3- Phenylpropanol

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). 

Hydrogenation of cinnamaldehyde has been studied extensively since selectivity has often been an issue. Under mild conditions the carbonyl group is reduced giving cinnamyl alcohol, whereas at elevated temperatures complete reduction to 3-phenylpropanol [122-97 ] results. It is possible to saturate the double bond without concomitant reduction of the carbonyl group through selective hydrogenation with a ferrous chloride-activated palladium catalyst (30), thereby producing 3-phenylpropanol [104-53-0]. 

Acetophenone, paraformaldehyde and diethylamine are first reacted to give CO-diethylamino-propiophenone. That is reacted with cyclohexylmagnesium bromide to give 3-diethylamino-1 -cyclohexyl-1 -phenylpropanol-1. 

To 1,320 parts of methyl isobutyl ketone is added 570 parts of 3-diethylamino-1 -cyclohexyl-1 -phenylpropanol-1 (2 mols) and the mixture is stirred until solution is complete. Then 500 parts (3.2 mols or 60% excess) of ethyl iodide are added. After filtration, the filtrate is diluted with an additional 300 parts of methyl isobutyl ketone and the solution is then heated at the reflux temperature (108°C to 110°C) for 9 hours. After cooling to 0°C, the precipitated solid material is removed by filtration, washed with isopropyl acetate and dried. Approximately 111 parts of product is obtained or a yield of 88.6% based on as-is starting material or 92.5% based on real starting material. 

Reaction of the chiral (45,5R)-oxazolidine 9. obtained from 3-pentanone and (-)-2-amino-l-phenylpropanol, with aldehydes gives predominantly a H -aldol adducts of high enantiomeric purity. The corresponding spn-adducts, formed in low enantiomeric excess, are isolated from the diaslereomeric mixture by chromatography 5. 

FeCl2, Fe(acac)3, and Fe(C104)3 instead of FeCl3, however, showed low activity. Tertiary alcohols, such as 3-phenylpropanol or cyclohexylmethanol instead of alkenes, are also adaptable to this reaction. 

Similar temperature effect using other racemic alcohols such as 2-hydroxymethyl-1,4-benzodioxane (4), 2-phenylpropanol (5), and 1-cyclohexylethanol (6) was also observed as shown in Fig. 8, obeying Equation 7. These results suggest that the temperature effect is widely applicable regardless of primary or secondary alcohols and an origin of lipase. 

Figure 4.29 An example of the use of ternary solvents to control mobile phase strength and selectivity in reversed-phase liquid chromatography. A, methanol-water (50 50) B, tetrahydrofuran-water (32 68) C, methanol-tetrahydrofuran-water (35 10 55). Peak identification 1 - benzyl alcohol 2 phenol 3 3-phenylpropanol 4 2,4-dimethylphenol 5 benzene and 6 -diethylphthalate. (Reproduced with permission from ref. 522. Copyright Elsevier Scientific Publishing Co.)...

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...

Storax resin is extracted from Liquidambar orientalis (Hammamelidiaceae) and Altingia and its major components are cinnamyl cinnamate and 3-phenylpropanyl cinnamate, with significant amounts of benzoic and cinnamic acids, and 3-phenylpropanol and cinnamyl alcohols [130,131]. The volatile content is very low and triterpenes (oleanonic and 3-epioleanolic acids and liquid ambronovic acid) have also been observed [130,132]. 

Very few enzyme-catalysed reactions involving the reduction of alkenes have achieved any degree of recognition in synthetic organic chemistry. Indeed the only transformation of note involves the reduction of a, (3-unsaturated aldehydes and ketones. For example, bakers yeast reduction of (Z)-2-bromo-3-phenylprop-2-enal yields (S)-2-bromo-3-phenylpropanol in practically quantitative yield (99 % ee) when a resin is employed to control substrate concen-tration[50]. Similarly (Z)-3-bromo-4-phenylbut-3-en-2-one yields 2(5), 3(,S)-3-bromo-4-phenylbutan-2-ol (80% yield, >95% ee)[51]. Carbon-carbon double bond reductases can be isolated one such enzyme from bakers yeast catalyses the reduction of enones of the type Ar—CH = C(CH3)—COCH3 to the corresponding (S)-ketones in almost quantitative yields and very high enantiomeric excesses[52]. 

In one study, various distinct types of polar modifiers to n-hexane were tested for 3-chloro-l-phenylpropanol (3CPP) and 1-phenylpropanol (IPP) enantiomer separation [53]. Thereby, alcohol modifiers turned out to be more effective displacers of the solutes from the adsorption places on the sorbent surface, yet aprotic polar modifiers provided higher separation factors (with ethyl acetate in n-hexane affording the best separations for these chiral alcohols). It is evident, though, that the optimal choice of polar modifier is strongly solute dependent and can therefore not be generalized. 

FIGURE 1.8 Effect of the mole fraction of polar modifier (ethyl acetate) in n-hexane on the reciprocal of the retention factor for the separation of 3-chloro-l-phenylpropanol enantiomers on a 0-9-(terf-butylcarbamoyl)quinidine CSP. Temperature, 22°C. (Reproduced from L. Asnin, and G. Guiochon, J. Chromatogr. A, 1091 11 (2005). With permission.)... 

NELjAc, ammonium acetate Npg, a-neopentyl-glycine DNZ, 3,5-dinitrobenzyloxycarbonyl Z, ben-zyloxycarbonyl Bz, benzoyl Ac, acetyl TFAE, 2,2,2-trifluoro-l-(9-anthryl)-ethanol IPP, 1-phenyl-propanol 2PP, 2-phenylpropanol 3CPP, 3-chloro-l-phenylpropanol ACN, acetonitrile EA, ethyl acetate. 

FIGURE 6.3 Plot of column efficiency against sample mass for three neutral compounds (3-phenylpropanol, caffeine, phenol), and three charged compounds (propranolol, nortriptyline, 2-NSA [2-naphthalenesulfonic acid]) on XTerra MS (15 x 0.46 cm, 3.5 pm particles). Mobile phase acetonitrile-formic acid (overall concentration 0.02 M) pH 2.7 (28 72, v/v) except for caffeine (12.5 77.5, v/v). Flow rate 1 mL min . Column temperature 30°C. Injection volume 5 pL. 

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