The Beckmann rearrangement is commonly used in organic chemistry to transform ketoximes into amides [1] - [9] . In particular, cyclohexanone oxime (1) is widely-used to manufacture ε-caprolactam (2) which is used industrially as the raw material for nylon-6. One proposed Beckmann rearrangement method for 1 involves an acid- catalyzed reaction. The lactam formed typically forms salts with acids, inactivating the acid catalyst. Thus, an excessive amount of acid is necessary to accomplish the reaction in a practical way. A large excess of base is also required for the neutralization and liberation of lactam 2, generating large amounts of byproducts such as ammonium sulfate [10] . Organic catalysts have been developed for sulfate-free Beckmann rearrangements, giving quite satisfactory results in the reaction of acyclic ketoximes and ten- or more-membered ketoximes under mild reaction conditions [11] - [16] . Unfortunately, these catalysts do not give satisfactory results for the reaction of 1, and yields of 2 are low. One of the best methods for the sulfate-free production of 2 is a vapor-phase method using various zeolite catalysts [17] , but a disadvantage of this route is that it requires a reaction temperature as high as 350˚C, which causes a massive energy cost and reactor heat deterioration problems. Recently, we developed catalysts combining cobalt salts and Lewis acids which were highly effective for the Beckmann rearrangement of cycloalkanone oximes [18] . In this paper, we focus on the use of more traditional acids, and report that combinations of cobalt salts and Brønsted acids are highly effective for the Beckmann rearrangement of cycloalkanone oximes under mild conditions, assuring more economical and environmentally-friendly process.

Catalytic use of various Brønsted acids is not particularly effective in the Beckmann rearrangement of cyclohexanone oxime (1), as shown in Table 1. In MeCN at 80˚C for 2 h, a 10 mol% of benzenesulfonic acid and trifluoro methanesulfonic acid gave ε-caprolactam (2) in a poor yield. Sulfuric acid, one of the most popular strong Brønsted acids, is used in industry for Beckmann rearrangements of 1. Even if the acid catalyst is deactivated by the formation of a salt (2∙H⁺) with 2, the catalyst should give a reasonable amount of 2. Nevertheless, sulfuric acid (10 mol%) does not accelerate the rearrangement reaction, and 2 was not detected.

^aA mixture of cyclohexanone oxime (0.5 mmol), Brønsted acid, and cobalt salt (10 mol%) was stirred in MeCN (1.0 mL) at 80˚C.

While examining catalysts for a sulfate-free Beckmann rearrangement of cyclohexanone oxime (1), it was found that the combination of a variety of cobalt salts and Lewis acids functions efficiently [18] . Cobalt salts block coordination of the oxime to the Lewis acid through the nitrogen atoms, and firmly coordinate with the Lewis acids added in order to promote the rearrangement reaction at the oxygen atoms in the oxime. We therefore decided to focus on the nitrogen blocking ability of cobalt ions to improve the activity of the acid catalyst for the rearrangement reaction by heightening the interaction between the acid catalyst and the oxygen atom of the oxime.

Use of a catalytic amount of a variety of cobalt salts alone is not particularly effective in the Beckmann rearrangement of 1. It is surprising that the combined use of benzenesulfonic acid and cobalt chloride provided a notable enhancement in the catalytic activity to give 2 in a 47.7% yield. Cobalt tetrafluoroborate is the best co- catalyst for the benzenesulfonic acid-catalyzed rearrangement of 1, affording 2 in 64.9% (2 h) and 88.3% (4 h) yields. Various Brønsted acids were examined for use as rearrangement catalysts. Unfortunately, the addition of cobalt tetrafluoroborate to 10 mol% sulfuric acid gave the same result as when cobalt tetrafluoroborate was used independently. A prolonged reaction time or a slightly increased amount of sulfuric acid was required to obtain 2 in a high yield, and the combination of sulfuric acid (20 mol%) and cobalt tetrafluoroborate (10 mol%) gave 2 in a yield as high as 86.3% by reaction at 80˚C for 24 h. In Table 2, the effect of reaction time on yield is shown in detail. As would be expected, subsequent reaction increases the yield of 2.

Although cyclooctanone oxime (3) is more reactive than cyclohexanone oxime (1) in Beckmann rearrangement reactions, use of either acatalytic amount of a cobalt salt or a Brønsted acid alone is similarly in effective at the rearrangement of 3, as shown in Table 3. Cobalt tetrafluoroborate is the superior co-catalyst for the trifluoromethanesulfonic acid and sulfuric acid-catalyzed rearrangements of 3, as was the case for 1 (Scheme 1). On the other hand, both benzenesulfonic acid and methanesulfonic acid with cobalt perchlorate gave lactam 4 in higher yields than with cobalt tetrafluoroborate. The combined use of sulfuric acid (20 mol%) and cobalt tetrafluoroborate (10 mol%) gave 4 in a 76.0% yield by reaction at 80˚C for 24 h.

It is clearly essential that the strong Brønsted acids used generate salts with the lactams formed and lose their catalytic abilities. Nevertheless, the catalytic amount of acid added continues promoting the Beckmann rearrangement of the oxime to provide the lactam in a high yield. Theoretical calculations confirm that the N-proto- nated cyclohexanone oxime (5) is more stable than the O-protonated cyclohexanone oxime (6) and the high energy transition state between 5 and 6 makes it remarkably difficult to complete the rearrangement (Figure 1) [19] . The aversion to form O-protonated oximes makes suppression of the acid-catalyzed Beckmann rearrangement of oximes more likely than salt formation between the acid catalyst and the lactam obtained. A plausible reaction mechanism for the Beckmann rearrangement involves acceleration by the cobalt salt coordinating to the nitrogen atom and the Brønsted acid protonation of the oxygen of the oxime (Figure 2).

The combination of a variety of cobalt salts with Brønsted acids (acids traditionally used in industrial processes) serves as an efficient catalyst for the Beckmann rearrangement of cycloalkanone oximes to the corresponding

^aA mixture of cyclohexanone oxime (0.5 mmol), sulfuric acid (20 mol%), and cobalt tetrafluoroborate (10 mol%) was stirred in MeCN (1.0 mL) at 80˚C.

^aA mixture of cyclooctanone oxime (0.5 mmol), Brønsted acid, and cobalt salt (10 mol%) was stirred in MeCN (1.0 mL) at 80˚C.

lactams, which has not been accomplished successfully with organic catalysts due to low reactivity of the oximes. The cobalt salts block N-protonation of the oxime, and the Brønsted acids strongly O-protonate, promoting the rearrangement. Choosing the correct cobalt salt to generate a more efficient combination catalyst is very important. This new method provides a low environmental load process to lactam formation under mild conditions.

HidetoshiYamamoto,MasahiroKomeda,AyanaOzaki,MichinoriSumimoto,KenjiHori,TsunemiSugimoto, (2015) Low Environmental Load Process for the Beckmann Rearrangement of Cycloalkanone Oximes by Brønsted Acid Catalyst with Cobalt Salts. International Journal of Organic Chemistry,05,147-152. doi: 10.4236/ijoc.2015.53016