Hydrogen Atom Transfer (HAT) Processes Promoted by the Quinolinimide-N-oxyl Radical. A Kinetic and Theoretical Study

Article abstract of DOI:10.1021/acs.joc.7b00687

A kinetic study of the hydrogen atom transfer (HAT) reactions from a series of organic compounds to the quinolinimide-N-oxyl radical (QINO) was performed in CH₃CN. The HAT rate constants are significantly higher than those observed with the phthalimide-N-oxyl radical (PINO) as a result of enthalpic and polar effects due to the presence of the N-heteroaromatic ring in QINO. The relevance of polar effects is supported by theoretical calculations conducted for the reactions of the two N-oxyl radicals with toluene, which indicate that the HAT process is characterized by a significant degree of charge transfer permitted by the π-stacking that occurs between the toluene and the N-oxyl aromatic rings in the transition state structures. An increase in the HAT reactivity of QINO was observed in the presence of 0.15 M HClO₄ and 0.15 M Mg(ClO₄)₂ due to the protonation or complexation with the Lewis acid of the pyridine nitrogen that leads to a further decrease in the electron density in the N-oxyl radical. These results fully support the use of N-hydroxyquinolinimide as a convenient substitute for N-hydroxyphthalimide in the catalytic aerobic oxidations of aliphatic hydrocarbons characterized by relatively high C-H bond dissociation energies.

Full text of DOI:10.1021/acs.joc.7b00687

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Article
Hydrogen Atom Transfer (HAT) Processes Promoted by the
Quinolinimide-N-Oxyl Radical. A Kinetic and Theoretical Study
Gino A. DiLabio, Paola Franchi, Osvaldo Lanzalunga, Andrea Lapi, Fiorella
Lucarini, Marco Lucarini, Marco Mazzonna, Viki Kumar Prasad, and Barbara Ticconi
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 23 May 2017
Downloaded from http://pubs.acs.org on May 24, 2017
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Hydrogen Atom Transfer (HAT) Processes
Promoted by the QuinolinimideꢀNꢀOxyl Radical.
A Kinetic and Theoretical Study
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Gino A. DiLabio,a Paola Franchi,c Osvaldo Lanzalunga,b * Andrea Lapi,b Fiorella Lucarini,d Marco
Lucarini,c Marco Mazzonna,b Viki Kumar Prasad,a and Barbara Ticconib
a
Department of Chemistry, University of British Columbia, Okanagan, 3247 University Way,
Kelowna, British Columbia, Canada V1V 1V7
b
Dipartimento di Chimica, Sapienza Università di Roma and Istituto CNR di Metodologie
Chimiche (IMCꢀCNR), Sezione Meccanismi di Reazione, c/o Dipartimento di Chimica, Sapienza
Università di Roma, P.le A. Moro, 5 Iꢀ00185 Rome, Italy
c Dipartimento di Chimica “G. Ciamician”, Università di Bologna, Via San Giacomo 11, Iꢀ40126
Bologna, Italy
d Département de Chimie, Université de Fribourg, Chemin du Musée 9, 1700 Fribourg, Switzerland
Email: osvaldo.lanzalunga@uniroma1.it
ABSTRACT: A kinetic study of the hydrogen atom transfer (HAT) reactions from a series of
organic compounds to the quinolinimideꢀNꢀoxyl radical (QINO) was carried out in CH3CN. The
HAT rate constants are significantly higher than those observed with the phthalimideꢀNꢀoxyl radical
(PINO) as a result of enthalpic and polar effects due to the presence of the Nꢀheteroaromatic ring in
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QINO. The relevance of polar effects is supported by theoretical calculations carried out for the
reactions of the two Nꢀoxyl radicals with toluene which indicate that the HAT process is
characterized by a significant degree of charge transfer enabled by the πꢀstacking that occurs
between the toluene and the N-oxyl aromatic rings in the transition state structures. An increase of
the HAT reactivity of QINO was observed in the presence of HClO4 0.15 M and Mg(ClO4)2 0.15 M
due to the protonation or complexation with the Lewis acid of the pyridine nitrogen that leads to a
further decrease of the electron density in the Nꢀoxyl radical. These results fully support the use of
Nꢀhydroxyquinolinimide (NHQI) as a convenient substitute of Nꢀhydroxyphthalimide (NHPI) in the
catalytic aerobic oxidations of aliphatic hydrocarbons characterized by relatively high CꢀH bond
dissociation energies.
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Introduction
The use of Nꢀhydroxyphthalimide (NHPI) as catalyst in the aerobic oxidative functionalization
of hydrocarbon has attracted a great attention in recent years. In the presence of metal and nonmetal
coꢀcatalysts, the NHPI/O2 system was found to efficiently catalyze the introduction of oxygenated
groups in aliphatic and alkylaromatic hydrocarbons.1
The key role played in the catalytic cycle by the hydrogen atom transfer from the organic substrate
to the phthalimideꢀNꢀoxyl radical (PINO) (HAT process, Scheme 1) has stimulated several kinetic
studies aimed at obtaining quantitative information on the reactivity of PINO and other structurally
related shortꢀlived Nꢀoxyl radicals towards a variety of CꢀH bonds.2,3
O
N
O
O
N
O
HAT
O
+
R
+
R
H
O
H
Scheme 1
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The HAT reactivity of shortꢀlived Nꢀoxyl radicals is strongly dependent on enthalpic effects based
on the difference between the OꢀH bond dissociation energy (BDE) in the Nꢀhydroxy derivative and
the CꢀH BDE of the substrates (eq 1). In this respect the high reactivity of PINO is associated with
relatively high NOꢀH BDE in NHPI (87 kcal/mol).4
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In addition to enthalpic effects, polar effects also play an important role in the HAT reactivity of Nꢀ
oxyl radicals.6 The HAT transition state (TS) structure is characterized by a partial degree of charge
transfer from the substrate to the Nꢀoxyl radical (Figure 1). The polar contribution is clearly
dependent on the ability of the substrate and the Nꢀoxyl radical to stabilize, respectively, the
positive and negative charges developing in the transition state (TS).
