Oxidative cleavage of β -aryl alcohols using manganese(IV) oxide

It was found that β -aryl alcohols can be cleaved to chain-shortened carbonyl compounds with direct formation of carbon monoxide by treatment with manganese(IV) oxide. A mechanistic scheme is proposed that accounts for the loss of one carbon atom. Carbon monoxide was detected by PdCl 2 /HCl reagent

The precise structure of manganese(IV) oxide depends on the method of preparation.][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Depending on the preparative method, the structure, composition and the reactivity of the active Mn(IV) oxide changes.The efficiency of active Mn(IV) oxide strongly depends on the percentage of the γ-form.Active γ-Mn(IV) oxide is sometimes significantly more effective than classical Mn(IV) oxide. 17It is also known that the water content of active Mn(IV) oxide has a strong influence on the oxidation power and the selectivity of its reactions.Manganese oxide, which contains water in 40-60% (weight%) is activated by heating at various temperatures (12-24 h at 100-130 °C). 19If there is excess water, the oxidizing power of Mn(IV) oxide decreases. 18,20According to a theory by Fatiadi et al. 1 the excess of water prevents the substrate from being selectively oxidized on the surface of the Mn(IV) oxide.On the other hand, the presence of hydrated Mn(IV) oxide is important to obtain an active reagent.For these reasons, the drying process must be carefully controlled. 2,13,18,21he choice of solvent is also very important for the use of Mn(IV) oxide in oxidations.Primary and secondary alcohols or water are normally not suitable as solvents because they are adsorbed on the active surface of Mn(IV) oxide and thus deactivate the reagent. 18A similar influence is observed with polar solvents (acetone, EtOAc, DMF and DMSO).However, these solvents including water, acetic acid or pyridine can be used at high temperatures without any problems.In the literature, most reactions have been carried out in chlorinated hydrocarbons, diethyl ether, THF, EtOAc, acetone, acetonitrile or in ionic liquids.The best results for the oxidation of benzyl 15 and allyl alcohols 14,15 are achieved in diethyl ether.3][24][25][26][27][28][29][30] In general, allyl alcohols can be oxidized with Mn(IV) oxide to the corresponding aldehydes with good-to-very good yields. 7- 10,19,20,31An important example for the oxidation of allyl alcohols is the preparation of retinal from vitamin A 1 . 12• when converting allyl alcohols into α,β-unsaturated esters or amides. 20The first method for conversion allyl alcohols into α,β-unsaturated esters and amides was developed by Corey et al. 20,25 The key step is the formation and subsequent oxidation of the cyanohydrin.The acyl cyanide initially formed by oxidation is converted into the corresponding α,β-unsaturated ester 25 or amide 20 by alcoholysis or aminolysis.• in the oxidation of propargylic, 32 heterocyclic benzyl alcohols, 33 and γ,δ-unsaturated alcohols. 34ropargylic alcohols can also be oxidized with Mn(IV) oxide to give alkynyl aldehydes or ketones. 32,35,36he oxidation of heterocyclic benzyl alcohols 25,33 and γ,δ-unsaturated alcohols 34,37 with Mn(IV) oxide is very effficient.Oxidative cleavage of the C-C bond of 1,2-diols, 37 for example to produce the corresponding diketones 37 can also be achieved with manganese dioxide.• when hydrating nitriles to amides, 38 • in dehydration and aromatization reactions, 39 • in the oxidation of amines to aldehydes, imines, amides and to diazo compounds. 40e oxidation of nitriles to amides with Mn(IV) oxide proceeds in good-to-very-good yields. 38Manganese (IV) oxide reacts also with the following functional groups: • with olefins as substrates for the cleavage of olefins or for the aromatization of cyclic olefins, 30,39,41,42 • with amines as substrates, oxidation to amides, imines 40 or with N-N coupling to diazo compounds, 5 • with diphenyl methanes as substrates, leaeding to oxidation to benzophenone 43 or with oxidative dimerization to 1,1,2,2-tetraphenylethane, 44 • with aromatic aldehydes as substrates leading to oxidation to carboxylic acids 5 , • with phosphines as substrates leading to oxidation to phosphine oxides. 5rakat et al. has shown that carboxylic acids (Table 1, entries 1-6), α-hydroxycarboxylic acids (Table 1, entries 7-9) or α-aminocarboxylic acids (Table 1, entries 10-13) react with Mn(IV) oxide with decarboxylation or with ammonia elimination producing the corresponding carbonyl compounds (Table 1).Barakat et al. assumed that the formation of ethylene from two citric acid molecules occurs through the reaction of two carbene intermediates.However, no additional experiments were carried out to detect the carbene intermediates (Table 1, entries 3-6). 5a The yields are not given in the literature. 5e corresponding carbonyl compounds or carbon dioxide are formed during the oxidation of alcohols or 1,2-diols with manganese dioxide (Table 2). 5a The yields are not given in the literature.b The reaction was carried out in diethyl ether.c The reaction was carried out in benzene. 5

