General Procedure for Bromine-Lithium Exchange

0r//i0-deprotonation, the bromine-lithium exchange method has not lost its significance it is the only way to generate a lithium derivative having one or more substituents and the metal in a relative position other than ortho, e.g.  

Some specially substituted lithiated aryl compounds, not accessible by deprotonation, e. g. 0r//i0-lithionitrobenzene [36] and ortho-lithiochlorobenzene [175], have been generated by Br—Li exchange at very low temperatures. 

THF (75 ml) is added to a solution of 0.11 mol of butyllithium in 77 ml of hexane with cooling to below 0 °C. The mixture is cooled to —90 °C and 0.10 mol of bromoarene (or 0.05 mol (11.8 g) of / -dibromobenzene dissolved in 15 ml of THF) is added over 5 min with cooling to between —80 and —90 °C. The cooling bath is removed and the temperature is allowed to rise to —50 °C (Note 1) and stirring is continued ( — 50 °C) for 15 min. Clear solutions or fine suspensions are formed, in the case of bromonaphthalene however, a thick yellowish suspension is obtained, while 1,4-dilithiobenzene also forms a (white) suspension. 

To prepare/j-LiQF Br, a solution of 0.10 mol of butyllithium in 70 ml of hexane is added over 10 min to a solution of 0.10 mol (23.6 g) of/ -dibromobenzene in 90 ml of THF. During this addition the temperature is kept between —80 and —90 °C. After removing the cooling bath, the temperature is allowed to rise to — 50 °C. A white suspension is formed (Note 2). This reaction has also been carried out in Et20 at room temperature [168, 220]. 

It is advisable to carry out derivatization reactions as soon as possible particularly in THF too much delay may give rise to reduced yields owing to reaction of butyl bromide with aryllithium. In most cases this alkylation causes an observable heat effect when the temperature is allowed to reach —10 °C in the case of 0-LiC6H4OCH3, however, this reaction is markedly slower. 0-LiC6H4F eliminates lithium fluoride at temperatures above —40 °C [221]. 

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