Distribution of Spin Density on Phenoxyl Radicals Affects the Selectivity of Aerobic Oxygenation of Phenols

Selectivity of Aerobic Oxygenation of Phenols

Article

Distribution of Spin Density on Phenoxyl Radicals Aﬀects the

∥

Yongtao Wang, Jun Guan, Bingbao Mei, Mengtian Fan, Rui Lu, Renfeng Du, Kaizhou Chen, Jia Yao,

Zheng Jiang,* and Haoran Li*

Cite This: https://dx.doi.org/10.1021/acs.inorgchem.9b02422

Read Online

ACCESS

Metrics & More

Article Recommendations

sı Supporting Information

ABSTRACT: Phenoxyl radical was generally suggested as the

intermediate during copper-catalyzed aerobic oxygenation of phenols.

However, the substrate-dependent selectivity has not been well

interpreted, due to insuﬃcient characterization of the radical

intermediate under reaction conditions. When studying the CuCl-

LiCl-catalyzed aerobic phenol oxidation, we obtained EPR spectra of

phenoxyl radicals generated by oxidizing phenols with the preactivated

catalyst. Upon correlation to the selectivity of benzoquinone, the

hyperﬁne coupling constant of para-site proton (a^H^,^p^a^r^a) was found to

be better than the Hammett constant. The catalysis mechanism was

studied based on EPR detection and the reaction results of phenoxyl

radicals under N or O atmosphere. It appeared that the chemo-

selectivity depended on the attack of activated dioxygen on phenoxyl

radicals, and the activation of dioxygen by [Cu Cl_n₊₁]⁻(n = 1, 2, 3) was suggested as the rate-determining step. Understanding of the

substrate-dependent selectivity contributed to predicting the chemoselectivity in the aerobic oxidation of phenols.

INTRODUCTION

very relevant to the Hammett constant, which is more suitable

for the reactivity at hydroxyl oxygen. Therefore, the more

suitable factor needs to be developed for phenol oxygenation.

There should be a relationship between the nature of the

phenoxyl radical and the oxygenation selectivity. However, a

clear description of this relationship is still absent, because only

■

The copper-catalyzed aerobic oxidation of phenols is not only

a crucial process in the body but also of great importance in

industrial processes. During the industrial production of

vitamin E, the oxidation of 2,3,6-trimethylphenol (2,3,6-TMP)

to 2,3,5-trimethyl-1,4-benzoquinone (TMBQ) is a crucial

sterically stabilized phenoxyl radicals, like 2,6-di-tert-butylphe-

process, where the most-used catalyst is CuCl with additives

noxyl radicals, are well characterized. Mu

ller et al. have

(

such as LiCl, NH OH·HCl, and ionic liquids). For various

isolated the 2,6-di-tert-butyl-4-Ph-phenoxyl radical, and

Mayer and co-workers have isolated and well characterized

the 2,4,6-tri-tert-butylphenoxyl radical and 2,6-di-tert-butyl-4-

para-hydrogen-substituted phenols, great eﬀorts have been

made to control the oxygenation selectivity, and a pathway

via phenoxyl radical is recommended. Our recently reported

a,4

(

4′-nitrophenyl)phenoxyl radical. Furthermore, with electron

work concerned the CuCl -catalyzed aerobic oxidation of

paramagnetic resonance (EPR), Brigati et al. have investigated

many para-substituted 2,6-di-tert-butyllphenoxyl radicals and

revealed the relationship between the hyperﬁne coupling

constant of meta protons and the O−H bond dissociation

,3,6-TMP and suggested that the TMBQ was majorly

formed by the attack of activated O on the phenoxyl radicals.

As a side reaction, polymerizations go through the same

intermediate, and the radical intermediate was suggested to

exist as a copper(I)−phenoxyl radical, which has a resonance

enthalpy.

Recently, we reported a solvent eﬀect study on the copper-

structure as copper(II)−phenolate.

catalyzed oxidation of 2,3,6-TMP, in which the active state of

catalyst was simulated by the reaction between CuCl−LiCl and

dioxygen in alcohols. This species showed highly eﬃcient

The substrate-dependent selectivity of oxygenation is

signiﬁcant. For instance, 2,6-di-tert-butylphenol (2,6-DTBP)

is much easier to produce benzoquinones than 2,6-

dimethylphenol, which is easier to polymerize. Moreover,

for the cross-coupling of phenols, the regioselectivity was also

found to be substrate dependent, and a pathway through

Received: August 10, 2019

phenoxyl radicals was recommended. Commonly, Hammett

constants were used to evaluate the reactivity of diﬀerent

substrates; however, the reactivity at para carbon may be not

XXXX American Chemical Society

Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry

Article

dehydrogenating activity on 2,3,6-TMP, giving the phenoxyl

radical. By the same way in this work, we used the CuCl−LiCl

catalyst as the model system and studied the aerobic oxidation

of various para-hydrogen substituted phenols in n-hexanol.

