Deoximation of Ketoximes to Ketones with Ammonium Chlorochromate/ Montmorillonite K10 in Dichloromethane

A convenient, mild and efficient method for oxidative cleavage of ketoximes to their parent carbonyl compounds with ammonium chlorochromate (ACC) / montmorillonite K10 in dichloromethane at room temperature is described.


Introduction
Oximes are highly crystalline compounds extensively used for the purification and characterization of aldehydes and ketones.The compounds can also be used as intermediates for the preparation of amides by the Beckmann rearrangement 1 , amines 2 , oxazoles (isoxazoles) 3 , nitrones 4 , nitriles 5 , methylene dioximes 6 and oxime-ethers 6 .However, since many valuable reactions have been developed to prepare oximes from non-carbonyl compounds 7 and oximes serve as efficient protecting groups for carbonyl compounds 8 , an efficient deoximation reaction is required.
In view of the importance of deoximation, several methods have been developed for the cleavage of oximes, such as acid-catalyzed hydrolysis 9 , oxidative reaction 10-12 and reductive reaction 13 .The most popular approach used for deoximation is oxidative reaction using chromium(VI) reagents 11a,14 .However, some of these methods have suffered from different disadvantages such as requirements for refluxing temperature, tedious work-up, drastic conditions, long reaction times 10 , undesired chemical yields 11 and use of expensive and toxic catalysts 12 .Therefore, a milder, more selective, non-hazardous and inexpensive reagent is still required for such transformations.With increasing environmental concerns, it is imperative that environmentally friendly reagents be developed.Recently, oxidative reagents adsorbed on inert inorganic support to eliminate those drawbacks, have been employed by several groups 12b,15 .
Montmorillonite clays known as a bronsted acid have a great impact on organic synthesis and offer a major breakthrough for the fine chemicals manufacturing industry 16 .These solid supports with lamellar swelling structure and large surface area may enhance selectivity in synthetic organic chemistry.Previously, oxidative deprotection of tetrahydropyranyl ethers using ACC/montmorillonite K-10 has been reported 17 .Herein, we wish to report an efficient and mild oxidative cleavage of ketoximes to ketones with ammonium chlorochromate/montmorillonite K10 at room temperature (Scheme 1).

Experimental
The starting materials, ketoximes were prepared according to literature 18,19 .Sonication was performed in Shanghai Branson-CQX ultrasonic cleaner with a frequency of 25 kHz and a nominal power 250 W. The reaction flask was located in the maximum energy area in the cleaner bath, where the surface of reactants is slightly lower than the level of the water.The reaction temperature was controlled by addition or removal of water from ultrasonic bath.

General procedure of oxidative cleavage of ketoximes to oximes
To a solution of ketoxime (1, 1 mmol) in dichloromethane (5 mL) 0.555 g, ACC/M K10 (1 mmol) was added.The mixture was stirred (or irradiated in ultrasonic cleaner) for a period as indicated in Table 1 at room temperature.The progress of the reaction was monitored by thin layer chromatography.After the completion of the reaction, the products were isolated by filtration the oxidant from reaction mixture.And then the solvent was recovered by evaporation under reduced pressure.The further purification was accomplished by column chromatography on silica (200-300 mesh, eluted with petroleum ether or a mixture of petroleum ether and ethyl acetate).All of the products are known compounds and were identified by comparison of their physical properties (melt point and boil point) and R f values with standard sample.

Results and Discussion
We observed the effects of different solvents on the reaction, and found that there was rarely transformation in the reaction of acetophenone oxime (1a) to acetophenone (2a) with ACC/M K10 in toluene or THF.Dichloromethane is the most suitable solvent in the reaction.The effect of the molar radio of 1a/oxidant (ACC/M K10) on the deoximation of 1a in dichloromethane was tested.The results were summarized in Table 1.As shown in the Table 1, when the molar radio of 1a/ACC/M K10 was 1:0.5, the yield of 2a was 83%.By increasing the molar ratio to 1:1 and 1:1.5, the yields of 2a increased to 96% and 94% respectively.The results showed that changing the molar ratio of 1a/ACC/M K10 had a significant effect on the yield, and the optimum molar radio was 1:1.The effect of support on the reaction was also observed.When the support was alumina or silica gel in the same conditions, 1a wasn't completely transformed to 2a.From the results above, the optimum reaction condition was chosen: ketoximes (1, 1 mmol), oxidant (1 mmol, ACC/M K10 is 0.555 g), dichloromethane (5 mL).Under this reaction system, a series of experiments for deoximation of ketoximes with ACC/M K10 in dichloromethane at room temperature were performed.The results are summarized in Table 2.
As shown in Table 2, ACC/M K10 was effective in promoting to deoximation of ketoximes to ketones in dichloromethane.For example, by using ACC/alumina oxidant, 2a and 2g were obtained in 76% and 61% yield respectively for 3-3.5 h in dichloromethane 11b , whereas with ACC/M K10, 2a and 2g were obtained in 96% and 97% yields for 2-3 h.
The different substituents in the benzene ring have some effects on the yield and the reaction time.The electron-donating substituents in the benzene ring can accelerate the deoximation (Table 2. 2c, 2f, 2g).In contrast, electron withdrawing substituents in the benzene ring decreased the reactivity (Table 2. 2b, 2d, 2e).Deoximation of 1h to 2h was carried out in poor yield (65%) for long time; it may be because of the effect of the steric hinderance.In addition, we found that aliphatic ketoximes (1i, 1j) were also transformed to the corresponding ketones with high yields in short time.We also did the experiments of deoximation of ketoximes to ketones in the presence of ultrasound.As shown in Table 2, the deoximation of 4-nitroacetophenoneoxime (1d) and 3nitroacetophenoneoxime (1e) was completely consumed for 2 h under ultrasound irradiation, while for 5-6 h in the above stirring reaction.It is apparent that ultrasonication can accelerate the deoximation of some ketoximes.The reason may be the cavitation produced by ultrasound 18 , which can cause reaction rapidly.
During the reactions, the color of the oxidant changes from orange to dark brown, providing visual means for ascertaining the progress of the oxidation.The mechanism for the present oxidation is still unclear.However, we assume it is similar to that of other chlorochromates.

Conclusion
In conclusion, we have described a convenient, mild and efficient method for oxidative cleavage of ketoximes to their parent carbonyl compounds with ACC/M K10 in dichloromethane at room temperature.
2 mol) was added within 15 min at 40 o C. The mixture was cooled until a yelloworange solid form.Reheated to 40 o C, a solution was obtained.M K10 (80 g) was then added to the solution with stirring at 40 o C.After evaporation in a rotary evaporator the orange solid was dried for 2.5 h at 50 o C. The content of ACC in ACC/M K10 was about 18.1%.

Table 1 .
The effect of molar ratio of substrate/ oxidant (ACC/M K10) on the oxidation of acetophenone oxime at room temperature

Table 2 .
Oxidative cleavage of carbon-nitrogen double bonds by using ACC/M K10 with or without ultrasound irradiation at room temperature * Without ultrasound irradiation