Ultrastrong gravity-induced unusual reactivity in radical addition of bromotrichloromethane to ethyl cinnamate

Article abstract of DOI:10.1246/cl.2010.174

Radical addition of bromotrichloromethane to ethyl cinnamate was carried out under an ultrastrong gravitational field (>2.5 × 10⁵ G), and ethyl 3-chloro-3-phenyl-2-(trichloromethyl) propionate (A), ethyl 3-bromo-3-phenyl-2-(trichloromethyl) propionate (B), and ethyl 2-bromo-3-phenyl-3-(trichloromethyl) propionate (C) were isolated by reversed-phase HPLC. To date, there has been no report of the synthesis of A and C at 1 G, and this would be the first example of a selectivity change induced by ultrastrong gravity.

Full text of DOI:10.1246/cl.2010.174

doi:10.1246/cl.2010.174
174
Published on the web January 30, 2010
Ultrastrong Gravity-induced Unusual Reactivity in Radical Addition
of Bromotrichloromethane to Ethyl Cinnamate
Yasuyuki Abe,1 Tsuyoshi Sawada,1 Makoto Takafuji,1 Tsutomu Mashimo,2,3 Masao Ono,3 and Hirotaka Ihara*1,3
1Department of Applied Chemistry and Biochemistry, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555
2Shock Wave and Condensed Matter Research Center, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555
3Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata Shirane, Tokai, Naka-gun, Ibaraki 319-1195
(Received November 20, 2009; CL-091032; E-mail: ihara@kumamoto-u.ac.jp)
Radical addition of bromotrichloromethane to ethyl cinna-
mate was carried out under an ultrastrong gravitational field
(>2.5 © 105 G), and ethyl 3-chloro-3-phenyl-2-(trichloro-
methyl)propionate (A), ethyl 3-bromo-3-phenyl-2-(trichloro-
methyl)propionate (B), and ethyl 2-bromo-3-phenyl-3-(trichloro-
methyl)propionate (C) were isolated by reversed-phase HPLC.
To date, there has been no report of the synthesis of A and C at
1 G, and this would be the first example of a selectivity change
induced by ultrastrong gravity.
(a) 8.0 × 105 G
(b) 1 G
Radical addition reactions of alkenes are among the most
fundamental reactions employed in organic synthesis and
polymer synthesis. For achieving reactivity control,1 many
researchers have carried out radical additions in the presence
of metal catalysts2 or under extreme conditions such as high-
pressure fields3 or high magnetic fields.4 The regio- and
stereoselectivity of the cycloaddition of alkenes to heterocycles
may change at high pressures, and this results in a decrease
in the activation volumes.3 It has been reported that radical
polymerization5 and photoreactions6 are accelerated in the
presence of a magnetic field since intersystem crossing between
the singlet and triplet states of a radical pair is facilitated by the
applied magnetic field.4
In this communication, we report an unusual radical
addition of alkenes in an ultrastrong gravitational field. This
method is based on the fact that in addition reactions carried out
under ultrastrong gravity, selective sedimentation of the reaction
species occurs. Recently, we have reported that molecular-scaled
graded materials can be obtained by the copolymerization of two
monomers with different molecular weights.7
In this study, we selected bromotrichloromethane (BTCM),
which is commonly used in radical addition reactions in the
presence of an initiator,8 as the reactant. To examine the radical
reactivity of the double bond, we selected ethyl cinnamate as the
substrate because the phenyl group and carbonyl substituent in
this compound influence the radical addition reaction via
electrostatic effects or steric effects.9,10
Radical addition was carried out using a mixture of ethyl
cinnamate, BTCM, and benzoyl peroxide (BPO) (Scheme 1).
The experiment was performed in an ultrastrong gravitational
Figure 1. Chromatograms of the products obtained at (a)
8.0 © 105 G and (b) 1 G.
field in a newly developed ultracentrifuge.11,12 150 ¯L of the
mixture (ethyl cinnamate:BTCM:BPO = 1:4:0.1)14 was sealed
in a stainless steel capsule and exposed for 24 h at 80 °C to a
gravitational field of 8.0 © 105 G generated by a centrifuge
rotating at 1.43 © 105 rpm. The resultant mixtures were analyzed
by reversed-phase HPLC.14 As shown in the chromatogram in
Figure 1a, three peaks (A, B, and C) appeared at retention times
of 11-14 min. Since the HPLC fractions absorbed light of
wavelength 220-250 nm, we confirmed that they contained the
phenyl group. These fractions were isolated for further analysis
by preparative HPLC. The total yield of A, B, and C was
approximately 70-90% in all cases.
On the basis of 1H NMR, H-H COSY, and high-resolution EI
mass spectral data, the major product B was confirmed to be ethyl
3-bromo-3-phenyl-2-(trichloromethyl)propionate.14 Further, the
melting point of B was confirmed to match that of the product
synthesized at 1 G.9 The minor products A and C were identified
to be ethyl 3-chloro-3-phenyl-2-(trichloromethyl)propionate and
ethyl 2-bromo-3-phenyl-3-(trichloromethyl)propionate, respec-
tively. To date, there has been no report of the synthesis of A and
C at 1 G. The identification of A and C was carried out in the
following manner. (1) The high-resolution FAB mass spectrum of
C showed a peak at m/z 394.8987, corresponding to bromo- and
trichloromethyl-substituted phenyl propionate (m/z 394.8984
for C12H12BrCl3O2Na). (2) The high-resolution FAB mass
spectrum of A showed a peak at m/z 350.9471, corresponding
to chloro- and trichloromethyl-substituted phenyl propionate
(m/z 350.9489 for C12H12Cl4O2Na). (3) The presence of ethoxyl
and ethylene groups in compounds A and C was also confirmed
O
C
CCl3Br
BPO
1
from their respective H NMR and H-H COSY spectra;14 thus,
H
C
H
C
H
C
C
C
OC2H5
C was confirmed to be a regioisomer of B. (4) The similarity in
the chemical shifts observed in the spectra of A and B suggested
that A was a 3-chloro-2-trichloromethyl adduct.
H
OC2H5
A
B
O
A, B = Br, Cl, CCl3
To investigate the influence of gravity on the product ratio,
the above-mentioned radical addition was carried out at different
Scheme 1.
Chem. Lett. 2010, 39, 174-175
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

