Oxidation of 1-phenylethanol

Figure 6.16. Aerobic oxidation of 1-phenylethanol catalysed by palladium complexes of a fluorous pyridine...

Figure 9.1 compares the synthesis of acetophenone by classic oxidation of 1-phenylethanol with stoichiometric amounts of chromium oxide and sulphuric acid, with an atom efficiency of 42%, with the heterogeneous catalytic oxidation with O2, with an atom efficiency of 87%, and with water as the only by-product. This is especially important if we consider the environmental unfriendliness of chromium salts the potential environmental impact of reactions can be expressed by the environmental quotient (EQ), where E is the E-factor (kg waste/kg product) and Q is the environmental unfriendliness quotient of the waste. If Q is... 

The empirical observation that (—)-sparteine 55 is necessary for catalysis implicates a base-promoted pathway in the mechanism. In the first step, a palladium alk-oxide is formed after alcohol binding, followed by p-hydride elimination of the alkoxide to yield a ketone product. On the basis of a kinetic study of the enantio-selective oxidation of 1-phenylethanol, it was revealed that (—)-sparteine plays a dual role in the oxidative kinetic resolution of alcohols, as a ligand on palladium and an exogeneous base " ... 

The air-oxidation of 1-phenylethanol to acetophenone in an aqueous alkaline solution has been chosen as a model reaction. The catalytic experiments were completed with the application of an in-situ electrochemical method for studying catalyst deactivation and the role of promoters. The potential of the catalyst, which was considered as a slurry electrode, was measured during the oxidation reaction. More details of the method can be found elsewhere 13,14). 

Figure 4. Anodic polarization curve of a Bi-Pt catalyst (Bi/Pts=0.39) and the conversion - catalyst potential relationship in the oxidation of 1-phenylethanol, in an aqueous Na2C03 solution a - Bi-Pt/alumina, Bi/Pts=0.20, b - unsupported Bi-Pt, Bi/Pt=0.39.

More recently, it was found that the incorporation of N-heterocychc car-bene ligands to the Cp lr moiety (Eq. 12) considerably enhances catalyst activity for alcohol oxidation reactions [50,51]. By way of example, the oxidation of secondary alcohols occurs with high turnovers, up to 3,200 for the oxidation of 1-phenylethanol and 6,640 for that of cyclopentanol (95% yield, 40 °C, 4 h) using the complex with the carbene derived from the tetram-ethyhmidazole (Eq. 12). 

Methyl thieno[3,2-r/][l,2,3]thiadiazole-6-carboxylate (MTTC) 50 has been shown to deactivate the P450 enzyme-catalyzed oxidation of 1-phenylethanol to acetophenone <1997B7209>. It was postulated that this was due to preferential enzymatic oxidization of MTTC. GC-MS analysis of the enzymatic oxidation products of compound 50 showed the major product to have a molecular mass of 188. Compounds 51 or 52 are possible structures assigned to this molecular mass although no other analytical method had been used for confirmation. 

Kagan et al.39 have shown that alkoxides of metals belonging to the lantanides are able to promote Oppenauer oxidations in catalytic amounts. Thus, 10 mol% f-BuOSmF is able to induce the oxidation of a number of alcohols in variable yields in the presence of a variety of aldehydes and ketones as oxidants.393 Yb(0/-Pr)3 in a 5 mol% quantity is able to catalyze the oxidation of 1-phenylethanol to acetophenone in 98% yield with butan-2-one as oxidant.39b Other lantanides provided a lower yield. 

The significant influence of carboxylic acid on these reactions prompted a fundamental investigation into its role in the aerobic oxidation of 1-phenylethanol catalyzed by 44a (0.5 mol %) [80]. At low concentrations (<0.62 mol %), acetic acid has a beneficial effect on the reaction rate (Fig. 3a). Beyond this concentration, acetic acid exhibits an inhibitory effect. Acetic acid also influences the catalyst stability (Fig. 3b). In the absence of acetic acid, the reaction proceeds only to low levels of conversion. At 0.75 mol % acetic acid, the reaction begins with a high initial rate, but the time-course deviates from the expected first-order dependence on [alcohol] (Fig. 3b). The first-order dependence observed when [AcOH] is > 2mol% suggests that the catalyst is more stable (albeit somewhat less active) under these conditions. 

Our results show that, as before, the attachment of the metal complex to the polymeric support has little effect on the yields of reaction compared to the homogeneous analogue, any small decrease in yield being more than compensated by the ease of removal of the catalyst from the product mixture. To show that 3 can be recycled a number of times, the oxidation of 1-phenylethanol to benzaldehyde was repeated five times using the same batch of supported catalyst. As seen in Table 2, the yields remain around 85% clearly illustrating the re-usability of the catalyst. 

From the results obtained for the oxidation of 1-phenylethanol to acetophenone, they have found that the system using IL-NHPI (10 mol%)-Co(OAc)2-02 in the ionic liquid [bmim][PFJ was reusable, hi the same system, various types of carbinols were transformed into the corresponding aldehydes and/or ketones in good yields. 

Fig. 13. Possible reaction scheme for the photocatalytic oxidation of 1-phenylethanol...

