Regioselectivity control of radiation-induced reaction: Electron beam-induced Fries rearrangement of sulfonamide within a β-cyclodextrin inclusion complex

Article abstract of DOI:10.1039/b606689e

EB (electron beam) irradiation of sulfonamide within a β-cyclodextrin (β-CD) inclusion complex in the solid state induced the solvent-free Fries rearrangement, which proceeded at a shorter reaction time with reversed regioselectivity by inclusion into the β-CD, compared with that of sulfonamide crystals; the β-CD as a restricted nanospace had a large effect on the reactivity and regioselectivity of the solvent-free EB-Fries rearrangement. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b606689e

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Regioselectivity control of radiation-induced reaction: electron beam-
induced Fries rearrangement of sulfonamide within a b-cyclodextrin
inclusion complex{
a
Jun Kato,* Hiroyuki Kakehata, Yasunari Maekawa and Takashi Yamashita
a
b
a
Received (in Cambridge, UK) 11th May 2006, Accepted 18th August 2006
First published as an Advance Article on the web 18th September 2006
DOI: 10.1039/b606689e
1
0
EB (electron beam) irradiation of sulfonamide within a
b-cyclodextrin (b-CD) inclusion complex in the solid state
induced the solvent-free Fries rearrangement, which proceeded
at a shorter reaction time with reversed regioselectivity by
inclusion into the b-CD, compared with that of sulfonamide
crystals; the b-CD as a restricted nanospace had a large effect
on the reactivity and regioselectivity of the solvent-free EB-Fries
rearrangement.
rearrangement. These characteristics arise from the geometrical
constraint of the guest molecules on inclusion into the b-CD.
Therefore, we expected that an EB-induced reaction in a nanoscale
cavity of b-CD, in which the motions of guest molecules are
constrained, could result in different reactivity (sensitivity and
selectivity) from that observed in the crystalline state. In this
communication, the solvent-free EB-induced reaction of the
inclusion complex of sulfonamide in b-CD was investigated,
compared with that of the sulfonamide crystals themselves.
The b-cyclodextrin inclusion complex of BSA (BSA/b-CD) was
prepared by precipitation from a mixture of a saturated aqueous
solution of b-CD as a host compound and equimolar amounts of
benzenesulfonanilide (BSA) as a guest compound. The precipitate
was filtered off and dried in vacuo to yield an inclusion complex
Due to the ability of EB (electron beam) to directly write
nanometer-scale patterns, it has attracted a great deal of attention
as a promising tool for nanolithography as well as future
1
nanodevice fabrication in a variety of fields. The development
of new EB-sensitive polymeric materials for these applications
should be possible via novel EB-induced reactions. Radiation-
induced reactions are generally complicated and not selective,
BSA/b-CD as a white powder in 91% yield. The formation of
1
BSA/b-CD was confirmed with H NMR in D
2
O. The H-5
11
2
proton inside of b-CD underwent a significant high-field shift
upon complexation (Fig. S1{), while the chemical shifts of H-1,
H-2, and H-4 protons outside of b-CD were not affected by
complexation. The high-field shift of the inner proton must be due
to a ring current effect of the aromatic rings of the guest molecule.
This result indicates the inclusion of the guest molecule (BSA) into
the b-CD cavity. The inclusion complex consists of BSA and b-CD
in a 1 : 1 ratio; evidence for which is given by the peak area ratio of
however, due to secondary reactions. Thus, we have investigated
3,4
selective EB-induced reactions of useful organic molecules in the
5
crystalline state and their application to EB-sensitive polymers.
One of the most interesting results is that the EB-sensitivity of
sulfonic acid derivatives is much higher than that of the corres-
ponding carboxylic acid derivatives; especially, the EB-induced
Fries rearrangement of arylsulfonamides which preferentially
4
yields aromatic amines. This reaction can be applied to novel
5,6
all protons of the BSA moiety to the H-1 proton of the b-CD
1
moiety in the H NMR spectrum in DMSO-d
EB-reactive polymers for nanolithography and nanofabrication
not only because reactive functional groups are transformed
selectively with the EB reaction but also because the EB reaction
can modify the properties of the material from acidic to basic.
b-Cyclodextrin (b-CD) has a cyclic repeated structure consisting
of seven glucose units. The cavity size and the inner hydro-
phobicity are suitable for encapsulating within it a variety of
6
.
Solvent-free EB-induced reaction of the 1 : 1 inclusion complex
BSA/b-CD was carried out as follows. A white powder of BSA/
b-CD (0.12 g) was placed in a stainless plate (18 6 10 6 4 mm),
which was covered with a Kapton film. The samples were
irradiated on a water-cooled copper plate with EB (acceleration
voltage: 1 MeV, beam current: 1 mA) at a dose rate of 2.9 kGy
7,8
smaller molecules such as aromatic compounds. The improve-
ment of the reaction rate and selectivity with b-CD inclusion
complexes has been reported in a number of thermal and
21
s
, using a cascade type electron accelerator (Dynamitron).
22
After EB irradiation of 0.10–10 MGy (0.054–5.4 mC cm ) in
8,9
dose, the reaction products were extracted with chloroform from
within b-CD, and the extracts were analyzed by GC and GC-MS.
In the solvent-free EB-induced reaction of the BSA/b-CD inclusion
complex, BSA as a guest molecule was completely consumed
before reaching a dose of 5 MGy, while the conversion of BSA
crystal itself under the EB reaction conditions was 28% even at the
same dose (Fig. 1). This result indicates that the BSA/b-CD
complex has a much higher EB-sensitivity than the BSA crystal
itself, and that the EB-induced reaction of BSA was promoted by
inclusion into the b-CD.
photochemical reactions. The complex formation with b-CD
could alter product distribution in the photochemical Fries
a
Department of Pure and Applied Chemistry, Tokyo University of
Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
E-mail: kato@rs.noda.tus.ac.jp; Fax: +81 4 7123 9890;
Tel: +81 4 7124 1501
b
Conducting Polymer Materials Group, Quantum Beam Science
Directorate, Japan Atomic Energy Agency (JAEA), 1233 Watanuki,
Takasaki, Gunma, 370-1292, Japan
{
Electronic supplementary information (ESI) available: Details of the
experiments, characterization of the products, NMR spectra of b-CD
moieties in the inclusion complexes, and X-ray diffraction patterns of
b-CD inclusion complex. See DOI: 10.1039/b606689e
4
The products were identified by GC-MS as previously. This
reaction yielded the Fries rearrangement products (ortho- and
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498 | Chem. Commun., 2006, 4498–4500

