Metal-free synthesis of substituted phenols from arylboronic acids in water at room temperature

DOI: 10.1016/j.cclet.2014.03.018

Source and publish data:

Chinese Chemical Letters p. 715 - 719 (2014)

Update date:2022-08-29

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Authors:

Jiang, Min

Yang, Hai-Jun

Li, Yong

Jia, Zhi-Ying

Fu, Hua Fu, Hua

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Article abstract of DOI:10.1016/j.cclet.2014.03.018

A convenient, efficient and practical metal-free method for the synthesis of substituted phenols from arylboronic acids has been developed. The protocol uses hydrogen peroxide as a hydroxylating agent, ammonium bicarbonate as an additive, and the reactions were conveniently performed in water at room temperature. The method shows an excellent tolerance of functional groups, so it will find a wide variety of applications in academic and industrial research.

Full text of DOI:10.1016/j.cclet.2014.03.018

Chinese Chemical Letters 25 (2014) 715–719

Contents lists available at ScienceDirect

Chinese Chemical Letters

journal homepage: w ww.elsevier.com/locate/cclet

Original article

Metal-free synthesis of substituted phenols from arylboronic acids in

water at room temperature

Min Jiang ^a, Hai-Jun Yang ^a,b,, Yong Li ^a,b, Zhi-Ying Jia ^b, Hua Fu ^b

^aBeijing Key Laboratory for Analytical Methods and Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084, China

^bKey Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology of Ministry of Education, Department of Chemistry, Tsinghua University,

Beijing 100084, China

A R T I C L E I N F O

A B S T R A C T

Article history:

A convenient, efﬁcient and practical metal-free method for the synthesis of substituted phenols from

arylboronic acids has been developed. The protocol uses hydrogen peroxide as a hydroxylating agent,

ammonium bicarbonate as an additive, and the reactions were conveniently performed in water at room

temperature. The method shows an excellent tolerance of functional groups, so it will ﬁnd a wide variety

of applications in academic and industrial research.

Received 6 November 2013

Received in revised form 22 January 2014

Accepted 20 February 2014

Available online 15 March 2014

ß 2014 Hai-Jun Yang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights

reserved.

Keywords:

Arylboronic acids

Substituted phenols

Oxidative

Metal-free

Synthetic method

1. Introduction

need for potentially toxic metal-based catalysts [10]. Several

groups have reported the oxidation of organo-boronic compounds

Phenols are important synthetic intermediates and are widely

used in the synthesis of pharmaceuticals, polymers, and natural

products [1]. Therefore, the synthesis of phenols has attracted

much attention. Recently, great successes have been made using

transition metals as catalysts to prepare phenols including

palladium [2] or copper-catalyzed [3] hydroxylation of aryl halides

with hydroxide salts to produce phenols. Arylboronics acids,

usually prepared from aryl halides (such as aryl bromides and

chlorides) or tosylates, are common chemicals [4] and have been

used in the synthesis of phenols by copper-catalysis [5]. Very

recently, we have developed a general copper-catalyzed transfor-

mation of arylboronic acids in water to different functionalized

aromatic systems including phenols [6]. Obviously the environ-

mentally benign transition metal-free approaches are preferred in

organic synthesis. Metal-free organocatalysis has been around for

over a century [7], but it was left largely unnoticed [8,9]. Only

recently, there has been a remarkable renaissance in organoca-

talysis because environmentally friendly methods can avoid the

to produce phenols using oxidants such as hydrogen peroxide [11].

Very recently, phenols prepared by photocatalysis from arylboro-

nic acids under light irradiation have been reported [12]. We

recognized that the transformation of arylboronic acids to phenols

was an oxidation procedure involved radicals. Herein, we report a

transformation and its mechanism of arylboronic acids to

substituted phenols with hydrogen peroxide and ammonium

bicarbonate under mild conditions.

2. Experimental

All reagents and solvents were obtained from commercial

suppliers and used without further puriﬁcation. Aryl boronic acids

were purchased from Alfa-Aesar, and other reagents were

purchased from Beijing Ouhe Technology Co., Ltd. All reagents

were weighed and handled in air at room temperature. Proton and

carbon magnetic resonance spectra (¹H NMR and ¹³C NMR) were

recorded using tetramethylsilane (TMS) in solvent of CDCl₃as the

internal standard (¹H NMR: TMS at 0.00 ppm, CHCl₃at 7.24 ppm,

¹³C NMR: CDCl₃at 77.0 ppm) or using tetramethylsilane (TMS) in

the solvent of DMSO-d₆as the internal standard (¹H NMR: TMS at

0.00 ppm, DMSO at 2.50 ppm; ¹³C NMR: DMSO at 40.0 ppm). The

EPR measurement was performed on a X-band EPR (10.0 GHz)

instrument JES FA200 (JEOL).

