Quadraphasic Phase-Vanishing Method: Application to Bromination Reactions that Produce Acidic By-Products

Abstract

A quadraphasic phase-vanishing method was developed that employs water as the fourth phase acting as an ‘acid scavanger phase’. This protocol worked well for bromination of aceto­phenones giving high yields of the corresponding α-bromo ketones.

Key words

fluorous solvent - quadraphasic - phase-vanishing method - bromination of acetophenones - acidic by-products

References

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6

Galden^® HT135 is a polyether-type perfluorinated solvent, which is commercially available as a heat transfer liquid (Solvay Solexis Inc.). Bp 135 °C, density = 1.72 g/mL at 25 °C, average molecular weight = 610. The general structure is shown in Figure [2] .

7

Typical Experimental Procedure for Bromination of Acetophenones.
Galden^® HT 135 (1.5 mL) was placed in a test tube, and then bromine (320.0 mg, 2.0 mmol) was introduced slowly by using a glass pipette. Since bromine is more dense than the fluorous phase, bromine sank to the bottom, forming two layers. A CHCl₃ solution (1.5 mL) of 4-chloroacetophenone (309.0 mg, 2.0 mmol; Table [1] , run 4) was then slowly added, which made the third layer. Then, 1.0 mL of 1 M aq solution of K₂CO₃ was added on the top, forming a four-phasic system. Then the test tube was covered with aluminum foil to protect from light and left overnight without stirring at r.t. After the bromine layer had disappeared and the fluorous phase became colorless, the upper two phases (aqueous and organic) were decanted. The organic phase was separated, washed with aqueous solution of Na₂SO₃, dried over MgSO₄ and concentrated. The residue was purified by a short column chromatography (silica gel, eluted with hexane-EtOAc) to give 420.4 mg (yield 90%) of 2-bromo-1-(4-chlorophenyl)ethanone as colorless microcrystals.

8

In a triphasic system (aqueous phase being omitted) bromination of acetophenone derivatives proceeded, however, pungent HBr gas evolved from the top layer.

10

With 1.0 equiv of Br₂, 44% of the dibromo-substituted arene was obtained along with 43% recovery of the starting material.