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Fig. 1 Conversions of benzenesulfonanilide (BSA) in the crystalline state
and the b-CD inclusion complex (BSA/b-CD) under EB irradiation
Fig. 2 Yields of each amine converted from benzenesulfonanilide (BSA)
within the b-CD inclusion complex plotted as a function of the absorbed
EB dose: o- and p-Fries products (r and &, respectively), aniline (m), and
the total of them ($).
(1 MeV, 1 mA).
para-form) and aniline. No trace of the meta-form could be
detected. As shown in Fig. 2, the combined yield of the three
amines based on the amount of BSA as BSA/b-CD reached its
maximum value of 55% with 2 MGy, then gradually decreased to
above, it appears that EB acts selectively on the guest (BSA) first
and then on the host (b-CD) to start deterioration of the b-CD
skeleton. It has been reported that addition of aromatic
hydrocarbons such as benzene can reduce radiation damage of
aliphatic ones such as cyclohexane owing to energy and charge
21% at 10 MGy as secondary reactions proceeded. The change in
the X-ray diffraction patterns of BSA/b-CD during EB irradiation
indicated that the b-CD skeleton of BSA/b-CD had higher EB-
stability than b-CD itself and was maintained up to 2 MGy, but
gradually deteriorated with further irradiation (Fig. S2{), which
roughly corresponds to the result shown in Fig. 2. Accordingly, EB
irradiation of BSA/b-CD induced the Fries rearrangement under a
constrained environment with a dose of up to 2 MGy to give three
amines in a high proportion of 86% (55% combined yield of
amines to 64% conversion) at a dose of 2 MGy (Fig. 2 and Table
S1{). Throughout the reaction, the ortho : para ratio of ca. 1 : 1.7
was maintained.
2,12
transfers.
The significantly high EB-sensitivity of the guest
molecules and high EB-stability of the host molecules with the
solid BSA/b-CD complexes may be due to the effect of b-CD as an
EB-antenna, which transfers the energy from the host to the guest
following ionization/excitation. In addition, the para-product was
predominantly formed in the EB-induced Fries rearrangement of
BSA/b-CD contrary to that of BSA crystals. The reversed
regioselectivity (ortho/para) must have been achieved by inclusion
of BSA into the b-CD. However, in the reaction of the guest
compounds with a tolyl group such as p-toluenesulfonanilide
(TSA) and phenyl p-toluenesulfonate (PTS), the proportion of the
para-product became only slightly larger in comparison with the
EB reaction in the crystalline state. We could also observe more
cage–escape product, aniline or phenol, in the b-CD complex
compared with the EB reaction in the crystalline state. This is
probably due to the existence of hydrogens in the b-CD cavity to
be abstracted by anilino radicals under high-energy radiation,
The product distribution in the reaction mixture after EB
irradiation (1 MGy) is shown in Table 1. In every case, the EB-
sensitivity of the guest molecules in b-CD increased about one
order of magnitude over that in the crystals. Although active
species are nonselectively produced for a variety of common
substrates by ionization/excitation in the primary process of
2
radiation reactions, in this system, from the results mentioned
a
Table 1 Product distribution upon the EB-Fries rearrangement of sulfonic acid derivatives within b-CD inclusion complexes
c
EB-products (%)
b
Conv. (%)
Substrate
o-Fries
p-Fries
PhXH
36.2
ortho : para
Proportion of amines (%)
BSA/b-CD
BSA crystals
TSA/b-CD
TSA crystals
PTS/b-CD
PTS crystals
a
46
7.5
70
9.7
74
7.1
b
12.9
24.0
5.3
13.4
7.8
20.9
6.7
6.1
6.2
4.6
1 : 1.6
3.4 : 1
1 : 1.2
2.2 : 1
1.7 : 1
—
70
31
30
30
30
,11
d
N.D.
18.5
10.3
17.2
,4
c
e
d
e
7.0
N.D.
d
Determined by GC. Conversion after EB irradiation for 5.75 min (1 MGy). Calculated on the consumed sulfonic acid derivatives. Not
e
detected. Proportion of ArOHs.
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Chem. Commun., 2006, 4498–4500 | 4499

