Evaluation of Polar Effects in Hydrogen Atom Transfer Reactions from

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Evaluation of Polar Effects in Hydrogen Atom Transfer Reactions from Activated Phenols Massimo Bietti, Erica Cucinotta, Gino A. DiLabio, Osvaldo Lanzalunga, Andrea Lapi, Marco Mazzonna, Eduardo Romero Montalvo, and Michela Salamone J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02571 • Publication Date (Web): 22 Jan 2019 Downloaded from http://pubs.acs.org on January 26, 2019

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The Journal of Organic Chemistry

Evaluation of Polar Effects in Hydrogen Atom Transfer Reactions from Activated Phenols Massimo Bietti,b Erica Cucinotta,a Gino A. DiLabio,c,d Osvaldo Lanzalunga,a* Andrea Lapi,a Marco Mazzonna,a Eduardo Romero-Montalvo,c Michela Salamoneb

a

Dipartimento di Chimica, Sapienza Università di Roma and Istituto CNR di Metodologie

Chimiche (IMC-CNR), Sezione Meccanismi di Reazione, c/o Dipartimento di Chimica, Sapienza Università di Roma, P.le A. Moro, 5 I-00185 Rome, Italy b

Dipartimento di Scienze e Tecnologie Chimiche, Università "Tor Vergata", Via della Ricerca

Scientifica, 1 I-00133 Rome, Italy. c Department

of Chemistry, University of British Columbia, 3247 University Way, Kelowna, British

Columbia, Canada V1V 1V7 d Faculty

of Management, University of British Columbia, 1137 Alumni Ave

Kelowna, British Columbia, Canada V1V 1V7

CORRESPONDING AUTHORS FOOTNOTE * E-mail: [email protected]; RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the journal that you are submitting your paper to)

1 ACS Paragon Plus Environment

The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

OH H3C

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O CH3 +

R

kH

H3C

CH3 +

X

RH

X

X = H, OCH3

log(k HmOMe/k HH) increase with increasing HAT polar ef f ects

Abstract. Evaluation of polar effects in hydrogen atom transfer (HAT) processes is made difficult by the fact that in most cases substrates characterized by lower bond dissociation energies (BDEs), activated from an enthalpic point of view, are also more activated by polar effects. In the search of an exception to this general rule we found that the introduction of a methoxy substituent in the 3position of 2,6-dimethylphenol results in a small increase in the OH BDE and a decrease of the ionization potential (IP) of the phenol. These findings suggest that the enthalpic effect associated with the addition of the meta methoxy group to 2,6dimethylphenol will decrease reaction rates, while the polar effects will increase reaction rates. Our model analysis of polar effects has been experimentally validated by comparing the reactivity of 2,6-dimethylphenol with that of 2,6dimethyl-3-methoxyphenol in HAT promoted by a series of radicals (cumyloxyl, galvinoxyl, 2,2diphenylpycrylhydrazyl, phthalimide-N-oxyl and benzotriazole-N-oxyl radicals). In line with our predictions the ratio of HAT rate constants (kHmOMe/kHH) is larger in cases where there is a greater contribution of polar effects in the HAT reaction i.e. in HAT promoted by N-oxyl radicals containing electron withdrawing groups or when more polar solvents are employed.


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Introduction Hydrogen atom transfer (HAT) reactions involving oxygen centered radicals have attracted considerable attention in recent years1,2 in view of their fundamental role in important chemical and biological processes. Relevant examples include the degradation of biomolecules, polymers and volatile organic compounds,2-4 reactions involved in photosynthetic systems5 and in the radical scavenging activity of phenolic antioxidants,2,3,6 enzymatic and biomimetic oxidation reactions,7 and useful synthetic procedures.8 Several experimental and theoretical studies explored the dependence of the kinetics of HAT processes on enthalpic effects based on the difference between the bond dissociation enthalpies (BDEs) of the XH bond cleaved and the OH bond formed in the reaction (eq. 1) and the relative stabilities of the reactant radicals SO and product radicals X. The role of enthalpic effects in HAT reactions has been clearly evidenced in several kinetic studies showing that HAT rate constants regularly increase by decreasing the XH BDEs.9

HAT SO

+

X SO

H

SO H

+

X

(1)

= RO , ROO , R2NO etc.