Corresponding author at: Beijing Key Laboratory for Analytical Methods and

Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084,

China.

E-mail address: cyhj@tsinghua.edu.cn (H.-J. Yang).

http://dx.doi.org/10.1016/j.cclet.2014.03.018

716

M. Jiang et al. / Chinese Chemical Letters 25 (2014) 715–719

Table 1

General experimental procedure for the synthesis of com-

Synthesis of phenol (2a) from hydroxylation of phenylboronic acid (1a) with

pounds 2a–y: 30% H₂O₂solution (2 mmol, 0.12 mL), ammonium

bicarbonate (1 mmol, 79.1 mg), arylboronic acid (1 mmol), H₂O

(2.0 mL) were added to a 10 mL Schlenk tube equipped with a

magnetic stirrer, and the reaction was performed under air at room

temperaturefor 2 h. After the reaction ﬁnished, 4 mLof HCl (1 mol/L)

was added to the solution till pH 2–3. The aqueous solution was

extracted with ethyl acetate (4 Â 5 mL), the combined organic phase

was dried over anhydrous Na₂SO₄, and the targeted products (2)

were obtained after the removal of the solvent. Data for three

representative examples are given here.

hydrogen peroxide: optimization of conditions.^a

MCO₃, solvent

B(OH)₂

H₂O, r.t., air, 2 h

Entry

MCO₃(equiv.)

NaHCO₃(1)

H₂O₂(equiv.)

Solvent

Yield (%)^b

0.5

–

CH₃CN

CH₃OH

H₂O

Trace

KHCO₃(1)

Methylparaben (2t): yield 98% (149 mg), white solid, mp

CsHCO₃(1)

NH₄HCO₃(1)

(NH₄)₂CO₃(1)

Na₂CO₃(1)

K₂CO₃(1)

125 8C. ¹H NMR (600 MHz, CDCl₃):

7.94 (d, 2 H, J = 8.94 Hz), 6.87

(d, 2H, J = 8.94 Hz), 6.25 (s, 1H), 3.89 (d, 3H). ¹³C NMR (150 MHz,

CDCl₃): 167.5, 160.4, 132.0, 122.3, 115.4, 52.2. GC–MS: m/z 152.2.

Naphthalen-1-ol (2w): yield 97% (140 mg), colorless solid, mp

109–112 8C. ¹H NMR (600 MHz, CDCl₃):

8.17 (m, 1H), 7.81 (m,

Cs₂CO₃(1)

NH₄HCO₃(1)

NH₄HCO₃(0.5)

–

1H), 7.48 (m, 2H), 7.44 (d, 2H, J = 8.3 Hz), 7.29 (dd, 1H, J = 7.6,

8.3 Hz), 6.80 (d, 1H, J = 7.6 Hz), 5.26 (s, 1H). ¹³C NMR (150 MHz,

CDCl₃):

d 151.3, 134.7, 127.6, 126.4, 125.8, 125.2, 124.3, 121.5,

120.7, 108.6. GC–MS: m/z 144.1.

NH₄HCO₃(1)

Dibenzo[b,d]furan-4-ol (2y): yield 96% (177 mg), white solid,

mp 135 8C. ¹H NMR (600 MHz, CDCl₃):

d 7.85 (d, 2H, J = 7.56 Hz),

Reaction conditions: phenylboronic acid (1a) (1 mmol), carbonate salt (0–

3.0 mmol), H₂O₂(0–3.0 mmol), water (2.0 mL), reaction time (2 h) at room

temperature under air.

7.48 (d, 1H, J = 8.25 Hz), 7.44 (d, 1H, J = 7.56 Hz), 7.38 (t, 1H,

J = 7.56 Hz), 7.28 (t, 1H, J = 7.56 Hz), 7.15 (t, 1H, J = 7.22 Hz), 7.00 (d,

1H, J = 8.25 Hz), 5.86 (s, 1H). ¹³C NMR (150 MHz, CDCl₃):

d 156.1,

Isolated yield.

144.2, 141.2, 127.3, 125.9, 124.7, 123.8, 123.1, 121.1, 113.8, 112.9,

111.9. GC–MS: m/z 184.1.

As shown in Scheme 1, the synthesis of phenol on gram scale

went well under the standard conditions, demonstrating the

practical applicability of the present method.

