1- Phenylethanol, and

Ethylbenzene Hydroperoxide Process. Figure 4 shows the process flow sheet for production of propylene oxide and styrene via the use of ethylbenzene hydroperoxide (EBHP). Liquid-phase oxidation of ethylbenzene with air or oxygen occurs at 206—275 kPa (30—40 psia) and 140—150°C, and 2—2.5 h are required for a 10—15% conversion to the hydroperoxide. Recycle of an inert gas, such as nitrogen, is used to control reactor temperature. Impurities ia the ethylbenzene, such as water, are controlled to minimize decomposition of the hydroperoxide product and are sometimes added to enhance product formation. Selectivity to by-products include 8—10% acetophenone, 5—7% 1-phenylethanol, and <1% organic acids. EBHP is concentrated to 30—35% by distillation. The overhead ethylbenzene is recycled back to the oxidation reactor (170—172). 

The DKR of secondary alcohols can be efficiently performed via enzymatic acylation coupled with simultaneous racemization of the substrates. This method was first used by BackvaU for the resolution of 1-phenylethanol and 1-indanol [38]. Racemization of substrate 18 by a mthenium catalyst (Scheme 5.11) was combined with transesterification using various acyl donors and catalyzed by C.antarctica B Hpase. From aU the acyl donors studied, 4-chlorophenyl acetate was found to be the best. The desired product 19 was obtained in 80% yield and over 99% ee. 

The above-described reverse reaction (viz. the Fe-catalyzed dehydrogenation of alcohols to ketones/aldehydes) has been reported by Williams in 2009 (Table 9) [58]. In this reaction, the bicyclic complex 16 shows a sluggish activity, whereas the dehydrogenation of l-(4-methoxyphenyl)ethanol catalyzed by the phenylated complex 17 affords the corresponding ketone in 79% yield when 1 equiv. (relative to 17) of D2O as an additive was used. For this oxidation reaction, l-(4-methoxyphenyl) ethanol is more suitable than 1-phenylethanol and the reaction rate and the yield of product are higher. 

Cripps RE, PW Trudgill, JG Whateley (1978) The metabolism of 1-phenylethanol and acetophenone by Nocardia T5 and iin Arthrobacter species. Eur J Biochem 86 175-186. 

To a much smaller extent non-enzymic processes have also been used to catalyse the stereoselective acylation of alcohols. For example, a simple tripeptide has been used, in conjunction with acetic anhydride, to convert rram-2-acctylaminocyclohexanol into the (K),(R)-Qster and recovered (S),(S)-alcohol[17]. In another, related, example a chiral amine, in the presence of molecular sieve and the appropriate acylating agent, has been used as a catalyst in the conversion of cyclohexane-1(S), 2(/ )-diol into 2(S)-benzoyloxy-cyclohexan-1 f / j-ol1 IS]. Such alternative methods have not been extensively explored, though reports by Fu, Miller, Vedejs and co-workers on enantioselective esterifications, for example of 1-phenylethanol and other substrates using /. vo-propyl anhydride and a chiral phosphine catalyst will undoubtedly attract more attention to this area1191. 

The first systematic investigations of the catalytic Friedel-Crafts-type reaction with alcohols and olefines were performed by Yamamoto and colleagues. After reporting the development of a Pd-catalyzed method for the allylation of different naphthol derivatives [24], the authors used Mo(CO)g for the Friedel-Crafts-type alkylation of electron-rich arenes with allyl acetates [25], The same molybdenum catalyst was additionally used for a Friedel-Crafts-type alkylation of arenes using 1-phenylethanol and styrene as alkylating reagents [26], However, Mo(CO)g is toxic and must be handled under strictly inert conditions. Thus, more stable Lewis acids were necessary. 

In addition to 1-phenylethanol and benzyl alcohol, cinnamyl alcohol has also been utilized as alkylating reagent. In contrast to the Bi(OTf)3-catalyzed Friedel-Crafts alkylation of benzyl alcohols, in which the corresponding acetate was shown to be more reactive than the free benzyl alcohol (Scheme 8), in this case the alkylation with cinnamyl alcohol or the corresponding acetate provided almost similar results. With 5 mol% BifOTfh. the desired allylated 2,4-pentanediones were isolated in good yields (Scheme 15). 

RuCl2(picphen)]Cl (picphen=few(picolinaldehyde)-(9-phenylenedi-imine) is made by condensation of picolinaldehyde and o-phenylenediamine) and the resulting Schiff base then treated with RuClj in ethanol. Kinetics were followed of the oxidation of secondary alcohols (benzhydrol, 1-phenylethanol and a-tetralol) to the corresponding ketones by [RuCl2(picphen)] "/NMO or Tl(OAc)3/water/30°C. The intermediacy of a Ru(V) oxo species was suggested [800]. 

In Figure 5 the conversion of 1-phenylethanol and the open circuit potential of alumina-supported catalysts are plotted as a function of reaction time. There is a striking difference between the curves of unpromoted (a, a ) and bismuth-promoted (c, c ) catalysts. When air is introduced to the reactor, the potential of the platinum-on-alumina catalyst quickly increases to the anodic direction and after one minute the catalyst potential is above -300 mV. One may conclude that there is practically no hydrogen on the platinum surface and after a short period an increasing fraction of platinum is covered by OH. The influence of bismuth promotion is a higher reaction rate (final conversion) and lower catalyst potential during reaction. 

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]. 

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). 

