Oxidation of 4-methoxyanilines to 1,4-benzoquinones using ceric ammonium nitrate (CAN)
Introduction
In the course of our work on the synthesis of various antitubercular terpenes1 and related compounds,2 we were challenged by the need to oxidize a relatively complex aniline to the corresponding benzoquinone.3 This Letter summarizes our successful development of ceric ammonium nitriate for that purpose.
The oxidation of aromatic amines to quinones is a potentially convenient way to generate the latter, since anilines are readily available via a number of processes, including the reduction of nitroarenes. While a number of methods have been reported for this oxidation,4, 5, 6, 7, 8, 9, 10, 11, 12 they can be tedious due to long reaction times, complicated work-up procedures, or low yields and often work best when using anilines soluble in water.
Ceric ammonium nitrate (CAN) is a powerful oxidant that has many uses in organic synthesis.13 This reagent is well known to oxidize electron rich aromatic groups. The removal of p-methoxyphenyl and related electron rich aromatic groups from amines has been established.14 For example, electron rich aromatics can be removed from secondary amines and secondary amides by oxidation with CAN.15 It is likely that such deprotections proceed via the formation of a quinone, but generally in these processes, the quinone is not the desired organic material. Other electron rich systems are readily oxidized by CAN to quinones,16 but it appears that the direct oxidation of substituted, unprotected anilines to quinones has not previously been reported.
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Results and discussion
We specifically wanted to accomplish the conversion of 1 into 2 (Eq. 1). To this end, 1 was treated with a variety of oxidants. After several attempts with known procedures17 that proved ineffective; we turned to ceric ammonium nitrate and found that a good yield of the quinone 2 could be obtained simply by stirringaniline 1 in the presence of the reagent in a 1:1 mixture of water and acetonitrile. Thus, an acetonitrile solution (4 mL) of 1 (0.6 mmol) was added dropwise into a 16 mL solution
Conclusion
We found that treatment of p-methoxyanilines with ceric ammonium nitrate afforded the corresponding 1,4-quinones in good yield. The efficacy of CAN as an oxidant suggests its potential applicability to many oxidation problems, some of which we plan to test. Results will be reported in due course.
Acknowledgment
This work was supported by the NIH (1R01-A159000-01A1) to whom we are very grateful.
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