American Journal of Chemistry 2015, 5(4): 91-95

DOI: 10.5923/[Link].20150504.01

A Study of the Substituent Effects on the O−H Bond

Dissociation Enthalpies of Phenol Derivatives Using the
ONIOM Method
Nguyen Minh Thong1,*, Thi Chinh Ngo2, Truc Xuyen Nguyen Phan3, Duy Quang Dao2,
Truong Van Nam1, Phan Thi Tuyet Trinh1, Pham Cam Nam4

1
The University of Danang - Campus in Kon Tum, 704 Phan Dinh Phung, Kon Tum, Viet Nam
2
Institute of Research and Development, Duy Tan University, 03 Quang Trung, Danang, Viet Nam
3
Department of Environment, Duy Tan University, K7/25 Quang Trung, Danang, Viet Nam
4
Department of Chemistry, University of Science and Technology - The University of Danang, 54 Nguyen Luong Bang, Lien Chieu,
Danang, Viet Nam

Abstract The O–H bond dissociation enthalpies (BDE) of various substituted phenol derivatives were determined using
the ONIOM(ROB3LYP/6-311++G(2df,2p):PM6) approach. Computed BDE(O–H)s of all phenol derivatives were in good
agreement with available experimental values, and also well correlated with the Hammett constants, σp. It is found that the
strong electron-donating NH2 and N(CH3)2 substituents induce a significant decrease in the BDE(O–H)s. On the contrary,
the strong electron withdrawing NO2 and CF3 groups result in an increase in BDE(O–H)s.
Keywords Bond dissociation enthalpies, Antioxidant, Phenol derivatives, ONIOM method

compounds in both experimental [10-14] and quantum

1. Introduction chemical [15-19] techniques. Although quantum chemical
study is already well established for accurately predicting
Phenolic antioxidants (ArOH) play an important role in BDEs, there are still many challenges in treatment of large
the prevention of several chemical and biological processes compounds.
including the biological ageing, foodstuff deterioration, The ONIOM approach, which is an integrated method
synthetic polymer degradation [1-3], etc. The function of proposed by Morokuma and co-workers [20-22], is an
phenolic antioxidants is a scavenger active against reactive efficient computational tool for the study of large molecular
oxygen species (ROS) such as superoxide anion radical, systems. In our previous studies, we performed an
singlet molecular oxygen and hydroxyl radical. There are integration of the ROB3LYP/6-311++G(2df,2p) level with
several mechanisms of phenolic antioxidant action, and the the semi-empirical PM6 method into a two-layer ONIOM to
net result of all mechanisms is similar to each other: reasonably produce accurate BDE(O–H)’s of phenolic
transferring hydrogen atom radical to the free radicals [4-8]. compounds. Deviation of calculated values from
A high rate of hydrogen atom transfer is expected to be experiment is ± (1–2) kcal/mol [23, 24].
related to a low O–H bond dissociation enthalpy (BDE). OH OH
Therefore, the BDE parameter (capacity to donate an H
atom) is a key feature for evaluating the antioxidant activity t -Bu t -Bu
of a natural compound. Sterically hindered phenols (Figure
1b) represent a large group of synthetic antioxidants widely
used in synthetic polymers stabilization [9]. It is
well-known that phenolic compounds act as chain-breaking
antioxidants. X X
Numerous attempts have already been investigated to
measure or predict the accurate BDEs of organic a b
X = H; t-Bu; CH3; CH3O; CH3CO; C6H5;
* Corresponding author:
CF3; CN; F; NH2; N(CH3)2; NO2; OH
thongsphoa@[Link] (Nguyen Minh Thong)
Published online at [Link] Figure 1. Structure of mono-substituted phenols (a) and sterically
Copyright © 2015 Scientific & Academic Publishing. All Rights Reserved hindered phenols (b)
92 Nguyen Minh Thong et al.: A Study of the Substituent Effects on the O−H Bond
Dissociation Enthalpies of Phenol Derivatives Using the ONIOM Method

