Benzylic alcohols, aerobic oxidation

Figure 5.5 Example of drastic activity enhancements. Aerobic oxidation of benzyl alcohol to benzaldehyde in scC02 over TPAP entrapped in aged ( , ) and fresh ( ) 75% methyl-modified silica matrix. (Reproduced from Adv. Fund. Mater., with permission.)...

Figure 5.8 Oxidation kinetics in the aerobic conversion of benzyl alcohol to benzal-dehyde in toluene mediated by 10 mol% TPAP either encapsulated in the sol-gel hydrophobic matrix A-Me3 or unsupported. (Reproduced from ref. 17, with permission.)...

Figure 32. Proposed mechanism for the aerobic oxidation of benzyl alcohol by Complex E. [Adapted from (212).]...

Recently, two reports (218, 219) appeared showing that (iminosemiqui-nonato)copper(II) complexes also catalyze the aerobic oxidation of primary alcohols (ethanol, benzyl alcohol) to the corresponding aldehydes and H202. Complexes J and K shown in Fig. 33 have been isolated as active catalysts and the former has been characterized by X-ray crystallography. Detailed mechanistic studies have been performed that again show the close resemblance to GO. 

Ishii and co-workers [109] reported the aerobic oxidation of various organic compounds catalyzed by (NH4)5H6[PV8Mo4O40] supported on active carbon. The catalyst showed high activity for oxidative dehydrogenation of various benzylic and allylic alcohols to give the corresponding carbonyl compounds in moderate to high yields. The catalyst can be recycled without loss of activity for the... 

FIGURE 3. Hammett plot for the aerobic oxidation of X-substituted benzyl alcohols with Mn(II)-Co(ll) nitrates and TEMPO in AcOH, in competition experiments. Reprinted with permission from Reference 129. Copyright (2004) Wiley-VCH... 

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]. 

The use of a novel N3O2 ligand set provided an unsaturated five-coordinated Cu complex (19), capable of performing the aerobic oxidation of benzyl alcohol to benzaldehyde in the presence of Cu(CF3S03)2 as initial oxidant, with 44 turnovers in 24 h [163]. The initial step produces the active bis-phenoxy radical species 20 (Eq. 13). Under exclusion of air, greatly reduced catalytic activity was observed, indicative of reoxidation of the active catalyst by O2, although the possibihty for H2O2 (which is a likely side-product) to act as oxidant could not be ruled out. 

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. 

A recent contribution reported by Aoshima and Tsukuda showed the aerobic oxidation of alcohols such as benzyl alcohol catalyzed by gold nanoclusters. These stable and durable clusters of less than 4 nm were prepared using thermosensitive vinyl ether star polymers previously obtained by living cationic polymerization. 

The partial oxidation of alcohols, to afford carbonyl or carboxylic compounds, is another synthetic route of high industrial interest For this, scC02 was investigated as a reaction medium for the aerobic oxidation of aliphatic, unsaturated, aromatic and benzylic acids with different catalytic systems, mainly based on the use of noble metals, both in batch [58-64] and in continuous fixed-bed reactors [65-70]. In this context, very promising results have been obtained when studying the catalytic activity of supported palladium and gold nanoparticles in the oxidation of benzyl alcohol to benzaldehyde these allowed conversions and selectivities in excess of 90% to be achieved [71-73]. 

An efficient and convenient methodology for the aerobic oxidation of alcohols catalysed by sol-gel trapped perruthenate and promoted by an encapsulated ionic liquid in supercritical carbon dioxide solution has been reported. The reaction is highly selective and useful for substrates otherwise difficult to oxidize.263 A four-component system consisting of acetamido-TEMPO-Cu(C104)2-TMDP-DABCO has been developed for aerobic alcohol oxidation at room temperature. The catalytic system shows excellent selectivity towards the oxidation of benzylic and allylic alcohols and is not deactivated by heteroatom-containing (S, N) compounds. The use of DMSO as the reaction medium allows the catalysts to be recycled and reused for three runs with no significant loss of catalytic activity.264... 

A new catalytic system consisting of a persistent macrocyclic aminoxyl radical and the couple Mn(N03)2-Co(NC>3)2 for the aerobic oxidation of alcohols to carbonyl compounds has been developed. The rate-determining step has been identified by studying the effect of substituents on the oxidation of benzyl alcohol. The chemistry of aminoxyl, amidoxyl, and imidoxyl radicals has been discussed.265... 

Although a suitable acceptor for the transfer dehydrogenation of benzylic alcohols has not yet been found, under the present conditions the low conversion of benzylic alcohols is only an apparent drawback. Indeed, it has a positive side as it allows us to fine-tune the system s selectivity. This makes the catalytic system unique among all the others known, operating both under aerobic and anaerobic conditions, that preferentially oxidize benzylic alcohols with respect to nonacti-vated secondary ones. 