(entries 1–5). When the amount of hydrogen peroxide was reduced

(entries 9 and 10), the yields decreased. Only trace amount of

phenol was observed in the absence of hydrogen peroxide (entry

11). Three equiv. of hydrogen peroxide gave the same yield (entries

4 and 12). Amount of ammonium bicarbonate was also investigat-

ed (entries 4, 13 and 14), and one equiv. of ammonium bicarbonate

was suitable (entry 4). Effect of solvents was explored (entries 4, 15

and 16), and water was more favorable (entry 16). Therefore, the

optimal conditions for the hydroxylation of arylboronic acids are as

follows: two equiv. of hydrogen peroxide as the hydroxylating

agent, one equiv. of ammonium bicarbonate as the additive

(adjusting pH value of the solution) in water at room temperature

for 2 h.

The characterization data and ¹H NMR and ¹³C NMR spectra of

compounds 2a–y can be found in Supporting information.

EPR measurement: 10

L ammonium biscarbonate (25 mmol) was quickly mixed

with 20 L DMPO (100 mmol) and 10 L H₂O₂(50 mmol), the

sample was subsequently transferred to an EPR ﬂat cell, and

spectra were taken by JEOL EPR spectrometer. Typical

mL Phenylboronic acid (25 mmol) and

spectrometer parameters were as follows: scan width 8 mT, center

ﬁeld 323.1 mT, time constant 0.1 s, scan time 2 min, modulation

amplitude 0.1 mT, microwave power 1 mW, microwave frequency

9.056 GHz. A typical hydroxyl radical (g = 2.0023, A_N= 1.50 mT,

A_H= 1.50 mT) and

A_N= 1.58 mT, A_H= 2.38 mT) were observed, and the result showed

occurrence of a phenyl free radical.

carbon central radical (g = 2.0023,

With the optimum reaction conditions in hand, the scope of

metal-free synthesis of substituted phenols was investigated. As

shown in Table 2, all the examined substrates provided excellent

yields, and all arylboronic acids were almost quantitatively

transformed into the corresponding substituted phenols within

2 h. The reactions could tolerate various functional groups

including ether (entries 8–10), C–Cl bond (entries 11 and 12),

C–F bond (entry 13), hydroxyl (entry 14), nitro (entries 15 and 16),

triﬂuoromethyl (entry 17), cyano (entry 18), acetyl (entry 19), ester

(entry 20), carboxyl (entries 21 and 22), naphthalene ring (entries

23 and 24), and O-heterocycle (entry 25) in the substrates.

Importantly, the work-up procedures were very simple, and the

pure targeted products were obtained only by extraction with

ethyl acetate after acidiﬁcation of the resulting aqueous solution

with 1 mol/L HCl.

3. Results and discussion

Hydroxylation of phenylboronic acid (1a) to the corresponding

phenol was used as a model to optimize reaction conditions

including carbonate salts, amount of carbonate salts and hydrogen

peroxide, and solvents. As shown in Table 1, eight carbonate salts

were screened in the presence of two equiv. of hydrogen peroxide

in water at room temperature for 2 h (entries 1–8), and sodium

bicarbonate, potassium bicarbonate, cesium bicarbonate, ammo-

nium bicarbonate, ammonium carbonate provided excellent yields

The reaction mechanism for the synthesis of substituted

phenols was also investigated by EPR. As shown in Fig. 1 (curve a),

NH₄HCO₃(0.79 g)

30% H₂O₂(1.1 mL)

typical hydroxyl free radical (black dot) (g = 2.0023,

B(OH)₂

A_N= 1.50 mT, A_H= 1.50 mT) in Fig. 1 (curve b) and a carbon

central free radical (star) (g = 2.0023, A_N= 1.58 mT, A_H= 2.38 mT)

in Fig. 1 (curve c) from the hydroxylation of phenylboronic acids

were observed. The simulation spectrum of the hydroxyl radical

and carbon central radical (Fig. 1 (curve d)) was in agreement with

the measurement. This result showed the presence of a phenyl

H₂O (10 mL), r.t., 2 h

0.80 g (yield 95%)

1.22 g

Scheme 1. Synthesis of phenol on gram scale under the standard conditions.

M. Jiang et al. / Chinese Chemical Letters 25 (2014) 715–719

717

Table 2

Metal-free synthesis of substituted phenols from arylboronic acids.^a

B(OH)₂

1.0 eq. NH₄HCO₃, 2.0 eq. H₂O₂

2 mL H₂O, r.t., 2 h

Entry

Yield (%)^b

Entry

Yield (%)^b

B(OH)₂

O₂N

B(OH)₂

O₂N

NO₂

B(OH)₂

F₃C

B(OH)₂

H₃COOC

B(OH)₂

MeO

HOOC

B(OH)

B(OH)₂

HOOC

B(OH)₂

OMe

B(OH)₂

OMe

B(OH)₂

Reaction conditions: arylboronic acid (1) (1 mmol), NH₄HCO₃(1.0 mmol), H₂O₂(2 mmol), water (2.0 mL), reaction time (2 h) at room temperature under air.

Isolated yield.