Moreover, we prepared the activated catalyst (2) by oxidizing

Scheme 2. Yields of 5 for CuCl−LiCl-Catalyzed Aerobic

Oxidations

CuCl−LiCl catalyst with O and obtained phenoxyl radicals by

oxidizing phenols with 2. EPR spectra were collected for

obtained phenoxyl radicals. Accordingly, an almost linear

relationship was established between the hyperﬁne coupling

constant of the para-site proton and the yield of benzoquinone

during the catalytic oxidation. Moreover, this relationship was

interpreted via further mechanistic study.

RESULTS AND DISCUSSION

■

CuCl−LiCl Catalyzed Oxidation of para-Hydrogen-

Substituted Phenols. The CuCl−LiCl catalyst system was

used in this study, where LiCl was the cocatalyst to provide

−

Cl and to help increase the solubility of CuCl. Suggested by

ESI mass spectrum results, the CuCl−LiCl catalyst existed in

−

n-hexanol as [Cu Cl ] (n = 1, 2, 3) (1) (Figure S3). We

n+1

explored the catalytic performance of the CuCl−LiCl system

on the oxidation of 2,3,6-TMP (4a) and 2,6-di-tert-butylphenol

,6-DTBP (4b) in n-hexanol. The main products were

detected to be benzoquinones, the same as that in a CuCl₂-

catalyzed system (Scheme 1). The side reaction was found to

Scheme 1. Catalytic Oxidation of 2,3,6-TMP and 2,6-DTBP

Figure 1. Relationship between the yield of benzoquinones and the

total Hammett constant (σ). The data were ﬁtted with the linear

function (red line): y = 23.3x + 51.4, R = 0.008.

selectivity should not depend on the electron distribution at

the hydroxyl oxygen.

Measurement of para-Site Spin Density at Phenoxyl

Radicals. The phenoxyl radical is the intermediate for both

oxygenation and oxidative coupling, and its unpaired electron

is delocalized and shared by the oxygen, ortho-carbon, and

para-carbon. We anticipated that the distribution of spin

density, which is aﬀected by the substituent groups, may cause

the diﬀerent selectivities of benzoquinone for diﬀerent phenols.

We began our investigations by oxidizing the phenols with

activated copper species 2, and we characterized the phenoxyl

radicals corresponding to 4a−4h with EPR. 2 was generated by

the reaction between 1 and dioxygen, and the characterizations

suggested it as an antiferromagnetically coupled copper(II)

species. Further characterizations on 2 is discussed in the

Supporting Information. After adding phenols into the solution

be dimerization and polymerization, leading to dimer,

polymers (detected by GPC, Figure S1 ), or biphenylquinone

(DQ). At full conversion, the yield of benzoquinone from 2,6-

DTBP (66%) was higher than that from 2,3,6-TMP (40%).

Moreover, for 2-tert-butyl-6-methylphenol (4c), 2,3,5-

trimethylphenol (4d), 2-methyl-5-iso-propylphenol (4e), 2,6-

dimethylphenol (4f), 2-iso-propyl-5-methylphenol (4g), and 1-

naphthol (4h), the yields of benzoquinones were also obtained

at 100% conversion, as shown in Scheme 2.

Factors Causing the Diﬀerent Yields of Benzoqui-

none. Suggested by Hay et al., the high selectivity of 5b was

caused by the steric eﬀect of Bu- group at the ortho site of 4b.

However, with a less steric group at the ortho site, 4d, 4g, and

of 2 at N atmosphere, we immediately collected EPR spectra

h gave more benzoquinone than 4a and 4f, and thus, the

for the solution and observed radical signals (Figure 2, black).

steric eﬀect could not be the main factor inﬂuencing the

selectivity. We tried to correlate the yield of benzoquinone

with the total Hammett constant (σ) of substituted groups,

which was obtained by adding the corresponding values of σ

and σ_o. As shown in Figure 1, the benzoquinone yield was

poorly related with the total Hammett constant (R = 0.008).

These Hammett constants were determined by the H NMR

chemical shift of OH in substituted phenols; therefore, the

The copper(II) species, like (μ−η :η -peroxo)dicopper(II)

complex, has also been reported to oxidize phenols toward

phenoxyl radicals.

Diﬀerent from the copper(II)−phenolate isolated by

6a−c

Higashimura et al.,

the phenoxyl radical we observed was

rather a “free” radical, though it was reasonable to assume a

copper(I) linked on it due to the broadened EPR signal. By

performing EPR simulations using Easyspin, the simulated

Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry

Article

Figure 2. Experimental (black) and simulated (red) X-band EPR spectra of phenoxyl radicals corresponding to 4a (a), 4b (b), 4c (c), 4d (d), 4e

e), 4f (f), 4g (g), and 4h (h) and the simulated hyperﬁne coupling constants were given in gauss. The radicals were formed upon addition of

phenols to a n-hexanol solution of 2 at room temperature.

