[(2R,5R,6S,9R)-6-Isopropyl-9-methyl-1,4-dioxaspiro[4.5]decan-2-yl]methyl 4-bromobenzoate

The title compound, C20H27BrO4, a 4-bromobenzoyl derivative of a stereoisomer of glycerol menthonide, synthesized as part of a study of 3-carbon stereochemical moieties, crystallizes with two crystallographically independent molecules in the asymmetric unit, the two molecules differing only in one of the C—O—C—C torsion angles around the ester O atom [−106.5 (7) and 146.1 (6)°]. The two molecules are crystallographically related by a pseudotranslation along the (011) diagonal of the unit cell, emulating a primitive monoclinic cell of half the volume. The translational symmetry is broken by the 4-bromobenzoate groups. The crystallographic assignment of the absolute stereochemistry is consistent with having started with (−)-menthone, the acetal C atom is R and the secondary alcohol is R. This brings the bromobenzoate into approximately the same plane as the menthyl ring and cis to the isopropyl group. The glycerol menthonide sections of the molecules interact with each other via C—H⋯O interactions, leading to the formation of chains either A or B molecules that stretch parallel to [010], forming column-shaped double chains. Interactions between neighboring columns are limited to van der Waals contacts.

The title compound, C 20 H 27 BrO 4 , a 4-bromobenzoyl derivative of a stereoisomer of glycerol menthonide, synthesized as part of a study of 3-carbon stereochemical moieties, crystallizes with two crystallographically independent molecules in the asymmetric unit, the two molecules differing only in one of the C-O-C-C torsion angles around the ester O atom [À106.5 (7) and 146.1 (6) ]. The two molecules are crystallographically related by a pseudotranslation along the (011) diagonal of the unit cell, emulating a primitive monoclinic cell of half the volume. The translational symmetry is broken by the 4-bromobenzoate groups. The crystallographic assignment of the absolute stereochemistry is consistent with having started with (À)-menthone, the acetal C atom is R and the secondary alcohol is R. This brings the bromobenzoate into approximately the same plane as the menthyl ring and cis to the isopropyl group. The glycerol menthonide sections of the molecules interact with each other via C-HÁ Á ÁO interactions, leading to the formation of chains either A or B molecules that stretch parallel to [010], forming column-shaped double chains. Interactions between neighboring columns are limited to van der Waals contacts.

Comment
The title structure was synthesized as part of a study of 3-carbon stereochemical moieties, specifically tri-substituted glycerol. Here menthone serves as a chiral auxiliary, freezing two carbons into a specific stereochemistry and influencing the stereochemistry of the third owing to the steric bulk of the menthone (Kiessling et al., 2009b). Previously a different stereoisomer was isolated as the 3,5-dinitrobenzoate derivative and its crystal structure was published (Kiessling et al., 2009a).
The starting material, glycerol menthonide, was originally prepared as an additive to spearmint gum by reaction of menthone with glycerol under acid catalysis (Greenberg, 1999). No further chemical analysis of the menthonide had been reported in the literature at that time. Later analysis revealed that glycerol menthonide exists in as many as six isomers, which proved to be difficult to separate (Kiessling et al. 2009b). However, conversion of the hydroxy group to an ester by reaction with 4-bromobenzoyl chloride yields a mixture of esters out of which the title compound crystallizes. Isolation of the crystals followed by sequential recrystallization from methanol/water yielded the title compound in > 97% purity in the form of colorless needles.
The title compound crystallizes with two crystallographically independent molecules in a monoclinic setting in the space group C2, Fig. 1. The two molecules, molecule A and B, are chemically identical and differ only in one on the torsion angles around the ester oxygen atom, C9-C8-O2-C1, which is -106.5 (7) ° in molecule A, and 146.1 (6) ° in molecule B. All other bonds, angles and torsion angles in both molecules are virtually identical, as can be seen in the overlay of the two molecules as shown in Fig. 2, and are within their expected ranges. The two molecules are not only very similar with respect to each other, they are also crystallographically related by a pseudotranslation found along the (0 1 1) diagonal of the unit cell ( Fig. 3.). The glycerol menthonide of the two molecules are transformed into each other by a translation of half a unit cell along this direction. The p-bromo benzoate moieties, however, do not obey the pseudotranslation, thus causing a doubling of the unit cell with respect to a theoretical smaller primitive monoclinic cell with the dimensions a = 22.5949, b = 5.5763, c = 16.0718 and β = 108.193.
Packing in the structure of the title molecule is dominated by a combination weak interactions and van der Waals interactions. Via pairs of bifurcated C-H···O interactions between phenyl H atoms and the ester carbonyl O atoms molecules A and B form dimers (Fig. 4, Table 1). The dimers have local non-crystallographic inversion symmetry with the p-bromo benzoate moieties of the A and B molecules related by a pseudo inversion center in the middle of each dimer. The glycerol menthonide sections of the molecules are also interacting with each other with both oxygen atoms of the gylcerol units acting as acceptors for weak C-H···O interactions from aliphatic C-H and CH 2 groups of neighboring glycerol menthonide moieties ( Table 1). The connections are between like molecules and to both sides of the molecules, which leads to the formation of chains of molecules of either A or B that stretch parallel to the (0 1 0) direction. The combination of both types of C-H···O interactions leads to the formation of column shaped double chains as shown in Fig. 4. The outside of these columns is dominated by methyl, methylene and aromatic H atoms and the bromine atoms, and interactions between neighboring columns are limited to van der Waals interactions.
supplementary materials sup-2 The refined Flack parameter of 0.000 (13) confirms the compound as a chiral and enantiopure molecule. The crystallographic assignment of the absolute stereochemistry is consistent with having started with (-)-menthone, and provides the stereochemistry of the acetal carbon and the esterified secondary alcohol of the glycerol chain. Specifically, the acetal carbon, C5, is R and the secondary alcohol, C2, is also R. This brings the bromobenzoate into approximately the same plane as the menthyl ring and cis to the isopropyl group.

