1- Phenylethylamine, resolution

In the resolution of 1 phenylethylamine using (-) malic acid the compound obtained by recrystallization of the mixture of diastereomeric salts is (/ )... 

Deamination, Transamination. Two kiads of deamination that have been observed are hydrolytic, eg, the conversion of L-tyrosiae to 4-hydroxyphenyUactic acid ia 90% yield (86), and oxidative (12,87,88), eg, isoguanine to xanthine and formycia A to formycia B. Transaminases have been developed as biocatalysts for the synthetic production of chiral amines and the resolution of racemic amines (89). The reaction possibiUties are illustrated for the stereospecific synthesis of (T)-a-phenylethylamine [98-84-0] (ee of 99%) (40) from (41) by an (5)-aminotransferase or by the resolution of the racemic amine (42) by an (R)-aminotransferase. 

In the resolution of 1-phenylethylamine using (-)-malic acid, the compound obtained by recrystallization of the mixture of diastereomeric salts is (/ )-1-phenylethylammonium (S)-malate. The other component of the mixture is more soluble and remains in solution. What is the configuration of the more soluble salt ... 

Racemization of amines is difficult to achieve and usually requires harsh reaction conditions. Reetz et al. developed the first example of DKR of amines using palladium on carbon for the racemization and CALB for the enzymatic resolution [35]. This combination required long reaction times (8 days) to obtain 64% yield in the DKR of 1-phenylethylamine. More recently, Backvall et al. synthesized a novel Shvo-type ruthenium complex (S) that in combination with CALB made it possible to perform DKR of a variety of primary amines with excellent yields and enantioselectivities (Figure 4.13) [36]. 

Example The discarded (-) phenylethylamine (3) from the resolution on page T 95 can be used to make other optically active compounds. 

Molecules having only a sulfoxide function and no other acidic or basic site have been resolved through the intermediacy of metal complex formation. In 1934 Backer and Keuning resolved the cobalt complex of sulfoxide 5 using d-camphorsulfonic acid. More recently Cope and Caress applied the same technique to the resolution of ethyl p-tolyl sulfoxide (6). Sulfoxide 6 and optically active 1-phenylethylamine were used to form diastereomeric complexes i.e., (-1-)- and ( —)-trans-dichloro(ethyl p-tolyl sulfoxide) (1-phenylethylamine) platinum(II). Both enantiomers of 6 were obtained in optically pure form. Diastereomeric platinum complexes formed from racemic methyl phenyl (and three para-substituted phenyl) sulfoxides and d-N, N-dimethyl phenylglycine have been separated chromatographically on an analytical column L A nonaromatic example, cyclohexyl methyl sulfoxide, did not resolve. 

Falk and Schlogl 42> as late as 1968 established the absolute configuration of compound 13a as (+) —(S)-4-carboxy[2.2]paracyclophane. They did this by kinetic resolution of the racemic carboxylic anhydride with ( —)-a-phenylethylamine this kinetically controlled amidation afforded the dextrorotatory compound (13) in 3.8% optical yield 42C The similar topology of the carboxyl-group environment in 13 and in a-substituted metallocene carboxylic acids (14), configurations con-... 

TAPA, see (+)- and (-)-a-(2,4,5,7-Tetranitro-9-fluorenylideneami-nooxy)propionic acid Tartaric acid, in resolution of a-phenylethylamine, 49, 93... 

A two-step approach, involving repeated use of the same enzyme, has been reported for the resolution of rac-l-phenylethylamine 56a (Scheme 2.34). Penicillin acylase, from Alcaligenes faecalis, was initially used in aqueous medium with (R)-phenylglycine amide 67 as the acyl donor. Under these conditions, the enzyme catalyzed the enantioselective acylation of 56a at pH 10-11. The product amide 68 was insoluble, and was collected and re-exposed to the enzyme at pH below 7.5. This resulted in the cleavage of the phenylglycinyl substituent. Excellent conversions, E values and enantiomeric excesses were achieved [36]. 

This was first experimentally verified for the [2.2]metacyclophane-4-carboxylic acid (55) which had to be prepared by an elaborate 7-step synthesis 771 in order to avoid an electrophilic substitution which might have led to a transanular ring closure (as had been observed in so many cases of [2.2]metacyclophanes)12). The resolution of 55 was accomplished via salt formation with (-t-)-l-phenylethylamine and gave the levorotatory acid ([a]D —9° in CHC13) which then was transformed into several optically active derivatives. The enantiomeric purity of 55 (and therefore of all compounds correlated with it) was confirmed by nmr spectroscopy of the diastereo-meric esters with (—)-l-phenylethanol77) as well as by HPLC of its diasteromeric naphthylamides 55). 

The chirality of methano[10]anulene-2-carboxylic acid (96) was derived from results of a kinetic resolution as outlined for cyclophanes in Section 2.9.3. The reaction of the anhydride of 96 with (—)-l-phenylethylamine as well as the kinetic resolution of 102 (unambiguously correlated with 96 via the acetyl derivative 99) with (+)-2-phenylbutanoic anhydride (Horeau s method) — affording an excess of (+)-carbinol 102 — led to the assignment of the descriptor (S) to (+ )-96 and all its derivatives U7). 

MeOH). A likely impurity is phenylethylamine from the resolution. Dissolve acid in ether-benzene (3 1), wash with 0.5N H2SO4, then H2O, dry over MgSO4, filter, evaporate and distil. [Dale et al. JOC 34 2543 1969, JACS 15 512 1973]. 

For racemic resolution of naproxen the use of cinchonidine, A/-alkyl-D-glucamine, dehydroabietylamine or (S)-a-phenylethylamine has been described. 

The procedure is illustrated in Expt 5.219 by the resolution of ( )-a-methyl-benzylamine (1-phenylethylamine) with the aid of tartaric acid. 

The more soluble salt must have the opposite configuration at the stereogenic center of 1-phenylethylamine, that is, the S configuration. The malic acid used in the resolution is a single enantiomer, S. In this particular case the more soluble salt is therefore (S)-l-phenylethylammonium (5)-malate. 

Sakai, K. (1999) Application of habit modification of diastereomeric salt crystals obtained from optical resolution via crystallization manufacture of enantiomerically pure 1-phenylethylamine,./. Org. Synth. Chem. Jpn, 57, 458-465. 

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