tional liquid-liquid biphasic system. In our preliminary work,5
we described the ring opening of an aziridine and indicated that
the use of silica-water reaction media had great potential for
use in a variety of chemical reactions. Although some examples
of the ring opening of aziridines with nucleophiles in water have
been reported to date, a catalyst6 and/or water-soluble organic
solvents7 are required for the reaction to proceed. From these
points of view, to expand the utility of this potentially valuable
strategy, we herein report on the reaction of aziridines with
water-soluble nucleophiles leading to ring-opening and ring-
expansion products. Since the efficiency of the ring opening of
an aziridine with sodium azide was satisfactory in our prelim-
inary study,5 cyanides and iodides as water-soluble nucleophiles
were investigated for ring opening of aziridines.
Ring Opening and Expansion of Aziridines in a
Silica-Water Reaction Medium
Satoshi Minakata,* Takahiro Hotta, Yoji Oderaotoshi, and
Mitsuo Komatsu*
Department of Applied Chemistry, Graduate School of
Engineering, Osaka UniVersity, Yamadaoka 2-1, Suita,
Osaka 565-0871, Japan
ReceiVed June 15, 2006
Although silica gel was found to be an effective solid medium
for the iodine-catalyzed aziridination of olefins with CT and
ring opening of aziridines with NaN3 in water, a variety of
porous materials were examined for the ring opening of an
aziridine with KCN to improve the efficiency of our preliminary
result (Table 1). The reaction of aziridine 1a with KCN in water
in the absence of a porous material at 80 °C did not proceed at
all (entry 1). When Silica Gel 60 was employed, regioselective
ring-opening product 2a was obtained in 69% yield. The silica
gel was found to be reusable without any special treatment, and
2a was produced in 65% yield in the second cycle and in
65% in the third cycle under the same conditions. When meso-
porous silica with a hexagonal array, MCM-41,8 was used in
the reaction, the desired ring-opening product was produced in
moderate yield. Neutral and basic alumina, 4 Å molecular sieves,
Celite 545, and Montmorillonite K10 were also positive for the
reaction, but Silica Gel 60 was found to be a very useful solid
medium.
The ring opening of various N-tosylaziridines with KCN was
investigated in water in the presence of Silica Gel 60, and the
results are shown in Table 2. Aziridine 1b was readily converted
to the ring-opening product in good yield with complete
regioselectivity (entry 1). When the reaction of sec-butyl-
substituted aziridine 1c was examined under the same conditions,
the reaction proceeded in moderate yield. Although the efficien-
cies of the reactions of 1d and 1e could be improved, the
complete regioselective ring opening of both aziridines was
observed, and the method was found to be applicable to the
ring opening of a hydroxylated aziridine. The bicyclic aziridines
1f and 1g were transformed to the corresponding ring-opening
products with trans configurations, respectively. Thus, the
presence of Silica Gel 60 enhanced the performance of all of
the ring-opening reactions.
Ring-opening reactions of N-tosylaziridines with water-
soluble nucleophiles proceeded in a silica-water reaction
medium. The system is applicable to a ring expansion of an
aziridine with potassium thiocyanate, leading to a thiazolidine
derivative.
The replacement of current organic chemical processes with
more environmentally benign alternatives is an important goal
from an ecological point of view.1 A great deal of interest has
developed regarding the use of aqueous media in organic trans-
formations because water is nontoxic, nonflammable, and in-
expensive and environmentally benign.2 Prompted by this, we
previously reported on the iodine-catalyzed aziridination of
olefins using chloramine-T (CT)3 in aqueous media by the addi-
tion of a phase-transfer catalyst (PTC).4 Since CT has an ionic
character, a PTC is generally used to permit the reaction to
proceed in water. An alternative potential process in aqueous
media has recently been devised based on the adsorptive nature
of silica gel.5 Silica is effective as an organic reaction medium
in water because the organic substrate is adsorbed to the silica
by hydrophobic interactions between the surface of the silica
and the organic molecule. In addition, the surface area available
for a reaction (surface area of the silica) in such a system should
be quite large compared with that of the interface in a conven-
Although the ring opening of 1a with metal chlorides and
bromides did not proceed at all, even in the presence of silica,
(1) (a) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and
Practice; Oxford University Press: New York, 1998. (b) Eissen, M.;
Metzger, J. O.; Schmidt, E.; Schneidewind, V. Angew. Chem., Int. Ed. 2002,
41, 414-436. (c) Special Topic Issue on Green Chemistry: Acc. Chem.
Res. 2002, 35, 685-816.
(2) (a) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media;
Wiley: Chichester, UK, 1997. (b) Organic Synthesis in Water; Grieco, P.
A., Ed.; Blake Academic and Professional: London, 1998.
(3) Ando, T.; Kano, D.; Minakata, S.; Ryu, I.; Komatsu, M. Tetrahedron
1998, 54, 13485-13494.
(4) Kano, D.; Minakata, S.; Komatsu, M. J. Chem. Soc., Perkin Trans.
1 2001, 3186-3188.
(5) Minakata, S.; Kano, D.; Oderaotoshi, Y.; Komatsu, M. Angew. Chem.,
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(6) (a) Reddy, M. A.; Reddy, L. R.; Bhanumathi, N.; Rao, K. R. Chem.
Lett. 2001, 246-247. (b) Chandrasekhar, S.; Narsihmulu, C.; Sultana, S.
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237. (b) Maligres, P. E.; See, M. M.; Askin, D.; Reider, P. J. Tetrahedron
Lett. 1997, 38, 5253-5256.
(8) (a) Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J. C.;
Beck, J. S. Nature 1992, 359, 710-712. (b) Beck, J. S.; Vartuli, J. C.;
Roth, W. J.; Leonowicz, M. E.; Kresge, C. T.; Schmitt, K. D.; Chu, C.
T.-W.; Olson, D. H.; Shepard, E. W.; McCullen, S. B.; Higgins, J. B.;
Schlenker, J. L. J. Am. Chem. Soc. 1992, 114, 10834-10843. (c) Grun,
M.; Unger, K. K.; Matsumoto, A.; Tsutsumi, K. Microporous Mesoporous
Mater. 1999, 27, 207-216.
10.1021/jo061239m CCC: $33.50 © 2006 American Chemical Society
Published on Web 08/19/2006
J. Org. Chem. 2006, 71, 7471-7472
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