Racemic 1-phenylethanamine

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... 

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. 

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

Attempts to achieve an asymmetric 1,3-proton shift reaction of (/ )-33, obtained from ethyl 3,3,3-trifhioro-2-oxopropanoate and (f )-l-phenylethanamine in 81 % yield, resulted in conversion into 34 in 89% yield, but without any reliably delectable enantiomeric excess.26 Even at 10% conversion, the Shiff base 34 formed is completely racemic. Imine 34 undergoes isotopic exchange in triethylamine/methanoI-r/4 at a rate 10 times slower than the isomerization of 33 to 34. The authors reason that if a 1.3-proton shift mechanism is operating, some enantiomeric excess would have to be observable in product 34 at low conversion. Since this is not the ease, a 1,5-proton shift to the carbonyl oxygen, via stabilized anion 37, to form achiral intermediate enol 38, was proposed.26... 

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. 

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. 

Phenylpropionylhydroxamic acid 50, which was prepared by enzymatic kinetic resolution of racemic 2-phenylpropanamide, was transformed to (-)-(5)-phenylethanamine 52 using the Lessen transformation to generate the products without eroding stereochemistry. ... 

Chiral bases available from plants are often used as chiral resolving agents for racemic acids. More commonly, chemists now use commercially available chiral amines such as (K,S)-l-phenylethanamine. 

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