H₂O₂ in WERSA: an efficient green protocol for ipso-hydroxylation of aryl/heteroarylboronic acid

Abstract

A mild, green, economic and efficient protocol has been developed for ipso-hydroxylation of aryl/heteroarylboronic acids to phenols using 30% aqueous H₂O₂ as an oxidant and WERSA (water extract of rice straw ashes) as a neat reaction medium. All reactions were carried out without using metal, ligand, activator or hazardous organic solvent with excellent yield within a very short reaction time at room temperature. Therefore, this appears to be the cleanest and greenest alternative protocol for ipso-hydroxylation of aryl/heteroarylboronic acids.

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Introduction

Phenols are ubiquitous in nature as they are the key structural constituents of various pharmaceuticals,¹ agrochemicals,² polymers³ and naturally occurring compounds mainly as polyphenols⁴ (natural antioxidants). Traditional methods for the preparation of phenols involve nucleophilic substitution of activated aryl halides, Cu-catalysed conversion of diazoarenes⁵ and Pd-catalysed conversion of aryl halides⁶ to phenols. But these existing routes require harsh reaction conditions due to inactive nature of starting materials. However, as a result of continuous effort of many research groups, arylboronic acids have replaced the traditional inactive synthetic precursor for phenols. Ipso-hydroxylation, the generalized method for the conversion of arylboronic acids to phenols is gaining enormous importance due to higher availability, stability and greater functional group diversity of arylboronic acids. As a result various protocols for ipso-hydroxylation of arylboronic acids were put forwarded using different catalysts such as biosilica–H₂O₂,⁷ I₂–H₂O₂,⁸ Al₂O₃–H₂O₂,⁹ PEG–H₂O₂,¹⁰ NH₂OH,¹¹ KOH–TBHP,¹² CuSO₄–phenanthroline,¹³ H₃BO₄–H₂O₂,¹⁴ Amberlite IR-120 resin,¹⁵ supported silver nano particle,¹⁶ organic hypervalent iodine(III)¹⁷ etc.

Even with all the existing protocols, majority of which found to be effective for conversion of arylboronic acids to phenols via ipso-hydroxylation, there is a serious need for “green” protocols with greater environmental and economical viability due to some unavoidable drawbacks of the reported protocols such as use of transition metal as catalyst, ligands, bases and harmful organic solvents. Recently Saikia et al., following the green chemistry tools have explored natural feedstock as green alternatives for carrying out two popular organic reactions Suzuki–Miyaura cross coupling¹⁸ and Dakin reaction.¹⁹ Inspired by their work and following the motion of “greening-up” here we wish to report a superb protocol for ipso-hydroxylation of arylboronic acids to phenols using WERSA (water extract of rice straw ashes) a highly abundant, cheap natural feedstock as neat reaction media and 30% aqueous H₂O₂ as oxidant. To the best of our knowledge this is the first report on ipso-hydroxylation of arylboronic acids to phenols using WERSA and we therefore believe that this is an outstanding alternative protocol for synthesis of phenols from arylboronic acids, as reaction condition is mild, straightforward and without use of metal, ligand, bases and solvents. Additional beauty of the protocol is the use of H₂O₂ as oxygen source rather than other oxygen sources like NaClO₂,²⁰ N-oxide,²¹ HOF²² as H₂O₂ is richer source of oxygen and forms water as byproduct.

Experimental

At the beginning we tried our first reaction with phenyl boronic acid (1 mmol) using 30% aqueous H₂O₂ (0.10 mL) as oxidant in WERSA (2 mL) (Scheme 1) which was prepared using the established procedure²³ to check the feasibility of the reaction. We monitored the reaction by TLC in every min and to our delight phenyl boronic acid fully converted to the desired product phenol within 10 minutes at room temperature. After that we moved on for optimization of oxidant H₂O₂ needed for full conversion taking phenyl boronic acid as model substrate. As a result of optimization as depicted in Table 1 we found that 0.20 mL of 30% aqueous H₂O₂ oxidant were sufficient to complete the reaction within 5 minutes. Along with mild reaction condition, excellent yield, lesser toxicity, operational plainness, cost effectiveness makes this hydroxylation protocol one of the cleanest and greenest alternative protocol ever.

Scheme 1 Ipso-hydroxylation of phenyl boronic acid to phenol.

