TEMPO as a catalyst

Our initial work on the TEMPO / Mg(N03)2 / NBS system was inspired by the work reported by Yamaguchi and Mizuno (20) on the aerobic oxidation of the alcohols over aluminum supported ruthenium catalyst and by our own work on a highly efficient TEMP0-[Fe(N03)2/ bipyridine] / KBr system, reported earlier (22). On the basis of these two systems, we reasoned that a supported ruthenium catalyst combined with either TEMPO alone or promoted by some less elaborate nitrate and bromide source would produce a more powerful and partially recyclable catalyst composition. The initial screening was done using hexan-l-ol as a model substrate with MeO-TEMPO as a catalyst (T.lmol %) and 5%Ru/C as a co-catalyst (0.3 mol% Ru) in acetic acid solvent. As shown in Table 1, the binary composition under the standard test conditions did not show any activity (entry 1). When either N-bromosuccinimide (NBS) or Mg(N03)2 (MNT) was added, a moderate increase in the rate of oxidation was seen especially with the addition of MNT (entries 2 and 3). 

Here we report the use of a readily prepared polymer immobilised TEMPO as a catalyst for alcohol oxidations.15 It was derived from a commercially available oligomeric, sterically hindered amine, poly[[6-[(l,l,3,3-tetramethylbutyl)amino]-l,3,5-triazine-2,4-diyl] [2,2,6,6-teramethyl-4-piperidinyl)-imino]-1,6-hexane-diyl[(2,2,6,6-tetramethyl-4-piperidinylimino]], better known as Chimassorb 944 (MW 3000 see figure 3 for structure). This compound is used as an antioxidant and a light stabiliser for plastics. It contributes significantly to the long-term heat stability of polyolefins and has broad approval for use in polyolefin food packaging.16... 

Scheme 8.3 PEG-supported TEMPO as a catalyst for oxidation reactions.

As opposed to TEMPO, PINO is a powerful H-abstracting radical because it forms a strong NO—H bond (in HPI). Accordingly, the synthetic proficiency of PINO as a catalyst in oxidation procedures endowed with low environmental impact has been investigated, and will be reported later. The reactivity features of PINO in the H-abstraction route are now commented on. 

NaClO, or else in the two-phase system but with a quaternary ammonium (viz. AUquat) ion as a phase-transfer catalyst, overoxidation to the corresponding carboxylic acid is obtained (entry 4). Therefore, by proper choice of the experimental conditions, a synthetically useful distinction in products formation can be made for the oxidation of primary alcohols, even though we are far from a satisfactory understanding of the reason behind this different behaviour. In fact TEMPO, as a well-known inhibitor of free-radical processes is allegedly responsible for the lack of overoxidation of an aldehyde to carboxylic acid (entry 3) this notwithstanding, TEMPO is also present under those conditions where the overoxidation does occur (eutry 4). Moreover, a commou teuet is that the formation of the hydrated form of an aldehyde (in water solution) prevents further oxidation to the carboxylic acid however, both entries 3 and 4 refer to water-organic solutions, and their... 

One of the most efficient methods for oxidation of primary alcohols to either aldehydes or carboxylic acids is the one, commonly known as the Anelli oxidation. This reaction is carried out in a two-phase (CH2Cl2/aq.buffer) system utilizing TEMPO/NaBr as a catalyst and NaOCl as the terminal oxidant The new system described here is an extension of the Anelli oxidation, but surprisingly, does not require the use of any organic solvents and replaces the KBr co-catalyst with the more benign, Na2B40y (Borax). The use of the new cocatalyst reduces the volume of the buffer solution and eliminates completely the need of a reaction solvent. The new system was successfully applied in the industrial synthesis of the 3,3-Dimethylbutanal, which is a key intermediate in the preparation of the new artificial sweetener Neotame. 

