2-Phenylethanol 2-Phenylethylamine

FIGURE 4.24 Adsorption chromatography of small molecules with a TSK-GEL G2500PWxl column. Column TSK-GEL G2500PWxl, 6 /tm, 7.8 mm X 30 cm. Sample (I) phenylacetic acid. (2) 3-phenylpropionic acid, (3) 4-phenylbutyric acid, (4) benzylamine, (5) 2-phenylethylamine, (6) 3-phenylpropylamine, (7) benzyl alcohol, (8) 2-phenylethanol, and (9) 3-phenyl-1 -propanol. Elution 0.1 M NaCIO, in water. Flow rate 2.0 ml/min. Temperature 65 C. Detection UV at 215 nm. 

By this method, for example, the absolute configurations of the following compounds were established (-)-2-phenylbutyric acid,[48] (-)-hydratropic acid,[48] (+)-0-acetyl-mandelic acid,t48] (-)-2-(7/-carbazolyl)propionic acid,t48] (+)-1 -phenylethanol,[48] (-)-menthol,t48] (+)-1 -phenylethylamine,[48] and 1-alanine ethylester.[48] The determination of the absolute configuration of bacteriochlorophylles c, d and e was made possible by the esterification of the phaeophorbides by CDI to imidazolides.[49]... 

The CSAs that have been used most widely are 2,2,2-trifluoro-l-phenylethanol (TFPE, la), 2,2,2-trifluoro-l-(l-naphthyl)ethanol (TFNE, lb), 2,2,2-trifluoro-l-(9-anthryl)ethanol (TFAE, Ic), 1-phenylethylamine (PEA, 2a), and l-(l-naphthyl)ethylamine (NEA, 2b). Both enantiomers of TFPE, TFAE (9), PEA, and NEA are commercially available. The fluoroalcohols are relatively acidic and interact strongly with solutes having one or more basic sites (Sect. IV-B). Amines 2 have been used most often as CSAs for organic acids or other acidic solutes (Sect. IV-C). A number of analogs of TFAE have been studied (Sect. III-C). 

Preparative scale reduction of oximes at a mercury or lead cathode in acid solution has been used in the conversion of the carbonyl function to amine. Originally, 30-50% sulphuric acid was used as solvent [195] but ethanol with dilute hydrochloric acid is usually satisfactory. Aliphatic and aromatic oximes give amines in 64-86% yields [196]. Aromatic ketoximes are also reducible in alkaline solution and acetophenone oxime has been converted to 1-phenylethylamine in a tri-potassium orthophosphate solution [197], The reduction of oximes in acid solution is tolerant of many other substituents as indicated by a number of examples [198, 199, 200. Phenylglyoxa monoxime in acid solution is however reduced at both the carbonyl and the oxime centres by sodium amalgam to yield 2-amino-1-phenylethanol [201]... 

We conclude this section with a brief discussion of ROA calculations. In a recent study revisiting the ROA of phenylethanol and phenylethylamine [153], Barron et al. have highlighted how straightforward routine measurements of ROA have become. It was noted that simulations of ROA have been performed for quite some time however, as both experimental measurement and computational ability advance so must the level of detail in the computational model. It was suggested that the inclusion of effects related to the dynamics of the system, and anharmoni-city of the potential energy surface, should be included to yield the most realistic and accurate ROA results. 

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 nitrous acid deamination appears to be as complex as the nitrosoamide reaction, and in a common solvent it appears that similar mechanisms are followed. For example, the nitrosonaphthamide of 1-phenylethylamine in acetic acid, and the reaction of 1-phenyl-ethylamine with nitrous acid in the same solvent yield 1-phenylethyl naphthoate (Table 7) and 1-phenylethanol respectively, both with 79-81% retention of configuration. These products are the intramolecular products from the respective reactions, and thte stereochemical results suggest that they are formed by a common path. Similar results were also found in the deaminations of S-cholC stanylamine 2-phenyl-2-butylamine ° and 1,2,2-triphenylethyl amine Also pertinent, is the finding that the acetates fi-om the deamination of n-propylamine in acetic acid, by the two methods, contained similar amounts of the isomeric product, isopropyl acetate the amount of isomerization observed was far greater than in the solvolysis of n-propyl tosylate in the same solvent... 

Distinct NMR resonances were first observed for the enantiomers of 2,2,2-trifluoro-l-phenylethanol in the presence of (/ )-phenylethylamine. With (/ )-2-naphthylethylamine the magnitude of the non-equivalence was increased. A systematic study of a series of aryl alcohols in the presence of amines showed a consistent correlation between the sense of non-equivalence and the absolute configuration of the alcohol. From the simple solvation models proposed, the reciprocality of the CSA approach is evident, i.e. if chiral A can be used to assay racemic B then chiral B can be used to assay racemic A. With this in mind 1 -(9-anthryl)-2,2,2-trifluoroethanol (15a) was developed as a CSA for chiral amines. It is also effective with alcohols, lactones, a-amino acid esters, a-hydroxy acid esters and sulphoxides and is the most widely used chiral solvating agent. Other more specific solvating agents have been developed. Kagan has developed A -(3,5-dinitrobenzoyl)-l-phenylethylamine,forexample, as a CSA specifically for the assay of chiral sulphoxides prepared from sulphides by a modified Sharpless oxidation (section 6.3.2). 

The resolution of a-methylbenzylamine also, called 1-phenylethylamine, has received considerable attention as occurs with 1-phenylethanol in the screening of appropriate biocatalysts for secondary alcohol resolution (Figure 9.23). Souza and coworkers have developed an efficient method for the resolution of a-methylbenzylamine in a continuous flow system using EtOAc and short residence times (40 min) [188]. Similarly, the combination of EtOAc and CAL-B has also served for the KR of boron-containing 1-phenylethylamine derivatives [189]. 

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