A-Phenylethanol

PO—SM Coproduction. The copioduction of propylene oxide and styrene (40—49) includes three reaction steps (/) oxidation of ethylbenzene to ethylbenzene hydroperoxide, (2) epoxidation of ethylbenzene hydroperoxide with propylene to form a-phenylethanol and propylene oxide, and (3) dehydration of a-phenylethanol to styrene. 

The oxidation step is similar to the oxidation of cumene to cumene hydroperoxide that was developed earlier and is widely used in the production of phenol and acetone. It is carried out with air bubbling through the Hquid reaction mixture in a series of reactors with decreasing temperatures from 150 to 130°C, approximately. The epoxidation of ethylbenzene hydroperoxide to a-phenylethanol and propylene oxide is the key development in the process. 

It is carried out in the Hquid phase at 100—130°C and catalyzed by a soluble molybdenum naphthenate catalyst, also in a series of reactors with interreactor coolers. The dehydration of a-phenylethanol to styrene takes place over an acidic catalyst at about 225°C. A commercial plant (50,51) was commissioned in Spain in 1973 by Halcon International in a joint venture with Enpetrol based on these reactions, in a process that became known as the Oxirane process, owned by Oxirane Corporation, a joint venture of ARCO and Halcon International. Oxirane Corporation merged into ARCO in 1980 and this process is now generally known as the ARCO process. It is used by ARCO at its Channelview, Texas, plant and in Japan and Korea in joint ventures with local companies. A similar process was developed by Shell (52—55) and commercialized in 1979 at its Moerdijk plant in the Netherlands. The Shell process uses a heterogeneous catalyst of titanium oxide on siHca support in the epoxidation step. Another plant by Shell is under constmction in Singapore (ca 1996). 

A three-step process involving the oxidation of acetophenone, hydrogenation of the ketone to a-phenylethanol, and dehydration of the alcohol to styrene was practiced commercially by Union Carbide (59) until the early 1960s. Other technologies considered during the infancy of the styrene industry include side-chain chlorination of ethylbenzene followed by dehydrochlotination or followed by hydrolysis and dehydration. 

The oxidation of a series of meta- and para-substituted a-phenylethanols shows that electron-donating substituents facilitate reaction (p = —1.01) . A similar study of primary aliphatic alcohols confirmed this trend p = —1.06 + 0.06). 

Kharasch and coworkers were the first to show that thiols and olefins cooxidize in an atmosphere of oxygen at room temperature to yield substituted 2-sulphinylethanols 81 (equation 45). Later on, it was demonstrated that a-mercapto-substituted hydroperoxides are formed as intermediates. Thus, Oswald found that cooxidation of thiophenol with styrene gave the corresponding 8-mercaptohydroperoxide 82 which subsequently underwent rearrangement to 2-phenylsulphinyl-a-phenylethanol 83 (equation 46). 

FIGURE 4.5 Chromatograms of a-phenylethanol enantiomers nsing (a) SFC and (b) open tubular column GC. Conditions (a) 12 cmx250 p.m ID capillary packed with 5-p.m porous (300 A) silica particles encapsulated with fS-CD polymethylsiloxane (10% w/w) and end-capped with HMDS, 30°C, 140 atm, CO2, FID, 10 cmxl2 p.m ID restrictor, (b) 25 mx250 p.m ID cyano-deactivated capillary cross-linked with fi-CD polymethylsiloxane (0.25 xm df) 130°C He FID. (Reprinted from Wu, N. et al. 2000. J. Microcol. Sep. 12 454-461. With permission.)... 

Chemoselectivity is often a major issue in the reduction of multifunctional organic substrates such as substituted conjugated enones. The corresponding unsaturated alcohols have found use as building blocks for pharmaceutically active molecules for example (i-amino-a-phenylethanol is used for the synthesis of (5-blockers which are the active molecules for controlling hypertension and other cardiac disorders. 

Pentryl (152) is obtained from the action of fuming nitric acid or mixed acid on Ai-(2,4-dinitrophenyl)ethanolamine, itself obtained from the reaction of 2,4-dinitrochlorobenzene with ethanolamine. Another route to pentryl (152) involves the nitration of A-phenylethanol-amine, which is obtained from the reaction of aniline with ethylene oxide. ... 

Figure 3. VCD and absorption spectra in the CH stretching region (a) a-phenylethanol, 0.074 M in ecu, path length O.IO cm, (b) (+)-a-phenylethyl isocyanate, 0.087 M in CCU, sample path length 0. IS cm. The time constant was 10 s, and the resolution was 6 cm. (Reproduced with the permission of North Holland Publishing Co., from ref. S9.)...