(

values of isotropic hyperﬁne splitting of proton (a ) were

splitting pattern (Figure S11). Though the calculation was not

so good, it can be found that the coordination of phenoxyl

obtained for each radical, and we ignored the a lower than the

half-peak width.

radicals at copper(I) had apparent inﬂuence on the a , which

According to the splitting types and simulated a^Hvalues,

these signals were assigned to phenoxyl radicals corresponding

to 4a−4g, respectively (Figure 2). Moreover, DFT calculations

could be the reason for diﬀerent a from reported values in the

literature. Nevertheless, the coordination Gibbs free energy

for 2,6-di-tert-butyl phenoxyl radical was 7.7 kcal/mol, and the

energy was 2.0 kcal/mol for the 2,6-dimethyl phenoxyl radical.

were performed to help assign a for protons with the same

Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry

(Figure 3 , R = 0.586). Consequently,

Article

Therefore, the coordination for the 2,6-dimethyl phenoxyl

radical on copper(I) was much easier than that for 2,6-di-tert-

butyl phenoxyl radical. Thus, it should be reasonable that the

Scheme 3. Reaction Results between 2 and Phenols

para a we obtained for the 2,6-dimethyl phenoxyl radical was

much smaller than that of the 2,6-di-tert-butyl phenoxyl radical.

Moreover, the EPR spectrum from 4h just showed a broad

peak, which should be caused by too many protons with close

but diﬀerent a^Hvalues; thus, the a^Hvalues could not be

obtained.

Arising from the magnetic interaction between an unpaired

electron and a proton, a^Hprovides important information

about the distribution of spin density. McConnell’s relation-

ship points that a reveals the spin density (ρ) on the adjacent

carbon atom (a = −Qρ, where Q is a constant for the similar

system). As a result of the resonance stabilization, other than

the hydroxyl oxygen, the spin density distributes mainly on the

ortho- and para-site of phenoxyl radicals.

Therefore, the phenoxyl radical from 4f possessed the least

spin density at the para-carbon, while the phenoxyl radical

from 4b possessed the most. Moreover, it could be found that

,6-di-tert-butyl-substituted radicals had more spin density at

the para-site than 2,6-dimethyl substituted radicals. Using the

same method, the phenoxyl radicals from 2,4,6-trimethylphe-

nol as well as 2,6-di-tert-bultyl-4-methylphenol were also

observed (Figure S12 ), and the a at the para-methyl group

of 2,4,6-trimethylphenol (1.03 gauss) was much less than that

DTBP (4b) reacted with excess 2 under N atmosphere.

However, when the reaction was performed under 2 atm O₂,

2% and 31% benzoquinone was obtained from 4a and 4b,

respectively. The main byproduct was the polymers for 2,3,6-

TMP (according to GPC analysis, Figure S13) and

of 2,6-di-tert-bultyl-4-methylphenol (11.2 gauss).

biphenylquinone (DQ) for p-H-DTBP (70% under N , 40%

H, para

Correlation of a

and the Yield of Benzoquinone.

under O ). Moreover, the O -labling experiment was

A linear correlation was suggested between the yield of

performed to conﬁrm the oxygen source. When 4a reacted

benzoquinones and the hyperﬁne coupling constant of the

with excess 2 under 2 atm O atmosphere, the GC-MS

H, para

para -site proton, a

analyses revealed that O was incorporated into 5a with a

proportion of ∼70% (Figure S14). This result is consistent

with the catalytic oxidation result, where 5a was proposed to

be partially generated from the C−C dimer, and the oxygen of

a should come from water.

Consequently, under N₂atmosphere, phenoxyl radicals

could only polymerize and give rise to polymers. Under O₂

atmosphere, however, phenoxyl radicals could react with O to

form benzoquinones. Based on the work of Berho and

Lesclaux, no reaction was observed between phenoxyl radical

and O , thus O must be activated. By DFT investigations,

Ghosh et al. recommended a bridging copper(II)−peroxoqui-

none complex as the intermediate to form benzoquinones.

Further, the superoxo−cobalt(III) complex, superoxo−

nickel(II) complex, and superoxo−copper(II) complex

were suggested to attack the phenoxyl radicals to form

benzoquinones. Consequently, the formation of quinones

was supposed here via the attack of cooper(I)-activated O₂

Figure 3. Relationship between the yield of benzoquinones 5a−5d,

H, para

5f, and the hyperﬁne coupling constant of para-site proton (a

) at

the phenoxyl radical. The data were ﬁtted with the linear function

(

the superoxo−copper(II) complex (3)) on the phenoxyl

radicals.

The reaction of phenoxyl radical with activated dioxygen (3)

(

red line): y = 9.73x + 27.9, R = 0.586.

the distribution of spin density could be a crucial factor for the

selectivity between oxidative coupling and oxygenation. More

spin density at the para-carbon should lead to increasing

selectivity of benzoquinone. The interpretation for this

relationship will be discussed later, after the mechanism

investigations.

controlled the chemoselectivity. The attack of 3 on phenoxyl

radical was a reaction between two radicals, i.e., between the p

orbital of para -site carbon and p orbital of oxygen (Figure 4).

Origin of the Relationship. The relationship between

H, para

quinone selectivity and a

may be interpreted by the

reactivity of the phenoxyl radical. The GC-FID and GC-MS

analyses were carried out to detect what was produced from

these phenoxyl radicals. As shown in Scheme 3, no

benzoquinone was formed when 2,3,6-TMP (4a) and 2,6-

Figure 4. Diagram of SOMO orbitals for a phenoxyl radical and

activated dioxygen (3).

Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry

along with the phenoxyl radical (Figure 5 ).