However, enthalpic effects alone are not able to account for the differences in reactivity and selectivity displayed by oxygen centered radicals in all HAT processes. Polarization of the HAT transition state (TS) due to the partial charge transfer from the substrate to the radical may determine a stabilization of the TS reducing the activation energy required for HAT as shown in Figure 1 for HAT promoted by oxygen centered radicals where the TS is stabilized by the charge separated resonance form b. These polar effects which add to the enthalpic one described above,10 3 ACS Paragon Plus Environment


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have been reported in particular for HAT reactions from O-H and C-H bonds to alkoxyl, peroxyl, aminoxyl and 2,2-diphenyl-1-picrylhydrazyl (dpph•) radicals.1a,11

SO

H a

X

SO

H b

X

.

SO + H-X

SO-H + X

.

Figure 1. Stabilization of the TS of HAT promoted by oxygen centred radicals by polar effects.

The quantitative analysis of the contribution of polar effects in HAT reactions promoted by radical species represents an important goal from a synthetic perspective since it might be helpful in the control of the reactivity and selectivity of these processes. It is not easy to evaluate the relative contribution of polar and enthalpic effects in HAT processes since, in most cases, they operate in the same direction of enthalpic effects. That is, substrates that are activated from an enthalpic point of view containing cleavable bonds, characterized by lower BDEs relative to an unactivated 4 ACS Paragon Plus Environment

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reference compound, are also activated by polar effects. para-Substituted phenols, in which both the OH BDE and the phenol’s ionization potential decrease with increasing substituent electron donating (ED) ability, are exemplars in which enthalpic and polar effects operate in the same direction. The evaluation of polar effects in HAT processes could be facilitated by the use of substrates where enthalpic and polar effects operate in opposite directions. In this respect, the introduction of a methoxy group in the meta position of phenolic substrates appears to be of particular interest. The m-methoxy group is normally electron withdrawing as indicated by its effects on the dissociation of benzoic acids in water (m = +0.12) and on the solvolysis of cumyl chlorides in 90 % acetone/water (m = +0.12, m+ = +0.047).12 However, Foti et al. showed that 3-methoxyphenol is more reactive than phenol in HAT reactions involving alkoxyl (cumyloxyl, CumO and tertbutoxyl, tBuO) and 2,2-diphenyl-1-picrylhydrazyl(dpph) radicals.13b These results were rationalized on the basis of enthalpic considerations: the O-H BDE of 3-methoxyphenol was determined to be lower than that of phenol both experimentally (BDE=1.0 kcal mol-1)14 and theoretically (BDE=1.25 kcal mol-1) by means of density-functional theory (DFT) calculations.15 Alternatively, the higher HAT reactivity of m-methoxyphenol as compared to phenol may also be explained by polar effects associated to the stabilization of the partial positive charge that develops in the TS, exerted by the methoxy group.16 Foti et al. emphasized that the m+(OMe) value becomes more positive as the electron-request at the 1-position increases, as is the case in phenoxyl radicals where Ois strongly electron withdrawing.13b In light of the foregoing, we decided to explore the role of polar effects in HAT reactions by examining the effect of the m-methoxy group in 2,6-dimethylphenol, an activated phenol more akin to natural phenolic antioxidants which are generally characterized by the presence of ED substituents in the ortho/para positions.14 On the basis of preliminar theoretical calculations, we expect that the presence of two ortho methyl groups reduce the BDE determined by the 5 ACS Paragon Plus Environment


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introduction of a m-MeO group, thus unmasking polar effects in HAT. For 3-methoxyphenol, the structure in which the –OMe group points “away” from the OH group is lower in enthalpy than the “toward” structure by about 0.5 kcal/mol. In the 3-methoxyphenoxyl radical, calculations predict that the structure in which the –OMe group points toward the OH group is lower in enthalpy than the “away” structure by about 2.3 kcal/mol, which likely results from much stronger Coulomb interactions between the methyl group of –OMe and -O• (see SI). The large differences between the parent and radical can be attributed to the fact that conversion of -OH into -O• strongly increases the electron withdrawing character of this group.13 In 2,6-dimethylphenol, sterics dictate that the – OMe group must be in the “away” orientation in both the parent and the radical. Consequently, the radical structure loses the ~2.3 kcal/mol stabilization that is present in the 3-methoxyphenoxyl radical. As a result, when is present at the 3-position of 2,6-dimethylphenol the –OMe group determines an increase in the the O-H BDE. We thus report the analysis of the difference in reactivity between 2,6-dimetylphenol (1) and 3methoxy-2,6-dimethylphenol (2) in HAT promoted by different classes of oxygen centered radicals (CumO, galvinoxyl (GO), phthalimide-N-oxyl (PINO), benzotriazole-N-oxyl (BTNO), 3quinazolin-4-one-N-oxyl (QONO) and 3-benzotriazin-4-one-N-oxyl (BONO)) and the N-centered radical dpph, the structures of which are displayed in Figure 2.