O
C
H
O
N
O
Figure 1. Polar transition state in the HAT process promoted by PINO
On the basis of enthalpic considerations, an increase in the HAT reactivity of Nꢀoxyl radicals can be
established by an increase of BDENOꢀH values of the corresponding Nꢀhydroxy derivatives. In aryl
substituted Nꢀhydroxyphthalimides and other aromatic hydroxylamines an increase of BDENOꢀH
values is observed with electron withdrawing aryl substituents which destabilize the resonance
structure with charge separation shown in Figure 2.7
Figure 2. Resonance structures of aryl substituted PINO radicals
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Electron withdrawing substituents are also able to increase the reactivity of the Nꢀoxyl radical
through polar effects on the HAT TS structure as a result of enhanced stabilization of the partial
negative charge that develops on the Nꢀoxyl radical at the TS.8 The enhancement of HAT reactivity
exerted by electron withdrawing substituents on Nꢀoxyl radicals has been reported in several kinetic
and product studies of the reaction of aryl substituted PINO and benzotriazoleꢀNꢀoxyl radical with
alkylaromatics and benzylic alcohols.7,9
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The decrease of the PINO electron density can also be affected by replacement of the phenyl with
an electron withdrawing Nꢀheteroaromatic ring (Nꢀhydroxyquinolinimide, NHQI, Figure 3). The
corresponding Nꢀoxyl radical (QINO) should be more reactive than PINO in HAT processes and
therefore NHQI may serve as a better catalyst than NHPI in the oxidations of organic compounds
using molecular oxygen as terminal oxidant. In this connection, Xia et al. showed that the catalytic
activity of NHQI in the aerobic oxidation of toluene is significantly higher than that of NHPI either
in the absence or in the presence of a metal cocatalysts.10 More recently it was reported that NHQI,
in combination with 4ꢀcarboxylꢀNꢀhydroxyphthalimide, showed excellent activity in the aerobic
oxidation of ethylbenzene.11
Figure 3. Structures of Nꢀhydroxyphthalimide (NHPI), Nꢀhydroxyquinolinimide (NHQI),
phthalimideꢀNꢀoxyl radical (PINO) and quinolinimide Nꢀoxyl radical (QINO)
In this study we report the ultravioletꢀvisible (UVꢀvis) and electron paramagnetic resonance
(EPR) spectroscopic characterization of QINO and a kinetic investigation of the HAT reactivity of
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QINO with a series of organic substrates including aliphatic hydrocarbons, alkylaromatics, alcohols,
ethers, aldehydes and amides. The results were compared with those found in the HAT processes
promoted by PINO. Theoretical calculations using a densityꢀfunctional theory (DFT) based
technique was carried out for the HAT reactions of PINO and QINO with toluene, selected for the
industrial relevance of the HAT from alkylaromatics to Nꢀoxyl radicals,1 in order to gain an insight
into the energetics of the HAT process involving these species. Since an increase of the QINO
reactivity in HAT process may result from the protonation or complexation with metal cations of
the heteroaromatic nitrogen, kinetic studies have been also investigated in the presence of Brønsted
and Lewis acids (HClO4 and Mg(ClO4)2) employed at 0.15 M concentration.
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Results
Generation and characterization of QINO
The QINO radical was generated in a quartz cuvette by adding a 0.5 M solution of cerium(IV)
ammonium nitrate in acetonitrile to a 1.0 M solution of NHQI at 25 °C, after which the UVꢀvis
spectrum was obtained. This method was used previously to characterize spectroscopically PINO
and other transient Nꢀoxyl radicals (Figure 4).3,12
O
N
O
O
N
O
(NH4)2Ce(NO3)6
-e, -H+
OH
O
N
N
NHQI
QINO
Figure 4. Generation of QINO by oxidation of NHQI with cerium(IV) ammonium nitrate
The UVꢀvis spectrum soꢀobtained has an absorption band centred at 380ꢀ390 nm. This band
overlaps with the absorbance region of cerium salts (see Figure S1 in the SI). Better UVꢀvis
spectroscopic characterization of QINO was obtained in a laser flash photolysis (LFP) experiment
as described in Scheme 2.13,14 Cumyloxyl radical (CumO•), generated by LFP at 355 nm of a 1 M
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solution of dicumyl peroxide in N2ꢀsaturated acetonitrile at 25 °C, abstracts a hydrogen atom from
NHQI (5 nM) yielding QINO (eq 2 in Scheme 2).15 This hydrogen atom abstraction reaction occurs
in competition with the βꢀscission of CumO• which leads to the formation of acetophenone and a
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methyl radical (eq 3 in Scheme 2, kβ ~ 6.5 × 105 sꢀ1 in CH3CN).13 Figure 5 shows the timeꢀresolved
spectra obtained. The firstꢀorder decay of the cumyloxyl radical recorded at its maximum
absorption wavelength (485 nm)14 is accompanied by the buildꢀup of the QINO absorption at 390
nm.
