Synthesis 2: Synthesis of 3-(2'-methoxy-5'-bromophenyl)-2,3-epoxy Phenyl Propanone, A Novel Epoxidated Chalcone Derivative

References: Moloney, G. P. J. Chem. Educ. 1990, 67, 617.
  Dixon, C. E.; Pyne, S. G. J. Chem. Educ 1992, 69, 1032.

Introduction

Bromination of deactivated aromatic compounds can be achieved using KBrO3 in the presence of acid, eq. 1. The active brominating agent under these conditions is most likely hypobromous acid.1

The aldol reaction involves the addition of a carbon nucleophile to a carbonyl group. The crossed aldol reaction carried out here, eq. 2, involves formation of the enolate of acetophenone. Formation of the enolate is followed by nucleophilic addition, proton transfer, and subsequent dehydration of the b-hydroxy ketone.2

Epoxidation of a,b-unsaturated ketones can be carried out using the sodium salt of hydrogen peroxide, eq. 3. The proposed mechanism for this reaction entails nucleophilic attack of the hydroperoxide on the b-carbon of the enone, followed by intramolecular displacement of the hydroxide ion.3

Procedure

Step 1. o-Methoxybenzaldehyde (6.8 g, 0.05 mol) was dissolved in glacial acetic acid (50 mL) and to this solution was added potassium bromide (6.0 g, 0.05 mol), potassium bromate (4.3 g, 0.025 mol), and distilled water (10 mL). The solution was refluxed for 30 min., in which time bromine was liberated up the condenser. The yellow solution was cooled slowly, and the resulting white needles were filtered off, washed with water, and recrystallized from aqueous ethanol to give 2-methoxy-5-bromobenzaldehyde (1) as white needles, lit mp 116 oC.

Step 2. Acetophenone (0.6 g, 5 mmol), ethanol (15 mL), and 2 M sodium hydroxide solution (12 mL) was stirred with a glass rod at room temperature for 5 min. 2-Methoxy-5-bromobenzaldehyde (1.05 g, 5 mmol) was then added and the resulting solution heated under reflux for 15 min. The yellow product was filtered, washed with cold water, and recrystallized from aqueous ethanol to give the chalcone derivative, 3-(2'methoxy-5'-bromophenyl)-1-phenylprop-2-enone (2), mp 49-50 oC.

Step 3. Acetone (40 mL) was added to 3-(2'-methoxy-5'-bromophenyl)-1-phenylprop-2-enone (0.96g, 3.022 mmol) and the mixture was stirred until a solution was obtained. To this was added methanol (10 mL) and 2 M sodium hydroxide (3 mL), and the solution was stirred for 5 min. An excess of 30% w/w hydrogen peroxide (1 mL) was then added dropwise and the resulting solution stirred at room temperature for 20 min. Distilled water (about 40 mL) was added to the solution to assist precipitation of the epoxide as a white solid, which was then recrystallized from aqueous ethanol to give the epoxide, 3, as fine white crystals, mp 105-106 oC.

References

  1. Harrison, J. J.; Pellegrini, J. P.; Swlwitz, C. M. J. Org. Chem. 1981, 46, 2169.
  2. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, Part B: Reactions and Synthesis, (second edition); Plenum: New York, 1983, pp 43-50.
  3. House, H. O. Modern Synthetic Reactions, (second edition); Benjamin: Menlo Park, 1972, p. 306.