Tetrahedron Letters
HI gas as a reagent for
molecules
a-alkylation reaction with two ketone
a,
⇑
a
b
a
Shoji Matsumoto , Seigo Koitabashi , Yasuhiko Otani , Motohiro Akazome
a
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33 Yayoicho, Inageku, Chiba 263-8522, Japan
GODO SHIGEN CO., LTD, 1365 Nanaido, Chosei-mura, Chosei-gun, Chiba 299-4333, Japan
b
a r t i c l e i n f o
a b s t r a c t
Article history:
To develop the utilization of HI as an ‘old but new’ reagent, we found that the reaction of acetophenone
Received 2 April 2015
Revised 14 May 2015
Accepted 19 May 2015
Available online 4 June 2015
analogues with HI gas proceeded to give an a-alkylated product, which is derived from the two ketone
molecules. It was possible to conduct the reaction in solvent-free and various organic solvents under
anhydrous conditions. From the investigation on the reaction mechanism, we proposed that HI acts as
an acid and a reducing agent.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Hydrogen iodide
Alkylation
Acid
Reduction
Solvent-free reaction
In the past decades, numerous numbers of reagents have been
reported for organic synthesis. Not only newly developed reagents,
but also reagents known well for many years to have potential as a
novel synthetic reagent. Acidic reagents are one of the important
types, and it is known that their acidity is critically dependent on
moisture. Hydrogen iodide (HI) is utilized for organic synthesis as
HI is noncorrosive to many metals under moistureless condi-
tions. Therefore, stainless steel, latex tubes, and glassware can be
used as an apparatus. To get anhydrous HI gas for the experiment,
we constructed the system depicted in Figure 1. It consisted of an
HI cylinder, argon cylinder (to exclude moisture in apparatus),
stainless tube, TygonÒ tube, control valve, flow meter (to visualize
a flow of gas), rubber septum (to pick up HI gas with a disposable
syringe), buffer pot (to prevent backflow into line system), and a
pot with aqueous NaOH (to neutralize HI gas). (Caution!: HI is cor-
rosive when in contact with moisture. The experiment should be
conducted with a fume hood.) The tube line was exchangeable
with a vacuum pump. Before filling the apparatus with HI gas,
the stainless tube is dehydrated by heating with a heat gun in
vacuo, and then filled with argon gas. HI gas was taken up through
a rubber septum with a syringe attached with a disposable needle,
and was then immersed into a reaction vessel to cause a small
decompression. The reaction vessel is useable as ordinary glass-
ware. And nitrogen gas was introduced into the vessel to release
the difference in pressure against the atmosphere. After all of the
reagent was introduced, the reaction was conducted under sealed
conditions.
an acid,1 reducing agent,
–3
4–6
nucleophile, and so on. HI is com-
2,7
8
mercially available as a 55–57 wt % aqueous solution for use as a
synthetic reagent. But, in some reactions, anhydrous conditions are
necessary to sustain the reaction. There are various methods for
forming anhydrous HI, such as the combination of tetrahydronaph-
9
10
11
12
13
thalene and I
2
,
RSH and I
2
,
ROH and I
2
,
RCOOH and I
2
,
etc.
They are useful in a laboratory-scale experiment, but always form
unnecessary by-products. Within the industrial sector, anhydrous
14
HI can be utilized for dry etching ITO films. It can also be used in
a gaseous state. In order to utilize anhydrous HI gas for organic syn-
thesis as an ‘old but new’ reagent, we herein report a novel a-alkyla-
tion of acetophenone derivatives with HI, along with the finding that
HI acts as both an acidic and a reducing reagent in that reaction.
O
Ar
O
HI
Ar
Ar
As is expected with an acidic reaction, we examined the reac-
tion of acetophenone with HI gas to promote the aldol reaction.
O
OH
Ar
Ar
To our surprise,
a-alkylated product, 1,3-diphenylbutan-1-one,
was obtained at a yield of 61% when 1 equiv of HI was treated with
acetophenone at 25 °C for 1 d under solvent-free conditions
⇑
(Table 1, entry 1). The product consisted of two acetophenone
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0