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Scheme 2
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0.04
0.03
0.02
0.01
0.00
0.03
b)
0.02
0.01
0.00
-0.01
0.02
a)
490nm
0.01
390nm
0.00
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-0.01
0
2e-6
4e-6
6e-6
0
2e-6
t (s)
4e-6
6e-6
t (s)
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λ (nm)
Figure 5. Transient absorption spectra measured 98 ns (●), 288 ns (○), 1
ꢁ
s (▼) and 2 ꢁs (∆) after
355 nm laser excitation of a solution of dicumyl peroxide (1 M) and NHQI (5 mM) in CH3CN at 25
°C under N2. Inset a: firstꢀorder buildup of the QINO absorption at 390 nm. Inset b: firstꢀorder
decay of the absorption of the cumyloxyl radical at 490 nm
The electron spin resonance spectrum of QINO was obtained at 298 K by UV photolysis of a
CH3CN solution containing NHQI 10 mM and 10% (v/v) of diꢀtertꢀbutyl peroxide. The spectrum
(see Figure 6) shows three main lines due to the coupling of the unpaired electron with nitroxidic
nitrogen (aN= 4.57 G).16 Each lines shows also unresolved hyperfine structure due to small coupling
of the unpaired electron with the nitrogen and hydrogen aromatic nuclei. A similar EPR spectrum of
QINO was obtained by oxidation of NHQI with cerium(IV) ammonium nitrate (CAN) in CH3CN at
25 °C (see Figure S2 in the Supproting Information). The 2nd derivative spectrum clearly showed
unresolved hyperfine structure due to small coupling of the unpaired electron with the nitrogen and
hydrogen aromatic nuclei.
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Figure 6. EPR spectrum of QINO recorded at 298 K during UV photolysis of a CH3CN solution
containing NQHI 10 mM and diꢀtertꢀbutyl peroxide (10% v/v)
NO-H Bond dissociation enthalpies (BDE) of NHQI
The BDENOꢀH of NHQI is a parameter of fundamental importance for the analysis of the HAT
reactivity of QINO. Its value, determined both experimentally and by theoretical calculations was
compared with the BDENOꢀH value of NHPI previously determined with the same
methodologies.2c,7a,d,8,17 The experimental determination of OꢀH BDE was carried out by the EPR
radical equilibration technique. For this purpose, we measured the equilibrium constant (Keq) for the
hydrogen atom transfer reaction between NHQI and a NHPI derivative whose OH BDE was already
known (Scheme 3). As a reference we choose 4ꢀCH3OCOꢀNHPI which is characterized by an OꢀH
BDE of 87.8 kcal/mol.18
Keq
QINO + 4-CH3OCO-NHPI
NHQI + 4-CH3OCO-PINO
Scheme 3
The initial concentration of Nꢀhydroxyimides were used to calculate Keq, while the relative radical
concentration were determined by means of EPR spectroscopy (see details and Figure S3 in the
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Supporting Information).19 On the assumption that the entropic term can be neglected
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BDENHQI=BDE4ꢀCH OCOꢀNHPI–RTln(Keq). From the experimentally determined radical concentrations,
3
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8
we obtained Keq= 1.20, from which, an OꢀH BDE of 87.7
±
0.6 kcal/mol for NHQI was calculated.20
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Theoretical calculations
Densityꢀfunctional theory (DFT) based calculations were performed to model the reactions of
QINO and PINO radicals with toluene. The B3LYP/6ꢀ31+G(2d,2p)21 level of theory was used as the
underlying method. The effects of noncovalent interactions in the reacting systems were modeled
with the dispersionꢀcorrecting potentials (DCPs) approach described previously.22 Although there
exists a number of more common approaches to correcting for the absence of dispersion in the
B3LYP (and other) methods, we elected to use the DCP approach in order to obtain results
comparable with those previously published for computational studies of the reactions between
PINO and phenols. The method we applied is abbreviated as B3LYPꢀDCP/6ꢀ31+G(2d,2p).
We computed the energyꢀoptimized structures of the reactants, preꢀ and postꢀreaction
(noncovalently bound) complexes and the cisoid (πꢀstacked) and transoid (nonꢀstacked) transition
state (TS) structures in an implicit solvent field (acetonitrile) using the SMD model of Marenich et
al.23 All nonꢀTS structures were verified to have only positive vibration frequencies and the TS
structures had a single imaginary frequency that lead to the corresponding preꢀ and postꢀreaction
species. The gasꢀ and solventꢀphase energyꢀoptimized Cartesian coordinates of the reactants, preꢀ
and postꢀreaction complexes, transition states and products are provided in the Supporting
Information.
The OꢀH BDEs for NHQI and NHPI OꢀH BDEs were computed using the restricted openꢀshell
(RO) version of CBSꢀQB3.24 All calculations were performed using the Gaussianꢀ09 program
package.25
The (RO)CBSꢀQB3 method predicts the gasꢀphase OꢀH BDEs in NHQI and NHPI to be 84.0 and
83.1 kcal molꢀ1 respectively,26 with a difference of 0.9 kcal molꢀ1 which is in line with the
experimentally determined
ꢀ
BDENOꢀH (0.7 kcal molꢀ1). The same approach predicts the CꢀH BDE
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of the methyl group in toluene to be 89.7 kcal/mol. For comparison, the B3LYPꢀDCP/6ꢀ
31+G(2d,2p) approach predicts the analogous BDEs in NHQI, NHPI, and toluene to be 80.0, 79.0,
and 88.8 kcal/mol, respectively. We attribute the lack of agreement between the (RO)CBSꢀQB3 and
B3LYPꢀDCP BDEs for NHQI and NHPI to delocalization errors associated with the underlying
B3LYP functional. This suggests that the B3LYPꢀderived barrier heights and reaction endergonicity
will be higher than the actual values (see below).
