Phenylethanamine

Chiral imines derived from 1-phenylethanone and (I. Sj-exo-l, 7,7-trimethyIbicyclo-[2.2.1]heptan-2-amine [(S)-isobornylamine], (.S>1-phenylethanamine or (R)-l-(1-naphthyl) ethanamine are transformed into the corresponding (vinylamino)dichloroboranes (e.g., 3) by treatment with trichloroborane and triethylamine in dichloromethane. Reaction of the chiral boron azaenolates with aromatic aldehydes at 25 "C, and subsequent acidic hydrolysis, furnishes aldol adducts with enantiomeric excesses in the range of 2.5 to 47.7%. Significantly lower asymmetric inductions are obtained from additions of the corresponding lithium and magnesium azaenolates. Best results arc achieved using (.S )-isobornylamine as the chiral auxiliary 3. 

Several methods for asymmetric C —C bond formation have been developed based on the 1,4-addition of chiral nonracemic azaenolates derived from optically active imines or enamines. These methods are closely related to the Enders and Schollkopf procedures. A notable advantage of all these methods is the ready removal of the auxiliary group. Two types of auxiliaries were generally used to prepare the Michael donor chiral ketones, such as camphor or 2-hydroxy-3-pinanone chiral amines, in particular 1-phenylethanamine, and amino alcohol and amino acid derivatives. 

This method, which in this empirical version has the same limitations as discussed above for the Horeau method, was recently employed in determining the absolute configuration of substituted 1 -phenylethanamines 254. 

The 1,3-proton shift reaction has also been applied to the synthesis of a-(perfluoroalkyl)-a-amino acids, specifically 3.3,3-trifluoroalanine.2 -26 Attempts to prepare the A-benzylimine of ethyl 3,3.3-trifluoro-2-oxopropanoate by direct condensation with benzylamine were very difficult due to the exceptionally high stability of the intermediate a-amino alcohol, which fails to dehydrate. By contrast, 1-phenylethanamine reacted with ethyl 3,3,3-trifluoro-2-oxo-propanoate to form ketimine 33 in 83 % yield.26 The 1,3-proton shift reaction of 33 is much faster than those of ketimines derived from perfluoroalkyl ketones or perfluoroaldehydes (see Table 5). Complete conversion in triethylamine required 6 hours at room temperature and afforded the isomeric Shiff base 34 in 92 % yield. Mild hydrolysis of Shifif base 34 gives a-amino ester 35, which in turn hydrolyzes to 3,3,3-trjfluoroalanine hydrochloride (36). 

Exercise 9-38 Suppose that you had six unlabeled bottles containing caffeine, hexachlorophene, phenacetin, DDT, 1,3-dimethyluracil, and 1-phenylethanamine. The nmr spectrum of each of these compounds is shown in Figure 9-43. Match the lettered spectra with the appropriate individual structures so the bottles can be labeled properly. Give your reasoning. 

Resolution of chiral acids through the formation of diastereomeric salts requires adequate supplies of suitable chiral bases. Brucine, strychnine, and quinine frequently are used for this purpose because they are readily available, naturally occurring chiral bases. Simpler amines of synthetic origin, such as 2-amino-1-butanol, amphetamine, and 1-phenylethanamine, also can be used, but first they must be resolved themselves. 

When 1 is added to a solution of a mixture of enantiomers, A and A, it associates differently with each of the two components to produce the diastereo-meric complexes A+ 1 and A 1. The nmr spectrum of the mixture then shows shift differences that are large compared to the uncomplexed enantiomers (because of the paramagnetic effect of the europium) and normally the resonances of the A+ 1 complex will be distinct from those of the A 1 complex. An example of the behavior to be expected is shown in the proton nmr spectrum (Figure 19-4) of the enantiomers of 1-phenylethanamine in the presence of 1. Although not all of the resonances are separated equally, the resolution is good for the resonances of nuclei closest to the metal atom and permits an estimate of the ratio of enantiomers as about 2 1 and the enantiomeric purity as 33%. 

Exercise 19-3 The specific rotation of optically pure 2-methylbutanoic acid is [a]D 19.34° (neat) (f = 21°). Assume that you resolved the racemic acid with (+)-1-phenylethanamine and obtained a rotation for the product of +10.1° (neat) (f= 21°) calculate the enantiomeric purity (in percent) of the resolved acid. What resuits would you anticipate if you used the (—)-amine in place of the (+)-amine What effect on your resolution would there be if the resolving agent contained 90% of the (+)-amine and 10% of the (—)-amine ... 

Exercise 19-5 When optically active 1-phenylethanamine is dissolved in racemic 1-phenyl-2,2,2-trifluoroethanol, the 19F nmr resonance shows two sets of doublets separated by 2 Hz at 56 MHz. With the racemic amine, only a doublet 19F resonance is observed. 