The oxidation of benzyl alcohol over Pd/AljOj and the oxidation of 1-phenylethanol over Au/Cu0/Ce02 were investigated in situ by XAS, where for inline product analysis, a flow-through ETIR transmission cell was used [21, 22]. In both the cases, the oxidation state of the catalytically active metallic phase (Pd and Au) was determined by XANES/EXAES measurements evaluated by simultaneous analysis of alcohol conversion using ETIR. 

Effective solvent-free peroxidative oxidations of 1-phenylethanol (Scheme 18.1) and/or some secondary aliphatic alcohols toward the corresponding ketones with tert-butylhydroperoxide (TBHP) under MW irradiation, catalyzed by copper(II)-alkoxy-triazapentadienato (Cu -TAP) [10, 11] complexes 1, 2, dicopper(II)-aminopolyalcoholate (Cu -APA) [12] complexes 3, 4, arylhydrazone-j8-diketonate (CuII-AHBD) complex 5 [13], mixed-N,S copper(II) and iron(II) complexes 6-11 [14] and by the tetranuclear copper(II) aryUiydrazone of malononitrile complex 12 [15], have been achieved (Scheme 18.2). 

Scheme 18.1 Oxidation of 1-phenylethanol under MW irradiation or conventional heating (CH) [10a, 11-15].

TABLE 18.1 Oxidation of 1-Phenylethanol with TBHP Under MW Irradiation Catafyzed by Cu" or Fe" Complexes"... 

Figure 18.1 Effect of the temperature variation on the acetophenone yield, in the MW-assisted solvent-free mild peroxidative oxidation of 1-phenylethanol catalyzed by 8-pydz. Reaction conditions are those indicated in Table 18.1.

Figure 19.1 (a) Oxidation of 1-phenylethanol (accumulation of acetophenone) at different temperatures. Conditions [1-... 

The competitive oxidation of 1-phenylethanol to acetophenone can be decreased by working with excess substrate. The polymeric membrane has been used in solvent-free conditions. For membranes with 25% loading and a cross-section in the range of 7-94 p,m, the correlation between film thickness and observed TON has been studied. A steady increase in the total oxidation products has been observed as a function of the overall photocatalyst content, and an inverse correlation between the... 

Fig. 23 Aerobic oxidation of 1-phenylethanol with bifunctional catalysts...

Biomimetic Cu(II) and Fe(II) complexes with bis- and tris-pyridyl amino and imino thioether ligands and vacant (or potentially so) coordination positions (Fig. y are active as catalyst precursors for the solvent- and halogen-free MW-assisted oxidation of 1-phenylethanol by TBHP, in the presence of pyridazine or other N-based additives. Maximum TOF of 5220 h (corresponding to 87% yield) was achieved just after 5 min of reaction time under the low power MW irradiation. The same authors reported" the catalytic activity of related copper, iron, and vanadium systems with mixed-N,S pyridine thioether hgands. The Cu and Fe complexes proved to be useful catalysts in various MW-assisted alcohol oxidations with TBHP, at 80 °C. Thus, 5-containing ligands can also be used to create effective catalyst precursors. 

Chemoselective oxidation of a secondary alcohol moiety can be also performed with ruthenium catalysts with phenylindenyl Hgand. The selective oxidation of 1-phenylethanol to acetophenone from a mixture of phenylethanol isomers, without oxidizing the other isomer, can then be achieved (Scheme 29). In general, only the secondary alcohol moieties are oxidized and the catalyst can be used for the chemical separation of isomers or specific oxidation of highly functionalized molecules. The OKR of unactivated racemic alcohols with dioxygen of air as the hydrogen acceptor was effectively performed at room temperature with [(aqua)Ru(salen)] com-... 

In fact, in the presence of the dicopper(II) [Cu2(Hedea)2(N3)2]-(0.25H2O) (Hedea = N-ethyldiethanolamine) complex with the Cu2(p—0)2 die-thanolaminate core, the oxidation of 1-phenylethanol is dramatically accelerated when the reaction mixture is subject to MW irradiation, achieving a very high yield of acetophenone (91%) after 15 min of reaction, in contrast with the 51% acetophenone formed after 30 min when using conventional heating. ... 

Scheme 47 MW-assisted solvent-free oxidation of 1-phenylethanol to acetophenone with a Mn catalyst. ...

Fernandes RR, Lasri J, da Silva MFCG, da SHvaJAL, da Silva JJR F, Pombeiro AJL. Bis- and tris-pyridyl amino and imino thioether Cu and Fe complexes. Thermal and microwave-assisted peroxidative oxidations of 1-phenylethanol and cyclohexane in the presence of various N-based additives. J Mol Catal A Chem. 2011 351 100-111. 

This can be a problem if it leads to insufficient substrate concentrations in the aqueous layer for efficient bioconversion rates, whereas this can give benefit if the substrate and product inhibition to the enzyme is problematic. For example, in the oxidation of 1-phenylethanol by alcohol dehydrogenase from Geotrichum candidum, adding hexane to the aqueous buffer increases the partition of the... 

---