In the present paper, we thus apply the choose a partitioning scheme for the two-layer ONIOM (as
ONIOM(ROB3LYP/6-311++G(2df,2p):PM6) approach to described in Figure. 2) that generates an accurate estimation
determine the BDEs of the O–H bonds of various of BDE(O−H) within 1–2 kcal/mol deviation. According to
substituents of sterically hindered phenols and this, each molecule is divided into two layers, the atoms at
mono-substituted phenols (as shown in Figure 1) in the the breaking bond is treated as a high layer while the leftover
gas-phase, and to assess the effect of various atoms of the molecule belong to the second layer, which is
electron-donating or electron-withdrawing groups at the treated as a lower layer. The ROB3LYP/6-311++G(2df,2p)
para-position on the change of the BDE. The obtained method is thus applied for the atoms in the high layer,
results for mono-substituted phenols will then be compared whereas the PM6 procedure is applied for the low one. In this
with identical group of substituents in para-position, in model (Figure. 2), the core layer which has only one oxygen
order to describe the effect of the two tert-butyl (t-Bu) atom and one hydrogen atom, relates to the target bond for
groups on studied enthalpies. In addition, our observation estimating BDE at the high level. The rest are defined as the
will also be compared to the available experimental data. low layer.
The relationship between the calculated BDEs and
Hammett constants will be also correlated.
3. Results and Discussion
2. Theoretical and Computational 3.1. Agreement between Calculated and Experimental
Methods BDE(O–H)s
In this part, the ONIOM(ROB3LYP/6-311++G(2df,2p):
All computations were performed using the Gaussian 09
PM6) approach were used to determine the BDEs of the
suite of program [25]. Geometry optimizations and
O–H bonds of 26 para-substituted sterically hindered
vibrational frequency calculations were conducted using the
phenols and phenols. The calculated BDE(O–H) values are
semi-empirical PM6 method. Vibrational frequencies
summarized in Table 1.
obtained at the PM6 level were subsequently scaled by a
In order to evaluate the reliability of employed
factor of 1.078 [26] for estimating the zero-point vibrational
computational approach for substituent effect description, it
energies (ZPE). The BDE value was determined from total
is necessary to compare the calculated and the experimental
enthalpies of the individual species in the gas-phase, as
values. From the calculated results for a series of substituted
follows:
phenols (as shown in Table 1), the largest deviation (ΔBDE)
BDE(ArO−H) = H(ArO•) + H(H•) − H(ArOH) between the calculated and the experimental BDE(O–H)
Where H’s are the enthalpies of different species at 298.15 values is 2.5 kcal/mol which is found in the case of
K and 1.00 atm. The enthalpies were estimated from the p-CH3CO-C6H2(t-Bu)2OH. For the other substituted
given expression: H(T) = E0 + ZPE + Htrans + Hrot + Hvib + compounds, the deviation are smaller and in the range from
RT. The Htrans, Hrot, and Hvib are the translational, rotational, –1.8 to 0.7 kcal/mol. The results also show that the
and vibrational contributions to the enthalpy, respectively. E0 BDE(O–H) values obtained from the ONIOM method are
is the total energy at 0 K and ZPE is the zero-point reasonably accurate and in agreement with the best
vibrational energy. The enthalpy value for the hydrogen experimental data with the deviation of only ±1.0 kcal/mol.
atom in the gas phase was taken at its exact energy of −0.5
3.2. Effect of Substituents on BDE(O–H)s
hartree at 0 K and thermal correction at the given
temperature is added the value of 2.5RT. The substitution of a functional group in the molecule
generally causes considerable changes in physico-chemical
properties. Therefore, the understanding of substituent effect
on O–H bond cleavage as well as on various molecular
properties is important. The substituent effects were
described in terms of ∆’BDEs, where ∆’BDE is the
difference between the bond dissociation enthalpies of the
substituted and the parent phenol, ∆’BDE = BDE(substituted
phenols) – BDE(phenol). Relationship between ∆’BDE
values and substituents was shown in Table 1 and Figure 3.
In the case of mono-substituted phenol, among the
electron-withdrawing group, NO2 has the strongest effect to
the BDE(O–H). The BDE value is 5.4 kcal/mol higher than
the ones of phenol. The other electron-withdrawing groups
Figure 2. Schematic description of two-layer proposed ONIOM model
like CH3CO, CF3, and CN induce an increase in BDEs in the
range from 2.1 to 3.7 kcal/mol compared with the BDE of
By improving the results of the previous paper [24], we phenol. In the case of electron-donating groups including
 American Journal of Chemistry 2015, 5(4): 91-95 93

t-Bu, CH3, CH3O, C6H5, F, NH2 and N(CH3)2, OH, the be interpreted knowing that electron-donating groups induce
BDE(O−H) values tend to be lower than the BDE(O–H) of the positive inductive effect (+I). This factor causes the
phenol. The largest decreases in BDE which are -6.3 and -6.9 strong polarization of the O–H bond, thus, decreases the
kcal/mol, are found for the strongest electron-donating NH2 BDEs, while the presence of electron-withdrawing ones in
and N(CH3)2 groups, respectively. The obtained results can molecule results in the increase of BDEs.
Table 1. Experimental and theoretical BDEs (kcal/mol) related to para-substituted molecules and Hammett constants σp

