Issue in Honor of Prof. Atta-ur-Rahman ARKIVOC 2007 (vii) 291-300
7: 1H-NMR (400 MHz, CDCl3) d 3.97 (3H, s), 7.47–7.54 (2H, m), 7.62–7.69 (1H, m), 7.98–8.04 (2H, m). Methyl mandelate (3). Compound 3 was prepared from mandelic acid (2) by reaction with excess ethereal diazomethane according to the standard procedure and purified by recrystallization from methanol. 1H-NMR (400 MHz CDCl3) d 3.75 (3H, s), 5.18 (1H, s), 7.31–7.48 (5 H, m).
Reaction of the sodium salt Na[3-H] with the a-bromoester 4 Methyl mandelate (3, 3.45 g, 20.8 mmol) was allowed to react with finely dispersed sodium metal (0.45 g, 19.6 mmol) in ether (55 ml). After 5 h the hydrogen evolution ceased and methyl a-bromophenylacetate (4, 4.43 g, 19.3 mmol) dissolved in ether (10 ml) was added in one portion. To enhance the solubility of the alcoholate in the solvent ether and to catalyze the displacement of bromine in 4 tetrabutylammonium iodide (80 mg, 0.2 mmol) was added and the mixture stirred at 20°C for 24 h. After addition of excess aqueous NH4Cl and separation of the organic phase the aqueous phase was extracted with ether (5×30 ml). The combined organic phase was washed with brine (2×50 ml), dried over Na2SO4 and the solvent removed on a rotary evaporator. The remaining oil (6.5 g) was analyzed by 1H-NMR spectroscopy. The result is given in table 1. The crude reaction product was dissolved in the minimum amount of methanol to obtain a clear solution and allowed to stand at -23°C for 20 h. The oxirane 8 (0.76 g, 23%) precipitated as a polycrystallinic modification, m.p. 127–129°C. Repeated recrystallization from pentane/dichloromethane furnished a polymorphic modification, m.p. 131–132°C, suitable for Xray structural analysis. The spectral data are identical with a reference compound prepared from 7 and methyl a-bromophenylacetate (4) by Darzens condensation. As shown by 1H-NMR integration ~35% of the oxirane 8 remained in the mother liquor. After depletion in compound 8 the combined crude products of several runs (10.3 g) were subjected to distillation up to 100°C at
0.1 mbar to remove volatile components. In the residue obtained the diastereomeric ethers 5 were enriched to 44% as shown by 1H-NMR integration. A sample of 3.5 g was chromatographed on 100 g silica gel (70–230 mesh) in a water cooled column (eluent: petroleum ether (40°C/60°C)/dichloromethane 4:1.2:3). The following fractions were eluted: Starting compound 4 (0.5 g); diastereomeric mixture of 9 (40 mg); diastereomeric mixture of 5 together with product 8 (1.1 g), ratio 5/8 1:~0.8; starting compound 3 (0.2 g). A further column chromatography on silica gel with petroleum ether/dichloromethane 1:9 furnished a pure sample of the diastereomers of 5. Dimethyl diphenylsuccinate (9) (diastereomeric mixture). meso-9. 1H-NMR (400 MHz, CDCl3) d 3.40 (6H, s), 4.39 (2H, s), 7.27–7.52 (10H, m). rac. 9. 1H-NMR (400 MHz, CDCl3) d 3.70 (6H, s), 4.26 (2H, s), 6.95–7.18 (10H, m). The data are in agreement with those found in ref. 5. Integration of the singlet at 4.39 (meso) and 4.26 (d,l) indicate a 1:1 mixture. ISSN 1424-6376 Page 298 ©ARKAT USA, Inc.