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OH H 3C

O CH3 +

H 3C

kH

R

CH3 +

X

RH

X

1 X=H 2 X = OCH3

R CH3

O

O

O CH3 Cumiloxyl radical CumO

Galvinoxyl radical GO

Aminoxyl radicals O N

O

O O

N

H3CO

MeOOC N

O

N

O

O

O

O

N

O

O

Phthalimide-N-oxyl radical 4-Methoxyphthalimide-N-oxyl radical 3-Quinazolin-4-one-N4-Carboxymethyl(PINO) (4-MeO-PINO) oxyl radical (QONO) phthalimide-N-oxyl radical (4-CO2Me-PINO) N N N O

Benzotriazole-N-oxyl radical (BTNO)

N

N F3C

N

N

N N

N

N

Me

O

O

6-Trifluoromethylbenzotriazole6-Methylbenzotriazole-N-oxyl radical (6-CF3-BTNO) -N-oxyl radical (6-Me-BTNO)

N O

O

3-Benzotriazin-4-oneN-oxyl radical (BONO)

O 2N N

N

NO2

O 2N 2,2-Diphenyl-1-picrylhydrazyl radical (dpph )

Figure 2. Hydrogen atom transfer from 3-X-2,6-dimethylphenols1-2 to radicals Rand structure of the radicals employed in the study.



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The dependence of polar effects on the electronic substituent effects has been assessed using two series of aryl substituted PINO and BTNO radicals containing both electron withdrawing (EW) and ED substituents. Solvent effects on the HAT reactions have also been explored with dpph and Noxyl radicals.

2. Results HAT from phenols 1 and 2 to alkoxyl and N-oxyl radicals was too fast to be followed by conventional spectrophotometry; in these cases the kinetic analysis was performed by ns laser flash photolysis (LFP). CumO was generated by 355 nm LFP of a 1.0 M solution of dicumyl peroxide in CH3CN (Scheme 1).

CH3 CH3 O O CH3 CH3

CH3 O CH3

h = 355 nm 2

CumO OH CH3 O CH3

H3C

O CH3

kH

+ X

CH3 OH CH3

H3C

CH3

+ X

1 X=H 2 X = OCH3

Scheme 1

As described previously, in CH3CN solution CumO displays a broad absorption band in the visible region of the spectrum centered at 485 nm.18 Under these conditions, HAT from phenols occurs in competition with CumO CCH3 β-scission.19 N-oxyl radicals were obtained following HAT from the corresponding N-hydroxy derivatives: 4-YN-hydroxyphthalimides

(4-Y-NHPIs),

6-Z-N-hydroxybenzotriazoles

(6-Z-HBTs),

3-

hydroxyquinazolin-4-one (NHQO) and 3-hydroxybenzotriazin-4-one (NHBO) to CumO produced 8 ACS Paragon Plus Environment

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as described above (Scheme 2).11j,20 The absorption spectra of the corresponding N-oxyl radicals were reported in previous studies.21 These species are stable on the millisecond timescale. When an excess of phenol 1-2was added, fast decays of the N-oxyl radicals were observed.

CH3 O CH3

+

CH3 OH + CH3

N OH

N O

OH H3C N O

O CH3

H3C

kH

+

N OH

CH3

+

X

X

1 X=H 2 X = OCH3

O N OH

=

X

N OH Y O 4-Y-NHPI

N

N N N OH 6-Z-HBT

N N

O NHQO

OH

O NHBO

N N

OH

Scheme 2

The second-order rate constants for HAT from 1 and 2 (kH in Schemes 1-2) were determined in CH3CN for the reactions with CumO, and both in CH3CN and chlorobenzene for the reactions with N-oxyl radicals, by following the decay of the radical absorption band as a function of substrate concentration. From the slope of the linear plots of the observed rate constants (kobs) against [substrate], the kH values were determined. The kinetic data determined by LFP are reported in Table 1.



