b Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology of Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084, China
Phenols are important synthetic intermediates and are widely used in the synthesis of pharmaceuticals,polymers,and natural products . 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  or copper-catalyzed  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  and have been used in the synthesis of phenols by copper-catalysis . Very recently,we have developed a general copper-catalyzed transformation of arylboronic acids in water to different functionalized aromatic systems including phenols . Obviously the environmentally benign transition metal-free approaches are preferred in organic synthesis. Metal-free organocatalysis has been around for over a century ,but it was left largely unnoticed [8, 9]. Only recently,there has been a remarkable renaissance in organocatalysis because environmentally friendly methods can avoid the need for potentially toxic metal-based catalysts . Several groups have reported the oxidation of organo-boronic compounds to produce phenols using oxidants such as hydrogen peroxide . Very recently,phenols prepared by photocatalysis from arylboronic acids under light irradiation have been reported . 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 CDCl3 as the internal standard (1H NMR: TMS at 0.00 ppm,CHCl3 at 7.24 ppm,13C NMR: CDCl3 at 77.0 ppm) or using tetramethylsilane (TMS) in the solvent of DMSO-d6 as 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).
General experimental procedure for the synthesis of compounds 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 temperature for 2 h. After the reaction finished,4 mL of HCl (1 mol/L) was added to the solution till pH 2-3. The aqueous solution was extracted with ethyl acetate (4×5 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. Methylparaben (2t): yield 98% (149 mg),white solid,mp 125°C. 1H NMR (600 MHz,CDCl3 ):d7.94 (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 ):δ 167.5,160.4,132.0,122.3,115.4,52.2. GC-MS:m/z152.2.
Naphthalen-1-ol (2w): yield 97% (140 mg),colorless solid,mp 109-112°C. 1H NMR (600 MHz,CDCl3 ): δ 8.17 (m,1H),7.81 (m, 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 ): δ 151.3,134.7,127.6,126.4,125.8,125.2,124.3,121.5, 120.7,108.6. GC-MS:m/z144.1.
Dibenzo[b, d]furan-4-ol (2y): yield 96% (177 mg),white solid, mp 135°C. 1H NMR (600 MHz,CDCl3 ):δ 7.85 (d,2H,J= 7.56 Hz), 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 ):δ 156.1, 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/z184.1.
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.
The characterization data and 1H NMR and 13C NMR spectra of compounds 2a-y can be found in Supporting information. EPR measurement: 10mL Phenylboronic acid (25 mmol) and 10mL ammonium biscarbonate (25 mmol) was quickly mixed with 20mL DMPO (100 mmol) and 10mLH2O2 (50 mmol),the sample was subsequently transferred to an EPR flat cell,and spectra were taken by a JEOL EPR spectrometer. Typical 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,AN= 1.50 mT, AH= 1.50 mT) and a carbon central radical (g= 2.0023, AN= 1.58 mT,AH= 2.38 mT) were observed,and the result showed occurrence of a phenyl free radical.
|Scheme 1.Synthesis of phenol on gram scale under the standard conditions.|
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,ammonium bicarbonate,ammonium carbonate provided excellent yields (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 investigated (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.
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.
The reaction mechanism for the synthesis of substituted phenols was also investigated by EPR. As shown in Fig. 1 (curve a), a typical hydroxyl free radical (black dot) (g=2.0023, AN=1.50mT,AH= 1.50 mT) in Fig. 1 (curve b) and a carbon central free radical (star) (g=2.0023,AN=1.58mT,AH=2.38mT) 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 radical . Therefore,a possible mechanism for the synthesis of substituted phenols is proposed in Scheme 2. Hydrogen peroxide transforms into hydroxyl radical (I) in the presence of NH4HCO3, treatment ofIwith arylboronic acid (1) produces an aryl radical (II),and combination ofIwithIIgives the target product (2).
|Fig. 1. In situ EPR spectrum on reaction of phenylboronic acid with hydrogen peroxide (trapped by DMPO): phenylboronic acid (5 mmol) and ammonium biscarbonate (5 mmol) was quickly mixed with H2O2(10 mmol), and DMPO was used (20 mmol) to trap the radical in the reaction. (a) Measurement spectrum; (b) simulated spectrum of hydroxyl radical; (c) simulated spectrum of phenyl radical; (d) simulated spectrum of hydroxyl radical and phenyl free radical|
In summary,we have developed a convenient,efficient and practical metal-free method for the synthesis of substituted phenols. The protocol uses readily available arylboronic acids as the starting materials,inexpensive hydrogen peroxide as a hydroxylation agent,ammonium bicarbonate as an additive (adjusting pH value of the solution),and economical and environmentally friendly water as the solvent,and the reactions could tolerate various functional groups and performed very well at room temperature. In addition,the work-up procedures for the present method were very simple,and the targeted products can be obtained by extraction only. Acknowledgment
The authors thank the National Natural Science Foundation of China (No. 21105054) for financial support. Appendix A. Supplementary data Supplementary data associated with this article can be found,in the online version,at http://dx.doi.org/10.1016/j.cclet.2014. 03.018.
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