AN EFFICIENT SYNTHESIS OF GEM-DIHYDROPEROXIDES AND 1,2,4,5-TETRAOXANES CATALYZED BYCHLOROSULFONIC ACIDAS A NEW CATALYST

Chlorosulfonic acid was used as an active, low-cost and reusable solid catalyst for conversion of ketones and aldehydes to corresponding gem-dihydroperoxides using 30% aqueous hydrogen peroxide at room temperature. The reactions proceed with high rates and excellent yields.


Material and instruments
Solvents, reagents, and chemical materials were obtained from Aldrich and Merck chemical companies and purified prior to use. Nuclear magnetic resonance spectra were recorded on JEOL FX 90Q using tetramethylsilane (TMS) as an internal standard. Infrared spectra were recorded on a PerkinElmer GX FT IR spectrometer (KBr pellets).
Caution: Although we did not encounter any problem with gem -dihydroperoxides, peroxides are potentially explosive and should be handled with precautions; all reactions should be carried out behind a safety shield inside a fume hood and heating should be avoided.

General procedure for synthesis of gem-dihyroperoxides:
To a mixture of carbonyl compound (1 mmol) and ClSA (0.0066 ml, 0.1mmol) in MeCN (3 ml) 30% aqueous H2O2 (1 ml) was added, and the mixture was stirred at room temperature for an appropriate time (Tables 2,3 and 4). After completion of reaction as monitored by thin-layer chromatography (TLC), the mixture was diluted with water (5 ml) and extracted by eth yl acetate (3×5 ml). Aqueous layer which contains SA and organic layer that contains products, was separated, dried over anhydrous Mg 2SO4, and F e b r u a r y 1 3 , 2 0 1 5 evaporated under reduced pressure. The residue was purified by silica-packed column chromatography (hexane-EtOAc) to afford pure gem -dihydroperoxides (Tables 2,3 and 4). Products were characterized on the basis of their melting points, elemental analysis and IR, 1 H NMR, and 13 C NMR spectral analysis and amount of peroxide in products has been determined by iodometric titration.

General procedure for synthesis of teraoxanes:
To a mixture of ketone (1 mmol) and ClSA (0.0066 ml, 0.1mmol) in MeCN (3 ml) gem -dihydroperoxide (1 mmol) was added and the mixture was stirred at room temperature for an appropriate time (Tables 5). After the completion of the reaction as monitored by thin -layer chromatography (TLC), the mixture was diluted with water (5 ml) and extracted with CH2Cl2 (3×5 ml). Then, aqueous layer and organic layer was separated, dried over anhydrous Mg2SO4 and evaporated under reduced pressure. The residue was purified by silicapacked column chromatography (hexane-EtOAc) to afford pure 1,2,4,5-tetraoxanes (Tables 5). Products were characterized on the basis of their melting points, elemental analysis and IR, 1 H N MR, and 13 C N MR spectral analysis.

RESULTS AND DISCUSSION
In an effort to establish the reaction conditions, various reaction parameters were studied to produce 1,1dihydroperoxycyclohexane by the model reaction of cyclohexanone with 30 % aqueous H 2O2 under catalytic effect of ClSA, so the results are summarized in Table 1. As we have seen in this Table, the best result in terms of yield and F e b r u a r y 1 3 , 2 0 1 5 reaction time was provided using MeCN as a solvent at room temperature with 0.1 mmol of catalyst loading (entry 6, table 1).
With optimized conditions in hand (aldehyde or ketones (1 mmol), aqueous 30% H 2O2 (3 ml), 0.1 mmol catalyst, MeCN (3 ml, r.t)) we began to study the scope of the reaction using a range of cyclic aliphatic ketones (Table 2), side chain aliphatic aldehydes and ketones (Table 3) and aromatic aldehydes and ketones (Table 4). According to results summarized in these tables, generally, both cyclic and side chain aliphatic ketones react faster than the aromatic ketones because of the conjugating of carbonyl group with aromatic ring to afford the corresponding gem -dihydroperoxides comparatively in higher yields. This conjugating cause that benzophenone recovered intact after 200 minutes. For cyclic ketones, cyclohexanone reacts faster than cyclopentanone in higher yield (table 2, entries 1a and 1d). Also, interestingly, the aromatic aldehydes and ketones substituted by electron-withdrawing substituent didn't react at all or they reacted in very long time with nearly low yields. It has been explained by Katja Zmitek and Co -workers [28]. They reported that the transition state for this reaction has positive charge on carbonyl group. So, this reaction has high negative reaction constant (ρ= -2.76) that suggests a transition state with a more developed charge in the rate -determining step [28]. For example, we observed that 4-N,N-dimethylamino bebzaldehyde reacts faster than 4-chlorobenzaldehyde (table 4, entry 3k). On the other hands, 4-nitro benzaldehyde converted very slowly to gem -dihydroperoxide in very low conversion (13%) and decomposed after 0.5 hour because of the powerful electron -withdrawing effect of NO2 group, (table 4, entry 3i). summing up, we suggest that Chlorosulfonic acid activates both carbonyl group and hydrogen peroxide. In fact, chlorosulfonic acid is a powerful acid, so generates H+ which activates the carbonyl group. On the other hands, the chlorine atom in chlorosulfonic acid is a powerful; electronegative atom, consequently it causes hydrogen peroxide (or gem-dihydroperoxide) more nucleophile via hydrogen bonding (scheme 3).     13 C NMR and IR) analysis and compared with the data reported in the literature and amount the peroxide is determined by Iodometric titration.
Moreover, It is interesting that aliphatic aldehydes react with only one molecule of hydrogen peroxide in carbonyl group, so 1,1-hydroxyh ydroperoxide derivatives were formed instead of their expected DHPs (table 3, entries 2h and 2i, scheme 4).  13 C NMR and IR) analysis and compared with the data reported in the literature and amount the peroxide is determined by Iodometric titration. F e b r u a r y 1 3 , 2 0 1 5 For the first time, terephthalaldehyde was reacted as a dialdehyde and we observed that both of the aldehyde groups has been converted to gem -dihydroeperoxide after 360 minutes (table 3, entry 3j). In addition, we have successfully converted 2-methyltheilnyl ketone as a heterocyclic ketone to corresponding gem -dihydroperoxide without any by-product (table 3, entry 3m). Like other our reported works, benzophenone was recovered intact after 200 minutes (table 3, entry 3n).
In the next step, we used some of the synthesized gem -dihydroperoxides as nucleophiles. These gem -dihydroperoxides reacted with ketones and variety of 1,2,3,4-tetraoxanes were produced. (Scheme 2, table 5). Reaction's condition is similar to synthesis of gem -dihydroperoxides condition.  13 C N MR and IR) analysis and compared with the data reported in the literature and amount the peroxide is determined by Iodometri c titration. c Isolated Yield.
Finally, this method for peroxidation of cyclohexanone (entry 1a, table 2) is compared with oth er reported methodologies in the table 6. As has been noted, this methodology is clearly better which really improves the time reaction, yields and reaction condition.

CONCLUSIONS
In conclusion, chlorosulfonic acid was explored as a high active, commercially available and simple catalyst towards the conversion of ketones and aldehydes to corresponding gem -dihydroperoxides. These reactions proceeded smoothly with low reactions time at room temperature to furnish the titled products in high to excellent yields. Chlorosulfonic acid catalyst exhibited a high reusability potential and has shown no significant loss of activity after three consecutive r uns (entry 1, Table 2). This catalyst makes the process affordable and economical.