Results and Discussion
There are many examples of the oxidation of a broad range of organic functional groups in the literature.However, there exists only one example of the oxidative cleavage of alcohols. 50In this work, a new oxidative cleavage method is presented to produce aldehydes/ketones starting from the corresponding β-aryl alcohols using manganese dioxide in nonpolar solvents (Table 3).A total of nine substrates was tested (substrate A to substrate I) in different reaction conditions.However, yields of the oxidative cleavage vary and are low-to-good.For comparisons, the Table is separated into β-aryl alcohols (substrates A to D), β-aryl-β-alkyl alcohols (substrates E and F), β-aryl-β-methoxy alcohols (substrates G) and β,β-diaryl alcohols (substrate H and I) (Table 3).Substrate A cleaves oxidatively to benzaldehyde in 25% yield with manganese dioxide as the oxidizing agent, supported on aluminum silicate (entry 1, Table 3). 43ubstrate B reacts under oxidative cleavage to give 2-naphthaldehyde in very low yield using potassium permanganate and manganese dioxide as the oxidizing agent and using a polar solvent such as acetone (entry 2, Table 3).The best yield was achieved by using non-polar solvent petroleum ether 60/70 (entry 4, Table 3).Substrate C was also tested by using different polar solvents and by addition of different oxidizing agents to manganese dioxide such as O 2 , KMnO 4 , tert-butyl hydroperoxide, H 2 O 2 , Al 2 O 3 /SiO 2 in order to increase the activity of the manganese dioxide and thus the yield of the product (entries 5-22, Table 3).The oxidative cleavage was supposed to be accelerated because the conversion is still high and there was still a lot of starting material that did not undergo oxidative cleavage.The best yield was achieved by using cyclohexane as the non-polar solvent and manganese dioxide as the oxidizing agent, supported on aluminum silicate (entry 22, Table 3).Manganese dioxide is known to exhibit poor activity in polar solvents, as described in the introduction.For this reason, it was suspected that the yield of product using substrate D is low because polar solvents such as acetone were used (entry 23, Table 3).
The assumption was, that the oxidative cleavage would proceed by a radical mechanism pathway, because very little polymer was always obtained.Therefore, when optimizing the reactions with β-aryl-β-alkyl alcohols, azobis(isobutyronitrile) AIBN was added as a radical starter.The best yield was obtained with cyclohexane as solvent (substrates E, entry29, Table 3).Substrate F reacts with the use of manganese dioxide on aluminum silicate to acetophenone with moderate yield (entry30, Table 3).
2-Methoxy alcohol (substrates G) reacts under the same reaction conditions to give ester with moderate yield.That is one of the most important results of our research.If the reaction conditions could be optimized for a broad range of substrates, the corresponding esters could be prepared directly from 2-methoxy-1alcohols, which is not yet known in the literature and would be very a useful method (entry31, Table 3).
In general, it can be said that β,β-diaryl alcohols (substrates H and I) are more reactive compared to β-aryl alcohols (substrates A to D) or β-aryl-β-alkyl alcohols (substrates E and F).Better yields were therefore obtained (entry 32, 33, Table 3).The assumption is that the β,β-diaryl alcohols are better able to form enol intermediates (see intermediate 4, mechanism) during the reaction and that intermediate 5 can be formed more easily. 45ere, the effect of permanganate on the reaction mechanism was not considered.The subject of the paper is oxidation with Mn(IV), use of Mn(VII) is not included.It is assumed that β-aryl alcohol first oxidizes to the corresponding aldehyde 2 (Scheme 1).In this step, α-aryl aldehyde 3 can polymerize.α-Aryl aldehyde 3 is known to polymerize when heated. 5 Compound 3 or 4 react again through oxidation to give α-hydroxy, α-aryl aldehyde 5.This can be cleaved to the corresponding product 6 either in the presence of AIBN and by a radical pathway or again by further oxidation by manganese(IV) oxide.This would produce carbon monoxide which was detected with PdCl 2 /HCl reagent. 46For this, a bubble counter was filkled with the yellowish liquid, which was connected directly to the round-bottom flask or reflux condenser.Attempted detection of carbon dioxide, with Ba(OH) 2 , 47 in all reactions gave a negative result.

