SCHEME 1. P r ep a r a tion of
2,6-Dibr om oben za ld eh yd es 1a -d via Meta la tion of
1,3-Dibr om oben zen es
Regiosp ecific Meta la tion of
Oligobr om oben zen es
Sergiusz Lulin´ski and J anusz Serwatowski*
Warsaw University of Technology, Faculty of Chemistry,
Noakowskiego 3, 00-664 Warsaw, Poland
serwat@ch.pw.edu.pl
Received J anuary 16, 2003
Abstr a ct: The metalation of selected oligobromobenzenes
with lithium diisopropylamide (LDA) was investigated. 1,3-
Dibromo-substituted benzenes were metalated without spe-
cial precautions since the resultant 2,6-dibromophenyllith-
ium intermediates are relatively stable under reaction
conditions: corresponding benzaldehydes were obtained in
good or moderate yields after subsequent quench with N,N-
dimethylformamide (DMF). Aryllithium compounds derived
from 1,4- and 1,2-dibromobenzene are much less stable, but
they could be trapped by the in situ use of chlorotrimeth-
ylsilane. The one-pot metalation/disilylation of 1,4-dibromo-
and 1,2-dibromobenzene afforded 1,4-dibromo-2,5-bis(tri-
methylsilyl)benzene and 2,3-dibromo-1,4-bis(trimethylsilyl)-
benzene, respectively.
phile.8 However, dichlorobenzenes are metalated readily
with ordinary butyllithium in THF at -75 °C. The
products 2,3-dichlorophenyllithium,9 2,6-dichlorophenyl-
lithium,10 and 2,5-dichlorophenyllithium9 obtained from
o-, m-, and p-dichlorobenzene, respectively, are relatively
stable at -78 °C. 2-Bromophenyllithium can be prepared
from 1,2-dibromobenzene and n-BuLi, but it is even less
stable than the 2-chloro derivative.2,11 The reaction of 1,2-
diiodobenzene with n-BuLi failed to yield 2-iodophenyl-
lithium.12
The metalation of arenes containing bromine as the
ortho-activating substituent was performed very recently,
showing that the presence of two bromine atoms in the
meta position gives best results as far as regioselectivity
and stability of organolithium intermediates are con-
cerned.13,14 The only earlier report describes the lithiation
of related compound, namely 2,5-dibromothiophene, as
a useful method for the synthesis of several 3-substituted
2,5-dibromothiophenes.15 Our results confirm that se-
lected meta-dibromosubstituted benzenes can be easily
and regioselectively metalated using LDA at the position
between bromine atoms as demonstrated by the prepara-
tion of corresponding 2,6-dibromobenzaldehydes (Scheme
1). This is in accord with the behavior of 1,3-difluoro- and
1,3-dichlorobenzene which are also metalated exclusively
at the ortho position adjacent to both halogen atoms.
Quite obviously, the hydrogen atom located between two
electronegative halogen atoms reveals stronger activity
(or acidity) than the hydrogen atoms neighboring to only
one halogen atom.16 2,6-Dibromophenyllithium was ob-
The ortho-directing ability of many common functional
groups in the metalation of substituted benzenes has
been extensively investigated and used for many years
in organic synthesis.1 Among halogens fluorine possesses
the strongest ortho-directing ability therefore the meta-
lation of fluorinated aromatics has received relatively
much attention. In addition, ortho-fluorinated aryllithi-
um intermediates are more thermally stable than their
heavier halogen analogues which reveal a strong ten-
dency to eliminate lithium halide due to the aryne
formation.2 The metalation of fluorobenzene with n-BuLi
is rather slow in THF at -78 °C.3 However, halogen
substituted fluorobenzenes XC6H4F are lithiated without
difficulty with n-BuLi (X ) F,4 Cl5,6) or LDA (X ) Br,5,6,7
I5) in the ortho position to the fluorine. The metalation
of chlorobenzene can be accomplished with sec-BuLi in
THF and the low temperature of ca -100 °C is crucial
since the product, i.e., 2-chlorophenyllithium, decomposes
at slightly higher temperature to form benzyne so it must
be trapped at this temperature by appropriate electro-
* To whom correspondence should be addressed. FAX: 48-22-628-
2741.
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10.1021/jo0340511 CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/28/2003
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J . Org. Chem. 2003, 68, 5384-5387