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The calculated solvent phase free energies associated with the reaction of QINO and PINO with
toluene in acetonitrile solvent are shown in Table 1. In the gasꢀphase, the reactants form fairly
strongly bound preꢀreaction complexes, with enthalpies of association of 8.4 (QINO) and 7.8
kcal/mol (PINO). However, the inclusion of entropic correction results in preꢀreactions complex
formation that are endergonic (2.6 kcal/mol in both cases, see Tables S1ꢀS2 in the SI). The
inclusion of estimates of the solvent effects increase the endergonicity of preꢀreaction complex
formation to 5.5 (QINO) and 4.6 (PINO) kcal/mol. These results are consistent with both the
relatively high polarity of the radicals and the differential in the polarity between the radicals.
Table 1. Reaction free energies, relative to reactants, of the hydrogen atom transfer from toluene to
QINO and PINO in acetonitrile solvent. The data were obtained using B3LYPꢀDCP/6ꢀ31+G(2d,2p)
with the SMD solvation (acetonitrile) model. All values are in kcal/mol
Reaction step
QINO + Toluene
5.5
PINO + Toluene
4.6
Preꢀreaction complex
Cisoid TS complex
Transoid TS complex
Postꢀreaction complex
19.6
21.8
13.3
20.6
23
14.4
Products
10.3
11.4
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The TS structures associated with the HAT reaction of QINO and PINO with toluene were found to
be πꢀstacked, or “cisoid” (Figure 7), rather than a “transoid” structure (i.e. nonꢀstacked, or open, see
Figure S43 in the SI). This finding is consistent with the calculated structure for the HAT identity
reaction for the toluene/benzyl27 and the phenol/phenoxyl28 couples. As was discussed in ref. 7, the
overlap of the aromatic moieties results in some degree of noncovalent bonding interaction between
them within the TS structure, thereby stabilizing the cisoid TS structure preferentially to the
transoid structure. In the case of the QINO/PINO reactions with toluene, the cisoid transition state
structures are 3.2 kcal/mol lower in free energy relative to transoid structures in the gasꢀphase (see
Tables S1ꢀS2 in the SI). The preferential stabilization of the cisoid TS structures persist in solvent
but the differential between the cisoid and transoid structures is reduced by ca. 1 kcal/mol (see
Tables S3ꢀS4 in the SI), presumably because the transoid TS structures are more stabilized by
interactions with the solvent field.
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The calculated free energy barrier height for the reaction between QINO and toluene is 19.6
kcal/mol. As expected on the basis of the arguments made above, this barrier is found to be 1
kcal/mol lower than that associated with the PINO reaction. Both barriers are expected to be overꢀ
estimated by ca. 2ꢀ3 kcal/mol on the basis that B3LYP predicts a larger differential between the
NHQI/NHPI OꢀH BDEs and the toluene methyl group CꢀH BDE than does (RO)CBSꢀQB3.
The lower free energy barrier in the QINOꢀtoluene HAT reaction is consistent with the fact that
there is a higher degree of charge transfer between the reactants in this system as compared to that
in the PINOꢀtoluene reaction. For example, our solventꢀphase calculations indicate that 0.47
electrons are transferred from toluene to QINOꢀtoluene in the cisoid TS complex, which is 0.06
electrons higher than in the analogous PINOꢀtoluene complex. For comparison, the degree of
charge transfer system in the transoid TS structures is 2ꢀ4 fold lower. This supports the notion that
the ring stacking interactions in the TS facilitates charge transfer and promotes HAT.
After the hydrogen atom transfer is completed, the calculations predict that the species involved in
the reaction will not remain complexed in acetonitrile. The enthalpies/free energies associated with
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complexation within the postꢀreaction complex are predicted to be +3.4/+13.3 kcal/mol for NHQIꢀ
benzyl and +4.7/+14.4 kcal/mol for NHPIꢀbenzyl, relative to the reactants in solvent. The final
dissociated products of the HAT reaction in solvent are 10.3 (QINO) and 11.4 (PINO) kcal/mol
higher in free energy than the reactants. On the basis of the differences between the B3LYP and
(RO)CBSꢀQB3 bond dissociation energies, our expectation is that the free energies of the two
reactions are closer to 7ꢀ8 kcal/mol.
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(a)
(b)
Figure 7. Optimized structures for the preꢀreaction, transition state, and postꢀreaction structures for
the reaction of (a) QINO and (b) PINO with toluene. Structures were obtained using the B3LYPꢀ
DCP/6ꢀ31+G(2d,2p) with the SMD solvation (acetonitrile) model. Key distances shown are in
Angstroms. Key: Carbon = grey; Hydrogen = White; Oxygen = red; Nitrogen = blue. The geometric
centers of the fiveꢀ and six membered rings are shown as purple spheres.
Kinetic study of the HAT from C-H bonds to QINO and PINO
Kinetic studies were carried out by UVꢀvis spectrophotometry generating QINO and PINO by
oxidation of NHQI and NHPI with cerium(IV) ammonium nitrate in CH3CN at T = 25 °C.3,12,29 The
decay of the Nꢀoxyl radicals was recorded at 390 nm and 380 nm for QINO and PINO, respectively.
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Using an excess of substrates (at least 10ꢀfold) to attain pseudo firstꢀorder conditions, clean first
order decays were observed with the Hꢀabstraction rate faster than the spontaneous decay of the Nꢀ
oxyl radicals and excellent linear fits were obtained by plotting the pseudoꢀfirst order rate constants
(kobs) as a function of the concentration of hydrogen donors. From the slope of these plots, the
second order rate constants for HAT (kH) were determined, as shown in Figure 8 for the reactions of
QINO with alkylaromatics.30
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0.25
Toluene
r2 = 0.997
Ethylbenzene r2 = 0.991
0.20
0.15
0.10
0.05
0.00
Cumene
p-Xylene
r2 = 0.992
r2 = 0.983
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
[Ar-R] (M)
Figure 8. Dependence of the observed rate constants (kobs) against [substrate] for the reactions of
QINO with alkylaromatics measured in CH3CN solution at T = 25°C by following the decay of
QINO at 390 nm.