Pd(II) catalysts have been widely used for aerobic oxidation of alcohols. The catalytic systems Pd(OAc)2-(CH3)2SO [14] and Pd(OAc)2-pyridine [15] oxidize allylic and benzylic alcohols to the corresponding aldehydes and ketones. Secondary aliphatic alcohols, with relatively high water solubility, have been oxidized to the corresponding ketones by air at high pressure, at 100 °C in water, by using a water-soluble bathophenanthroline disulfonate palladium complex [PhenS Pd(OAc)2] [5d]. The Pd catalyst has also been successfully used for aerobic oxidative kinetic resolution of secondary alcohols, using (-)-sparteine [16]. 

Our own work in the area of aerobic oxidations was inspired by the exquisite research performed on the structure and reactivity of the binuclear copper proteins (7), hemocyanin and tyrosinase, and by the seminal contribution of Riviere and Jallabert (8). These two authors have shown that the simple copper complex CuCl - Phen (Phen = 1,10-phenanthroline) promoted the aerobic oxidation of benzylic alcohols to the corresponding aromatic aldehydes and ketones (Fig. 2). 

Such a simple mechanistic proposal accomodated the observation that highly activated, benzylic alcohols were good substrates due to the enhanced lability of their a-hydrogen atoms. In contrast, aliphatic alcohols are far less reactive towards H-radical abstraction and, accordingly, poor conversions should ensue. However, it was rather disturbing to note that allylic alcohols, such as geraniol and nerol, displayed poor reactivity in this system. Furthermore, it was observed that the aerobic oxidation of aliphatic alcohols invariably resulted in the rapid formation of a green copper(II) salt, with concomitant deactivation of the catalyst. 

Recently two heterogeneous TPAP catalysts were developed which could be recycled successfully and displayed no leaching In the first example the tetraalkylammonium perruthenate was tethered to the internal surface of mesoporous silica (MCM-41) and was shown [ 101] to catalyse the selective aerobic oxidation of primary and secondary allylic and benzylic alcohols (Fig. 17). Surprisingly, both cyclohexanol and cyclohexenol were unreactive although these substrates can easily be accommodated in the pores of MCM-41. No mechanistic interpretation for this surprising observation was offered by the authors. 

In 2000, Yamaguchi et al. [116] synthesized a ruthenium-based hydroxyapatite catalyst, with the formula (RuCl)10(PO4)6(OH)2. This catalyst could also be recycled and displayed a reasonable substrate scope in the aerobic alcohol oxidations (Eq. 30). TOFs reported in this case were generally somewhat lower, on the order of 1 h 1 for 2-octanol to 12 h 1 for benzyl alcohol. The fact that distinct Ru-Cl species are present at the surface points in the direction of a hydridometal mechanism. 

TABLE 8 Results of the aerobic oxidation of benzyl alcohol in supercritical C02 at 150 bar and 353 K (Grunwaldt and Baiker, 2005). 

In summary, we have developed a recyclable heterogeneous catalyst for the bleach oxidation of alcohols and polyols. In contrast to previously reported systems, neither a chlorinated hydrocarbon solvent nor a bromide cocatalyst is necessary to achieve good activity. Besides bleach-oxidation, PIPO is also effective in the CuCl/nitroxyl catalysed aerobic oxidation of benzyl alcohol. A further advantage of our system is that PIPO is readily prepared from inexpensive and commercially available raw materials. We believe that it will find wide application in organic synthesis. 

General procedure for the aerobic oxidation of benzylalcohol with CuCl/PIPO as catalyst In a glass reaction vessel was placed benzyl alcohol (1.08 g 10 mmol), n-hexadecane (2 mmol), CuCl (10.0 mg 0.1 mmol), PIPO (31.8 mg 0.1 mmol based on nitroxyl) and 25 ml DMF. The resulting reaction mixture was stirred at 25 °C under an oxygen atmosphere. The samples were analysed on GC [Chrompack CP-WAX 52 CB column 50 m x 0.53 mm]. 

Another improvement is the use of a Ru/TEMPO catalyst combination for the selective aerobic oxidations of primary and secondary alcohols to the corresponding aldehydes and ketones, respectively (Fig. 1.22) [72]. The method is effective (>99% selectivity) with a broad range of primary and secondary aliphatic, allylic and benzylic alcohols. The overoxidation of aldehydes to the corresponding carboxylic acids is suppressed by the TEMPO which acts as a radical scavenger in preventing autoxidation. 

---