Copper® bromide purification

Copper bromide was prepared according to J. L. Hartwell, Org. Syn., Coll. Vol. 3, 186 (1955) the salt was dried under reduced pressure over P2Os prior to use. The checkers observed that good results could be realized by using a commercially available copper bromide of higher than 95% purity from Wako Pure Chemical Industries, Ltd., Japan, without purification. 

A suspension of dimethyl sulfide copper bromide (17 g, 82 mmol) in 600 mL of dry diethyl ether under argon was cooled to —78°C, and methyl lithium (1.6-Af solution in diethyl ether, 100 mL, 160 mmol) was added. The reaction mixture was allowed to warm until clear and was then recooled to —78°C. A solution of compound 37 (16 g, 39 mmol) [Eq. (9)) in 150 mL of dry diethyl ether was added. After 0.5 h at —78°C the solution was allowed to warm to —40°C and maintained at this temperature for an additional 0.5 h. The reaction mixture was then washed with water (4 x 300 mL), dried (MgS04), and concentrated. Purification by column chromatography (AcOEt-petroleum ether, 10 90) gave compound 38 (15.69 g, 94%). 

Note 11). The residual activated magnesium is rinsed once with 200 mL of dry diethyl ether, and the supernatant layer is transferred via cannula to the copper bromide-dimethyl sulfide slurry (Note 12). The reaction mixture is slowly warmed to -10°C, and then 16.78 g (17.42 mL, 125 mmol) of hexanoyl chloride is added dropwise via syringe after which the reaction mixture is warmed to room temperature. After stirring for 3 hr, the reaction mixture is filtered through a 75-g layer of Celite 545 (Note 13) and the filter cake rinsed with three 100-mL portions of diethyl ether. Concentration of the filtrate under reduced pressure yields the a-silyl ketone which is utilized without further purification (Note 14). 

Lithium wire (3.2 mm diam.), carbon tetrachloride, triphenylphosphine, MgBrEtaO, copper bromide-dimethyl sulfide complex, hexanoyl chloride, methyllithium, p-toluenesulfonic acid monohydrate, potassium hydride, and 18-crown-6 were purchased from Aldrich Chemical Company, Inc. and used without further purification. 

Materials. MMA (Sigma-Aldrich)was distilled before use. a- bromoisobutyric acid (98%), isobutyric acid (99 /o), copper bromide I (99,999%), copper bromide 11(99,999%), 1,1,4,7,10,10-hexamethyltriethylenetetramine (HEMA) (97%), 4,4 -dinonyl-2,2 -dipyridyl (dNbpy) (97%), tetrahydrofurane (THF) (99%), methanol (99%), hydrochloric acid (25%), aliguat 336, toluene (99%) were purchased from Sigma-Aldrich and used as received without further purification. 

Prepare copper(i) bromide from 75 g (0.33 mol) of crystallised copper(n) sulphate as detailed in Section 4.2.27, p. 428, and dissolve it in 40 ml of 48 per cent hydrobromic acid heat the solution to boiling and add o-chlorobenzene-diazonium bromide solution as detailed above. When all the latter has been introduced, continue to pass steam through the mixture until no more organic material distils. Follow the procedure, including purification, given for p-bromotoluene. Collect the o-bromochlorobenzene (a colourless liquid) at 200-202 °C. The yield is 85 g (89%). 

The excess of copper cyanide and the use of a polar, high-boiling point solvent makes the purification of the products difficult. In addition, elevated temperatures (up to 200°C) lower the functional group tolerance. The use of alkali metal cyanides or cyanation reagents such as cyanohydrins, a catalytic amount of copper(I) iodide and kalium iodide, allows a mild, catalytic cyanation of various aryl bromides. 

---