The kH values are collected in Table 2 for the reactions of QINO and PINO with
alkylaromatics and in Table 3 for the other hydrogen atom donors. In Table 2 are also reported the
kH values for the HAT reactions of QINO with alkylaromatics in the presence of either 0.15 M
HClO4 or 0.15 M Mg(ClO4)2 in CH3CN. Linear plots of kobs against [substrate] are reported in
Figures S4ꢀS39 in the Supporting Information.
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Table 2. Second order rate constants (kH) for hydrogen atom transfer (HAT) from alkylaromatics to
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QINO and PINO measured in CH3CN at T = 25 °C.
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kH (Mꢀ1sꢀ1) a
Substrate
QINO
PINO
0.11
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0.2
2.8b
0.33c
1.5
0.95d
28b
2.4c
1.17d,e
2.9
57b
3.7c
1.3
1.3
0.93
0.65
9.7b
1.2c
0.57d
0.68d,e
0.15
1.9b
0.11
CH3
0.11
0.45b
0.07
H3COC
0.036
0.11b
0.022
a Average of at least three independent determinations. Error ± 5%. Statistically corrected for the
number of labile hydrogens. Correlation coefficients 0.982<r2<0.999. In the presence of 0.15 M
HClO4. c In the presence of 0.15 M Mg(ClO4)2. d See Ref. 12.e In the presence of 0.1 M HClO4.
b
Table 3. Second order rate constants (kH) for hydrogen atom transfer (HAT) from aliphatic
hydrocarbons, alcohols, aldehydes, ethers and amides to QINO and PINO measured in CH3CN at T
= 25 °C.
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kH (Mꢀ1sꢀ1) a
Substrate
QINO
0.034
PINO
0.014
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0.54
0.15
0.032
0.012
CH3OH
0.55
3.8
0.29
2.1
CH3CH2OH
(CH3)2CHOH
0.55
0.19
2.2
1.0
0.19
0.14b
a
Average of at least three independent determinations. Error ± 5%. Correlation coefficients
0.972<r2<0.999. See ref. 12.
b
Discussion
The data shown in Tables 2ꢀ3 indicate that the presence of the Nꢀheteroaromatic ring in QINO
results in a significant increase in HAT rate constants involving all the substrates. The higher
reactivity of QINO compared to PINO can be rationalized on the basis of both enthalpic and polar
effects. We found that the BDENOꢀH value for NHQI determined experimentally by the EPR radical
equilibration technique is ca 0.7 kcal/mol higher than that of NHPI, and 1.1 kcal/mol by the
B3LYPꢀDCP approach in solvent. The introduction of an electronꢀwithdrawing nitrogen atom into
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the aromatic ring of NHQI results in a destabilization of the chargeꢀseparated resonance structure of
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the Nꢀoxyl radical (see Figure 2),2c thereby increasing the BDENOꢀH
.
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The reactivity of Nꢀoxyl radicals in the HAT processes is determined by both the enthalpic
requirements of the CꢀH and NOꢀH bond dissociation energies and by the polar effects that may
stabilize the activated complex.6 The introduction of an N atom in the aromatic ring of QINO leads
to a stabilization of the activated complex by increasing the electron density on QINO. Figure 7
shows an example of these stabilizing effects in the TS for the HAT from substituted toluenes.
The computational modelling of the benzylic hydrogen abstraction from toluene by QINO and
PINO provides additional insights on the role of charge transfer stabilization of TS structures. The
hydrogen transfer occurs by the same mechanism described in the previous study on the reactions of
activated phenols with PINO and other Nꢀoxyl radicals.6g,8 The preꢀreaction complex that is formed
between the reactants has a cisoid structure that is stabilized through πꢀstacking interactions (see
Figure 7). Relative to the separated reactants, the complexes have free energies of 5.5 (QINO) and
4.6 (PINO) kcal/mol. The cisoid arrangements are maintained in the TS structures, allowing a
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charge transfer contribution to the HAT process through the πꢀoverlap between the benzylic and
QINO aromatic rings.31 The calculations support the expectation that the inclusion of a nitrogen
atom in the aryl ring of the abstracting radical, as in QINO, allows for a greater degree of charge
transfer in the TS. Specifically, 0.06 more electrons are transferred between the QINO and benzyl
moieties in the TS structure than in the analogous TS structure involving PINO.
The kH values for the HAT from alkylaromatics to QINO reported in Table 2 show an increase
along the series cumene > ethylbenzene > toluene, as expected from the series of decreasing CꢀH
BDEs from the tertiary CꢀH bond of cumene (BDE = 83.2
1.2 kcal molꢀ1)32 and is in line with the HAT promoted by PINO in
±
1 kcal molꢀ1)32 to the primary CꢀH
bond in toluene (BDE = 89.7
±
acetic acid2b and in CH3CN (see Table 2). For the series of substituted toluenes, as expected for a
HAT process promoted by electrophilic radicals and in accordance with the enthalpic and polar
effects discussed above, the kH values increase with the electron donating strength of the aryl
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X
H
substituent. When the log(kH /kH ) values for the reactions of QINO with substituted toluenes were
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plotted against the OkamotoꢀBrown substituent constants σ+, good Hammettꢀtype correlations was
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obtained (Figure 9).33 The negative
σ+ rather than the
ρ
value (ꢀ0.99),34 as well as the better linearity obtained with the
σ
constants, are in accordance with the significant polar effects associated to the
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development of a partial positive charge on the benzylic position in the HAT TS.
1.0
2
r = 0.94
p-OCH3
p-CH3
0.5
0.0
H
m-I
p-COCH3
-0.5
-1.0
p-CN
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
0.8
σ+
Figure 9. Hammett plot for the reaction of substituted toluenes with QINO in CH3CN at 25°C.