When Wistar rats were exposed to 50, 300 or 600 ppm [0.22, 1.30 and 2.60 g/m ] ethylbenzene intermittently for up to 16 weeks, the urinary recovery of metabolites increased with dose but not linearly. The metabolic pattern of ethylbenzene was affected by exposure level but not by the duration of administration. The amounts of 1-phenylethanol and -hydroxyacetophenone increased with increasing exposure, but those of phenylglyoxylic acid and hippuric acid decreased (Engstrdm et al, 1985). 

In principle, these systems constitute commercially interesting catalytic alternatives to classical Cr- and Ce-based oxidants. From a practical viewpoint, however, it is essential that the catalyst retain its activity over long periods of time. In one experiment with 1-phenylethanol and AAnafk and TBHP the catalyst was recovered, dried and reused without loss of Cr A... 

However, the products stereochemistry found when using 1-phenylethanol and diphenylmethanol as donors is close to that observed in H2 addition conditions, thus suggesting the occurrence of two consecutive steps,... 

Exercise 19-7 (-F)-Lactic acid has the l configuration. On the basis of the following transformations, deduce the absolute configurations of (—)-1-phenylethanol and (+)-1-phenylethyldimethylsulfonium fluoroborate. Write equations to show the structure and configuration of the products in each step. Reactions 5 and 7 both give E with the same sign of rotation. 

FIGURE 19 Effect of temperature on the chiral resolution of (a, c) 1-phenylethanol and (b, d) camphor on capillary containing the Chiralsil-nickel CSP (SFC). (From Ref. 94.)... 

The chiral TEMPO-derivative 87 has been shown to be an active catalyst for the oxidative kinetic resolution of 1-phenylethanol and derivatives. Catalyst loadings are in a practically very useful range (0.5-1 mol%) and hypochlorite is an attractive oxidant. Clearly, a more readily accessible catalyst would be desirable. In this respect, the Shi ketone 88 is advantageous. It must, however, be used in large excess and... 

Oxidation of alcohols to carbonyl compounds using the stable nitroxyl radical TEMPO (41) as catalyst is a well-known preparative method [42, 43], Hypochlorite or peracetic acid is usually used as the final oxidizing agent and ca. 1 mol% of the catalyst 41 is used. In 1996 Rychnovsky et al. reported the synthesis of the chiral, binaphthyl-derived TEMPO analog 42 [44]. Table 12.1 lists the results obtained with 0.5-1 mol% of catalyst 42 [44], In these oxidation reactions 0.6-0.7 equivalents of sodium hypochlorite were used as the final oxidizing agent (plus 0.1 equiv. potassium bromide) in a two-phase system containing substrate and catalyst 42 in dichloromethane at 0 °C. As shown, the best selectivity factors (> 5) were observed for 1-phenylethanol and its derivatives as substrates. 

Alternatively, a chiral imidazolium salt generates a chiral-activated ester which allows for the kinetic resolution of chiral secondary alcohols. Chan and Scheidt described this reaction of racemic 1-phenylethanol and cinnamaldehyde [62]. The enantiodiscrimination was explained by the chiral intermediate formed between the chiral imidazolium salt and cinnamaldehyde, which has sufficient facial selectivity to react preferentially with the (R)-stereoisomer of 1-phenylethanol. 

A CLEA prepared from CaLB was recently shown to be an effective catalyst for the resolution of 1-phenylethanol and 1-tetralol in supercritical carbon dioxide in continuous operation [47]. Results were superior to those obtained with Nov 435 (CaLB immobilized on a macroporous acrylic resin) under the same... 

In the series of / -(+)-1-phenylethylamine, / -(+)-1-phenylethanol and R- +)- -phenylethylthiol Barron et al. (1989) examine the influence of heteroatom Rydberg p-orbitals on the ratio of polarized to depolarized ROA spectra. They explain the intensities of the methyl antisymmetric deformation band as injection of a large electric quadrupole contribution from the Rydberg orbitals, which are, as a crude calculation shows, of sufficient extension. 

The deeper oxidation of ethylbenzene over TS-2 can be explained with the slower diffusion of 1-phenylethanol and aeetophenone formed in the zeolite pores where they could undergo additional oxidation to aeetophenone or other products, respectively. Another possible reason could be some differences in the local geometry of the titanium sites due to the different framework structure of the two titanium silicalites. 

In addition to the above mentioned products, traces of benzaldehyde are detected. The amount of benzaldehyde increases in the course of the reaction and is higher over TS-2 catalyst. It is probably formed after a C-C bond break in the side chain of 1-phenylethanol or acetophenone. Another by-product - ethylbenzoquinone, is observed in the experiments without solvent and in ethanol under standard conditions. The ethers derived from 1-phenylethanol and the solvent - methanol or ethanol, are also found. 

In a side reaction enolizable ketones may give rise to varying amounts of silyl enol ethers. On hydrolysis, these silyl enol ethers are reconverted into the starting material. Thus, even on complete hydrosilylation, product formation is not quantitative and the secondary alcohol is accompanied by the ketone to the extent in which the silyl enol ether was formed. Thus, the hydrosilylation of 1-phenylethanone and its enol form with diphenylsilane affords the corresponding silyl ether and silyl enol ether and subsequent hydrolysis gives 1-phenylethanol and 1-phenylethanone13. 0 0H... 

For 1-phenylethanol and 1-phenylethyl amine, Pr(hfc)3 induced larger shifts than Eu(hfc)3, and did so at lower concentration [51]. Still, the concensus appears to be that no single CSR is superior with all possible ligands. 

Scheme 8-5 Alcoholysis between 1-phenylethanol and vinyl acetate [76].

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