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Table 1. Second-Order Rate Constants kH (M-1s-1) for HAT from 3-X-2,6dimethylphenols 1 and 2 to alkoxyl and N-oxyl radicals measured at T=25 °C kH (M-1s-1) a OH

OH

R

Solvent

H3C

CH3

H3C

CH3

OCH3

a

1

2

CumO

CH3CN

3.7×107

3.6×107

PINO

CH3CN C6H5Cl

3.3×104 3.8×105

7.1×104 4.7×105

4-CO2Me-PINO

CH3CN C6H5Cl

4.0×104 6.6×105

9.3×104 7.2×105

4-CH3O-PINO

CH3CN C6H5Cl

2.2×104 2.6×105

2.6×104 2.9 ×105

BTNO

CH3CN C6H5Cl

6.2×103 8.0×104

7.3×103 7.4×104

6-CF3BTNO

CH3CN C6H5Cl

1.8×104 1.8×105

2.6×104 2.7×105

6-CH3-BTNO

CH3CN C6H5Cl

6.0×103 6.1×104

7.0×103 6.1×104

BONO

CH3CN C6H5Cl

7.2×104 7.8×105

1.0×105 8.5×105

QONO

CH3CN C6H5Cl

1.2×105 8.5×105

2.0×105 9.8×105

Error ± 5%.

Figure 3 shows sample plots of kobsvs the concentration of 1 and 2 for the decay of the BTNO radical at 490 nm measured in CH3CN at T=25 °C. The kobs vs [substrate] plots for the reactions of CumO and of the other N-oxyl radicals with phenols 1-2 are reported in the SI as Figures S1-S32.


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25

2

20

-1

kobs (s )

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


1

15

10

5

0 0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

[ArOH] (mM) Figure 3. Plots of the observed rate constant (kobs) against [ArOH] for the reaction of BTNO with 1(●) and 2(▲) measured in CH3CN at T = 25ºC, kobs values were obtained following the decay of BTNO at 490 nm.

The rate constants for HAT from 1-2 to GO and dpph were determined spectrophotometrically in CH3CN by following the decay of the pertinent visible absorption bands centered at 428 nm and 517 nm, respectively.22,23 Reaction of 1 and 2 with dpph has been also investigated in benzene, tetrahydrofuran (THF) and isooctane for the analysis of solvent effects. Clean first-order decays were found and linear dependencies of kobs on the concentration of the phenols were obtained (Figures S33-S42 in the SI). From the slope of these plots the kH values were determined. All the kinetic data for HAT from phenols 1 and 2 promoted by GO and dpph are reported in Table 2.



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Table 2. Second-Order Rate Constants kH (M-1s-1) for HAT reaction from 3-X-2,6dimethylphenols 1 and 2 to GO and dpph measured at T=25 °C kH (M-1s-1) a R

Solvent

OH

OH H3C

CH3

H3C

CH3

OCH3

a

1

2

GO

CH3CN

0.53

0.25

dpph

CH3CN

0.11

0.11

THF

0.028

0.027

Benzene

1.22

0.77

Isooctane

4.6

3.0

Error ± 5%.

Theoretical calculations The gas-phase OH BDEs and the vertical IPs for 1 and 2 were computed using the restricted open-shell (RO) version of CBS-QB3,24 as implemented in the Gaussian-16 program.25 The OH BDE calculated for 2,6-dimethylphenol (83.9 kcal/mol) is in accordance with the experimental value reported in the literature (84.5 kcal/mol)14b and is 0.2 kcal/mol lower than that calculated for 3-methoxy-2,6-dimethylphenol (84.1 kcal/mol). This is consistent with the weak electron withdrawing effect of the 3-methoxy substituent in the dimethylated phenol. The calculated vertical IP for 3-methoxy-2,6-dimethylphenol is 7.8 kcal/mol lower than that of 2,6-dimethylphenol (185.4 vs. 193.2 kcal/mol) in accordance with the more easily oxidizable methoxylated aryl ring. Both the vertical and adiabatic ionization potentials follow the same trend in solution. For example, in acetonitrile, we computed (RO)CBS-QB3 adiabatic and vertical IPs of 139.7 and 144.5 kcal mol-1, 12 ACS Paragon Plus Environment

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respectively, for 2,6-dimethylphenol and 134.5 and 139.1 kcal mol-1 for 2,6-dimethyl-3methoxyphenol. In PhCl, we computed adiabatic and vertical IPs of 147.1 and 151.8 kcal mol-1, respectively, for 2,6-dimethylphenol and 142.2 and 146.0 kcal mol-1 for 2,6-dimethyl-3methoxyphenol.