Article

As discussed before, the larger a of para-site proton indicates

the greater spin density at para-site carbon, which means a

higher SOMO coeﬃcient for the p orbital of para-carbon.

Additionally, the coeﬃcients of the frontier molecular orbital

have been successfully used to evaluate the regioselectivity and

preferred, resulting in a higher yield of benzoquinone.

However, for phenoxyl radicals with more spin density at the

hydroxyl oxygen, the C−O polymerization among radicals

should be preferred, leading to decreasing the yield of

benzoquinone. The C−O dimer was included in the polymers

in Scheme 4.

reactivity of addition reactions. A higher SOMO coeﬃcient

for the p orbital of para-carbon should lead to higher selectivity

and higher reactivity for the formation of benzoquinone.

Consequently, it could be reasonable that the regioselectivity

The production of benzoquinones was suggested here to go

through a bridging copper(II)−peroxoquinone complex, and

−

the [Cl Cu OH] was generated along with the product.

was positively correlated with the a of para-site proton at the

Kitajima et al. have prepared the P type Cu/O

reaction of LCu(II)OH complex with H

proposed that 2 was generated by reaction between

species by the

phenoxyl radical.

;

thus, we

Proposed Mechanism. During the process of CuCl−LiCl-

catalyzed oxidation of 2,3,6-TMP (Scheme 1a), the same

phenoxyl radical as that obtained by the reaction between 2

and 2,3,6-TMP was suggested by EPR. Consequently, the

resting state of the catalyst should be a copper(I) species (1),

−

[Cl Cu OH] and H O . The [Cl Cu OH] was suggested

2 2 2 2

to be a bis(μ-hydroxo)dicopper(II,II) species (Figure S9B,

Table S2) and was nearly EPR silent (Figure S15, black). Its

reaction with 2,3,6-trimethylphenol only showed the mono-

nuclear Cu(II) signal in the EPR spectrum (Figure S15 , red),

while the reaction of 2 with 2,3,6-trimethylphenol showed the

phenoxyl radical signal and no mononuclear Cu(II) signal

−

(

Figure S15, purple). Thus, the [Cl Cu OH] could not

oxidize phenols to phenoxyl radicals.

To verify the proposed mechanism, we investigated the

change of quinone concentration with reaction time. The

formation of quinones at the beginning of the reaction could

be well ﬁtted with the linear function (Figure S16 ). Based on

the proposed mechanism, the formation rate of quinones

should also be aﬀected by the distribution of spin density.

Consequently, when correlating the ﬁtted formation rate with

H, para

Figure 6 ), which corresponded to the proposed mechanism.

at phenoxyl radical, we obtained a positive relationship

Figure 5. X-band EPR spectrum detected at 5 h of the catalysis

reaction shown in Scheme 1a.

The proposed catalysis mechanism is shown in Scheme 4.

The reaction was initialized by the reaction between dioxygen

Scheme 4. Proposed Mechanism

Figure 6. Relationship between the formation rate of benzoquinones

a−5g and the hyperﬁne coupling constant of para-site proton

H, para

) at the phenoxyl radical. The data were ﬁtted with the linear

function (red line): y = 0.000475x, R = 0.573.

CONCLUSION

In summary, the substrate-dependent benzoquinone selectivity

was interpreted with the distribution of spin density at the

■

phenoxyl radical. The positive linear relationship was

H, para

established between the a

and the yield of benzoquinones.

and the catalyst 1, giving the activated catalyst 2. 2 oxidized

phenols with its eﬀective dehydrogenating activity, yielding

phenoxyl radicals and 1, as well as H O . The activating of

dioxygen by 1 was recommended as the rate-determining step

and led to the formation of 3. For phenoxyl radical with more

spin density at the para-site, its reaction with 3 should be

Phenoxyl radicals were detected after the oxidation of phenols

with 2, which was the simulated activated catalyst during the

reaction, and was formed by the oxidation of the catalyst (1)

with dioxygen. It was found that phenoxyl radicals could only

polymerize under N₂atmosphere but could produce

benzoquinones under O atmosphere. Consequently, while

Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry

The Supporting Information is available free of charge at

Article

polymers were formed by the reaction among radicals, the

main pathway to produce benzoquinones was proposed to be

injected into the ﬂask at room temperature to start the reaction. The

excess 2 was used here for full conversion. After 10 min, the reaction

was quenched by 0.5 mL of water; the yields were determined by gas

chromatography, and the products were detected by GC-MS and

GPC.

the attack of activated O on phenoxyl radicals, and the

phenoxyl radical with higher spin density at its para-carbon

should prefer this pathway rather than the competitive

coupling. These ﬁndings contribute to our understanding of

the aerobic oxidation of phenols, as well as to the nature of

phenoxyl radicals. We hope this work could provide a clue for

the control of selectivity in phenol oxidations.

ASSOCIATED CONTENT

sı Supporting Information

■

https://pubs.acs.org/doi/10.1021/acs.inorgchem.9b02422.