175
the chlorine atoms in A, we expected that the second addition of
the ethyl cinnamate radical to a chlorine atom would afford A
instead of the bromo adduct B.
Under the ultrastrong gravity, a high-pressure of 104 Pa is
generated; this leads to a decrease in the number of molecular
degrees of freedom and an increase in the formation of
regioisomer C. Although the above-mentioned pressure is
not too high, it affects the regioselectivity of the first radical
addition reaction, as in the case of the topochemical reaction.13
Regioisomer C is formed in a large amount because the
activation volume associated with the radical addition to the ¢-
position of ethyl cinnamate is less than that associated with the
addition to the ¡-position.
8.0 × 105 G
4.0 × 105 G
2.5 × 105 G
1.0 × 105 G
1 G
In conclusion, we report the first example of a chemo- and
regioselectivity change in a radical addition reaction carried out
in an ultrastrong gravitational field. By carrying out the reaction
in an ultrastrong gravitational field, we could obtain two new
compounds A and C. There is no notable change in the observed
selectivity, and the detailed mechanism of the formation of A
and C remains to be clarified. Nevertheless, the unique results of
this study encourage us to use the proposed radical addition
method in polymer chemistry and for the synthesis of novel
organic compounds.
Figure 2. Chromatograms of the products obtained at various
gravitational fields.
This research was supported in part by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology and the Kumamoto University
Global COE Program of the Global Initiative Center for Pulsed
Power Engineering.
References and Notes
Gravity/105 G
1
2
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Figure 3. Influence of gravitational field on chemo- and
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3
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It is clear that product A is obtained only at gravitational
fields stronger than 2.5 © 105 G and that the product ratio of C
increases remarkably when the gravitational field is stronger
than 2.5 © 105 G. Therefore, we conclude that ultrastrong
gravity induces the formation of A and C, which is an unusual
phenomenon.
The mechanism underlying the formation of B can be
explained as follows: BPO (radical initiator) reacts with a
bromine atom to yield a trichloromethyl radical, which then
attacks the ¡-carbon of ethyl cinnamate. Subsequently, the
bromine atom in BTCM reacts with the ¢-carbon of the ethyl
cinnamate radical to afford B. In this reaction, a small amount of
C, which is a regioisomer of B, is formed as the by-product
(Figure 1b). Under normal conditions, this mechanism is
considered to be reasonably accurate.
When the addition reaction was carried out in an ultrastrong
gravitational field, the product ratio of A and C increased. We
assumed that the formation of A depended on the selective
molecular sedimentation caused by the ultrastrong gravity. The
separation of ethyl cinnamate from BTCM by this selective
molecular sedimentation could possibly interrupt the reaction
of the bromine atoms in BTCM with the ¢-carbon of ethyl
cinnamate. Although we could not identify the exact source of
4
5
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12 An ultracentrifuge apparatus has been designed by T. Mashimo
of Kumamoto University and developed at the Japan Atomic
Energy Agency (JAEA). This ultracentrifuge can generate
ultrastrong gravitational fields stronger than 1 MG at a constant
temperature within «2 °C.
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14 Supporting Information is available electronically on the
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index.html.
Chem. Lett. 2010, 39, 174-175
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/