Benzoic Acid as an Efficient Catalyst for Synthesis of Phenols

A straightforward synthesis of phenols from aryl boronic acids has been demonstrated using benzoic acid as a catalyst. Variety of arylboronic acids bearing electron rich and electron withdrawing substituents gave the respective phenols in good yields.


Introduction
Phenol and its derivatives are versatile intermediates in agrochemicals, pharmaceuticals, polymers and different natural products.The classical methods for the syntheses of phenols involves Dow's process, Hock's process 1 and hydrolysis of diazonium salts 2 . Unfortunately, these processes suffered from harsh reaction conditions and inferior yield. Therefore, in last few decades, due to versatile nature, easy availability and greater stability arylboronic acids are explored as a new synthetic precursor for the synthesis of phenol.
In past decade, various protocols were reported for the synthesis of phenol from arylboronic acid and the catalysts used were CuSO 4 -phenanthroline, 3 KOH-TBHP, 4 benzoquinones, 5 organic hypervalent iodine (III), 6 NaClO 2 , 7 N-oxides, 8 I 2 -H2O 2 , 9 H 3 BO 4 -H 2 O 2 , 10 Al 2 O 3 -H 2 O 2 , 11 lactic acid-H 2 O 2 , 12 , Amberlite IR 120 resin, 13 supported silver nano particle, 14 etc. However, these methods are associated with certain unavoidable drawbacks such as use of transition metal catalysts, base additive, ligands, high reaction temperatures, excess oxidizing agent and toxic organic solvents.Therefore, to avoid such drawbacks, there is a serious need for more simple and convenient protocols toward the ipso-hydroxylation of arylboronic acids under mild reaction conditions. Herein, we report simple and efficient route for benzoic acidcatalyzed oxidative hydroxylation of arylboronic acids using H 2 O 2 as oxidant. Table 1 Benzoic Acid Catalyzedipso-Hydroxylation of Boronic Acid  Herein, the potentiality of benzoic acid is investigated using commercially available phenylboronic acid (1a) as a model substrate and subjected for oxidative hydroxylation with H 2 O 2 in various solvents (Table 1). The precise quantity of the benzoic acid required to achieve maximum yield was screened and found that 20 mg is enough to attain the complete conversion (Table 1, entry 4). When we have used 20 mg of benzoic acid as catalyst and we obtained 96% of isolated yield (Table 1, entry 4). By lowering the catalyst loading to 10 mg resulted a lower yield (87%) ( Table 1, entry 5). However, increase in the catalyst loading to 50 mg did not significantly improve the yield (Table 1, entry 3). Among the various solvents, only water provided the desired phenol in aquantitative yield (96%) within 15 min (Table 1, entry 4) while in chloroform, tetrahydrofuran (THF), diethyl ether and acetonitrile the reaction did not go to completion after prolonged reaction time ( Table 1, entries 6-9).

Results and discussion
With the optimized reaction conditions in hand, we next examined the substrate scope of this benzoic acid-initiated ipso hydroxylation of structurally and electronically diverse arylboronic acids with H 2 O 2 ( Table 2). Arylboronic acids bearing electron withdrawing groups such as -NO 2 , -Cl, -CHO, -COCH 3 , -CN and electron donating groups like -Me, -OMe, -NH 2 , -OH, -I were used and provided the desired phenols in good yields irrespective of their positions. Results are summarized in the table 2.

Conclusion
In the present work, we have disclosed benzoic acid as versatile, inexpensiveand commercially available reagent for the hydroxylation of organoboronic acid to phenols in the presence of H 2 O 2 .A variety of electronically diverse arylboronic acids were transformed to the corresponding phenols in good yields.We believe that this environment friendly protocol can be useful to industrial scale phenol synthesis.
General procedure for ipso hydroxylation: To a stirred solution of phenylboronic acid (entry 1) (1 mmol) in water (2 mL) was added benzoic acid (20 mg). To the above mixture was added hydrogen peroxide (0.5 mL) and stirred at room temperature for 15 min. After completion, the reaction mixture was diluted with water and extracted with ethylacetate (3 x 10 mL). The ethylacetate layer was washed with brine and concentrated under reduced pressure to give the product (96%).