EXPERIMENTAL SECTION

Additional experimental details and spectral data (PDF)

■

General Methods. All reagents were purchased from commercial

sources without further treatment unless otherwise noted. UV−vis

experiments were carried out on a TU-1901 spectrophotometer

AUTHOR INFORMATION

■

(

Purkinje General Instrument Co., Ltd., China) equipped with a

Corresponding Authors

thermostat using a 1 cm modiﬁed cuvette. UV−vis−NIR spectra were

recorded on a UV-3600 Shimadzu spectrophotometer using a 1 cm

cuvette. CV was performed on a CHI630 electrochemical analyzer

Zheng Jiang − Shanghai Synchrotron Radiation Facility,

Shanghai Institute of Applied Physics, Chinese Academy of

Sciences, Shanghai 201204, P. R. China; orcid.org/0000-

(

CH Instrument, China). The CW-EPR spectra were recorded on a

002-0132-0319 ; Email: jiangzheng@sinap.ac.cn

Bruker A300 EPR spectrometer at 9.8 GHz. Electrospray ionization−

mass spectrometry (ESI-MS) measurements were performed on an

Agilent 1260/6120 mass spectrometer (Agilent, America), and the

detection was in negative ion modes. Gas chromatography−mass

spectrometry (GC-MS) experiments were carried out on a Shimadzu

GC/MS-QP2010 system (Shimadzu, Germany). GC-FID measure-

ments were performed on GC-2010 (Shimadzu, Japan) instrument.

Gel permeation chromatography (GPC) was performed at Waters

Haoran Li − Department of Chemistry, ZJU-NHU United R&D

Center and State Key Laboratory of Chemical Engineering,

College of Chemical and Biological Engineering, Zhejiang

University, Hangzhou 310027, P. R. China; orcid.org/

0000-0001-5294-8731 ; Email: lihr@zju.edu.cn

Authors

515 with an RI 2414 as the detector.

Catalytic oxidation of phenols. In a two-neck ﬂask (25 mL)

Yongtao Wang − Department of Chemistry, ZJU-NHU United

R&D Center, Zhejiang University, Hangzhou 310027, P. R.

Jun Guan − Department of Chemistry, ZJU-NHU United R&D

Center, Zhejiang University, Hangzhou 310027, P. R. China

Bingbao Mei − Shanghai Synchrotron Radiation Facility,

Shanghai Institute of Applied Physics, Chinese Academy of

Sciences, Shanghai 201204, P. R. China

Mengtian Fan − Department of Chemistry, ZJU-NHU United

R&D Center, Zhejiang University, Hangzhou 310027, P. R.

orcid.org/0000-0001-8734-097X

Rui Lu − Department of Chemistry, ZJU-NHU United R&D

Center, Zhejiang University, Hangzhou 310027, P. R. China;

equipped with a magnetic stir bar, 5 mmol phenol, 1 mmol CuCl, and

mmol LiCl were added with 10 mL of n-hexanol. The mixture was

stirred under N atmosphere for dissolution, and then the N was

replaced by O₂and an O₂balloon (1 atm) was equipped. The

reaction was performed at 343 K and 800 rpm. The commercial

reactants and products were used as the standard for gas

chromatography. The conversion and yield were determined by gas

chromatography using the standard curve, and the products were

detected by GC-MS and GPC.

Formation of the activated catalyst 2. In the glovebox, a 0.09

M solution of complex 1 was prepared by adding 1.5 mmol of CuCl

and 3 mmol of LiCl to 15 mL of n-hexanol, and the mixture was

stirred at 333 K for 3 h. After ﬁltration, the ﬁltrate was characterized

by spectroscopy. The concentration of copper ion in the ﬁltrate was

measured to be 0.0887 M using atomic absorption spectroscopy

Renfeng Du − Department of Chemistry, ZJU-NHU United

R&D Center, Zhejiang University, Hangzhou 310027, P. R.

(

AAS). In the glovebox, 6.2 mL of 0.09 M n-hexanol solution of 1

the ﬁltrate) was injected into a pressure-resistant reaction ﬂask. After

it was removed from the glovebox, the ﬂask was charged with 1 atm

Kaizhou Chen − Department of Chemistry, ZJU-NHU United

R&D Center, Zhejiang University, Hangzhou 310027, P. R.

orcid.org/0000-0002-7147-5973

Jia Yao − Department of Chemistry, ZJU-NHU United R&D

Center, Zhejiang University, Hangzhou 310027, P. R. China;

O , and another 20.0 mL of O was injected in via a gastight syringe;

then, the solution was stirred at room temperature for 5 h. The

reacted O was quantiﬁed by a gastight syringe to be 5.5 mL. The

concentration of Cu(II) was calculated to be 82 mM (92% of total

copper) by comparing the d−d transition bands with standard CuCl

solution in n-hexanol. Thus, a Cu /O ratio of 2.07:1 was obtained for

. The dark brown species 2 persists for several days at room

Complete contact information is available at:

temperature but precipitates immediately with small amount of water

or methanol.

https://pubs.acs.org/10.1021/acs.inorgchem.9b02422

EPR Spectroscopy. To detect phenol radicals, the fully generated

solution of 2 was packed in a 5 mm quartz EPR sample tube sealed

Author Contributions

These authors contributed equally.

