Structure of racemic duloxetine hydro­chloride

Duloxetine hydro­chloride (trade name Cymbalta) is marketed as a single enanti­omer (S)-N-methyl-3-(naphthalen-1-yl­oxy)-3-(thio­phen-2-yl)propyl­am­in­ium chloride, C(18)H(20)NOS(+)·Cl(−), which is twice as effective as the (R)-enanti­omer in serotonin uptake. Here, we report the crystal structure of duloxetine hydro­chloride in its racemic form (space group Pna2(1)), where it shows significant differences in the mol­ecular conformation and packing in its extended structure compared to the previously reported (S)-enanti­omer crystal structure. Mol­ecules of this type, comprising aromatic groups with a single side chain terminated in a protonated secondary amine, are commonly found in active anti­depressants. A Cambridge Structural Database survey of mol­ecules with these features reveals a strong correlation between side-chain conformation and the crystal packing: an extended side chain leads to mol­ecules packed into separated layers of hydro­phobic and ionic hydro­philic phases. By comparison, mol­ecules with bent side chains, such as racemic duloxetine hydro­chloride, lead to crystal-packing motifs where an ionic hydro­philic phase is encapsulated within a hydro­phobic shell.