Describe a non-chromatographic method for the separation of the enantiomers of rac- 1-phenylethanamine. 

One possibility to separate the enantiomers of rac- 1-phenylethanamine is to form diastereomeric salts with an enantiomerically pure chiral acid, e.g. (R,R) tartaric acid or (S)-2-hydroxysuccinic acid. These can be separated from each other by recrystallisation as a consequence of their different solubilities. Note, however, that the separation process is not complete at this stage since the amines are now present as salts. The separated salts must be treated with a strong base, e.g. aqueous sodium hydroxide, to convert them back to the free amines which can then be extracted into an organic solvent. After drying the extract distillation of the solvent leaves the pure amine. 

CAS 98-84-0 618-36-0 2627-86-3 (S) 3886-69-9 (R) EINECS/ELINCS 223-423-4 Synonyms 1-(Aminoethyl) benzene 1-Amino-1-phenylethane o-M ethyl benzenemethanam i ne Methyl-o-benzylamine o-Phenethylamine 1-Phenylethanamine 1-Phenylethylamine Phenyl-1 ethylamine o-Phenylethylamine (R)-1-Phenylethylamine... 

Phenylethanamine. See a-Methylbenzylamine Phenylethane. See Ethylbenzene Phenylethanoic acid butyl ester. See Butyl phenylacetate... 

Nature is the source of a number of different resolving agents that are used to prepare separable diastereomeric pairs from enantiomers. In this experiment, we use (+)-tartaric acid (19), which is produced from grapes during the production of wine, to resolve racemic 1-phenylethanamine (20), as shown in the resolution scheme outlined in Figure 7.5. Conversion of the enantiomers of 20 into separable diastereomers involves an acid-base reaction with 19. The diastereomeric salts that result have different solubilities in methanol and are separable by fractional... 

Measuring the optical rotation (Sec. 7.5) of the 1-phenylethanamine recovered in this experiment allows you to determine whether it is the (+)- or (—)-enantiomer and the extent to which optical purification is achieved. If you are to do this part of the experiment, consult with your instructor for special experimental directions. 

Diastereomer Formation and Isolation Place 15.6 g of (-i-)-tartaric acid and 210 mL of methanol in the Erlenmeyer flask and heat the mixture to boiling using flame-less heating. To the stirred hot solution, cautiously add the solution recovered from the polarimeter and 7.5 g of racemic 1-phenylethanamine. Allow the solution to cool slowly to room temperature and to stand undisturbed tot 24 h or until the next laboratory period." The amine hydrogen tartrate should separate in the form of white prismatic crystals. If the salt separates in the form of needlelike crystals, the mixture should be reheated until a//the crystals have dissolved and then allowed to cool slowly. If any prismatic crystals of the salt are available, use them to seed the solution. 

Remove the diethyl ether from the solution by simple distillation. (Alternatively, use one of the techniques discussed in Section 2.29.) Then distill the residual 1-phenylethanamine under vacuum with a shortpath apparatus (Fig. 2.37b). It will be necessary to use electrical heating for the distillation because the amine has a boiling point of 94-95 °C (28 torr). 

Analysis Determine the yield of the resolved 1-phenylethanamine (20). Combine your product with that of another student to give a total of 3 g of 20. Weigh the combined product accurately, and then transfer it quantitatively into about 30 mb of methanol. Measure the volume of the methanolic solution accurately. It is the weight, in grams, of the 1-phenylethanamine divided by the vo/ume of the solution, in mL, that provides the concentration cfor Equation 7.7. Transfer the solution to the polarimeter sample tube, measure the observed rotation, and determine the specific rotation of the sample by using Equation 7.7. Optically pure (Ft)-(+)-1-phenylethanamine has [a] -i-30° (c = 10, CH3OH). 

Transfer the recovered diethyl ether to a container for nonhalogenated organic liquids, and put the methanolic filtrate from isolation of the less-soluble amine tartrate either in this same container or in a special container from which the more-soluble amine tartrate could be recovered consult your instructor for specific directions. Place the methanolic solution of 1-phenylethanamine either in a container so labeled or in the one labeled for nonhalogenated organic liquids. Transfer the sodium hydroxide solution into a container so labeled the tartaric acid salt it contains can be recovered. 

Given the value for the specific rotation of optically pure 1-phenylethanamine, calculate the optical purity of the sample of resolved amine for which you... 

Pasteur s observation of the fortuitous resolution of the tartrates by crystallization of the racemate is an exception to the general methods required for separating enantiomers. The more usual case involves converting the racemic mixture into a mixture of diastereomers, which may then be separated on the basis of differing physical properties, such as solubility. The resolution of 1-phenylethanamine (Sec. 7.6) is representative of this approach. 

Illustrate how to resolve racemic 1-phenylethanamine (shown below), using the method of reversible conversion into diastereomers. 

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