Resolution of ortho- and meta-substituted 1-phenylethylamines with isopropylidene glycerol hydrogen phthalate

The hydrogen phthalate of isopropylidene glycerol 1. previously reported us an efficient resolving agent of p-substituted 1-phenylethylamines. was als o found to resolve selected o- and,m-isomers. In particular, the (S)-enanti omers of 1-(2-methylphenyl)ethylamine 2. 1-(3-methylphenyl)ethylamine 3. 1- (2-chlorophenyl)ethylamine 4 and 1-(3-methoxyphenyl)ethylamine 5 were obtai ned in good yields and very high enantiomeric excess (e.e.) by selective cr ystallization of the respective salts with (S)- or (R)-1. The e.e.s of the resolved substrates were determined by chiral HPLC analysis. The (S)-config uration of (-)-3 was established according to Raban's procedure. Optical ro tations of non-racemic free amines 2 and 3 are reported. The success of the resolutions presented and of the precedent ones using 1 indicate: that the position of the substituent on the 1-phenylethylamine Framework does not a ffect the resolution. showing the uncommon versatility of 1 in the resoluti on of monosubstituted 1-phenylethylamines. (C) 2001 Elsevier Science Ltd Al l rights reserved.