Table 3 shows the rate constants for the HAT from a series of hydrogen atom donors. Rate
constants for the HAT from CꢀH bonds in unactivated aliphatic hydrocarbons (cyclohexane and
adamantane), as expected, are significantly lower than those determined with alkylaromatics. The
increase in reactivity observed for QINO as compared to PINO is of fundamental importance with
these substrates which are characterized by relatively high CꢀH BDE values (99.5 kcal/mol for
cyclohexane, 96.2 and 98.4 kcal/mol for tertiary and secondary CꢀH bonds respectively in
adamantane).32
The higher reactivity observed in HAT from alcohols, ethers (THF), amides (DMF) is in line with
the enthalpic and polar effects associated with electron rich CꢀH bonds in
α position to heteroatoms,
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able to stabilize the partial positive charge that develops on carbon in the HAT.
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The presence of the heteroaromatic nitrogen in NHQI allows a further activation of the
corresponding Nꢀoxyl radical in HAT processes by adding Brønsted or Lewis acids in fact the
protonation or coordination of the N atom decreases the electron density on QINO (Figure 10).35
An increased electrophilicity of QINO would result as a consequence of the destabilization of the
charge separated resonance structures shown in Figure 10. In this context, it should be mentioned
that through complexation of NHQI with cobalt and copper ions it was possible to improve the
activity of NHQI in the oxidation of toluene. This activating effect has been interpreted on the basis
of an electronꢀwithdrawing effect produced by the complexation of the Nꢀheteroaromatic ring with
the metal salts. The complexation of NHQI with CuCl2 has been also confirmed through real time in
situ FTIR spectral analysis.10
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O
O
O
O
N O
N O
N O
N O
N
H
N
H
N
N
O
O
O
O
Mg2+
Mg2+
Figure 10. Resonance structures of QINO in the presence of Brønsted or Lewis acids
In order to investigate the effect of acid additives on the QINO reactivity in HAT process, kinetic
studies with alkylaromatics were also investigated in the presence of 0.15 M HClO4 and 0.15 M
Mg(ClO4)2.
Considering the electron withdrawing effect of the two imidic carbonyls, the pKa value for
piridinium cation (pKa = 12.3 in CH3CN)36 is much higher than that of HClO4 (pKa = 2.0 in
CH3CN),36 thus the protonation of QINO to give QINOH+● in 0.15 M HClO4 should be almost
quantitative. Accordingly, a variation of the UVꢀvis spectra of QINO, generated by oxidation of
NHQI (1.0 mM) with CAN (0.5 mM) in CH3CN, was observed as a function of increasing the
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[HClO4] up to the value of 0.15 M (see Figure S40 in the SI).
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The data reported in Table 2 indicate increases in reactivity of more than one order of magnitude, in
the presence of 0.15 M HClO4 for all the alkylaromatics tested. This is consistent with the
previsions based on the favorable enthalpic and polar effects associated with the protonation of
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QINO. It should be noted that a smaller increase of the kH value for the HAT from alkylaromatics
(ethylbenzene and pꢀxylene, see Table 2) in the presence of HClO4 was also observed for PINO in a
previous study.12 The increase of reactivity with PINO has been attributed to the protonation of
imidic carbonyl groups.
Compared to HClO4 a lower degree of activation was observed in the presence of 0.15 M MgClO4.
For example the kH value for the HAT from toluene to QINO increased from 0.2 Mꢀ1sꢀ1 to 0.33 Mꢀ1sꢀ
1 by addition of the Lewis acid. This behavior reflects a minor decrease of electron density in QINO
as compared to the perchloric acid.
The increase of QINO electrophilicity caused by the protonation of the heteroaromatic nitrogen is in
accordance with the more negative
ρ value (ꢀ1.8) determined in the Hammett correlation (see
Figure S42 in the SI) for the HAT process from substituted toluenes to QINO observed in the
presence of 0.15 M HClO4.
In conclusion the results reported in this study clearly indicate that QINO has greater hydrogen
abstracting ability than PINO in HAT processes from all the classes of organic compounds
investigated. This supports the use of Nꢀhydroxyquinolinimide (NHQI) as a convenient substituted
for Nꢀhydroxyphthalimide (NHPI) in the catalytic aerobic oxidations of substrates such as aliphatic
hydrocarbons that have relatively high CꢀH bond dissociation energies.
Experimental Section
Materials
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Acetonitrile (HPLC grade), Nꢀhydroxyphthalimide (NHPI), (NH4)2Ce(NO3)6, Mg(ClO4)2 and
HClO4 were commercially available and used as received. Nꢀhydroxyquinolinimide (NHQI) was
synthesized by reaction of pyridineꢀ2,3ꢀdicarboxylic acid anhydride37 with hydroxylamine
hydrochloride following a procedure reported in the literature.10
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Toluene, ethylbenzene, cumene, pꢀxylene, pꢀmethoxytoluene, mꢀiodotoluene, 4ꢀ
methylacetophenone, pꢀtolunitrile, cyclohexane, adamantane, methanol, ethanol, 2ꢀpropanol,
tetrahydrofuran, N,Nꢀdimethylformamide, pꢀchlorobenzaldehyde were commercially available at
their highest purity and used as received.
Kinetic Studies
QINO and PINO were generated by oxidation of the corresponding Nꢀhydroxyimides (NHQI and
NHPI) (1 mM) with cerium(IV) ammonium nitrate (CAN) 0.4 mM in CH3CN at 25 °C.