Conclusions
The development of new methods with heterogeneous reagents that are easy to prepare and easy to separate from the reaction environment is particularly important for organic synthesis.Manganese(IV) oxide can be counted among such reagents.It was shown for the first time that β-aryl alcohols are oxidatively cleaved with Mn(IV) oxide to the corresponding aldehydes.However, the conversion and yield of the reaction are only lowto-good.It is possible that conversions and yields could be increased by switching to non-polar solvents (e.g.petroleum ether).

Experimental Section
Methods and analysis methods Solvents Solvents were dried using standard methods.Cyclohexane, ethanol, benzene and toluene were dried over sodium, distilled off and stored over molecular sieves 3Å or 4Å under argon.Methanol was dried over magnesium, distilled and stored over 3 Å molecular sieves under argon.1,4-Dioxane, THF and diethyl ether were first dried over potassium hydroxide, then over sodium, distilled and stored over molecular sieve 4 Å under argon.EtOAc and acetone were dried over phosphorus pentoxide, distilled and stored over molecular sieves 4Å or 3Å under argon.Dichloromethane was dried over potassium carbonate and distilled.Chloroform and the remaining chlorinated and/or fluorinated solvents were freshly distilled before use.Working with exclusion of air and moisture was carried out under an inert gas atmosphere (argon 5.0 from the company "Sauerstoffwerk Friedrichshafen GmbH").β-Mn (IV) oxide (pyrolusite) was used in all reactions.The reagent is commercially available and was purchased from Sigma-Aldrich with MDL No.: MFCD00003463.

Chromatography
Analytical thin-layer chromatography on silica gel foils (silica gel 60 F 254 ) from E. Merck, Darmstadt or aluminum oxide foils (Al 2 O 3 150 F 254 ) from Mancherey-Nagel GmbH & Co. KG.The substances were detected by UV light (λ = 254 nm), staining with iodine or the spray reagent 2,4-dinitrohydrazine solution.The preparative column chromatography was carried out in gravity columns with silica gel 60 (0.06-0.2 mm) from Roth.The cyclohexane and EtOAc solvents used were distilled before use.

Synthesis of manganese(IV) oxide supported on aluminum silicate (Al
Aluminum silicate (30 g) was added to a solution of KMnO 4 (1.9 g) in destilled water (50 mL).The water was then removed.The powder was ground and added to a solution of MnSO 4 (4.9 g) in water (50 mL).Then it was filtered through Celite and washed with plenty of water.Then it was dried in a drying oven for three days.

Table 2 .
5xidation of alcohols with manganese dioxide by Barakat et.al.5

Table 3 .
The oxidative cleavage of alcohols to aldehydes or ketones

Table 3 .
Continued a β-Mn (IV) oxide (pyrolusite) was used in all reactions.The reagent is commercially available and was purchased from Sigma-Aldrich with MDL No.: MFCD00003463.b No selective reaction.c Not determined.d All yields were determined by the isolation of products.