3. Discussion The calculated OH BDE and IP values for 2,6-dimethylphenol (1) and 3-methoxy-2,6dimethylphenol (2) theoretically calculated fully support the initial hypothesis that enthalpic and polar effects in HAT from these activated phenols operate in opposite directions. If enthalpic effects dominate the HAT reaction, 1 would be expected to be more reactive than 2. On the other hand, if polar effects are more important, 2 would exhibit greater reactivity than 1. Kinetic analysis of HAT from phenols 1 and 2 to CumO (Table 1, entry 1) indicates that the introduction of the methoxy group in the 3-position of 2,6-dimethylphenol results in a negligible effect on the rate constant kH. This result is noteworthy since it can be rationalized on the basis of enthalpic effects associated with the slightly higher OH BDE value calculated for 2. These effects compensate the polar ones that would favor HAT from 2. A different outcome was observed in HAT from phenol and m-methoxyphenol promoted by CumO where the latter substrate was two times more reactive than the former (see ref. 13b and entry 1, Table 3). The increase in kH measured on going from phenol to m-methoxyphenol is consistent with our prediction that two methyl groups in the ortho positions of 1 and 2 significantly reduce the BDE determined by the introduction of m-MeO group, allowing the unmasking of polar effects. This supports the notion that 3-methoxy-2,6-dimethylphenol represents a suitable probe for the exploration of polar effects in HAT reactions. Hydrogen abstraction from 1 and 2 promoted by N-oxyl radicals occurs with lower rate constants as compared to CumO• (Table 1). This reflects the much lower BDE value of the NOH bond in N13 ACS Paragon Plus Environment


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hydroxylamines (78-89 kcal/mol)11j as compared to the OH bond of 2-phenyl-2-propanol (104.7 kcal/mol).26

Table 3. Second-Order Rate Constants kH (M-1s-1) for HAT from phenol and 3-methoxyphenol to alkoxyl, N-oxyl and dpph radicals measured at T=25 °C. kH (M-1s-1) a OH

OH

R OCH3

CumOa PINO 4-CO2Me-PINO 4-CH3O-PINO

1.2×109

2.4×109

2.0×102

1.3×103

7.7×102

2.7×103

2.4×102

7.2×102

80

2.4×102

4.1×102

1.7×103

61

1.6×102

2.9×103

9.7×103

4.8×103

1.6×104

0.1

1.4

BTNO 6-CF3BTNO 6-CH3-BTNO BONO QONO dpph b a

In hexane. b In cyclohexane. Ref. 13b

In all cases, the presence of the 3-MeO group results in an increase in kH (Table 1, entries 2-8), indicating that with these radicals the contribution of polar effects to reactivity is more important than that of enthalpic effects. These results align with our recent finding that the transition structures for HAT from activated phenols to N-oxyl radicals are characterized by a significant 14 ACS Paragon Plus Environment

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contribution of charge-transfer deriving from -stacking between the phenolic and N-oxyl aromatic rings.11j A similar outcome was observed in HAT from phenol and 3-methoxyphenol promoted by N-oxyl radicals where the latter substrate was observed to be between 2.6 and 6.5 times more reactive than the former (see entries 2-9, Table 3). The higher increase in kH observed in the latter systems by introducing the 3-MeO group again reflects the attenuating effect of the EW power of the O exerted by the two methyl groups in the ortho positions of 2. The analysis of the kinetic data of Table 1 for HAT from 1-2 to N-oxyl radicals also shows a significant dependence on the structure of the N-oxyl radical. As already reported in a previous study,11j the relative reactivity of the N-oxyl radicals employed (QONO>BONO>PINO>BTNO) follows