TEMPO-catalysed oxidation of alcohols to carbonyl compounds with buffered aqueous NaOCl has found broad application, even in large-scale operations. Indeed, this selective methodology involves the use of safe, inexpensive inorganic reagents under mild reaction conditions. A new supported catalyst PEG-TEMPO 11, soluble in organic solvents such as CH2CI2 and AcOH, but insoluble in ethers and hexanes, was prepared and proved to be an effective catalyst for the selective oxidation of 1-octanol with various stoichiometric oxidants. When 11 was used at 1 mol% as a catalyst in combination with KBr (10 mol%) a slight excess of buffered bleach (pH = 8.6) as the terminal oxidant, partial over-oxidation of 1-octanol to octanoic acid was observed (91% yield in... 

The use of Cu in combination with TEMPO also affords an attractive catalyst [200, 201]. The original system however operates in DMF as solvent and is only active for activated alcohols. Knochel et al. [202] showed that CuBr.Me2S with perfluoroalkyl substituted bipyridine as the ligand and TEMPO as cocatalyst was capable of oxidizing a large variety of primary and secondary alcohols in a fluorous biphasic system of chlorobenzene and perfluorooctane (see Fig. 4.69). In the second example Ansari and Gree [203] showed that the combination of CuCl and TEMPO can be used as a catalyst in l-butyl-3-methylimidazolium hexafluorophosphate, an ionic liquid, as the solvent. However in this case turnover frequencies were still rather low even for benzylic alcohol (around 1.3 h 1). 

TEMPO being expensive agent, its efficient recycling is very desirable. It cannot be reused in ionic liquid after ether extraction, due to its good solubility in ether. In contrast, the use of insoluble acetamide-TEMPO, as a stable reagent, rendered product isolation by extraction, and the catalyst recycling is also possible (Scheme 14.5). 

A good method for the direct conversion of alcohols to carboxylic acid uses 2,2,6,6-tetramethylpiperidin-l-oxyl (TEMPO) 51, in conjunction with the co-oxidant sodium chlorite (NaC102) and sodium hypochlorite (NaOCl) as a catalyst. See M. Zhao, J. Li, E. Mano, Z. Song, D. M. Tschaen, E. J. J. Grabowski and P. J. Reider, J. Org. Chem., 64 (1999), 2564. 

An efficient and mild procedure has been described for the oxidation of different types of alcohols to carbonyl compounds using TEMPO as the catalyst and (dichloroiodo)benzene as a stoichiometric oxidant at 50 °C in chloroform solution in the presence of pyridine [157]. Under these conditions, 1,2-diols are oxidized to p-hydroxyketones or p-diketones depending upon the amount of PhICh used. Interestingly, a competitive study has shown that this system preferentially oxidizes aliphatic secondary alcohols over aliphatic primary alcohols [157], while the PhI(OAc)2-TEMPO system selectively converts primary alcohols into the corresponding aldehydes in the presence of secondary alcohols. 

Scheme 12 Selective oxidation of methyl a-glucopyranoside using TEMPO as a pre-catalyst...

While Yu et al. [15] reported the palladium-catalyzed ortho trifluoromethylation of arenes with an electrophilic trifluoromethylation reagent (Scheme 19.9), Liu and coworkers [69] developed a nondirected C-H trifluoromethylation method using the nucleophilic Ruppert-Prakash (TMSCFj) reagent (Scheme 19.43). Thus, indoles underwent trifluoromethylation in moderate yields at the C-2 position or, when the C-3 position was free, at the C-3 position in the presence of a Pd /bis-oxazoline catalyst, cesium fluoride, PhI(OAc)2 as the stoichiometric oxidant, and TEMPO as a radical trap. Similar to Yu s method, the mechanism was proposed to involve the formation of an Ar-Ph -CEj intermediate that reductively eliminates to form the Ar-CFj bond. 