Mono-substituted phenols Sterically hindered phenols

Substituent σpd
Calc. Expt.a ∆BDEb ∆’ BDEc Calc. Expt.a ∆BDEb ∆’ BDEc
p-H 87.3 88.0 -0.7 0 83.1 82.8 0.3 -4.2
p-t-Bu 85.5 85.3 0.2 -1.8 81.8 81.2 0.6 -5.5 -0.20
p-CH3 85.1 86.1 -1.0 -2.2 81.4 81.0 0.4 -5.9 -0.17
p-CH3O 81.8 82.6 -0.8 -5.5 79.8 79.7 0.1 -7.5 -0.27
p-CH3CO 90.0 90.3 -0.3 2.7 85.6 83.1 2.5 -1.7 0.50
p-C6H5 85.7 85.0 0.7 -1.6 82.0 81.2 0.8 -5.3 -0.01
p-CF3 91.0 91.4 -0.4 3.7 86.4 N/A N/A -0.9 0.54
p-CN 89.4 90.1 -0.7 2.1 85.1 84.2 0.9 -2.2 0.66
p-F 86.5 87.2 -0.7 -0.8 82.6 N/A N/A -4.7 0.06
p-NH2 81.0 80.8 0.2 -6.3 78.2 80.0 -1.8 -9.1 -0.66
p-N(CH3)2 80.4 80.3 0.1 -6.9 78.1 N/A N/A -9.2 -0.83
p-NO2 92.7 93.8 -1.1 5.4 87.3 86.7 0.6 0 0.78
p-OH 82.5 82.2 0.3 -4.8 80.4 N/A N/A -6.9 -0.37
a
Ref. [27]
b
∆BDE = ∆BDEcalc. ─ ∆BDEexpt.
c
∆’BDE = BDE(C6H5-nXnOH) − BDE(C6H5OH)
d
Ref. [28]

Figure 3. Effect of substituents on BDE(O–H)s of mono-substituent phenols and sterically hindered phenols
94 Nguyen Minh Thong et al.: A Study of the Substituent Effects on the O−H Bond
Dissociation Enthalpies of Phenol Derivatives Using the ONIOM Method

A similar tendency is observed in the case of sterically The correlation coefficients in mono-substituent phenols
hindered phenols, but the differences in BDE values are and sterically hindered phenols reached 0.93 and 0.96,
considerably larger than those of mono-substituted phenols. respectively. Linear regressions show that the ONIOM
In fact, BDEs of sterically hindered phenols with method satisfactorily describes the dependence of the
electron-withdrawing and electron-donating groups are all expected linear BDE versus Hammett constant. The
lower than the ones of phenol. The decrease in BDEs is BDE(O−H) value increases with the increase in the
caused by the presence of two electron-donating tert-butyl electron-withdrawing ability of the substituent. This is a very
groups in ortho-positions to the phenolic O–H bond. BDE of important conclusion because this can be utilized in the
sterically hindered phenols with the strongest synthesis of novel phenolic derivatives with enhanced
electron-withdrawing NO2 group is the same to that of antioxidant properties.
phenol. On the other hand, the largest BDE(O–H) decrease
which are –9.1 and –9.2 kcal/mol, are achieved by the strong
electron-donating NH2 and N(CH3)2 groups, respectively. 4. Conclusions
3.3. Relationship between the Calculated BDEs and In this paper, the bond dissociation enthalpies of
Hammett Constants para-substituted phenols and sterically hindered phenols in
the gas-phase were investigated using ONIOM(ROB3LYP/
The Hammett equation (and its extended forms) has been
6-311++G(2df,2p):PM6) approach. The calculated results
one of the most widely used means for the study and
are in very good accordance with available experimental data.
interpretation of organic reactions and their mechanisms.
In addition to the character of substituents, the influence of
Hammett constants σm (for substituent in meta position) and
number of substituents was also evaluated. The largest
σp (for substituent in para position) obtained from the
decrease in BDE(O–H)s results from the strong
ionization of organic acids in solutions can successfully
electron-donating NH2 and N(CH3)2 groups. On the contrary,
predict equilibrium and rate constants for a variety of
the strong electron withdrawing NO2 and CF3 groups result
families of reactions [28].
in an increase in BDE(O–H)s. Therefore, the improvement
Hammett constants correlate very well with the changes in
of the phenolic antioxidant effectiveness, i.e. the decrease of
BDE(O−H) in the case of phenols [15]. The correlation
the BDE(O–H), can be accomplished by the substitution of
between calculated BDE values and Hammett constants, σp,
electron-donating groups at the para position.
for mono-substituent phenols and sterically hindered phenols
is presented in Figure 4. The equations obtained from the
linear regression are as follows: ACKNOWLEDGEMENTS
BDE (kcal/mol) = 7.63σp + 86.01 (R2 = 0.9329)
(mono-substituent phenol) This research is funded by Vietnam National Foundation
BDE (kcal/mol) = 5.83σp + 82.43 (R2 = 0.9561) for Science and Technology Development (NAFOSTED)
(sterically hindered phenol) under grant number 104.06-2013.21.

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