the

order

of

BDENO-H

values

of

the

corresponding

N-hydroxylamines

(NHQO>NHBO>NHPI>HBT). Moreover, in the series of aryl substituted PINOs and BTNOs kH increases by increasing the EW power of the aryl substituent. The increase in the EW character of the substituents determines an increase of the OH BDE (enthalpic effect) coupled with a stabilization of the partial negative charge that develops in the N-oxyl radical in the -stacked HAT TS.11j Rate constants for HAT from 1-2 to N-oxyl radicals have been also determined in chlorobenzene for the purpose of evaluating the role of solvent effects. As shown in Table 1, kH values in PhCl are about one order of magnitude higher than those measured in CH3CN. This observation is in agreement with Ingold’s model for kinetic solvent effects for HAT processes,6c with the rate constants that increase by decreasing the solvent β2H values that is by decreasing solvent hydrogen bond accepting (HBA) ability (β2H = 0.44 and 0.13 for CH3CN and PhCl, respectively).27 It should be noted that the differences in kH for 1 and 2 measured in PhCl are much smaller than those found in CH3CN. This suggests that the contribution of polar effects to the HAT reactivity is smaller in the less polar solvent PhCl. The smaller contribution of polar effects in PhCl is such that an inversion of reactivity is observed in HAT promoted by BTNO where kH was observed to 15 ACS Paragon Plus Environment


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slightly decrease on going from 1 to 2 (kH = 8.0×104 and 7.4×104 M-1s-1, respectively) as previously reported for the enthalpic controlled HAT reactions promoted by alkoxyl radicals. The final oxygen centered radical tested in this study is the phenoxyl radical GO. Rate constants for HAT from 1 and 2 to GO are much smaller than those measured with alkoxyl and N-oxyl radicals, as expected on the basis of the significantly lower OH BDE of GOH (77.7 kcal/mol).28 The kH value measured for 1 (0.53 M-1s-1) is more than double of that measured for 2 (0.25 M-1s-1), and this is indicative of a HAT process where the enthalpic effects dominate. In fact, HAT promoted by GO can be considered as a reference, where polar effects should be negligible in view of the close structural relationship between GOH and 1 and 2. For the reactions of 1 and 2 with dpph, it was possible to measure the rate constants in several solvents (CH3CN, THF, benzene and isooctane, see Table 2). As reported above for the reactions promoted by N-oxyl radicals, kH values measured in the polar solvents CH3CN and THF are much smaller than those measured in apolar solvents such as benzene and isooctane. In THF and MeCN very similar kH values have been measured for 1 and 2 while, in benzene and isooctane, 1 is always more reactive than 2. This result can be again rationalized on the basis of dominant enthalpic effects as observed in HAT reactions promoted by tert-alkoxyl radicals. The kH(2)/kH(1) ratio increases by increasing solvent polarity. This suggests that the polar contribution to HAT increases in the presence of more polar solvents which are able to better stabilize the partial positive charge that develops in the HAT transition state. In a given solvent, the relative reactivity of 2 and 1 toward different radicals can be taken as a suitable criterion for the evaluation of polar effects in HAT reactions. These can be conveniently compared using log(kHmOMe/kHH) values, which are listed in Table 4. We note that the log(kHmOMe/kHH) values listed in Table 4 increase from negative to positive values with increasing polar contribution to the HAT process. This occurs by increasing solvent polarity or


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by increasing the EW ability of substituents in the abstracting radical. These observations align with our initial hypotheses.

Table 4. log(kHmOMe/kHH) values determined for HAT from 3-X-2,6-dimethylphenols 1 and 2 to CumO, N-oxyl, GO and dpph radicals measured at T=25 °C R

Solvent

log(kHmOMe/kHH)

CumO

CH3CN

-0.012

PINO

CH3CN C6H5Cl

0.333 0.092

4-CO2Me-PINO

CH3CN C6H5Cl

0.366 0.038

4-CH3O-PINO

CH3CN C6H5Cl

0.073 0.047

BTNO

CH3CN C6H5Cl

0.071 -0.034

6-CF3-BTNO

CH3CN C6H5Cl

0.211 0.176

6-CH3-BTNO

CH3CN C6H5Cl

0.067 0

BONO

CH3CN C6H5Cl

0.143 0.037

QONO

CH3CN C6H5Cl

0.222 0.062

GO

CH3CN

-0.326

dpph

CH3CN THF Benzene Isooctane

0 -0.016 -0.200 -0.186



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4. Conclusions We showed in the present study that the introduction of a 3-methoxy substituent in 2,6dimethylphenol results in a small increase in the OH bond dissociation energy (decrease of HAT rates by enthalpic effect) and a decrease of the ionization potential of the phenol (increase of HAT rates by polar effects). In light of the foregoing, we propose a method for evaluating polar effects in HAT reactions involving OH bonds in activated phenolic compounds, one of the most important HAT reactions, by comparing the HAT reactivity of 2,6-dimethyl-3-methoxyphenol and 2,6dimethylphenol toward different abstracting radicals (CumO, N-oxyl, GO and dpph). In line with our predictions we found that the log(kHmOMe/kHH) values increase with increasing the polar contribution to the HAT process e.g. by increasing the EW power of radical substituents or by increasing solvent polarity. It can be envisaged that the results reported in this study will be helpful in the control of the reactivity and selectivity of HAT reactions involving phenolic OH bonds.