∥

with a rubber cap. After purging with N , the radical was formed by

Funding

the addition of a stock solution of phenols and was immediately

detected at 298 K. The least-squares ﬁttings of EPR spectra were

performed using Easyspin 5.1 with the garlic function.

Oxidation of Phenols by 2. The n-hexanol solution of 2 was

This work was supported by the National Natural Science

Foundation of China (21573196), the Fundamental Research

Funds of the Central Universities, and the National High

Technology Research and Development Program (863

Program) of China (SS2015AA020601).

prepared by stirring the n-hexanol solution of 1 under 2 atm O at

room temperature for 5 h, and then the solution was purged by three

N /vacuum purge cycles. Next, 1.5 mL of solution of 2 was injected

Notes

into a pressure-resistant reaction ﬂask charged with 1 atm N or 2 atm

O . The concentrated n-hexanol solution of phenols (0.02 mmol) was

The authors declare no competing ﬁnancial interest.

Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry

Yamada, Y.; Okamoto, K.-i.; Moro-oka, Y. Synthesis, Structure and

Article

Iwata, Y.; Kitajima, N.; Higashimura, H.; Kubota, M.; Miyashita, Y.;

Reactivity of Phenoxo Copper(II) Complexes, Cu(OAr)(HB(3,5-

ACKNOWLEDGMENTS

■

The authors would like to gratefully thank Hongxian Han and

Zhaochi Feng from the Dalian Institute of Chemical Physics,

Chinese Academy of Sciences, and Jiadan Xue from the

Department of Chemistry, Zhejiang Sci-Tech University, for

resonance Raman spectroscopy. The authors also thank Xinyu

Wang and Fahe Cao from the Department of Chemistry,

Zhejiang University, for EPR and cyclic voltammograms.

Pr pz) ) (Ar = C H -4-F, 2,6-Me C H , 2,6-Bu C H ). Chem. Lett.

1999, 28, 739−740. (c) Higashimura, H.; Kubota, M.; Shiga, A.;

Fujisawa, K.; Moro-oka, Y.; Uyama, H.; Kobayashi, S. Radical-

Controlled ” Oxidative Polymerization of 4-Phenoxyphenol by a

Tyrosinase Model Complex Catalyst to Poly(1,4-Phenylene Oxide).

Macromolecules 2000, 33, 1986−1995.

335 −6336. (b) Endres, G. F.; Hay, A. S.; Eustance, J. W.

7) (a) Hay, A. S.; Blanchard, H. S.; Endres, G. F.; Eustance, J. W.

Polymerization by Oxidative Coupling. J. Am. Chem. Soc. 1959, 81,

REFERENCES

■

(

1) (a) Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski,

M. C. Aerobic Copper-Catalyzed Organic Reactions. Chem. Rev.

013 , 113 , 6234 −6458. (b) Wendlandt, A. E.; Suess, A. M.; Stahl, S.

S. Copper-Catalyzed Aerobic Oxidative C-H Functionalizations:

Polymerization by Oxidative Coupling. V. Catalytic Specificity in

the Copper-Amine-Catalyzed Oxidation of 2,6-Dimethylphenol. J.

Org. Chem. 1963, 28, 1300−1305.

(8) (a) Lee, Y. E.; Cao, T.; Torruellas, C.; Kozlowski, M. C. Selective

Trends and Mechanistic Insights. Angew. Chem., Int. Ed. 2011 , 50 ,

Oxidative Homo- and Cross-Coupling of Phenols with Aerobic

Catalysts. J. Am. Chem. Soc. 2014, 136, 6782−5. (b) Nieves-Quinones,

Y.; Paniak, T. J.; Lee, Y. E.; Kim, S. M.; Tcyrulnikov, S.; Kozlowski, M.

C. Chromium-Salen Catalyzed Cross-Coupling of Phenols: Mecha-

nism and Origin of the Selectivity. J. Am. Chem. Soc. 2019, 141,

10016. (c) Reiss, H.; Shalit, H.; Vershinin, V.; More, N. Y.; Forckosh,

H.; Pappo, D. Cobalt(II)[Salen]-Catalyzed Selective Aerobic

Oxidative Cross-Coupling between Electron-Rich Phenols and 2-

Naphthols. J. Org. Chem. 2019 , 84 , 7950.

(9) (a) Altwicker, E. R. The Chemistry of Stable Phenoxy Radicals.

Chem. Rev. 1967 , 67 , 475 −531. (b) Fitzpatrick, J. D.; Steelink, C.;

Hansen, R. E. Phenoxy Radical Intermediates. II. The Oxidative

Detoxification of Phenols in Incense Cedar Heartwood. J. Org. Chem.

1062 −87. (c) Punniyamurthy, T.; Rout, L. Recent Advances in

Copper-Catalyzed Oxidation of Organic Compounds. Coord. Chem.

Rev. 2008 , 252 , 134 −154. (d) van der Vlugt, J. I.; Meyer, F.

Homogeneous Copper-Catalyzed Oxidations. Top. Organomet. Chem.

2) Bonrath, W.; Eggersdorfer, M.; Netscher, T. Catalysis in the

007, 22, 191−240.

Industrial Preparation of Vitamins and Nutraceuticals. Catal. Today

007, 121, 45−57.

