Determination of the absolute configuration of (-)-abietic acid via its (4R,5R,9R,10R)-7,13-abietadien-18-yl p-bromobenzoate derivative

# 2006 International Union of Crystallography All rights reserved The absolute configuration of the title bromo derivative of abietic acid, C27H35BrO2, has been determined. The structural analysis confirms the absolute stereochemistry for ( )-abietic acid proposed by Bose & Struck [(1959). Chem. Ind. (London), pp. 1628–1630] on the basis of optical rotatory dispersion measurements. The molecule exhibits a trans anti 6/ 6/6 tricyclic hydrocarbon skeleton, with the cyclohexane ring in the expected chair form and the two cyclohexene rings, the double bonds of which are conjugated, in half-chair conformations.

The absolute configuration of the title bromo derivative of abietic acid, C 27 H 35 BrO 2 , has been determined. The structural analysis confirms the absolute stereochemistry for (À)-abietic acid proposed by Bose & Struck [(1959). Chem. Ind. (London), pp. 1628-1630] on the basis of optical rotatory dispersion measurements. The molecule exhibits a trans anti 6/ 6/6 tricyclic hydrocarbon skeleton, with the cyclohexane ring in the expected chair form and the two cyclohexene rings, the double bonds of which are conjugated, in half-chair conformations.

Comment
Abietic acid (1) is a major acid component of pine rosins which are abundant natural chemicals having many industrial applications, including as paper sizings, polymerization emulsifiers, adhesive tackifiers, printing ink resins and waterproofing materials (McCoy, 2000). Most of the acids in pine rosins have also shown interesting biological properties and are of interest as potential therapeutic agents (Alvarez-Manzaneda et al., 2006). Abietic acid has been widely used as a chiral synthon for the preparation of terpenoids and natural products, confirming their stereochemistry (Arnó et al., 2003). It has been used as a standard of known absolute configuration in circular dichroism experiments by Hartl & Humpf (2000) and Proni et al. (2003), but without crystallographic confirmation of the absolute configuration.
Abietic acid is characterized by a steroid-like carbon skeleton, named 'abietane' in accordance with the IUPAC recommendations, which was chosen as the fundamental parent structure with the numbering pattern as depicted in the scheme. The structure of the title compound (1) has been confirmed by X-ray analysis previously by Okada & Takekuma (1994) and Matsubara et al. (1993). However, the only insight into its absolute configuration has been by optical rotatory dispersion experiments (Bose & Struck, 1959). Following our determination of a crystal structure of a compound prepared from abietic acid (Blake et al., 2006), we found a lack of crystallographic evidence for the absolute configuration of abietic acid itself. We therefore decided to embark on such a study by preparing simple derivatives of abietic acid containing significant anomalous scatterers: these include the p-bromo ester derivative (3) of the abietanol (2) obtained by standard reduction of abietic acid (1). A singlecrystal X-ray study established the connectivity and the absolute configuration of (3) (Fig. 1), thereby confirming the absolute configuration of (À)-abietic acid as 4R,5R,9R,10R.
The molecule exhibits a trans anti 6/6/6 tricyclic hydrocarbon skeleton in which the cyclohexane ring A has a typical chair form. Cyclohexene rings B and C, containing conjugated double bonds, have half-chair conformations. Thus, the relative stereochemistry is trans fusion for the A/B ring junction, anti between C9 hydrogen and C10 methyl (abietane numbering), and coplanar for the B/C ring junction. The ester linkage is located at C18 and the isopropyl group at C13. The structure is unsolvated. Bond lengths and angles lie in the ranges normally observed for such sterically non-strained molecules (Cambridge Structural Database, Version 5.27, May 2006 update;Allen, 2002).

Experimental
Compound (3) was synthesized starting from commercially available (À)-abietic acid, so the relative stereochemistry of centres C4, C5, C9 and C10 was fixed from the outset. Reduction of abietic acid under standard conditions, followed by esterification with p-bromobenzoyl chloride, afforded the bromo ester derivative (3). Diffraction-quality crystals were obtained by recrystallization from hexane.