HAT reactions of QINO with alkylaromatics were investigated either in the absence of acid
additives or in the presence of HClO4 (0.15 M) or Mg(ClO4)2 (0.15 M). After the generation of the
Nꢀoxyl radicals, an excess of substrate was added in order to operate under pseudo firstꢀorder
conditions (final concentration 1.8ꢀ300 mM) and the absorbance change was monitored at 390 nm
for QINO and 380 nm for PINO. For all the substrates investigated each kinetic trace obeyed a firstꢀ
order kinetics. Secondꢀorder rate constants were obtained from the slopes of plots of the observed
rate constants kobs vs substrate concentration. Rate constants are reported as the average of at least
three independent determinations with an error ± 5%.
Acknowledgements. Thanks are due to the Ministero dell’Istruzione, dell'Università e della Ricerca
(MIUR) for financial support and to the CIRCC, Interuniversity Consortium of Chemical Catalysis
and Reactivity. We thank Prof. M. Bietti and Dr. M. Salamone for the use of LFP equipment. GAD
thanks the National Sciences and Engineering Research Council of Canada, the Canadian
Foundation for Innovation and the University of British Columbia for financial support and
Compute Canada for access to computational resources.
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Supporting Information Available: Instrumentation. Determination of the OꢀH BDE values by
EPR measurements. UVꢀvis spectroscopic characterization of QINO. EPR spectrum of QINO
obtained by oxidation of NHQI with cerium(IV) ammonium nitrate (CAN) in CH3CN at 25 °C.
EPR spectrum of irradiated CH3CN solution containing diꢀtertꢀbutyl peroxide, NHQI and 4ꢀ
CH3OCOꢀNHPI. Plots of kobs vs [substrate] for the reactions of QINO and PINO with
alkylaromatics, aliphatic hydrocarbons, alcohols, aldehydes, ethers and amides. UVꢀvis spectra of
QINO in MeCN/[HClO4] (0ꢀ0.2 M). Hammett plot for the HAT process from substituted toluenes to
PINO in CH3CN and to QINO in CH3CN/HClO4 0.15 M. Gasꢀ and solventꢀphase (acetonitrile)
computational results for HAT reaction of QINO/PINO with toluene. Optimized structures of the
transition states for the reaction of QINO and PINO with toluene. Cartesian coordinates of the
optimized structures of the reaction steps. This material is available free of charge via the Internet at
http://pubs.acs.org.
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References and notes
(1)
R. A.; Arends, I. W. C. E. Adv. Synth. Catal. 2004, 346, 1051ꢀ1071. (c) Recupero, F.; Punta, C.
Chem. Rev., 2007, 107, 3800ꢀ3842. (d) Coseri, S. Catal. Rev. 2009 51, 218ꢀ292. (e) Melone, L.;
(a) Ishii, Y.; Sakaguchi, S.; Iwahama, T. Adv. Synth. Catal. 2001, 343, 393ꢀ427. (b) Sheldon,
,
Punta, C. Beilstein J. Org. Chem. 2013, 9, 1296ꢀ1310. (f) Wertz, S.; Studer, A. Green Chem. 2013,
15, 3116ꢀ3134. (g) Chen, K.; Zhang, P.; Wang, Y.; Li, H. Green Chem. 2014, 16, 2344ꢀ2374, and
references cited therein.
(2)
(a) Ueda, C.; Noyama, M.; Ohmori, H.; Masui, M. Chem Pharm. Bull. 1987, 35, 1372ꢀ1377.
(b) Koshino, N.; Cai, Y.; Espenson, J. H. J. Phys. Chem. A 2003, 107, 4262ꢀ4267. (c) Amorati, R.;
Lucarini, M.; Mugnaini, V.; Pedulli, G. F.; Minisci, F.; Recupero, F.; Fontana, F.; Astolfi, P.; Greci,
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L. J. Org. Chem. 2003, 68, 1747
2003, 68, 9364ꢀ9370.
−1754. (d) Koshino, N.; Saha, B.; Espenson, J. H. J. Org. Chem
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8
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(3) (a) Galli, C.; Gentili, P.; Lanzalunga, O.; Lucarini, M.; Pedulli, G. F. Chem. Commun., 2004,
2356ꢀ2357. (b) Brandi, P.; Galli, C.; Gentili, P. J. Org. Chem., 2005, 70, 9521ꢀ9528. (c) Galli, C.;
Gentili, P.; Lanzalunga, O. Angew. Chem. Int. Ed. 2008, 47, 4790ꢀ4796. (d) Coniglio, A.; Galli, C.;
Gentili, P.; Vadalà, R. J. Mol. Catal. B: Enzym., 2008, 50, 40ꢀ49. (e) Coniglio, A.; Galli, C.;
Gentili, P.; Vadalà, R. Org. Biomol. Chem., 2009, 7, 155ꢀ160.
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(4)
The initial value of 88.1 kcal molꢀ1 has been recalculated using the corrected OꢀH BDE
value for the reference compound BHT (ref. 5).
(5)
(a) Mulder, P.; Korth, H.ꢀG.; Pratt, D. A.; DiLabio, G. A.; Valgimigli, L.; Pedulli, G. F.;
Ingold, K. U. J. Phys. Chem. A 2005, 109, 2647ꢀ2655.(b) Capraro, M. G.; Franchi, P.; Lanzalunga,
O.; Lapi, A.; Lucarini, M. J. Org. Chem. 2014, 79, 6435ꢀ6443.
(6) (a) Minisci, F.; Punta, C.; Recupero, F.; Fontana, F.; Pedulli, G. F. J. Org. Chem. 2002, 67,
2671ꢀ2676. (b) Minisci, F.; Punta, C.; Recupero, F.; Fontana, F.; Pedulli, G. F. Chem. Commun.
