Tetrahedron Letters
Microwave-assisted silica-supported aluminum chloride-catalyzed
Friedel-Crafts alkylation
Laurine R. Zupp b, Veronica L. Campanella b, DiAndra M. Rudzinski b, François Beland c, Ronny Priefer a,b,
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a College of Pharmacy, Western New England University, Springfield, MA 01119, USA
b Department of Chemistry, Biochemistry, and Physics, Niagara University, NY 14109, USA
c SiliCycle Incorporated, Quebec City, QC, Canada G1P 4S6
a r t i c l e i n f o
a b s t r a c t
Article history:
Microwave irradiation is a popular method in organic synthesis to achieve high yields in shorter reaction
times. This decreases total ‘man-hours’ in a synthetic setting. Another technique used in organic chem-
istry to decrease manual manipulations, is solid support reagents. The benefits of this approach is that
upon completion of a reaction, a simple filtration can be performed which expedites the work-up and also
produces less organic waste. Friedel-Crafts alkylation has been explored using microwave chemistry as
well as with solid-supported reagents. In comparison with traditional heating, as well as with AlCl3, supe-
rior yields were observed with silica-gel bound aluminum chloride (Si-AlClx) when microwave irradiated
for only 5 min.
Received 29 June 2012
Revised 25 July 2012
Accepted 30 July 2012
Available online 4 August 2012
Keywords:
Friedel-Crafts alkylation
Microwave irradiation
Silica-gel bound aluminum chloride
Ó 2012 Elsevier Ltd. All rights reserved.
Solid-support chemistry is a methodology which utilizes a solid
scaffold or resin for the synthesis of a variety of molecules.1,2 Its
application is useful for biological and organic synthetic pro-
cesses.1,2 The concept of solid-supported chemistry has evolved
since Merrifield first applied it toward the successful synthesis of
a tetrapeptide in 1963.3 Originally, amino acids were covalently
bonded to solid resins, such as polystyrene to help synthesize long
peptide chains. This approach was ultimately expanded to organic
synthesis and has been utilized with solid-supported reagents and
scavengers.4 A recent comparison study of reductive amination
with sodium cyanoborohydride and silica-gel bound cyanoborohy-
dride demonstrated that the supported reagent increased the per-
cent yield while decreasing the time needed to complete the
reaction.5 These solid-supported reagents possess many advanta-
ges over traditional synthesis processes, however the quicker and
easier workups, and hence decreased number of ‘man-hours’, is
the economic driver for this class of research.
Yet another popular approach to decrease the number of ‘man-
hours’ for organic synthesis is to employ microwave heating to
accelerate reactions. This has been an increasingly popular tech-
nique in organic chemistry since the 1980s. There are many publi-
cations on the ‘specific microwave effect’ however strong evidence
exists that the increased reaction rate is a purely thermal event.6 A
recent study reported that the use of SiC vials, which absorb the
microwave irradiation, provided virtually identical yield and reac-
tion rates to those with Pyrex vials, suggesting that the enhance-
ment with microwave irradiation is exclusively thermal in nature.7
Herein, we wish to report the use of a solid-supported reagent,
specifically, silica-gel bound aluminum chloride (Si-AlClx) in con-
junction with microwave irradiation (MWI) in Friedel-Crafts alkyl-
ation in hopes to accelerate not only the reaction time, but also the
overall synthetic manipulation time. A number of reagents have
been used to accelerate this C–C bond forming reaction, with some
being assisted with microwave irradiation. Yamamoto reported
successful 15 min reactions in MW with a molybdenum (II) com-
plex with o-chloranil.8 Bachari et al. utilized an iron-folded sheet
mesoporous material (Fe-FSM-16) under MW irradiation to benzy-
late various aromatics in 15–45 min.9 Zu and coworkers employed
Lewis acid ionic liquids under MW heating to synthesize a key
10
intermediate of coenzyme Q10
.
Another popular solid reagent in
Friedel-Crafts chemistry with microwave-assisted organic synthe-
sis is montmorillonite K-10. This has been used on indoles11 as well
as to synthesize dihydrocoumarins.12 Aluminum trichloride (AlCl3)
is the most common reagent utilized in both Friedel-Crafts alkyl-
ation and acylation reactions. Unfortunately, the anhydrous form
may be harmful for humans as well as the environment. Upon
opening, AlCl3 reacts with the moisture in the air liberating hydro-
chloric acid gas. According to the material safety data sheet
(MSDS), this chemical is harmful when inhaled, ingested, or ab-
sorbed through the skin. Exposure to AlCl3 corrodes the mucous
membrane, eyes, and skin, causes blindness, chronic bronchitis,
sore throats, erosion of tooth enamel, nose bleeds, and severe
burns. Since the reagent reacts with air, it must be weighed out
quickly and carefully. It has however been successfully examined
in conjunction with MWI in the synthesis of indanones.13
Silica-gel bound aluminum chloride (Si-AlClx) is
replacement for the traditional AlCl3. It has been utilized in the
a milder
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Corresponding author. Tel.: +1 413 796 2416; fax: +1 413 796 2266.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.