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regioselectivity control in radiation-induced reaction using the
b-CD restricted nanospace. These results should provide a
breakthrough in finding useful high sensitive and selective
radiation-induced reactions for nanolithography and nanofabrica-
tion by reaction-field control. Further studies on the EB-induced
reactions in a restricted matrix are underway.
Notes and references
1
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A. Dutta, S. P. Lee, Y. Hayafune and S. Oda, J. Vac. Sci. Technol., B,
Fig. 3 Proposed mechanism of the EB-Fries rearrangement of sulfona-
mide and sulfonate within b-CD inclusion complexes: (a)–(c) BSA/b-CD,
(d) TSA/b-CD and PTS/b-CD.
2000, 18, 2857.
2
3
(a) Y. Tabata, Y. Ito and S. Tagawa, CRC Handbook of Radiation
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which aids the escape of anilino radicals from the cage of b-CD.
These results show that b-CD as a restricted nanospace has a large
effect on the EB-Fries rearrangement, suggesting that other EB-
induced reactions could also be controlled by appropriate choice of
reaction spaces.
1990; (c) Farhataziz and M. A. J. Rodgers, Radiation Chemistry,
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The proposed mechanism of the EB-Fries rearrangement of
b-CD inclusion complexes is shown in Fig. 3. This reaction
proceeds through two radicals generated by the homolytic cleavage
at the S–X bond via ionization/excitation by radiation, in analogy
with the photo-Fries rearrangement. There are two possibilities for
the directions of the guest molecules in the b-CD cavity; namely
the aniline group (a) or the benzenesulfonyl group (b, c) is included
in the b-CD cavity. In the former case (a), benzenesulfonyl radical,
which is produced by EB-induced scission of the S–N bond,
cannot attack the anilino radical residue because both para- and
ortho-positions are sterically blocked by b-CD. On the other hand,
the anilino radical in (c) can be attacked by the sulfonyl radical in
b-CD at the wider open end of the b-CD to give a preferentially
para-substituted one due to the steric hindrance with b-CD in (b).
Since TSA and PTS with a methyl group are included shallowly in
the b-CD cavity owing to the methyl group as shown in (d), para-
selectivity should be smaller than that of BSA/b-CD. The depth of
inclusion can also be understood by the magnitude of the high-
field shift of the inner H-5 proton of the b-CD moiety upon
4
5
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1
complexation in the H NMR spectra (Fig. S1{).
In conclusion, EB irradiation of an inclusion complex BSA/
b-CD induced the Fries rearrangement under a constrained
environment which led to changes in reaction rate and selectivity.
To the best of our knowledge this is the first example of
12 (a) M. S. Matheson, Annu. Rev. Phys. Chem., 1962, 13, 77; (b) M. Burton
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500 | Chem. Commun., 2006, 4498–4500
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