Properties In terms of molecular structure,<unk>  has a phenethylamine skeleton, with a phenolic hydroxy- group, an alcoholic hydroxy- group, and an N-methylated amino-group. Alternatively,<unk>  might be described as a phenylethanolamine with an N-methyl and p-hydroxy substituent. The amino-group confers basic properties on the molecule, whereas the phenolic –OH group is weakly acidic: the apparent (see original article for discussion) pKas for protonated<unk>  are 9.55 (phenolic H) and 9.79 (ammonium H). Common salts of racemic<unk>  are its hydrochloride, C9H13NO2.HCl, m.p. 150–152°, the oxalate (C9H13NO2)2.C2H2O4, m.p. 221–222 °C, and the tartrate (Sympatol), (C9H13NO2)2.C4H6O6, m.p. 188–190 °C. The presence of the hydroxy-group on the benzylic C of the<unk>  molecule creates a chiral center, so the compound exists in the form of two enantiomers, d- and l-<unk> , or as the racemic mixture, d,l-<unk> . The dextrorotatory d-isomer corresponds to the (S)-configuration, and the levorotatory l-isomer to the (R)-configuration. Racemic<unk>  has been resolved using ammonium 3-bromo-camphor-8-sulfonate. The enantiomers were not characterized as their free bases, but converted to the hydrochloride salts, with the following properties: (S)-(+)-C9H13NO2.HCl: m.p. 178 °C; α = +42.0°, c 0.1 (H2O); (R)-(−)-C9H13NO2.HCl: m.p. 176 °C; α = −39.0°, c 0.2 (H2O) (−)-Synephrine, as the free base isolated from a Citrus source, has m.p. 162–164 °C (with decomposition). The X-ray structure for<unk>  has been determined. Synthesis Early and seemingly inefficient syntheses of<unk>  were discussed by Priestley and Moness, writing in 1940. These chemists optimized a route beginning with the O-benzoylation of p-hydroxy-phenacyl chloride, followed by reaction of the resulting O-protected chloride with N-methyl-benzylamine to give an amino-ketone. This intermediate was then hydrolyzed with HCl/alcohol to the p-hydroxy-aminoketone, and the product then reduced catalytically to give (racemic)<unk> . A later synthesis, due to Bergmann and Sulzbacher, began with the O-benzylation of p-hydroxy-benzaldehyde, followed by a Reformatskii reaction of the protected aldehyde with ethyl bromoacetate/Zn to give the expected β-hydroxy ester. This intermediate was converted to the corresponding acylhydrazide with hydrazine, then the acylhydrazide reacted with HNO2, ultimately yielding the p-benzyloxy-phenyloxazolidone. This was N-methylated using dimethyl sulfate, then hydrolyzed and O-debenzylated by heating with HCl, to give racemic<unk> . Structural relationships Much reference has been made in the literature (both lay and professional) of the structural kinship of<unk>  with ephedrine, or with phenylephrine, often with the implication that the perceived similarities in structure should result in similarities in pharmacological properties. However, from a chemical perspective,<unk>  is also related to a very large number of other drugs whose structures are based on the phenethylamine skeleton, and although some properties are common, others are not, making unqualified comparisons and generalizations inappropriate. Thus, replacement of the N-methyl group in<unk>  with a hydrogen atom gives octopamine; replacement of the β-hydroxy group in<unk>  by a H atom gives N-methyltyramine; replacement of the<unk>  phenolic 4-OH group by a –H gives halostachine. If the<unk>  phenolic 4-OH group is shifted to the meta-, or 3-position on the benzene ring, the compound known as phenylephrine (or m-synephrine, or "Neo-synephrine") results; if the same group is shifted to the ortho-, or 2-position on the ring, o-synephrine results. Addition of another phenolic –OH group to the 3-position of the benzene ring produces the neurotransmitter epinephrine; addition of a methyl group to the α-position in the side-chain of<unk>  gives oxilofrine (methylsynephrine). Four stereoisomers (two pairs of enantiomers) are possible for this substance. Extension of the<unk>  N-methyl substituent by one methylene unit to an N-ethyl gives the hypotensive experimental drug "Sterling #573"/"Aethyl-Sympatol". The above structural relationships all involve a change at one position in the<unk>  molecule, and numerous other similar changes, many of which have been explored, are possible. However, the structure of ephedrine differs from that of<unk>  at two different positions: ephedrine has no substituent on the phenyl ring where<unk>  has a 4-OH group, and ephedrine has a methyl group on the position α- to the N in the side-chain, where<unk>  has only a H atom. Furthermore,<unk> " exists as either of two enantiomers, while "ephedrine" exists as one of four different enantiomers; there are, in addition, racemic mixtures of these enantiomers. The main differences of the<unk>  isomers compared for example to the ephedrines are the hydroxy-substitutions on the benzene ring.<unk> s are direct sympathomimetic drugs while the ephedrines are both direct and indirect sympathomimetics. One of the main reasons for these differential effects is the obviously increased polarity of the hydroxy-substituted phenyl ethyl amines which renders them less able to penetrate the blood-brain barrier as illustrated in the examples for tyramine and the amphetamine analogs.
Synephrine
Norepinephrine
Norepinephrine 
Dopamine
Dopamine 
Adrenomedullin
Catecholamine
Octopamine