Ultrasound-promoted dimerization of benzylic halides

Article abstract of DOI:10.1080/00397911.2012.675459

Simple and straightforward coupling of benzylic compounds was achieved by sonicating benzylic halides in the presence of magnesium.

Full text of DOI:10.1080/00397911.2012.675459

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Ultrasound-Promoted Dimerization of
Benzylic Halides
Olga V. Gozhina a , Ivar K. Thomassen a & Tore Lejon a
a Department of Chemistry, University of Tromsø, Tromsø, Norway
Accepted author version posted online: 03 Jan 2013.Version of
record first published: 05 Apr 2013.
To cite this article: Olga V. Gozhina , Ivar K. Thomassen & Tore Lejon (2013): Ultrasound-Promoted
Dimerization of Benzylic Halides, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 43:14, 1867-1870
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Synthetic Communications1, 43: 1867–1870, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.675459
ULTRASOUND-PROMOTED DIMERIZATION OF
BENZYLIC HALIDES
Olga V. Gozhina, Ivar K. Thomassen, and Tore Lejon
Department of Chemistry, University of Tromsø, Tromsø, Norway
GRAPHICAL ABSTRACT
Abstract Simple and straightforward coupling of benzylic compounds was achieved by
sonicating benzylic halides in the presence of magnesium.
Keywords Benzylic halide; coupling; Grignard; ultrasound
INTRODUCTION
Carbon–carbon-bond forming reactions are important tools in organic syn-
thesis and there are a number of methods available, ranging from simple substitution
reactions to more elaborate catalytic ones. In general, it is more complicated with
more substituted reacting centers.
When coupling benzylic compounds, methods used include transition-metal-cat-
alyzed coupling of halides[1,2] and oxidative additions.[3] Other methods include
single-electron transfer (SET) in the reaction of lithium thiolates with trityl halides,
which has been studied in detail.[4] SET is also involved in the chemoselective reductions
of vicinal dihalides with magnesium in methanol.[5] However, most couplings of
benzylic halides are reductive couplings using organometallic compounds as catalysts.
Examples include the dimerization in the presence of vitamin B12 and Ti(III) citrate,[6]
electrochemical coupling in lithium perchlorate solution using magnesium electrodes,[7]
zinc in aqueous media,[8] ruthenium carbonyls,[9,10] and iron(II) oxalate.[11]
It was therefore surprising when it was discovered that attempted substitution
on boronates[12] in some cases led to homocoupling of the halide, if the formation of
Received March 2, 2012.
Address correspondence to Tore Lejon, Department of Chemistry, University of Tromsø,
NO-9037, Tromsø, Norway. E-mail: tore.lejon@uit.no
1867

1868
O. V. GOZHINA, I. K. THOMASSEN, AND T. LEJON
Scheme 1. Reaction of Grignard reagent with boronates.
Grignard reagent was performed with ultrasound in a one-pot procedure. This was
never observed when utilizing preformed Grignard reagent (Scheme 1).
RESULTS AND DISCUSSION
The most surprising fact about the coupling reaction was that it was faster than
the addition to the boronate, and the scope and limitations of the reaction was there-
fore investigated. It was soon clear that the reaction did not proceed with alkyl
halides or aromatic halides. On the other hand, it worked well with both primary
and secondary benzylic bromides, while tertiary benzylic bromides were unreactive
(Table 1).
Table 1. Coupling of benzylic halides under sonication
Starting material
Yield (%)
1-a-Bromomethyl-naphtalene
9-Bromofluorene
Bromo-diphenylmethane
40
91
75
23
12a
a-Bromotoluene
4-Bromo-a-bromotoluene
4-Methyl-a-bromotoluene
2-Methyl-a-bromotoluene
2-Bromo-a-bromotoluene
48
61
13a
3-Bromo-a-bromotoluene
19a
31
3-Methyl-a-bromotoluene
3-Trifluoromethyl-a-bromotoluene
4-Trifluoromethyl-a-bromotoluene
2-Trifluoromethyl-a-bromotoluene
Triphenylmethylbromide
28
4a
No reaction
No reaction
82b
1-a-Chloromethyl naphthalene and 9-Bromofluorene
aIsolated by preparative TLC.
bAll three possible products formed.

ULTRASOUND-PROMOTED DIMERIZATION
1869
However, isolated yields were often disadvantaged by the fact that the
coupled product was difficult to separate from the by-product produced from the
protonation of non-coupled Grignard reagent. An experiment was performed with
a-chloromethyl naphthalene and 9-bromofluorene to evaluate the importance of
the halide. In this case all three possible compounds were formed, which indicates
that the structure of the starting material is more important than which halide is
employed. Reactivity seems to be influenced by both steric and electronic factors
as yields were less when the aromatic moiety was substituted with strongly electron-
withdrawing groups, and triphenyl methylbromide did not react at all. Prolonged
reaction time did not result in greater yields for any of the substrates.
EXPERIMENTAL
In a typical experiment, a three-necked flask equipped with an argon inlet, a
condenser, and a dropping funnel was charged with magnesium turnings (60 mmol)
and 1 or 2 crystals of iodine. A small amount of tetrahydrofuran (THF) was added
to cover the magnesium, and a solution of halide (100 mmol) in THF (50 mL) was
added dropwise. The reaction was performed in an ultrasound bath, keeping the
temperature of the mixture below 30 ꢀC by the occasional addition of ice. After the
addition was complete, the reaction mixture was sonicated for 3 h before it was
quenched with 5% aqueous hydrochloric acid (50 mL). After separation, the water
phase was extracted with diethyl ether (3 Â 20 mL). The organic phases were then
combined and dried over anhydrous magnesium sulfate, and the solvent was removed
under reduced pressure. Column chromatography was performed on silica using
pentane to elute any impurities and 5% ethyl acetate in pentane was used to elute the
product. All spectroscopic data were in accordance with earlier published data.[13–19]
ACKNOWLEDGMENT
A grant from the Norwegian Science Foundation to O. V. Gozhina is greatly
acknowledged.
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