Preparation and structural analysis of (±)-threo-ritalinic acid

Acta Crystallogr C. 2013 Nov;69(Pt 11):1225-8. doi: 10.1107/S010827011302595X. Epub 2013 Oct 19.

Abstract

Hydrolysis of the methyl ester (±)-threo-methyl phenidate afforded the free acid in 40% yield, viz. (±)-threo-ritalinic acid, C13H17NO2. Hydrolysis and subsequent crystallization were accomplished at pH values between 5 and 7 to yield colourless prisms which were analysed by X-ray crystallography. Crystals of (±)-threo-ritalinic acid belong to the P21/n space group and form intermolecular hydrogen bonds. An antiperiplanar disposition of the H atoms of the (HOOC-)CH-CHpy group (py is pyridine) was found in both the solid (diffraction analysis) and solution state (NMR analysis). It was also determined that (±)-threo-ritalinic acid conforms to the minimization of negative gauche(+)-gauche(-) interactions.

Keywords: (±)-threo-methyl phenidate; (±)-threo-ritalinic acid; Ritalin®; crystal structure; gauche+–gauche- interactions; hydrolysis.

MeSH terms

  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Magnetic Resonance Spectroscopy
  • Methylphenidate / analogs & derivatives*
  • Methylphenidate / analysis
  • Methylphenidate / chemical synthesis
  • Methylphenidate / chemistry
  • Molecular Structure
  • Stereoisomerism

Substances

  • Methylphenidate
  • ritalinic acid