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3438. (b) Cai, Y.; Koshino, N.; Saha, B.; Espenson, J. H. J. Org. Chem 2005, 70, 238ꢀ243. (c)
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Org. Chem. 2016, 81, 11924ꢀ11931.
(13) Avila, D. V.; Brown, C. E.; Ingold, K. U.; Lusztyk, J. J. Am. Chem. Soc. 1993, 115, 466ꢀ470.
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(16) The aN value of QINO is higher than that previously reported for PINO (aN = 4.76) in
accordance with the electron withdrawing effect of the QINO Nꢀheteroaromatic ring (see ref. 7a).
(17) Da Silva, G.; Bozzelli, J. W. J. Phys. Chem. C 2007, 111, 5760ꢀ5765.
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(18) The value of 88.9 kcal molꢀ1 reported in ref. 7a has been recalculated using the corrected OꢀH
BDE value for the reference compound BHT (ref. 5).
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(19) Franchi, P.; Mezzina, E.; Lucarini, M. J. Am. Chem. Soc. 2014, 136, 1250−1252.
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(20) The error in the BDE measured by EPR (±0.6 kcal/mol) is related to the error reported for the
original BDE measurement of NHPI used as reference (ref. 2c). However, ꢀBDEs errors in the EPR
measurements are generally smaller (less than 0.3 kcal/mol). The accuracy of the EPR method relies
on the fact that even relatively large errors in the measurement of radical concentrations and
therefore of the equilibrium constant, Keq, give rise to small errors in the ꢀBDEs because of the
logarithmic relation connecting these two quantities.
(21) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648−5652. (b) Lee, C.; Yang, W.; Parr, R. G. Phys.
Rev. B 1988, 37, 785−789.
(22) (a) Torres, E; DiLabio, G. A. J. Phys. Chem. Lett. 2012, 3, 1738ꢀ1744. (b) DiLabio, G. A.;
Koleini, M.; Torres, E. Theor. Chem. Acc. 2013, 132, 1389.
(23) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2009, 113, 6378ꢀ6396.
(24) Montgomery, J. A., Jr.; Frisch, M. J.; Ochterski, J. W.; Petersson, G. A. J. Chem. Phys. 2000,
112, 6532−6542.
(25) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;
Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A. et al. Gaussian 09, revision D.01;
Gaussian, Inc.: Wallingford, CT, 2009.
(26) The computed gasꢀphase BDEs are lower than the experimental BDE values measured in polar
solvents due to hydrogen bond of the Nꢀhydroxylamines with the solvent, see ref. 8.
(27) DiLabio, G. A.; Johnson, E. R. J. Am. Chem. Soc. 2007, 129, 6199ꢀ6203.
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(28) Harshan, A. K.; Soudackov, A. V.; HammesꢀSciffer, S. J. Am. Chem. Soc. 2015, 137, 13545ꢀ
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13555.
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(29) The use of LFP technique for the generation and reactivity studies of shortꢀlived aminoxyl
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radicals is limited to very fast reaction processes (in the
much faster than those reported in the present study.
ꢁs and ms timescale, see refs. 8, 13bꢀc),
(30) The pseudo firstꢀorder rate constant for the decay of QINO is described by the equation kobs
=
kd + kH [ArꢀR] where kd is the QINO self decay rate constant. Thus in the plot of kobs vs [ArꢀR] the
intercept on the kobs axis ([ArꢀR] = 0) should not be on the origin but should be equal to kd. Since
the extrapolated intercept value is always subjected to significant errors, a precise kd determination
using this approach is not allowed.
(31) It is rather difficult to determine with accuracy the contribution of charge transfer from πꢀ
stacking between the aryl rings of PINO/QINO and aromatic substrates to the HAT process since it
is summed to the enthalpic and other polar effects, also present in the nonꢀaryl hydrocarbons. On
these basis a direct comparison of the relative weight of these effects with different substrates is not
possible.
(32) Luo, Y.ꢀR. Comprehensive Handbook of Chemical Bond Energies, CRC Press: Boca Raton,
2007.
(33) A similar behaviour in Hammett type correlations has been reported for hydrogen abstraction
promoted by other electrophilic radicals. Pryor, W. A.; Lin, T. H.; Stanley, J. P.; Henderson, R. W.
J. Am. Chem. Soc. 1973, 95, 6993. Walling, C.; Jacknow, B. B. J. Am. Chem. Soc. 1960, 82, 6113.
Gilliom, R. D.; Ward, B. F., Jr. J. Am. Chem. Soc. 1965, 87, 3944. Kennedy, B. R.; Ingold, K. U.
Can. J. Chem. 1966, 44, 2381. Russell, G. A.; Williamson, R. C., Jr. J. Am. Chem. Soc. 1964, 86,
2357. Pearson, R. E.; Martin, J. C. J. Am. Chem. Soc. 1963, 85, 354. Huyser, E. S. J . Am. Chem.
Soc. 1960, 82, 394.
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(34) The
ρ
value is in line with those determined for the reactions of substituted toluenes with PINO
5
6
in AcOH (ꢀ1.3) (ref. 2d) and in CH3CN (ꢀ1.0, see Figure S41 in the Supporting Information)
7
(35) The good hydrogen abstracting ability of QINOH+•, generated from acidꢀbase reaction of
NHQI and 4ꢀcarboxylꢀNꢀhydroxyphthalimide, was taken into account to explain the high catalytic
activity in the aerobic oxidation of ethylbenzene (ref. 11).
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(36) Izutsu, K. Acid-base Dissociation Constant in Dipolar Aprotic Solvents, Alden Press Oxford
(1990).
(37) Gould, K. J.; Hacker, N. P.; McOmie, J. F. W.; Perry, D. H. J. Chem. Soc. Perkin Trans. 1
1980, 1834ꢀ1840.
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