3- Phenylpropanols, oxidation

Friedel-Crafts. 2-Phenylpropanol results from the catalytic (AlCl, FeCl, or TiCl reaction of ben2ene and propylene oxide at low temperature and under anhydrous conditions (see Friedel-CRAFTS reactions). Epoxide reaction with toluene gives a mixture of 0-, m- and -isomers (75,76). 

Figure 8 Plot of the initial rate of the enzyme-catalyzed oxidation of 1-phenylpropanol as a function of % ee. The solid line represents a fit of the data to the Michaelis-Menten formalism for competitive inhibition where [S] = [ -(60)] and [ ] = [ -(60)]. The total alcohol concentration was maintained constant at lOmM.100...

Cinnamic alcohol can be dehydrogenated to give cinnamaldehyde and oxidized to give cinnamic acid. Hydrogenation yields 3-phenylpropanol and/or 3-cyclo-hexylpropanol. Reaction with carboxylic acids or carboxylic acid derivatives results in the formation of cinnamyl esters, some of which are used as fragrance materials. 

Aromatic and aliphatic aldehydes can be oxidized after careful and individual optimization of the reaction conditions to carboxylic acids (Eq. (7), Table 12). With aromatic aldehydes yields are excellent, with aliphatic aldehydes good to satisfactory. The electrolyte has to be less alkaline than normal to suppress the aldol condensation. 2-Phenylpropanol is best oxidized at low temperatures to render the cleavage to benzoic acid more difficult, at 70 °C benzoic acid becomes main product (47 %). Double bonds in y,8- or even a,P-position are not touched in the oxidation. 

Enantioselective addition of (C2//5)2Z/i to CJlsCHOIn the presence of (— )-l, diethylzinc adds to C6H5CHO to provide the (R)-adduct. The optical purity of the catalyst (1) has a marked effect on the rate and also on the optical purity of the adduct. Thus (-)-PDB of only 10-20% ee provides (R)-l-phenylpropanol in 80-90% ee and about 95% chemical yield. This nonlinear effect in catalyzed asymmetric oxidations and aldolizations has been noted previously.2 It may be a result of the molecularity of the reaction or of the aggregation or ligand exchange of the catalyst. 

The tri-2-phenylpropylborane formed can be oxidized and hydrolyzed to 2-phenylpropanol-l, thus representing [as with aluminum alkyls (146)] an overall anti-Markownikoff hydration of a-olefins. Besides employing trialkylboranes as a source of boron hydrides, similar additions have been accomplished by heating olefins with boron hydride-amine complexes. As the latter are not as oxygen-sensitive, they are easier to handle (73) ... 

The overall acceptance of hydrogen by a reducing reagent is demonstrated by item 10 of Table 8.5. Here, the diethyl ester of diazodicarboxylic acid (diethyl azodi-carboxylate [DEAD]) serves to oxidize 1-phenylpropanol to phenylpropanone while it is reduced to diethyl hydrazo-dicarboxylate in the process. Although the details are sketchy, a possible pathway is shown in Scheme 8.7. 

Scheme 8.7. A representation of a possible pathway for the oxidation of a secondary alcohol (1-phenylpropanol) to the corresponding ketone (phenylpropanone) with diethyl azodicar-boxylate (DEAD) (see Mitsumobu, O. Yamada, M. Bull. Chem. Soc. Jpn., 1967,40,2380 and Mitsunobu, O. Synthesis, 1981,1).

The substance is excreted mostly unchanged, but an oxidation of the methyl and isopropyl group can also occur, leading to benzyl alcohol and 2-phenylpropanol and their carboxylic acids [89]. 

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