Table 1 Effects of the amount of 30% H₂O₂ and time in the ipso-hydroxylation of phenyl boronic acid in WERSA at room temperature^a

Entry	30% H2O2 (mL)	Time (min/h)	Yield^b (%)
a Reaction conditions: phenyl boronic acid (1 mmol), 30% H2O2 in WERSA (2 mL) at room temperature.b Isolated yields.c Reaction carried out without WERSA.
1^c	0.10	24 h	Trace
2	0.10	10 min	92
3	0.15	7 min	95
4	0.20	5 min	98

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With the optimized condition, we then carried out numbers of reactions with different electron-rich and electron-poor arylboronic acid to study the substrate scope using this newly designed protocol. According to our expectation, reactions proceeded very smoothly converting various electron-donating and electron-withdrawing groups bearing arylboronic acids to phenols with very good to excellent yield within very short reaction time (Table 2). Results showed that substrate containing electron withdrawing groups were more efficient than electrons donating ones. Moreover, we readily carried out the reaction with some heteroarylboronic acids (Table 2). Till now, there is no earlier report on ipso-hydroxylation using such a mild, green and economic reaction condition. Therefore, this seems to be an evergreen protocol with a wide range of substrate scope for ipso-hydroxylation of arylboronic acids to phenols.

Table 2 Conversion of aryl/heteroarylboronic acid to phenols in H₂O₂–WERSA system at room temperature^a

Entry	Starting materials	Products	Time (min)	Yield^b (%)
a Reaction conditions: aryl/heteroarylboronic acid (1 mmol), 30% H2O2 (0.2 mL for each substrate) in WERSA (2 mL) at room temperature.b Isolated yields.
1			5	98
2			10	92
3			7	95
4			10	94
5			15	90
6			10	92
7			6	95
8			8	94
9			8	97
10			10	92
11			15	90
12			15	91

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Results and discussion

Nucleophilic activation of H₂O₂ is a general fact to use H₂O₂ as oxidant; as a result numbers of bases have already been used to activate H₂O₂ by abstracting a proton so far. Here in this protocol we used only WERSA with H₂O₂ as a neat reaction media for ipso-hydroxylation of arylboronic acids to phenols. Perhaps the exact role of WERSA for the reaction is not clearly understood yet. However, literature²⁴ reveals that rice straw ashes contains oxides of SiO₂ (74.31%), Al₂O₃ (1.40%), Fe₂O₃ (0.73%), TiO₂ (0.02%), CaO (1.61%), MgO (1.89%), K₂O (11.30%), Na₂O (1.85%), P₂O₅ (2.65%) as primary ingredients. Thus water extract of rice straw ashes may contain KOH, NaOH which may be responsible for making WERSA basic enough for nucleophilic activation of H₂O₂ by abstracting its proton. Therefore we proposed a plausible mechanism for ipso-hydroxylation of arylboronic acid to phenol using H₂O₂ in WERSA (Fig. 1).

Fig. 1 A plausible mechanism for ipso-hydroxylation of arylboronic acids to phenols.

Recyclability of WERSA is another attractive feature of this protocol. We reused WERSA upto 5^th cycle without significant lose of efficiency (Table 3). Taking phenyl boronic acid as model substrate we carried out the WERSA recyclability test. After completion of the reactions, products were extracted with diethylether and WERSA separated from product was washed with more diethylether and reused. Thus we can consider WERSA as a reusable homogeneous catalyst.

Table 3 Recyclability of the catalytic system^a

Entry	Run	Time (min)	Yield^b(%)
a Reaction conditions: phenyl boronic acid (1 mmol), 30% H2O2 (0.2 mL) in WERSA (2 mL) at room temperature.b Isolated yields.
1	1^st	5	98
2	2^nd	5	98
3	3^rd	5	96
4	4^th	7	94
5	5^th	10	90

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Conclusions

In conclusion, we have developed a green, mild, efficient and aerobic protocol for ipso-hydroxylation of arylboronic acids to phenols using H₂O₂ as oxidant in WERSA at room temperature. With these mild reaction conditions, our method is very compatible with various electron-donating and electron-withdrawing groups at ortho, meta and para positions on the aromatic ring. In addition, all reactions occur in shortest reaction time without using any activating agent, metal, ligand and organic solvent. From the environmental and economical point of view, we believe that this is the most greener and efficient protocol for ipso-hydroxylation of arylboronic acids to phenols. All these advantages make H₂O₂–WERSA a very adaptable and competitive catalyst system, consequently can be used as clean and safer alternative for various other reactions in laboratory as well as in industry in near future.

Acknowledgements

BC gratefully acknowledges UGC, New Delhi (grant no. 42357/2013) and DST-SERB (No. SB/FT/CS-161/2012) for financial assistance. ES is thankful to the Department of Science and Technology (Government of India) for INSPIRE-Fellowship and SAIF, NEHU-Shillong for spectral data.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra21354a

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