3) (a) Takehira, K.; Shimizu, M.; Watanabe, Y.; Orita, H.;

(

Hayakawa, T. A Novel Synthesis of Trimethyl-p-Benzoquinone:

Copper (II)−Hydroxylamine Catalysed Oxygenation of 2,3,6-

Trimethylphenol with Dioxygen. J. Chem. Soc., Chem. Commun.

989, 1705−1706. (b) Shimizu, M.; Watanabe, Y.; Orita, H.;

Hayakawa, T.; Takehira, K. Synthesis of Alkyl Substituted p-

Benzoquinones from the Corresponding Phenols Using Molecular

Oxygen Catalyzed by Copper(II) Chloride-Amine Hydrochloride

Systems. Bull. Chem. Soc. Jpn. 1992 , 65 , 1522 −1526. (c) Bodnar, Z.;

Mallat, T.; Baiker, A. Oxidation of 2,3,6-Trimethylphenol to

967 , 32 , 625 −628. (c) Becconsall, J.; Clough, S.; Scott, G. Electron

Magnetic Resonance of Phenoxy Radicals. Trans. Faraday Soc. 1960,

6, 459−472.

10) Mu

ller, E.; Schick, A.; Scheffler, K. Oxygen Radicals XI. 4-

Phenyl-2, 6-Di (tert -Butyl) Phenoxyl. Chem. Ber. 1959, 92, 474−482.

(11) (a) Manner, V. W.; Markle, T. F.; Freudenthal, J. H.; Roth, J.

P.; Mayer, J. M. The First Crystal Structure of a Monomeric Phenoxyl

Radical: 2,4,6-Tri-tert -Butylphenoxyl Radical. Chem. Commun. 2008 ,

Trimethyl-1,4-Benzoquinone with Catalytic Amount of CuCl . J.

Mol. Catal. A: Chem. 1996 , 110 , 55 −63. (d) Sun, H.; Harms, K.;

Sundermeyer, J. Aerobic Oxidation of 2,3,6-Trimethylphenol to

Trimethyl-1, 4-Benzoquinone with Copper (II) Chloride as Catalyst

in Ionic Liquid and Structure of the Active Species. J. Am. Chem. Soc.

56 −8. (b) Porter, T. R.; Kaminsky, W.; Mayer, J. M. Preparation,

Structural Characterization, and Thermochemistry of an Isolable 4-

004, 126, 9550−9551. (e) Wang, C.; Guan, W.; Xie, P.; Yun, X.; Li,

H.; Hu, X.; Wang, Y. Effects of Ionic Liquids on the Oxidation of

,3,6-Trimethylphenol to Trimethyl-1,4-Benzoquinone under Atmos-

pheric Oxygen. Catal. Commun. 2009, 10, 725−727.

4) (a) Ling, K.-Q.; Lee, Y.; Macikenas, D.; Protasiewicz, J. D.;

Arylphenoxyl Radical. J. Org. Chem. 2014, 79, 9451−9454.

12) Brigati, G.; Lucarini, M.; Mugnaini, V.; Pedulli, G. F.

Determination of the Substituent Effect on the O −H Bond

Dissociation Enthalpies of Phenolic Antioxidants by the Epr Radical

Equilibration Technique. J. Org. Chem. 2002 , 67 , 4828 −4832.

(

Sayre, L. M. Copper(II)-Mediated Autoxidation of tert -Butylresorci-

nols. J. Org. Chem. 2003, 68, 1358−1366. (b) Evtushok, V. Y.;

Suboch, A. N.; Podyacheva, O. Y.; Stonkus, O. A.; Zaikovskii, V. I.;

Chesalov, Y. A.; Kibis, L. S.; Kholdeeva, O. A. Highly Efficient

Catalysts Based on Divanadium-Substituted Polyoxometalate and N-

Doped Carbon Nanotubes for Selective Oxidation of Alkylphenols.

ACS Catal. 2018, 8, 1297−1307. (c) Wanna, W. H.; Ramu, R.;

Janmanchi, D.; Tsai, Y.-F.; Thiyagarajan, N.; Yu, S. S. F. An Efficient

and Recyclable Copper Nano-Catalyst for the Selective Oxidation of

Benzene to p-Benzoquinone (p-BQ) Using H O (aq) in CH CN. J.

13) Wang, Y.; Wang, G.; Yao, J.; Li, H. Restricting Effect of Solvent

Aggregates on Distribution and Mobility of CuCl in Homogenous

Catalysis. ACS Catal. 2019, 9, 6588−6595.

(b) Tribble, M. T.; Traynham, J. G. Nuclear Magnetic Resonance

14) (a) Ritchie, C. D.; Sager, W. F. An Examination of Structure-

Reactivity Relationships. Prog. Phys. Org. Chem. 2007 , 2 , 323 −456.

Studies of ortho -Substituted Phenols in Dimethyl Sulfoxide Solutions.

Electronic Effects of Ortho Substituents. J. Am. Chem. Soc. 1969, 91,

(

79−388.

15) Itoh, S.; Kumei, H.; Taki, M.; Nagatomo, S.; Kitagawa, T.;

Catal. 2019, 370, 332−346.

