroquinones decrease in the order of 1 > NICS(1) values of the B ring in 117 is only 1.12, much smaller
93>105, and those of catechols decreased in the order 47 > than those of 116 and 118. The smaller the NICS(1) value is,
117 > 118. It is worth noting that there are also two linear the unstability the compound is. So the O-H bond dissocia-
correlations between pKa1 values of hydroquinones or cate- tion energy of 117 is larger than those of 116 and 118. This
chols and the numbers of the benzene rings, respectively also tells us that we should be cautious when we make the
(Figure 10), which shows the existence of the phenyl ring correlation between the oxidation potentials, proton and
J. Org. Chem. Vol. 75, No. 21, 2010 7255
JOC Article Zhu et al.

FIGURE 12. Dependence of the relative oxidation potentials of the

FIGURE 13. Dependence of the relative proton dissociation en-
various hydroquinones and catechols in DMSO on the correspond-
ergies of the various hydroquinones and catechols in DMSO on the
ing ionization potentials in the gas phase.
corresponding proton dissociation energies in the gas phase.
hydrogen dissociation energies of hydroquinones or catechols,
and the numbers of the benzene rings, respectively.
9. Solvation Effects. As well-known, unlike the electron
transfer, hydrogen atom and proton transfer in gas-phase,
these processes in solution for hydroquinones and catechols
are not only dependent on the structures of hydroquinones
and catechols but also dependent on the nature of solvent. To
quantitatively estimate the relative contribution of the solva-
tion effect to the thermodynamic driving forces of these three
processes, the plots of the relative ionization potentials,
proton dissociation, and hydrogen dissociation energies in
the gas-phase against the relative oxidation potentials, proton
dissociation and hydrogen dissociation energies in DMSO
were made, respectively (Figures 12-14).
From eqs 10-12, we know that
 
ΔGsol ¼ ΔGg þ Gsol ð39Þ
FIGURE 14. Dependence of the relative bond dissociation energies
From Figure 12-14, it is clear that of the various hydroquinones and catechols in DMSO on the
  corresponding bond dissociation energies in the gas phase.
ΔGsol ¼ 0:35ΔGg þ 0:78 for electron transfer process ð40Þ
dissociation processes, which not only indicate that bond
  dissociation energies of the O-H bonds in hydroquinones
ΔGsol ¼ 0:34ΔGg - 22:25 for proton transfer process ð41Þ
and catechols are similar in the gas-phase and in DMSO but
  also show that gas-phase thermodynamic driving forces and
ΔGsol ¼ 0:87ΔGg - 1:41 for hydrogen atom transfer process solvation energies are tracking the same physical parameter:
ð42Þ the appropriate physical property seems to be charge densities
of the molecules.
According to eq 39, we obtained that
 Conclusions
ΔGsol ¼ - 0:65ΔGg - 0:78 for electron transfer process ð43Þ
Hydroquinones and catechols are well-known two-electron
 reductants which play important roles in chemistry, biology,
ΔGsol ¼ - 0:66ΔGg þ 22:25 for proton transfer process ð44Þ
industries, and our environmental science. In this work, the

ΔGsol ¼ - 0:13ΔGg oxidation potentials, pKa (pKa1 and pKa2) values and bond
dissociation energies (BDE1 and BDE2) of 118 important
þ 1:41 for hydrogen atom transfer process ð45Þ p- and o-hydroquinones in DMSO were predicted for the first
time by using DFT method and the PCM cluster continuum
From the slopes of the plot lines and eqs 40-45, it is
model. The calculated results agree well with the available
clear that 65%, 66%, and 13% of the gas-phase ionization
experimental determinations, respectively. From this paper,
potentials, proton dissociation energies and hydrogen atom
we get
transfer energies are offset by the solvation in the liquid
phase oxidation potentials and proton and hydrogen atom (1) The oxidation potential scales of each series of H2Q
transfer energies, respectively; the reason could be that no are 0.970-2.987 V for p-H2Q, 1.247-3.050 V for o-
charge separation was made in the hydrogen atom transfer H2Q, 1.051-1.608 V for 1,4-H2NQ, 0.856-1.357 V
process whereas they were made in ionization and proton for 1,4-H2AQ, and 0.824-1.104 V for 9,10-H2AQ.
7256 J. Org. Chem. Vol. 75, No. 21, 2010
Zhu et al.
JOC Article
(2) The pKa1 scale of the hydroquinones in DMSO ranges The intramolecular hydrogen bonds in five-membered
from 2 to 21.5 for hydroquinones and from -1.7 to rings are weaker than those in the six-membered rings.
17.7 for catechols, and the pKa2 scale ranges from The entropic contribution to the hydrogen bond
9.4 to 28.1 for hydroquinone anion and from 11.5 to Gibbs free energies are very small.
31.9 for catechol anions. (6) Solvation effects on oxidation, proton release, and hy-
(3) BDE1 scale of H2Q in DMSO ranges from 70 to drogen atom release process were systematically studied.
92.1 kcal/mol for hydroquinones and from 77.7 to
91.3 kcal/mol for catechols. BDE2 scale of H2Q in Acknowledgment. Financial support from the National
DMSO ranges from 59 to 84.9 kcal/mol for hydro- Natural Science Foundation of cChina (Grant Nos. 21072104,
quinones and from 60 to 86 kcal/mol for catechols. 20921120403 and 20832004), the Ministry of Science and
(4) All the five parameters correlate well with the Hammett Technology of China (Grant No. 2004CB719905) and the
substituent parameters (for p-H2Q, EoxNHE(H2Q•+/ 111 Project (B06005) is gratefully acknowledged. The
H2Q) = 1.66Σσp þ 0.54, pKa1 = -5.69Σσp þ 16.54, calculations were performed on a Nankai Stars super-
pKa2 = -5.19Σσp þ 23.91, BDE1 = 3.43Σσp þ 82.29, computer at Nankai University.
BDE2 = 4.64Σσp þ 67.70; for o-H2Q, EoxNHE(H2Q•+/
H2Q) = 1.85Σσp þ 0.46, pKa1 = -5.53Σσp þ 13.28, Supporting Information Available: Comparison of theoret-
pKa2 = -5.24Σσp þ 26.70, BDE1 = 3.54Σσp þ 82.08, ical proton, electron and hydrogen atom transfer driving
BDE2 =3.82Σσp þ 75.93), which hints we can get these forces of phenols in DMSO with the corresponding some
parameters as long as the structures of the hydroqui- available experimental data. The calculated gas phase Gibbs
nones were known. free energies and solution phase solvation energies in DMSO
(5) Concerning the same molecule, the hydrogen bond for hydroquinones at neutral, radical cation, radical and
energies in different charge and spin states are in the anion states. This material is available free of charge via the
order of anion > radical > radical cation ≈ neutral. Internet at http://pubs.acs.org.

J. Org. Chem. Vol. 75, No. 21, 2010 7257