In the second example Ansari and Gree [107] showed that the combination of CuCl and TEMPO can be used as a catalyst in l-butyl-3-methylimidazolium hexafluoro-phosphate, an ionic liquid, as the solvent. However in this case turnover frequencies were still rather low even for benzylic alcohol (around 1.3 h ). 

Synthesis of aldehydes from alcohols is an important transformation in several applications. In small scale oxidations still chromic acid is being used as a stoichiometric oxidant of alcohols, which leads to a large amount of toxic waste and it is also expensive. Catalytic routes have been reported using palladium catalyst [18], or TEMPO (see also Figure 15.13) as a radical catalyst for the oxidation of alcohols [19], or combinations of TEMPO and copper [20] related work is mentioned in the references of these articles. The mechanism of... 

The application of ionic liquids as a reaction medium for the copper-catalyzed aerobic oxidation of primary alcohols was reported recently by various groups, in attempts to recycle the relatively expensive oxidant TEMPO [150,151]. A TEMPO/CuCl-based system was employed using [bmim]PF6 (bmim = l-butyl-3-methylimodazolium) as the ionic liquid. At 65 °C a variety of allylic, benzylic, aliphatic primary and secondary alcohols were converted to the respective aldehydes or ketones, with good selectiv-ities [150]. A three-component catalytic system comprised of Cu(C104)2, dimethylaminopyridine (DMAP) and acetamido-TEMPO in the ionic liquid [bmpy]Pp6 (bmpy = l-butyl-4-methylpyridinium) was also applied for the oxidation of benzylic and allylic alcohols as well as selected primary alcohols. Possible recycling of the catalyst system for up to five runs was demonstrated, albeit with significant loss of activity and yields. No reactivity was observed with 1-phenylethanol and cyclohexanol [151]. 

A convenient procedure for the oxidation of primary and secondary alcohols was reported by Anelli and co-workers (8,9). The oxidation was carried out in CH2CI2 with an aqueous buffer at pH 8.5-9.5 utilizing 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO, 1) as the catalyst and KBr as a co-catalyst. The terminal oxidant in this system was NaOCl. The major disadvantage of using sodium hypochlorite or any other hypohalite as a stoichiometric oxidant is that for each mole of alcohol oxidized during the reaction one mole of halogenated salt is formed. Furthermore,... 

Very recently, Hu et al. claimed to have discovered a convenient procedure for the aerobic oxidation of primary and secondary alcohols utilizing a TEMPO based catalyst system free of any transition metal co-catalyst (21). These authors employed a mixture of TEMPO (1 mol%), sodium nitrite (4-8 mol%) and bromine (4 mol%) as an active catalyst system. The oxidation took place at temperatures between 80-100 °C and at air pressure of 4 bars. However, this process was only successful with activated alcohols. With benzyl alcohol, quantitative conversion to benzaldehyde was achieved after a 1-2 hour reaction. With non-activated aliphatic alcohols (such as 1-octanol) or cyclic alcohols (cyclohexanol), the air pressure needed to be raised to 9 bar and a 4-5 hour of reaction was necessary to reach complete conversion. Unfortunately, this new oxidation procedure also depends on the use of dichloromethane as a solvent. In addition, the elemental bromine used as a cocatalyst is rather difficult to handle on a technical scale because of its high vapor pressure, toxicity and severe corrosion problems. Other disadvantages of this system are the rather low substrate concentration in the solvent and the observed formation of bromination by-products. 

Another interesting observation from the data in Figure 2 was the effect of the catalyst concentration on the aldehyde selectivity (curves 2 in 2a-c). As mentioned earlier, at this moderate reaction temperature, the only by-product present in measurable quantities was hexanoic acid, formed as a product of the over-oxidation of 2. Contrary to what was reported in the literature for other TEMPO based oxidations of alcohols (20,21), the current catalyst system, particularly at higher... 

Here we report on a new TEMPO based catalyst system for the oxidation of primary and secondary alcohols selectively to aldehydes and ketones using NaOCl as a terminal oxidant. 

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