Fukuzumi, S. Oxygenation of Phenols to Catechols by a (μ -η :η -

Peroxo)Dicopper(II) Complex: Mechanistic Insight into the

Phenolase Activity of Tyrosinase. J. Am. Chem. Soc. 2001, 123,

(

5) (a) Lee, J. Y.; Peterson, R. L.; Ohkubo, K.; Garcia-Bosch, I.;

Himes, R. A.; Woertink, J.; Moore, C. D.; Solomon, E. I.; Fukuzumi,

S.; Karlin, K. D. Mechanistic Insights into the Oxidation of

Substituted Phenols via Hydrogen Atom Abstraction by a Cupric-

Superoxo Complex. J. Am. Chem. Soc. 2014 , 136 , 9925 −9937.

16) Stoll, S.; Schweiger, A. Easyspin, a Comprehensive Software

708−6709.

Package for Spectral Simulation and Analysis in Epr. J. Magn. Reson.

2006, 178, 42−55.

b) Wang, G.; Wang, Y.; Yao, J.; Li, H. Insight into 2,3,6-

Trimethylphenol Oxidation by Comparing the Difference between

Cupric Acetate and Cupric Chloride Catalysis. Mol. Catal. 2019, 472,

(17) Amorati, R.; Pedulli, G. F.; Guerra, M. Hydrogen Hyperfine

Splitting Constants for Phenoxyl Radicals by DFT Methods:

Regression Analysis Unravels Hydrogen Bonding Effects. Org. Biomol.

Chem. 2010, 8, 3136−3141.

(18) McConnell, H. M. Indirect Hyperfine Interactions in the

Paramagnetic Resonance Spectra of Aromatic Free Radicals. J. Chem.

Phys. 1956, 24, 764−766.

(

0−16.

6) (a) Higashimura, H.; Fujisawa, K.; Moro-oka, Y.; Kubota, M.;

Shiga, A.; Terahara, A.; Uyama, H.; Kobayashi, S. Highly

Regioselective Oxidative Polymerization of 4-Phenoxyphenol to

Poly(1,4-Phenylene Oxide) Catalyzed by Tyrosinase Model Com-

plexes. J. Am. Chem. Soc. 1998, 120, 8529−8530. (b) Fujisawa, K.;

Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry

Article

19) Berho, F.; Lesclaux, R. The Phenoxy Radical: UV Spectrum and

Kinetics of Gas-Phase Reactions with Itself and with Oxygen. Chem.

Phys. Lett. 1997, 279, 289−296.

(

20) Ghosh, S.; Cirera, J.; Vance, M. A.; Ono, T.; Fujisawa, K.;

Solomon, E. I. Spectroscopic and Eectronic Structure Studies of

Phenolate Cu(II) Complexes: Phenolate Ring Orientation and

Activation Related to Cofactor Biogenesis. J. Am. Chem. Soc. 2008,

21) Zombeck, A.; Drago, R. S.; Corden, B. B.; Gaul, J. H. Activation

30, 16262−16273.

of Molecular Oxygen. Kinetic Studies of the Oxidation of Hindered

Phenols with Cobalt-Dioxygen Complexes. J. Am. Chem. Soc. 1981,

22) Company, A.; Yao, S.; Ray, K.; Driess, M. Dioxygenase-Like

03, 7580−7585.

Reactivity of an Isolable Superoxo −Nickel(II) Complex. Chem. - Eur.

J. 2010, 16, 9669−9675.

23) (a) Houk, K. N.; Sims, J.; Duke, R. E.; Strozier, R. W.; George,

J. K. Frontier Molecular Orbitals of 1,3 Dipoles and Dipolarophiles. J.

Am. Chem. Soc. 1973, 95, 7287 −7301. (b) Houk, K. N.; Sims, J.;

Watts, C. R.; Luskus, L. J. Origin of Reactivity, Regioselectivity, and

Periselectivity in 1,3-Dipolar Cycloadditions. J. Am. Chem. Soc. 1973,

5, 7301 −7315. (c) Rozeboom, M. D.; Tegmo-Larsson, I. M.; Houk,

K. N. Frontier Molecular Orbital Theory of Substitutent Effects on

Regioselectivities of Nucleophilic Additions and Cycloadditions to

Benzoquinones and Naphthoquinones. J. Org. Chem. 1981 , 46 , 2338 −

345. (d) Mirzaei, S.; Khosravi, H. Predicting the Regioselectivity of

Nucleophilic Addition to Arynes Using Frontier Molecular Orbital

Contribution Analysis. Tetrahedron Lett. 2017, 58, 3362−3365.

(

24) Kitajima, N.; Fujisawa, K.; Fujimoto, C.; Morooka, Y.;

Hashimoto, S.; Kitagawa, T.; Toriumi, K.; Tatsumi, K.; Nakamura,

A. A New Model for Dioxygen Binding in Hemocyanin. Synthesis,

Characterization, and Molecular Structure of The μ -η :η Peroxo

Dinuclear Copper (II) Complexes,[Cu (HB (3, 5-R pz) ₃ )] ₂

O )(R= Isopropyl and Ph). J. Am. Chem. Soc. 1992, 114, 1277−

291.