2-Bromofluorobenzene1

[1072-85-1]  · C6H4BrF  · 2-Bromofluorobenzene  · (MW 175.00)

(starting material for coupling reactions; useful benzyne precursor)

Physical Data: bp 156-157 °C; bp 58-82 °C/50 mmHg; d 1.601 g cm-3; n20D 1.5340.

Solubility: sol dichloromethane.

Form Supplied in: liquid; widely available.

Coupling Reactions.1

2-Bromofluorobenzene reacts with palladium in DMF containing Tri-n-butylamine to yield 2,2-difluorobiphenyl (eq 1).2

Ullmann-type Coupling.

2-Bromofluorobenzene can be coupled with amines using a copper catalyst (eq 2).3

Generation of Benzyne.4

Benzyne can be generated by treatment of 2-bromofluorobenzene with lithium amalgam or Magnesium(eq 3). This procedure for benzyne generation has been used for the synthesis of bridged polycyclic molecules such as triptycene (eq 4).5

An alternative procedure for the generation of benzyne is based on the use of n-Butyllithium. Under these conditions, benzyne reacts with pyrroles in a [4 + 2] cycloaddition (eq 5).6

Very efficient cycloaddition occurs when benzyne is generated from 2-bromofluorobenzene and magnesium in the presence of a furan. This method has been applied to the synthesis of analogs of the antitumor agent ellipticine (eq 6).7

Benzyne generated by the same procedure has reacted with isoindoles to yield dibenzoazanorbornanes (eq 7).8

Germacyclopentadienes react with benzyne to afford dibenzogermanorbornanes (eq 8).9 Silacyclopentadienes react with benzyne similarly (eq 9).10

Related Reagents.

2-Bromoiodobenzene.


1. Knight, D. W. COS 1991, 3, 481.
2. Brenda, M.; Knebelkamp, A.; Greiner, A.; Heitz, W. SL 1991, 809.
3 Greiner, A. S 1989, 312.
4. Hoffman, R. W. Dehydrobenzene and Cycloalkynes; Academic: New York, 1967.
5. Wittig, G. OSC 1963, 4, 964.
6. Davies, J. W.; Durrant, M. L.; Walker, M. P.; Malpass, J. R. T 1992, 48, 4379.
7. Gribble, G. W.; Saulnier, M. G.; Sibi, M. P.; Obaza-Nutaitis, J. A. JOC 1984, 49, 4518.
8. Carpino, L. A.; Padykula, R. E.; Barr, D. E.; Hall, F. H.; Krause, J. G.; Dufresne, R. F.; Thoman, C. J. JOC 1988, 53, 2565.
9. Schriewer, M.; Neumann, W. P. JACS 1983, 105, 897.
10. Marinetti-Mignani, A.; West, R. OM 1987, 6, 141.

Luis Castedo & Enrique Guitián

CSIC and University of Santiago de Compostela, Spain



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