Silica-Water Reaction Media: Its Application to the Formation and Ring Opening of Aziridines

Article abstract of DOI:10.1002/anie.200352842

Olefins can be converted into aziridines by using a chloramine-T/I ₂ system, and silica and water as the reaction medium (see picture). Moreover, the ring-opening reaction of the resulting aziridine with an azide or a cyanide ion proceeds in th

Full text of DOI:10.1002/anie.200352842

Angewandte
Chemie
Reaction Media
Silica–Water Reaction Media: Its Application to
the Formation and Ring Opening of Aziridines**
Satoshi Minakata,* Daisuke Kano, Yoji Oderaotoshi,
and Mitsuo Komatsu*
In recent years, the demand for environmentally benign
organic-chemical processes has increased and this issue must
be considered, from the ecological point of view, in the future
design and implementation of new synthetic methodologies.[1]
Organic reactions in aqueous media have been the subject of
considerable attention in terms of achieving more environ-
mentally friendly synthetic transformations.[2] On the other
hand, aziridines[3] are useful synthetic intermediates for a
variety of organic syntheses and they are frequently present as
important substructures of biologically active compounds.
Thus, the development of an efficient synthetic route to
aziridines represents an attractive task for organic chemists
and, as a result, a variety of methodologies have been
exploited.[4]
Figure 1. Proposed path for the formation of aziridines in a water–
silica system.
Table 1: A comparison of silica gel 60 and MCM-41 as surface media for
the formation of aziridine from styrene by using CT in Water.[a]
Entry
Silica [g]
CT
[mmol]
Specific surface
Yield
[%]
area [m2 gÀ1
]
We recently reported on the iodine-catalyzed formation of
aziridines from olefins by using chloramine-T (CT)[4k] in
aqueous media by the addition of a phase-transfer catalyst
(PTC).[4l] The use of PTC to permit the reaction in aqueous
media is a general method because of the ionic character of
CT. An alternative potential process in water was devised
based on the adsorptive nature of silica gel. Although the
application of silica gel to organic synthesis has been widely
investigated,[5] to the best of our knowledge its use in organic
reactions in aqueous media has not been exploited.[6] Silica
would be effective as organic reaction media in water because
the organic molecule as a substrate would be expected to be
adsorbed to the silica by hydrophobic interactions between
the surface of the silica and the organic molecule (Figure 1).
Herein we report on the iodine-catalyzed formation of
aziridines from olefins by using CT and the ring opening of
the resulting product in a silica–water system, in which the use
of silica (silica gel or MCM-41) showed unique results.
Although the reaction of styrene with CT in the presence
of K2CO3 and a catalytic amount of I2 in water did not proceed
at all, the addition of silica gel to the system led to the
production of the desired aziridine (Table 1). For example,
when styrene (1.0 mmol) was treated with CT (2.0 mmol),
K2CO3 (2.0 mmol), and I2 (10 mol%) in the presence of silica
1
2
3
4
silica gel 60 (0.25)
silica gel 60 (0.5)
silica gel 60 (0.5)
MCM-41 (0.25)
2.0
2.0
4.0
2.0
640
640
640
1060
32
55
85
80
[a] Reaction conditions: styrene (1.0 mmol), CT (2.0 or 4.0 mmol), I2 (10
mol%), K2CO3 (2.0 mmol), silica (0.25 or 0.5 g), H2O (1.5 mL), RT, 3 h.
Ts =p-toluenesulfonyl.
gel 60[7] (0.25 g) in water, N-(p-toluenesulfonyl)-2-phenyl-
aziridine was obtained in 32% yield (entry 1). An increase in
the amount of the silica gel used to 0.5 g improved the yield of
the product (entry 2), but additional amounts failed to
improve the efficiency of the reaction. The use of four
equivalents of CT under the conditions of entry 2gave the
best result, an 85% yield of the aziridine (entry 3). From the
difference in efficiency of the reactions (entry 1 versus
entry 2), the product yield appears to be dependent on the
specific surface area of the silica gel. Recently, mesoporous
materials have attracted considerable attention in organic
synthesis as solid acids or supports.[8] MCM-41,[9] one of such
mesoporous silicas with a hexagonal array of uniform
mesopores, was evaluated in the present aqueous system to
synthesize aziridines. The use of MCM-41 led to a positive
result, even when the reaction was carried out with two
equivalents of CT and 0.25 g of silica (entry 4). A reaction