Experimental
All chemicals were purchased through ThermoFisher Inc. and used without further purification. Glycerol menthonide was prepared according to the published procedure (Greenberg 1999). GC/MS data was obtained using a Varian CP 3800 with Saturn 2000 ion trap MS. Column: Varian CP 5860, WCOT fused silica 30 m × 0.25 mm, coating CP-Sil. Carrier gas: He 1.2 ml/min. Temperature Program: initial temperature 473 K, ramp 20 K/min to 533 K hold 14.5 min. NMR data were obtained at Bucknell University using a Varian 600 MHz instrument and CDCl 3 , data are reported as p.p.m. from TMS and coupling constants are in Hz. Melting points were obtained on a MelTemp and are uncorrected. TLC was done with Analtech 2520 plates.
In a 50-ml round-bottom flask were placed glycerol menthonide (5.02 g, 22.0 mmol), 4-bromobenzoyl chloride (4.96 g, 23.0 mmol) and pyridine (10 ml). The flask was fitted with an air reflux condenser, drying tube and a magnetic stir bar. The flask was heated to reflux of the solvent while stirring for 2 h. The contents of the flask were then added to water (30 ml) and methyl tert-butyl ether (MTBE, 20 ml) and separated. The aqueous layer was extracted twice with MTBE (20 ml). The combined organic layers were washed with 10% HCl (2 × 15 ml), 10% Na 2 CO 3 (2 × 15 ml) and saturated NaCl (15 ml

Refinement
Reflection 2 0 0 was obstructed by the beam stop and was omitted from the refinement. The structure shows pseudotranslation along the (0 1 1) diagonal. The p-bromo benzoate moieties do not obey the pseudotranslation and cause the doubling of the unit cell. The largest residual electron density peaks are located close to the bromine atoms, 0.84 Å from Br1 and 0.82 Å from Br2. The relatively large residual electron densities found (4.00 and 3.78 e Å -3 ) are associated with correlation effects due to the pseudotranslation exhibited by the structure. Q1, located close to Br1, is at a position that agrees with the position of Br2 translated along the direction of the pseudotranslation. Q2, on the other hand, reflects Br1 translated by half a unit cell along (0 1 1) (Fig. 5).
H atoms attached to carbon atoms were positioned geometrically and constrained to ride on their parent atoms, with C-H distances of 0.95 (CH ar ), 0.99 (CH 2 ), 0.98 (CH 3 ) or 1.00 Å (C-H) and with U iso (H) = 1.2 U eq (C) or 1.5 U eq (C methyl ) for methyl H. Fig. 1. Displacement ellipsoid style view of the two molecules A and B of the title compound. Ellipsoid probability is at the 50% level.      (8)