Experimental Section Materials. CH3CN (spectrophotometric grade), dicumyl peroxide, galvinoxyl (GO), 2,2diphenyl-1-picrylhydrazyl radical (dpph), N-hydroxyphthalimide, 1-hydroxybenzotriazole, 6trifluoromethyl-1-hydroxybenzotriazole and 6-hydroxybenzotriazin-4-one were used as received. 4Methoxy-N-hydroxyphthalimide,

4-methoxycarbonyl-N-hydroxyphthalimide,

6-methyl-1-

hydroxybenzotriazole and 3-hydroxyquinazolin-4-one were synthetized according to the literature.10b.21 2,6-Dimethylphenol, phenol and 3-methoxyphenol are commercially available. 3methoxy-2,6-dimethylphenol was prepared according to the literature.29 Laser flash photolysis experiments Laser flash photolysis experiments were carried out with an Applied Photophysics LK-60 laser kinetic spectrometer providing 8 ns pulses, using the third armonic (355 nm) of a Quantel Brilliant18 ACS Paragon Plus Environment

Page 19 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


B Q-switched Nd:YAG laser. The laser energy was adjusted to  10 mJ/pulse by the use of the appropriate filter. All the experiments were carried out in a 3.5 mL Suprasil quartz cell (10 mm  10 mm) at T = 25  0.5 °C under magnetic stirring. For the reactions of alkoxyl radicals with phenols , the irradiated N2-saturated CH3CN solutions contained dicumyl peroxide (1 M), or di-tert-butyl peroxide (2 M) and the phenols (0.05-5 mM) while for the reactions of N-oxyl radicals with phenols the N2-saturated CH3CN solutions irradiated contained dicumyl peroxide (1 M), N-hydroxylamines (5.0 mM) and phenols (0.05-50mM). Data were collected at individual wavelengths with an Agilent Infinium oscilloscope and analyzed with the kinetic package implemented in the instrument. Rate constants were obtained by monitoring the change of absorbance at the maximum absorption wavelengths of the alkoxyl or N-oxyl radicals by averaging 3-5 values. Each kinetic trace followed a first-order decay and kobs values were obtained by exponential fit of the absorbance decay traces. Second order rate constants were obtained from the slopes of the linear plots of kobs vs [substrate]. The kH values are the average of at least two independent experiments, with typical errors being ± 5%. Spectrophotometric kinetic studies For the reactions of phenols with GOand dpph a solution of substrates 1-2 was added into the solution of GO (6 M) or dpph (80 M) in CH3CN or other solvents in the spectrophotometric cuvette (final concentration 1-60 mM) thermostated at 25 °C. The absorbance changes at 428 nm and 517 nm for the experiments with GO and dpph, respectively, were recorded. For all the substrates investigated each kinetic trace followed a first-order decay and kobs values were obtained by exponential fit of the absorbance decay traces. Second order rate constants were obtained from the slopes of the linear plots of kobs vs [substrate]. The kH values are the average of at least two independent experiments, with typical errors being ± 5%. It was verified that the decay of the absorbance in the absence of the substrate was negligible in the time span of the kinetics.



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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. GAD thanks the National Sciences and Engineering Research Council, Canada Foundation for Innovation, and the BC Knowledge Development Fund for funding. ERM is grateful for the support provided by the Government of Mexico through CONACyT (Ph.D. Scholar/Scholarship 308773/472432).

Supporting Information Available: Absorbance vs time data for the decay of radicals and dependence of kobs for the decay of the radicals on the concentrations of phenols 1-2. Absorbance vs time data for the decay of radicals and dependence of kobs for the decay of the N-oxyl radicals on the concentrations of phenol and 3-methoxyphenol. Cartesian coordinates of optimized geometries and energies. This material is available free of charge via the Internet at http://pubs.acs.org.

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Evaluation of Polar Effects in Hydrogen Atom Transfer Reactions from

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