using MCM-41 might proceed effectively because of its larger
specific surface area, which is nearly double that of silica
gel 60.
[*] Dr. S. Minakata, Dr. D. Kano, Dr. Y. Oderaotoshi,
Prof. Dr. M. Komatsu
Department of Applied Chemistry
Graduate School of Engineering, Osaka University
Yamadaoka 2-1, Suita, Osaka 565-0871 (Japan)
Fax: (+81)6-6879-7402
Avariety of olefins were examined for this silica-mediated
preparation of aziridines in water by using the iodine catalyst-
CT system (Table 2). In the presence of MCM-41 (0.25 g),
K2CO3 (2.0 mmol), and an iodine catalyst (20 mol%), 1,2-
dihydronaphthalene was reacted with CT (2.0 mmol) to
afford the corresponding aziridine in 75% yield. Other
E-mail: minakata@chem.eng.osaka-u.ac.jp
komatsu@chem.eng.osaka-u.ac.jp
[**] This work was partially supported by a Grant-in Aid for Scientific
Research from the Japan Society for the promotion of Science.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2004, 43, 79 –81
DOI: 10.1002/anie.200352842
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Communications
Table 2: Silica–water-mediated formation of aziridines from various
efficiency of the reaction is dependent on the extent of
adsorption of olefins to the silicas, strongly suggesting that the
reaction occurs on the surface of the silicas.
olefins.[a]
olefin
aziridine
yield [%]
MCM-41 Silica gel 60
To show the generality of this media in organic synthesis,
the ring opening of N-(p-toluenesulfonyl)-2-n-hexylaziridine
with NaN3 or KCN was examined. The reaction of the
aziridine with NaN3 or KCN in water in the absence of silica
did not proceed. When silica gel 60 was added, however, the
reaction proceeded to afford the regioselective ring-opening
products (Scheme 1).
75
75
68
68
53
64
7
26[b]
49
4[c]
42[c]
27[d]
70[d]
56[c]
72[d]
58[c]
Scheme 1. Application of silica–water system to the ring opening of
2-hexyl-N-(p-toluenesulfonyl)aziridine with NaN3 or KCN.
61[b,d]
59[d]
In summary, a new organic transformation in water by
exploiting the adsorptive nature of silica is demonstrated; the
formation of aziridines and their ring opening are used as
examples. Applications of the present system to other organic
reactions are now in progress, as the use of this system
represents an environmentally benign organic synthesis.
[a] Reaction conditions: olefin (1.0 mmol), CT (2.0 mmol), I2 (20 mol%),
K2CO3 (2.0 mmol), silica (MCM-41; 0.25 g or silica gel 60; 1.0 g), H2O
(1.5 mL), RT, 3 h. [b] Silica gel 60 (0.5 g). [c] Trans only. [d] Cis only.
cyclic olefins such as cyclohexene and cyclopentene were also
used with the MCM-41 system resulting in the formation of
aziridines in good yields. When these reactions were carried
out with silica gel 60 (1.0 g), aziridines were also obtained in
good yields. In spite of the fact that a larger amount of silica
gel 60 (1 g; surface area: 640 m2) was employed, compared to
that of MCM-41 (0.25 g; surface area: 265 m2), better results
were achieved when the latter system was used, thus
indicating that specific properties of MCM-41, which is a
mesoporous solid and has an hexagonal array, may have
played a role in these reactions. Although the formation of
aziridines from acyclic olefins mediated by MCM-41 pro-
ceeded with a low yield, the same reactions with silica gel 60
gave the desired aziridines in moderate to good yields. The
origin of this might be differences of the pore sizes of the
MCM-41 and silica gel 60. As the average pore size of the
MCM-41 used in this system is 25 Š, about half that of silica
gel 60 (60 Š), we assume that the high degree of freedom of
acyclic olefins suffers from difficulty in interacting with the
surface of the MCM-41. On the other hand, allylic alcohols
gave the corresponding aziridines in good yields with either
MCM-41 or silica gel 60. It is possible that the hydroxyl group
of these olefins may assist in the adsorption of olefins to the
surface of the silicas.[10] This prediction is supported by the
fact that the aziridination of trans-2-hexene scarcely pro-
ceeded under the same conditions.
Received: September 11, 2003 [Z52842]
Keywords: aziridines · cyclization · nitrogen heterocycles ·
.
silicates · water chemistry
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80
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[11] See Supporting Information.
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