This is similar to the process in which ethylbenzene is oxidized by air to the hydroperoxide, then treated with propylene in the presence of transition metal oxides or salts to yield a-phenylethanol and propylene oxide (18), although, as Mayo points out (21), Co is a poor catalyst in this reaction. 

A side-chain t-alcohol group as in (99.4) undergoes cyclodehydration when heated with sulphuric acid. Annulation of a phenylethanol with a nitrile and sulphuric acid can give fairly high yields of an isoquinoline the usefulness of nitriles in the synthesis of heterocycles has been reviewed [3332a]. 

Scheme 8-9 shows a simple illustration of the concept for acetophenone production by oxidation of the corresponding alcohol a-phenylethanol [7]. The older oxidation with chromium oxide leads to some side products and the atom efficiency is only 42%. Modern homogeneous or heterogeneous catalyzed oxidation results in an atom efficiency of 87% (MW 120 + 18 (water) =138 120/138 = 0.87). 

Equimolar amounts of cinnamic alcohol and Na-dichromate mixed with water, and refluxed 3 hrs. cinnamaldehyde. Y 91% conversion 87%. - Similarly during 2 hrs. a-Phenylethanol acetophenone. Y 96% conversion 50%. - This oxidation by neutral aq. Na-dichromate is particularly recommended for benzylic alcohols. F. e. and limitations s. D. G.Lee and U. A. Spitzer, J. Org. Chem. 55, 3589 (1970). 

Because of the equilibrium between styrene and a-phenylethanol under the reaction conditions, some loss of deuterium label in the starting material can occur as the hydration reaction nears completion. When the concentration of alcohol is minimal in the early stages of the reaction, however, the return path is negligible, and loss of label is not detected. 

The similar N,0 heterobidentate ligands include -aminoalcohols such as -amino-a-phenylethanol (APE) (77) and its N-substituted derivatives (Fig. 9). The terdentate 0,N,0 ligand, bis(2-hydroxy-2-phenylethyl)benzylamine (HPBA) (78) proved to be efficient in samarium-catalyzed enantioselective transfer hydrogenation of acetophenone derivatives, providing excellent enantioselection. 

It was proposed by Laxmi and Backvall that the mono- and dihydide pathways could be distinguished by studying the racemization of deuteurated (5)-a-phenylethanol, as described in the following Scheme, where M represents some metal complex catalyst ... 

The indirect propylene oxidation process via ethylbenzene hydroperoxide (Halcon process) is displayed in Eq. (6.12.12). Ethylbenzene, obtained by the acid-catalyzed Friedel-Crafts alkylation of benzene with ethylene, is converted with air into ethylbenzene hydroperoxide. The hydroperoxide epoxidizes propylene and generates the co-product a-phenylethanol that is later dehydrated to styrene. Styrene is a major industrial chemical used mainly as monomer for polymers such as polystyrene or styrene-containing copolymers ... 

In the peroxidation reactor ethylbenzene is converted with air at 146 °C and 2 bar to form a 12-14 wt% solution of ethylbenzene hydroperoxide in ethylbenzene. The reaction takes place in the liquid phase and conversion is limited to 10% for safety reasons. The reactor is a bubble tray reactor with nine separate reaction zones. To avoid decomposition of the formed peroxide the temperature is reduced from 146 °C to 132 °C over the trays. In the epoxidation reactor the reaction solution is mixed with a homogeneous molybdenum naphthenate catalyst. Epoxidation of propylene in the liquid phase is carried out at 100-130 °C and 1-35 bar. The crude product stream (containing PO, unreacted propylene, a-phenylethanol, acetophenone, and other impurities) is sent to the recycle column to remove propylene. The catalyst can be removed by an aqueous alkali wash and phase separation. The crude PO, obtained as head stream in the crude PO column, is purified by distillations. The unconverted reactant ethylbenzene can be recycled in the second recycle column. The bottom stream containing a-phenylethanol is sent to the dehydration reactor. The vapor-phase dehydration of a-phenylethanol to styrene takes place over a titanium/alumina oxide catalyst at 200-280 °C and 0.35 bar (conversion 85%, selectivity 95%). 

In a similar operation a-phenylethanol was dehydrated by entrapped polystyrenesul-fonic acid to styrene, which in turn, was hydroformylated by heterogenized Rh2Co2(CO)i2 (Scheme 24-44) (Gelman, 2003a). 

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