Highly Efficient Method for Synthesis of Benzoquinones Using Hypervalent Iodine(III) Reagent and Sodium Bisulfate

Abstract A rapid, one-step, novel approach for the conversion of benzamides into benzoquinones using (diacetoxyiodo)benzene(III) and sodium bisulfate has been developed in aqueous acetonitrile at room temperature. The developed protocol is applicable to several types of substituted benzamide derivatives to get the corresponding benzoquinone products. The developed methodology offers mild reaction condition, short reaction time, and moderate to excellent yields. This is one of the most simple and environmentally benign protocols for synthesis of benzamide derivatives. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.] GRAPHICAL ABSTRACT

Therefore, there is need to develop dynamic and feasible protocols for the transformation of benzamide to benzoquinone, which can activate under milder reaction conditions. Considering these issues, we focused our attention toward the expansion of a novel protocol for the synthesis of quinone derivatives.

RESULTS AND DISCUSSION
Our research group is mainly working on the hypervalent iodine reagents. During our study we found that (diacetoxyiodo)benzene(III), which is readily available and frequently used in several oxidative transformations, can be used for the synthesis of quinones from benzamides. Thus for our initial studies, we used benzamide as a starting material. It was observed that when benzamide oxidized using (diacetoxyiodo)benzene, a lower yield (15%) of quinone was isolated after long reaction time in water-acetonitrile (1:1) as a solvent. It was found that during the reaction many other unidentified by-products were also formed. Further screening of reagent and reaction conditions revealed that (diacetoxyiodo)benzene in the presence of sodium bisulfate leads to formation of a single product with good yield within short reaction time (Scheme 2). Scheme 1. Some methods for synthesis of benzoquinones.

SYNTHESIS OF BENZOQUINONES 469
It was reported in the literature that the treatment of (diacetoxyiodo)benzene with sodium bisulfate leads to the formation of reactive hydroxy (phenyl) iodonium ions, [18] and we thought that reactive hydroxy(phenyl) iodonium ions may accelerate the formation of quinone from benzamide. Further investigation of reaction found that 5 equivalents of (diacetoxyiodo)benzene and 1 equivalent of sodium bisulfate is suitable for conversion of 1 equivalent of benzamide to quinone (Table 1).
Under these reaction conditions various solvent systems were tried, and it was found that water-acetone-dichloromethane are suitable solvents, but lower yields were obtained as compaired to the water-acetonitrile (1:1) solvent system.
To study the prospective and general applicability of the developed methodology, various benzamides containing different functional groups were investigated, and results are summarized in Table 2. It was observed that 2-methyl benzamide and 2-chlorobenzamide reacted smoothly to obtained good yield of respective benzoquinone derivatives ( Table 2, entries 2-4).It is remarkable to mention that in case of para substituted methoxy, the deprotection followed by oxidation was observed ( Table 2, entry 6), whereas in the case of meta-substituted methoxy no deprotection was observed ( Table 2, entry 5). Similarly para-substituted hydroxy and amino benzamide converted into benzoquinone (Table 2, entries 7 and 8).
It was observed that para-methyl benzamide and 2,5-dimethyl benzamide gives substituted products instead of quinone (Table 2, entries 9 and 10). Reaction of aliphatic amides does not take place with this reaction system (Table 2, entry 11).
In summary, we developed a new application of (diacetoxyiodo)benzene(III) and sodium bisulfate system in aqueous acetonitrile for synthesis of benzoquinonesfrom corresponding benzamides. The advantages of the present method are use of simple shelf reagents, mild reaction conditions, and good yields.
General Procedure for Synthesis of Benzoquinone Derivatives ( Table 2, Entry 1) (Diacetoxyiodo) benzene (5 mmol, 1.61 g) and NaHSO 4 ÁH 2 O (1 mmol, 0.138 g) were stirred for 10-15 min at room temperature in aqueous solution of acetonitrile (5 ml water and 5 ml acetonitrile). In this reaction mixture benzamide (1 mmol) was added and stirring was continuing until reaction went to completion, as monitored by thin-layer chromatography (TLC). After completion of the reaction, the reaction mixture was quenched with water and further extracted with chloroform (3 Â 10 ml). The combined chloroform layers were washed with water (3 Â 20 ml), dried over Na 2 SO 4 , and concentrated on a rota-evaporator to get the crude residue. The residue was further purified by column chromatography on silica gel using ethyl aceate-hexane (1:9) as an eluent to afford pure benzoquinone.